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for Reagents OrganicSynthesis
v.Jl
VOLUME TWENTY ONE
Tse-LokHo National Chiao Tung University Republicof China
@WTI.EYINTERSCIENCE A JOHNWILEY & SONS.INC..PUBLICATION
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FOREWORD When my friend and colleague Prot'essorTse-Lok Ho invited me to write a Foreword tbr Volume 2l of the Fieser/Ho Reagentsfor organic Synthesis,I felt honored since this serieshad been, and is, of immensevalue in my research.In addition, my memories of Mary and Louis Fieserand their friendshipover the yearsare very precious.
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The very first syntheticorganicexperimentthat I carriei out (as an MIT sophomore in 1946)was the preparationofn-butyl bromide from n-butyl alcohol using the first edition of Louis Fieser'sExperimentsin organic chemistry ( 1935).I went on to carry out most of the other experimentsin the manual, and added the later editions of the books to my personal library. The third edition, which appeareclin 1955, contained an innovation: A sectionat the end of some 50 pagesthat provided valuableinformation on a collection of useful organic reagentsand solvents.In the early 1960sduring lunch with Mary and Louis, I mentionedmy indebtedness to them for havingprovidedthat concisesummaryon reagentsand suggestedthat they considerexpandingit into a largerreferencework. I think it likely that other colleaguesmay have made similar proposals.In any event, Mary and Louis in due coursewent on to producethe first volume of Reagentsfor organic synthesis (1961')'alarge (1457 pp) work, going far beyondwhat I had hoped for, thar achievedimrnediatesuccess.I believethat this volume was the first full documentation of the ..organic reagent" revolution that occurred in the 1945-1965 period, the result of which was an cnormousincreasein the ability of chemiststo constructcomplex organicmolecules. That incrcasein the power ol synthesis,which probably was closerexponential than linear with respectto the numberof availablereagents,was just the beginning.The continuing series ol'volumes,2l with the appearance of this book, testifiesto the continuedvigor of reagent discoveryand developmentand to the importanceof this areaof chemistry. Thc Fiesersdeservcenormouscredit lbr their role in advancingresearchin the steroicl field during the period 1940-1960throughtheir threelandmarkmonographs on this important classof compounds.It is rcmarkablcthat thcir impact on the community of synthetic organicchemiststhrough the seriesRcagentslbr organic Synthesisis also large beyond calculation.But then,Mary and Louis Fieserwere remarkablepeople.To Tse-Lok Ho has lallentheirmantleand the responsibility to continuethisclassicseriesin the serviceofsynthetic chemistry,and sciencein general.It is clear liom Ho-FieserVolumeslg_21 that the Reagentsseriesis in strong hands.I recall the sageadvice that Tse-Lok included in the Prelhceof volume 20: "For a task perfectlydone,first havethe tool sharpened." Each new 'olume adds greatly to the toolbox and to the luster of the whole series.Tse-Lok Ho deservesour deepestthanksfor his heroic eftbrt, incluclingpreparationof all the text and tirrmulas,proofreadingand, of course,readinga massiveamountof original literature. on behalfof the syntheticcommunity,I conveyour bestwishesfor future success.
E. J. Coney
PREEACE
+nflffiez Tdi'a+ ? --6frff
Learn, then apply constantly Does it impart a joyful feeling? -Analects
My quoting of another segment of the teachings of Confucius here is, by my interpretation, due to its relevance to the work of synthetic organic chemists. Learning tiom experience is essential to efficiently achieve set goals that give people intellectual satisfaction.Of course,experiencesaccumulatedby othersare also of enormousvalue.As is well known to readersofReagentsfor Organic Synthesis,this seriesservesto facilitate the role of knowledgeassimulation. volume 21, which covers the chemical literature from the period 1999-2000, is the first of the seriesto appearin the twenty-firstcentury.The dawning of this new century brings many unexpectedevents.Fortunately,among the more pleasantconstantshuman beingsenjoy is scientificprogress.For example,biotechnologythat is primarily hasedon organicchemistryseemsready to blossom. To be sure,organic synthesishas yet to attainperf'ection.The enormousachievements "green chemistry" in this field are well recognized,at least by people in the field. While attractsmuch current attention,it must be emphasizedthat active participation of the syntheticchemistsis required.Conducting difficult chemistry in aqueousmedia, in the lluorous phase, in supercriticalfluids, or without any solvent, is a great yet profitable challenge,and it behoovesus to pursuetheseareasvigorously.Accordingly,pertinentintbrmationis includedin volumesof the Reagentsfor organic Synthesisseries. Every chemist is interestedin the Nobel Prize.Organic synthesisreceivedits shareof limelight in the year 2001 as a result of the award going to three distinguishedpioneers of asymmetric synthesis:william Knowles, Bany Sharpless,and Ryoji Noyori. Their contributionsand profound influencesare apparentfrom pagesin this series' I am deeply gratefulto my respectedmentor,ProfessorE. J. Corey of Harvard University, who succeedsProfessorLouis F. Fieser to occupy the Sheldon Emery chair of Organic Chemistry,for writing a Forewordfor this volume. His unsurpassedinnovations in the realm of chemical synthesis,which include the creationof innumerableand invaluable reagents,are the major sourceof nourishmentto sustainthe growth ofour science'
Tsr-Lor Ho
CONTENTS
GeneralAbbreviations xi ReferenceAbbreviations xv Reagents 1 Author Index 499 SubjectIndex 561
GENERAL ABBRBVIATIONS Ac
acetyl
acac ADDP
acetylacetonate l,l'-(azodicarbonyl)dipiperidine
AIBN An aq Ar
2,2'-azobisisobutyronitrile p-anisyl
ATPH 9-BBN
aluminum tris(2,6-diphenylphenoxide) 9-borabicyclo[ 3.3.l ]nonane -diol l, l' -binaphthalene-2,2'
BINOL Bn Boc frpy
aqueous aryl
benzyl t-butoxycarhonyl 2,2'-bipyridyl benzotriazol-l -yl
Bt Bu
n-butyl
Bt. I lJ-c-6
benzoyl l8-crown-6
c-
a()t
cyclo cerium(lV)ammonium nilratc catalytic bcnzyloxycarbonyl I ,5-cyclooctadiene 1,3,5-cyclooctatriene
Cp cp*
cyclopcntadienyl 1,2,3,4,5-pentamethylcyclopenradienyl
CSA C1 cr clarn D,{BCO DAST Jha I)BN
I 0-camphorsulfonic acid cyclohexyl 1,4,8,I I -tetraazacyclotetradecane 1,4-di azobicyc1o12.2.2)octane (diethylamino)sulfurtrifl uoride
CAN aat
Cbz t'rrd
I)BU I)CC r)DQ J.' I)EAD
dibenzylideneacetone 1,5-diazobicyclo[4.3.0]non-5-ene 1,8-diazobicyclo[5.4.0]undec-7-ene M N' -dicyclohexylcarbodiimide 2,3-dichloro-5,6-dicyano1,4-benzoquinone diastereomerexcess diethyl azodicarboxylate
GeneralAbbreviations
\lcs
DIAD Dibal-H DMA DMAP DMD DME DMF DMPU DMSO dpPb dppe dppf dppp DTTB E
diisopropYl azodicarboxYlate diisobutylaluminum hYdride N,N-dimethylacetamide 4-dimethYlaminoPYridine
\to\1
dimethyldioxirane 1,2-dimethoxYethane N,N-di methylformamide N,N' -dimethYlProPYleneurea
\lVK \BS \CS
dimethyl sulfoxide 1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)ethane 1,2-bis(diphenylphosphino)ferrocene 1,3-bis(diphenylphosphino)propane 4,4' -di-t-butYlbiPhenYl
\\to
COOMe
rcC
en DT
EVE Fc Fmoc
Fu HMDS HMPA
enantlomerexcess ethylenediamine ethyl ethYlvinYl ether ferrocenyl 9-fluorenYlmethoxYcarbonYl turanyl hexamethYldisilazane hexamethYlPhosPhoricamide
hv
Hx I Ipc kbar LAH LDA LHMDS LTMP LN lut M MAD MCPBA Me MEM Men
\tr \IS
\rTO
\IS
N-iodosuccinimidcN-methylmorPhohne.\'<
\u
nucleophile
()c
PEG
octyl pyridinium chlortxhrt-m pyridinium dichromate poly(ethyleneglr col '
Ph
phenyl
nhen Ph( Ptr
I ,10-phenenthrolinc' phthaloyl
PDC
P\IB P\IHS Pr
isoPinocamPheYl kilobar ligand lithium aluminum hYdride
Ra\i RC\1 R
lithium diisoProPYlamide lithium hexamethyldisilazide lithium 2,2,6,6-tetramethylpiperidide lithium naPhthalenide
..rlcn
menthyl
N-bromosuccinimrde N-chlorosuccinimrd.'
\r
()
methYl methoxYethoxYmethYl
methl'ltnoxorhodrum methyl vinl'l ketonr'
N-methylpyrrolidonc' naphthyl I p-nitrobenzenesullonr
\\IP \p
light n-hexYl iso
2,6-lutidine metal methylaluminum bis(2,6-di-r-butyl-4-methylphenoxide) acid m-chloroperoxybenzoic
mesitll methoxl methl I methanesulfonlI t mt-rrl' molecularsieres
R.\\IP
s \\tP .cn5. SE\t \ES
pivaloyl p-methoxybenzllorl rnc ht\a poly(methYlhY'drosr
n-propyl pyridine quaternaryonlum lon (R)- l -amino-2-methor; Raneynickel ring closuremetathe\li perfluoroalkyl
secondary solid N,N'-ethYlenebistsalr (S)- l -amino-2-metho sensitizer
2-(trimethYlsiltl)etho lrthl l] 2-[(trimethYlsill
tris(dimethYlaminotsu tetrabutylammoniumf IBDPS t-butYldiPhenYlsilll I TBDMS t-butYldimethYlsilr f,\SF IBAF
GeneralAbbreviations
Mes MOM
mesityl
Ms MS MTO MVK
methoxymethyl methanesulfonyl (mesyl) molecularsieves methyltrioxorhodium methyl vinyl ketone
NBS NCS
N-bromosuccinimide N-chlorosuccinimide
NIS NMO NMP
N-iodosuccinimide N-methylmorpholine N-oxide N-methylpyrrolidone
Np Ns
naphthyl p-nitrobenzenesulfonyl
Nu
nucleophile
Oc
octyl pyridinium chlorochromate pyridinium dichromate poly(ethyleneglycol) phenyl
PCC PDC PEG Ph phen Pht
I , I O-phenenthroline phthaloyl
Piv
pivaloyl
PMB PMHS
p-methoxybenzyloxymethyl poly(methylhydrosiloxane)
Pr
n-propyl pyridine quaternary onium ion (R)-I -amino-2-methoxymethylpynolidine
pv Q' RAMP RaNi RCM R' (s, salen SAMP sens. SEM SES TASF TBAF
Raneynickel ring closuremetathesis perfluoroalkyl secondary solid N,N' -ethylenebis(salicylideneiminato) (S)- 1-amino-2-methoxymethylpynolidine sensitizer 2-(trimethylsilyl)ethoxymethyl 2-[(trimethylsilyl)ethyl]sulfonyl tris(dimethylamino)sulfur(trimethylsilyl)difluoride tetrabutylammoniumfluoride
TBDPS r-butyldiphenylsilyl TBDMS t-butyldimethylsilyl
xiv
TBS Tf THF THP Thx TIPS
GeneralAbbreviations
t-butyldimethYlsilYl trifluoromethanesulfonYl tetrahYdrofuran tetrahydroPYranYl t-hexyl triisopropylsilYl
TMEDA N,N,N',N'-tetramethylethylenediamine trimethylsilyl TMS p-tolYl Tol tosyl (P-toluenesulfonYl) Ts TTN
2-(trimethYlsilYl)ethYl thallium trinitrate
Z
benzyloxYcarbonYl
A
heat
))))
mlcrowave
TSE
REFERENCEABBR] ACIEE ACR
Angew Chem. Int. Ed Ea Acc. Chem. Res.
ACS
Acta Chem. Scand.
AJC AOMC BC BCSJ
Aust. J. Chem. Appl. Organomet.Chem Bioorg. Chem.
BRAS
Bull. Chem. Soc. Jpn. Bull. Russ.Acad. Sci
CC
Chem. Commun.
CEJ
Chem. Eur. J.
CJC CL CPB
Can. J. Chem. Chem. Lett. Chem. Pharm.Bull.
CR EJIC
Carbohydr. Res. Eur. J. Inorg. Chem.
EJOC
Eur. J. Org. Chem.
H HCA
Heterocycles
Helv. Chim. Acta J. Am. Chem. Soc. J. Carbohydr.Chem. JCCS(T) J. Chin. Chem. Soc. tTarp JCR(S) J. Chem.Res.(Synopsrs JACS JCC
JCS(PI ) J. Chem. Soc. Perkin Tran J. Fluorine Chem. JFC J. Heterocycl. Chem. JHC J. Org. Chem. JOC J. Org. Chem. USSR (Ent JOCU JOMC MC NJC OL OM PAC PSS
J. Organomet.Chem. MendeleevCommun. New J. Chem. Organic Letters Organometallics PureAppl. Chem.
RCB RJGC
PhosphorusSulfur Silicon RussianChem. Bull. Russ.J. Gen. Chem.
RJOC
RussianJ. Ore. Chem.
REFERENCEABBREVIATIONS ACIEE ACR ACS AJC AOMC BC BCSJ
Angew. Chem. Int. Ed. Engl. Acc. Chem. Res. Acta Chem. Scand. Aust. J. Chem. Appl. Organomet. Chem. Bioorg. Chem.
BRAS
Bull. Chem. Soc.Jpn. Bull. Russ.Acad. Sci.
CC
Chem. Commun.
CEJ
Chem. Eur. J.
CJC
Can. J. Chem. Chem. Lett. Chem. pharm. Bull.
CL CPB CR EJIC EJOC H
Carbohydr. Res. Eur. J. Inorg. Chem. Eur J. Org. Chem. Heterocycles
HCA JACS
Helv. Chim. Acta J. Am. Chem. Soc. JCC J. Carbohydr. Chem. JCCS(T) J. Chin. Chem. Soc. (Taipei) JCR(S) J. Chem.Res. (Synopsis) JCS(PI ) J. Chem. Soc. perkin Trans. I JFC J. Fluorine Chem. JHC J. Heterocycl.Chem. JOC J. Org. Chem. IOCU J. Org. Chem. USSR (Engl. Trans.) JOMC J. Organomet.Chem. MC Mendeleev Commun. NJC New J. Chem. OL OM PAC PS.t RCB RJGC RJOC
Organic Letters Organometallics Pure Appl. Chem. PhosphorusSulfur Silicon RussianChem. Bull. Russ.J. Gen. Chem. RussianJ. Org. Chem.
xvi
s SC SL SOC T TA TL
Abbreviations Reference Synthesis Synth. Commun. Synlett Synth. Org. Chem. (Jpn.) Tetrahedron Tetrahedron:Asymmetry
firrk
TetrahedronLett.
ackt. Ikaetbtion-
R
r-. :::<::r !Cnl!'f .'.'.r-: J
h,'rr
P,/('(
rcak
enhldridc. !1. t-nobe enbtior- .' \. ()-l lc.tox!
itathtq
:q -"1:li. , rn U!'3tlT)('nlI
\r ': [) i ttr-ri.. R ! ':r. I' Llrn.l l{ ,r('
oximc ()-c
tcrldr.
.fu lnbadacs. ':j.::,'!: ulth thc rc!8( :--:r
i
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lkohot
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)
:
l - c c( ' - F I l
l. fcaorlbcorll
tril
t.thcr lonmtiot 'ri:-i:-: :'r ftfm J-r-Ctr r' -' I r'.itUIr' Jriir'rCntU ,-.r.
tcdr
l{::rJ.gr:-
lr"toorto. di('r ( lr,tn cloagoia
.-:: r.i:r,'n .rllr lett.n - ' ::{:5il
Acetic acid. Deacylatiot anom".i.."nt..,t'
Peracetyrated
sugars can be regioserectivery
tZhang, I.,Kovac,p JCc 1g,461(19gr.
deacetylated
at the
Acetic anhydri cle.20, 1
*rrn?"Slrltation'
I Assisted bvmicrov ketones - readily --qu'y
Acetoxy isothiocvannr..
z acerates ono"ur^2'!,'!::o:r.' arin" ur.t
under unoergo enolacetylation
:::#',se';le';ana''a'k rff::-?i;#-{ffi #;ilni:*tdff Acetoneoxime 0_r Arylamin es., l"tit"vltn"tulfonate' compounds reacdon*t*',i....ff,'linc are converted into - "r/ra'unes aryramineson jErdik, cu-cataryzed 8.,Daskapan, T.sc 2g,3gg9 (1g9g). Acetonyltriphenytnt
,,{"::;::?:i;i!!:ii *, :- ::;::',"'
ach ieved ."*f ; ;';'"uJ,n-in* ", i"n' i,,,jff :l iT..J;: rj, a n o"^ * _ . . v t u e u ;;,,f o f l r n r n e t h1", r cu, a n0,., be rHon,y_S.,Lee,c._F, TL40,23gg(lggg).
+ Acetorybenzql trichloroacedmidate.
,l#H :'fi;ffi f:f,fuft:'9;;,flfiffirTilr Acet1lac.e_ton,ato(dicarbonyl)rhodium. Lnarn elongation, ,.
;::?jil:T_,",i^,|Ji,#,"ffi;H,;:JiITil:J#;::#:"3H;l:i
l-Acylbenzotriazoles
)
N-Acyl-5,5-dimethyloxazolidin-2-ooes. As latent aldehydes.t Dibal-H n
(
OH
(acac)Rh(CO)2 +
o)sil'., I
K 2 : R3
Wadsworth condensation. rBach. S.G..Nichol'vr J..Bull,S.D.,Davies,
Rr"')
co i PhH 60' H2O2 - MeOH
nr"'il'y\
OH
R2
NaHCO3
of Conversion of RHgCI to RCHO is readily accomplishedunder H2-CO.2 Promotion atom. this reaction by DABCO indicates its possible role as ligand for the mercury tZacuto,M.J.,Leighton,J.L.JACS122'858'7(2000)' 2Sanaf,S.T.,Leighton, l.L. OL2' 3205(2000)'
R
+
(acac)Rh(C2H4)2
RB(OHtr
with allyltrichtorosilanes.z
N ll Ph'--AH
Acetylacetonato(diolefi n)rhodium. are Aryl transfers. Transfer reactions involving arylboronic acids and aldehydes is evident.r tBuiP by A largeaccelerationeffect catalyzedby (acac)Rh(cyclooctene)2. and nitroMichael addition. Asymmetric arylation of l-alkenylphosphonates2 (S)-BINAP' alkenesroccurs in the presenceof (acac)Rh(ethylene)2and
aY*o'
Acylhydrazones. Imine surrogates. In the Manruch hydrazonesinsteadof unstableiminc-rt. r
+ (s)-BINAP
| , y'*o' t l
+
sn*,/ \-
rManabe,K., Oyamada,H., Sugita.K.. Kt-hrr rKobayashi,S., Hirabayashi,R. JACS lll. t*r
Acyl nitrates. tlx Nitration.t Whenimmobilized. (6 examples. 86- lt1 goodregioselectivity
LRodrigues, J.A.R., Filho, A.P.O.,Moran. PJ I
dioxane - H20 100"
- NHBz
ee > 98%
rUeda,M., Miyaura,N. "IoC65' 4450(2000). 2Hayashi, M' 'IACS121,11591(1999)' Y.,Ogasawara, T.,Takaya, T., Senda, lHayashi,T., Senda,T., Ogasawara, M. JACSl2l' 10116(1999)'
N-Acetylcysteine' The Amidines.t The title compoundcatalyzesthe addition of ammonia to nitriles. groups' functional many with compatible are reactionconditions rLanee.U.E.W.,Sch?ifer, E', Mack'H'TL40'1067 (1999)' B., Baucke,D., Buschmann,
1,3,5-triazir 2-Acyloxy-4,6-dimethoxyEsters.t Preparedfrom 2-chloroto ak undergotransacylation compounds
J.8.,Kaminski,2.J.,Gora.J 5 19 Kaminska,
N-Acyl-N-(pentafl uorophenyl )meihra N-Acylation.t Amides are formed examples,62-99Vo).
8., Nakao.J..\luralrr Kondo,K., Sekimoto, L-Acylbenzotriazoles. pDicarbonyl compound.s,t c-Acylation reported(18 examPles,36-92Vo). rKatritzky, A. JOC 65' 3679(2000)' A.R.,Pastor,
of ketones with these reagents are
Acylzirconocene chlorides. Acyl anion equivalents.t Additrcn mode.This Pd-catalyzedreactionprorrd
Acylzirconocene chlorides
N-Acyl-5,S-dimethyloxazolidin-2-ones. As latent aaehydes.t Wadsworth condensation.
Dibal-H reduction affords aldehydes for the Emmons-
I Bach,J.,Bull, S.D.,Davies, S.G.,Nicholson, R.L.,Sanganee, H.J.,Smith,A.D. TL 40,667i(19gq.
Acylhydrazones. It , i,:,'ntotionof C . -1
.:., \111.
Imine sutogales. In the Mannich reaction and cyanide addition, the use of these hydrazonesinstead of unstableimines is advantageous.rAllylation may also be performed with allyltrichlorosilanes.2
*. Pn.--{H
r..: .ichvdesare t, -'rident.l h
.
end nitro-
NHBz
*'nf'\). # rrJIX
Manabe,K., Oyamada,H., Sugita,K., Kobayashi,S. JOC 64,9054 (1999). : Kobayashi,S., Hirabayashi, R. "/ACSl2l, 6942(lggg\.
Acyl nitrates. Nitration.t Whenimmobilized,the acyl nitrateseffectmononitrationof areneswith goodregioselectiviry (6 examples, 86-lO0Eo). Rodrigues, J.A.R.,Filho,A.P.O.,Moran,p.J.S.SC29,2t6g (tggg\.
2-Acyloxy-4,6-dimethoxy-1,3,5-triazines. Esters.t Preparedfrom 2-chloro-4,6-dimethoxy-1,3,5-triazine and RCooH these compoundsundergotransacylationto alcoholsin the presenceof MgBr2. Kaminska, J.8.,Kaminski, Z.I.,Gora, J. S 593(l999). r.:
nrtriles.The
N-Acyl-N- (pentafl uorophenyl)methanesulfonamides. N-Acylation.t Amides are formed on reaction of these reagents with amines (36 cxamples,62-99Va). y Z56, 5943(2000). Kondo,K., Sekimoto, E.,Nakao,J.,Murakami,
tccnts are
Acylzirconocene chlorides. Acyl anion equivalents,t Addition of the title reagentsto enonesoccursin the 1,2mode. This Pd-catalyzedreaction provides unsaturatedhydroxy ketones.
l-Alkenyldichloroboranes
cl
Go.
Co'Zi
Alkenylsulfones. Alkenylation.: Frec cc'ptedby thesereagenL:
n CaHru
PhtvleA
CaHrz 88%
o
(R)-MOP =
? o
I Hanzawa,Y. Tabuchi,N., Saito,K., Noguchi, S., Taguchi.T. ACIEE 38,2395 ( I 999).
Alane.20,2 Reductionof phosphineoxides.tchemoselective reductionof phosphine oxidesin thepresence of sulfoxides areobserved withAlH, in refluxingTHF. 'Bootle-Wilbraham, A., Head,S.,Longstaff, J.,Wyatt,P.TL 40,526i (1999). Alkenylboronic acids and esters. 20, 3 2H-chromenes.t Condensation of alkenylboronic acids with salicylaldehydes constitutesa methodfor the synthesisof 2H-chromenes.
Ecrtrand, F..Quicler-Srrc. B
\'-A I koxycarbon;-l t trii-r1 N-Alkoxycarbonybit :hc transfer of the alkorr, Jcnvativesare readill prel
\ r.uh313. T..Nagaoka. ) . Tc
cHo + OH
(Ho)28-." R3 ll \*,
R2NH ' R - i -Z^-....'..1,a ll I
dioxane90
\AoA
R3
, c-Alkoxyalkyl)trincthyl R2
Allylamines.2 Acylium ion precursors such as carbinolamines alkenylboronates react with in the presenceof BF.,'oEt,. Benzylic amines are similarly obtained by replacing alkenylboronateswith the aryl analogues. Diels-Alder reactions,' A synthesisof 2.6-disubstituted(also more highly substituted) 3-cyclohexenolsis basedon cycloadditionwith preassemblage of alkadienolsand alkenylboronates. oxidation of the cycloadductswith Me.,No completesthe process.
Alkoxymethyl anion c :rJucc-fission of alkorrrr i.llcicnt alkenes.
Bno-SiMe3+
"/
lWang, F'inn,M.G.OL2,4063(2000). Q., rBatey,R.A.,Mackay,D.B.,Santhakum (1999\. ar,Y.JACSl2l, 5O75 rBatey,R.A.,Thadani, A.N.,Lough,A.J.JACS121,450(1999). 1-Alkenyldichloroboranes.20, 3 As dienophiles.t Thesereagentsare activein the Diels-Alder reactionat relatively low temperatures(e.g., * l0'). The adductsafford alcoholsreadily. tZaidlewicz. M., Binkul,J.R.,Sokol,W.JOMC 580,354(1999).
Alkoxycarbeniun io r()sether with Bu.NBFr{ * rth allvlsilanes and srlrI e
( iurcnb€rger. C.. Sreckhan. L \ jg':r.S..Suzuki. S..\amgm
(c-Alkoxyalkyl)trimethylsllanes
Alkenylsulfones. Alkenylation.t Freeradicalssuchas thosegeneratedfrom alkyl iodidesare interceptedby thesereagents.
c tI
lrtn O""'
?
. ? #taPh
t-Bu2O2 Phct A
o
^',,"
H
wo tl
57% (exo:endo=8'.2\
ulc oxides in
rBertrand, F.,Quiclet-Sire, B.,Zard,S.Z.ACIEE38,1943(1999).
ii\ Ialdehydes
N-Alkoxycarbonyl (triflyl)anilides. N-Alkoxycarbonylation.l Excellent leaving group properties of triflylanilides make the transfer of the alkoxycarbonyl residue to amines very efficient. Both Boc and Cbz derivatives are readily prepared. rYasuhara, T., Nagaoka, Y, Tomioka,K. ICS(Pl ) 2233(1999).
-R3 ^R,
n
Alkoxymethyl anian equivalents.t Photoinducedradical electron-transferconditions induce fission of alkoxymethylsilanes and the addition of ROCH2 groups to electrondeficientalkenes.
f..nvlboronates . obtained by
:
irighly substi,.Ladienolsand
k
, Irroccss.
t:
(cr-Alkoxyalkyl)trimethylsilanes.
r irt relatively
BnO_SiMe3+
-,1-,COOMe -l CN
P h - P h /M e C N - M e O H + CN
BnO:..2\,COOMe I CN 64%
Alkoxycarbenium ions.2 Low-temperature electrooxidation of the reagents ltogether with BuaNBFa-CH2C12)generatesthe carbenium speciesthat can be intercepted rrith allylsilanes and silyl enol ethers. Gutenberger, G., Steckhan, E.,Blechert, S.ACIEE37,660(1998). Suga,S.,Suzuki,S.,Yamamoto, A., Yoshida,l.JACS122,10244QC[l0).
Alkylaluminum chlorides
Alkylaluminum chlorides. Cyclization of alkcnylsilanes.r alkynesis effectedby EtAlClr.
Stereoselective intramolecular vinylsilyation of
.\sao,N., Shimada, T..Yamamtxr. l :Stoltz, B.M.,Kano,T..Corer.EJ I 'Ge. M., Stoltz,B.M.,Corer.t..J 0I 'Toro,A., Nowak, P, Deslongcham 'Yin. J.,Liebeskind, L.S../ACSt:l
SiMe3 trrArer-
+ cH?ct,
r-(\-4\
78.
Llln |
\/
|
l' |
Alkyl chloroformates. Phenols.t Cyclization t'f j the contextof a synthesisoi ('-rr
R
Fuganti, C.,Sena,S..tall{l ,ler9 cycloadditions. More examples of the RAlclr-catalyzed Diels-Alder reactions2r and [5 + 2]cycloadditions are shown in the following equations:
o
.'\a\zo\
o
A/. \-Al ) | i l T
cH2ct2
y'-or="
Me2PhsiV
78
Reductivebromination. _ rcagents(e.g.,isopinocampherlh
r'\,r\.ao\
^t),^) t t t l
MeAlCl2
Alkyldibromoboranes.
/---,\.
)
Alkyl (diphenylphosphono nctr (Z ) - a, F Unsuurated cslrn.rcactron)using theseestersls std rcasentsare (l) reactionof rPtrO .rlkoxycarbonylation of (PhOr-FO ,'t the methylphosphonate arr ro
ores
Me2PhSi
Kabalka, G.W.,Wu,Z..Yu.J. TL tt.
rl
V'
.rtlditionof baseto (PhO;,PtOr\lc .\ndo.K. JOC 64.8406r 1999,
-l l k1'l(3-hydroxyphenyl )diphco! Wittig reactions,t These rc rcactlon with carbonyl comF)or r!'mo\,edby base.
NIC-1lactone
-cN
f1
,pN
A,,,ot
(."'\
rr ""oo"y,-j-53,
Meooc \'^'/+T/ ;;. cH2ct223' to*v "1(v
:'oy,^-|X/,.
R=CHO
(+)-maritimol
75% TpMo(CO)2
TpMo(CO)2
6 : o.-z\
fi I I
i
ll
+ V* ll
EtArc".
;;;- -
o_\r n \{>
\/J\
R- v
hv
;i
ot)1
o'..FAR)-12
n
Ru.:c'll.M.G..Warren,S."/CSr Pr,, !{
{ Ik1'liminotris(dimethylamino ; Esters.t Transesterificatro :nrinophosphoranes. ll:rnkumiuan, P.,Verkade. J.G.J(X'a
{lk1'l methyl carbonates. ,Vethoxyarenes,t Phenoli u I)\lF. 150'). Comparingro drnr ,thcralkyl group largerthan prop; l'errrsa. A.. Selva,M.. Tundo.P. Zrd
Alkyl methyl carbonates
n; ..tl\ ation of
IAsao,N., Shimada,T.,Yamamoto, Y JACS121,3797(1999). rStoltz,B.M.,Kano,T.,Corey,E.J.JACS122,9044(2000). 'ce, M., Stoltz,B.M.,Corey,E.J.OL2,192'1(2000). 'Toro,A., Nowak,P.,Deslongchamps,P. JACS122,4526(2000). 'Yin, J.,Liebeskind, L.S."/ACS121,5811(1999). Alkyl chloroformates. Phenols.t Cyclization of 3,S-alkadienoic acids is readily effected, particularly in the contextof a synthesisof C-aryl glycosides. rFuganti, C.,Sena,S.Sf 1241(1999).
dr::Jrctions2l
Alkyldibromoboranes. Reductive bromination.t Aromatic aldehydes are converted into ArCH2Br by these dibromide)( I 2 examples,65-87Vo). reagents(e.g.,isopinocampheylboron G.W, Wu,Z.,Yu,J. rL4l,5161 (20N). Kabalka, Alkyl (diphenylphosphono)acetates. (Z)-or,pUnsaturated esters.t The condensationwith aldehydes(Emrnons-Wadsworth reaction) using these esters is stereoselective.Two convenientpreparativemethods for the reagentsare (l) reaction of (PhO)zP(O)Hwith bromoaceticesters in dichloromethane,(2)
: TES
I
.
.'-a-y' I _ Yl " .\n f
_{'v
(_., la^e
alkoxycarbonylationof (PhO)rP(O)Me with CICOOR. In the latter protocol, becauseanions of the methylphosphonateare very unstable,the acylating agents must be present before additionof baseto (PhO)zP(O)Me. .{ndo,K. IOC 64,8406(1999). Alkyl(3-hydroxyphenyl)diphenylphosphonium salts. Wittig reactions,t These reagents are water soluble. Product isolation from their rcaction with carbonyl compounds is also facilitated as the phosphine oxide can be removedby base. M.G.,Warren,S.JCS(PI ) 50-5(2000). Russell, .\ l kyliminotris(dimethylamino)phosphoranes. Esters,t Transesterification using enol esters as acyl donors is catalyzed by the rminophosphoranes. P, Verkade, J.G.JOCU,9063 (1999). Ilankumaran,
+ ,-aritimol
- -l-\
^-
- --\-\
Alkyl methyl carbonates. Methoxyarenes.t Phenols undergo O-methylation with methyl carbonates(K2COjI)\tF, 150"). Comparing to dimethyl carbonatethe unsymmetricalcarbonateswith the , 'ther alkyl group larger than propyl can be used in an open flask. A., Selva,M., Tundo,P, Zordan,F.5L272 (2000). Pcrosa,
I -Allylb€nzotriazole
I -Alkyl-3-methylimidazolium
salts. Reaction media- The low-melting salts (ionic liquids) are now routinely employed as reaction media. 1-Butyl-3-methylimidazorium tetrafluoroborate and hexafluorophos_ phate are particularly popular. Besides those described in various sections of this volume, their use in the Ni(acac)r-cataryzed autoxidation of aromatic aldehydes,r reduction of aldehydeswith BujB,2 wittig reactions,3 Diels-Alder reactions4-uy u" mentioned. Many reactlons are acceleratedand the workup procedure for most of them is facilitated. By using (PhH)aRuoBFaas catalyst, the hydrogenation of arenes in reacilon media containingionic liquid and water has been described.5 Friedel-crafts and related reactions conducted in a dialkylimidazolium haloaluminate appear in increasing frequency. The sptitting of ethers with simultaneous acylation to afford alkyl benzoatesis a recent example.6 IHowarth,I. TL 41, 6627(2000). 'Kabalka, G.W.,Malladi,R.R.CC 2191(2000). rl-e Boulaire, V, Gree,R. CC 2195(2000). aFischer, T., Sethi,A., Welton,T.,Woolf,J. TL 40,793 (1ggg). 5Dyson, P.J.,Ellis,D.J.,parker,D.G.,Welton,T. CC 25'(tr)gg). 6Green, L., Hemeon, I., Singer,R.D.Zt 41, 1343(2000). Alkyl methyt sulfides. Pauson-Khand reaction,t The surfides have catalytic effects on both rntramore_ cular and intermolecular version of the reaction. rSugihara, T.,Yamada, M., yamaguchi, M., Nishizawa, M. 5L771 (rg9g\.
,rN--'{
G"
Rrrntzl\..{R.ScrJr
{llrlbomn
rtageots. Hommllylic anit :::lmc'thrI v lr Itrenz:Jdr Reaction tirt at ::tc .uh\tratL'\Sothat n
-q"
R = H
R = M N-Alkyl trifluoroacetaldehyde imines. Fricder-crafts reaction-t r-Aryr-2,2,2-trifluoroethylamines are readiry formed from the Lewis acid-cataryzedreaction of cF,cH:NR with activated arenes (e.g., indole).
$Pentcnok. \lL : :hc adductsgtrei l-q
rGong,Y.,Kato, K., Kimoto,H. SZ l05g (2000). Allylbarium reagents. Preparation, I The suitabre form of BaI2 for reactron with ailyilithiums is obtained from stirring Ba with 1,2-diiodoethane in ethercontarningNa2S"Oa. IDuval,8., Zoltobroda, y. TL 41,33:.(2000\. G.,Langlois, I -Allylbenzotriazole. 2-Alkyl-1,3-butadienes-.r This reagent undergoes alkyration at the ct-position. By reaction with trimethylsilyl chloride, a valuable four-carbonbuilding block is obtained. The latter compoundon further alkylation and pyrolysrsgives 2-arkyl-r,3-butadienes.
i :
, ;-Alll I tbromorri
(n-Allyl)bromotricarbonylruthenium(I)
/N--N
z N - -N
rr
rl
#d*?.,,",#./ 6r--',
lf i"\.d t"f h,rs',.LrDfC. :t: ,n of I \l riny
rKatritzky, D., Wang,X. JOC 64,1888(1999). L., Toader, A.R.,Serdyuk, l:ll!'dla
u n rl l l a t e a : : ,' l l t O
Allylboron reagents. Homoallylic amines.t
Water is critical in the asymmetric allylboration of Ntrimethylsilylbenzaldimines with B-allyldiisopinocampheylborane. Reaction with alkcnyl epoxides.z The Lewis acid nature of the boranes is felt by the substratesso that rearrangementoften precedesallylation'
.6^.Y( .f OH
g" f
(
R
l\.eee, NaOH - H2O2
t : . 1n 1( ) l c -
R = H (78%)
R = Me (817o)
: , , tt t r e d lc. tC.8.'
9
9
0
'
3
.
:
4
:
b
4
.
1
4-Pentenols.3 Alkenes undergo allylboration with allyldibromoborane. Oxidation of the adductsgives 2-substituted4-pentenols.
y'\,aa'2; e ' \ +NaOH l - H2o2
ft. R\,.On
;terned
P.V.,Brown,H.C.ACIEE3S'825(1999). Chen.G.-M.,Ramachandran, :Zaidlewicz, M.P.OL2,3897(2000). M., Krzeminski, 'Frantz, D.A.OL 1,485(1999). D.8.,Singleton,
; r i i ' , t lB .y ,'.r.rined. ci:a\.
t n-Allyl)bromotricarbonylruthenium(I). cyclopentenones.t A 12 + 2 * llcycloaddition involving an alkene, an allylic carbonate,and carbon monoxide occurs under the influence of the Ru(I) complex'
AllylPallailium
comPlexes
Biaryk.: UnsYmmetrical hr rnvolving Art and terahutllet bi s(allYlPalladiumchloridet'
co .
\.-1/
//
,'\ ll
*
(q3-caH5)RuB(co)3 r
ll
t MeOOCO
A.. Koshino.H'. \aliata- T ( / Satake. :\lowery.M.E..DeShong. P tOC g-
Et3N/rHF 12o"
\12-
Alll'lsamarium halides. Allyl selenides.t Allllsarnel RSeCHICH{H1 (7 examPles't
T' OL 2'949 QOOO)' I Morisaki' Y , Kondo' T'' Mitsudo'
Coniugate addition to niod
'Tffi::'*:1_T:?)Tl?3?T;llil,Ii,",I:i.il:: nrvrN'hvf Y:HlJff to Cleft'l^t,"l"r;ethane' ascatalvst' (Thiolsareoxidized *. ;"*il;'-bu'toort in dtcnt IBu'SnH-(Ph:P)'Pdcl2-HoAcl il;;;;;" isolation') foreasY itt"toott ,i. (1999)' A' T 55' 6931 A'' Guibe'F ' Loffet' r6i6bonguila,A'M , Merzouk'
Huang.Y.,Chen'R. SC$' ll-5 ' :fi :Bao.W..Zheng,Y..Zhang.\' ,f(-R'!
Alll'lsilanes. Allytations. OPening of un ro the order of addition of the rc1
are formed' Allvlnickel bromide' and heterocycles ilienes'tCarbocycles of Ctclization
CoHrs
.,\
O t ^
r-Z
-T\
[(-n,",1, /-]"
^*;;i ,)-\
T i C l a ;4 ' S l
64Yo
T'V' rRadetich,B', RajanBabu'
LF:v;
/
{,SiMq
(1998)' JACS120' 8007
^**Til;;'#l:"fucomgtlx l:T:1 ::: meoti;1":#:iiH':T:l'T]:1""'"'I; and 2-t2-nvridvl)imidazole ;;;Ro *.":;ff allYlacetates' with acetals
rr
Allylation of nascentI-tos-l :nrred with TsNH2, SnCll. ard :rom imines in the Presencec :r'placementof allYlstannar't r ..itron of aldehYdesaffords hom
ilYl tProPt l. 3-B i s(trimethYls ;onesponding ProPYne.ls us'
A'
.rlanes.5
Pd
Anonc 1
Meo..,r,oSiMes
/:N:
NAOAC.DMSO
\/
,*\
\r /1*)
CooMe
)
)
\rcooMe
+ ( 2 3 :1 ) 95%
l
\,,'
l
ueasif SiMe3
+ \
Allylsilanes
l1
Biaryls,2 Unsymmetrical biaryls are formed from a cross-coupling reaction involving fuI and tetrabutylammonium triaryldifluorosilicates. The catalyst is bis(allylpalladium chloride). rSatake, A., Koshino,H., Nakata,T. CL 49 (1999). 2MoweryM.E., DeShong,P . IOC 64,3266(1999).
n RSH and r ,.rt.tlyzed ( \;Jlled
to
Allylsamarium halides. Allyl selenides.t Allylsamarium bromide reacts with alkyl selenocyanatesto- give RSeCHTCH4H2 (7 examples,87-9 5Va). Conjugate addition to nilroalkcnes.z 8,e-Unsaturatednitro compounds are formed. rHuang, Y.,Chen,R. SC30,3775(2000). :Bao,W., Zheng,Y.,Zhang,Y. JCR(S)732 (1999).
Allylsilanes. Allylntions. Opening of unsymmetrical acetalsproceedsregioselectively according to the order of addition of the reagentand catalyst.l
CeHre
1 " "
o,,\^ \ z"
-T-
Y"
TiC[; Z\,SiMe3 {.SiMe3;
)r-..1!r hy treatr: i.tcne silyl
, 1 -
,,_)
CoHrs
poHrs
+ cH2cr2
1 ' . 9 1
TiCla
Allylation of nascent N-tosylimines is observed when the carbonyl compounds are mixed with TsNHr, SnClr, and NCS,2 while chiral homoallylic amines can be obtained from imines in the presence of a rr-allylpalladium catalyst, the advantage being the replacementof allylstannaneswith allylsilanes.rWhen YbClr is used as catalystthe allylation of aldehydesaffordshomoallyl silyl ethers.a 3,3-Bis(trimethylsilyl)propene, which is available from semihydrogenation of the corresponding propyne, is useful for the preparation of (E)-P-hydroxyvinyltrimethylsilanes.s
COOMe
MeeSi-1- *r | SiMeg
OH -'\"-
-cHo+ "' ' -
versigz-.-1=-,, -\2
cHzclz _60. _ _20" S4To
Allylsilanes
For allylation using allyltrichlorosilanes, a new protocol consists of AgOTs and DMPU.6 The chlorinated silanesreact with benzoylhydrazonesand tosylhydrazonesreadily in DMF. therebyopeningup an expedientroute to homoallylic amines.T Reactinn with oxygen heterocycles. l,2-Dioxolanes and tetrahydrofurans are formed from reaction with ozonides8and epoxides.erespectivelv.
Me3si..-1 -
^-o
z----r
LXv
)
sncra
-;;
^-O
Y
/-1
V
ue3si=,r-./\J
| 6" - u-
\
6,10/o
Reaction with benzotriazol-l-ylmethylamines.4-Silylmethyl-1,2,3,4-tetrahydroquinolinesrO and 4-chloropiperidinesrr are the products from Lewis acid-catalyzed reactions of allylsilanes with N-aryl-N-(benzotriazol-1-yl)methylamines and the N,Nbis(benzotriazol-I -yl)methylamines, respectively.
[ ' - : e m r \. . l r l r 1 1 q l t \lr.ureme- \ . T.**r- J . \iiemurt- K . \.r'ilrn
l'cr.\.\\'at\rn.JG h-rct. Il ..\n.cinr G ('.--l:rtkr. I . heru-i. ii i.rr r.hr. S . llrrahrrl . r . - . r l u , rP . ll. [:;_ \ , \-i::i.\.Krmure-\ I \r::-:.zi\.\R.('r \ \r:::ri\. .\ R . Lu. Z P::r Z -ll . \\ivrpi. I i : ' . : . L \ l . S m : t hJ D
llllklennrncs. .4lhlations. .;-:J.
{ll:
Ttrr'rt.r1r(rt,
l.rjl\;1rrrt!-. rra a ftr
N-1\
ni:*\z * frrfeaSi...",,iJ
(** c{2ct2
)^-
-78
a\
A
'vf
i
c 8SYo
\-)
[3 +2]Cycloadditions.t2 Certain allylsilanesbehave as 2-silylated 1,3-dipolesin the presenceof Lewis acids. Their reaction with unsaturatedcompoundsleads to fivememberedrinss.
l{.'rn 'irtri
allr larr
r-B\ ,'rtr B o-Lctoriacs. .{
:.1:-:A 3\ !'mPlo\ lng n
CISO2N=C=O
-{
si(cHPh z)Mez
Me2(Ph2HC)Si,,J,
Na2so3
L-^: \18\ ..1,;1rrell1 " (:. ::k- rr-\ctrralxjorl
/'r'\o H
e . C C Hydroxypentenylation,t3 Sequential delivery of two substituents from Si to an acetal function accomplishesthis chain extension.
-s OMe
pnAoHl" *
o'Si'-tt\
)
BF3.OEI2 | CH2C!2
KF tH2O
OMe OH
Ph.J\,\,,,\ 77Yo(syn:anti 62:38)
/ ' \
Allvlstannanes
\gOTs and h
.r,zrrfl€SI€&d-
!
rl
: , , l u r a n sa r e
.l :l tctrahydror..,.:J-catalYZed r'. .::rtlthe MN-
rEgami,Y., Takayanagi,M., Tanino,K., Kuwajima,l. H 52,583 (2000). rMasuyama, Y., Tosa, J., Kurusu, Y. CC 10'15(1999). rNakamura, K., Nakamura, H., Yamamoto,Y. JOC 64,2614 (1999). aFang,X., Watkin, J.G., Warner, B.P TL 41, 447 (2000). i Pnncet, B., Anselme, G., Pornet, I. SC 29,3329 (1999). 6Chataigner,1., Piarulli, U., Gennari, C. TL 40,3633 (1999). rKobayashi, S., Hirabayashi, R. "IACS 121,6942 (1999). f Dussault,PH., Liu, X. TL 40,6553 (1999). ' Sugita,Y., Kimura, Y., Yokoe, L TL 40, 587'7(1999). r{)Katritzka, A.R., Cui, X., Long, Q. SC 36, 371 (1999). I I Katritzky, A.R., Luo, 2., Crt X. JOC 64, 3328 (1999). , lrPeng,Z.-H., Woerpel,K.A. OL2, 13'79(2000). r r F r o s t L, . M . , S m r t h ,J . D . ,B e r r i s f o r dD , .J.TL40,2183 (1999).
Allylstannanes. Allylations. Allylation of aldehydeswith tetraallyltincan be conductedin ionic liquids.rThereactionofbifunctionalreagents containingallylstannylandsilyl groupswith 1,2-diketones pathwaytakesplaceat thetin end.2 via a photoinduced electron-transfer
o * eu:snl'\sit'ter
,n\tn
-l*"
en\]
sirr,r".
o 90Yo
lc..
i dipoles in
n.:.
-,tds to five-
Homolytic allylation of alkenyl iodides with allylstannanessis catalyzedby either AIBN or EhB. a-Ketoximes, A three-component assemblage of c-ketoximes via a free radical pathway employing RI, CO, and RSO2CH:NOBz is initiated by allyltributylstannane end AIBN. Actually, introduction of another alkyl iodide at the end changesthe products from the cr-ketoaldoximebenzoatesto ct-diketonemonoxime derivatives.a
/ \^
R r + c o . Ir. ::,'ln Si to an
Ph-^.-\..-OBz
d \ ^
4*snBu3 AIBN / PhH ^
R..rr.z^'r:" -oBz i l t 5
/N"
Ts N
I
.
\
t.: a2 38)
,t
+ co + \
t.\,..i-
.oBz
4\.snau' AIBN / PhH ^
"_\..z
N
bet
t4
Alumina
I'actones.s carbonylation of radicals derived from ("y-, 6-, e-) iodoalkanols is followed by a back-transfer of the iodine atom (net insertion of co to the c-I bond). The subsequentlactonization is an ionic process,therefore Et.N is required.
\.nrltrtxr.
Frr.\r
if !c:rr lhr;ll-37.ra*
a*
i:* vttrj
rrn alurmna'
'.r
R
,Iu"f,*'. "o -
y'\t
snau,
A|BN / Et3N
c F vJi:s\: ra..r. .r:::; (i .-.'r:; (l
*.-4.**' \o
hexane 80"
n =1 , 2 , 3
Fa-tr F Jra R.lu:ru:r S. \lu::rrr. I .S Ca.n5.tl -S G.cc l{
47-91Vo tlnminum-
rGordon, C.M., McCluskey , A. CC l43l (lggg). 2Takuwa,A., Saito, H., Nishigaichi, y. CC 1963 (lg9g). 3Miura, K., Sairo,H., Itoh, D., Hosomi, A. fL40,gg4l (lggg). aRyu, L, Kuriyama, H., Minakata, S., Komatsu, M., yoon, J.-y, Kim, S. ,IACS l2l, l2lg0 Oggg\. sKreimerman,S., Ryu, I., Minakata,S., Komatsu,M. OL2.3gg (2000).
Rcdtctions. '
--':e'q11 -r-!: .:rnrlrl t
,\Jt
rn-r1rl Cr-rtlltX
i'rcrnrnl
rerjrr.l . ' " ! - - a . : : . t l - K F i r - ,{
Allyltriethylgennane.
Ra.:^::, n ,,i ercrr 'u:J \: ; rteu fffjl
Homoallylamines,t A chemoselective reaction with imines without affecting aldehydes can be achieved with cH2:cHcH2GeEt. in the presence of BF.,.oEt, and HoAc in MecN at 0o. Bronsted and Lewis acids activate the imine substrates.
tldthda t fra . r'.=1t.at,,einichrd
rAkiyama, T., Iwai,J.,Onuma,Y.,Kagoshima, H. CC2lgl (lggg).
LVxdt
agctttg-
:-r r ,l'. r:ti
.l\r. chl
Allyltris(2-methoxymethoxyphenyl)phosphonium
bromide. 7,3-Dienes,t The wittig reaction with this reagent with aldehydes affords conjugated dienes with high cls-selectivity (averaging 96:4). However, yields are moderatedue to steric congestion of the transition state.
(
A
>
(o"" \.,\,,,\,/CHO
+
--Jo
t( w
Ff" tl. l
\ ri"t { r ^l
BuLr/ THF --;:*
B r \
-
i}e.::
Llrrr:r. ..*d.
\l r"
,
9 8 Y o( Z : E = 9 6 : 4 )
'Wung, El KhouryM., Schlosser, M. CEJ6,420(ZOOU. Q., Alumina. N'Alkylation,t been reported.
Gas-phasealkylation of amines with arcohols over "y-alumina has
oxidations. Dramatic improvement has been claimed in handling aluminasupported Mno2 for oxidation.2 Potassium ferrate deposited on alumina can be used to remove a terminal [CH2O] unit from propargylic alcohols.s
' t -
_ L : ,
rh
\
,rI. \l
: r
llrr
lil-r
[ t \
ff.r_-J__:f,&
rflu:".ict:r! \f
:r\(i
j (-:
!q--
clridtfl.F a.yu. Itz*f4 nln
fl:'',
-r
\l
T
:ia
ir"r
!r- :'u-J
\ 5
[nr-:
!.r: iarr
\l
i.1^--
ll trt nz :
Aluminum chloride
!:
,elkanolsis (--I bond).
15
Nonaqueousproceduresfor oxidation of mandelic estersaand the cleavageofp-nitrophenylhydrazonesand semicarbazonesinvolves treatmentwith ammonium chlorochromate adsorbedon alumina.s Valot,F.,Fache,F.,Jacquot, R., Spagnol, M., Lemaire,M.TL40,3689(1999). :stavrescu,R., Kimura,T., Fujita,M., Vinatoru,M., Ando,T. SC 29,1'r.19(lggg). 'Caddick,S.,Murtagh, L., Weaving, R. Zt 40,3655(1999). rZhang,G.-S.,Gong,H. SC29,3149(1999). 'Zhang, G.-S.,Gong,H.,Yang,D.-H.,Chen,M.-F.SC29, 1165(1999).
I
-,r(1999)
Aluminum. Reductions. Aluminum with NH4CI in methanol reducesnitroarenesto arylaminesr on ultrasound irradiation. on the other hand, Al-KoH induces hydrazoareneformation.2 Under similar conditions (Al-NaOH) reductive dimerization of araldehydesoccurs.3 concerning reductive dimerization in aqueous media, it is interesting to note that changingAI-KF to Al-FeF2 system causesreduction to ATCH2OH only.a Reduction of arenesby Al in ionic liquids is efficient. For example,pyrene is fully saturated(847oyield) and 9, lO-dimethylanthracenegives the 9, l0-dihydro derivative (8lvo).5 Aldehydes from nitroalkenes.6 By using Al-NiCl2.6H2O in THF, nitroalkenes are convertedinto aldehydes(9 examples,60-88Vo). Epoxide opening. Aluminum and an organomercury chloride mediate reaction of !'poxideswith acyl chloridesto furnish estersofchlorohydrins.T ^l
r(
Jcs affords r relds are
A Phl'
cl')rR o .
3
-
pr.rl-r-,.o-rr
R tl
o
-"'ove 9Hscl
96% \rgaraja, D., Pasha,M.A. TL 40,7855 (1999). Xhurana,J. M., Singh, S. JCS(PI) 1893(1999). Srhade.D.A., Kawaji, T., Sawada,T., Mataka, S., Thiemann,T., Tsukinoki, T., Tashiro,M. ./CRiS) :lr)(1999). l-r L.-H.. Chan,T.H. OL2, lI29 (2000). tJams, C.J.,Earle, M.J., Seddon,K.R. CC 1043(1999). 3czbarua,M.S., Bez, G., Barua, N.C. Ca 325 ,1999\. l - : z z r o .F . A . ,B o b b ,R . A . 2 5 5 , 1 8 5 1( 1 9 9 9 ) .
aas c: '.-.rluminh r..i.:ng aluminani ,.rn bc usedto
{fuminum chloride. 20, 12-13 Deprotection. Ethers are cleaved with AlClr-NaI without solvent.r Friedel-crafts reactions. Phenylsulfenylation is conveniently canied out using N-r"'nr lthiophthalimide.2 Acylation of benzodioxin derivativesrin the presenceof Alclj-)\1.'\ without solvent is regioselective.This complex behavessimilarly to Alcl3-DMSo .:J AlClI-DMF.
Aluminm
r!rr*
I,o--o,r
--+
r
4oAcooMrrcr3-DrvA
f
ll
(Y"l I
.f' ^oAcoor "
VoAcooMe
o (15 : 85) 97%
Formylation of ferrocene can be accomplished by reactlon with triethyl orthoformate in bromobenzeneat room temperature(92% yieldl.4 Somewhat lower yields are obtained in benzeneor dichloromethane. Reaction of areneswith phCCl, in an ionic liquid ( N-butylpyridinium chloroaluminate)givesdiaryl ketones.. Rea*angemenrs. Anl surfonatesundergo Fries-type rearrangement when exposed to .'\I6-1,-t na, - undc.rmicron.aveirradiation.6 -\ l.rmal o ->c migration of an oxymethyl group to afford spirocyclic productsTis rr'.rlrzedhr erposing dibenzodioxepinsto AlCl. Other Lewis acids are less efficrent.
IGhiaci, M., Asghari,J. SC 29. 9?.r , 2Suwa, S., Sakamoto,T., Kikugar:_, 'Suarez. A.C.TL40.3523 r ld9, aTang,J., Liu, X.-F., Zhang, L.-) . )t, )Rebeiro, G.L., Khadilkar, B.Il. SC J 6Moghaddam, F.M., Dakamin. It.G j TColeman, R.S., Guernon,J.M.. Roh oMa, S., Wei, e. EJOC 1939 (20m, 'Song, Y.-S.,yoo, 8.R., tre. G.-H . Jr roSudo, T., Asao, N., Gevorgyan.\.. )i " Lee, C.W TL 40, 2461 (199q ',xi,z.,Li,P. A C I E E 3 9 , 2 9 5 0( t m ,
Aluminum hexafluoroantimooe plactones.t Acidchlondc
o\ct R R
-{-l&R /:/
L-
o''''-*-A H cH2c'2 RR
\$-/--
b...-J-
R = Me
gSYo
Hydrosilylation.e''' Traditional methods of hydrosilylation involve the use of transitionmetal catalysts.However,Lewis acidssuch as Alclr also show such reactivity. Diels-Alder reactions.tt Addition of Alcrr to r-ethyl-3-methyrimidazolium chloride forms a chloroaluminate ionic liquid. This substance acceleratesand enhances the selectivityof Diels-Alder reactions. cyclopentadienes.t2 Replacement of the metar moiety of zirconacyclopentadienes that are readily available from alkynes by the [RCH] unit of an aldehyde is accomplished by an AICIr caralyzedreaction.
Aluminum tris(2,6-diphenylphco AAolreaction o,p_Unsaru condensation with phCHOat the11
t
l
\z\ l_
^,-\,/ r (
.ZrCp2 + \ R
R Atcl3
R'-CHO
K.
R l
ll >-R'
R--Y
R
-
-\-"--\rcHo
l R i
I H\-,
rNelson, S.G.,Wan, Z.,peelen,T.J.. Sp
2-chloroallyl sulfuxides.s Allenyl sulfoxides undergo addition of HCr in the presenceof AlCl.-HrO.
K
*
|
r
-\,.\-\ I cHo
a-Alkoxybutylation.2 A rela1.r of enolatesin THF-toluene mrxture. .
Aluminum tris(2,6-diphenylphenoxide)'ATPH
-_r) /'aAcoolt'tu
t7
rGhiaci, M., Asgharl,J. SC 29,973 (1999). 2Suwa,S., Sakamoto,T., Kikugawa,Y. CPB 47,980 (1999). 3Suarez,A.G. rL 40, 3523 (1999). aTang,J., Liu, X.-F., Zhang,L.-Y., Xu, X.-L., Zhang, P.-R.SC 30, 1657 (2000). sRebeiro, G.L., Khadilkar, B.M. SC 30, 1605 (2000). 6Moghaddam,F.M., Dakamin, M.G. TL 41,3479 (2000). TColeman,R.S., Guernon,J.M., Roland,J.T. OL2,271 (2000).
8Ma,s.,wei,Q.EJoc 1939(2ooo). eSong, LN.OM18,3109(1999). Y.-S.,Yoo, B.R.,Lee,G.-H.,Jung,
e:::. ,)(hoformate \:. .:- ,rrcobtained
IoSudo,T., Asao, N., Gevorgyan, V., Yamamoto,Y. JOC 64,2494 (1999). I rLee, C.W. TL 40,2461 (1999). t2x| 2., Li, P.ACIEE 39, 2950 (2ooo).
r. .. r. ehloroalumi1 ; ' ' . r h c ne x p o s e d s r . , . r i p r o d u c t siT .- -'tlicient.
Aluminum hexafluoroantimonate. plactones,l Acid chloridescondense to give B-lactones. with aldehydes
oY"'
+
O tt ,{
Al(SbF6)3 / i-Pr2NEt CHzClt 25i
-
H- \.,-\-.
Vo L-l
9rn
HN
93Yo I Nelson,S.G.,Wan, 2., Peelen,T.J.,Spencer,K.L. TL 40, 5635 ( 1999).
r HCI in the rr. .rc the use of p., ..r'h reactivity. -:::-t:r Iirnidazolium a:.::-'.irfldenhances
ATPH. 20,14-15 Aluminum tris(2,6-diphenylphenoxide), in the carbonylcompoundsshowregioselectivity Aldol reaction a,B-Unsaturated with PhCHOat the1-positionafterenolaluminationwith ATPH.I condensation
;^,*Til
-(---J=rcHo
^a-
63yo
. .lopentadienes o:r.1L\.:- :. llccomPlished
A-^-\
ATPH ;
84To LDA,PhCHO
cHo a-Alkoxybutylation.2 A relay attack of epoxides has been observed in the reaction of enolatesin THF-toluene mixture. The coordinatedTHF is involved.
IE
1-[c'(Amino)arylmethyl]benzotriazoles
Ammonium molybdate. a-Ketols.t Epoxides are co at room temperature(l I examplc
o
*Jl-/*' t ^ \r"-\.''""
LDA' THF
| R,\'--R'
orr" (^\1" V
oh t 4) \-Pt.
I Ismail.N.. Rao.R.N.CL 841rll-::r. Antimony.
o'
admixture of ATPH with Addition to aromatic nuclei,3 complexes formed upon fucoclaresusceptibletoattackbynucleophiles(e.g.,enolates,/-BuLi)atanucleal position.
" oo^"ffi)co^".od oH
cr
o'.r
v
15To
43Yo
.{l Homoallylic alcohok. mediatedby activated Sb-KF Li. L.-H.,Chan,T.H.rl 41.5ffic ': Antimony(V) fluoride. Carbonyl chloride fuoridc. rreatmentwith SbFs.
K.O.JFC9l, lrr' Hoge,B.,Christe,
A rcnediazonium o -benzeoedis Aryl halides,' Decomprxrt emmoniumhalide furnishesan I
rsaito. S., Shiozawa, M., Nagahara' T', Nakadai, M"Yamamoto' H' "/ACS 122'7841 (2000)' 2saito. S.,Yamazaki,S', Shiozawa,M., Yamamoto,H' Sf 581 (1999)' rSaito. S., Sone,T., Murase, M., Yamamoto, H' 'IACS 122' 10216 (2000)'
Aluminum tris(2,6-diphenylphenoxidelalkyllithium' are ^y-stannyl ketones2derivedfrom cycloalkenones Fragmentation 1-Iodor and areamphiphilic' ketones.The reagentcombinations convertedinto unsaturated
I '
ATPH / BuLi
-
PhMe - Et2O
a-'/ I
w
o 93% rKondo,Y., Kon-i, K., Ooi, T., Maruoka, K TL 40,9041(1999). K. ACIEE39,414(2000) rKondo,Y, Kon-i, K., Iwasaki' A., Ooi, T', Maruoka.
1-[ot-(Amino)arylmethyl]benzotriazoles with these feagents to Aminobenzylation of phenols,t Sodium phenolates react
Blrbero.M., Degani,1..Dugherr"S
{renesulfonic acids. .Vannich-typereaction. S j\c!-llent catalystsfor the con&o
4>'u.OMe * PhcHo + ll \z
NHz
furnish Mannich-tYPeProducts. IKatritzky,A.R.,Abdel-Fattah,A'A.A',Tlmoshenko'D'O''Belyakov'S'A''Ghivirigia'I'Steel'PJ' JOC 64,601r (1999).
\l:nabe. K.. Mori. Y. Kobava-shr. S
Arenesulfonicacids
Ammonium molybdate. a-Ketols,t Epoxides are converted to ketols by ammonium molybdate tetrahydrate at room temperature(l 1 examples,92-96Vo). rlsmail,N., Rao,R.N.CL844(2000). Antimony.
L
\TPH with l a nuclear
Homoallylic alcohols.t Allylation of carbonyl compounds in aquebus media is mediatedby activated Sb-KF. rLi, L.-H.,Chan,T.H.rt 41,5009(2000). Antimony(V) fluoride.
-.,
oH
\. \a\" tl 15o/o
Carbonyl chloride fluoride.t treatment with SbF5.
Phosgene exchanges one of its chlorine atoms on ffr'
fil
lHoge,B., Ch-riste, K.O.JFC 94,107(1999). Arenediazonium o-benzenedisullfonimides. Aryl halides.t Decomposition of these salts (1) in the presence of a quaternary ammonium halide furnishes aryl halides.
n , o ""dirr\
,.. .r,kcrrones t
_
N lt ArN,* -ls:--'.9) o- \b (1) Barbero, M., Degani,I., Dughera, S.,Fochi,R. JOC 64,3448(1999). Arenesulfonic acids. Mannich-type reaction,t Sulfonic acids bearinga long chain (e.g., dodecyl) act as !-\cellentcatalystsfor the condensationin water.
:r:--e reagentsto
l,.J. . .t e e P r . : . : : . r . 1S
\lenabe, K., Mori, Y., Kobayashi,S. Sf 1401(1999).
20
B-(2-lvido-2-propenyl)-1,3,2-dioxoborinane
Arylboronic acids. Glycosylation,l The glycosylationof unprotectedsugarscan be accomplished whentheyareactivatedby arylboronicacidssuchas L.
Z\X o l l l ott')t\
Barium permanganate.
H
Oxidation,t Solvenrthis reagentor MnOl.
'ry
rFirouzabadi, H., Karimi.B . Al
(1) Benzenesulfenyl chloridcN-Arylimidazoks.2 complex in the air.
Arylation of imidazoles is efficiently catalyzed by a copper
Cyclnpropane ring q regioselectivityof ring open
rOshima,K., Aoyama,Y. JACS121,2315(1999). 2Collman,J.P.,Zhong,M. OL 2, 1233(2000).
Il /\
Arylp-nit to theiraryl estersby thesereagents. aminoacidsareconverted Aryl esters.t Protected rPudhom, (1999). T. TL 40,5939 K.,Vilaivan, 2.3-Azetidinediones. with aminesgivespeptides. Pepti.des,t Reactionof theheterocycliccompounds
o\-.R' ^Jf,
tJ
ETOOC'
-oMe 'OM.
PhS PhS(
Graziano, M.L.,Iesce.\l.R . C
3-Benzenesulfenyl-2-(N
l' +R"NH2+o'1^rr* NHR"
R
rAlcaide, B., Almendros, P., Aragoncillo, C. CC 757 (20OO).
1,3,2-dioxoborinane. B -(2-Azido-2-propenyl)Allylation.t The reagentreactssmoothlywith aldehydesto afford azidohomoallyl alcohols. Tanaka, T.,Azuma,T., Fang.\
(o-?t"z \v,o
lNs; DBU
/o'
I
?.Y o N .
RCHO; NaOH - H2O2
YY
OH N.
.V-Benzenesulfenylsuccinil Sulfenylation. I Acr lsr
Ketonesgive low yields und 'Salunkhe,A.M., Ramachandran, P.V.,Brown, H.C. TL N, 1433 (1999).
Huang, C.-H.,Liao,K.-S..Dc.
rr. ^J :lccomplished
Barium permanganate. Oxidation.l Solvent-free oxidation of allylic and benzylic alcohols is possible with this reagentor MnO2. rFirouzabadi, H., Karimi,B., Abbassi, M. JCR(S)236(1999).
93.r..'J by a coPPer
Benzenesulfenyl chloride. Cyclopropane ring opening.r regioselectivity of ring opening.
ens, /
I / \ O M e +
ETOOC"'46y" ilf:. 5\ these reagents.
Reaction conditions have great influence on the
ETOOC
Phscti cct4 PhSCI- py lCHzClz
bOOUe
PhS +
Etooc".,XcooMe
1lYo 7SYo
5SYo 0Yo
rGraziano, M.L.,Iesce,M.R.,Cermola, F.S 1944(1999). ts. * ..\ peptides 3-Benzenesulfenyl-2-(N-cyanoimino)thiazolidine. Sulfenylation,r Ketones and amines are sulfenylated with the reagent I under very mild conditions.
.-S.
I- N . FNCN SPh .i:: :.1ezidohomoallyl
(1) N. Sf 33 (2000). Tanaka, T.,Azuma,T., Fang,X., Uchida,S.,Iwata,C.,Ishida,T.,In,Y.,Maesaki,
F.
^( N3
.V-Benzenesulfenylsuccinimide. Sulfenylation,r Acylsilanes and aldehydes undergo acid-catalyzed a-sulfenylation. Ketonesgive low yields underthe samecondsitions. Huang,C.-H.,Liao,K.-S.,De,S.K.,Tsai,Y.-M.fL 4l,39ll (2ON).
Benzenethiol
Benzenesulfonamide. N-Benzenesulfonyl al.ilimines.r Aldehydes are readily converted to ct-tosyl sulfonamides by reaction with PhSO2NH2,elimination of TsH is accomplished with NaHCOT'
NHSOzPh
Tolso2Na PhsozNHZ
R_CHO -
HcooHi H2o
R'
N.so2Ph
NaHCO3
-r-- S O 2 T o l
*rl
rChemla,F., Hebbe,V, Normant, J.-F.S 75 (2000).
Benzenethiol. 16, 327-329; 19, 19; 20, 20-21 are Thioimidi.c esters.t These estersare convenient precursorsof amidines and they preparedfrom nitriles and PhSH in the presenceof HBr' Hydration of 3-aryl-2-propynols.2 Alkenyl sulfides are lormed as intermediates and these undergo hydrolysis with sulfuric acid in EtoH to afford a-ketols. Michael-aldol reaction tandem.3 Addition of lithium benzenethiolate to conju-
Deoxygenation ol silaneswith retentiono The reagent attacks tlx very bulky (e.g..r-buty Ckavage oI aryl cleavedunder nonhldrt
reactive.T o-Aminotrnu
gated esters in the presence of aldehydes is followed by an aldol reaction in a stereoselectivemanner.
o ? t pnAH. foo
o H O PhsH / cH2c12
en\{o PhS/
p-Methoxybenzyl
t
is valuable when orrd:
80% (syn : anti 92:8)
had been reported pnr alone.
Dechlorothiolation.a Activatedtrichloromethylgroups(e.g.,in Rcocclr) are conand verted to the benzenethiomethylresidues using PhSH-PhSNa' Both substitution a,ct'ct-trichloroand chloroform However, hydrodechlorinationoccur on such treatment. toluenedo not reactin the samemanner.
E\"",s
PnsH-r:x ?"ar,, 100o/o
: B a a t i ,R . , G o u v e m e u r\. rWaters,M.S., Cowen.J J 'Kamimura,A., Mitsudcn
rRomero-Ortega,M.. Fua 'Satoh,T., Kubota. K. rl"Cuadrado,P.,Gonzalez'Chakraborti, A.K.. Na1al * Y u ,W . , S u , M . , G a o .\ - '
Benzimidazolium Bromination
bro
and '
not react, therefore p-n
a-Thioaldehydes.s A method for homologation of aldehydes accompanied by lithiated simultaneous introduction of an cr-PhS group involves reaction with the + (PhSH r-BuOK). PhSK with chloromethyl phenyl sulfoxide and subsequenttreatment
Oxidation of alcohc 'Ozgun,B., Degirmenha
Benzimidazolium brornochromate
o__s-Ph Ir.:.r
.trn\crted to cr-tosyl sulfon-
Ph.v/^-rr/,CHO
PhSH- fBuOK
tn.r.-^'.-^^,
, - . , , m p l i s h e dw i t h N a H C O : .
H
I SPh
oH N
tl R,.
r--.
730
-SOrPh -
., )rs of amidinesand they are
Deoxygenation of s,yt epoxides.6 Alkenylsilanes aro generated from the epoxy silanes with retention of configuration, when they are exposed to phs,-i in -7g.. THF at The reagent attacks the silylated carbon atom regioselectivery unress the s'yl group is very bulky (e.g.,r_butyldiphenylsilyl group). clcavage of aryr esters. A-ryl acetates, benzoates, pivarates, and tosylates are cleavedunder nonhydrolyricconditions (phSH, K2COr,NMp;;_),';;,;., are less reactive.T o-Aminobenzenethiolis also useful for tiis purpose.
Jr I t :: rll
.irc tbrmed as intermediates :l\)rd0-ketols. 'rr hcnzenethiolate to conju.:r :rldol reaction in a stereo-
o o'\
r-
.
syn ; anti 92:8)
t: .. . c 9.. in RCOCCIj)areconSli i'':S\a. Buh substitutionand r - ,rtrl1l1rn and ct,ct,ct-trichloro-
Bt\,4P 100.
Y
=y;. :
|i.-r'n' 9sn
OH
I
f\
i
l
Y
COOMe
l
COOMe 93%
,,,r^r:#:::";l::Kroir!,*
cteavage.B rhe chemoserective cleavage withphSH_Snclo
,"*;;;.il;."ffi ;;1iJ'il',?;,^);T[:11."#,:;J:""1;Ti *:.o^"r:.rneur. V..Mioskowski. .,1111: C.s e29( legel. waters' M's ' cowen'J A ' Mcwi'iamr'r-c p.E., 'Kamimura, , rra"rigr"*, Askin,D. TL 4r, l41(2000). A.,Mitsudera. H.,Asano, S.,Kidera, S.,fi"i"f,,,A. JOC 64,6353 rRomero-Oftega, (1999). M., Fuentes, ,:r,rl.1.
A.,-Gonzalez,C , M;;d.r,;., K u b o r aK.. T L 4 l . 2 t 2 t 1 2 0 0 0 ) .
Cruz,R. S 225(lggg).
A.M.rL 4r.r| | I (2000). llljjlf:l ^":nzarez_Nogar. L na(rabonr, A.K.. Nayak,
SPh
7
n
:J.-hvdesaccompaniedby . r et r o n w i t h t h e l i t h i a t e c PhSK(PhSH + /-BuOK).
M.K- Sharma, L. JoC g, si2l (tgssl. 'Yu.W.. Su.M.. Gao.X., yang,2., Iin, Z. TL 41,aOri irOOOf . Benzimidazolium bromochromate. Bromination and oxidationr This reagent brominates arenes. Deactivated rings do not feact' thereforep-nitroacetophenone gives rrr-bromo-p-nltroacetophenone. oxidation of arcohorsto carbonyl products is also observed in moderateyields. Ozgun,B., Degirmenbasi, N. JC 29, 763(lgg{).
Benzotriazol-l-yl
alkyl carbonate
Benzotriazole. I,S-Disubstituted pyn'olidinones.t
4-Benzyloxybutanal.
l-Substituted 5-(1-benzotriazolyl)pyrrolidinones are available in one step from primary amines, benzotriazole, and 2,5-dimethoxy-2,5dihydrofuran. The benzotriazolyl group is readily replacedby nucleophiles.
+ '..np M"o-+oMe + RNH2
*Y-Y*'
HoAc> "#np
N=N
R
Acetals.t l,3-Diols can be prore. cyclic acetalsis by catalytic hydrogenar is instigatedby the releasedpriman hrd
OH
OH
*
cHo
\r^o
N=Ni 70To rPowell,N.A.,Rychnovsky, S.D."/OC61.:Ol
lKatritzky, A. R.,Mehta,S.,He,H.-Y.,Cui,X. JOC 65,4364(2000). Benzyltriethylammonium
1 I/-Benzotriazol-1-yl mesylate. N-Mesylation.r Mesylation of an amine in the presence of hydroxyl groups is possible with this reagent.Primary amines are more reactive than secondaryamines.
tetrathiorml Disulfi.des. Alcohols are con\.enc catalyzed) and reaction with the reagc organic disulfides are cleaved by tlr r trappedby Michael acceptors.r
rKim,S.Y.,Sung,N.-D.,Choi,J.-K.,Kim, S.S.TL 40,117(1999).
(1 II-Benzotriazol-1 -ylmethyl)trimethylsilane. Homologation of carboxylic aci.ds.t A reaction sequence for the homologation starts from a reaction of BtCHrSiMe., with RCOCI. After O-triflation, treatment with either TsOH and then BuaNF (aliphatic series) or NaOMe then HCI (aromatic series) completes the transformation.
fol^ot v
lBnrEr.\i
rKatritzky,A. R., Zhang,S.,Fang,Y. OL 2, 3789(2000).
O - (Benzotriazol- 1-yl)- N,N,N',N' -tetramethyluronium tetrafl uoroborate. Ether cleavage.t This reagent catalyzes cleavage of THP, silyl, and 4,4'dimethoxytrityl ethers. rRamasamy, K.S.,Averett,D. SL709(1999).
Cleavage of propargyl carbamaratreatment with I equiv of the terarh irradiation.
rSrnha, S.,Ilankumaran, P.,Chandrasekaran S I Prabhu, K.R.,Sivanand, P.S.,Chandrasc\ar ' Sinha,S.,llankumaran, P.,Chandrasekara S
Benzyltrimethylammonium
Benzotriazol-1-yl alkyl carbonate. Amides.t Reaction with a carboxylic acid followed by aminolysis leads to amides. rl-ee,J.S.,Oh, Y.S.,Lim, J.K.,Yang,W.Y.,Kim, I.H., Lee,C.W.,Chung,Y.H.,Yoon,S.J.SC 29, 2547(1999\.
diphenltpt Stille coupling.t The title compc residues.On precipitatingRrSnop(O rF are facilitated.
Zhang,S.,Marshall,D., Liebeskind. L.S..rOC
Benzyltrimethylammonium
lf":
:
E: -' t-__'
I -benzotriazolyl)pyrrolidinones :rezole. and 2,5-dimethoxY-2,5i.r nucleophiles.
4-Benzyloxybutanal. Acetals,t 1,3-Diols can be protectedas substituted1,3-dioxanes.Cleavageof the cyclic acetalsis by catalytic hydrogenation in which an intramolecular exchangereaction is instigated by the releasedprimary hydroxyl group.
R
ol-ru\\Y R
I i l
diphenylphosphinate
aar'-r--
R'
3r or
*
9HO
\,,^orn
*r'Y*' H2 / Pd(OH)2-C
+
oLo,"
N=N
rPowell, N.A.,Rychnovsky, S.D."IOC64,2026(1999).
r :.. nrcsenceof hydroxyl groups t ' . . : . i r \ d t h a ns e c o n d a raym i n e s .
\: " .L'quencefor the homologation \ir!-r O-triflation, treatment with )r x \ :t )\tc. then HCI (aromatic series)
oni u m tetrafl uoroborate. . rj.rlc of THP, silyl, and 4,4'-
ll, Lr
: hr aminolysisleadsto amides. \\ . Chung,Y.H.,Yoon,S.J.SC 29,
Benzyltriethylammonium tetrathiomolybdate. Disulfides. Alcohols are converted to disulfides on activation with Dcc (cucl catalyzed) and reaction with the reagent (9 examples, 45-ggZo).t On the other hand, organic disulfides are cleaved by the title reagent and the resulting thiolates can be trappedby Michael acceptors.2
(Yo' v
CuCl,DCC
O.^t"'-O
lBn(Et)3Nl2MoSa
88%
cleavage of propargyr carbamates.3 The amino-protecting group is removetl on rreatment with l equiv of the tetrathiomolybdate salt in MeCN with urtrasound irradiation. p, Chandrasekaran, Sinha,S.,Ilankumaran, S. I55, l4i6g 01ggg\. : Prabhu,K.R., Sivanand, p.S.,Chandrasek alirn,S.ATCIEE39, 4316(2000). 0lggg). p.,Chandrasekaran, Sinha,S.,Ilankumaran, S. ZZ 40,.7il Benzyltrimethylammonium diphenylphosphinate. stille coupling.l The title compound is an effective scavenger of organotin rcsidues.on precipitating Rjsnop(o)ph2 the cu-catalyzed Stilre coupling reacrions ere tacilitated. Zhang,S.,Marshall, D., Liebeskind, L.S.JOC 64,2jg6(1ggg).
f,f'-BiE
l, l'-Binaphthalene-2.2'-diol. BINOL
Benzyltrimethylammonium tetrachloroiodate. Hydroximoyl chlorides.t Chlorination of aldoximes by this reagent at room temperatureis rapid. rKanemasa. A., Kakinami,T. 256, 1057(2000). H., Kamimura, S.,Matsuda,
Benzyltriphenylphosphonium peroxodisulfate. Oxidation,l Primary alcohols are oxidized to aldehydesunder solvent-freeconditions with this reagent and aluminum chloride as catalyst. Reaction in the presenceof other Lewis acids including FeClr, BiClr, andZnCl, are less efflcient. rHajipour, S.E.,Adibi,H. CL 460(2000). A.R.,Mallakpour,
Benzyl N-vinylcarbamate. Arylethylamines.t The title compound is transformed into an alkylboronic acid via hydroboration and its Suzuki coupling with ArI affords ArCH2CH2NHCbz. rKamatani, L.E.JOC 64,8743(1999). A., Overman,
Binaphane. Asymmetric hydrogenation r (R,R)-Binaphane ( I ) is preparedfrom l.l' -bi-2.2'naphthol in five steps. Its Ru complex is useful for asymmetric hydrogenation of trisubstitutedenamides.
f
1,1'-Binaphthalene-2,2' -iliol (modifed > Cyanations, Aluminum compleres with diarylphosphine oxide groups posses cyanation of aldehydesrand imines: '*'irh
in a manner analogous to the Reisscr asymmetric Strecker synthesis is apphc reactivity of MejSiCN than HCN in rlre g
catalytic amount while supplying stoichro
2\/
(A
C(
Al.dol transfer.a An aluminum con replacementof the carbinol moiety of an I the aldol and an aldehyde in dichlorot transformation.
rHamashima, Y.,Sawada, D., Kanai,M.. Shrbc rTakamura, M., Hamashima, Y, Usuda,H.. K:a 'Takamura, M., Funabashi, K., Kanai,M.. Stxh 'Simpura,L, Nevalainen, V.ACIEE39.3.111 r!
(1)
lXiao,D., Zhang,Z.,Zhang,X. OLl, 16'79(1999).
1,1' -Binaphth alene-2,2' -diol' BINOL. Resolution.t The cyclic boronate ester derived from racemic BINOL and BHl SMe2 preferentially forms a diastereoisomerwith r-proline, thereby (R )-BINOL can be isolatedby crystallization.On decompositionof the complex(S)-BINOL is recovered. rShan, 2Z., Xiong,Y.,Zhao,D.255, 3893(1999).
I,l' -Binaphth alene-2,2' -diol-galliurn/lld 2-Aryloxy alcohols.t meso-Epoxrh Ga-Li linked BINOL complex with high
rMatsunaga, S., Das,J., Roels,J., Vogl.E.\l . M. "/ACS122,2252(2000).
1,1' -Binaphth alene-2,2' -diol-porassiurn/ Addition to imines.t The hererd (l-PrO)1Yb and r-BuOK catalyzes rhe ar N-phosphonimines.
rYamada, K., Harwood,S.J.,Griiger,H.. Shrb.s
I,l'-Binaphthalene-2,2'-diol-potassiurn/yttrrbium complexes
\rmcs by this reagent at foom
:f' :o57(l0OO).
h - : Le
:i t\ des under solvent-freeconditions Rcaction in the presenceof other
1,1'-Binaphthalene-2,2'-diol (modified)-aluminumcomplexes. cyanations. Aluminumcomprexes of BINoLs (1) that are armedat c-3 andc-3' with diarylphosphine oxidegroupspossess bothLewis acidandbasecenters.Asymmetric cyanationof aldehydesr andimines2with Me.SicN, andof quinolinesandisoquinolines3 in a manner analogousto the Reissertreaction is successful(ee- 7G-902o).The asymmetricstrecker synthesisis applicableto conjugated.aldimines and the higher reactivityof MersicN thanHCN in the presence of l0 molToof phoH enablesits usein catalyticamountwhile supplyingstoichiometric HCN asthecyanidesource.
.:llclent.
t,,
tr.:' .' :nrcd into an alkylboronic acid via r:: -:. \rCH.CH.NHCbz.
(1)
'r R
I , is preparedfrom 1,1'-bi-2,2''r asvmmetric hydrogenation of
Aldol transfer.a An aruminum complex of BIN'L is capable of cataryzing the replacementof the carbinol moiety of an aldol. Thus, addingthe complex to a mixture of the aldol and an ardehyde in dichloromethane at room temperature completes the transformation. Hamashima, Y.,Sawada, D., Kanai,M., Shibasaki, M. JACSli2l, 2641(19gg). rThkamura, y., Usuda,H., Kanai,1,f., M., Hamashima, if,ii^"ti, M. ACIEE 39,1650(2000). 'Takamura, M., Funabashi, K., Kanai,M., Shibasaki, frl.]aCS 122,6327 (2000). rSimpura, L, Nevalainen, V.ACIEE39,3422(2000\. l,l' -Binaphth alene-2,2,-diol_galiumlithium complexes. 20,24_25 2-Aryloxy arcohors.t meso-Epoxrdes are op"n"o by phenors in the presence of the Ga-Li linked BINOL complex with high enantioselectivity.
#1))13?ri;iTirl;;fr*,,,
(':
. ctl tiom racemic BINOL and proline,thereby(R )-BINOL can -,'nrplex(S)-BINOLis recovered.
J, Vogr, E.M, yamamoto, N.,rida, r, yamaguchi, K.,Shibasaki,
1,1'-Binaphth alene-2,2,-diol_potassium/ytterbium complexes. Addition to imines.) The heterobimetallic complex derived from BINOL, ll-PrO).,Yb and l-BuOK catalyzes the asymmetric reaction between nitroalkanes and .V-phosphonimines. Yamada, K., Harwood,S.J.,Grriger,H., Shibasaki, M. ACIEE 3g,3504(1999).
l.I'-Binaphthalene-2,2'-diol-titanium complexes
1,1'-Binaphthalene-2,2'-lliol-titaniumcomplexes. 15,26-27;16,24-25;17,28-30; 18, 4344; 19, 25; 20,25-27 Enantioselective isomerization.t Epoxides of enol esters provide chiral a-acyloxy ketones and chiral starting materials. 4-Substituted butenolides, 2-siloxyfurans react with aldehydes2and with imines3 at C-5 to give chiral products. The hydroxyalkylbutenolides formed can be incorporated into the catalyst system thus rendering the aldol reaction autoinductive. Chiral sulfuxides.a A catalytic oxidation of organothiomethylphosphonatesenables the preparation of enantiomerically pure sulfoxides. a,a -Disubstituted amine*s Addition of two Grignard reagentsto a nitrile leads to the products. If a chiral BINOL-Ti complex is introduced in between the additions, the oroductsare enantioenriched.
BnO_CN
-J-'<"< o', NIeMsBr> NreMsBr .. ,zcl / B.ox)-Nhz
EtN.4sBr; @ >
C5 Mukaiyama aldol reaction Reasonably good enantioselection is observed when the catalyzedreaction of ketene silyl acetalsderived from thioesterswith aldehydesis conductedin supercriticalfluoroform.6 The homoaldol version involving 1-ethoxy-1+rimethylsiloxycyclopropane as donor employsa catalystpreparedfrom (l-PrO)2Ti(binol)and Me.,SiOTf.7 2-(a-Hydroxyallql)-1,3-butadienes.E A syntheticprocessfor thesecompoundsinvolves reaction of aldehydeswith 2,3-butadienylstannane. A BINOT-Ti complex combined with synergisticreagentsuchas l-PrSBEt2constitutesa superiorcatalyticsystem.
'Martin,S.F.,Lopez,O.D.TL 40.89{9, l( aCapozzi, M.A.M.,Cardellicchio. C.. Frrr 5Charerte, A.B.,Gagnon, A. ZA 10.l96l , l oMikami,K., Matsukawa, S.,Kayalu.\-. I TMartins, E.O.,Gleason, J.L.OI l. lil_r, "Yu,C.-M.,Lee,S.-J.,Jeon, M. JCStp I , j '/Nakamura, Y.,Takeuchi, S.,Ohgo.'t'..Cr.
1,1'-Binaphthalene-2,2'-diol(modfi Chiral benzylic alcohols.) Thc enantioselectively by 3,3'-bis(2.5{rhc IHuang,W.-S.,Pu,L. JOC 64, 4222r tlIrr 1,1'-Binaphthalene-2,2'-diol(modifi Aldol reactionr A catalytica*r BINOL has beendeveloped.
Hetero-Diels-Alder reaction.:'l ef-fectivechiral catalysts for the srrrx diene.Linkage of the BINOL morerr r
'lshitani,H.,Yamashita, y., Shimizu.H.. Xr rKobayashi, S.,Kusakabe, K., Ishitanr. H (
1,1'-Binaphth alene-2,2' -diol derivcd Mukaiyama aldol reaction.: Th servesas a catalystfor the aldol reactr selective)is observed.
.Y \.,\
Bu3Sn.
P h ' c H o*
-
-.-- - c \
i-prsBEt/,(i-pro)4ri
1.,;^-*;-
,r,{"r.1
ll 81% (98%ee)
(R)-I-Phenylpropanol." In this preparative example, the repeated usage of a 6,6'-bis(tridecafluorooctyl)silylated BINOL in catalyzing the reaction of PhCHO with EtrZn has been demonstrated. rFeng,X., Shu,L., Shi,Y.JACSl2l, I 1002(1999). 2Szlosek, M., Figadere,B. ACIEE39, 1799(2000).
CC
\agayama,S.,Kobayashi, S.,/ACS122.ll j
Bis[(1,1'-binaphthalene-2,2,-diol )-k Michael reaction,t Lanthanide_a derivative are stable, storable, and reusa
Bis[(1,1,_binaphthatene-2,2,_diot)_3_methyt]ether 29
rs. 15. lr-17: 16,24-25:17,28-30;
rMartin,
o: -'' ,. L.\tersprovide chiral a-acyloxy
"Mkami, ;$!:l:,!f,T#:fi:?i'l;:;:i":,"# K..Marsukawa. t , ":, tkariya,f. TL 41,jg31(2000). Ilr_u!, O,Gleason, I.L. OLt, 1643 (tgg;). "Y"1":,-U t Jeon. M.JCS(pI )3557(lgee). ,Jl; !: _t..:l,. y.,Takeuchi, r\akamura. y.,Curran, S.,Ohgo, D.p TL 41,57(2000).
r:- .i11[aldehydesrand with imines3 r::- - .:Jes lormed can be incorporated a.' : .rutoinductive. (,::.,::,'rhlomethylphosphonates enables S
\ ( - -nard reagentsto a nitrile leadsto n'.: r ..JJ in betweenthe additions.the
I.JeMgBr
\
snO.'dz
,NHz
S.F.,Lopez, O.D. TL 40, 8g4g(1ggg).
G,Naso, p ,ACS F,rorrore,,a, 121,4708 (lsss)
1,1'-Binaphthalene-2,2,_diol (modified)_zinccomplexes. chirar benzyticalcohors.t The additionoi oipt"nytrinc to aldehydesis rendered enanrroselecrively by 3,3,_bis(2,5_dihexyloxyphenyl)_ l, I ,_bi_2_naphthol. rHuang, pu,L. JOC64, W.-S., 4222(1999). 1,1'-Binaphthalene_2,2, _diol(modifi ed)_zirconiu complexes. Ardorreaction' a .r,l.ri.-:"..:: 19,25-26 :':'"-um asymmetric versionusinga Zr complex BINOL hasbeenO"u",oo".j.ru,rric of 3,3,_diiodo_ Hetero_Dieh_Alder';::f:
":-prexes or3,3'-diaryr-BrNol are
.hi,"r;;,"ffi
,:^,T:fi'rTl# :f*.,':: d iene. Linkage orthe BrNoL .",",,; ;;;;*#"T,:ffi
rr.
. :r.rnttoselection is observedwhen
n . . . ::,,nr rhioesterswith aldehydesis
t : l:,
L'-
' - :hr lsiloxysyclopropane as donor . \lc SiOTf.T -- \.\\ lbr thesecompoundsinvolves :ri\()[_-Ti complex combinedwith ' ..'relrtic system.
::,Xlll 3;:ilnd,
Ishitani.H..yamashita. ". ,nlT::: 'nooayashi. l;.Kobayashi,s. "//(s r22. s403t2000). S..Kusakabe. K.. tshrtani. H. OL 2. 1225r200Ol. I, l' -Binaphth alene-2,2, -diol derived
,",,.y::::#r:?::,f:,.o:". "^'-
selective) i. our.ru.a
20-crown.6.
rhe ";;;;".
r-on comprexarion withpb(orr),
aldolreactionin aq EtoH at 0". High
ot^,*"...i"",
ivrty(syn-
r^"-)o\ I o.'
\-o.--J
81% (98%ee) (1)
.ric. the repeatedusage of a : rhc reaction of phCHO with
\agayama, S., Kobayashi, S. -/ACS122, 11531(2000).
Bis[(1,1,-binaphthalene-2,2,.dio| )_3-methyl]ether. Michaet reaction.t Lanthanide_alo.,;;";; .;.plexes of rhis "dimeric" Jerivative arestable,storable, BINOL una."uruUI""nOr.";rr.O.
-diyl heteroesters 1,1'-Binaphthalene-2,2'
.Y \.4LA
o
G
M
(1)
rKim, Y.S., Matsunaga, S., Das, J., Sekine, A., Ohshima, T., Shibasaki, M. JACS 122,6506 (2000).
1,1' -Binaphth alene-2,2' -diyl heteroesters. 4-Alkynones.t The B-alkynylboronates act as alkynyl group donors of an enone. Hydrogenation 2 Easity prepared monodentatephosphoramidite ligands containing a BINOL residue are employed in conjunction with (cod)2RhBFa in asymmetric hydrogenationof dehydroaminoacid derivativesand ct-substitutedacrylic esters(ee>t 99Va
Hydroformylation.l A poll'mer-r catalyst for asymmetric hydroforml L propene)to afford branched aldehr'&s.
reachable). Conjugate additian. A phosphoramidite ligand (1) is useful for chiral induction during reactionoforganozincreagentswithenonesrand4.4-disubstituted 1,5-cyclohexadienonesain the presenceof Cu(OTf)2.
o
ot
Ph
o ' F P-N
o
/""'
Ph
(1)
Allylic tlisplacements.s The mixed phosphite of BINOL and phenol serves as a ligand to make up a catalyst with [(cod)IrCl]2 for the allylic substitution. Remarkable rate enhancement and increase in yield and ee are realized when the reaction is performed with BuLi-ZnCl2 also. Hetero-Diels-Alder reaction.b In the cyclocondensationof the Danishefsky diene and aldehydes in the presence of 2, a remarkably high asymmetric amplification is realized.
C h o n g ,J . M . , S h e n ,L . , T a y l o r ,N . J . . I A C Sl : rvan der Berg, M., Minnaard, A.J.. Schudd I-'eringa,B.L. JACS 122, I1539 (2000r. 'Naasz, R., Arnold, L.A., Pineschi,l\t.. Kclk ' l m b o s ,R . , B r i l m a n ,M . H . C . , P i n e s c h r\.l . I 'Fuji, K., Kinoshita,N., Tanaka,K.. Karahc 'Furuno, H., Hanamoto,T., Sugimoto.)'.. lru -Nozaki, K., Shibahara,F., Hiyama. T. C1.64
I,l' -Binaphth
alene-2,2' -iliyl siloxan-
CyclosilylationI
Yttrocene
compounds while
incorporating
asymmetric induction is poor.
I
cr
a sll
I,l'-Binaphthalene-2,2'-diylsiloxane
;:o '='@
3l
O' P " " ^
o' ' o- l I 3 vu (2)
rr .
'lrhasaki. M. JACS 122,6506(2000).
Hydroformylation.T A polymer-supported (RS)-BINAPHOS complex 3 serves as catalyst for asymmetric hydroformylation of gaseoussubstrates(e.g., 3,3,3-trifluoropropene) to afford branched aldehydes. I .. ., r.rn\ I group donorsof an enone. n:J:, rhosphoramiditeligands containing ,\rth (cod)2RhBFain asymmetric r: ar.: r -.uhstitutedacrylic esters(ee ) 997o p:.: I i. usefulforchiralinductionduring in 1.5-cvclohexadienonesa { : .::.uh\tituted
(3)
,
pi::: ,'1 BINOL and phenol servesas a x ':.; .rllrlic substitution.Remarkablerate i:.:../iJ *hen the reactionis performed
Chong,J.M., Shen,L., Taylor,N.J. JACS 122, lB22 (ZOOO). :van der Berg, M., Minnaard, A.J., Schudde,8.p., van Esch, J., de Vries, A.H.M., de Vries, J.G.. Fcringa,B.L. JACS 122, I I 539 (2000). ')iaasz, R., Anrold, L.A., Pineschi,M., Keller, 8., Feringa,B.L. JACS l2l, I 104 ( 1999). ' l m b o s ,R . , B r i l m a n ,M . H . G . ,P i n e s c h iM , . , F e r i n g aB , .L. OLl,623 (lggg). 'Fu1i, K., Kinoshita,N., Tanaka,K., Kawabata,T. CC 22gg Oggg\. Furuno,H., Hanamoto,T., Sugimoto,Y., Inanaga,J. OL2,49 (2000). ).iozaki, K., Shibahara,F., Hiyama, T. CL 694 (2000).
l. l' -Binaphth
:l .- ':J!'nsationof the Danishefskydiene rt,^ . high asymmetric amplification is
alene-2,2' -diyl siloxane.
cyclosilylationr compounds while
Yttrocene incorporating
esymmetric induction is poor.
1 catalyzes the conversion of a silyl group from
polyenes to cyclic
hydrosilane reagents. However,
-methyl)tindibromide Bis(1,1'-binaphthalene-2,2'
\L
^'"'@/\
9H
"-..P'--' Y'1,,2
,u-*r'
\z
Bis(acetonitrile)(1,5-cyclooctadi€trc ft
' Muci,A.R.,BercaqJ.E.TL 41.7609(200U.
Aryl transfer. The aryl group of . the influence of the ionic Rh complex,
Bis[1-(1,1'-Binaphthalene-2,2'-methyl)-3-methylimidazol-2,2'-ylidene]palladium(II) iodide. Heck reactionr The carbene complex 1 is very stable to air, water, and high temperature. It also survives silica gel chromatography. Preliminary investigations of I indicateits catalyticactivity in the Heck reaction.
\\ tM1
Bis(acetonitrile)cyclopentadienyl( trio tetrafluoroborate.
Slugovc, C.,Ruba,8.,Schmid,R., Kirchr
tl tt \J
I Oi, S.,Moro,M., Fukuhara, H., Kawanrd
Isomerization Efficiency for tb ketonesby intramolecular redox isomcr CpRu(PPhj)2Cl-NH4PF6l,but there is d the substrates.The catalyst is readily pr
t.r/*-
tt-
(1)
I Clyne,D.S.,Jin,J.,Genest, E.,Gallucci,J.C.,RajanBabu,T.V. OL2, ll25 Q0O0). Bis(1,1'-binaphthalene-2,2'-methyl)tin dibromide. Enantioselective benzoylation.t The title compound 1 catalyzes selectivebenzoylation of racemic 1.2-diols.
n'\-\Z'r -
Ph/-voH+Phcocl
/'
jlwasaki, F.,Maki, T., Onomura,O.. Nat st
(1)
oH
phr''t
rffi v\?
|
(1)
,,B r
sri
Br
Bis(acetonitrile)dichloropalladium( tIl 25-26; 17, 30-3 I ; 18, 4445: 19, 26 Thia-Claisen rearrangemenlt h chiral bicyclic thiolactams via a rhio effected with assistanceof (MeCN).pdC
,n,10-Jh ""oJr*F\ S.....^/.Ph
Na2CO3 THF - H2O (50 : 1)
Allylic displacernents. For achieri alkenols to form 2-vinylpiperidinc , VeCN)zPdClz is needed because tl: throughout the reaction.
Bis(acetonitrile)dichloropalladium(tr)
9H :
v
oH +
-;-OBz ph..' \./---
l ph'
-\./- -OH
i
(er 92:8) 41o/o
J
rlwasaki,F.,Maki, T., Onomura,O., Nakashima, W., Matsumura, Y. JOC 65,996 QUn).
Bis(acetonitrile)(1,5-cyclooctadiene)rhodium(I) tetrafl uoroborate. Aryl transfen The aryl group of ArSnMej is transferred to N-sulfonyliminesr under the influence of the ionic Rh complex. lm ida zol'2,2'-ylidenelpalladium(II) .rable to air, water, and high PreliminarYinvestigationsof I
I T:
r Oi, S.,Moro,M., Fukuhara,H., Kawanishi,T., Inoue,Y.fL4,9259 (1999').
Bis(acetonitrile)cyclopentadienyl(triorganophosphine)ruthenium(I) tetrafluoroborate. Isomerization
Efficiency for the transformation of allyl alcohols to saturated ketonesby intramolecular redox isomerization is improved by using these complexes [vs. CpRu(PPh)2Cl-NH4PF6l, but there is the disadvantageof limited substitution patternson the substrates.The catalyst is readily preparedfrom RuClj.3H2O. : Slugovc,C., Ruba,8., Schmid,R., Kirchner,K. OM 18,4230(1999).
r tt.2. ll25 (20O0)-
ldt.
r'.
::J I catalYzes setective benzoYla-
Bis(acetonitrile)dichloropalladium(Il). 13, 33, 2l l, 236; 14, 35-36; 15, 28-29; 16, 25-26; 17,30-31; 18, 44 45; 19, 26 Thio-Claisen rearrangement.t Introduction of a side chain to the c-position of chiral bicyclic thiolactams via a thio-Claisen rearrangement at room temperature is effected with assistanceof (MeCN)2PdCl2.
,,oJ-\
Ph,',(
|
|
)-Nvz\ MeoJ 5=.-r1--tn a
\
V' 2
J":tr (exo: endo 3:1\ 650/o
/
\,
(MeCN)2PdCl2
Br
Na2co3
Sn
Br
lHf_tr2v
( 5 0; 1 )
Allylic displacements. For achieving dehydrative cyclization of N-Boc-7-amino-2alkenols to form 2-vinylpiperidine derivatives,2 only a catalytic amount of ,\{eCN)2PdCl2 is needed because the Pd(II) species maintains its oxidation state throughout the reaction.
Bis(acetonitrile)dichloropalladiun(II)
OBn
OBn MOMO
MOMO
(l\4eCN)zPdClz THF 25'
rWatson,D.J., Devine, P.N., Meyers..{.1. II, rYokoyama, H., Otaya, K., Kobayashr. H. (2000). rLautens,M., Renaud,J.-L., Hieb€n. S. ./..1( rYang, F.-Y.,Wu, M.-Y., Cheng,C.-H- l.f CS sFielder,S., Rowan, D.R., Sherbum. Il.S .{(
OH fung opening of 1,4-oxa-1,4-dihydronaphthalenewith R2Zn proceedsin the presence of (MeCN)2PdCl2to afford cls-2-alkyl-1-hydroxy-1,2-dihydronaphthalenes.l Acylboration, Allenes are functionalized to give 2-acylallylboronates on reaction and acyl chlorides.a with bis(pinacolato)diboron
R + R"COC| + R'
]-o. |
l-d
p-L B-B
I 'o1-
Bis(allyl)dichlorodipalladium.
20. l9
Allylic displacements. Glycine dr with an allyl carbonate.rBINAP medral is rapid. The reaction with 2-bromo-1.3{ren Similarly, 3-bromo-3-alken-I -ynes are s butaLrieneproducts.aIn this reaction.
(tr4eCN)zPdClz
addedlieand.a
PhMe 80"
MeO Stille coupling.s An expedient synthesisof [6]dendraleneinvolves coupling of 2,3bis(trimethylstannyl)-1,3-butadienewith 3-iodosulfolene and pyrolysis. A lesser amount of [8]dendraleneis also produced.
Ph'\<
+
!-o 1
Br
iraEA
MeO
"g
* '".rn\'n""'
In contrast to the other Pd catall.sr^s gioselectiveformation of branched prod Alkylative cyclization. A Pd-card a C-Pd bond can undergo cyclization r
r*AArO" cArO"'
tl
o r S - " " o ) a - J l l 30%
43%
l A V
l A V
[8]dendralene
[6]dendralene
NCJ I
tl
CN
+ Phl-\
CN
The cationic rr-allylpalladium rhar r alyzes cyclopropanation with cinnaml l r
Bis(allyl)dicblorodipalladium
OBn
,.toMo 5!
Ja.-'.: ir rth R.Zn proceedsin the presence l. Jihrdronaphthalenes.r rl :rrc ]-acylallylboronateson reaction d
rWatson, D.J.,Devine,P.N.,Meyers,A.l. TL 41,1363(2000). 2Yokoyama, H., Otaya,K., Kobayashi,H., Miyazawa,M., Yamaguchi,S., Hirai, Y. OL 2, 2427 (2000). rl-autens, M., Renaud, J.-L.,Hiebert,S.JACS122,1804(2000). aYang,F.-Y.,Wu, M.-Y., Cheng,C.-H..IACS122,'1122(2000). 5Fielder, S.,Rowan,D.R.,Sherburn, M.S.ACIEE39,4331(2000).
Bis(allyl)dichlorodipalladium. AIIyIic displacements.
20, 29
Glycine derivatives are C-allylated via Zn-chelate enolates
with ana\l carbonare.r BINAPmediated asymmetric a\lation asslstedb.[ microwa\os2 is rapid.
+
The reaction with 2-bromo-1,3-dienes to form allene products3 is more remarkable. Similarly,3-bromo-3-alken-l-ynesare susceptibleto transpositionalsubstitution,forming butatrieneproducts.aIn this reaction, 2,2'-bis(diphenylphosphino)-1,1,-biphenyl is the
'.reCNl2PdCl2
added ligand.a
e^Me 80.
l .
^ Jr'ndraleneinvolves coupling of 2,3:,'lc'neand pyrolysis.A lesseramount
MeO
z-
^-\<
. {]
Br
!_o-
*".
FO MeO
l((_roctl '):,
d p b =r! p/rHF
Ph'\coc\XCooMe COOMe 45To
,.,..n\.n"
In contrast to the other Pd catalysts, the [(cjHr)pdcl]2-cy3p system promotes the regioselectiveformation of branched products from l-alken-3-yl acetates.5 Alkylative cyclization. A Pd-catalyzed Michael reaction product that still contains a C-Pd bond can undergo cyclization with an allenyl group.6 V
rr i l /\'r\t"\,/ -/
r-- 9oz / \
tl
tl
ll
ts-J
43To
l a
V
NCJ I
tl
CN
+
CN
prl \cr.r
*"\r\
a
NC-\
/
,/TCN
Ph
cN
71Yo
il tl
/'\r'\//\r' il tl
[6]dendralene
The cationic n-allylpalladium that is ligated to 2-imidazolyl-3-methylpyridine catalyzes cyclopropanation with cinnamyl acetate.l
Bis(allyl)dichlorodipalladiurn
r_
./r :.2
[2 +2 +2]Cyclatinqiz substituted fulvenes.
NV\
1-ro\*-lr" ph'\,
oRc *
EtO- _ OSiMq
BF4
E/
"""*l;ffi-
A
F(....:
t^a"ooEt
* Ph'\"'XcooEt Arylsilanes.tl
(22 : 1)
The com'
disilane is catalyzed by rhe F phosphine. This ligand acrrr:
87Yo
donor.
Coupling reactions. Carbostannylation of the palladacyclopentadieneintermediatesderived from two molecules of alkynoic estersleads to dienoic estersthat also bear a reactive stannyl residue.s
[<-Pdc,],:::€
Ph
+ :-cooEt
\
PhMe 50"
SnBu3 77o/o Homocoupling of aryl iodides to form biaryls with this complex in the presenceof tetrabutylammonium fluoride has been carried out in DMSO at 120".o a-Arylalkenyl ethers are easily prepared in a coupling reaction involving ArI and ctalkoxyalkenyl(hydro)silanes or a-alkoxyalkenyl(hydroxy)silanes.r0 The reaction conditions are compatible with a wide array of functional groups. couple with R3M-MRj to give 1,2-bis[-(triorganometMany 1,2,7,8-nonatetraenes
;Kazmaier, U., Zumpe, F.L. ACIE rBremberg, U., Larhed, M., Mobr 'Ogasawara, M., Ikeda, H.. Ha1-a 'Ogasawara, M., Ikeda, H.. ObrF 'Blacker, A.J., Clarke, M.L., L,oft 'Meguro, M., Yamamoto, y. .fOC -Satake, A., Koshino, H., Nalau. 'Shirakawa, E.,Yoshida,H.. :l-& 'Albanese, D., Landini, D.. penso Denmark, S.8., Neuville. L. OL I Kang, S.-K., Baik, T.-G., Krrlel . -Radhakrishnan, U., Gevorgyao-\ Shirakawa,E., Kurahashi, T.. \'or
I 2-Bis(benzenesulfonyl )ethy Cyclic acetals. Derivaru leadsto 2-benzenesulfonylm ;rclic acetalsresistacidhydro
allo)vinyllcyclopentanes that can be transformed into ring-fused 1,2-dimethylenecyclobutanesvia demetalativecoupling. | |
r-/"
.//
MRs
Hol
5^"dfjil
G
BnO
h^ \
G = NTs, C(COOE02,CPh2. CHOBz,CHOBn
- ,ro:S
I OMe
MRs M=Si,R=Me M=Sn,R=Bu
tlery, F., Rollin, P., De Lucchr. O
1,2-Bis(benzenesulfonyl)ethylene
r_
[2 + 2 + 2]CyclotrimeriTation.l2 substitutedfulvenes.
. zl N.vz\
,/z
'-"oa*'l^,,
k
3F,
An unusual trimerization of l-alkynes furnishes
E/'''
--;;,
"*-*
l((_ eo.,l L\
)2
R:-..:dppf PhMe 70"
, =-^-TcooEr
R/-
Arylsilanes.t3 The conversion of ArBr into ArsiMe3 on reaction with hexamethyldisilane is catalyzed by the pd-complex in the presence of (2-hydroxyphenyl)diphenylphosphine. This ligand activates both pd and si by providing both a soft and a hard donor.
7'. '
::.- relladacyclopentadiene intermedin .:.,1. to dienoic estersthat also bear a
.---\ fr'..
-#.
/
'-^-\ ff.
\\
/ e n /
ETOOC 77Yo [. " :: rhis complex in the presenceof r . : . ) \ 1 S Oa t 1 2 0 " . e r . -: -Lnsreactioninvolving ArI and cttt. :: rr rsilanes.l0The reaction condiBi. -: up\. ro give 1,2-bis[-(triorganometl-\lR E- :rl{, nng-fused 1,2-dimethylenecy-
rKazmaier,U., Zumpe, F.L.ACIEE 38,1468(1999);39, 802(2000). 2Bremberg, U., Larhed,M., Moberg,C., Hallberg,A.,rOC g, l0g| (lggg). rOgasawara, M., Ikeda,H., Hayashi,T. ACIEE 3t, rc42 e}OO). aOgasawara, M., Ikeda,H., Ohtsuk,K., Hayashi,T. CL776 (2ON). sBlacker, A.J.,Clarke,M.L.,Loft, M.S.,Williams,J.M.J.OLl, 1969(lggg). 6Meguro,M., Yamamoto, y. JOC 64,694 l1'ggg). TSatake, A., Koshino,H., Nakata,T. CL 49 .lggg\. sshirakawa, 8., Yoshida,H., Nakao,y, Hiyama,T. JACS121,4290eggg.). 'Albanese, D., Landini,D., Penso, M., petricci,S.SZ 1990999). roDenmark, S.E.,Neuville,L. OL2,32Zl (2000). IIKang,S.-K',Baik,T.-G., Kulak,A.N.,Ha.y.-H..Lim, y, park,r. JACS r22, [5290 (20oo). lrRadhakrishnan, U., Gevorgyan, V.,yamamoto,y. CC lgTl ?OOO\. lrShirakawa, E., Kurahashi,T.,yoshida,H., Hiyama,T. CC 1895(2000). I l.Bis(benzenesulfonyl)ethylene. Cyclic acetals. Derivatization of diols with this disulfone under basic conditions leads to 2-benzenesulfonylmethyl-I,3-dioxa cycles.r In protection of carbohydrates,these cyclic acetalsresist acid hydrolysis but can be cleaved by reducing agents.
oo^lP MRs
=--\
.Y
+
Q
r-.4 l
^.
rn-"ag*l
HO-1 HO----r.-\
l
. ,^i',';,.,,r^
Bno-$t BnO
NaH - Bu4NBr
I OMe
MRa r,r=Sr.R=Me r.r=Sn.R-Bu
BnoJ)t BnO 99%
CheryF.,Rollin, P.,De Lucchi,O., Cossu,S. TL 41,2357(2000\.
I OMe
Bis(benzonitrite )dichloropalladium(Il)
Bis(benzonitrile) [bis(1,4-diphenylphosphino)butane]palladium(0). pl'actones.t with the pd-comprex, [2 + 2]cycloaddition between aldehydes and ketene forms B-substituted B-lactones in very high yields. The adduct from crotonalde_ hyde is easily transformed into sorbic acid.
o
-\-I,. v
t H
o
l
ii +
tAH
,
^
?{-
-\,F
9
o
e\ * ...\..^.,.cooH s-ornicXcio
,.\,
rFranks, R.J., Nicholas,K.M. OM 19. t.l rKantam, M.L., Rahman, A., Bandlopd 5Ma, S . ,L i , L . O L 2 , g 4 1 e U : / | . . .
Bis(1-benzyl-3,5,7-triaza-| _azcxrb Oxidations.t Varioussubstan andhydrazon'es to carbonylcompou I Wu,
M., yang, G., Chen, Z. SC 30. -tt :,
' Hattori, T., Suzuki,Y., Uesugi,O., Oi, S., Miyano, S. CC 73 (2000).
Bis(benzonitrile)dichloropalladium(Il).
13,34; lS, 29; lg, 4647 ; 19, 27; 20, 30_31 claisen rearrangement,t The catalyzed rearrangementof methoxycarbonylmethyl allyl ethers is stereoselective,in contrast to the thermal version. coupling reactions. The catalyst system for the Sonogashiracoupling that incrudes l-Bu3P is useful for room temperaturereaction with aryl bromides.2 ph----
+
Br-ph
Bis[l,l' -bi-2,2,-hydroxynaphth-]y 2-Aryloxy alcohols.t Theseel From meso-epoxides, chiral p.oA,ri. complex.Reactionwith simpleBI\( dueto phenolate exchange (r.e..BI-\(
a co
(PhcN)zPdclz-(rBu)gP ph----:-ph Cut,i-pr2NH / dioxane 94%
Carboxylative coupling of allylstannanes (50 atm) affords unsaturated esters.3
and allyl
halides
under carbon dioxide
o
.{-snaur* c'.z1 lIffffi
$oM
Matsunaga, S., Das,J., Roels,J.. Voel.E y. JACSr22.22s2Qffiu.
97Yo Dehalogenafion.a The catalyst supportedon mesoporoussilica is useful for dehalogenation of aryl halides under hydrogen. 3-Allylfurans.5 Concurrent allylation and cyclization involving allenyl ketones and allyl bromides is catalyzed by (phCN)rpdC!.
pn,,
o\(phcN)2pd'2 ,8, / - * - ^ _-u _J_ \ _ - P h // K2co3iMecN
R
Bis[chloro(I,5-cyclooctadiene)iridiaa Aziridines.t Aziridines are otrax and ethyl a-diazoacetatein the prexncr Enynes.2 l_Alkynes are dimenz dependent on the phosphine ligand butatienes.
(y .R \_/
//_
rHiersemann, M. SL 1823 (1999). 2Hundertmark, T., Lirtke, A.F., Buchwald, S.L., Fu, G.C. OL 2, l72g (ZO0O).
Phz(Me)Si '
tt^d,rn
ltuwrrrur[
\
\
til'"*--
-
Bislchloro(1,5-cyclooctadiene)iridium(I)l
nlladium(0)' rr.:-:::.,'nbetween aldehYdesand !:. I rc adduct from crotonalde-
c I
k
-
,/.\,,^,,,COOH sorbicacid
). lt. -16-17:19,27;20,30-31 l€ir'.::rloi methoxycarbonylmethyl I a:. :,lll.
3Franks, R.J.,Nicholas, K.M. OM 19,1458(2000). aKantam,M.L., Rahman,A., Bandyopadhyay, T., Haritha,Y. SC 29, 691(1999). sMa,s., Li, L. oL2,941 (2ooo).
Bis(1-benzyl-3 ,5,7 -triaza-l-azoniatricyclo[3.3.1.13'7]decane peroxodisulfate. Oxidations.t Various substancesare oxidized by the title reagent:alcohols, oximes, and hydrazonesto carbonyl compounds and thiols to disulfides. I wu, M., Yang,G., Chen,Z. SC 30,3127(2000).
Bis[1,1'-bi-2,2'-hydroxynaphth-3-ylmethyl] ether-gallium/lithium complex. 2-Aryloxy alcohols.t These glycol monoethers are formed by epoxide opening. From meso-epoxides,chiral products are obtained in the presenceof the linked BINOL complex. Reaction with simple BINOLs is complicated by erosion of enantioselectivity due to phenolateexchange(i.e., BINOL and phenolatenucleophile).
i. - 'rr:hira coupling that includes | -: ::rtdes.l
94Yo .rlrdes under carbon dioxide
-
ol
t
tt
z\,/\d\/
,
rMatsunaga, K., Shibasaki, N., Iida,T., Yamaguchi, S., Das,J., Roels,J., Vogl,E.M.,Yamamoto, M. "/ACS122,2252(2000).
97o/o
:,,u: silica is useful for dehalo: rnrolving allenYlketonesand
BisIchloro(1,5-cyclooctadiene)iridium(I)]. Aziridines.t Aziridines are obtained in one step from aliphatic amines, aldehydes, and ethyl a-diazoacetatein the presenceof [(cod)IrCl]2. Enynes.2 l-Alkynes are dimerized. T\e (E/Z) ratio of the products is strongly dependent on the phosphine ligand that is added. lert-Alkylalkynes afford 1,2,3butatienes.
lFl
:\
,/o\./ \\il
,rt
t., tff)0).
Ph2(Me)Si, Phr(Me)Si
R
\
[(cod)lrcl]2- R3P Et3N/ cyclohexane
\
\-gHg;1vs;p6,
R3P= Ph3P
95o/o EIZ 98:2
R3P= Pr3P
62Yo EIZ 11 :89
Bis[chloro(1,5-cyclooctadiene)rhodium(I)]
N'N-Disubstituted hydroxylamines.3 The k complex, together with BINAp, forms a homogeneoushydrogenation catalyst for nitrones.
['ood,
rKubo,T., Sakaguchi, S.,Ishii,y. CC 625 eOO$. 2Ohmura, T.,Yorozuya,S.,yamamoto,y., Miyaura,N. OM 19,365(2000). 3Murahashi, S.-I.,Tsuji,T., Ito, S. CC 4Og(2000).
CC Ga - ror
Bis[chloro(1,5-cyclooctadiene)rhodium(I)]. Functionalization ofunsaturated compounds. Hydroacylation ofalkynes, allenes, and alkenesusing 2-hydroxyaraldehydesaffords aryl ketones.r
d\>aoH
t
t
l
\r'\'-H
tl
-.-4
./r
='\rx",.
+(Yo'tr
r(cod)Rhc'2 ayoHlXH
Tffi**Y (83
17)
72Y" cis-l-Alkenylboronates are obtained from the reaction of 1-alkynes with pinacolatoborane and catecholborane, which is catalyzed by [(cod)Rhcl]r-i-pr.,p (Et.N) in cyclohexane.2 A merry-go-round alkylation leading up to four contiguous norbomyl groups in a benzene ring has been achieved.3
Q-*or,,*C## PhMe 100"
Racemization of N-acyl a-atnino acids.a A phosphine is included in the reaction mixture. The mild conditions of the racemization have implications in kinetic resolution as well as low pressure asymmetric hydrogenation at high conversion. Under such conditions, the occurrenceof racemization results in a decreaseof ee. Acylation, Acylation at an a-position of N-(2-pyridyl)amines by a combination of co and an alkene (e.g., ethylene) is conducted with the aid of [(cod)Rhcl]2. The pyridyl substitutentin the substratesis essential.s
Aldolreactions. Reductivealdohz: methyl syn-2-methyl-3-hydroxyalkanoarr consists of [(cod)RhCl]2, Me-Duphos interdependenceof the metal, ligand. and beenwitnessed.
With CO-H2 under pressure, the Rh r and then cyclizationinvolving remotesrlr OSiMe3 'tda
r\
\-V R
;
Methylation.s On promotion br. rh methylation with MeX to afford ArMe.
Kokubo, K., Matsumasa,K., Nishinaka.y. Itrr rOhmura, T., Yamamoto,y., Miyaura, N. ./ACS I 'Oguma, K., Miura, M., Satoh, T., Nomura. Il . 'Hateley, M.J., Schichl,D.A., Kreuzfeld.H.-J . I 'Chatani, N., Asaumi, T., Ikeda, T, yorimrsu. S r 2000). 'Taylor, S.J., -Hollmann, Morken, J.p. JACS l2l, 122O2rtfF) C., Eilbracht,p. I56, 16g5 (20O, 'Hossain, K.M., Takagi,K. CL l24t (1999t.
BisIchloro(diphenylphosphinobutanc )rt Intramolecular ene reaction r Intern to undergoan intramolecular enereacuonI<
(dgooRr
Cao,P.,Wang,B.,Zhang,X.JACS122,6tX)rfr
Bis[cNoro(diphenylphosphinobutane)rhodium(I)]
r!!ilr'\.
rogether with BINAP, forms
[(cod)RhCl]2
ru\ 1g :^< r1000).
l{ r Jroacylation of alkynes, allenes, I I s : ,' n . ' t .
"{*
-)r-l^rn
-N^Ph
\)
Aldol reactions. Reductive aldolization of methyl acrylate furnishes predominantly methyl syn-2-methyl-3-hydroxyalkanoatesin moderate yields.6 The catalyst system. consists of [(cod)RhCl]r, Me-DuPhos and Cl2Si(H)Me. For this reaction, significant interdependenceof the metal, ligand, and hydride source for reactivity and selectivity has beenwitnessed. With CO-H2 under pressure, the Rh complex mediates hydroformylation of alkenes and then cyclization involving remote silyl enol ethers.T
r\ (83 : 17) 72o/o
rl: ,i rrf l-alkynes with pinacolatobo(EtjN) in cyclo[,.,.-: RhCl]1-i-PriP norbornylgroupsin abenc1,:::Ju()us
L
\)
i-PrOH 160"
OSiMe3
( )
o*\
CO / ethylene
-osiMe3
? t
\.+-/
[(cod)RhCl]2
CO - H2lQH2C!2 90"
R
atr r.._,,fJ R
Methylatian.s On promotion by the Rh complex, arylzinc compounds undergo methylation with MeX to afford ArMe. rKokubo,K., Matsumasa, Y.,Miura,M., Nomura,M. BCSJ72,303(1999). K., Nishinaka, :Ohmura,T.,Yamamoto, Y., Miyaura,N. JACS122,4990(2OOO). rOguma,K., Miura, M., Satoh,T., Nomura,M. JACS122,10464(2000). {Hateley,M.J.,Schichl,D.A., Kreuzfeld,H.-J.,Beller,M. TL 41,3821(2O0O). sChatani, N., Asaumi,T., Ikeda,T., Yorimitsu,S., Ishii, Y., Kakiuchi,F., Murai, S. "/ACS122, 12882 (2000). nTaylor,S.J.,Morken,J.P.JACSl2l, 12202(1999). -Hollmann, c., Eilbracht, P.r56, 1685(2000). 'Hossain, K.M.,Takagi,K. CL l24l (1999).
t
Bis[chloro(diphenylphosphinobutane)rhodium(I)]. Intramolecular ene reaction.t Internal 1.6-enynesare induced by the Rh-complex to undergo an intramolecular ene reaction (cycloisomerization).
, p:. .rhine is included in the reactron fr:rr rmplicationsin kinetic resolution lr.,c :t high conversion.Under such of ee. in i -t.'arease bY a combinationof .:Jr ltamines I : t of rrd :: r d: [(cod)RhCl]2. The PYridYl
o-\-/ - AgSbF6 t(dppb)Rholl, ,H,
+
\_l 85%
Cao,P.,Wang,B.,Zhang,X. JACS122,6490(20OO).
Bis(sJzr-collidine)halogen@hexafluorcphosphate
Bis[chloro(pentamethylcyclopentadienyl)methylthioruthenium]. Subst'ttution rcactinns,t Replacement of the hydroxyl group of l-alkyn-3-ols on reaction with alcohols, thiols, and amines is accomplished at room temperature in the presenceof binuclear complex 1 and NHaBFa.
I -Haloallcyne s and I -haloalLcaa. conjugated acids are treated with thesc p for such a reaction with alkenoic acids r supportsa positive charge well (e.g.. crn
Oxidation.a Alcohols are oxid.rz Activated benzylic alcohols undergo orr
ct. 7s1 ,cp. Ru-Ru ,cp, \r/ .", (1)
r{
Cyclaisomertzatian,2l,o-Diynes undergocyclizationto provideconjugatedenynes on exposureto thetitle complex.
cx{
i'/-\ J-"\.-/
o
(1)
...................................*
Rousseau, G.,Marie,J.-X.SC29, 3705(lgg, rClausen, R.P.,Bols,M. JOC 65,2'lg7effil 'Homsi, F.,Rousseau, G. TL 40,1495(lggg, 'Rousseau, G.,Robin,S. 24 41,8881(20Or
o
NHaBFa/ MeOH
72Yo
rNishibayashi, Y.,Wakrji,I., Hidai,M. JACS122,ll0l9 (2C[,O). 'Nishibayashi, M., Wakiji,I., Hidai,M. ACIEE39,2909(2000). Y.,Yamanashi,
Bis(sym-collidine)halogen(I) hexafluomphosphate. 15,30; 17, 155; 18,49:19,29;20,33 Bromoallenes.r This reagent transforms c-diazo estersinto ct-bromo-a, B-unsaturated
Bis( 1,5-cyclooctadiene)nickel(0).
Addition to al.lcynes. Carboxylarrc achievedvia Ni(0)-catalyzed addition. In r and acyl groups can be used.Thereforea I be synthesized.
estersat low temperatures. Halolactonization.2 A method for the preparation of all-cis 2,3-dihydroxycyclohexanemethanolvia a bicyclic bromolactone is as follows:
? K -
SnBu3
R = Me.9
, 4 .
,oa cooH L\1,'".
o \
OH
?'{
\<" \_,
'
++
!{"' (_,Fot
A synthesis of allylic alcohols from r enceof Ni(cod):, Bu:P, and Et1B.l Cyclopentenones.a n-Allylnickel c nvlative cycloaddition with CO and alkrn
Bis(1,5-cyclooctadiene)nlckel(0)
irrutheniuml. hri:,.rrl groupof l-alkyn-3-olson in the lcl:.red at room temPerature
I-Haloalkynes and 7-haloalkcnes.3 The Hunsdiecker reaction occurs when the conjugated acids are treated with these positive halogen salts. There is a stricter limitation for such a reaction with alkenoic acids as they must be ct-unsubstituted,and the B-carbon supportsa positive charge well (e.g., cinnamic acid and analogues). Oxidation.a Alcohols are oxidized to carbonyl compounds in good yields. Activated benzylic alcohols undergo oxidative cleavageand ipso-bromination.
I
d."'
[{],**.
e-'4
-;---1-
oH
:l:r"::,'n to provide conjugatedenynes
4..-n,\
,1 ^
o
MeoW 67v.o
/-\
\
^ -\,/Y +
n
\
,/,/
72%
:/a: -re.:9o9(2000). 17,155;18,49;19,29;20,33 r 15..r,)): p-unsaturated t,- :'.ri'r.\intoct-bromo-ct,
:Rousseau, G.,Marie,l.-X. SC29,3705(1999). :Clausen,R.P.,Bols,M. JOC 65,279'l(2W0). 'Homsi,F.,Rousseau, G. TL 40,1495(1999). 'Rousseau, G.,Robin,S.TL41,8881(2000). Bis( 1,5-cyclooctadiene)nickel(0). Addition to allcynes. Carboxylationr and carbostannylation2of alkynes are readily achievedvia Ni(0)-catalyzedaddition. In the latter process,stannanesbearing allyl, alkynyl, and acyl groups can be used.Therefore a great variety of trisubstitutedalkenylstannanescan be synthesized.
ar3: .r of all-cis 2,3-dihYdroxYcYclo-
t'.
(cod)zNi+
R---E-Ph PhMe80"
SnBu3 R = Me, siMes
)
('.-('' ("
. - o \
t
,c
82Yo
L\1,""'
Meo* I
|
\\,/
cH2ct2 25
+-
I{"t (-)-o"
\\ \-rtnt" R
Ph
A synthesis of allylic alcohols from alkynes and aldehydes is conducted in the presenceof Ni(cod)2,BujP. and Et.rB.r Cyclopentenones.a n-Allylnickel complexes derived from enals undergo carbonvlative cvcloaddition with CO and alkynes.
Bis(1J-cyclooctrdlenc)ntckel(0)
\
'{
(cottlzNi
G;i
.rt't*,-\
Y -
MeOOC_-^
PM"
lr >{ bue
*COOMo/CO:
A combination of a hydrosilane I Valuable applications to the slnthc: are found.T
o
OSiMeg
9SYo
ao)
41
(cod)zNii
Me3sicl/co i M€oH
(o) H oMe I \ J
(^|\* \-4"',zcao H
Yo
45Yo
Cyctoffiitbns and cyclization. 2-Alken-7-ynonesundergoa 12 + 2 + 2lcycloThis processis derivatives'5 alkenesto give cyclohexene additionwith electron-deficient complementaryto the Diels-Alder reaction.
o
o \-n'
+
/
R'
R:
(*o)rNi, \ 6 Ph3P/rHF
|n"
^ rU
, . , K o i z u m i .T . H u S a i t o ,S . , N a k a g a w aS :Shirakawa,8., Yamasaki,K., Yoshrda.H Huang,W.-S., Chan, J., Jamison.T.F. Ol -Garcia-Gomez,G., Moreto, J.M../AC'SI 'Seo, J . , C h u i , H . M . P , H e e g ,M . J . .\ t o n q ' Choudhury,S.K., Amarasinghe.K. K.D . Tang,X.-Q., Montgomery,J. JACS lll.
Bis( 1,5-cyclooctadiene)rhodiumt Cyclobutanone
It
cleavage.
B
hydroxyphenyl)cyclobutanones as a rs fully substituted is a determinanl f
are tfansformedinto In the presenceof Ni(cod)2-TMEDA,certain2-alken-7-ynones an electrophileis whether on depending or bicyclo[3.1.0]hexanes, bicyclo[3.3.0]octenes added.6
(R=H) (cod)zNi- TMEDA:
[(cod,:R'I
Ar.P :a 'o'
R'
Stannylations.r Rh-catalvzed Jrfferentcoursesdependingon the o
,$',.
[(cod]2Rh]8F.
RO \
*;;
Bis(1,5-cyclooctadiene)rhodium(I) tetraffuoroborate
E-lCOritc/CO:
MeOOC- li\i l
\r.oH
OMe I btrrte
o
A combination of a hydrosilane and Ni(cod), directs reductive cyclization of alkynals. Valuable applications to the synthesis of pyrrolidines, indolizidines, and quinolizidines are found.T
95% a"^-t'^-\-^
I
i
I
9',',zcno H
ca I
- BurP (cod)zNi i......................._
Et3siH/rHF
"osiEt. (' 9 : 1 8SYo
45Yo
lcn---lnones undergo^ 12+ 2 + 2lcycloThis processis tre .iclohexenederivatives.5
Bis(1,5-cyclooctadiene)rhodium([)
::rC :\ Fle
Saito,S., Nakagawa,S., Koizumi, T., Hirayama,K., yamamoto,y. JOC 64,39:.5 (lggg\. rshirakawa, 8., Yamasaki, K., Yoshida, H., Hiyama, T. JACS l2l, 10221 (lggg). 'Huang, W.-S.,Chan,J., Jamison,T.F. OL2,4221 e00CD. 'Garcia-Gomez, G., Moreto, J.M..IACS 121, 878 (1999). 'Seo, J., Chui, H.M.P, Heeg, M.J., Montgomery,J. JACS l}l,476 (lggg). 'Choudhury S.K., Amarasinghe,K.K.D., Heeg, M.J., Montgomery,J. JACS 121,6.7-lS(lggg). 'Tang, X.-Q., Montgomery,J. JACS 121,6098 (1999).
cyclobutanone
cleavage,t
tetrafl uoroborare. Benzannulated
lactones are obtained from 2-(ohydroxyphenyl)cyclobutanones as a result of Rh insertion. Whether the benzylic position is fully substituted is a determinant factor for giving rise to J-lactones or s-lactones.
-tE
gna:n 2-alken-7-ynonesare transformed into rs. depending on whether an electrophile is
hD -fiFe/7-n R=H 86%
R=Me 78%
stannylations.2 Rh-catalyzed reaction of RISnH with propargyl ethers follows differentcoursesdependingon the organicresidueR.
l.
-wilA
"T,,,
Ro\ #ffi
*o\.. R'= Me
*o^Y'n"' *""/ R'= Bu
Bis(dibenzylideneacetone)palladium(0)
B enzyl alcohols.3 Catalyzed by (cod)2RhBFa-NaF,phenyltrialkylstannanestransfer the phenyl group to aldehydes(11 examples,52'92Vo). Reduction.a Ketones are reduced enantioselectivelyby hydrosilanes in the presence of this Rh complex and a chiral diphosphinyl ferrocene ligand' Isomerizatians The isomerization of allylic alcohols to B,B-disubstituted aldehydes by the Rh complex is rendered enantioselective(ee 72-867o in 6 examples) by the
The process involving aryltrialkor Changeof reactioncood couplings.lo from vinyltrimethylsilar silylstyrenes
lisand L.
+ y'tsslet
ph-l
--4h,,n,
-i+tFe
A facile synthesis of 2-arYl-1. allenes.r2Ionic liquids prove to bc
(1) jMurakami.M., Tsuruta,T., lto,Y. ACIEE39,2484(2000). 2Mitchell.T.N.,Moschref,S.-N.SL 1259(1999). r|-i, C.-J.,Meng,Y JACS122,9538(2000). aKuwano. M.' Ito'Y. BCSJ73' 485(1999)' M., Shirai,J.,Takahashi, R.. Sawamura, sTanaka, K., Qiao,S.,Tobisu,M., Lo, M.M.-C.'Fu,G.C.JACS122'9870(2000)'
chlorides.r3
Cyclopropanol cleavage.tt l-S rng to afford l-alken-3-ones. Altboo ransformation, PdCl2 without phoqt
Bis(dibenzylideneacetone)palladium(0). Arylamines and diaryl ethers. Polyhaloareneshave been employed in N-arylation.' By using certain carbene ligands, rapid reaction with chloroarenes at room temperature has been demonstrated.2The (dba)rPd-t-BuiP system has a wide scope of arylation including that of indole and carbamates.3(Formation of N-dimethylaminoindole from 2chlorophenylacetaldehydeN,N-dimethylhydrazone is novel.a)A more complicated ligand for arylationof aminesby aryl chloridesis 1.5
,^Jv HO
Ph
Annulation,ts o-Iodoaryl clan * ilh unsaturatedcompounds.Ring f<
- rBuONa (dba)2Pd cyz?
| n
r\r'f
i
woJ (1)
(y'\\(cN I
ll
\.,\r
92%
Coupling involving unactivated aryl halides and ArONa is successful under similar 7 conditionslbut l-BuONa is unnecessary).6 Cross-couplings. The coupling of aryl iodides and iodoalkeneswith alkenylsilanolso or alkenylsilacyclobutanes,eis very efficient in furnishing styrenesand conjugated dienes.
fr
+ lltD
v
n = l
y'fcN
\4,
+
Bis(dibenzylideneacetone)palladium(0)
ial
: henl'ltrialkylstannanestransfer
I
in the presence 6s.r rr h1'drosilanes x.::rnd. a.. ,:,'l: to B,B-disubstitutedalde-l-86% in 6 examPles)bY the r ::
The process involving aryltrialkoxysilanes is an alternative to Stille and Suzuki couplings.r0Change of reaction conditions permits the synthesis of either styrenes or Bsilylstyrenesfrom vinyltrimethylsilane.I I
(dba)2Pd
4r n
KF, BuaNCl MS-4A/ PhMe
ph-l
86%
+ ZtsiMes I
Pd(oAc)2
vn:V
-siMe3
EuaNOAc MS-4A/ NIeCN
g0o/o
A facile synthesis of 2-aql-1,3-dienes has been realized from aryl halides and allenes.r2Ionic liquids prove to be a superior media for the Heck reaction with aryl rr chlorides.
\ h,
..i 7-1..185 (t999). l:: e870(2000).
-' 'ten employedin N-arylation.r -. ,roarenesat room temperature lr, " -.r. a wide scope of arylation ll. r " l \ -Jrmethylaminoindolefrom 2.:l 'r A more complicatedligand I : : ,
L<-
cyclopropanol cleavage.ta 1-Substitutedcyclopropanols undergoesoxidative opening to afford 1-alken-3-ones.Although many other pd reagents are also useful for this transformation,PdCl2 without phosphineligand is an exception.
Ho.
;jF
3
Ph/\'/V
98% Annulation.ts o-Iodoarylcyanidesandthe homologousarylacetonitriles areunited u ith unsaturated compounds. Ring formationresults.
(J(, .(t, -*r O Jy d>acN
92Yo
(dba),Pd
Ph'\)V
(dba)2Pd-Et3N .=t\rh
/T\
n=1,2
d {:()\a
.:.:..::,rloalkenes with alkenylsilanols8 .trrenes and conjugateddienes.
si:::
R
is successfulunder similar
ft^t* \.^.t
. l|J 'l'
(dbaDPd-EhN ffi*t' o"lr;l,o
Ofa_
Bis(dibenzylideneacetone)platinum(0)
Heterocycle formation, 4-Alkenyl-1,3-oxazolidinesare readily preparedfrom vinylA synthesisof isoquinoepoxidesand N+osylaldimines in the presenceof (dba)rPd-dppe.16 achieved'r7 is similarly allenes pyridines from and lines
o.
TBSO \:6:
d
R
B_B
P. b
a-,4**' I(*,,
(dba)2Pd- dppp
\rJ--,
MeCN - Na2CO3 '100"
R'= Bn,t-Bu,CH2CH2CN
and carbostannylation of allenes.ts Allylstannanes are obtained from aryl iodide hexamethylditin. Arylation,te Ketonesand malonateestersare arylated.Bis(l,l'-di-r-butyl)ferrocene is a ligand that is used. IBeletskaya, A.G.,Guilard'R. S' 1459(1999)' I.P, Bessmertnykh' 2Stauffer, J.P.,Hauck,S.I.,Hartwig'J'F'OL2' 1423(2000)' S.R.,Lee,S.,Stambuli' L'M' JOC 64' rHartwig,J. F., Kawatsura, KH', Alcazar-Roman' M., Hauck,SI', Shaughnessy, (999). 55'7s aWatanabe, T., Nishiyama,M. ACIEE 39' 2501(2000)' M., Yamamoto, 5Bei.X., Guram,A.S.,Turner,H.W.,Weinberg'WH' TL 40' 123'l(1999)' 6Mann,G., Incarvito, A.L.' Hartwig,J. F.JACSl2l'3224 (1999)' C., Rheingold, ?Shelby, Kataoka, J' F JACS122'10718(2000)' Hartwig, G., Mann, N., Q., 8Denmark. S.8.,Wehrli,D. OL2,565 (2000). eDenmark, l2l'5821 (1999). S.8.,Choi,J.Y.,IACS r0Mowery, P.JOCg' 1684(1999). M.8.,DeShong, rrJeffery, (1999);41,8445(2000). T. TL 40,16'13 l2Chang, (2000)' H.-M.,Cheng,C.-H.JOC 65' l'76"1 rrBohm.VPW., Herrmann,W.A. CEJ6' l0l7 (2000)' raOkumoto. H., Jinnai,T., Shimizu,H., Harada,Y., Mishima,H', Suzuki,A' SL 629(2000)' rsl-arock,R.C.,Tian,Q., Pletner,A.A JACSl2l' 3238(1999)' r6Shim. Y. H 52,885(2000). J.-G.,Yamamoto, I?Diederen, , H.-W'' Hiemstra'H', t'/rieze'K' TL 40' 4255 J.J.H.,Sinkeldam,R.W., Fruhauf ( 1999). IsYang, F.-Y.,Wu,M.-Y.,Cheng,C.-H.TL40' 6055(1999)' reKawatsura, M., Hartwig,J. F. ./ACSl2l' 14'73(1999)'
Silyborationof alkylidenccYclq and(dba)2Pd.2
+ phMe2
Ci-\
Allylboranes.l
Displaccm
tdba)2ft-PhrAs-Et3N. Bis(dibenzylideneacetone)platinum(0). Hydroboration and silylboration. Hydroboration of allenes with (dba):Pt as the catalystshowsregioselectivitydependenceon the phosphineligands''
IYamamoto,Y., Fujikawa,R., Yrnrn :suginmoe,M., Matsud4T., Io, Y..lA 'Murata.M., Watanabe, S.,Masud..Y
Bls(dtbenzyltdenercetonc)plrdnum(0)
d::.r. .rre readily preparedfrom vinylr i'-: -Jppe.i6A synthesisof isoquino-
86o/o
rBso. . -fd \-c- *or-r,o+bf a_
760/o
l
:: ,'htainedfrom aryl iodide and
F.
Silyborationof alkylidenecyclopropanes involvesdifferent C{ and(dba)2Pd.2
bondsusing (dba)2Pt
,:L-dBis( l, l'-di-t-butyl)fenocene
fr ,.
a.
, , 1 . : . t + 2 3( 2 0 0 0 ) . L.M. JOC 64, :: .\lcazar-Roman, (dba):Pd x f l t .
; .
f .'tf
'1999).
I
l : l . 1 : 1 1( 1 9 9 9 ) r r l0O0).
Jt l::
C9^ " \ :uzuki.A. 5L629(2000).
Ir: F,
J+ + Phr.-6: + PnMe2si-tb.t
I
It,'*1Ph2PMe
* SiMe2Ph
.:rr. H., Vrieze,K. TL 40, 4255
Allylboranes.l Displacernent of allyl halides with pinacolborane is promoted by (dba)2Pt-Ph.'As-Et3N. 'i allenes with (dba)zPtas the h . . in.' ligands.l ?:.
:
Yamamoto, Y., Fujikawa,R.,Yamada, A., Miyaura,N. CZ 1069(1999). :Suginmoe, M., Matsuda,T., lto,Y. JACS122,I 1015(2000). 'Murata, M., Watanabe, S.,Masuda,Y. TL41,5877 (20C/]\.
Bb{ddlr 50
Bisldicarbonylchlororhodium(I)l
Bisldi-t-butyl(hydroxy)tinchloridel. Deacylation, Thereagentcatalyzescleavageof estersin methanol. tOrita, A., Sakamoto, K., Hamada,Y., Otera, J. SI 140 (2000).
Regarding substitution effecs, a h cyclopropane moiety significantly enlum derivatives afford only one regioisorcr.t regioselectivity dependenceon catalyst fa
Bis[dicarbonylchlororhodium(I)] and bis[(1,5-cyclooctadiene)chlororhodium(I)]. Epoxide opening.t The monoepoxide of a diene is regioselectively attacked by nucleophile (ArNHR, ROH) at the allylic position using [Rh(co)2cl]2 as catalyst,affording antil,2-arnno alcohols and alkoxy alcohols. The results are apparently complementaryto those obtained from the Pd-catalyzed process. Addition to multiple bonds. Hydroboration of i-alkynes with catecholborane (when i-Pr3P and Et.N are also present) gives (Z)-l-alkenylboronates.2 On the other hand, dehydrogenativecoupling3 between styrenesand pinacolboraneis observed.
Ph---\ l(cod)Rhclh
I
, l E = COOMe
o
\\-d
o
L
84Yo Under hydroformylation conditions, amines effect hydroaminomethylation to alkenes in an anti-Markovnikov sense.a's
Cl--\
I
+ EtzNH
By employing substrates poss€ssltrt alkenylcyclopropane,the cycloadditioo lc Intramolecular Pauson-Klund ra The reaction exhibits modest asymmctrk
t(""o*]]: EtrN._.,\,-_r'Et, co-Hr 67Yo
Cycloadditions. Cycloheptenones are prepared from l-alkenylcyclopropane derivatives via a [5 + 2]cycloaddition.6'7Improvement of stereoselectivity (retention) by the use of tRh(CO)rCll, is recognized.A synthesis of (+)-aphanamol I has been realized based on such a cycloaddition involving an allenic double bond as the two-carbon component.8
ts","
rFagnou, M. OL2,2319(z0mt. K., Lautens, :Ohmura,T.,Yamamoto, Y., Miyaura N. .lAC 'Murata,M., Watanabe, S.,Masuda,Y. irl '|. lEilbracht,P.,Kranemann, C.L., Barfackcr.L 'Rosche, P.f55, 3917(1999). T.,Eilbracht, ^Wender, P.A.,Dyckman,A.J.,Husfeld"C.O-Wender. P.A.,Glorius,F.,Husfeld,C.O..L.! 'Wender, P.A.,Zhang,L. OL2,2323(2ffit qWender, P.A.,Dyckman,A.J.,Husfcl4 C.O. "Wender, A.J.OLl,20E9 ( 19 P.A.,Dyckman, :Wender, P.A.,Conea,A.G.,Sato,Y, Sun L :Jeong, N., Sung,8.K., Choi,Y.K.JACSIZL
lRh(co)2crl2
Bis[dicarbonyl(formyloxy)triphenytpft Under rrrm Conjugate additian.t ( g-ketoesters, l-alkynes, etc) are indrn
PhMe A
(+)-aphanamol-l
\{ichael fashion.
Bisldicarbonyl(formyloxy)triphenylphosphlneruthenium(I)l
: :'.tersin methanol'
F
5l
Regarding substitution effects, a heteroatom substituent in a l,I-disubstituted cyclopropane moiety signiflcantly enhancesreaction rates. I,l-Disubstituted cyclopropyl derivatives afford only one regioisomer.eOf synthetic importance is the obervation of regioselectivity dependenceon catalyst for certain substrates.r0
rl ,.
lRh(CO)zcllz
I
l-alkynes with catecholborane
lr :. ,'i
On the other hand, ,.ienl lboronates.2 l p : :'.,.lborane is observed. 'l-
.
\
I
p-f\LB
E = COOMe
I
|
93%
(Pn:P)snnonPhMe A
I
x-t-
\ 81o/o
84To c:: :, : hl droaminomethylation to alkenes
-! .
-
- .
I
::_\ -=rr\rA
Uetz
By employing substrates possessing a 2-alkenylcyclobutanone unit instead of the II alkenylcyclopropane,the cycloaddition leads to 4-cyclooctenones. Intramolecular Pauson-Khand reaction,r2 Fused cyclopentenones are formed. The reaction exhibits modest asymmetric induction when a chiral BINAP is present.
from l-alkenylcyclopropane p:::.rr'd t1.:-.i:t of stereoselectivity(retention)by : - )-aphanamolI has been realized F.. .i-.::.:e double bond as the two-carbon
IFagnou, M. OL2,2319(2000). K., Lautens, 2Ohmura, Y., Miyaura,N. JACS122' 4990(2W). T.,Yamamoto, rMurata,M., Watanabe, S.,Masuda,Y. fL 40,2585(1999). lEilbracht,P.,Kranemann, C.L., Barfacker,L. EJOC 1907(1999). 5Rosche, T., Eilbracht,P.T 55,391'l(1999). 6Wender, P.A.,Dyckman,A.J.,Husfeld,C.O.,Scanio,M.J'C. OL2' 1609(2000). TWender, P.A.,Glorius,F.,Husfeld,C.O.,Langkopf,E., Love,l.A. JACS12f ' 5348(1999)' 8Wender,P.A., Zhang,L. OL 2, 2323(2000). eWender, P.A.,Dyckman,A.J.,Husfeld,C.O.,Love,J.A', Rieck'H. JACSl2l' 10442(1999)' l0Wender, A.L OL1,2089(1999). P.A.,Dyckman, rrWender, P.A.,Conea,A.G., Sato,Y., Sun,R. JACS122'7815(2W). rrJeong,N., Sung,B.K., Choi,Y.K.JACS122,6'17l(20OO).
.7
Bis[dicarbonyl(formyloxy)triphenylphosphineruthenium(I)]. Conjugate addition.t Under neutral conditions, various carbon pronucleophiles (B-ketoesters, l-alkynes, etc) are induced by the title complex to add to enones in the
I
67To
.OBn
(+)-aphanamol-l
Michael fashion.
(t
Bis(2,4-dichlorophenyl)chlorophosphate
Bis(dimethylamino)methaoc.
x.
[(Ph3P)Ru(co)2p(ocHo)]2
\.^)-" 3
. * "
tl
COOMe
cooMe
Isoflavanones.r o_Hvdror isoflavanonesdirectly.
67%
ll
--
+
\('Z'n r\
[(Ph3P)Ru(Co)2p(OCHO)]2
--Ph
74yo Enol esters.2 The regioselectiveaddition ofcarboxylic acids to alkynes rs extendableto diynes. rPicquet,M., Bruneau,C., Dixneuf,p.H.f 55, 3937(lggg). 2Kabouche, A., Kabouche,2., Bruneau,C., Oixn"ut p.H . JCR(S)I24j
|l9gg\.
Hydrosilylation.l Efficient synthesisof (Z)-r-silylalkenes from r-alkynes by this Ru complex is reported.
[(cvmene)Rucr2]2 Ph3Si, CH2C|245"
\-/
,Ph
94o/o
s,anors'2 Autoxidation of silanes in the air is catalyzed by [(p-cymene)Rucl2]2. This oxidation, which gives silanols ofinverted configuration, i, um"nuti" to large_scale
production.
Ring'crosing metathesis-3 cycric arkenes are obtained by heating dienes with [(pcymene)RuCl2l2and cysp in dichloromethane under neon light. 'Na,Y.,Chang, S. OL2,1887(2000). .Ko. S..Chang.S..//CS r22, t20n (2000). l*",t 'Fiirstner, A., Ackermann,L. CC 95 .lggg). Bis(2,4-dichlorophenyl)chlorophosphate. Hydroxyr activation.t Alcohols become activated on reaction with this reagent and it is possible to use them in situ to form alkyl azides. In other words, it requires only admixture of ROH, ClpO(OAr)2, DMA', and NaN.r in DMF to complete the transformation. rYu,C.,Liu, B., Hu, L. OL2, Ig5g(2M0\.
Rampa.A.. Br
2,2' -Bis(diphenylphosphino t.i F 32-36; 17, 34-38; 18, 39_4t : 19 Iridium(I) complexes
Bis[dichloro(p-cymene)ruthenium].
Ph3siH + --ph
rValenti,p., Belluti, F.,
CarbonylcysliTation.t The r to promote formation of 2_crc Pauson-Khandreaction. Mo."o* e Shibata,T., Thkagi,K. JACStn.%: Palladium( II ) complexes
N-Arylations. Aryl bronudr displacement with BocNHNH. r derivatives,2both by catalysis *.
hydrazonesby this method pror.rd diphenyl- 1,2-ethanediaminecan bc
Ph n'"trAon
t'Y,-\ .
(-z(
-binaphthyl 2,2'-Bis(diphenylphosphino)-1,1'
IJ
COOMe
Bis(dimethylamino)methane. Isoflavanones.r o-Hydroxydiphenylethanones condense with the reagent to form isofl avanonesdirectly.
67Yo
':.\f'z'^
NMer NMe2
MeO
(J
EtOH A
o
MeO
74To
o: ..::ho\) lic acidsto alkynesis
l*' (1999). 124'7 Pf: . ( R,s-,r
rValenti,P.,Belluti, F., Rampa,A., Bisi, A. SC 29, 3895 (1999).
2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl.13,36-37;14,3844;15,34;16, 32-36; 17, 34-38; 18, 39-41; 19, 33-55 ; 20, 4144 Iridium(l) complexes
Z . .rlrlalkenesfrom l-alkynes by this
Carbonylcyclizatian.t The use of [(cod)IrCl]2 in conjunction with BINAP and CO to promote formation of 2-cyclopentenones provides an alternative method to the Pauson-Khandreaction. Moreover, chiral products are obtained (9 examples,82-977o ee). I Shibata,T., Takagi,K. ./ACS122,9852(2000).
r ' c : :
PhqSi -
\:,/
Ph
94Yo
r i.: .- .atalyzed by [(p-cymene)RuCl2]2' d . :.:rruration,is amenableto large-scale s i. ,btainedby heatingdieneswith [(pu:.i:: n!'onlight.
Palladium(I I ) complexes N-Arylations. Aryl bromides containing electron-withdrawing group(s) undergo displacement with BocNHNH2 to afford ArN(Boc)NH2 'and sulfoximines to N-aryl derivatives,2both by catalysis with Pd(OAc)2-BINAP. Introducting an aryl group to hydrazonesby this method provides a new route to indoles.r Chiral diamines such as 1,2diphenyl-1,2-ethanediaminecan be arylated once at each nitrogen atom.a
Ph tr*-r Ar n *
"'Y\ 9r ,.
"')Pd(OAc),/ (S)-BINAP fBuONa, PhMe80"
\_Z\p.N_-y-Ph H f n
C)l*"' I rHr
L i. . :ic'd on reaction with this reagent and r. :,';Jcr. In other words, it requiresonly in DMF to complete the ::.r \a\,
"V "
i
"'Yil-J \,,/\N H
-binaphthyl 2,2'-Bis(diphenylphosphino)-1,1'
A synthesis of 2-arylaminotropones from 2-tosyloxytropone extends the scope of this method.5 Hydroaminatinn. The addition of arylamines to styrenesto afford N-arylbenzylamines is promoted by Pd(OTf)r-BINAP, although catalytic systems constituting other Pd(II) salts with TfOH are also effective.6 Faster reactions are observed with styrenes that are relatively electron poor, and those bearing an ortho-substituent fumish products in high yields. Allylation.
Chiral products are obtained from cr-acetamido-p-ketoesters.T Hetero-Diels-Alder reaction. High enantioselectivity is observed for this process using chiral cationicPd([) complexes.s Allylic displacement. The asymmetric version of the conventional displacement is improved (in ee) by using diethylzinc as a baseto deprotonatethe pronucleophiles.e Ene reaction,tO An expedient route to chiral cr-hydroxy esters is based on the ene reaction of alkenes with ethyl glyoxylate in the presenceof (S)-BlNAP-(bisacetonitrile)palladium hexafluoroantimonate. The tolyl-BINAP analogueis an evenbetterligand. tWang,Z.Skerlj,R.T.,Bridger,cJ.TL40,3543 (1999). rBolm,C..Hildebrand, J.P.JOC 65,169(2000). 'Wagaw,S.,Yang,B.H.,Buchwald, S.L.JACSl2l,l}25l (1999). rCabanal-Duvillard, I., Mangeney, P.TL 40,3877(1999). sHicks,F.A.,Brookhart, M. OL2,2l9 (20N). bKawatsura, M., Hartwig,J.F../ACS122,9546(2000). TKuwano, R., Ito, Y. JACS121,3236,]r999D. 8Oi,S.,Terada, 8., Ohuchi,K., Kato,T.,Tachibaba, Y.,Inoue,Y. JOC9,8660 (1999). 'Fuji, K., Kinoshita, N., Tanaka, K. CC 1895(1999). l{}Hao, J.,Hatano,M., Mikami,K. OL2,4059(2000). Platinum complexes Baeyer-Villiger oxi.dotion.t A BINAP-PI complex has been used to catalyze the reaction of meso-cyclohexanoneswith H2O2. Diels-AWer reaction.2 BINAP-PI(II) complexes with perchlorate and hexafluoroantimonate counterions are highly effective catalysts for the enantioselectiveDiels-Alder reaction. The correspondingPd(II) complexeshave comparable(and for certain substrates, somewhatinferior) reactivity. rPaneghetti, C.,Gavagnin, R., Pinna,F.,Strukul,G. OM 18,5057(1999). rGhosh, A.K.,Matsuda, H. OLl,2157 (199Y.
'Takaya,Y., Ogasawara, M., Hayashi,T. TL a. 2Hayashi, T., Senda,T., Takaya,y., Ogasararr Ruthenium(I I ) compIexes
Asymrnetric hydrogenation A prec from asymmetric hydrogenation of 2.3-b I,l,l-trifluoroalkan-2-ols can be synthcs
ketones.2 A general method for acccss heteroaromaticketonesais by asymmemc I
t-P... \,'
-,"iRd Ar At
(t' Catalysts containing chiral 1,2_diamir been developed for the hydrogenation of alcohols.5
6,6'-Bis(aminomethyl)_BlNAp is a prcc :Beghefto, V, Matteoli,U., Scrivanti, A. CC 155 :Kuroki,Y.,Asada, y., Iseki,K- I[ D., Sakamaki, 'Ohkuma, T., Koizumi,M., Ikehira,H., yokozerr 'Ohkuma, T., Koizumi,M., yoshida,M., No1.on 'Ohkuma, T., Ishii, D., Takeno,H., Noyon. R_,l,l 'ter Halle,R., Colasson,8., Schulz,8.,SpagDoI Silver(l) complexes
AAol reactions. A combination of A1 diastereoselective--enantioselective aldol rert
Rhodium complexes Conjugate ad.ditions. Arylborates generated in situ from ArBr are effective as asymmetric addendsr to enones in the presenceof a Rh-complex derived from BINAP and (acac)rRh(CzLlq)z.Theygive excellent chemical yields and ee (>9lvo, often 99o/o).ln these processes (such as conjugate addition to alkenylphosphonates2),the use of arylboroxines (ArBO)1 instead of arylboronic acids is advantageousbecause catalytic activity of the Rh complex decimatedby large amount of water can be avoided.
+ PhcHo
,F)
)anagisawa, A., Matsumoto, y., Asakawa, K.. ).ea
2,2'-Bis(diphenytphosphino)-1,1,-binaphthyt 55
-r . .. ,\\tropone extendsthe scopeof this ' .:\ renesto afford N-arylbenzylamines F. ilr:.- .i.tems constitutingother Pd(II) salts rt ^<-ned with styrenesthat are relatively E:.: :-:nrsh productsin high Yields. fr. : r'ecetamido-B-ketoesters.T !r: -.]!'c(lvity is observedfor this process
rTakaya,Y., Ogasawara, M., Hayashi, T. TL 40,6957 (lggg). 2Hayashi,T., Senda, T., Takaya,Y.. Ogasawara,M. "/ACSl2f , I1591 (1999). Ruthe nium( I I ) c ompl exes
Asymmetrb hydrogenation A precursor of ( gs)-cHIRApHos has been obtained from asymmetric hydrogenation of 2,3-bis(diphenylphosphinoyl)-1,3-butadiene.rchi_ral l,l,l-trifluoroalkan-2-ols can be synthesized from enol acetates of the trifluoromethyl ketones.2 A general method for accessing secondary alcohols from aromatic3 and heteroaromaticketonesais by asymmetric hydrogenation with the complex l.
rr... :. .1f the conventional displacement is I : i!-rrotonate the pronucleophiles.e $.::,. .,-hldroxy esters is based on the ene bc r:c*'nce of (S)-BlNAP-(bisacetonirile)LA.Pa:rjtrlue is an evenbetterligand. I +... :<. 1999). l'e.
(1) D' r. ) 9 t
.: 'ue.Y JOC9,8660 (1999).
'-P - mplex has been used to catalyzethe gr.:.:.r'\e\ with perchlorate and hexafluoro21,.r .1. lbr the enantioselectiveDiels-Alder r hr.:' .()mparable(and for certainsubstrates,
i , , ' , f l t 5 0 5 7( 1 9 9 9 ) .
catalysts containing chiral l,2-diamine ligands in addition to (modified) BINAp have been developed for the hydrogenation of a-amino ketones to furnish chiral l.2-amino alcohols.5 6,6'-Bis(aminomethyl)-BlNAP is a precursor of a polymer-bound ligand.6 iBeghetto,V., Matteoli,U., Scrivanti, A. CC 155(2000). : Kuroki,Y.,Asada,D., Sakamaki, Y., Iseki,K. TL 41,4603(2000). 'Ohkuma, T., Koizumi,M., Ikehira,H., yokozawa,I., Noyori,R. OL2,659 (2000). 'Ohkuma,T., Koizumi, M., Yoshida,M., Noyori,R. OLZ, l74g (2000). 'Ohkuma, T., Ishii, D., Takeno,H., Noyori,R. JACS122,6510(2M0\. "terHalle, R., Colasson, B., Schulz,E., Spagnol,M., Lemaire,M. TL 41,643(2000). Silver(I) complexes Aaol reactians' A combination of Agorf, (R)-BINAP, and RrsnoMe promotes a diastereoselective--enantioselective aldol reaction of enol trichloroacetateswith aldehydes.l
o o H ts:i:iJ rn situ from ArBr are effective as rn : ': 3 Rh-complex derived from BINAP ts:-.:-rr r reldsand ee (>9lVo, often 99Vo).In the use of [\-: : alkenylphosphonates2), catalytic because advantageous Dl, :.:Js is avoided. be water can F 3:'. unt of
(R)-BINAP - AgOTf
+
PhCHO
-----------+
R3SnOMe
/-lA,n (,
M e O H .T H F
(major) Yanagisawa,A., Matsumoto, Y., Asakawa, K., Yamamoto, H. JACS l1l,892
(1999').
-binaphthyl 22'-Bis(di-p-tolylphosphino)-1,1'
2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl + l,l'-Bi-2,2'-naphthol copolymer. Alkylation I hydrogenation.t The dual activity for the transformation of ketoaldehydes by complexes of (diamine)RuCl2 with this copolymer is clearly demonstrated. Alkylation of the formyl group with organozinc reagents (e.g., Et2Zn) followed by hydrogenation of the ketone is readily accomplished. lYu, H.-B.,Hu,
rYanagisawa, A., Kageyama,H.. Sr 38,3701(1999). 2loh, T.-p.,Zhou, J.-R.TL 41. 526 Tin(ll) complexes
Aziridines,t The reacuo aziridinecarboxylic esters.A cq
Q.-S.,Pu,L../ACS122,6500(2000).
rJuhl,K., Hazell, R. G., JorgenscnI 2,2' -Bis(diy-tolylphosphino)- 1,1' -binaphthyl. N, O.Bis(ethoxycarbonyl)hydn
Copper(I) complexes Addition
to N-tosybWimines. Protected ct-amino acids are obtained from the addition to ethyl glyoxylate under the influence of CuPF6-[p-tolyl]BINAP. Indoler and allyltributylstannane2 are typical addends.The c-hydroxyamine precursor of the imine can be used in the reaction with enol silyl ethers,sbut a higher (room) temperature is
Lossen rearrangemcnl, followed by mild basetreaunenl
-ocoot
needed.
R-COOH + Htt'
\ cooEr
NHTs l +
Etooc^oH
OSiMe3 ) +
V'pn
Ar iiot buCloa+
i-o,
NHrso Srn Etooc'
Ar
Reduction. cr,p-Unsaturatedestersaand ketonessare reduced asymmetrically, using poly(methylhydrosiloxane) as the hydrogen source. Conjugate reduction.6 p,B-Disubstitutedo,p-unsaturatedestersundergo asymmetric reduction by polymethylhydrosiloxane in the presenceof t-BuONa and a complex derived from CuCl and a slightly modified (i.e., p{olyl) (.9)-BINAP. rJohannsen, M. CC 2233(1999). 2Fang,X., Johannsen, M., Yao,S., Gathergood, N., Hazell,R. G., Jorgensen,K. A. JOC U,4844 (l999). 3Ferraris, D., Dudding,T.,Young,8., Drury,WJ., Leckta,T. JOC 9,2168 (1999). aApella,D.H., Moritani,Y., Shintani,R., Feneira,8.M., Buchwald,S.L.JACS121,9473(1999). sMoritani,Y.,Apella,D.H., Jurkauskas, V., Buchwald,S.L.JACS122,6797(20W). 6Appella,D.H., Moritani,Y., Shintani,R., Ferreira,8.M., Buchwald,S.L.JACS121,9473(1999). Silver(I) complexes Allylation, Allyltrimethoxysilanes are useful donorsr and the reaction of aldehydes with allylstannanescan be carried out in an aqueousmedium.2
rAnilkumar,
R., Chandrasekhar.S.. S
Bis(ethylenedichloro)platin.m Ring opening. 1,2_Cyclo alcoholsin thepresence of theh rBeyer,J., Madsen,R../ACS l2(). l2l
Bis(iodozincio)methane. 1,2-Cyclopropanedials. Cq a-diketonesaffordsthe vic-diolsd R
R
'
+ o'X 'o
Enol ethers.3 The title cor methylenation of estersusing TrCl. Conjugate addition,a Addio the presenceof MerSiCl leads to r chainelongation.
iii
i
Bis(iodozlnclo)methane
+ l.l' -Bi-22''naphthol copolymer' g!:r ::\ for the transformation of ketoalde6 . :..polvmer is clearly demonstrated' by 8... :.'agents (e.g.' EtzZn) followed
rYanagisawa, Y., Asakawa,K., Matsumoto,Y.,Yamamoto,H. ACIEE A., Kageyama,H., Nakatsuka, 38,3701(1999). 2loh, T.-P.,Zhou,J.-R.TL 4L, 5261(2O0O). Tin(II) complexes Aziridines,) The reaction of a-imino esters with diazoalkanes provides aziridinecarboxylic esters.A copper(I) complex can also be used.
ttr.J
'Juhl,K., Hazell,R. G., Jorgensen, K. A. JCS(Pl)2293(1999).
the | :t-emtno acids are obtainedfrom and Indoler rc ..: CuPF6-[p-tolyl]BINAP' the imine of precursor cr-rr,Jroxyamine 3 is hc:-. hut a higher (room) temperature
N, O-Bis(ethoxycarbonyl)hydroxylamine. Lossen rearrangement.t Condensation of a carboxylic acid with this reagent followed by mild basetreatment leads to primary amines with one less carbon.
.,OCOOEI +Dcc R-COOH+HN'
'cooet
'Ar
)-:
F
cucloa -
"-o,
NHTso
,rooaS'n
o tl R
N-O.. | tsO
Et3N / H2o +R-NH2
o4-ci
rAnilkumar, M.TL4l,5291 (2000). S.,Sridhar, R.,Chandrasekhar,
Bis(ethylenedichloro)platinum. Ring opening. I,2-Cyclopropano sugarsafford 2-alkyl glycosides on reaction with alcohols in the presenceof the Pt complex. rBeyer,J.,Madsen,R. JACS120,12137(1998).
using |\e:"ner: are reducedasymmetrically' Itl.
r'
rl cr.i-unsaturatedestersundergo asymmetnc prt-.nce of t-BuONa and a complex derived lr .r,BD{AP.
Bis(iodozincio)methane. 1,2-Cyclopropanediols. Consecutive nucleophilic addition of the reagentr to a-diketones affords the vic-diols that can be trapped with Ac2O and MerSiCl.2
R \
, K' A' JOC U' 4844 i ii:rcll. R. G., Jorgensen IOC 9,2168 (1999)' lr(1999)' E \1 Buchwald,S.L.JACS121,94'13 (20[0)' i 122,6797 /ACS L rIJ S.L.JACSl2l'9473 (1999)' , F.rt Buchwald,
u.<:.ll donorsr and the reaction of aldehydes IlLr'' ui medium.2
o
R
,
o
'
*/
rzn'
n 'znl
R
R
'
;;* ,oYo,
Enol ethers,3 The title compound is an alternative to the Tebbe reagent for methylenation of estersusing TiCl2 as catalyst in THF at room temperature. Conjugate additian.a Addition of bis(iodozincio)methane to enals and enones in the presenceof MerSiCl leads to reactive species that allow further functionalization or chain elongation.
Bismuth(IlD bromide
*"
Y* o
Me35iCl
tznAznl
*rAz*' ) lZn'
l
RY\R'
/"'
l OSiMea
4.2
tr.oI),,,__oyorer
oSiMe3
lMatsubara,S.,Yamamoto,Y., Utimoto,K. SZ 1471(1998). 2ukai,K., Oshima,K., Matsubara, S. JACS122,12047(2W0). 3Matsubara, S.,Ukai, K., Mizuno,T., Utimoto,K. CL825 (1999). aMatsubara, S.,Arioka,D., Utimoto,K. Sf 1253(1999).
Bis(2-methoxyethyl)aminosulfur trifluoride. Allqlfluoridcs. This reagent(MeOCH2CH2}NSF3,convertsalcohols into fluorides,l and with SbCl3as catalyst,thiono compoundsare convertedinto gem-difluorides.: Acylfluorides.3 Carboxylic acids are readily transformed into acid fluorides by this reagent in the presence of i-Pr2NEt. Weinreb amides can be prepared henceforth. N-Protected chiral o-amino acids are derivatized without racemization.
'Boyer,8., Keramane,E.-M., Roque.J.-p. 2Bajwa, J.S.,Vivelo, J., Slade,J., Reprc.O-
Bismuth(Ill) chloride. 15,37; l& 52 Beckmannrearrangemenlt \\d is completedwithin minutes(10 examp
Sulfonyhtion. Doping of Tfr sulfonylation of arenes.2Apparently. d Halogen exchange,a An al\.t I versa by using the proper BiXs) wirh r the halide substratesis primary < seco
ll-al,G.S.,Pez,G.P.,Pesaresi, R.J.,Prozonic, F.M.,Cheng,H. JOCU,7048 (1999). 2lal, G.S.,Lobach,E., Evans,A. JOC 65,4830(2000). 3Ttrnoori, A.R.,White,J.M.,Georg,G.I. OLz,4091 (2W0).
\ B r \*
Bismuth. 20,44 Nitroarene redaction.t Either azoarenesor azoxyarenes can be obtained on the reaction of nitroareneswith Bi-KOH in methanol. Allylbismuth reagents,2 Formation and use of these reagents in situ for allylation ofcarbonyl compounds can be achieved.Thus, an allylic acohol, after conversion into the iodide, readily afford the reagent by treatrnent with Bi.
'Thakur, A.J., Boruah, A., prajapati, D.. So :Repichet, S., Le Roux, C., Dubac,I. TL a. 'Repichet, S., tr Roux, C., Hernandez. p. D 'Boyer, B., Keramane,E.M., Arpin, S., Mo
Bismuth(Il!
ILaskar,D.D., Prajapati,D., Sandhu,J. S. JCS(PI)67 (2000). 2Miyoshi,N., Nishio,M., Murakami,S.,Fukuma,T., Wada,M.BCSJ73,689 (2000).
triflate. Preparation.l An improved med mixing PhlBi with 3 equiv of TOH mlxture to warm to room temperature.
Bismuth(Ill) acetate. Azlactones.t Bi(OAc)r is a useful catalyst for the preparation from ct-amino acids.
2,3-Dihydro-4-pyridones.2 Th6. rron of Danishefsky's diene and imincs. remperaturein the presenceof Bi(OTf r.
'Monk, K.A., Sarapa,D., Mohan,R.S.SC30, 3167(2000).
Bismuth(Ill) bromide. 20, 4445 BenryIation,t Alcohols form benzyl ethers on standing with BnOH in the presence of BiBrr (solvent: CCla). Selective desilylation.2 In aq MeCN, this salt catalyzes hydrolysis of a t-butyldimethylsilyl alkyl ether while preserving aryl derivatives.
Sulfunyhtion.3 Heating mixtures draryl sulfones. Acylation.a B(0Tf).] is an effoct rertiary propargylic alcohols are ace$lar.
Bismuth(Ill) triflate
tttoD"^to'^\.^orss
ttto:O,--oYoH
BiB13 MeCN- H2O
93o/o
'Boyer, B., Keramane,E.-M., Roque,J.-P.,Pavia,A.A.TL4l,289l (2W). 2Bajwa, J.S., Vivelo, J., Slade, J., Repic, O., Blacklock, T. TL 41,6021 (2000).
I
9\
Bismuth(Ill) chloride. 15,37; 18, 52; 19,37; 20, 4546 Beckmann reanangement.t With microwave assistance,the catalyzed rearrangement is completedwithin minutes (10 examples,7V90Vo). F,. .,,nvens alcoholsinto fluorides,' ne\: :nto gem-difluorides.2 l.:,'nned into acid fluorides by this de. ean be PrePared henceforth. ut :aiemizatton.
Sulfonylation. Doping of TfOH with BiCl, affords a catalysr system for sulfonylation of arenes.2Apparently, the reactive speciesis Bi(OTf)..3 Halogen exchange.a An alkyl bromide can be changed to a chloride (and vice versa by using the proper BiX3) with retention of configuration. The reactivity pattern of the halide substratesis primary ( secondary< tertiary.
I -,,( il.7M8 (1999). \
,Br
,/tt.''
D\i::!-nes can be obtained on the t|^'.: reagentsin situ for allylation rL. :.,rhol. after conversioninto the
)
tl 5t r-/ 73.689(2000).
r a:.Fsrationfrom a-amino acids.
rrr.Jrng with BnOH in the Presence csrr.rzes hydrolysis of a r-butyldi-
Bicl3
+
\
,Cl
A-",
rThakur, A.J., Boruah, A., Prajapati, D., Sandhu,J. S. SC 30, 2105 (2000). rRepichet,S., Le Roux, C., Dubac,1.TL40,9233 (lgg9\. rRepichet, S., Le Roux, C., Hernandez, P., Dubac, J., Desmurs, J.-R. JOC g, g7g Oggg). "Boyer, B., Keramane, E.M., Arpin, S., Montero, J.-L., Roque, J.-p. I55, l97l (l9gg).
Bismuth(IlD triflate. Preparation.t An improved method for the preparation of Bi(orf), consists of mixing PhlBi with 3 equiv of rfoH in dichloromethane at -78o and allowing the mixture to warm to room temperature. 2,3-Dihydro-4-pyridones.2 These are the hydrolytic products from the condensation of Danishefsky's diene and imines. The condensationis efficeintlv achieved at room temperaturein the presenceof Bi(OTf)3. Sulfunylation.3 Heating mixtures of arenes and arenesulfonyl chlorides generares diaryl sulfones. Acylation.a Bi(orf)? is an effective catalyst for acylation. Thus, in its presence tertiary propargylic alcohols are acetylatedin good yields. ILabrouillere,M., Le Roux,C., Gaspard, H., Dubac,J. TL 40,285(1999). :Laurent-Robert, H., Garrigues, B., Dubac,J. SZ 1160(2000). 'Repichet, S.,Roux,C.L.,Hernandez, P.,Dubac,J.,Desmurs, J.-R.JOCg,6479 (lggg). 'Orita,A., Tanahashi, C., Kakuda,A., Otera,I. ACIEE 19, 2877(20N).
Bis(tosyloxyethyl)diphenylsilane
Bis(pentamethylcyclopentadienyl)cerium tetraphenylborate. 2-Aryl-2,3-dihydro-4-pyranones.t The hetero-Diels-Alder reaction of Danishefsky's diene and aromatic aldehydesis catalyzedby the metallocenium complex. The adductsare readily hydrolyzed. 'Molander,G.A., Rzasa,R.M. ./OC64, 1215(2000).
Bis(phenylthio)methane. Methane polyanion.
Generation of organolithium speciesfrom this reagent can be achievedby either deprotonation and./orreductive cleavageof the C-S bond(s).r
OH awn
sPh
OH
BuLi.R2co [\Sen
L i, D T T B : R J
lrn
;"""
i\-P
OH Ln,
sPh
L''u"D O H R , lr(zl--,
rKim,B.M.,Cho,J.H.TL&,5333'tggg
Bis(tributyltin) oxide. 13,4t42: lS Oxepanes.l 2-(ct-Hydroxya$ tutionof 6,7-epoxyalcohols.An epo mediationof (BurSn)zO. The corresp yields.
rFoubelo, F., Gutierrez, A., Yus, M. TL 40, Sl77 (1999).
IBis(2-pyridyldimethylsilyl)methyl]lithium. Alkenylsilanes. The precursoabis(2-pyridyldimethylsilyl)methane,is available from 2-trimethylsilylpyridine via lithiation, reaction of the resulting 2-PyMe2sicH2li with 2-PyMe2SiH. Lithiation of bis(2-pyridyldimethylsilyl)methane with BuLi in ether and treatment with carbonyl compounds furnish alkenylsilanesin good yields.l
4'N
Nz\
BuLi ; RR'CO
4-n
\As,-yn' /\ A
\A.,^siV
R'> R in bulkiness
Matsumura,R., Suzuki,T., Sato,K., Ob {1, 7701(2000).
Bis (2,2,2-tnfluoroethyl)acytmetbylpl
Functionalized alkcnes. (ZyF, nates by the Emmons-Wadsworth ree preparedfrom the cr-bromo-c_phosph
o
rltami,K., Nokami,T.Yoshida, I. OL2, 1299(200CD.
)'Bis(2-tosyloxyethyl)diphenylsilane. Protection of amines.t Reagent I is prepared from diphenyldichlorosilane by the following sequence: reaction with vinylmagnesium bromide, hydroboration of the resulting divinylsilane, and tosylation. The 4-diphenylsilapiperidines that are formed with primary amines can be cleaved by exposureto Csfl BurNF in THF or DMF.
????? r-c Pr.-o o-\ CFr
Yu,W.,Su,M., Jin,J. TL 40,6725,l999t Tago,K., Kogen,H. OL2, 1975e(J/J[t.
3,3-Bis(2,2,2-trifluoroethyl)phosphonates
E{|l lborate. 'D::. - .{lder reaction of Danishefsky's It:.. rr-ntum complex. The adductsare
Ph,r-r Si Ph'\-
6l
/OTs \
OTs
(r) h:-':. .pcciesfrom this reagentcan be kcr:irr of the C-S bond(s).r
c\
3H -R'
'R'
-<.^,
L r, D r r B a
n K
oH I
n>\Z\
R' I
n'
rKim, B.M., Cho,J.H.TL 40, 5333(t999).
Bis(tributyltin) oxide. 13,4142;15, 39; 18, 54; 19, 4O;20,50 Oxepanes't 2-(ct-Hydroxyalkyl)oxepanes areobtainedby an intramolecularsubstitution of 6,7-epoxyalcohols.An epoxidethat is part of a glycidyl ethersystemreactsby mediationof (Bu.sn)2o.The corresponding glycidyl estersaffordrelatedproductsin low yields.
(Bu3Sn)2O / PhMe; + Eu(OT03
&:'.:t:.r lrilyl)methane,is availablefrom f ::. :.'sulting 2-PYMe2SiCH2Liwith lr.< ^:th BuLi in ether and treatment l g ' . . :r r e l d s . l
.4t !,-
x tl
\A",'\',R' ,/\
| I
R
r} -€ss
'Matsumura, R., Suzuki, T., Sato, K., Oku, K., Hagiwara, H., Hoshi, T., Ando, M., Kamat, Vp. TL
4r,7701(2000).
Bis(2,2,2-trifluoroethyl)acylmethylphosphonates. Functionalizedalkcnes. (Z)-Enonesare accessiblefrom the acytmethylphosphonatesby the Emmons-wadsworth reaction.rsimilarly, (E)-a-bromoacrylates havebeen prepared from thec-bromo-ct-phosphonoacetate esters.2
O tl
(
,,\-f'-"
/-cFs
o-1 CFs
r.J :r,,m diphenyldichlorosilaneby the r..-::: bromide, hYdroboration of the that are formed with p3:.,..:lapiperidines f
b.;-\F in THF or DMF.
\u. W.,Su,M., Jin,J. TL40,6725(1999). Tago,K., Kogen,H. OL2, 1975(20N).
(Me35i)2NK
o ,\:
Ph
95o/o (all Z-)
ds-2,3-Bis(trimethylsilyl)cyclopropanone
2-Bis(trifl uoromethylsulfonyl)amino-s-chloropyridine. Triflation,t The stereochemical outcome in the O-triflation of p-keto esters (K salts) with this reagent is solvent dependent:(E)-selective in THF, (Z)-selective in DMF. lShao,Y., Eummer,J.T.,Gibbs,R.A. Ol, 62'7(199r. \
2,2' -Bis(2-trimethylsilylethoxyrnethor.vF 2- (TrimethyIsily I) ethory methylation_: towardsilyl enolethersin thepresence of S
o+
N, O-Bis(trimethylsilyl)acetamide. Proton acceptor.t In the displacement reaction of allyl carbonates with nitroalkanes,the presenceof this silylated acetamideaffords good diastereoselectivity.
co
. NSiMe3
t/'(
OSiMe3
+
OCOOMe
(
l
Noz
cH2ct2
Noz
I Ishihara, K., Nakamura, H., yamamoto, H..lr{C!
85Yo Methyl p-nitrosoacryIate.2 Methyl 3-nitropropionate is partially deoxygenatedby N,O-bis(trimethylsilyl)acetamide. In the presence of a cyclic conjugated diene the conjugated nitroso compound is trapped as a Diels-Alder adduct.
.NSiMe3
or*),
OSiMe3
\cooM"
o*a""""" c'lua.""""l
Nucleotide phosphates.3 Nucleoride phosphatesin dichloromethane by bis(tnrn bis(trimethylsilyl)acetamide and a catalyuc :
X = CHz 57% X = CHzCHz 21%
rTrost,B.M., Surivet,J.-P.JACS122,6291(2000). 2Tishkov, A.A., Lyapkalo,I.M., Ioffe, S.L.,Strelenko, Y.A.,Tartakovsky, V.A. OL2, 1323(2000). cis-J 3-Bis(trimethylsilyl)cyclopropanone. Furans.t The reaction of this reagent with cr-ketomethylenephosphoranesunexpectedly affords furans.
t".t'^,_
ro
Me3Si
ph3p:
Bis(trimethylsilyl) peroxide. 20, 5 I Nef reaction.t Nitronate ions are orrd Addition to double bond.2 Alkenes r acetoxy alcohols on reaction with Me,SiX promotionby a Lewis acic.
Me3Si]-
uesilo\n R = Me 70%
'Takanami, T., Ogawa, A., Suda, K. TL 41, 3399 (2N0).
Shahi,S.P.,Vankar, Y.D.SC 29,4321(tc)ggt. -Sakurada, I., yamasaki, S.,G
3J-Bis(trimethylsityl)propene.
3-Piperideines.r Desilylative con&ns primary amine (CFTCOOH promotion) resuh
Messi.rl + | SiMe3
\*.R N
CF3COO-
i,
MegSil-
* (77 : 23)
(o\*
4-Amino-I-trimethylsilyl- I-buUnel: ll reagent.Silylatedhomoallylic aminesare obu
Pnncet,B.,Anselme, G.,pornet,J.JOMC Sg2.y Pnncet, 8., Gardes-Gariglio, H., porner,J. JO.VCI
3,3-Bis(trime\lsilyt)propene
!g\ ridine. ! .: ric O-triflation of p-keto esters (K i ,-.( -'-tr\ e in THF, (Z)-selective in DMF.
2,2'-Bis(2.trimethylsilylethoxymethoxy)_1,1, -binaphthyl. 2-(Trimethylsilyt)ethoxymethylation.t The ether I behavesas an electrophile towardsilyl enolethersin thepresence of SnCla.
F
anfr
I :.:.'.r\\n of allyl carbonateswith nitrod. :::.,rdi good diastereoselectivity. \:
?Y--o -\_oa..,"",
\..V
r.'-
C: ".
(1)
Noz
I Ishihara, K., Nakamura, H., yamamoto, H. JACS 121,7720 Oggg\.
85To uu, ::,,pronate is partially deoxygenatedby ?\':.c of a cyclic conjugated diene the D:: . \lder adduct.
(l'o
\i,il
c'
\"oo""
)c r,'e
X = CHz 57o/o X = CHzCHz 21Vo
!. \ i
ro,\- ,siMes
\-\.d
Tanalovsky,V.A.OL2, 1323(2000).
uns1 .i::h o-ketomethylenephosphoranes
Bis(trimethytsilyl) peroxide. 20. 5 I Nef reaction.t Nitronate ions are oxidized at room remperature. Addition to doubre bond-2 Alkenes are converted to either chlorohydrrns or I,2acetoxy alcohols on reaction with Me.,siX (x : cl, oAc), MerSioosiMe., and with promotionby a Lewis acid. Nucleotide phosphates.r Nucreotide H-phosphonates are oxidized to the phosphatesin dichloromethane by bis(trimethylJlyr) peroxide in the presence ot N.o_ bis(trimethylsilyl)aceramide and a catalyticamountof MerSiOTf. rShahi, y.D. SC 29,4321(1ggg). S.P.,Vankar, rsakurada, I., Yamasaki, S , c.l , Iida.T., Kanai,M., Shibasaki, M. JACS122,t24s(2000). 'Kato, ili:!:l .lggg\. y SL 1796 T., Hayakawa, 3,3-Bis(trirnethylsilyl)propene. 3-Piperideines.I Desilylative
condensation of this reagent with HCHO and a pnmary amrne (CFjCOOH promotion) results in the heterocycleformation.
"*t'n
. ox,*cF3coo+
'r'te:sitfA i," / Cr*
Me3Si/\-
o ,,lg
70To
(77
R'= H
(o\*
. 23)
4-Amino-I-trimethylsilyl-I_butenes.2 Iminium ions are readily trapped with this reagent.Silylatedhomoallylic aminesare obtained. Princet,B., Anselme,G., pornet,J. JOMC 5g2,34 Oggg\. :Princer, 8., Gardes-Gariglio, H., pornet,I. JOMC 604:iiO
fzOOOt.
9-BBN 9-Borabicyclo[3,3.1]nonane,
Bis(trimethylsilyl) sulfi de. Thiols.t Preparation of thiols from alkyl halides is readily carried out with a combination of (MerSi)zS and BuaNF (9 examples,68-94Vo).
Borane-amines.13,42;18, 58; 19, 43-41.2 Boraneadductswith tertiary aminesrn (".9.,1' and22)havebeenprepared for hldn
1Hu,J.,Fox,M.A. JOC 64,4959(1999). \/
9-Borabicyclo[3.3.1]nonane, 9-BBN. 14, 52-53; 15, 4344; 17, 49-50; 20, 52 Aminoethyl extension.t Hydroboration of benzyl N-vinylcarbamate with 9-BBN followed by a Suzuki coupling with aryl or alkenyl substratesaccomplishesa synthesisof theseamines (still in protected form). Cyclopropanes.' Rryt- and alkenylcyclopropanes are readily prepared from propargyl bromide via hydroboration and Pd-catalyzedcoupling of the B-hydroxyborates with aryl and alkenyl halides.
H , / q\
as
Br
|
+€
{u'o' rHF ^;
--*oH*
PhBr (Ph3P)4Pd
Cyclization. A rare but documented C-{ boranemoiety and a ketoneis againrevealed.l
bond formation involving an organo-
OTBS g-BBN;
./V*r/
\,2
| -BH:
) (1)
Reductions. syn-Selectivereduction of observedwith borane-pyridine in the preserx predominatein the reductionwith LiBHEr,{
(PhrP)4Pdcatalyzesremoval of the R SC the transforrnationof 1,6-epoxy-o,B-unsarur tcrs by the borane-dimethylaminecompler Allyl group scavengers.l In the solrd" nitrogenby an N-allyloxycarbonylgroup can the presenceof a borane-aminecomplex.
Brown,H. C., Kanth,J.V.B.,Dalvi,p.V. Zaidles Brown,H. C.,Kanth,J.VB.,Dalvi,p.V. Zairlleu Uartoli, G.,Bosco, M., Bellucci, M.C.,Dalpozzo I '\larcantoni, E., Alessandrini, S.,Malavolta. \t . g R JOC64,1986(1999). l-ipshutz, 8.H.,Buzard,D.J.,Vivian,R.W.11.{). { I)avid,H.,Dupuis, L., Guillerez, M.-G..Guibe.F l (iomez-Martinez, P, Dessolin, M., Guibe.F...{lh.
CrO3- HOAC
MeOOC
Reduction of lactams.a Tertiary lactams are transformed into tertiary amines. 9BBN holds an advantage over borane because it does not complex with amines and therefore no excessreagent is required. B-Methyl-BBN.5 B-Methyl-BBN traps N-unsubstituted aldimines as stable adducts from their N-trimethylsilyl derivativesduring methanolysis. rKametani, L.E.JOC9,8743 (1999). A., Overman, zSoderquist, J.A.,Huertas,R., Leon-Colon,G. TL 41, 4251(2000). rBoeckman. R.J.ZL 41,603(2000). Jr.,R.K.,Mitchell,L.H.,Shao,P.,Lachicotte, aCollins, B.TL40,3673(2000). CJ.,Lanz,M., Singaram, sChen.G.-M.,Brown,H.C.JACS122,421'1(2000).
Boron tribromide. 13,43; 14, 53-54; lg. -s9. Ring contraction.t 3-Methoxypipendrn [38r, in dichloromethane.This reactionis a rar
!""-"'oru"
R .l
-N' R'
I
8Br, :^
Boron tribromide
r: readilY carried out with a
)a.,j:(.. .l;I
15.:: -r+.17,49-50;20,52
Borane-amines. 13,42; 18,58; 19,43-44;20,53 Boraneadductswith tertiary aminesin which one of the alkyl groupsis tertiary (e.g.,1' and22)havebeenpreparedfor hydroboration.
XX,,I
'BHs
!r:.. r. \'-r'inylcarbamatewith 9-BBN I . --.::.rtes accomplishesa synthesisof lr.(- i. readily preparedfrom propargyl with aryl il::- : rhe B-hYdroxYborates
.cPhBr \
rr,,P)oPd
J
I -.
.: l,rrmation involving an organo-
x_,J--
)
l'eH.
(1)
(2)
Reductions. syn-Selectivereductionof 1,3-diketones3 and a-alkyl-B-keto estersais observedwith borane-pyridine in the presenceofriclo. on the other hand, anri-products predominatein the reductionwith LiBHEt3-CeClr. (PhTP)4Pdcatalyzes removal of the Rrsor group from aryl perfluorosulfonates5and the transformationof 1,6-epoxy-o,B-unsaturated esters6to 6-hydroxy-a,B-unsaturated estcrs by the borane-dimethylaminecomplex. Allyl group scavengers.l In the solid-phase peptide synthesis, the protection of nitrogenby an N-allyloxycarbonylgroup can be removedby a pd(O) catalyz.ed,reaction in the presenceof a borane-aminecomplex. Brown,H. C., Kanth,J.VB.,Dalvi,P.Y.,Zaidlewicz,M. JOC 65,4655(2000). ,lgggl'. Brown,H. C., Kanth,J.V.B.,Dalvi,P.V, Zaidlewicz , M. JOC 64.6263 Bartoli,G.,Bosco,M., Bellucci,M.C.,Dalpozzo, R., Marcantoni, 8., Sambri,L. OLZ,45 (2000). '\larcantoni,ts.,Alessandrini, S., Malavolta, M., Bartoli,G., Bellucci,M.C.,Sambri,L., Dalpozzo, R .J O C6 4 , 1 9 8 (61 9 9 9 ) . l-ipshutz, 8.H.,Buzard, D.J.,Vivian,R.W.fL 40,6871(1999). l)avid,H.,Dupuis, L.,Guillerez, M.-G.,Guibe,F. Tl,41,3335(2000). (lomcz-Martinez, P, Dessolin, M., Guibe,F.,Albericio,F.JCS(pI ) 28'71(1999).
Boron tribromide. 13, 43; 14, 53-54;18, 59; 19, 45; 20, 54 Ring contraction.t 3-Methoxypiperidinesundergoring contractionon exposureto 13Br,in dichloromethane. This reactionis a rare transformationof piperidines. li:
r:in.iorrned into tertiary amines' 9-: r\ not complex with amines and
ua. ^.lrtuted aldiminesas stableadducts . r' i r ' t:
';.,^'r',-ove R-t \"/
I
A,
BB4l CH2C|2
R R-/--\
\*\-a'
A,
r:. - . { ) ) . ;r: : I 11.{1.603(2000). fl
. r h r a n i ,K . A . , V a n S y n g e l ,K . , B o e l e n sM , . , C o n t r e r a sJ,. , D e K i m p e , N . , K n i g h t ,D . W . T L 4 l , 2 S 0 . l :rn0).
Boron trifl uoride etherate
Boron trichloride. 13, 43;14, 54; 15,44; 18,59-60; 19, 4546; 20, 54-55 Ether cleavage. Trityl etherssuffercleavageselectively.lPhenolsarereleasedfrom tuOCH"Rwith BCl,.2
=t"'\".toK
Dealkylation.a Tertiary amines are c amines on treatment with Ac2O-BFj.OEt,. y-Ketoesters.s Fischer carbene compl BF, serve as acyl anion equivalentsin a con;
tt'\r.o',
:1p
9Li 9104
Benzal chlorides.3 Chlorodeoxygenation of aromatic aldehydes is readily accomplishedwith BClr in refluxing hexane(9 examples,76-99V"). Alkenyldichloroboranes.a The species that are useful for Suzuki coupling can be preparedfrom alkenylsilaneswith BClr in dichloromethane. lJones, A. JOC 65,263(2000). G.B.,Hynd,G.,Wright,J.M.,Sharma, 2Brooks, P.R.,Wirtz,M.C.,Vetelino, M.G.,Rescek, D.M.,Woodworth, G.F.,Morgan,B.P,Coe,J.W. JOC 64.9719(1999). rKabalka, G.w.,wu, z. TL 41,579(2000). 4Babudri, F.,Farinola, G.M.,Naso,F.,Panessa, D. JOC 65, 1554(2000).
Boron trifluoride etherate. 13, 4347; 14, 54-56; 15, 4541; 16, 4447; 17, 52-53; 18, 6043 ; 19, 4648: 20, 5 5-57 Heterocycles, Alkenyl and aryl boronates deliver their organic residues to the aposition of the nitrogen atom of cyclic carbinolaminesto replace the hydroxyl group.l Synthesisof 2,3,5-trisubstituted furans.rfrom a catalyzedreactionof alkynyl boratesand
RF^.oFt^ -;*
RAlrlo(co)u
oBF: RALror,
Reactions of alkyne-cobalt complcxet propargylic alcohol containing a juxtaposed propargylic hydroxyl on treatment with BF,
involved.6Complexesof vic-diolsgive decon
Ph
o'' :
I
B F :- C €
enones,is achievedin one step.
-JOH /
\
\N,^oH
+
r? to-B.7-e,
6ooan
.J
BF3.OEt2
.oH
\n,Y
cH2ct2 78" - 25"
6ooen 93%
Fusedoxepanearrays are derived from regioselectiveoxacyclization of polyepoxides.r
o
X"A"
,
lto -
-. o=.u
BF".OEb cH2ct2 - 40"
\
Rearrangements. Cyclic ketones un :rdroxyalkyl azides.sRegioselectivity is dr Iir.ckmann rearrangement of ketoxime c: ::'mperatur€.
There is a change in the regiochemica :strahydropyridylallyl ether by BF3.OEt.. Tl :ition involving cyclic ketones and aldehrd :lr'nt of hydroxyalkyl epoxides.rr Ultimarc -.eloalkenes.
Boron trifluorid€ etherate
20,54-55 T . .' 19.15-461 from Phenolsarereleased . .cicctively.r
3:
Deallqlation.a Tertiary amines are converted into the acetamides of secondary amines on treatment with AcrO-BF..OEtr. y-Ketoesters.s Fischer carbene complexes in which the oxygen atom is bonded to BF2 serve as acyl anion equivalentsin a conjugate addition.
Et3Si.
-
\
'\Ao.-. 91%
OLi
OBF,
nAvro(co),#
o tl
4"oor.
*Arot.ol.
R
"
'cooMe
56%
: .rromaticaldehydesis readily accomf. -6-99qr). lj-: -.. a. : .irL'useful for Suzuki coupling can be -.'nr!'thane. h. .r
r,5 161(1000). \1 \\irodworth,G.F.,Morgan,B.P.,Coe,J.W
Reactions of alkyne-cobalt complexes. The hexacarbonyldicobalt complex of a propargylic alcohol containing a juxtaposed benzyloxy group suffers elimination of the propargylic hydroxyl on treatment with BFr'OEt2. An intramolecular hydride transfer is involved.6Complexesof vic-diols give deconjugatedalkynones.T
f,5. r 55.1(2000).
Ph
'n. 15. -15-47;16, 4441 ; 17, 52-53; 18,
g'
OH
o:., -. Jcli\er their organicresiduesto the al .,rnrne\to replacethe hydroxyl group r' n - . ..rtal\ /ed reactionof alkynyl boratesand
| V
.o'
QH : ::
OEt;
*\*,
__^/oH /
\
\*,,,%tu =
'. - 25
6OOen 93%
r,-
of polyepoxides'3 .-'lc'ctive oxacyclization
Rearrangements. Cyclic ketones undergo ring expansion on reaction with hydroxyalkyl azides.sRegioselectivity is dependenton steric and electronic factors. Beckmann rearrangement of ketoxime carbonatesv has been observed at room tcmperature. There is a change in the regiochemical course for Claisen rearrangementr0of a retrahydropyridylallyl ether by BF3'OEI2.The problem in stereocontrolof the aldol re.rction involving cyclic ketones and aldehydescan be solved by way of the rearrangenrent of hydroxyalkyl epoxides.lrUltimately, it rests on the proper choice of the haloalkenes.
Boron trifluoride etherate
z\
i p-cymene
ov\
tI
a\ o)o)
a-amino-B-hydroxy acrds catalyzedprocesshas adr upon Ctwo stereocenters
(*,J COOBn
n -f*o*
I
\*/ fooen
I
ov^
| ,r..o.,, t - - _ MeCN
oHo\r} --+>Z\-*l l]--l-,J W-=\4U' O
EtoocN./
*4o.,
COOBn
febrifugine
Dehydration. 'n P..tf rr ith a dicobalt hexacar tirrmedby dihydroxr'latr i -alkynones.
imidazole-SiMe3 ; + / CH2Ct2 BF3.OEt2
-=\
imidazole-SiMe3 ;
OH I
C
SnCla/ CH2C12
Alkenyl methyl sulfides.t2 BF.r.OEt2 plays a role in promoting the Homer condensation. Mannich-type reactions.t3 Aldimines are activated in preference to aldehydes by BFj.OEt2 (0.2 equiv * 10 equiv Hzo) toward condensationwith silyl enol ethers. reaction of an araldehyde with a symmet(E)-Styrenes.ta The BF.1.OEI2-catalyzed
Cyclic mutation. ln -rehangefbr an aziridinc - hain.The transformation
rical ketone leads to styrenes.
r4-'r7cHo I ll 9a'
+O{
aJ-
BF3.oEtz 4 | ll hexane \Acl
\ 88%
syn-1,2-Amino alcohols.ls It is possible to utilize 1-oxygenated allylstannanesto prepare enantioenrichedsyn-1,2-amino alcohol derivatives that are potential precursorsof
Boron trifl uoride etherate
a-amino-B-hydroxy acids, B-amino-ct-hydroxyacids, and aza sugars.This tsFr.oErrcatalyzed processhas advantagesover other methods becauseit stereoselectively creates two stereocentersupon C-C bond formation.
n
rZ\rtN-:
^Ho.r'1
W-'-Yu'
B.
Etooc_
f\ort'r"
+
N.J
f\ove
a\/':
t TBSO
BF3.oEt2
SnBu3
ETOOC
cts2cl2 -78
R
nAoet
'N.J \.-\-
R = i-Bu
IJ
OTBS 90%
febrifugine Dehydration.r6 Propargylic arcohors are readiry dehydrated after comprexation with a dicobalt hexacarbonylresidue. Interestingly, renewed treatment of the diols (lbrmed by dihydroxylationof the double bond) with BF..OEt, leadsto the deconlugated -1-alkynones.
if.L
OH |
_
Co2(CO)6
-
Co2(CO)6
BF3'oEt2 *:Z\--
/
\*.
-R'
I osoaNMo: I gr,.oe,, i
I ., . . r role in promoting the Horner
_
.Co2(CO)6
^\t"\.-
ll
el. .:-::rated in preferenceto aldehydesby :rn.ationwith silyl enol ethers. l. d '-.,-:r,rnof an araldehydewith a symmet-
:
.# .ycl t
t
o
/
-R'
cyclic mutation. Intramolecularallylation leads to formation of a carbocycle in -'rchangefbr an aziridine when the heterocyclecontains an allylsilane moiety in a side .hain.The transformation is initiatedby BF.,.OEt..r7 l
88Yo
BF3.OEt2 cH2ct20,
:trlrze 1-oxygenatedallylstannanesto n :-::\.ttlves that are potentialprecursorsof rk'
-\
N
Ts
r^.-/\.
(..),,,,-NHt.
*
(2-2.8 :
a\."'\ (.-J..,,-NHrs 1)
A twofold intramolecular Friedel-Crafts alkylation servesto create the tricyclic skeleton of the pseudopterosins.rx
Bromine trifluoride. 19, 48 Tifluoromethyl ethers.t These etherr into xanthatesand then treatedwith BrF,. Halogen exchange. Replacement oi r affords a simple approach to potentialll am the synthesisof CF.CH2OCFIfrom CF.CH-(
rBen-David, I., Rechavi, D., Mishani,E.. Rozen.S rHudlicky,T., Duan,C., Reed,J.W.,Yan.F..lluJl (2000). OMe
rBatey.R.A.. MacKay, D.B., Santhakumar,V "IACSl2l, -507-5 (1999). r B r o w n .C . D . ,C h o n g ,J . M . . S h c n ,L . T 5 5 , 1 1 2 3 3( 1 9 9 9 \ . r M c D o n a l d ,F . E . ,W a n g ,X . , D o , 8 . , H a r d c a s t l eK, . L O L 2 , 2 9 l ' 7 ( 2 0 0 0 ) . rDave. PR., Kurnar,K.A., Duddu, R., Axenrod,T., Dai, R., Das, K.K., Guan, X.-P, Sun, J., Trivedi, N . J . ,G i l a r d i ,R . D . " r O C 6 5 , 1 2 0 7( 2 0 0 0 ) . 5Barluenga,J., Rodriguez,F., Fananas,FJ. CEJ 6, I 930 (2000). " D i a z . D . , M a r t i n .V . S .T L 4 1 , 7 4 3 ( Z O 0 O ) . rDiaz. l).. Martin. V.S. Z1.40. 28 | 5 ( 1999). s S m i t h .8 . T . , G r a c i a sV , . ,A u b e ,J . J O C 6 5 , 3 7 7| ( 2 0 0 0 ) . ')Anilkumar, R., Chandrasekhar, S. 7L 41, 5427 (2000). r " T a k c u c hY i , . , H a t t o r i ,M . , A b e , H . , H a r a y a m aT, . S l 8 l 4 ( 1 9 9 9 ) . r l B a l d w i n .S . W . ,C h e n ,P . .N i k o l i c , N . , W e i n s e i m e rD, . C . O L 2 , I 1 9 3( 2 0 0 0 ) . r r s t e p h a nE, . , O l a n r ,A . . J a o u e nG , . T L 4 0 , 8 5 71 ( 1 9 9 9 ) . r r A k i y a m aT , . , T a k a y a J, . . K a g o s h i m aH . . CL947 (1999). r r K a b a l k aG , . W . ,L i , N . - S . ,T e j c d o r D , . . M a l l a d i ,R . R . ,T r o t m a n ,S . J O C 6 4 , 3 1 5 7( 1 9 9 9 ) . r 5 M a r s h al ,fJ . A . ,G i l l , K . . S e l e t s k yB, . M . A C I E E 3 9 , 9 5 3 ( 2 0 0 0 ) . L r ' S o l eMr .. A . , M a r t i n ,V S . 7 1 4 0 , 2 8 1 5( 1 9 9 9 ) . l r B e r g m e i e rS, . C . .S e t h ,P . PJ. O C 6 4 , 3 2 3 1( 1 9 9 9 r . I n H a r r o w v e nD, . C . .S i b l e y ,G . E , . M f. L 4 0 , 8 2 9 9 ( 1 9 9 9 ) .
B-Bromocatecholborane-acetic acid. Cleavage of MOM ethers,t This coml of the methoxymethyl group from prrxc dichloromethane.Complicationsariseif acet are formed in the caseof protected3-aminr4 Y u .C . ,L i u ,B . ,H u ,L S . T L 4 l , 8 l 9 ( 2 0 0 0 r .
2-Bromoethyl acetate. Amine protection.t SecondaryamrncThe products are reverted to RR'NH on p*r benzophenone. Cossy, J.,Rakotoarisoa, H.TL41,2097t2UXt' Bromoform. a-Methoxycarboxylic acids.t lcadsto the acids.
Treatrnc
Yabuuchi, T., Kusumi,T. CPB47,684( 1999, Bromine. 13,47',14,56 57; 15, 41; 78, 64; 19,48; 20' 57-58 Su$oxides.t Thc oxidation of sulfidcs with the brominc hexamethylenetetramine complexis a rapidand high-yieldingprocess(7 cxamples.9l-987o). Oxidation.z Bromine adsorbedon alumina (0.77 mmol/g) is useful as an oxidant 1br alcohols.It is stablein a stoppcredbottle lbr severalmonths.The oxidation is carried out in thc solid state. Cleavage of tertiary alcohols.\ Bromine-K.CO, in chloroform at 0o performs a ketones. retro-Barbierreaction.Thus, cyclic tertiary alcoholsgive o-r-bromoalkyl rShaabani. H.R.SC30,265(2000). M.B.,Safaei, A.,Teimouri, rl-ove,B.8.,Nguyen,B.T.SC30,963(2000). rZhang, W.-C.,Li,C.-J.JOC650,5831(2000).
B romomethydiisopropoxyborane. 1,3-Diols.t Allylic alcoholsare selecrr horates.Radical cyclization followed hr or nrocess.
,Yo' Y*j'"Y v
o-, Br/
Bronomethydiisopropoxyborane
\)n :crves to createthe tricyclic skele-
Bromine trifluoride. 19, 48 Trifluoromethyl ethers.t These ethers are formed when alcohols are transformed into xanthatesand then treated with BrFj. Halogen exchange. Replacement of other halogen atoms by fluorine using BrFl affords a simple approachto potentially anestheticfluorinatedethers.2Examplesinclude the synthesisof CFICH2OCFjfrom CFTCH2OCF2CI. :Ben-David, I., Rechavi, D., Mishani,E.,Rozen,S.JFC 97,75(1999). rHudlicky,T., Duan,C., Reed,J.W.,Yan,F.,Hudlicky,M., Endoma, M.A., Eger,E.l. JFC 102,363 (2000).
OMe
t . l < i r r s( 1 9 9 9 ) . ,i :. 19l7 (2000). , R . l ) a s . K . K . , G u a n ,X . - P . ,S u n ,J . , T r i v e d i ,
d
B-Bromocatecholborane-acetic acid. Cleavage of MOM ethers,t This combination of reagentsenables smooth removal of the methoxymethyl group from protected l,3-diols and l,3-amino alcohols in dichloromethane.Complicationsariseif aceticacid is omitted.For example,1,3-oxazines areformed in the caseof protected3-aminopropylmethoxymethylethers. Y u .C . ,L i u ,B . ,H u ,L S . T L 4 l , 8 1 9( 2 0 0 0 ) .
: ,l{XX)).
I e g g) . I ) / 2 . I 1 9 3( 2 0 0 0 ) .
t:
2-Bromoethyl acetate. Amine protection.t Secondaryaminesare protectedby alkylation with this acetate. The products are revertedto RR'NH on photolysis in the presenceof 4,4'-dimethoxybenzophenone. (2000). H. TL 41,209'7 J.,Rakotoansoa, Cossy,
I
" r ' . r nS. .J ( ) ( " 6 4 , . 1 1 5( 17 9 9 9 )
I I
'
r,,
Nt ) ) .
L
Bromoform. a-Methoxycarboxylic acids.t lcadsto the acids.
Treatment of ketones with CHBr,, KOH in methanol
\hbuuchi,T., Kusumi,T. CPB47,684(1999). :.: 20.57-58 :ir thc hromine-hexamethylenetetramine 9 | -98o/c). - r.rtrrples. ,r).77 mmol/g) is useful as an oxidant ., .crcral months.The oxidationis carried
Bromomethydiisopropoxyborane. 1,3-Diols,t Allylic alcoholsare selectivelytranstbrmedinto 1,3-diolsvia the mixed horates.Radical cyclization followed by oxidative C-B bond cleavagecompletesthe process.
K ('O, in chlorofbrrn at 0" performs a .. rirc t'r-brclmoalkylketones. i
-
'Yo' Y-j'"Y
N t ) ) \t/
."''tZO-o'OY | \)
,,)
( M e 3 S i ) 3 S-i H A I B N; NaOH - H2O2
a--/on t l \-\-oH
74%
72
N-Bromosuccinimide
rBatey, R.A.,Smil,D.V.TL 40'9183(1999)' 49;18,65-67;19' 50-5 1; 20' N-Bromosuccinimide. 13,49;14,57-58; 15, 50-5 1; 16, 58-59 bromination in acetone'r Brominations. Hydrochloric acid is a catalyst for arene Deactivatedarenesare brominated with NBS-CFTCOOH-H2SO4'2 Somehydroxylatedheterocyclesarereadilybrominated(e.g.,2.hydroxypyridineto2bromopyridine) by reaction with NBS-PhlP'r Propiolic acids undergo Reaction with unsaturated acids and derivatives. in the presence of a quaternary halodecarboxylation at room temperature with NXS from alkenoic acids can be ammonium salt.4Analogous Hunsdiecker reaction products usedin situ for Heck couPling.s
r Sugimoto,O., Mori, M., Tanji, K. TL 4O.717"it I rNaskar D., Roy, S. JOC 64,6896 (1999). sNaskar,D., Roy, S. 256, 1369 (2000). nNaskar,D., Roy, S. ,/CS(P/) 2435 (1999t. TPatrocinio. A.F.. Moran. P.J.S.,/OMC 603. ::fr ,: sTatsugi,J., Tong, 2., Amano, T., Izawa. Y. H 5-1, eKarimi, B., Seradj,H., Ebrahimian,G.R. 51, lr5t "Karimi, B., Ebrahimian,G.R, Seradj,H. O/, l. I '
P-Bromotri(pyrrol-1-yl)phosphoniumbru Formamidines,r This well-knownrcag lbr reactionwith primaryaminesto furnishto
NBS, Bu+N(OCOCFa)
4"oott
R-NH2.
to(oo"),
H
Ph3sb- Licl -Et3N
NMer
I
rt=\
+(r"-t ( '
Y o
81o/o
Conjugatedamidesare cyclizedto afford B-bromo-o-lactams'6 hydrolysis on exposure to Acylsilanes.l 2-Silyl-1,3-dithianesundergo oxidative or barium hydroxide)prevents NBS in aqueousacetone.Addition of a base(triethylamine further conversionof the productsto carboxylic acids' l.Alkyt-7-azaisatins,sT-AzaindolesarebrominatedatC-3withbromine.TreatmentoftheproductswithNBsinDMSotransformsthemintotheisatins.
Delarue, S.,Sergherart, C.TL40,5487(1999'
t 1.3-Butadien-1-yl)dimethylsulfonium tctlr Alkenyl epoxides.t A three-compont'n rldehyde,and the dienylsulfoniumsalt.
ETOOC
N B S, DIVSO 60'- 80'
N
"n-cHo*
y'€!/ BFa
+ *"- Yt' I
NHAC
R 87 -90Yo
Rowbottom, M.W.,Mathews, N., Callagher. T ,/( acetalization with triethyl Acetalization. The use of NBS as a catalyst for although fbrmation of orthotbrmate" shows chemoselectivity in favor of aldehydes, is present 1,3-propanediol when ketone acetalsis also feasible.1,3-Dioxanesare formed in the reaction.r0 rAndersh, B., Murphy,D.L.,Olson,R'J SC30,2091(2000)' 2Duan,J., Zhang,L.H., Dolbier,W. R' SL 1245(1999)'
' 2.3-Butadien-1-yl)tributylstannane.
Preparation.t A simple route to this rt .rith BuiSnLi. Note that coupling of l.-l-hut :lds to the triphenyl analoguebut the coup - hange.
(2,3-Butadien-l-yl)tributylstannane
! lr.
l r r .- : ' t ;1 E . 6 5 - 6 71:9 , 5 0 - 5 1 ; 2 0 , - .Lrc-ne bromination in acetone.l
c " it H.so..r D:- :i-J r!-g..2-hydroxypyridine to 2lcntutites. Propiolic acids undergo thc presenceof a quaternary \\.. n : :..,i\ lrom alkenoicacidscan be
^/\r\E{
I Sugimoto, O., Mori, M., Tanji, K. TL 40,7477 (tggg). rNaskar, D., Roy, S. JOC 64,6896 1ggg). 'Naskar. D . . R o y .S . i . 5 6 . 1 3 6 9( 2 0 0 0 ) . 'Naskar. D.. Roy. S. JCS/p/) 2435 tl9g9). Patrocinio, A.F., Moran, pJ.S. JOMC 603,220 (2000). fTatsugi, J., Tong, 2Z.,Amano, T., Izawa,y. H 53, ll4i (2000). 'Karimi, B., Seradj,H., Ebrahimian,c.R. Sa 1456 (1999). ')Karimi, B., Ebrahimian, G.R, Seradj, H. OL l, 173,7 Oggg\.
P-Bromotri(pyrrol- I -yl)phosphonium bromide. Formamidines.r This weil-known reagentfor peptide synthesisactivatesformamides for reaction with primary aminesto furnish formamidines.
R-NH2
+
i
o
81%
o
HtaNMez l
'
F \ T (,ru-7--e'.
o
i.PT2NEt > R,N\',,NM",
Br-
.r.tlnt\.t'
r)
rc hldrolysis on exposureto . ,'r hariumhydroxide)prevents
Delarue, S.,Sergherart, C. TL 40,5497.lggg).
ld
x: !:.
.: .rr C--3 with bromine. Treat:ntothe isatins.
, -N
t 1,3-Butadien-1-yl)dimethylsulfonium tetrafluoroborate. Alkenyl epoxides.r A three-componentcondensation reactioninvorvesan anion, an eldehyde,and the dienylsulfoniumsalt.
o F
R
^,-cHo
+
4\y'\t'. BF
y I
+
Etooc --vcooEt . Na*
| NHAc
-.-:: cnrcr, -40-23
cooEr Ph-T>-'\-"\Lcbdet Ot
I NHAc
90%
Rowbottom, M.W, Mathews, N., Gallagher, f. JCS(Pt) 3g2:.(lgg8t. L
Ct(
irrr ".",ut ru, on with triethyl .'hrdes. although formation of shcn 1,3-propanediolis present
r2,3-Butadien-1-yt)tributylstannane. Preparation.t A simple route to this reagentis by reactionof 1,4-dichroro-2_butyne "i ith Bu,Snli. Note that coupling of 1,3-butadien-2-ylmagnesium chloride with ph.sncl lcadsto the triphenyl analoguebut the coupling with BujSnCl proceedswithout skeletal . hanse.
1-t-Butoxycarbonyl-I -tosylhydrazine
2-f-Butoxycarbonyl-3-trichloromethyloxazir Hydroxylamines.t Various alcohols an
BuzsnV Bu3sncr
with this reagentafterdeprotonation.
\
ctus-Vt
\-t
I
rFoot,O.F.,Knight,D.W.cc 975(2000).
-
|
tn"n\^
,n.snct,
l-Butyl azidoacetate. The cr a-Azido-phydroxyalkanoates.t useful for the preparationof serinehomologu
t/\
re1,3-Butadien-2-ylation.t The nucleophilic site of the allenylmethylstannane with agent is the central carbon atom of the allene moiety. Its reaction [Ti(IV)-catalyzedl diene unit' aldehydesand acetalsaffords products possessinga conjugated
2:".n CHO f + ,z-1 I ll
rLuo.M.. Iwabuchi,Y., Hatakeyama, S. CC 267(1999)' N-f -Butoxycarbonyl-O'(2-pyridylsulfonyt)hydroxylamine' reaction of p-dicarbonyl Cafiamoylatio,n,t Hydroxamic esterscan be synthesizedvia compoundswith reagent1, which is readily obtained'
r
o
f
^
a synthesisof t-butyl indole-2-carboxylate.
\
\.,'
N3
o-\-
o1{"+
>["4il-",+''' Nl..\lurel S..Mitsuhashi. Kondo,K., Morohoshi,
(1) rHanessian,S., Johnstone,S- JOC 64,5896 (1999)'
-tosylhydrazine. 1-l-Butoxycarbonyl-1 carbonyl compoundsundergoreductivecondensation hydrazines.t substituted by selective from 1,2-di-t-Boc-l-tosylhydtazine prepared is which with this reagenr, hydrogenolysis.
Tt N-NH2
o<
.oo
1 ' b
THF. EIOH
n
-7,
-\
N - NH
\1. ()/ a 1.,Shibuya. \emoto,H.,Ma,R.,Suzuki,
tlfix), A..Amrein.S.ACIEE39,3080 Studer.
o 84To
rGrehn,L., Ragnarsson, U. 255,4843(1999)'
.rmphiphilic[COl component.
6-(/-Butyldimethylsilyl)-1,5,6-trimethl-l-1.4 Radical generation.t The title reagc'nl! includr :nitiatingmanytiee radicalreactions.
Tt NaBHa
t-Butyldimethylsiloxymalononitrile. a-Siloxy amides.t A rapid reaction ,.f compoundsin MeCN at 0o leadsto o-\rlot
r-Butyldiphenylsilyl chloride. Silylation.' Selectivemonosilr'lationoi \ u . C . .L i u .B . .H u .L . S .7 L 4 1 , 4 2 8 (1l t x x l l
/-Butyldiphenylsilyl
chloride
2-l-Butoxycarbonyl-3-trichloromethyloxaziridine. Hydroxylamines.l Various alcohols and carboxylic acids undergo O-amination with this reagentalterdeprotonation. lFbot,o.F.,Knight,D.w. cc 915(2000).
'- tn) '
:;. l.'- J
/-Butyl azidoacetate.
\-^-\\
.
,'i the allenylmethylstannane reIr' reaction[Ti(IV)-catalyzed]with
a-Azido-phydroxyalkanoates.r The condensationproducts with aldehydes are useful for the preparationof serinehomologues.The adductwith PhCHO can be used in a synthesisof r-butyl indole-2-carboxylate.
dieneunit. l E . , ' :',rusated
, lnrrr lamine. s* . .'.rhc.izedvia reactionof B-dicarbonyl tr-.
(,''Y-cHo . N3 A \_,2
/ _ o_\_
a.11&" \./
N: b+
l
lvscl - Et3N cN2ct2
Ot{"4 -1*GH"+ Kondo,K., Morohoshi, S.,Mitsuhashi, M., Murakami, Y. CPB47, 1227(1999).
t- Butyldimethylsiloxymalononitrile.
ni.
t :
undergo reductive condensation iltrc- I -tosylhYdrazineby selective
Y
Ts'N -NH -
t
-1
a-Siloxy amides.t A rapid reaction of amines and TBSOCH(CN), with carbonyl .ompoundsin MeCN at 0'leads to a-siloxy amides.The title reagentbehavesas an ,rmphiphilic[COl component. \!'moto,H., Ma, R.,Suzuki,I., Shibuya, M. OL2,4245(2OOO).
6-tt-Butyldimethylsilyl)-1,5,6-trimethyl-1,4-cyclohexadiene. Radical generation.t The title reagentservesas a surrogateof tributyltin hydride in ritiating many free radical reactions,including reductionof organichalides. .tudcr,A.,Amrein,S.ACIEE39.3080(2000).
o-.(\ 0
:- Butyldiphenylsilyl chloride. 84Yo
Silylation.t Selectivemonosilylationof symmetricalprimary l,n-diols is possible. ) :. C..Liu, 8., Hu, L.S.TL 4l,428l (2000).
polymer bound 2-t-Butylimino-2-diethylamino-3-methylperhydro'1,3,2-diazaphosphorine'
i-o-
t-Butyl hydroperoxide metal salts. 19, 5l-53',20,61-62 in moderate yields by Oxidations. Ketones are cleaved to afford carboxylic acidsr of unsaturated epoxidation Relor-t-BuOOH in acetic acid at 100'. vanadium-catalyzed complex is cobalt-phosphine alcoholsin liquid carbondioxide is feasible.:A resin-bound alsocffectivcas a catalystlor oxidation'' Interestingly,c-silylatedallylalcoholsaretransformedintoCt-silyl-B-hydroxy ketonesaon oxidation with (l-PrO)oTi-t-BuOOH'
lKim, K., Le. K. 'tL 195'7(1999).
+'*-
(rPrO)aTi- I-BUOOH
o o H l l =
T
l-Butyl isocyanide. Reaction with nitro compounds.t
Hom
tives is observed.
\-si--oan
>< l-BuOOH in the presence Allyl alkyl ethers are converted to ketoness on reaction with This oxidation temperaturc. room at of a catalytic amount of cro.1 in dichloromethane does not affcct THP, TBS, and MOM ethers' alkenes by Pd(oAc): is Arylation of alkcnes.(, Coupling reaction of arenes with reoxidant. Note, this is as a carried out in the presencc ol' benzoquinone ancl l-BuooH
,-N a'
lDumestre,P, El Kaim, L., Gregoire.A. ('C'--:
l
n o t a H c c k r e a c t i o n ( i n v o l v i n g A r H i n s t e a do f A r X ) ' r G u r u n a t hS. . , S u d a l a iA , . Sa 559( 1999). r P e s i r i ,D . R . , M o r i t a ,D . K . , W a l k e r T , . , T u m a s , W 'O M 1 8 ' 4 9 1 6 ( 1 9 9 9 ) ' r L e a d b e a t eN r ,. E . ,S c o t t 'K . A . J O C 6 5 ' 4 7 7 0 ( 2 0 0 0 ) ' r F a s s l e rJ, . , E n e v ,V . , B i e n z 'S . H C A 8 2 ' 5 6 1 ( 1 9 9 9 ) ' 5Chandrasekhar, T 5'L 1063(1999)' S.' Mohanty, P.K, Ramachander, r ' J i aC , . , L u , W . , K i t a m u r aT Y O L l , 2 O 9l ('1999)' F u j i w a r a , . ' ,
Butyllithium. 13,56; 14,63-68; 15, 59 61 . Various usesof BuLi lor & Lithiation. reactwith aldiminesto provide precursor\(tf
l'uransare readily preparedvia alkylation ,.i i Allenamidesare functionalizedat thc o-p tion. Thus, on introductionof an alkynl I cha rcaction can be prepared.3Lithiation oi ihe O -C transsilylation.{5 cngenders
13,55;18,14:19,54 /-Butylhypochlorite. Nitrosoarenes.N.Arylhydroxylaminesundergooxidation(5examples,88-92Vo).
P-
(1999)' rDavey, M.H.,Lee,V.Y, Miller,R.D.,Marks,TJ IOC 64' 4916
polymer 2.1-Butylimino-2-diethylamino-3.methyIperhydro-l,3,2.diazaphosphorine, bound. N.Acylation.|Thepolymer-supportedbaseladequatelyservesforuseinthe acylationof weakly nucleophilicamines'
oAN)
f-l oANAR
u".l: f_A.
-;-
\-^ " \
|
llll R'
Butvllithium t : irr/aphosphorine, polymerbound
>.
I I __.{-\_ \ru' \--l )*-r,-*
t. :rl
-'rrlic acidsrin moderateyieldsby ..,rrlr zed epoxidationof unsaturated .,,und cobalt-phosphinecomplex is
r |A
\--r*(1)
;.rn.lirrmed into ct-silyl-p-hydroxy lKim, K., Le. K. SL 1957(1999).
o o H
l-Butyl isocyanide. Reaction with nitro compound.s.l Homologation to afford ct-oximino amide derivatives is observed.
7'i---""' .retr()nwith t-BuOOH in the presence temperaturc This oxidation .rt r(x)111 ts : .rrcncswith alkenesby Pd(OAc)2 is this Note' reoxidant' a UuOOH as
it r r . : \
'lr
r,rl6(1999).
l l
('i I 199(l)'
r _
r(. j
.
r,)(lI.
rDumestre,P, El Kaim, L., Gregoire,A. CC 715 (1999)'
'74-'l'7; L9,54-59',20,62-65 Butyllithium. 13, 56; 14, 63-68; 15, 59-61'.17,59-60; 18, that subsequently ethers include deprotonation for Bul-i of Lithiation. Varioususes tetrahydro2-Alkylidene pyffolidin-3-ones.r of precursors rcact with aldiminesto provide 2-sulfonylmethylenetetrahydrofuran.r of furansare reaclilypreparedvia alkylation lithiaAllenamidesare lunctionalizedat the ct-positionby virtue of thc regioselective Pauson-Khand the of precursors valuable chain, tion. Thus, on introductionof an alkynyl or allenyl alcohols reactioncan be prepared.rLithiation of the silyl ethersof propargyl * C transsilylation.r' c n q e n d e rOs
,.:r,) o\idation(5 examples'88-927o)' h.l. lei6
Pr
( 1999).
polymer lpt rhr dro- 1.3.2-diazaphosphorine' t-
63%
in the ..r I eticquately serves for use
P-r
o4uAR Pf oA*
(-. -\\
BuL: -^--\. R ;* I
lll I
R'
"--
oAr.rAR N,4o(CO)6
.,\'-^
t
q
t
F
o
Butvllithium
il
v. -:i<
a
ll
t ? ? n
BuLi; >
oHc..,/\ i l l \z\NN/e,
]:Y-fi / r)-
"
\Z\Nvr",
/
MeO
-
\
/
oEt + Bu-Lt OEt
81Yo
of the silyl enol The above revefse tlrook rearrangementalso occurs during treatment gives an PhcHo with with BuLi. Quenchingthe enolate ether of o-bromoacetophenone aldol product.6 createsa new nng' Halogen-lithium exchangefollowed by intramolecular substitution presence of two The Such a method is the basis of a benzodihydrofuran synthesis. exchangeablehalogenatoms(2,6-disubstitutionpattern)makesitpossibletointroduce al C-7.7 anotherfunctionalitY
The halogen-lithium exchange of regioselectivityin ether and toluene.r: N-Acylntion.ts Primary arylamirrs subsequentexposureto an ester at lo$ tem Wittig reanangements.tt Solvent e ment of benzYl ProPargYlethers.
'b""-
BuLi/ THF
fi{osivreo VBr
7 4o/o
Br B u L i/ T H F
)'-.-.o",
t
i
\,"\Br
l
l
\Br
HCONMe2
oYo Et2O , O" EtzO-THF - hexane -110' 62%
f1^
lYt i l
V\cHo 76Yo
by Sn-Li exchangeand O,Cs-Dilithio enolatesare generatedfrom p-stannyl ketones enolization.n Alkenes'(Phenylsulfinylmethyl)diphenylphosphineoxideisreadilydeprotonated sulfoxides.' for condensarionwith aldehydes,affording (8)-alkenyl phenyl by elimination of terminated is olefination Julia-Lythgoe of the A sulfoxide version r') vicinal hydroxyl and phenylsulfinylgroupson treatmentwith BuLi Solventdependence,solventdependenceoftheproductsarisingfromeither with BuLi has been isomerizationor elimination of propargylic acetalsrron treatment witnessed.
rAmombo, M.O., Hausherr,A., Reissig.H -L' 2Edwards,G.L., Sinclair,D.J.TL&' 39-1-rt l9 rxiong, H., Hsung,R.P, Wei, L.-L', Beq. CJ aSakaguchi,K., Fujita, M', Suzuki,H.. Htges sstergiades,LA., Tius, M'A. JOC 64"15t '1rl' 6Comanita.B.M., Woo, S., Fallis' A.C. fL a. TPlotkin,M., Chen, S., Spoors'P.G.IL 41. 8Ryu, I., Nakahira, H., Ikebe, M., Sonoda \ . evanSteenis,J.H., van Es, J.J.G.S.'van dcr G roSatoh.T.. Hanaki, N', Yamada,N., Asarrc. T rrLe Strat,F., Maddaluno,J.TL4l' 5367 tlffi r2Wang,X., Rabbat,P.,O'Shea,P.,Ttllyer. R . rrooi, T., Tayama,E., Yamada' M.' Mantob I raTomooka,K., Harada, M., Hanji' T.. Natar. 1
,.j
Butyllithium
Eto. -oEt
Et2O
/
NMe2 MeO
81%
oEt + Bu-Li
_-lr;-
OEt
I
f,.-
1l:
It r.
- Juring treatmentof the silyl enol rhc cnolatewith PhCHO gives an s n e wr i n g . . . . r r . u h s t i l u t i ocnr e a t e a ': .rnthesis.The Presenceof two ::r , makes it possible to introduce
/oEt
ttt- 40.
)
/:c--/
MeO
I
F.C=C-J MeO
The halogen-lithium exchange of 2,5-dibromopyridine also shows different regioselectivity in ether and toluene.12 N-Acylation.t3 Primary arylamines form amides on dilithiation with BuLi and subsequentexposureto an ester at low temperature. Wittig rearrangements.t4 Solvent effects dominate the mode of Wittig realrangement of benzyl propargyl ethers.
o o H
r l l
-_.r^\-
I
pn
'4siM".
"bfu *G(."".fl.o.--q
74lo
0% E t 2 o ,o ' Et2O-THF- hexane - 110" 62%o
55Yo
14To
4%
8Yo
Yr l
\-^cHo 76%
:i I kctonesbY Sn-Li exchangeand rl: l- ..
l: f,_-
t
rLnc oxide is readily deprotonated . phcnylsultoxides." r,,n is terminatedby elimination of ' n ts i t h B u L i . r 0 rhc products arising from either \rn treatmentwith BuLi has been
rAmombo, M.O., Haushen,A., Reissig,H.-U. SL 1871 (1999). r Edwards.G.L.. Sinclair,D.J. TL 40, 3933 ( 1999). 'Xiong, H., Hsung,R.P.,Wei, L.-L., Berry, C.R., Mulder, J.A., Stockwell,B. OL2,2869 (2OO0). lsakaguchi, K., Fujita, M., Suzuki, H., Higashino, M., Ohfune, Y TL 4l' 6589 (2000). 5Stergiades, 1.A.,Tius, M.A. JOC 64,'154'1(1999). nComanita,B.M., Woo, S., Fallis,A.G. TL 40, 5283 (1999)' -Plotkin, M., Chen, S., Spoors,P.G.TL 41,2269 (2000)' rRyu, 1., Nakahira, H., Ikebe, M., Sonoda,N., Yamato, S., Komatsu, M. ./ACS 122' l2l9 (2000). 'van Steenis,J.H., van Es, J.J.G.S.,van der Gen, A. EJOC 2781 (2000). rSatoh,T., Hanaki, N., Yamada, N., Asano, T. T 56,6223 (2000). rLe Strat.F.. Maddaluno,J.TL41,536'7 (2000). rWang,X., Rabbat,P.,O'Shea,P, Tillyer, R., Grabowski,E.J.J.,Reider,PJ. TL 41,4335 (2000). 'Ooi, T., Tayama, E., Yamada, M., Maruoka, K. SL'129 (1999)' 'Tomooka, K., Harada, M., Hanli, T., Nakai, T. CL 1394 (2000)'
TMEDA
Butvllithium-N,N,N'N"tetramethylethylenediamine'
LI
Butyllithium-2-(N,N-dimethylamino)ethanol' Lithiationofpyrid'ines.3-MethylpyridineisregioselectivelylithiatedatC-6with thisbasesystem,lwhichismarkedlydifferentfromitsbehaviortowardLDA(benzylic lithiation,).2-Chloropyridinebehavessimilarly'2
,*k 7\-6
N--w
Buli - TMEDA EtzO - 100'
rMathieu, J.,Gros,P, Fort,Y'CC951(2000)' rChoppin,S.,Gros,P.'Fort,Y'OL2,8O3(2000)'
a
\1
Butyllithium-potassium r-butoxide' Cyclization.lFusedl-vinylcyclopropanesareformedonlithiationofallylsulfides that bear an alkenyl chain at the ct-position'
/ (
SPh
-\Z\
CeH
BuL.,.BuoK -rHF CA l+ L-lX'"'*,'l
a- K",r,, 81Yo
Lithiation.rn-Methoxybenzoicacidand3,5-dimethoxybenzoicacidarelithiatedat c-4.2 rCheng,D., Knox, K.R., Cohen,T' JACSl22' 412 (2000)' S TL 41' 3 157 (2000)' 2Sinha.S., Mandal, B., Chandrasekaran,
|
17-i 9' ll s-Butyllithium . 14, 69; 16, 56; 18, Lithiation of aromatic compounds' H are lithiated at the ortho position'' Indole-2-carboxylic esters'1 Benzlhc mates followed by addition of alkyl oralatc treafl indole-2-carboxylicestersynthesison
"",[,2-
r
t'oot-cooEt L\,
Li-- -oLi
MeaSivNHMe
n \/e
rshinozuka, T., Utsumi, T', lnagaki' M ' Asao\a- \ rCapriati,V., Florio, S', Luisi, R ' Russo'\"' Salt-c
$il^g'K
19' 60; 20' 664'l Butyllithium-N,N,N'N' -tetramethylethylenediamine' enablessubstitutionat C-3'l Lithiation. The facilelithiationof p-sitylalkanamides
O
,N--v ./\
/
Alkylntion of benzylic acetals" It tu allylation of a dimenc : second-staged the alkYlation. firsrstaged
BuLi- TMEDA
-
rHF 78'
trrt".si$t'lttt"
o Meqsi Me.sicr I ll ' Me:rsiVNHMe
oxazolinylepoxidesunderlithiationat-l00..lsomerizationoftheoxiranyllithiums to2-acy|oxazolinesoccursonwarming,thereforealkylationmustbeconductedatlow temDerature.2
OMe I
( / \
^\v Y
b l
tr\+" \ r ' H
I MeO
n
"
s-Butyllithium
t'r. -rlcctively lithiated at C-6 with ^rhrvior toward LDA (benzylic
BuLi - TMEDA
i-b
Et2O
,c#
,/
,f.f=-A
x,5
100'
lY;
t
U
/
\J ,NV \
x_6
[r ::] r.i ()n lithiation of allyl sulfides
rShinozuka,T., Utsumi, T., Inagaki,M., Asaoka,M. JCS(P1)2433 (1999). 2capriati,V, Florio, S., Luisi, R., Russo,V., Salomone,A. ZI 41, 8835 (2000).
/-]t-
\
1.,'
t-\z\^
u8ni7
81Yo
s-Butyllithium . 14, 69; 16, 56; 18, 77-79; 19, 6O4l Lithiation of aromatic compounds. Hydrazides of the constitution ATCONHNMe2 are lithiatedat the orthoposition.r Indole-2-carboxylic esters.2 Benzylic lithiation of l-butyl N-(o-alkylphenyl)carbamates followed by addition of alkyl oxalates also prompts cyclization and completes an indole-2-carboxylicestersynthesison treatmentwith CFTCOOH.
.,rbcnzoicacid are lithiated at
""'', l#":"",.l-rYor-cooEt (Y f r- ''oo'-cooE' \Alr 9il^6.K LUU^"r<] h( ai:
5SYo
1 9 .6 { ) :2 0 , 6 6 - 6 7 at C-3.r :. . cnablessubstitution
L i -- - o l i
Alkylatinn of benzylic acetals.:\ It has been shown that s-Buli is the best base for allylation of a dimeric acetal.Note that n-Buli functions well in the rhe second-staged first-stagedalkylation.
','=S $NMe OMe
, . , =S
( a \
o
il
\
ue s YNHMe
I :r -::lrtron of the oxiranyllithiums ilr.. .,:i,,nmust be conductedat low
OMe
l : l /
i
o{V l O
l
trvo Y MeO
H
I
( u \
l
\
r
Zt"..B'
/
i
o{\-/
s-BuLi;
r\-fo t
(
YI
MeO
O
I /-)
l
\
l
l-Butvllithium
lMcCombie, S.W.,Lin, S.-I.,Vice,S.F.fZ 40, S'f67 Q999). 2Allen,D.A. SC 29,447(199q. rRagot,J.P.,Prime,M.8.,Archibald,S.J.,Taylor,R.J.K.OL2, 1613(2000).
OEt
t,BuL €:
oEt
s-Butyllithium-N,N,N'N'-tetramethylethylenediamine. 18,78-79;20,67-68 Lithiation. Indoles are lithiated at c-7 when the nitrogen atom is protected by a 2,2-diethylbutanoylgroup.'Aminoallenes are availableby two routes: from reaction of lithiated 1-silylalkynes with oxazolidines2 and reaction of propargylic substrates with amines,3after the latter undergo a-lithiation and Li-Cu exchanse.
An interestingsynthesisof kainic acrd . mide, which undergoescyclizationto lbrm a
,.oH
r-
I p^/-
O,
I
f lf
fPh +l l l N'
|
H
SiMe3
s-Buli- TN.4EDA pnAruH
-
|
(i-PrO)aTi
,ntY"
^""
SiMe3
-N-
oLo
-r-Y"
n/r'
s-BuLi- TMEDA CuCl-2LiCl/ THF
oAo
AYN l l ItteoV
o
\
ll
\,/
s 3--
Pn - l t \Pn
R lt .o .\-<
X
I HOOC../,rlv Indolizidines.o The t-Boc derivative of azacyclononeneoxide is deprotonatedat an o-position of the epoxidering by .I-RLi-TMEDA. A transannularreactionfollows.
.1."k
*-*llo +" tltt
N
H
cooH kainicacid
Halogen/lithium exchanges. Alic-r tn with certain alkenes (vinyl sullides. r rnr pcntanes.3
740h ./l
r F u k u d aT, . , M a e d a ,R . , I w a o , M . 7 5 5 , 9 1 5 1 ( 1 9 9 9 ) . 2Agami,C., Comesse,S., Kadouri-Puchot, C. TL 41,6059 (2000). rDieter,R.K., Nice, L.E. TL 40, 4283 (199q. aHodgson,D.M., Robinson,L.A. CC 309 (1999).
/-Butyllithium. 13,58; 15, 64-65; 16, 56-57; 18,79-81; 19, 6t*63; 20,68-69 Lithiation, The terminusof a polyenecan be lithiatedon treatmentwith l-Bul-i, permittingchainextension by alkylation.r
x
\\.
"
/ R
X = Ar, SPh.SiPh.
Lithium alkynoxides are generatedlrtx Thesespeciesreactwith keto estersin a rc'm
r-Butyllithium
oEt
I
l( n0)
oEt
t-BuLi/ Et2O
oEt
oEt
|ru:13,"
mint. lti. T8-19: 20, 67-68 :: - :rtrosen atom is ProtectedbY a a- - ^\ t\\o routes: from reaction of ,,1 ProPargYlicsubstrateswith r'
i
PhwcHo
{ . -,..hanse. An interestingsynthesisof kainic acid2startsfrom ct-lithiationof an N-benzylbenzamide, which undergoescyclizationto form a dihydroisoindolone(dearomatization).
"OH
I
E
: -
pnANH
|
^/,'
,ntY"
O
s-BuLi- HN,4PA
4\^rXrn
SiMe3
'f -Y"
o
r THF
(rn
r',r"oV
40'
dJ \.2 MeoU-1*1rn Ph
n/r'
l,
E
s4o
I
n
i
i l . o
.\-< HOOC../rlv
I
---
NH
A
t,, ) /o-\ t1"=o
o
o*.
tcooH - n.' Oxidcis deprotonatedat an ..1:r nularreactionfollows.
.
i''< \., l l N - {'Ph Ph
kainicacid
Halogen/lithium exchanges, After treatment with t-Buli, l-iodo-3-alkynesrcact with certain alkenes (vinyl sulfides, vinylsilanes, styrenes)to give alkylidenccyclopentanes.r
_,.ro' 7 4Yo
/l ,t \ \ + \\
^
t-BuLr/Et-o
\ /
v'/
4
//
,//
o */-\R
R
X = Ar, SPh,SiPhs
;.
19.6l-63; 20,68-69 ]lr.rtcdon treatmentwith r-Buli,
with l-Buli. Lithium alkynoxides are generatedfrom ethyl 2,2-dibromoalkanoates Thcsespeciesreactwith keto estersin a remarkablemanner,yielding cyclalkenones.l
84
R
1-Butyl-3-methylimidazoliumsalts
.cooEt
x 'Br Br'
t-Buli/Etzo 1.
+ -78 r'
Etooc fr 'r \f
lLR - - o l i l , - + (
*'
RB )-l-4"
ll FtT-" --nl
o
R -+(
R
)'-/"
ll t"fin
R' The elaborationof a polyunsaturated5:9-fusedring system5basedon transannularaddition of an alkenyllithium species to a triple bond following the Br-Li exchange of a bromoalkeneis clean and elesant.
(N.4e3Si)2NLi / THF ;
...............-..-........."* t-BuLi -96.; HOAc
Deallylation. Allyl ethersare cleavedby t-Bul-i via an S*2' process.6 Addition to styrenes. t-Butyllithium (other alkyllithiums also) adds to the terminus of styrenes.Benzylic carboxylationis feasible.Whenthe substratescontainan allyloxy or benzyloxy group the allyl or benzyl residueis transferto thc benzylic position.T
\Ao)
lChen.W.,Xu, L., Chatterton, C.' Xiao,J. CC llrl
Dehydrogenauo at -78' is rr
rreatmentwith t-BuN:S(Cl)Ph
rMarkovskii,L.N., Dubinina,T.N.,Levchenco. E5 rMukaiyama,T., Matsuo,J.' Yanagisawa, M. CL l( rMukaiyama,T., Matsuo,J., Kitagawa,H CL l:5(
f-Butyl propynoate. Protection of l,2-diols.t Acetal forrn reaction) at room temperature in the preserx l.4-diols do not react in a similar maru acetonidesare hydrolyzed(e.g.' aq HOAc t h rAriza,X., Costa,A.M.,Faja,M.' Pineda'O..\ih
t - B u l i / E ^t 2r to' ^
;ilil
L-Butyl-3-methylimidazolium salts. 20' 70 Allylic disptacements't Palladium-catl been carried out in ionic liquids at room temp
(11examples,9V99Ed.2 Coniugated ketones,l 44-60o/o
,t)ph
rStafford. S. S.,Barrett,D. G.' Suf J. A., Gonzales,
N-(t-Butyl)phenylsulfinimidoyl chlorideOxidation of alcohols- This stable n dichlorination and then treatment with PhS reactive speciesgeneratedin the Swern and I oxidation of alcohols is performed in dt
>( o. o
"
r-BuOCONHOMs, and the subsequenttrealm benzyl alcohol in MeCN. Benzyl carbamatesI
\Ao,. 72To
r V i l l i e r s ,P , S o u l l e z D . , l e ,G . f 5 5 , 1 4 0 3 1( 1 9 9 9 ) . , . , R a m o n d e n c , YP 2Clayden,J., Tchabanenko,K. CC 317 (2000). rwei, X., Taylor,RJ.K. ACIEE 39, 409 (2000). aShindo,M., Sato,Y, Shishido,K. "/ACS121,6507 (1999). 5Myers,A.G., Goldberg,S.D. ACIEE 39,2'132(2000). 6Bailey,W. F., England,M.D., Mealy, M.J., Thongsomkleeb,C., Teng,L. OL2,489 (2OOq 7Wei,X., Taylor,R.J.K. ICS(P I I 109 (2000). )
/-Butyl methanesulfonyloxycarbamate. Lossen rearrangement.t A modified version of the rearrangment fbr degradation of carboxylic acids is via reaction of the coresponding acid chlorides RCOCI with
!-Butylsulfi nYl chloride. Amide radicak.t After O-sulfinllauo the N-O bond. Trapping of the N-radicd method has been applied to a formal synthcs
M"o{] 'o)'{
t-BuSOCl/i-Pr2NEt cH2ct2
N-
r*T<
Ph25e2
{
o
{
,-Butylsulfinyl chloride
:,->v"-tY* 11
Ff
M;|o
n
R'
I '
.).tcr.ni basedon transannularadl,,sing the Br-Li exchangeof a
>( o q TBSO 44-60Yo
t-:' f,
, r.rln Sr2' process.6 ;thiutnsalso)addsto the termlnus ,' rubstratescontain an allyloxy or ,, thc benzylicPosition.T
/-BuOCONHOMs, and the subsequenttreatment with zinc triflate, 2'6-di-r-butylpyridine' benzylalcoholinMeCN.BenzylcarbamatesRNHCooBnareobtained. rStafford, S. S.,Barrett,D. G., Suh,E' M', Feldman'P'L' JOC 63' 10040(1998)' J.A., Gonzales, I -Butyl-3-methylimidazolium salts. 20, 70 have Allylic displacements.t Palladium-catalyzed allylic displacement reactions temperature' room been carried out in ionic liquids at rChen.W., Xu, L., Chatterton, C., Xiao, J' CC 1247(1999)' N-(t-Butyl)phenylsulfi nimidoyl chloride. by N,Noxidntion of alcohols. This stable reagent,r prepared from r-BuNH2 as the fashion same in the functions PhSAc, with dichlorination and then treatment efficient which With oxidations. Corey-Kim and reactive speciesgeneratedin the Swern presence of DBU oxidation of alcohols is performed in dichloromethane in the (1 1 examples,90-99Vo).2 enolates on conjugated ketones.t Dehydrogenation of ketones via their lithium -78' convenient' is very treatment with r-BuN:S(Cl)Ph at A.V "/oC(UssR)9, |435 (|973). lMarkovskii, 8.S.,Kirsanov, T.N.,Levchenco, L.N.' Dubinina, rMukaiyama,T., Matsuo,J.,Yanagisawa, M. CL lO72(2000)' rMukaiyama, H. Cf 1250(2000)' T.,Matsuo,J', Kitagawa, f-Butyl propynoate. (via a double Michael Protection of l,2-diols.l Acetal formation with this ester to l,2-diols (1,3- and is limited reaction) at room temperature in the presenceof DMAP conditions that survive acetals l,4-diols do not react rn a similar manner). These bases' with cleaved acetonidesare hydrolyzed (e.g., aq HOAc) but they can be rAriza,X., Costa,A.M.,Faja,M.' Pineda, O', Vilanasa'J'OL2' 2809(2000)'
OH
/-Butylsulfi nyl chloride. homolysis at Amide radicals.t After O-sulflnylation, hydroxamic acids undergo This structures. to cyclic bond. Trapping of the N-radical by an alkene leads the N-{ method has been applied to a formal synthesisof peduncularine'
I
r .
(' . lcng. L.0L2,489 (2000)
M"ofl
*o)*{
t-BusOCl/ iP12NEt CH2C!2 Ph2Se2
: thc rearrangmentfor degradation lr. r':'.-:' :rJtng acid chloridesRCOCI with
- \ o
-sePh
-{
l-,
rueo-,\
r-
-=*
) peduncularine
(r-Butylthio)azoarenes
' Lin, X., Stien,D., Weirneb,S.M. ZZ 41, 2333(2000). 2-(l-Butylsulfonyl)allyl chloroformate. Amine protection.l Carbamates are formed at room temperature or below. The removal of the protecting group, is most expediently achieved by treatment with a polymer-bound secondary amine. The released fragment is trapped and the isolation of amines is uncomplicated. 'Carpino,L.A.,Philbin,M. JOC 64,4315(1999).
Calcium hypophosphite. Reduction of arenediazonium ions. (e.g., MeCN) to remove amino groups fro
yields are obtained from substratesthat conu
2-(t-Butylsulfonyl)phenyliodine(II! diacetate. Hypemalent iodine reagents.' This compound is obtained from t-butyl 2-iodophenyl sulfone by oxidation with H2O2-Ac2O.It can be transformedinto reagentssuch as 1 and 2.
\ l P
\ l o
id=o
is="
\_y'-\o
\__/-\*,.
(1)
(2)
rMacikenas, D., Skrzypczak-Jankun, 8., Protasiewicz, J.D.,IACS121,7164(1999). 1-t -Bu.tyl-lH -tetrazol-5-yl sulfones. (Z)-Alkenes,t These sulfones are very stable and participate in the Julia olefination with improvedyields. rKocienski, P.J.,Bell,A., Blakemore, P.R.SI,365(2000).
rMitsuhashi, T., Suzuki.H. fL ll. H., Kawakami,
Carbon dioxide. Carbonates and carbamates, In th alcohols combine with CO, to afford carho different conditions2,and with a Mg-Al mr The preparationof dimethll < carbonates.3 supercritical carbon dioxide in the pres methoxide) is successfully carried out.' Carbamates are formed by trapping th. with alkyl halides.sThe initial step is Fn
Heatins aminesand oxetanesat 40 atm lead
[--l +COz+R,NH l
^
2,4-Dihydroxyquinazolinesare obtaincd of an aminesuchas DBt'.' in the presence
(l-Butylthio)azoarenes. Hydrazones.t Reaction of ketones with these reagents conveniently introduces an arylhydrazono group to ketones.
CN
-r)
NHz
o
*A ' C a p o s c i a l l iN , . , D e l l ' E r b a ,C . , N o v i , M . , P e t r i l l o , G.,TavaniC , . 254,5315 (199S)
Reaction medium,
By virtue of it-sar
its increasingapplicationsas a reactionnrc with oxygen and PhCHO, rhodium
T
.:l r(rom temperature or below. The !r:., r rntl\ achieved by treatment with a N ':.:::r!-nt is trappedand the isolation of r: .
It. lF ..'.: ;. ,rbtainedfrom r-butyl 2-iodophenyl ! :: :: ' : , rn.ncdinto reagentssuchas 1 and 2.
t . - ' /
o
: . '-l
t'NT.
(2\ \
(1999). / 1(.t12l,'7164
rJ participatein the Julia olefination
Calcium hypophosphite. Reduction of areneiliazonium ions.t This reagent is used in nonaqueous media (e.g., MeCN) to remove amino groups from aromatic rings after diazotization. Good yields are obtained from substratesthat contain electron-withdrawing groups. rMitsuhashi, T., Suzuki,H.TL 41,5567(2000). H., Kawakami,
Carbon dioxide. Carbonates and carbamates. In the presence of phosphine-CBra and base, alcohols combine with CO2 to afford carbonates.rMixedcarbonatesare obtainedunder different conditions2,and with a Mg-Al mixed oxide as catalyst, epoxides formed cyclic carbonates.r The preparation of dimethyl carbonate from acetone dimethyl acetal and supercritical carbon dioxide in the presence of a metal catalyst (e.g., dibutyltin methoxide,)is successfullycarriedout.a Carbamates are formed by trapping the condensation products of amines and CO2 with alkyl halides.5 The initial step is promoted by electrogeneratedsuperoxide ion. 6 Heatine amines and oxetanesat 40 atm leads to 3-hydroxyalkyl carbamates
120" *'*;7oaAAn" > l-l L-o * co2 + R2NH 40atm I 2,4-Dihydroxyquinazolinesare obtained when 2-cyanoanilinesare treatedwith CO2 of an aminesuchas DBU.7 in the presence
rcagentsconvenientlyintroducesan
o lt R-')r N
OH CN NHz
'il-\_/-
R=Ph
/:\
96%
ZtA* DBU / Dl\'lF
\.{*Ao,,
Reaction medium. By virtue of its attributes supercritical carbon dioxide deserves its increasing applications as a reaction medium in synthesis.These include epoxidationn with oxygen and PhcHo, rhodium-catalyzed hydroboration,' Pd(0)-catalyzed 1,4' I hydroarylation of enonesr{)and Heck reaction in the presenceof Pd-C,r cafbonylation of aryl halides,r2Glaser coupling of l-alkynes (mediated by cuCl) using a solid base (NaOAc),rr as well as scandium(IID perfluorooctanesulfonate-catalyzedDiels-Alder and Ia hetero-Diels-Alder reactions.
(1998). r c. r54,5315
Cartronlldh
Carbon disulfide
Investigations have shown that in Pd-catalyzedreactions in supercritical carbon dioxide, superior results are obtained with catalysts containing fluorinated ligands [e.g., (CFTCOO)rPdand (F6-acac)Pd vs. their respectivehydrogenanaloguesl.rs Continuous, selective hydroformylation in supercritical CO2 using (acac)Rh(CO)2immobilized on silica as catalyst'o shows certain advantages.A version of asymmetric hy(SubcriticalCO, gas accelerates droformylationin this medium has also beenreported,.rT solventlesssynthesis involving solid reactants,r8including hydrogenationand hydroformylation.) The regioselective and enantioselectivenickel-catalyzed hydrovinylation of styrenesin supercritical CO, make 3-arylpropenesavailable in an optically active form.re Improvement in the performance of the Pauson-Khand reaction in supercritical media is due to thorough dispersion of catalytic metal species.Besides CO2,20supercritical ethylene has the sameeffect.2r Water and supercritical carbon dioxide form an excellent medium for hydrogenation of unsaturated aldehydes to allylic alcohols with ruthenium(Ill) chloride and a waterbecausethe limitation pertaining to gas-liquid-liquid mass soluble triarylphosphine,22 transfer is eliminated due to the very high solubility of reactantgas. IKadokawa, (1999). S.,Karasu,M., Tagaya, H., Chiba,K. JCS(P1)2205 J.,Habu,H., Fukamachi, 2Kim,S.-L,Chu,F.,Dueno,E.E.,Jung,K.w. JOC 64,45'18 (1999). rYamaguchi, K., Ebitani,K., Yoshida, T.,Yoshida, H., Kaneda, K. JACSl2l,4526 (1999). rSakakura, T. JOC 64,4506(1999). T., Choi,J.-C.,Saito,Y,Masuda, T., Sako,T., Oriyama, 5Casadei, M.A., Moracci,F.M.,Zappia,G., Inesi,A., Rossi,L. JOC 62,6757(1997). ('Ishii,S.,Zhou,M., Yoshida, Y.,Noguchi,H. SC29,3207(1999). TMizuno, T., Okamoto, N., Ito,T.,Miyata,T. rL 41, 1051(2000). n|-oeker. F..Leitner.W. CEJ6.201I (2000). eCarter, C.A.G.,Baker,R.T.,Nolan,S.P.,Tumas,W. CC 341(2000). '"Cacchi,S.,Fabrizi,G.,Gasparrini, I'-.,Pace,P, Villani,C. SL650(2000). rrCacchi, F.,Villani,C. Sa 345( 1999). S.,Fabrizi,G.,Gasparrini, l2Kayaki, Y.,Noguchi,Y.,lwasa,S.,Ikariya,T., Noyori,R. CC 1235(1999). rr|-i,J.,Jiang,H. CC 2369(1999). raMatsuo, J.,Tsuchiya, T.,Odashima, K., Kobayashi, S. Cf 178(2000). rsShezad, N., Oakes,R.S.,Clifford,A.A., Rayner, C.M.TL 40,222'l(1999). '"Meehan, A.J.,Reek,J.N.H.,Kamer,PC.J.,van Leeuwen,PW.N.M.,Poliakoff,M. N.J.,Sandee, cc t497 (2000). rTFrancio, G.,Leitner,W. CC 1663(1999). rEJessop, D. CC 693(2000). P, Wynne,D.C.,DeHaai,S.,Nakawatase, 'eWegner; A., LeitnetW. CC I 583( 1999). 2{)Jeong, N., Hwang,S.H.,Lee,Y.W.,Lim, J.S.JACSll9,10549 (1997). rrJeong, N., Hwang,S.H.ACIEE39,636(2000). ?rBhanage, B.M.,Ikushima, Y, Shirai,M., Arai,M. CC 1277(1999). Carbon disulfide. 1,3-Dithincycles.t 1,3-Dithianesand 1,3-dithiepanes are formed from 1,3- and 1,4dihalideson reactionwith CSr and NaBH4. Isothiocyanates.z Sequential treatment of organic azides with PhrP and CS2 gives isothiocyantes.This processcan be applied to a synthesisof isocyanatoalkylphosphonates.
rWan,Y, Kurchan, L.A., Kutatela A.N.,Bamhurst, rSikora,D., Gajda,T. Pss 157,201(2000). Carbon monoxide.20, 72 Diaryl diketones.t Highly hindered anl CO to provide the 1,2-diketones. lNudelman, 422(1999t. N., Schulz,H. "|CR(S) lf Carbonyl(chloro)hydridotris(tricyclohexl The Ru complex is a h HydrogenationI of alkenes.2 Terminal alkerr Silylation reagentsand the Ru complex as catalyst. Dehalogenation,s Haloarenes are redn: that can be generatedin situ from [(codtRuCl'
lyi, C.S.,Lee,D.W. OM 18,5152(19991. rYi,C.S.,He,Z.,Lee,D.W, Rheingold, A.L..Lam. rCucullu,M.E.,Nolan,S.P,Beldenain, T.R..Gnrhh
Carbonyl(chloro)hydridotris(triphen-r-lphoq Double-bonil migration.t Deconjugatrt
SnBu3
(Ph:P.Q:
Bu3Sn/\-.\..CooMe
(Ph.P
Qr
Bno*cooMe Silyl group transfer.2'r Allylsilanes an! alkenessuch as styrenesand vinyl ethers.lt r.
ErO'\
+
siMe3
>i
\
'Wakamatsu, H.. Nishida,M., Adachi,N.. \lon. \l rKakiuchi,F.,Yamada, A., Chatani, N.. Murar.S . F 'Marciniec, B., Kujawa,M., Pietraszuk, C. O.rt19.l
Carbonyldihydridotris(triphenylphosphiac t Addition reactions.t'2 Electron-dc-ticr ketones, add to unsaturatedsilanes in thc p extensionoccursat the ortho Dositionof thc C
Carbonyldihydridotris(triphenylphosphine)ruthenium(II)
-.1!tronsin supercriticalcarbon diox, ,ntaining fluorinated ligands [e.g.'
lr a. f' l . Ia t i -
lr & F*-h._
t' s .
. .lrogcnanalogues].1s '-:rtrcalCO2using(acac)Rh(CO)2 imA version of asymmetrichy.,]rrretlS. '-'J. - tSubcriticalCO2 gas accelerates .ncluding hydrogenationand hydro. j nickel-catalyzedhydrovinylationof .,. .rrlablein an optically activeform.re Khund reactionin supercriticalmedia - - rc.. BesidesCO2,20supercriticaleth,. .\ccllent medium for hydrogenation :uthcnium(Ill) chloride and a waterpcnaining to gas-liquid-liquid mass
ni.: rl-^ r, i)l reactantgas.
(d r l
s..
: : . , \ r . H . . C h i b a ,K . J C S ( P I ) 2 2 0 5 ( 1 9 9 9 ) ' :<-l r1999). ' . ::rcJa.K. JACS l2l, 4526 (1999)( )n\ ama,T. JOC 64,4506 (1999). . , : . L . J O C 6 2 . 6 1 5 ' 7( 1 9 9 ' 7 ) . 1999).
tt
.
: ;
r..1.rlfi)0). 11.650 (2000). _ . . ( ) 9 9) . :. (( 1135(1999). r I r8 (2000). {). rl2l (1999). i rrn Leeuwen, PW.N.M., Poliakoff, M
F '
rr
' hel (1000).
It
lr II
l (x x ) .
I le
1Wan,Y.,Kurchan,A.N., Bamhurst,L.A., Kutateladze,A.G.OL2,1133 (2000). zsikora,D., Gajda,T. PSS157, 201 (2000).
Carbon monoxide.20,72 Diaryl d.iketones.t Highly hindered aryllithiums such as mesityllithium react with CO to provide the 1,2-diketones. rNudelman, N., Schulz,H. JCR(S)422(1999). Carbonyl(chloro)hydridotris(tricyclohexylphosphine)ruthenium. Hydrogenation,r The Ru complex is a homogeneoushydrogenation catalyst. Silylation of alkenes.2 Terminal alkenes give 1-silylalkenes using vinylsilanes as reagentsand the Ru complex as catalyst. Dehalogenation.3 Haloarenes are reduced in basic media with a related complex that can be generatedin situ from [(cod)RuCl:], and CyjP underhydrogen' rYi. C.S..Lee,D.W. OM 18,5152(1999). rYi, C.S.,He,Z.,Lee,D.W.,Rheingold, A.L., Lam,K.-C. OM 19,2036(2000). rCucullu.M.8..Nolan.S.P,Belderrain, T.R.,Grubbs,R.H.OM 18,1299(1999). Carbonyl(chloro)hydridotris(triphenylphosphine)ruthenium. estersis observed. Double-bond migration,t Deconjugationof ct,P-unsaturated SnBu3 r
Bu3sn,.\*cooMe
( P h{ P ) 3 R u ( C O ) C | H
--;;;*
SnBu3
Bu3sn.,lwcooMe 80%
' ' '" -'--'-;
(Ph"P)1Ru(CO)ClH
ano*cooMe
Bno*cooMe
Silyl group transfer,)' Allylsilane, *a ",ttrtt"nes serveas silyl group donors to alkenessuchas styrenesand vinyl ethers.It is apparentlya metathesisreaction.
g,Pl#l|o)I Eto,,\ + \r,siMeo .,o,,\rt'""'
( 1997). . il5-19 i-- r19991.
:Icpanesare formed from 1,3- and 1,4:r.rnic azideswith PhlP and CS2 gives r:hcr i s of isocyanatoalkylphosphonates.
rWakamatsu, H., Nishida,M., Adachi,N., Mori,M. JOC65,3966(2000). rKakiuchi,F.,Yama
Cerium(IV)ammoniumnitrateCAN
TBSO r
Z)f'\o t t l \.,/
I|
(ph3p)3Ru(CO)CtH
+ ph--E--siMes
o
-
Debenzylatinn Tertiary amtnes conl secondaryamines.a
7
::
Ph
^
PhAN'5no
=
'Hams, P.W.R.,Rickard, C.E.F.,Woodgate,P.D.JOMC 5t9, 168 (1999). rKakiuchi, F., Sonoda,M., Tsujimoto,T., Chatani,N., Murai, S. Ct l0g3 0999).
1,1'-Carbonyldiimidazole. 13, 66; 16, 64; 18, 85; 20, 73 oxazole.t Ethyl isocyanoacetateis converted in ethyl oxazole-4-carboxylate on reaction with this reagent in the presenceof HCooH and Et.,N. The parent heterocycle, which is no longer commerciallyavailable,is easilyobtained.
ll
-t'\4"\
Nitrile oxi.de formation.' Oxidarrre derivatives is advantaseous.Side reactionsc:
Shafer, C.M.,Molinski,T.F.1153.1167(2000).
NOH i
l
il
Catecholborane. Conjugate addition.t B-Alkylcatecholboranes, obtained from hydroboration of alkenes,serveas a sourceof radicalsin the addition. rOllivier, C.,Renaud, P.CEJ5,1468(l999).
Ph,
+
--1
/
Ph
cooH
Oxi.dative cyclizntions. Cycloproprl cipation of a juxtaposed hydroxyl group lead
Cerium(IV) ammonium nitrate CAN. 13, 67-68;14,74-75;15,70-72;16,66;17,6g: 18, 85-87; 19, 67-69: 20, 7 3-7 5 Protection and deprotection. Tetrahydropyranyl ether cleavage is catalyzed by CAN at pH 8.r Acetonidesare formed from diols underthe influenceof CAN.2 cyclic acetals are deprotected.In certain cases, the method is superior to that using pyridinium tosylate-acetone.3
OH
/--1.\ ( t
\-V
H I I
o
OH
^-{,",-\ ( t
4a H/
Y
l
3,6-Dihydroxyphthalic esters are ohta.u treated with CAN.7
l
53%
Me3SiO
^R,ZV\'R,t
-p
OSiMe3
t
_
1
\af€f,
I
/-=.'i1 ( i l | t-Y o
Oxidative cleavage. carboxylic acids.o
p-Silyl ketoncs
CeriumfiV) ammonium nitrate CAN
o
TertiarY amines containing a benzyl group are converted to Debenzylation secondaryamines.a
.)7
:
'to
_. _,-.-...Bn^ P h . N U : ll -,,\a'\
\ 11 9 9 9 ) . ( 7 _r 0 8 - l( 1 9 9 9 ) .
SJtq
t_'
-.:
i. ]il.
n-.r .:r L'th)'l oxazole-4-carboxylateon (t ,:i .rnd Et,N. The parent heterocycle, il , -'.unr'd.
85Yo oxide formation.5 Oxidative formation of these species from oxime derivatives is advantageous.Side reactions can be avoided' Nitrile
NOH
i
Ph
l
-
cooH
/
Ph
DMF O'
Ph 69Yo
,htained from hYdroboration of
r f '
partlOxidative cyclizations' Cyclopropyl sulfides undergo ring opening with oxycycle'o a new cipation of a juxtaposed hydroxyl group leading to t p,' ; -' k"
ll.
--l-75:
15,7V72: 16, 66:'l7' 68;
. . c'thcrcleavageis catalyzedby - ' t t c r n l l u e n coef C A N . 2 -' nrc'thodis superiorto that using
,: - '/-+") w OH
-
CAN lils3A / NieOH
p-ketoestersare 3,6-Dihydroxyphthalicesters are obtained when bisenolsilylated treated with cAN.?
H 5
53%
cooR'
oSiMeg
R,2\)\oR,
NaHCO3/ MeCN
R
cooR'
.L)
;.-w ,-
Me3SiO
Oxidative cleavage. B-SilYl ketones suffer cleavage to generate unsaturated carboxylicacids.8
Cerium(III) chlorideheptahydrate
i-(cooH SiMe3
MeCN - H2O
60"
o
\ 667o
l D o
Unusual decomplexation. A highly strained cycloalkyne cannot be produced from its hexacarbonyldicobalt complex on reaction with cAN. Instead, carbonylation at the two nascentsp-hybridized carbon sites is observed.e
'Montalban,A.G., Wittenberg,L.-O.. \tcKrlh
(\cor(co)u
Me2CO- H2O
IJ
81Yo
Cerium(IID chloride heptahydrate-sc Hydrolysis of p-methoxybenzt-l cth. performed in refluxing MeCN. Remarl essentiallythe sameconditlons. Dehydration.t B-Ketols are dehrd system. Dealkylation.a
Note that heating the l-alkyne
complexes with amines in toluene alone leads 2-alke-
namides.l0 rMarko, I.8., Ates, A., Augostyns, B., Gautier,A., Quesnel,Y, Turet, L., Wiaux, M. TL 40, 5613 ( 1999). 2Manzo,8., Barone,G., Panilli, M. SL 887 (2000). rAtes,A., Gautier,A., Leroy, B., Plancher, J.-M., Quesnel,y, Marko, I.E. TL 40, l'lgg (1ggg). 4Bull, S.D., Davies,S.G.,Fenton, G., Mulvaney,A.W, prasad,R.S., Smith, A.D. CC 337 (2000). 5Arai, N., Iwakoshi,M., Tanabe,K., Narasaka, K. BCSJ 72,22j7 (lggg). 6Takemoto,Y, Furuse, S., Hayase, H., Echigo, T., Iwata, C., Tanaka,T., Ibuka, T. CC 2515 (lggg). Tlanger, P, Kohler, V. CC 1653 (2ON). 8Hwu, J.R., Shiao,S.-S.,Tsay,S.-C. JACS 122,5899 (2000). 'Tanino, K., Shimizu,T., Miyama, M., Kuwajima, I. JACS 122,6116 (2000). rosugihara,T., Okada,Y., Yamaguchi, M., Nishizawa,M. SZ 768 (1999).
Cerium(Il!
chloride heptahydrate.14,'15--'17;15,72--73;16,67-68; 18, 87; 20, 75 a-Chloro enones.t a,B-Epoxy ketones undergo ring opening and dehydration, but changing the solvent system from aq MeOH to MeCN stops the dehydration step. The behavior of 2,3-epoxycyclopentanonediffers from that of the cyclohexanonehomologue in that the product dehydratesmuch more readily. The regioselectivity of epoxide opening mediated by CeClj is opposite ro rhar by TiClo.
Regioselective rcn substituentof aromatic carbonyl comrrr refluxing MeCN.
cHo
frY
r
OBn
rCappa, A., Marcantoni, E., Tonegianr. L.. B 64.5696(1999). :Di Deo,M., Marcantoni, 8., Torregianr. F-, t 6s, 2830(2000). 'Bartoli,G., Bellucci,M.C., Petrini.\l . \1 (2000). rYadav, J.S.,Reddy,B.V.S.,Madan,C.. l{a.hr
Cerium(III) isopropoxide-diethl'lzincPinacol coupling.t Aldehydes rc to98:l).
Cerium(III) isopropoxide-diethylzinc
-/
o
, loH
l t ^ ,
a\"'
CeCl3
( I \
o tl .\^ \r)''
6a'
t l \,/\On
f'I
__.l
tt-
ir:.. iennot be producedfrom I:'.-:c.rd.carbonylationat the
CH2Cl2
o )-'-.o
t\6Cl l
rMontalban,A.G., Wittenberg,L.-O., McKillop, A. TL4O' 5893 (1999)'
Cerium(IID chloride heptahydrate-sodium iodide' Hydrolysisofp.methoxybenzylethers.Thecleavageofp-methoxybenzyletherslis performed in refluxing MecN. Remarkably, alcohols are converted to iodides2 under
B1%
.u.'nealone leads 2-alke-
the sameconditions. essentially this Dehyilration.s B-Ketols are dehydrated in refluxing acetonitrile to enones by system. Dealkylation.a Regioselective removal of an alkyl group from an o-alkoxy salts in substituent of aromatic carbonyl compounds is by treatment with the combined refluxins MeCN.
:,'
l- . Wiaux,M. ZI 40, 5613
.,4','cHo fr
'\ \ |r, ri
\"t"^/.
I rL10,t799(1999). rh.A.D.CC337(2000).
OBn
C e C l 3 . 7 H 2 O- N a l MeCN
A
rYt'o ?o, OBn 90%
T. CC2515(1999). Ihuka. - rX)).
,-:
16.r,7-68;18r87;20,75 g :r:rng and dehYdration,but lr. :'. lhc dehydrationsteP.The f ::.: .\e lohexanonehomologue 1". , rcl,
is opposite to that
rCappa, E.,Tonegiani,E, Bartoli,G', Bellucci'M C'' Bosco'M ' Sambri'L "/OC A., Marcantoni, 64,5696(199e). 2Di Deo.M., Marcantoni, E, Bartoli,G', Bellucci'M'C ' Bosco'M" Sambri'L JOC h'.,Tonegiani, 65,2830(2000). rBartoli.G., Bellucci,M.C., Petrini,M., Marcantoni, E', Sambri'L'' Tonegiani'E' OL 2' 1'l9I (2000). 4Yadav, J.S.,Reddy,B.V.S.,Madan,C , Hashim,S'R CI 738(2000)'
Cerium(III) isopropoxidediethylzinc. Pinacolcoupling'|Aldehydesselectivelyprovidedn'i.pinacols(anti/syn-9:| to 98:1).
Cesium carbonate
M e -? S ilO (i-PrO)3Ce- Et2Zn
R-CHO
+
Me3SiQ
*-Y*
R''.t-aR
lVe3SiCl / THF
:
OSiMe3
OSiMe3
Hydroquinolines.6 Reactive hetertx methylanilinesby treatmentwith Cs,CO, a readily affordsadducts.
(9-49 : 1)
y'-fct t
'Groth,U., Jeske,M. ACIEE39,574(2000\.
i
. l-oE, l
l
Vr.rri
il' Cerium(IV) sulfate-iodine. Ringcleavage.t 2-Alkylcycloalkanones arecleavedto giveketoesters.
Pyridines.l The intramolecular Drci cyanooximiesaromatizeby a double elrmu at room temDerature.
o
61To rHe, L., Kanamori, M., Horiuchi, C.A. "/CR(S) 122 (lggg\.
?\
Cerium(IV) triflate. 20. 75 Iodoetherificatinn.t Ce(orf). is a catalystfor functionalizationof alkenes(e.g., withiodinein MeOH).
A o',f
\
Nc^X
X = CN, COOET
Alkylation.E
'Iranpoor, N.,Shekarriz, M. 256,5209(2000).
+Y
via alkylation
A modification
descntr
of the N-diphenylmethr ler
(ethylene glycol) as solvent, promotion br r
Cesiumcarbonate.13,7O;14,71-7 8; 15,73-75; lB, 87-88; 19,'l0; 20,j 6 Aryl ethers.t with cs2co.1as base,aryl mesylatesact as phenolateions because desulfonylation occursin situ.
/'\y'oNas
t%Brt - t
Noz F-.,r^
* I) \l
Cs2CO3 DMSO 80"
oY\
NOr t -
i l ArV
l
onto a polymer support (PEG ester).
' D i n s m o r eC , . J . ,Z a r t m a n , C . B . T L 4 0 . - j 9 8 9r l q X r P a r r i s hJ, . P , D u e n o , 8 . E . ,K i m , S . - 1 .J, u n g .K \ [ 'Salvatore, R.N., Flanders,V.L., Ha, D.. Jung. K r D u e n o ,8 . 8 . , C h u , F . , K i m , S . I . ,J u n g ,K . $ . r I _ r -Chu, F., Dueno, 8.8., Jung, K.W. 7L 40. l8J- , I "Steinhagen, H., Corey,E.J.ACIEE 38. l9l8 r te -Bland, D.C., Raudenbush,B.C., Weinreb.S.\l r "Sauvagnat,B., Lamaty,F.,Lazaro,R., Martrrrz-
9SYo o-Alkylations. carboxylic acids undergo o-alkylation in DMF at room temperature.2Replacement of the chlorine atoms of the Merrifield resin by carbonateor carbamate groups is efficiently accomplished by reaction with alcohols or amines and carbon dioxide in the presenceof Cs2Coj and tetrabutylammonium iodide.i There are related reports on etherificationaand mixed carbonateformation.s
Cesiumfluoride.13,68;14,79;15,15-|6 77 78 Disulfides.t Organoboranes are sult Organoborates aremorereactive. 2- Cyanomethyl- 1,2-dihydroqui noIin ct conveniently effectsalkylationat C-2ofqur
{tll
Iii
Cesium fluoride
r,te3sio ^,-\ X
:
-R
=
Hydroquinolines.6 Reactive heterodienes are generated from N-mesyl-2-halomethylanilines by treatment with CszCOr at low temperature.Interception of heterodienes readily affords adducts.
OSiMeg
F
.:,:
y'fo
* rl \or,
\A**
Cs2CO3 cH2ct2 -78'
all-) \.
\..r
L r \ ek c t oe s t e r s .
tt
oet
Ms 78To
Ms
Pyridines.l The intramolecular Diels-Alder adducts of alkadienoic esters of C[cyanooximiesaromatizeby a doubleelimination processon exposureto Cs2CO',in DMF at room temperature.
c _cooEl alo6
o',
. : r , , n a l i r a t i oonl ' a l k e n e s( e . 9 . '
Cs2CO3
+
DIVIF
NCAX
X
X = CN, COOET
X=CN, R=H
67Yo
described for the synthesis of amino acid derivatives via alkylation of the N-diphenylmethyleneglycine ester consists of the use of polysubstrate (ethylene glycol) as solvent, promotion by microwave inadiation, and linking the Alkylation.s
. . 1 9 .7 0 ;2 0 '7 6 ions because .,.t irsPhenolate
,l
Noz
Y")A 4",V 95%
i:..
Ir:
.r.rlltion in DMF at room \lcrrrlield resin bY carbonateor :: * rth alcohols or amines and . ..rrnmoniumiodide.r There are '- -ttl()n.
A modification
onto a polymer support (PEG ester). l D i n s m o r eC . . J . ,Z a r t m a n C , . B . T L 4 0 ' 3 9 8 9( 1 9 9 9 ) ' rParrish.J.P. Dueno, 8.E., Kim, S.-1.,Jung,K'W SC 30, 2681 (2OO0)' rSalvatore.R.N., Flanders,V.L., Ha, D., Jung, K.\y' OL2'2'797 (2000)' lDueno, E.E., Chu, F., Kim, S.l', Jung, K.W TL 40, 1843(1999)' 5Chu,F'.,Dueno, E.8., Jung, K W. TL 40, 1841 (1999)' ('steinhagen,H., Corey,E.J.ACIEE 38, 1928( 1999)' rBland, D.C., Raudenbush,B.C., Weinreb,S.M OI 2' 4007 (2000)' ssauvagnat,B., Lamaty,F., Lazaro' R', Martinez,I'TL4l' 6371 (2000)'
18,88-89;19'7O-72;20' Cesiumfluoride.13,68;14,79:15,75-76;16,69-70:17,68; '7'1-'78 of csF' Disulfides.t organoboranesare sulfurizedwith sulfur in the presence aremorereactive Organoborates A combinationof MejSicH2cN and csF 2-Cyanomethyl-1,2-dihydroquinolines.2 effectsalkylationat C-2 ofquinoliniumsalts' conveniently
Cesium hvdroxide
ZY\
\i\i/
f.
Me.Si v cN MecN ))))
Me
an
Chiral auxiliaries and catalysts. L8' 89-9i Chiral d.erivatizing agents. (S)-O-ac by treatmentwith AcCl and the SOCI:.: lobtained from chiral diols via displacerne stages.2C2-symmetricbis-sulfoxides are ar
\A*"-'--cll Me
t-
55To
Annulatio n.t /rans-3,4-Disubstituted tetrahydrothiophenesare obtained from conjugated carbonyl compounds and chloromethyl trimethylsilylmethyl sulfide in a reaction mediated by CsF. When the conjugated carbonyl component bears a chiral auxiliary, the
with diacetone-o-glucoseand then Grigna from chiral N,N-dibenzyl ct-aminoketo amination.aQUIPHOS (1) is readily prepar
processis amenableto synthesisof enantiopurederivatives. R
Me3si^g^a,
* *Nto*
COX
\--.-ij
N.4eCN 0 - 20'
J
90-95%
Organotin halide cleanup.a Residual tin halides are a nuissance of organic reactionsthat generatethem as coproducts.A method using a 2:l mixture ofCsF and CsOH on silica to scavengethe tin halides (from dichloromethaneor THF solutions) is effective. lKerverdo, M. TL 41,6053(2000). S.,Gingras, rDiaba,F.,Le Houerou, M., Gerval,P.JOC 65,907(2000). C.,Grignon-Dubois, rKarlsson, H.-E.OL l, 1667(1999). S.,Hogberg, rBdelson, 8.S.,Stoltz,8.M., Corey,E.J.TL 40,6729 (2000)
Kinetic resolutions' Baylis-Hillmar reactivity toward Pd(O)-catalyzedsubsttt e chiral DMAP derivative 37 and the au developed as catalysts for enantio.'clo enantioselective acylation with the atd ol presenceof a cinchona alkaloids is a good
2\
"-A/ PPh2
NH Cesium hydroxide. Alkynylation. This base (monohydrate) is an excellent catalyst for alkynylation of carbonyl compoundsrand selectiveN-monoalkylation of primary amines.r Cesium hydroxide suppressesoveralkylation, and therefore is very useful in the exclusive tbrmation of secondaryamines from amino acids. Alkylations. An ether synthesisrfrom alcohols and alkyl bromides is promoted by CsOH and BuaNl in the presenceof molecularsieves4A in DMF at room temperature. Carbanion generation,a A l:l mixture of CsOH and CsF suspendedin dichloromethane or THF is very effective for generation of carbanions from l-trimethylsilylalkynes, 2-trimethylsilyl-1,3-dithiane,trifluoromethyltrimethylsilane,and silyl enol cthers.all throughdesilylation. rTzalis,D., Knochel,P.ACIEE38, 1463(1999). rsalvatore, R.N.,Nagle,A.S.,Schmidt,S.E.,Jung,K.w. OL 1, 1893(1999). rDueno, E.E.,Chu,F.,Kim,S.-I.,Jung,K.W IL 40, 1843(1999). rBusch-Petersen, J.,Bo,Y, Corey,E.J.TL 40,2065(1999)-
,,NH
^'/'.-.,\ " i
PPh2
l 1
\v (2)
a lle
Chiral auxiliaries
v*
N Me
55%
are obtainedfrom con]: ,rhrophenes .:hrl:il1'lmethylsulfidein a reaction ::rn()ncntbearsa chiral auxiliary, the
[:: rl n.
':
E .:-:
and catalysts
Chiral auxiliaries and catalysts. 18, 89-97 ; 19,'72-93 ; 20, 7 8-lO3 Chiral derivatizing agents. (S)-O-acetyllactyl chloride is prepared from lactic acid by treatment with AcCl and the SOCl2.r Unsymmetrical 1,2-bis(phosphanyl)ethanesare obtained from chiral diols via displacement of the cyclic sulfates using R2PLi in two stages.2C2-symmetricbis-sulfoxides are accessiblefrom reaction of bis-sulfinyl chlorides with diacetone-o-glucoseand then Grignard reagents.r Useful ligands can be prepared from chiral N,N-dibenzyl c-aminoketones by Grignard reactions and reductive amination.aQUIPHOS (1) is readily preparedin large scale from r--glutamic acid.5
itl\C\.
R )-20
'N'
COX
!i' \s,
Ph (1)
90-95%
:.rlrdcs are a nuissance of organic 1,'d using a 2:1 mixture of CsF and or THF solutions)is :.ihloromethane
{ ir
Kinetic resolutions. Baylis-Hillman adducts are deracemized by exploiting their reactivity toward Pd(0)-catalyzed substitution, using chiral ligand 2.6 Both the planar chiral DMAP derivative 37-eand the axially chiral analogue(4)r0 and 5rrhave been developed as catalysts for enantioselective acylation. Benzylic alcohols undergo enantioselectiveacylation with the aid of 6.r2 Methanolysis of meso-anhydridesin the presenceof a cinchonaalkaloidsis a good way to desymmetrizesuch compounds.r3'ra
'rt(' 65.907(2000).
,: rrccllent catalystfor alkynylation : r r;.ttl()nof primary amines.2Cesium : rr is very useful in the exclusive
llr hr:
a\
f^yi-"fr "--)-
. rnd alkyl bromidesis promotedby k r . .. -, -1.\ in DMF at room temperature. r - : ('.OH and CsF suspendedin di-
tr'' ,:i,,n of carbanionsfrom 1-trimethyland silyl enol f , ' :r1!-thlltrimethylsilane,
I
.-.
.1. l89l(1999). .l)q).
_lrn, *ft$]* Ph
v
:t.:.
x.',
f'-> -
O_\.,^\-2
9 _ "
(2)
(3)
rA fE,, .A af '^
rc?,u- ry (4)
(5)
(6)
Chiral auxiliaries and catalvsts
Halogenatians. Fluorination of ketones can make use of 7,rs although the enantioselectivity is only moderate. Of the active methylene compounds, fluorination in the presenceof dihydroquinine esters is adequate.16 A synthesis of B-amino-a-hydroxy acids involves iodination of substrates such as 8, which is attended by spontaneous cyclization.lT
\r")^-jiiLil{,. /-^jvo
(, (7)
(108)
(8)
Alkylations. Ketone alkylation has been mediated by 9,r8 and the process also exhibits excellent regioselectivity in favor of the more highly substitutedposition. Using allyl estersas electrophiles and a Pd(0)-catalyst, ligand ent-2te furnishes suitable support (a similar alkylation of azlactonesemploys ligand 220). The enantioselectivealkylation of N-protected cr-amino esters has been studied with many chiral catalysts,including spirocyclic ammonium salt l0A,2rwhile (10B) containing two binaphthyl components is an effective mediator for alkylation of protected gtycine underphase-transfer conditions.22 B-/-Boc-aminoacid derivatizedwith (+)-pseudoephedrineenablesenantioselectivealkylation of the ensuing amides.23Note the enolate derived from 11 remains chiral, alkylation products are produced in high ee.2a
Esters of a chiral trans-2-(2-naphthalc with excellent diastereofacial(hence enanu formed into chiral homologues via formatx and subsequental\' 10-camphorsulfonamide The alkylation productsof SAMP-hrdrl to chiral 1-amino nitrilesand ketones.: {.
have been studied in the context of their c: alkylation of their N-acyl28"and N-methrltlu Under phase-transferconditions a qu: Darzenscondensation.2e
I LJ
n --iR
r12
R=Me I R=Ph F
Displncements involving allylic systcs receive considerableattention.Improvemc the Pd-catalyzed reaction include imrrrc mesitylethylamine,rrpyridylphenylphosph
(10A)
from o-glucosamine.3rPhospholanessuch excellentlisands.ra
Chiral auxiliariesand catalysts
:],rke use of 7,1s although the n "r.::\lc-ne compounds,fluorinationin \ .rnthesis of B-amino-ct-hydroxy t: s fi .ihrch is attendedbv soontaneous Ph/\/.COOEt a'\ ' N - \ H OMe 7 tBuOOC
.
"
/t\A
il
'rn (10B)
8)
r:.: -:.rlcd by 9,'8 and the processalso i:l
(11)
9
:: hrehll substitutedposition.Using
-.,::.: t,Ir-2refurnishessuitablesupport . cl : .::r'.rnoestershas been studiedwith .;:: .alt l0A,2rwhile (10B) containD - ::rtor for alkylation of protected , ::,, acid derivatizedwith (*)-pseux o : ' - - r.uing amides.2rNote the enolate f : . ,-- rrtxiuced in high ee.2a 't
Esters of a chiral trans-2-(2-naphthalenesulfonyl)cyclohexanolundergo alkylation with excellent diastereofacial(hence enantiomeric)selectivity.25 Glycolic acid is transformed into chiral homologuesvia formation of 1,3-dioxolanonewith N,N-diisopropylI 0-camphorsulfonamide and subsequentalkylation.26 The alkylation productsof SAMP-hydrazoneswith N-tosylaziridinecan be convertied to chiral 1-amino nitriles and ketones.2T 4,5,5-Trisubstitutedoxazolidinonessuch as 12 have been studied in the context of their capacity for inducing enantioselectivity during alkylation of their N-acyl28,and N-methylthiomethylderivatives.28h under phase-transferconditions a quaternized cinchona alkaloid is used in the Darzenscondensation.2')
I = F
1-( ,>-F
:\ _:rn -ot
x@ { -
F
,10A)
oAtt-R' -^-7--\ \ /
R > (12) R = Me, R'= COEI R = Ph, R'= CHzMe Displacements involving allylic systems. Allylic substitution reactions continue to receive considerableattention.Improvement by microwave is noted.3oNew ligands for the Pd-catalyzed reaction include iminophosphine 13, which is derived from lmesitylethylamine,rrpyridylphenylphosphine 14,32and the phosphinite 15, obtained from o-glucosamine.rrPhospholanessuch as 16,17, lg, preparedfrom mannitol, are excellentligands.sa
Chiral auxiliaries and catalysts
-g,?-.# Fe \l-,,
=<+>(13)
(15)
(14)
(22\
Y
a''(" \A^-
oj.-(
Xofr'-'n
ix^ "^i-' " l
H 7 -
(16)
(17)
Metallocene-catalyzedring opening ol and organometallic reagentsa2proceeds ur based on the planar chiral ferrocenyl unrt presenceof both the r-acceptor phosphon
cently synthesized4S-ligand is 26.il Chiral ligands related to BINAP and us. text are 274sand28.46The aldimine represr
(18)
--}-sur" There is a remarkable reversal of enantioselectivity for reactions involving a bis(oxazoline) ligand 19 by merely changing the oxygen arms.3514-Diphenytphosphinoethyl) oxazolines20 representa secondgenerationof theseclassof ligands,being superiorto the lower homologues(the phosphinomethylcompounds)and as effective as the wellknown benzologue.36Placing the phosphorus atom at a bridgehead of the norbornadiene skeletoncreatesrelatively rigid phosphinooxazolines(21).37The planar chirality of the modified ferocene moiety in 22 is responsible for the stereochemicalcourse of the allylic substitution,so in thesecasesthe stereocenterin the oxazolinering plays at most a
B; (25)
minor role.38 With ligand 23 derived from B-pinene, the reaction of cinnamyl 2(benzenesulfonyl)vinylethers shows that vinylogous sulfonatesare viable substrates.r') A study on the acyclic fN-ligands 24 manifests the importance of substituent effects (bestwithR:NMe).ao
(27')
(oY*
a/-(t-Butoxycarbonyloxy)butenolide rs n
f,,"
chirality. In a formal synthesisof aflatorrn subunit.{tAllllic a-; rhe furanobenzofuran "chiral i with PhSO2Na, the products are reaction leading to branched products *rd
R=H,Bz
(1e)
(20)
(21)
and the I colinoyl-1,2-cycloheanediamine#
Chiral auxiliaries and catalysts
Ph'\94_o
tn-t ,u*t*l rn Vo
A
(15)
, I
-
a-:a" : I lt vp_\
A
H.^)--
Fe
-<>t'-
| -,,-
(22\
Y l
\
Y
R(rl.x#-
n
" l n'
,i-)
NPh'PPh t,H
Ph-P-Ph
ffY
(24\
(23)
Metallocene-catalyzedring opening of 7-oxabicyclo[2.2.l]hepteneswith alcoholsal proceedswith very high ee. Novel fS-ligands (e.g.' 25)' and organometallicreagentsa2 based on the planar chiral ferrocenyl unit,a3render good electronic control due to the presenceof both the tr-acceptor phosphorus group and the donor thioether. Another reS-ligandis 26.44 cently synthesized,fl Chiral ligands related to BINAP and used in the Pd-catalyzedallylic displacementcontext are 27a5and28.16The aldimine representativesof the latter seriesare not effective.
(18)
r..
. :,]r rcactionsinvolvinga bis(oxa-
t-1-Diphenylphosphinoethyl) lr,:::.' hr., . ..r.. of ligands,being supertorto 1r:. ,:.J' r and as effective as the wellc. , , hndgeheadofthe norbornadiene 'l:: ,- ll t The planarchirality of the .tc'tcochemical courseof the al[r : tc: ::'.corazolinering playsat most a ;: -' J. the reaction of cinnamYl 2-
-->_SH,r" n
<+> (25)
"^
|
(26) AT
I tlAAr
are viable substrates.re E -. ..rll()nates !. - .nrn()rtanceof substituenteffects
At
N\, I
Ar (27)
(21)
(28)
1-(r-Butoxycarbonyloxy)butenolide is readily transformed into aryloxy analogueswith chirality. In a formal synthesisof aflatoxin B, such a reaction precedesthe elaboration of the furanobenzofuransubunit.4TAllylic acylals also afford chiral sulfones in the reaction "chiral aldehyde" equivalents.asThe Mo(0)-catalyzed with PhSO2Na, the products are reaction leading to branched products with excellent ee is catalyzed by trans-N,N'-dipi' analogue29.50It also and the bis(oxazolin-4-carbonyl) colinoyl-1,2-cycloheanediamineae
102
Chiral auxiliariesand catalYsts
has proven to be valuable in the preparation of 3-substituted 1,4,6-alkatrienesfrom2,4'6alkatrienylcarbonates.By using ligand 30, productsare obtainedin good ee.sl
rq ":x'rY
Variable enantioselectivities are obsen presenceof ligand 35.63p-Hydroxyaldehld with a chiral allyltitanium species36.s *b pared from 37 by various organometallicn mercially available and inexpensive' are ! mediated allylation, even though thev trx Allylation such as that effected by 3E affon lation.67
-\\.,,\NH ,,.NH
o/'",(*-r\
5l'r^f") ono"'Y
LO
(30)
(2e)
o._rr\
of epoxides and aziridines. An observation that concerns the by SiCla in the presenceof 3l indicates a enantioselectiveopening of meso-epoxides beneficial effect of the o-methoxy group to form an octahedralcomplex.srB-Titanoxy A chiral Cr-salen radical intermediatesare involved when using 32 to open epoxides.ss complex has been used to mediateepoxide opening with KHF2. Although the ee values
HOD
opening
(34)
are moderate,this is the first reportof fluorohydrinformationby such a method.s{ 2,2-Disubstitutedepoxidescan be resolvedon reactionwith MerSiNr in the presence of a chiral (salen)CrN,complex.ssGood enantioselectivityis associatedwith the enanwith MerSicN mediatedby (pybox)Ybcl.r.s6sitioselectiveopening of rueso-epoxides
.o ' )-cno \ /
/-o1-
o
multaneousactivationof both epoxideand cyanideis indicated' chiral vinylglycidols containing a quaternary carbon center are obtained from prodracemic vinyl epoxidesvia ring opening with 2-methoxybenzylalcohol. One such of (-)-malyngolide.sT uct hasbeenusedin a synthesis proximal Co-salencomplexesthat are part of a dendrimershow cooperativereactivity 33 is the optimal cal in catalyzingepoxidering openingwith water.s8'Chromium-complex with MeiSiNj's8b reaction on azides to chiral meso-azindines rtng fbr conve B-amino alyst
all
N.^ -o UT
d N 3 Ticl2
(32)
The chiral sulfoxide 39 is valuable l-or ; reaction with aldehydes (low ee with keto aldehydeshas certainsyntheticuse'6" such ar { I, I -Bis(borylmethyl)ethylenes D 1.5-diols of bidirectionalsynthesis usuallyhigh.
t\?
(31)
(37)
(33)
several protocols have been developed for the preparation of Addition to c-.4, chiral cyanohydrinsor their trimethylsilyl ethers.Catalytic systemsincluding vanadyl-salen are eft'ective. complex,5e(pybox)YbClj,60zirconium-TADDOLate,6r and the 34-titanate62
Chiral auxiliaries and catalysts
from 2,4,6F, . -.i l.-1.6-alkatrienes a:- -:.rlncdin goodee.sr
Variable enantioselectivitiesare observed during allylation of aldehydes in the presenceof ligand 35.63p-Hydroxyaldehydescan be allylated in the unprotectedform with a chiral allyltitanium species36,64whereas c-hydroxyaldehydes are readily prepared from 37 by various organometallic reactions.65cinchona alkaloids, being commercially available and inexpensive, are suitable chiral promoters for the indiummediated allylation, even though they induce only moderate enantioselectivities.oo alkyAllylation such as that effected by 38 affords products useful for substrate-based lat10n.
-Ph
Hot'-en
5l'r^r") ,r
l h
t.: -
(\
-7-\
"l-
..!.r\ation that concerns the :rc presenceof 31 indicates a '.,hcdralcomplex.s2 B-TitanoxY ' cpoxides.5r A chiral Cr-salen KHF.. Althoughthe ee values
1-
<+>
HOl-v
(36)
(35)
(34)
. ,'n bv sucha method.5a " s ith Me.SiNj in the Presence :.. i\ associatedwith the enanSi-'Jntcd by (pybox)YbCl,.56
.o - !cHo r y
Fo{-
o
,.rtc'd.
! t!'
6,>9
%o"'Y
(30)
^, n center are obtained from . ^rnz1I alcohol. One such Prod-
tt/.-
/
i-PrOOC,.. " n
('"' I B )-: (J
/
Ph
-J
J
i-ProoCT
(38)
(37)
I
3
':r('r \how cooperativereactivity . :-c()nlplex33 is the optimalcat-
I
:.'. ()n reactionwith Me.SiNq.s8b
The chiral sulfoxide 39 is valuablefor assemblageof 1-butenolideson lithiation and The 1-selectivealkylation of 40 with reaction with aldehydes(low ee with ketones).6E use.6e aldehydeshas certain synthetic such as 41 are useful assemblingplatforms that allows 1,1-Bis(borylmethyl)ethylenes Diastereoselectivityand enantioselectivityare 1,5-diols.T0 bidirectional synthesis of usuallyhigh.
,-/
'N"
H
,
(33) h. l:.
\ ',dt X-,:'1 0
.:lcloped fbr the PreParationof , .r stcrlSincludingvanadyl-salen : rlrc3{-titanaten:areeffective.
-)-
-)-o
v
9r|i-)
-,rr"d N
)
( OTBS
/(3e)
/
(40)
Chiral auxiliaries and catalysts
Phosphoramideligands represe lation and aldol reaction. Their prq Aldol reactionwith l-proline as eratinganri-diols.3s Transitionstar
@t'-l'Td (41\
A direct synthesisof chiral propargylic alcohols from l-alkynes and aldehydesin the presenceof Zn(OTf)2, Et3N, and (+)-N-methylephedrinehas a broad scope.TrSeveral new ligands are found suitable for inducing asymmetric addition of R2Zn (mostly diethylzinc) to aldehydes.These include 42,1243,1344,1445,7sand 46.16Other B-amino which is more alcohols that show desirable features are 3-exo-morpholinoisoborneol,TT stable in air than the dimethylamino analogue, (S)-2-(pynolidin-1-y1)-1,z,2-trtphenylethanol,T8 and a polymer-supported N-alkyl-o,ct-diphenyl-l-prolinols.Te N,N-Dibutylnorephedrineis useful in a solvent-free reaction.80
!-< \/-NH
ri. ,'N=
\h('n
.\h V\:/
Zn
i' oH
ry:'n1en
">t;;'
TS (42)
\.r\N
(44)
(43)
eY1 t t l " (45)
,r+''"-^
Ph
H :- Ph
oH
catalyzedby Et2Zn-Ph1PSin the p dazolidinones8T serveas chiral aur zolidinones. In employing 4-r-hur equiv of a base leads to s,rn product
(47)
Aldol-type reaction of the tnn cneglycinewith aldehydesin the chonidiniumsalt leadspredominan A prior derivatizationof gll coh the way to anti-2,3 -dihydroxycarho
Chiral blactones are formed in t stoichiometry)in the presenceof tlx derivedfrom o-bromoenolatesare F From a TiClo-catalyzedBallrs roisoborneol,chiral adducts ens interestingaddend becauseeithc changingthe solvent.'rs Another r ligand51."('
'N-\
\-Jt" (46)
Practically perfect asymmetric autocatalystsof the (2-alkynyl-5-pyrimidyl)alkanol series havebeenidentified.8rA l-butylalkynylresiduefulfills the role ofproper bulkinessand moderate electron-withdrawing power. Quartz also induces enantioselectiveaddition of i-Pr2Zn to this heterocyclic aldehyde,82by virtue of its morphological chirality and acidity, which enable differentiation of the enantiofacesof the aldehyde upon coordination with the oxygen and nitrogen atoms.Chiral sodium chlorate crystals have the sameeffect.82o
,t??i {,,}t'.li (4e)
Chiral auxiliariesand catalysts
h il::-
l-r
)--' f, _..-
'-.'nr l-alkynes and aldehydesin the ..inne has a broad scope.TlSeveral ::nretric addition of R2Zn (mostly JJ.-' 45.'s and 46.16Other B-amino which is more :.h,rlinoisoborneol,TT 1,2'2-triph1-yl)5 r-1-(pynolidin-t--prolinols.Te N,N-Dibutyl.:rphenvl
Phosphoramideligands representedby 47 are valuable for Lewis base-catalyzedallylation and aldol reaction. Their preparationsare detailed.8l Aldol reaction with l-proline as catalystsahas been extendedto ct-ketols thereby generating anti-diols.8sTransition state 48 is consistentwith the results of aldol condensation catalyzedby EqZn-Ph.,PS in the presenceof a bisprolinol.86a-Amino acid derived imidazolidinones8Tserve as chiral auxiliaries in the same manner as the corresponding oxathe presenceof one or two zolidinones. In employing 4-r-butylthiazolidin-2-thione,88 series. enantiomeric products of opposite equiv of a base leads to syn orr"= R
Ph,
a
Phl--
N. /o
Ji s1, r
-)
N'P'f
\!,
I
,iY
ci
o.1..11>o\.ii,
i N-J?
)-a Y
(48)
(47)
(44)
Aldol-type reaction of the trimethylsilyl-t-butyl keteneacetalof N-diphenylmethyleneglycinewith aldehydesin the presenceof an N-anthracen-9-ylmethyl-O-benzylcinesters.se chonidinium salt leadspredominantlyto (2S,3R)-9-hydroxy-ct-amino paves chiral 5,6-diphenyl-1,4-dioxan-2-one glycolic into acid A prior derivatizationof process.e{) aldol+ype by an acids the way to anti-2,3-dihydroxycarboxylic Chiral blactones are formed in the condensationof keteneacetalswith a-diketones (2: I stoichiometry)in the presenceof the bis(oxazoline)-Cu(OTfbcomplex49.erAldol adducts derived from cr-bromoenolatesare precursorsof chiral ct,B-epoxyalkanoicesters.'lnl From a TiCl4-catalyzedBaylis-Hillman reaction in the presenceof l0-methylthioisoborneol,chiral adducts ensue.e4The acryloyl derivative 50 is a particularly interesting addend because either (R)- or (S)-alcohols can be prepared by merely Another variation employs hexafluoroisopropylacrylate and changingthe solvent.Ts lisand 5L.'Jb
(46)
r.
':, l-alkynyl-5-pyrimidyl)alkanolse.:lrll\ the role of properbulkinessand .:)Jucesenantioselectiveaddition of . nrorphologicalchirality and acidity, r:rc'aldehydeupon coordinationwith
c-
:: cn stalshavethe sameeffect.82u
Itl
I D(
i?i-i
{-io,.li (4e)
Aor# (50)
(51)
Chiral auxiliaries and catalysts
The Cu(Il)-catalyzed reaction of silyl enol ethers with oxomalonic esters in the presence of a bis(oxazoline) ligand constitutes the first step of an accessto chiral B-hydroxy acids.eTEnantioselective Mukaiyama aldol reaction performed in the presence of 52,e8 and that in aqueous ethanol has been accomplished to a certain degree of success (32-85Voee).ee Excellent diastereoselectivity (anti-selective) and enantioselectivity are observed in the reaction between phenylthioacetic esters and aldehydes.A B-bromodiazaborolidine (53) mediatesthe condensation.rm 1-;-Sparteine is useful in a synthesisofo-substituted serines from ethyl 2,5-diethoxy-3,6-dihydropyridine-3-carboxylate on reaction with aldehydes.ior A catalytic asymmetriccyanosilylationof carbonyl compoundswith MejSiCN using either a carbohydrate-based phosphineoxide (54)r02or the monolithium salt of a chiral salen ligandr03has been studied. Comparing to the BINOL analogues,the reaction involving 54 does not require phosphineoxide additivesto attain high levels of asymmetric induction, the catalytic activity is higher, and MejSiCN can be introducedrapidly.
Chiral Mannich reaction is als methylsilyl ether and N-alkylideneca by (S)-N,N-phthaloyl-r-leucinechlon<
During addition of Et2Zn to .\'-sl metric induction is rendered by 55 an aryl group from ArSnMe. asymmetnc
(s5)
(56
Homoenolatespeciesderivedfrom a-substitutedacrylic estersof isosorbide(via Sml2 reduction)can be usedto genratechiral ry-butvrolactones.l()a
The addition of organolithiumstr thylethylamineforms mainly one dra tion, therefromchiral aminesare ararl
//-\
(-P A*"
v'
Ta-
ct-Sulfinyl carbanions also add t isopinocampheylborane is an allrl t whereashigh-leveled1,6-asymmetn -1.5-dicyclohexyl-2-vinyl1,3-dioxola
Ph P Ph-ll
o
N'B'o
o
Ori o
Streckerreaction to establisha rx ' capableof creatingeither a tertiar) The peptido-imine60 provesto be an of aldimines.r2o On catalysisof tlx
.V-benzhydrylaldimines affordsc-amu
(53)
(54)
Addition to C:N. Substrate-based synthesisof chiral amines often relies on the availability of enantiopure imine derivatives. An improved preparation of chiral sulfinimine building blocks employs titanium(IV) ethoxide to promote condensationof chiral To1S(O)NH2with carbonyl compounds.r0s An asymmetric synthesisof B-amino estersinvolves reaction of chiral sulfinimines in which the sulfinyl group is linked to C-10 of an isobornyl system.r06Generation of a dehydroglycinamide fiom 2,10camphorsultamis readily achieved by treatment with Me.,Al and the O-benzyloxime derivativeof methyl glyoxylate.The dehydroglycinamideis receptiveto fiee radicalswith high diastereofacialdiscrimination.I07
o\.o\ N,
N ' 1.Ph
^), (58)
Chiral auxiliaries and catalysts
I ,r\()malonicestersin the pres: .rn accessto chiral B-hydroxy ,rrnedin the presenceof 52,e8 a certain degree of success
r. I. . rr r.'.
r : - .:ntl()selectivityare observedin i :. ..ic'.. A B-bromodiazaborolidine s . - - ' . - , r n a s v n t h e s iosf o - s u b s t i t u t e d rr- . : ..irborylate on reaction with - ,nrpoundswith MejSiCN using 'hc nronolithiumsalt of a chiral \ r t I a n a l o g u e st h . e r e a c t i o ni n -
I
h: .rttainhigh levelsof asymmett: \ t . . ( \ can be introducedrapidly. \: ' . lre cstcrsof isosorbide(via SmI2
Chiral Mannich reaction is also successful between endo-2-acetylisobornyl trimethylsilyl ether and N-alkylidenecarbamateprecursors,ro8and with aldimines activated by (S)-N,N-phthaloyl-r-leucinechloride. r0e During addition of EtZn to N-sulfonylimineslr0and N-phosphonylimines,lrlasymmetric induction is rendered by 55 and 56, respectively.N-Sulfonylimines also accept the aryl group from ArSnMe., asymmetrically in the presenceof 57.tt2
r'z\1\ 9M" ^rW '.'-t-X VQ-r /yo" Phod/*"'" #o!",dY"H l''n
(s5)
r\
A
(s7)
(56)
t:
The addition of organolithiums to imines derived from an optically active ct-naphthylethylamineforms mainly one diastereomer.rrs Hydrazones58 undergo radical addition, therefromchiral aminesare available.rra cr-Sulfinyl carbanions also add to chiral sulfinimines stereoselectively.rrs Allyldiisopinocampheylboraneis an allyl transfer agent reactive toward N-silylaldimines,rr6 whereashigh-leveled1,6-asymmetricinduction is observedduring the addition of (R,R)r7 4,5-dicyclohexyl-2-vinyl1,3-dioxolane to aldimines.r Streckerreactionto establisha new stereocenteris subjectto asymmetricinduction, capableof creatingeither a tertiaryrrsor quaternarycarbon atomrlein the presenceof 59. The peptido-imine60 provesto be an excellentligand for the Ti(IV)-mediatedcyanation of aldimines.r2{)Oncatalysis of the bicyclic guanidine 61 the addition of HCN to N-benzhydrylaldiminesaffordscr-aminonitrile derivativeswith moderateto good ee.r2r
Ph -_
-.
P Ph'il
o
(54)
-lrral aminesoften relieson the irtlr()\ed preparation of chiral ,i.ic' tr) promotecondensation of \ ..i rnnretricsynthesisof B-amino ., .: thc sulfinyl group is linked to :.'hrdroglycinamidefiom 2,10r: \lc',Al and the O-benzyloxime | .. n.. .- r. rcceptiveto free radicalswith ,r. I | -
o\ro: NJ- .._ph N-
*)l
"'.t-RXi*v 3
H
H
'oJ/) )*
(58)
:
')
(5e)
t^r-
Chiral auxiliaries and catalysts
o aftc
o .^o
H
(60)
(61)
It is interesting to note that .1r?/i-selectivityof aldolization (with t--proline promotion) involving hydroxyacetoneas the donor is switched in the Mannich reaction.Thus .syn2-hydroxy-3-aminoketonesare obtainedas major products.r22 a-Branchedaminescan be synthesizedfrom aldiminesor ketimines.A chiral version involving hydrosilylation of N-aryl ketimines with PMHS adopts ethylenebis(11rtetrahydroindenyl)titanium difluoride as a precatalyst,r2sdiarylmethylamines Additinn to C:C. Chiral ct-arylpropanoic esters are generated by the union of arylketeneswith alcoholsin the presenceof 62.124 An arylselenomethoxylating agentthat dependson an o-(ct-methylthioethylgroup to exert its enantioselectivityis preparedin situ from the diaryl diselenideby treatmentwith bromine and AgOTf.r2sAnother chiral reagentis endo-3 -bornylselenyl tri fl ate.I26 Cyclopropanoneacetalswith a quatemarycarbon atom in chiral form can be established by addition of bisoxazolineJigatedallylzinc reagentsto the cyclopropenes.r2T The tBuLi/(-)-spateine combination favors Br-Li exchangeand also promotesenantioselection in the intramolecularadditionof :ryllithium to an o-alkenylsidechain(e.g.,indolinesynthesis).r2fr'tzv Moderateasymmetricinductionis shown in the hydroarylationof norbornenein the presenceof63.r30 Cyclizationof dienesand enynesto form five-memberedrings proceedsenantioselectively in the presenceof Pd complexesof chiral ligands such as 64rrr and those of the bis(oxazoline) typ".'t' The intramolecularPauson-Khandreactionfinds anotherversion in chiral titanocene I3l catalysis.
(\") s=-- "_s/_o" t"' o_<") *-"./. \-11-7 _i5_ e.. (62)
(63)
(64)
Mi.chael reactions. A 4N-ligand (65) for the Cu(OTf)r-catalyz.ed conjugate additionby diethylzinchas beendeveloped.r3a Substrate-directed asymmetricinduction in the addition of ct-aminoradicalsis the basis of a necinebase synthesis.r3s With a chiral
Al-salen complex, the addition of hydrae acyl groups is ct,B-unsaturated,excellent very valuable for the synthesisof p-amino
A synthesisof 2,8-dioxabicyclo[3.-1 addition of formaldehyde SAMP-hydral ct-alkylation, with hydrolytic reorganizarro 66 was discovered after screening a L Michael reaction to enones compound. "
line)-Cu(SbFu)2catalyst between silyl erd lishes two adjacent stereocentersfavonrq keteneacetalsand alkylidenemalonicesters alkylidene group is quite far away from rhc,
Another conjugateaddition involving l.. alyzedby 67.rarFor the addition of nirroall viable chiral auxiliary and rrans-2,5dinrrh,
o
rA.\
\),auj|l,\r @PPh2N-z) (6s)
H P-X
J /Yt 'H ug )-{ L/rrc
o
(67)
By using N-anthracen-9-ylmethyl-O-h the conjugateaddition of nitromethanero l a mixture of (R/.9)adductsin a 85:15 rauo for conversioninto (R)-baclofenhydrochlc
spasmscausedby spinal cord injury. Also r catalyst for the synthesis of methyl drhl<
Chiral auxiliaries and catalysts
Al-salen complex, the addition of hydrazoic acid to mixed imides in which one of the acyl groups is cr,B-unsaturated,excellent enantioselectivity results. Thus, this process is very valuable for the synthesisof B-amino acids.r36 derivativesconsists of conjugate A synthesisof 2,8-dioxabicyclo[3.3.0]octan-3-one addition of formaldehyde SAMP-hydrazone to a,P-unsaturated E-valerolactone and
(61)
lc d x
(with L-prolinepromotlon) .,i:,r11 :r \lannich reaction.Thus sYn..-:'
ll
d.rA i.r
- - ,rr ketimines.A chiral version l'\lHS adopts ethYlenebis(13-
[ : r-.
r chiral fbrm can be established The /rhc cyclopropenes.l2T
r-
: .rl\opromotesenanlioselection .rdc chain(e.g.,indolinesYnthe''.rJrtrarylationof norbornenein
.lr.rrllmethylamines e. ,:. .rr!' gcncratedby the union of agentthat A. , .1..'lcnomethoxylating in prepared -n,rntioselectivityis r chiral - .rndAgOTf.r2sAnother t.r
Lt
r.l :-
:rJ rings proceedsenantioselec.uch as 64rrr and thoseof the
f:.
rhcr rersion in chiral titanocene
cr-alkylation, with hydrolytic reorganization of the functional groups.137 66 was discovered after screening a library of 100 ligands for the copper-catalyzed Michael reaction to enones compound.l38The asymmetric reaction using the bis(oxazoline)-Cu(SbF6)2catalyst between silyl enol ethers and N-alkenoyloxazolidin-2-onesestablishes two adjacent stereocentersfavoring the anti arrangement.rleThat between silyl keteneacetalsand alkylidenemalonicestersis surprisingly effective despite the fact that the alkylidene group is quite far away from the chiral environmentcreatedon coordination.raO Another conjugateaddition involving l,3-dicarbonyl compoundsand nitroalkenesis catatyzedby 67.14rFor the addition of nitroalkanesto 2-cycloalkenones,l-proline is the most viable chiral auxiliary andtrans-2,5-dimethylpiperazineis a most beneficial additive'ra2
9?-i:D @PPh,N-/ (66)
(65)
ff.#,a
\t /tto t--
C\<") \-11 -7 (64)
f':
!". L
C u(OTf)2-catalYzed conjugate .lrrr'ctcdasymmetricinductionin With a chiral I ha\c synthesis.r3s
orr
\;|/
(67)
By using N-anthracen-9-ylmethyl-O-benzyldihydrocinchoniniumbromide as catalyst, the conjugateaddition ofnitromethane to l-phenyl-3-p-chlorophenyl-2-propen-l-oneyields a mixture of (R/,f) adductsin a 85:15 ratio.ra3After recrystallization,the product is suitable for conversioninto (R)-baclofenhydrochloride, which is an important drug for treatmentof spasmscausedby spinal cord injury. Also wonhy of mention is the application of a similar catalyst for the synthesis of methyl dihydrojasmonate under conditions of solid-liquid
110
andcatalysts Chiralauxiliaries
phase-transfercatalysis.ra On the other hand, N-(2-alkenoyl)-4-phenyloxazolidin-2-ones for generatare Michael acceptorswith builfin diastereofacialcontrol. Therefore a method merely to consist evolves acids ing enantiopureB-substituted1-butyrolactam-1-carboxylic complexes'ras base-Ni(Il) glycine Schiff with adducts form to of using the chiral substrates synthesized syn-2,3-Disubstituted4-pentenoic esters of high optical purity have been in serving 68 Sulfoxide stage' first in the protocol trapping and using the Michael reaction equivalent'rab anion vinyl a Michael donor role, is a chiral
Optically active B-lactones are readill p The p using 72 as the chirality inducer.r5r'r5: ar ketenes of + 2lcycloaddition The acids. 12
P nine leadsto numerouscjs-2,3-disubstituted Reports on the advancesof asymmetric l" of diazoalkanesto N-(2-alkenoyl)oxazolidin 73, showing cooperativechiral control bv thc ral ligand. l5aAn intramolecular cycloadditron
a chiral cyclic N,N'-dimethylaminal unit ady 74) proves very successfulin the asymmetnc nitronelacksstereoselectivity.lss
o
Me3Si
\
(68)
5*
quite effiAmination of silyl enol etherswith azodicarboxylicacid derivativesis usually complex.raT cient when conductedin the presenceof C2-symmetricbis(oxazoline){u(OT0: is fused to a cycloadditions. A chiral 2,2'-bipyridine (69) in which each nucleus ferrocene has found use in a CuOTf-catalyzed asymmetric cyclopropanation.ra8 evaluated in The catalytic activities of chiral biaryl ligands 70 and 7l have been of the introduction aziridine formation. The former is treated with borane-THF before in is used latter the while addends(N-benzhydrylaldiminesand ethyl diazoacetate),rae conjunctionwith(MeCN)aCuBF.topromotethetransferoftheTsNgroupfrom Ar group becausethey phI:NTs to alkenes.t50 The best are those with 2,6-disubstituted formation clearly define the steric and electronic profile of the active site and discourage of inactiveL2M2 sPecies.
_?_
Bn ,/-N1
/
t''*/ \
crgdozR borcr. R=Cl,Me
(72)
Alkenoylation of a camphor-basedclc On ten (for nitrile oxides).rsn dipolarophiles crc enantioselective are activatedto undergo I l'-binaphthr The 2,2'-bis(benzamido-1, 7( Compler ing the Diels-Alder reaction'rs8 Ise tractiverecyclingpossibility.
Fe
?_<.=<
O
? -r5-
tnt/*K
Fe
(6e)
/
\-Nf , H
(70)
(71)
(7s)
Chiral auxiliariesand catalysts
. - :r,,rI t-.1-phenyloxazolidin-2-ones Ttrerelbrea method for generatlf': t \ . . .rcidsevolves to consist merelY ! . ' - :e hirf base-Ni(Il) complexes.las l : ' ::-.r1purity have been synthesized ' Sulfoxide68 in serving t:. . r.t .tag.e. F:'
optically active Blactones are readily prepared by ketene-aldehyde cycloaddition The products are excellentprecursorsof B-amino using 72 as the chirality inducer.r5r,rs2 acids. The [2 + Z]cycloaddition of ketenes and imines in the presenceof O-benzoylquinine leadsto numerouscis-2,3-disubstituted B-lactams.r5l Reportson the advancesof asymmetric1,3-dipolarcycloadditionsinclude the reaction of diazoalkanesto N-(2-alkenoyl)oxazolidin-2-ones catalyzedby Mg or Zn complexes of 73, showing cooperativechiral control by the achiral oxazolidinone auxiliary and the chiral ligand.r5aAn intramolecularcycloadditionof the samekind from substratescontaining a chiral cyclic N,N'-dimethylaminalunit adjacentto the dipolarophilicdouble bond (i.e., 74) provesvery successfulin the asymmetricsense,althoughthe reactionof an analogous nitronelacksstereoselectivity.l55
Bn
/ 5*.+'-*/"'\ \
-:J dcrivativesis usuallyquite effi.,,razoline){u(OTfl)2complex.raT '.ihrch each nucleusis fused to a ) la8 :r. cr clopropanation. rr-:l -rl .rnd 7l have been evaluatedin d.
,/-N1
$:[ l'':90
cr.dorR borcr. R=Cl,Me
Ph
Ph
(73)
(72)
(74)
t 1 . : - THF before introductionof the
' , -' '' while the latter is used in ::.lc'r of the TsN Sroup from ri. ...n'trtutcd Ar groupbecausethey 1.. . 'ltc r discourageformation and hE-.
Alkenoylation of a camphor-basedcyclic acylhydrazideleads to substrate-defincd On temporary(in situ) derivatizationwith 75, enals dipolarophiles(lor nitrile oxides).r56 cycloadditionwith nitrones.rsT are activatedto undergoenantioselective complex of Yb(OTfl. is capableof catalyT.The 2,2'-bis(benzamido-1,1'-binaphthyl) Complex 76 has a very high stability and theretbrean ating the Diels-Alder reaction.rs8 tractiverecyclingpossibility.r5')
O
I) (70
\-il .
tnt/r{
t,l'^l Ar/--p-Ar)o{ ^
H
(71)
A'.. .iu*
/
(7s)
Ph-so
l
sor6
I Ph (76)
/
Chiral auxiliariesand catalysts
Asymmetric Diels-Alder reaction and its applicationsbasedon catalysisby bis(oxaThis methodhas been zoline)copper(Il)complexeshave been publishedin full details.160 4-aminodihyfurther extendedto the synthesisof 2,3-dihydropyran-6-ylphosphonates,r6r dropyrans,l62and piperidones.l63Note that both epimeric amines are accessibleby merely changing the diene substrate,that is, (E)- versus (Z)-configuration. Diazolidinone 75 servesas a chiral catalystthat also activatesenals (actualdienophilesbeing the
acids such as the [2.2]paracyclophaneden' been used. Ketones representedby 83 are a new gencn epoxidationof alkenesby [email protected] Ketond For example epoxidationof cis-alkenes.r75 doublebond.
iminium ions).r64 Hetero-Diels-Alder reactions involving N-phenethyl-(2-pyridylmethylene)imine A Cr complex 77 is useful for the synthesisof as the dienophile have been reported.r6s whereasa (salen)Cr(Ill) complex is involved in trisubstitutedtetrahydro-4-pyranones,r66 |67 thosereactionwith I -amino-3-siloxv-I .3-butadienes.
il_"F y'--n
o N 9 H
tl-.\
i l l
v
&q
(80)
(81)
sbF6 /77\
H,
o /\
Compund 78 is among the new transitionmetal catalyststhat have fbund good use in the decomposition of diazo compounds and delivery of the metal carbenoids to (79) possesses a stereogenicphosphoruscenter and Iminodiazaphospholidine alkenes.r68 is now known. The Zn chelate its applicability to effect asymmetriccyclopropanationr6e of 80 is effectivefor the Simmons-Smithreactionof allylic alcohols.rT0
.) Ph- Nr
,*1,,,t
t'*2
Me2N' Ph
(78)
(7e)
Epoxidations. Grafting tantalum onto silica to form a useful catalyst fbr the Sharpless asymmetric epoxidation of allyl alcohols is contrary to the inefl'ective titanium species on a similar support.rTrVanadium-complexedchiral hydroxamic
(83)
Poly-t--leucinerT6 and a polymeric BINOL lhe epoxidationofenones. Poly-l-leucine imm An air- and moisture-stableionic liquid rn -hiral (salen)Mn(Ill) complexesthat are usedr Ketone reductions. Corey's oxazatnrolr 'r,rane reduction. A cheap borane source for tl
:lro modifications,for example, using aluml :r'rivative85.r82
The use of LiBHa to reduce an arylborarx .rows good results.l83Ketone reductionurth r hich the polyhydroxy outer rim is derived f r rth ee valuesexceedins95Vo.t8a
Chiral auxiliariesand catalvsts il: t : .
l:t
_
t . . :
. ..r\cd on catalysisby bis(oxa:. i.rils.16r) This methodhasbeen . :.hosphonates,r6l 4-aminodihy-:te amines are accessibleby ...,2t-configuration.Diazolidi: . ractual dienophilesbeing the . r r rl - r3 - p y r i d y l m e t h y l etni m e ine -' r' useful for the synthesisof ('rr lll)complex is involvedin
ll3
acids such as the [2.2]paracyclophanederivative glr72 and the crowded g2r?3 have been used. Ketones representedby 83 are a new generation of catalysts for mediating asymmetric epoxidation of alkenes by [email protected] Ketone 84 exhibits desirable characteristicsin the epoxidation of cis-alkenes.r75 For example, it does not cause isomerization of the doublebond.
H V _ *)pi^ o
v
s
N 9 H
\4
(80)
(81)
(82)
o
^1. 4 .o
ro-i,,,rt
H C.:
ri I
. that have tbund good use in ,'l the metal carbenoidsto 'rr'nic phosphoruscenterand . now known. The Zn chclate .rlcohols.lr0
,\ F-
\-1 H ' . ) N Ph
79)
h
rnr a useful catalyst for the .L()ntrary to the inel'fective
ll
' r r r p l c x e dc h i r a l h y d r o x a m i c
I
o
(83)
:\4" -Yo
oa/
\
(84)
Poly-r--leucinerT6 and a polymeric BINoL-zinc complexrTThave been evaluatedfor the epoxidationof enones.Poly-l-leucine immobilized on silica is alsoeffective.rT8 An air- and moisture-stableionic liquid in the reaction media facilitatesrecovery of chiral (salen)Mn(Ill) complexesthat are usedin asymmetricepoxidation.rTe Ketone reductions. corey's oxazaborolidine continues to be a popular catalyst for boranereduction.A cheapboranesourcefor the reductionis LiH-BFj.OEtr.r80 There are also modifications,for example, using aluminum(Ill) ethoxide,r8rand the sulfbnamide derivative85.r82 The use of LiBHo to reduce an arylborane derivative g6 prepared from tartaric acid .hows good results.r8s Ketone reduction with NaBHo in the presenceof a dendrimerin Nhich the polyhydroxy outer rim is derived from glucose results in secondary alcohols ivith ee valuesexceeding95To.tta
tt4
Chiral auxiliaries and catalysts
A route to chiral alcohols from enon (Meerwein-Ponndorf-Verley reduction r irc are attached to the monoterpene skelettx group.relAromaticketonesare reducedhr tl
G
N-r
T{
I
(9
(8s)
(86)
In free radical reduction mediated by chiral hydrostannanes,there is a remarkable enhancementof enantioselectivityby Lewis acids.r85 when using a hydrosilanein the ke_ tone reduction,Rh complexesof87,r8688,r87and g9rs8servewell as chiral catalysts. A Lewis acid shows a remarkable enhancementof enantioselectivity during fiee radical reduction by some stannanes.rse Accordingly, borohydride reduction of 1,3diaryl-1,3-propanediones in the presenceof the cobalt complex 90 convenientlyprovides chiraldiols.re0
Asymmetric hydrogenation With crx hydrogenationof | - aryl-I,2-propanediones. r but the secondreduction follows when the ten trans-diols.le3
Ph
r
Ph-<
Nts
7,;''*
/\
€> <>
(tn
1"",'- f"
<+>
(87)
(88)
Ar
Ar
l__s t t \
o'
,/:N.
/
Fd
2-Azanorbornyl-3-methanol(93) shorrs I rransferhydrogenation.rea On binding to Ru. rnd the ferrocene-based ligand 96r%are ahle genationof 1,3-diketones.
,N1 / co 'o-(,H.
\
b
r?f, \\-\-ot
aY'< )' \Arr l
a'\,/
(8e)
(e0)
(e3)
(e4)
)
.
j
Chiral auxiliaries and catalvsts
tl5
A route to chiral alcohols from enones relies on stereoselectivehydride transfer (Meerwein-Ponndorf-Verley reduction) from the isoborneol moiety after the substrates are attached to the monoterpene skeleton through Michael reaction with a lo{hiol group.re'Aromatic ketonesare reducedby the systemof r-BuoK-l-proH and 91.1e2
r3u
(e1)
86,
F. .:' ' .rnL'\.there is a remarkableenf, '. .;.rnga hydrosilanein the ke' ' ' . . . . r i c - la l sc h i r a lc a t a l y s t s . -nrntioselectivityduring free B: -,,rrrhl'dride reduction of 1,3ra rl: - .' rlcr 90 convenientlyprovides
Asymmetric hydrogenation with complex 92 to mediate the asymmetric transfer hydrogenationof 1-aryl-1,2-propanediones, the acetyl group is preferentially transformed, but the secondreduction follows when the temperatureis raised from 10oto 40", furnishins trcns-diols.le3
(e2) 2-Azanorbornyl-3-methanol(93) shows its value as a chiral ligand in Ru-cataryzed rransferhydrogenation.rea on binding to Ru, cr-symmetric diphosphines(94,95, etc.)res rnd the t'errocene-based ligand 9fre0 are able to exert their steric influencesdurins hvdrogenationof 1,3-diketones.
68
tr-
\_t -'r (
--:
Ar
n
,,^
\\ - / / , / \
\
,N1 Co.
r.rH rf l ( |
/ /-\
01
0
\-\-o*
z>r.P< l l
|
\
\Ap-r l ) a--J
(e3)
/
(e4)
r
)-een2
\-rrn, '
(e5)
PPh2
(-z< [""n'**"
(e6)
116
Chiralauxiliariesandcatalysts
carAmong the effective diphosphine-Ru-diamine complexes used for catalyzing atoms phosphorus the in which member one is enantioselectively bonyl hydrogenation re7 are attachedto a l2,2lpatacyclophaneunit. in the The principle of asymmetric activation-deactivation has been demonstrated racemic of Ru complex a of consisting system a catalytic using ketones of hydrogenation following dimethyl-BlNAP and two chiral diamines.re8The principle is depicted in the diagram.
(es1 substrate
[ _
trs)-*al @ u_ L=:l ffffffffffffffff/nr-*fl g
_____\ llrst-catl l(s)AJ ----)PRoDUcr
l-
:
,
| | rn;-cat1""'l(n)-oeact I -_)
asym Platinum catalysts modified by cinchona alkaloids have been developed for of complex Ru the and metric hydrogenation of ct-keto acetalsreeand a-keto esters,2O0 chiral 2-(MeO)BIPHEP 97 has been developedfor B-keto sulfone reduction.2Ol p-keto esters Ruthenium-basedasymmetric hydrogenation of ct-arylacrylic acids and
Good resultshave been obtained from h1d of indolesurt cationiczirconocenecatalyst,205 2-(MeO)BIPHEP-Ru a and of 2-pyroneswith Very efficient ligands that complementt' ' are l0l.: droaminoacids(and derivatives) 87 with Rh+ has the versatilityof catalrnne and conjugateaddition.2r'
usesthe bipyridylbisphosphine98 (and its enantiomer)'202
OMe
HO
o MeO
PPh2
MeO
PPh2
MeO
PPh2
MeO
PPh2
(J
Pl
Ph2P.Rh/
(} OMe
(101)
il
(e7)
(cod)zRhBF+ The ferrocenyldiphosphineligand 99 constitutes a catalytic system with Seccompounds'2{)3 alkylidene for synthesizing ct-alkylsuccinic acid derivatives from the using acetates enol of ondary acetatesin chiral form are accessiblefrom hydrogenation the catalytic system of (cod)2tthBF4-100.2s
The paradoxconcerningthe generattonc and,\'-t I -r-l 't N-( l -phenylvinyl)acetamide of sutrsu mode .r()odon the groundsthat the stere(^-iE :hc catalyticcycle determinesthe
Chiral auxiliaries and catalysts
tt7
carF i..-'. used for catalYzing atoms 1- .irruh the PhosPhorus n :..:- heen demonstratedin the lt::' : ,'i a Ru comPlexof racemrc r: . :. dePictedin the following
-
r
L.
I
substrate
PRODUCT
J
)
e a- :
-
,.: heen develoPedfor asYm and the Ru comPlex of c ' :.. '.-.I,tnereduction'2ol u*. ,-:rlic acidsand p-ketoesters
Good results have been obtained from hydrogenationof tetrasubstitutedalkeneswith a ?06 of indoles with a bis(ferrocenylphosphine)-Rhsystem, cationic zirconocenecatalyst,205 and of 2-pyroneswith a 2-(MeO)BIPHEP-Ru complex.2{)7 Very efficient ligands that complement (cod)2Rh+salts for hydrogenationof dehyand 103.2r0A combinationof ligand 102,20') droamino acids (and derivatives)are 101,208 87 with Rh+ has the versatilityof catalyzingasymmetrichydrogenation,hydrosilylation, and conjugateaddition.2rI
OH
----( I
)" oH
a-
a-Y':'.,.--
12 \PPhz
\-\r{
PPh2
I FOH ,.'\\,/ \ : \ b x (101)
-/^ Ho1 Ho"'\ ) " (/-o,
Ho
ro r-.. o o
Ph2d\
\oeen, 6.!",oeen'
-\u
..'PPh2 Rh
/\ ^
NJ\ \--r
(102)
(103)
98
r-:1.,.rttc systemwith (cod)zRhBFr Sec| ::.- .1ik\lidenecompounds.203 uslng acetates i.:: :r'nition ofenol
The paradoxconcerningthe generationof oppositeenantiomersin the hydrogenation of N-(l-phenylvinyl)acetamideand N-(l-t-butylvinyl)acetamidewith 104 is now understoodon the groundsthat the mode of substratcdocking at the migratory insertionstepof the catalyticcycle determinesthe stereochemicaloutcome.2rr
Chiral auxiliaries and catalYsts
f18
\11
H.
NHAc
\ D .
ANH
Y i r' l-'oY1n.^ ;
,i-l
I "
NHAc a Ph/\ 99% ee
rl ,,\J '-;n''' . \o/ "'( ."'' \,1
/
r12
b
\4
S
/
BFA \
Accessto bicyclic enonesfrom 1.6-en1n
cnantioselectiveby installing a chiral t-bu cr-benzylidene-aroylacetamidesto furnish -1
z'J*{' ->-; I ri H.
Yti-ri-,"^*t^' { l''1.,X
,\,
Heterocyclic analoguesof BINAP, such ar -bis(diphenylphosp 2,2',5,5' -tetramethyl-4,4' and testedin the Heck reaction.22rIncorporarx sulfinyl group to a double bond elicits eru intramolecularHeck reaction.222 Opticallr a ides are produced from (R)- 1-t-butylsulfin1lc1 Palladacycle (109) and its analogues ind
rearrangement of allylic imidates.22rFor a thioamides, it is convenient to allylate thr dine.225 This processinvolvesa thio-Claisenn Enantioselectivedeprotonation of ketorrs sium bis[N-benzyl-N-(ct-phenethyl)] amide,: :" tonationof enolates.227
(104)
/
NHAc \,/ I
I
l
/
L >-\
H.
do9in ,.' A \ |/ / t - ->NH
i fi- ),pn4 / " \ \ l
PhA
/
\,/
,)1n./' +
+
NHAc I
>f'^\ I
rnduction when the amide moiety is denrc ,rne.22e Chiral ligands for the Pauson-Khand horane(111) derivedfrom (+)-pulegone is an
99% ee PPh2 Other enantioselectivereactions. Severalasymmetricreactionsworth mcntioning are the cu-catalyzeilallylic oxidationin the prcsenccof l05,r1r l06,r1ror l07rr5with loxiclationof sulfides(/-BuooH Tirvl in the prescnceof a 4,4'-dimer of butyl perbenzoate, the reductiveaminationby chiral t-butylsulfinamidc,rrr B-aromatic3-hydroxyestrane,rr('the with ol'phcnols C-arylation gfyoxylate ene reactionpromotedby Yb(OTf )r andent-73.2tE aryllcad reagcntsundcr the influenceof brucine,rr"and the C-H bond inscrtion by Rh-
PPh2
\/ ro;--
----\L-N'
Pd F"CCOO' \
d
,
P
1. (108)
(1Ull
carbenoids.:lo
MeO
H P h NJ VOH
*4-on H P h (105)
A Y2
rt
H".|_N (^\"" i3
(106)
(107)
Enantioselectivecyclization of carbanrtx -rn lead to cis- or trans-1,2-disubstitured c t'232 ' BuLi-( - )- sparteine.23
Chiral auxiliariesand catalysts
\
H
'
= -.1
a;.-Kn1,Lp[
NHAc +
:
I n l -\---NH
-.,,^\ rtl
/
..
99% ee
119
Heterocyclic analoguesof BINAP, such as the bis(benzothiophene)108 as well as the have been prepared 2,2',5,5'-tetramethyl-4,4'-bis(diphenylphosphino)-3,3'-bithiophene, and testedin the Heck reaction.22rIncorporation of a chiral o-(N,N-dimethylamino)phenylsulfinyl group to a double bond elicits enantioselectivity at the B-carbon during the intramolecular Heck reaction.222Optically active 5-arylcyclopenten-l-yl r-butyl sulfoxides are produced from (R)-1-r-butylsulfinylcyclopentene.223 Palladacycle (109) and its analogues induce chirality of N-allylalkanamides during rearrangement of allylic imidates.22aFor a synthesis of a-branched chiral 4-alkenethioamides, it is convenient to allylate thioamides of (*)-trans-2,5-diphenylpyrrolidine.22sThis processinvolves a thio-Claisen rearrangement. Enantioselectivedeprotonation of ketones is achieved by using a homochiral magneOn the other hand, 110 is excellentfor prosium bis[N-benzyt-N-(ct-phenethyl)]amide.226
BF;
tonationof enolates.227 Access to bicyclic enones from 1,6-enynesby the Pauson-Khand method is rendered enantioselective by installing a chiral f-butylsulfinyl group at C-1.228Cyclization of a-benzylidene-aroylacetamidesto furnish 3-arylindanones is subject to 1,5-asymmetric
lO{
-t'
* -.-Rh
NHAc
--,,l--l
induction when the amide moiety is derived from a bulky 4-substitulted oxazolidin-2one.22eChiral ligands for the Pauson-Khand reaction have also been studied. Phosphineborane(1L1) derivedfrom (+)-pulegone is an example.2r0
S
99% ee SiMer PPh2 u
)l
r l_
nctric rcactionsworth mentioning , , r l 0 5 . r r r1 0 6 , : r o 1 r l 0 7 r r 5w i t h / rn thc prcscnccof a 4,4'-dimcr of the hr chirall-butylsulfinamidc,rrT i' phenols with ol' 7-1.r C'-arylation j rhr-C-H
hond inscrtionbY Rh-
PPh2
(108)
\/ .o>__-+_-'-\{-N' -Y F"ccoo'Pd>r i"
y<5
(10e)
I
OH
[iYiJ"'.
,)-\4
( 11 0 )
A
| 1...H Ph '}^? -f
.A/-rn
BHe (111)
(107)
Enantioselective cyclization of carbanions derived from N,N-diisopropylcarbamates can lead to cis- or trans-1,2-disubstituted cyclopentane derivatives by treatment with I'232 r-BuLi-( - )-sparteine.23
Chiral auxiliariesand catalysts
A cyclization roure to 2-substituted (e.g., cinnamyl) pynolidines and piperidines in_ amines bearing a 3-chloropropyl or 4-chlorobutyl chain, re_ spectively. Asymmetry is induced by (-)-sparteine.233 volves cyclization ofN-Boc
rBuisson,D., Azerad,R. IA 10, 2997 (1ggg). 2Fries,G., Wolf, J., Pfeiffer, M., Stalke, D., Wemer, H. ACIEE 39,564 (2000). rKhiar, N., Alcudia, F., Espartero,J.-L., Rodriguez,L., Fernandez ,1. JACSl22,i5gg (2000). aReetz,M.T., Schmitz,A. TL 40, Zi3'1, 274l (1ggg\. sBrunel,J.M., Consrantieux,T., Buono, G. JOC g,g940 0999). 6Trost,8.M., Tsui, H.-C., Toste,F.D. JACS 122,3534 (2000). 7Ie,y., Fu, G.c. cC I l9 (2ooo). "Tao,B., Ruble, J.C., Hoic, D.A., Fu, G.C. JACS 121,5091 (1999). vBellemin-Laponnaz, S., Tweddell,J., Ruble,J.C., Breitling, F.M., Fu, G.C. CC 1009 (2000). r0Spivey, A.C., Fekner,T., Spey,S.E. JOC 65,3154 (2000). r r s a n o ,T . , I m a i , K . , O h a s h i ,K . . O r i y a m a ,T . C L 2 6 5 i t 9 9 9 t . r2vedejs,E., Daugulis, .lggg). O. JACS 121,5g13 r3Bolm,C., Gerlach,A., Dinter, C.L. SL 195 0999). '"Chen,Y, Tian, S.-K., Deng, L. JACS 122,9542 (200U. rsTakeuchi, Y, Suzuki,T., Saroh,A., Shiragami,T., Shibata,N. JOC 64,570g (1999). r6shibata,N., Suzuki, 8., Takeuchi,y JACS 122,1072g(2000). rTcardiflo,G., Gentilucci,L., Tolomelli, A., Tomasini,C. SL 1727 Oggg). r8saito,S., Nakadai, M., yamamoto,H. SL 1107 (2000). roTrost.B.M.. Schroeder.C.M. -/ACSl2t, 6759 ( | 9q9 r. / " T r o s r .8 . M . . A r i z a . X . J A C Sl 2 l , l 0 7 2 7 t l g g g t . 2rOor,T., Takeuchi, M., Kameda,M., Maruoka, K. "/ACS122,522g e0O0.,. 220oi,T., Kame
tsFuji, K., Ohnishi, H., Moriyama. S.. Tanrl r^Reetz. M.T.. Haderlein.G.. Angermund.X rTTrost, B.M., Toste,F.D. "/ACS12l. -t_iJ-r, I 'ETrost,B.M., Crawley,M.L., Lee. C_8.l"tC t'Kaiser, N.-F.K., Bremberg,U., Larhed. \t '"Glorius, F., pfaltz, A. OL l, 141(1999t 'rTrost, B.M., Hildbrand, S., Dogra. K. l.t( I -rBrunel, J.M., Legrand,O., Reymond.S . B 'rGansriuer, A., Lauterbach,T., Bluhm. H.. \ ']Bruns, S., Haufe, G. JFC 104, 247 (ZUn, 'iLebel, H., Jacobsen,E.N. Za 40, 7-je.r11q '6Schaus, S.8., Jacobsen,E.N. Oa 2. l0Ol ,: "Trost, B.M., Tang,W., Schulte,J.L. Ol 2. I 'r'Breinbauer, R., Jacobsen,E.N. AClEf t. "bLi,Z., Fernandez, M., Jacobsen,E.\. Ol I 'eBelokon, Y.N., North, M., parsons.T. Ol_2 '')Aspinall, H.C., Greeves,N., Smith. p\l Il 'rOoi, T., Takaya,K., Miura, T., Ichikau.a.H. "rHamashima, Y, Kanai, M., Shibasalii.\l ,1 ''Bolm, C., Muniz, K. CC 1295 0c)99t. {BouzBouz, S., Cossy,J. OL 2, 501 eXn, ''Colombo, L., Di Giacomo,M. TL q. lg-"'Loh, T.-P, Zhou, J.-R.,yin,Z. OL l. 1855r --Micalizio, G.C., Roush,W.R. Oa 2. {6 | r l0 ''"Renard, M . , G h o s e zL , .TL40,6237 tlW, "'Reggelin, M., Gerlach,M., Vogt, M. EI(X-"Banett, A.G.M., Braddock,D.C., de Konrnr LFrantz.D.8.. Fiissler.R.. Caneira, E.l\1./.{; :Paleo,M.R., -'Lawrence, Cabezza,l.,Sardina,F.J.J(X- | C.F.,Nayak, S.K., Thits, L.. Z*r 'Dangel. 8 . D . . p o t t .R . O L 2 , 3 0 0 j r 2 0 0 0 r 'Asami, M., ''Kawanami, Watanabe,H., Honda, K.. Inou. Y, Mitsuie, T., Miki, M.. Salam '-Nugent, W.A. CC 1369(tggg). -'Reddy, K.S., Sola,L., Moyano, A., pencan_! "Hodge, P, Kell, R.J., Ma, J., Morris. H. .;t/C '"Sato, f ., Saito,T., Soai,K. CC 2471 (2000, ' Shibata,T., Yonekubo,S., Soai, K. ACIEE A ':Soai, K., Osanai,S., Kodowaki, K., yonekub 'r"Sato, I., Kodowaki, K., Soai, K. ACIEE g. "Denmark, S.8., Su, X., Nishigaichi.y. Cc< 6 4 , 1 9 5 8( 1 9 9 9 ) . ''List, B., Lemer, R.A., BarbasIII, C.F. "/A(5 | ''Notz, W, List, B. -/AC.! 122,i386 eOOOt. '"Trost, 8.M., Ito, H. -/ACS 122, 12003 eXn, '-Kim, T.H., Lee, G.-J. TL 41, 1505(2C{[t. "Crimmins, M . T . , C h a u d h a r yK, . O L 2 . 7 : - 5 r J "Horikawa, M., Busch-petersen, J., Coret..EJ 'Andrus. M.8., Sekhar.B.B.VS., tr,teredirh. t' Audrain, H., Jorgensen,K.A. ,/ACS122. I l5{
Chiral auxiliaries and catalysts
inn . .\ rrolidines and piperidines re' chain' 4-chlorobutyl or l, :-r,,pvl
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t24
Chiral auxiliaries and catalvsts
rs5Dakternieks, D., Dunn, K., Perchyonok,VT., Schiesser.C.H. CC 1665 ( 1999). rsoYamanoi, Y., Imamoto,'1.JOC 64,2988 (1999). rsTKuwano, R., Uemura,T.. Saitoh,M., Ito, Y TL 40,1327 (1999). rENHeldmann, D.K., Seebach,D. HCA 82, 1096 (1999). rseDaktemieks, D., Dunn, K., Perchyonok,VT., Schiesser,C.H. CC 1665( 1999). pl)Ohtsuka, Y., Kubota,T.. Ikeno. T., Nagata,T., Yamada,T. SL 535 (2000). r"rNode,M.. Nishide. K., Shigeta,Y, Shiraki,H.. Obata,K. JACS 122, 1927(2OOO). r')rMurata,K., Ikariya, T., Noyori, R. JOC 64,2186 ( 1999). r"rKoike,T., Murata, K., Ikariya. T. OL2,3833 (2000). r"aAlonso,D.A., Nordini, S.J.M.. Roth, P, Tarnai,T., Andersson,PG.. Thommen, M., Pinelkow. U. loc 65,3r l6 (2000). ' ' s B l a n c ,D . , R a t o v e l o m a n a n a - V i dV a ,l , M a r i n e t t i A , . , G e n e t ,J . - P S L 4 8 0 ( 1 9 9 9 ) . r'16lreland, T., Grossheimann,G., Wieser-Jeunesse, C., Knochel, P.ACIEE 38,3212 (1999). r')7Burk,M.J., Hems,W., Herzberg.D., Malan, C., Zanotti-Gerosa,A. Ol 2, 1173 Q000). r')8Mikami,K., Korenaga.T., Ohkuma.T., Noyori, R. ACIEE 39.3707 (2000). r""Studer,M., Burkhardt,S., Blaser,H.-U. CC 1'727(1999). r')('LeBlond,C.. Wang,J., Liu, J., Andrews,A.T., Sun,Y.-K. JACS 121,4920 (1999). r0rBertus,P, Phansavath,P, Ratovelomanana-Vidal, V, Genet, J.-P, Touati, A.R.. Homri, T., Hass i n e .B . B . 7 A 1 0 , 1 3 6 9( 1 9 9 9 ) . r o : P a i ,C . - C . , L i n . C . - W . . L i n , C . - C . , C h c n , C . - C . , C h a n , A . S . C . ,W o n g , W . T . J A C S 1 2 2 , 1 1 5 1 3 (2000). r')tBerens,U., Burk, M.J., Gerlach,A.. Hems,V\t.ACIEE 39, l98l (2000). r " r J i a n g , X i a o , D . , Z h a n g ,Z . , C a o , P . ,Z h a n g ,X . A C I E E 3 8 , 5 l 6 ( 1 9 9 9 ) . Q., r ( ' 5 T r o u t m aM n ,. V . . A p e l l a .D . H . , B u c h w a l d ,S . L . " / / C S 1 2 1 , 4 9 1 6( 1 9 9 9 ) . r""Kuwano,R., Sato, K., Kurokawa,T., Karube,D., Ito, Y. JACS 122.7614 (2000) r ( ' i F e h rM , . F . ,C o n s i g l i o G , . , S c a l o n eM , . , S c h m i d ,R . J O C 6 4 . 5 7 6 8( 1 9 9 9 ) . r{'8l-i,W.. Zhang,Z.. Xiao, D., Zhang, X. IOC 65,3489 (2000). ro"YoneharK a ,. , O h e , K . . U e m u r a ,S . J O C 6 4 , 9 3 l JI ( 1 9 9 9 ) . r r { ' C h e nY, . . L i , X . , T o n g .S . ,C h o i . M . C . K . .C h a n ,A . S . C .7 1 -4 0 . 9 5 7 ( 1 9 9 9 ) . r l l Y a m a n oY , . , I m a m o t o .T . J O C 6 4 . 2 9 U 8( 1 9 9 9 ) . r l r G r i d n e v I, . D . , H i g a s h i ,N . , ! m a m o t o T . . J A C S1 2 2 . 1 0 4 8 6( 2 0 0 0 ) . r ' r A n d r u s ,M . 8 . , A s g a r i ,D . 7 5 6 . 5 7 7 5 ( 2 0 0 0 ) . r lrKohmura,Y., Katsuki,T. TL 4l, -394I (2000). rrsMalkov,A.V., Bella, M., Langer,V., Kocovsky,P. OL 2, 3017 (2O00r. rruBolmC , ., DabardO , . A . G .s I . 3 6 0 ( 1 9 9 9 ) . r r T B o r gC , . , C o g a n ,D . A . , l r l l m a n ,J . A . T L 4 0 . 6 7 0 9( 1 9 9 9 ) . r r s Q i a nC , . , W a n g ,L . f A 1 , 2 3 4 ' / ( 2 0 0 0 ) . r ' " S a i t o ,S . . K a n o ,T . , M u t o , H . , N a k a d a i ,M . , Y a m a m o t oH , . J A C S ' 1 2 18, 9 4 3 ( 1 9 9 9 ) . I o D a v i e s ,H . M . L . , H a n s e nT, . , C h u r c h i l l ,M . R . J A C S1 2 2 ,3 0 6 3 ( 2 0 0 0 ) . I r T i e t z e , l - . F . ,T h e d e ,K . , S c h i m p f ,R . , S a n n i c o l oF, ' .C C . 5 8 3( 2 0 0 0 ) . r r rB u e z o ,N . D . , M a n c h e n oO , . G . ,C a n e t e r o J, . C .O L 2 , 1 4 5I ( 2 0 0 0 ) . I t P r i e g o , J . , C a n e t e r o J, . C .S L 1 6 0 3( 1 9 9 9 ) . rrrDonde,Y, Overman,L.E. JACS 121,2933 (1999). rr5Hc,S., Kozmin, S.A., Rawal,VH. "/AC-S122, 190 (2000). rr"Henderson,K.W., Kcm,W.J., Moir, J.H. CC 479 (20001. r r r A s e n s i oG , . , C u e n c aA , . , M e d i o - S i m o nM , . , G a v i n a ,P .T L 4 0 , 3 9 3 9( 1 9 9 9 ) . rrsAdrio,J., Carreyero,C. JACS l2l,l4l I (1999). rrePridgen,L.N., Huang, K., Shilcrat, S.. Tickner-Eldridge,A., DeBrosse,C., Haltiwanger,R.C. SL t6t2 0999\. rr')Verdaguer, X., Moyano,A.. Pericas,M.A., Riera,A., Maesffo,M.A., Mahia, J. JACS 122, 10242(2000).
ChlomtJ
r r r D e i t e r sA, . , H o p p e , D. ACIEE3t,546 (l+r.l IlTomooka, K., Komine, N., Sasaki,T.. Shrmr4u rISerino, C., Stehle, N., Park,YS., Flono. S.. tk
Chloramine-M. Epoxidntion.t
A combination of chlrrar
yields an epoxidation agent. r Y a n g ,D . , Z h a n g , C . , W a n g ,X . - C . - / A C Sl 2 : . ! , '
Chloramine-T.20,
103
Chlorination,t
Heterocyclic kerenc a
( l0 examples, 80-92Vo).
H /N
|
Ph',
\-/
l_N/--
FO
.^tr ,.,a:-
H
rLiu,8., Wang,M.-X.,Huang. Z.-T.SC29.-l:rl
Chlorine dioxide. Alcohols.t Oxidation of trialkylalumu aflbrds alcohols(3 examples,85-90% r.
rKuchin, A.V..Dvornikova, 1.A.,Nalimova. L\u r
Chloroborane. Hydroborationr The dioxanc comp hydroborationagcnt. rKanth, J.VB.,Brown,H.C.OL 1,315(l99gt
Chloro( 1,5-cyclooctadiene)cyclopentadieo
Unsaturated ketones. A three-comJrrr and an enone while introducing a chlonne aro chloro-4-alkenylketonesris achieved.\rViri
liom allenesand enonesis effectedby CptcrrJ
Chloro(1,5-cyclooctadiene)cyclopentadienylruth€nium(I) 125 , t f i 6 - i( 1 9 9 9 ) .
, 1665(1999). < lO(x)). l : 2 . 1 9 2 7( 2 0 0 0 ) .
l ' ( ; . . T h o m m e n ,M . . P i t t e l k o w U , .
r-. r
( :r r!
rl llt0 (1999). i(7r.838.3212(1999). \ ( ) 1 . 2 .' 1 1 7 3( 2 0 0 0 ) . .- r- r1000).
Chloramine-M. Epoxidation.t A combinationof chloramine-M,phCHO, and benzyltriethylammonium yields an epoxidationagent. rYang,D., Zhang,C.,Wang, X.-C. JACS122,4039(2000).
Chloramine-T. 20. lO3 Chlorination't Heterocyclicketeneaminals undergochlorination with thrs reagenr ( l0 examples,8C|927a).
llt.1920(1999). I ' . f o u a t i .A . R . , H o m r i , T . , H a s -
;. i
I
) i ,rr I
\\irns. W.T. JACS 122, ll5l3 lr)lx)). ., I999). , ) 9 ()l .
I ll .
6J
H - N
l-
Ph,.
N/-
FO
l-l chloramine r .- N.
t"?1
,:"",,
(
N' H
Pht FO
t",
B5o/o
r6H 12000). 1999).
I '
'[-iu,8., Wang,M.-X.,Huang, Z.-T.SC29,1211(lg()g).
I
'l
r r l D e i t e r sA , ., Hoppe, D. ACIEE3g,546 (1999). r r r T o m o o k aK, . , K o m i n e ,N . , S a s a k iT, . , S h i m i z u ,H . , N a k a i ,T . T L 3 9 , 9 7 1 5 ( 1 9 9 g ) . rrrSerino, C., Stehte,N., Park,YS., Florio, S., Beak, p. JOC 64. il60 (1999).
J1'
.-,1999).
Chlorine dioxide. Alcohols.I Oxidation of trialkylaluminumswith ClO2 in ether at room temperarurc aflirrdsalcohols(3 examples,85-902o).
I
Kuchin, A.V.,Dvornikova, I.A.,Nalimova. I.yu.RC'B48,2001( 1999). r :1 . ltgl-l ( 1999).
i
N ) l
F I
Chloroborane. Hydroboration' The dioxanc complex of this borane is a hiehlv reacrive hydroborationagent. rKanth, J.VB.,Brown,fl.C.OL 1.315(1999\.
'i
.lt '
:,tr I999).
i
, .C.SL l i r o r s c .C . , I { a l t i w a n g e rR
i
\lrhia. J. JAC.! 122. 10242(2000J.
Chloro(1,5-cyclooctadiene)cyclopentadienylruthenium(l).20, 104 unsaturated ketones. A threc-component couplingthat lincarly combinesa 1-alkync and an enonewhile introducinga chlorineatom at C-2 ofthe original alkyne,giving (E)-5chloro-4-alkenylketonesris achieved.with 3-hexynol as activatoqa 1,5-dienesynthesis liom allenesand enonesis effecredby Cp(cod)RuCland CeCl3.7H2Oin DMF.:
t26
Chloro(l-rc
Chloro(1,5-cyclooctadiene)pentamethylcyclopentadienylruthenium(I)
CoHrs
- Sncla CpRu(cod)Cl
O
c6H13\
. \,,\
O
C.'
",^,.^'.-,.\
MeaNCl / DNiF
+ Ph-cooH
Ph----
,G
60.
7 5 %( E : Z > 1 5 : 1 )
,/z R.^\ZC-
+
tl
- Sncla cpRu(cod)cl
O ll \.,2.-*,
NH.cr/ Dt\ilF_H/o 100"
*-\.,,J{'-.,,^\r' ' ' t
t(
l
cpRu(cod)cr> -0^,-^-..
ocooMe \.'
+
MesSi-CHNz I
o
Allylic substitutions.t Successfulsubstitution of allylic carbonateswith retention of conligurations using carbon and nitrogen nucleophiles has been carried out in the presenceof Cp(cod)RuCl-NH4PF6.
. ,T-)
Ph---
."Xfi:r"
-
U (77
a) ,^lV l 1 ' 23)
5-M ethylene-2-oxytetrahydropyrans.' alcoholsand allyl alcoholsfurnishesthe c (at 80"). acetals
OH
LX
(o' * /
\
y-Butyrolactones.a Homopropargyl alcohols undergo catalyzed oxidationisomerization.The oxidizing agentis N-hydroxysuccinimide.
OH
\*",,n,u OH
- BuaNBr CpRu(cod)Cl
l_\r *ott
f-\ ooloo OH
(Z)-l,S-Hexadienyl carboxylates.o Cr substituted l,3-butadienes proceeds in hrg reaction involves the disubstituted double ho Sulfur compounds. Displacement of room temperature. Linear products also I
o )-o /
a \.,1.-.,,C''rHrt
62Yo
I
OH (-)-muricatacin
rTrost,B.M.,Pinkerton, A.B. "/ACS121,1988( 1999). 2Trost, B.M.,Pinkerton, A.B. JACS121,4068( 1999). rMorisaki,Y.,Kondo,T.,Mitsudo,T. OM 18,4742(1999). aTrost,B.M.,Rhee,Y.H.JACSl2l, I 1680( 1999).
Chloro(1,5-cyclooctadiene)pentamethylcyclopentadienylruthenium(I). l,3-Dienes.t2 Two types ofreactions involving l-alkynes leading to 1,3-drenesare illustratedin the followins.
an carbonates.51,2-Bis(phenylthio)alkanes catalytic conditr< disulfide under diphenyl functional groups (esteq silyl, etc.) directll t
rLePaih,J.,Derien,S.,Dixneui P.H.CC 1.1-17 rl ?LePaih,J.,Derien,S.,Ozdemir, I., Dixneuf.PH rDerien,S.,Ropartz, L., Le Paih,J.,Dixneuf.PH rFujiwhara, T.,Hori,Y. Oa l. l6-1 M., Nishikawa, 5Kondo,T., Morisaki,Y., Uenoyama, S.,Wada.K, 6Kondo, T., Uenoyama, S.,Fujita,K., Mitsudo.T
Chloro( 1,5-cyclooctadiene)triisopnopylpbr Diaryl ketones.t N-Pyrazylaldimines r readily hydrolyzed to the ketones.
Chloro(1,5-cyclooctadiene)tripropylphosphinerhodium(I)
lrut:.ntunttll
-.
c o H rt 3
l
Cp.Ru(cod)cl
Il
+ Ph-COOH +
Ph:
,.^\.,.\,,,\-
dioxane 23"
o^A,A/ot'
I Ph
98%
-5qo (E:Z>15:1) Cp.Ru(cod)Cl
Ph----
+
Me3S|-CHN2
;;;:
u".si$siM"' Ph
o 7 2 Y o( E : Z 7 0 : 3 0 ) t:
*
,:e carbonateswith retentionof hes bcen carried out in the
lo.f (77
5-Methylene-2-oxytetrahydropyrans.3 Regioselective coupling of propargyl alcohols and allyl alcohols furnishes the cyclic hemiacetals (at room temperature) or acetals(at 80").
OH
Cp'Ru(cod)Cl
L X +
23)
\ R=H, allyl
.1crso catalYZed oxidation1.,
I ,r)'.t
rCrrHrt
OZ-/o
I OH
)-muricatacin
tadirnr lruthenium(t). are n- .,rkrncs leadingto 1,3-dienes
(z)-1,5-Hexadienyl carboxylates.a codimerization of vinyl carboxylates with 2substituted 1,3-butadienesproceeds in high yields with excellent regioselectivity' The reaction involves the disubstituted double bond of the diene. Sulfur compound.s. Displacement of allylic carbonates with thiols takes place at room temperature. Linear products also predominate from reaction with secondary carbonates.5 1,2-Bis(phenylthio)alkanes are formed when l-alkenes are treated with diphenyl disulfide under catalytic conditions ([Ru] catalyst, toluene, 100").6 Various functional groups (ester,silyl, etc.) directly bonded to the double bond are tolerated. rLe Paih,J., Derien,S.,Dixneuf,P.H.CC 1437(1999). rl-e Paih.J.. Derien,S.,Ozdemir,I., Dixneuf,P.H../ACS122"1400(2000). 'Derien,S.,Ropartz,L., Le Paih,J., Dixneuf,P.H.JOC 64' 3524(1999). rFujiwhara,M., Nishikawa,T., Hori,Y. OL 1, 1635(1999). sKondo,T., Morisaki,Y., Uenoyama, S.,Wada,K., Mitsudo,T. JACSl2l' 865'1(1999)' 6Kondo,T., Uenoyama, S.,Fujita,K., Mitsudo,T. JACSl2l' 482(1999).
Chloro( 1,5-cyclooctadiene)triisopropylphosphinerhodium(I). Diaryl ketones.t N-Pyrazylaldiminescouple with aryl halides and the products are readily hydrolyzed to the ketones.
128
l{-blo.r
chloride 2-Chloro-1,3-dimethylimidazolinium
-) ri*\
+ Ar'-X
\*An
(cod)Rhcrf
t*-
.,*,;d disl,me 160"
nrAH
+
o
Chloro(cyclopentadienyl)bis(triphenylphosphine)ruthenium(I). (Z)-Enedianes.r a-Diazo ketones dimerize with decomposition on exposure to the Ru-complex. As more than statistical quantitites of cross-reactionproducts are obtained from an ct-diazo ketone with either ethyl diazoacetateor trimethylsilyldiazomethane, the method has a preparativevalue for the correspondingunsymmetrical (Z)-enones.
R-(
.b
+
N^'z
tcgor,
lt(
/
A
+
r
\
H
A'AA"
rlshiyama,T., Hartwig,J. JACS122,12043(2000).
t:Nz
Y^ru
n,Aor
,f
S ll
Ph
CpRu Cl(Ph3P)2
-;;,;* cHct360"
R-{
.b
COOET
a-Heterosubstituted ketones.2 When ct-diazo ketones are treated with the Ru catalyst in the presence of amines or thiols, a-amino ketones and a-thio ketones are formed in excellent yields. rDel Zotto,A., Baratta,w., Verardo,G., Rigo,P.EIOC 2195(2000). 2DelZotto,A., Baratta,w., Rigo,P."/CS(P1)3079(1999). B-Chlorodicyclohexylborane. Enolboration.r Reaction of ct-bromoketones with this reagent and triethylamine (enolboration) followed by addition of aldehydes and oxidative workup leads to anti-a bromo- p-hydroxyketones. lBrown,H.C.,Zou,M.-F.,Ramachandran, (1999). P.Y.TL 40,78'15
Assorted transformations.: Thc primary alcohols to chlorides. ol& presenceof hexamethylenetetramln
foxides, preparation of ureas and carh from oximes.
rShimizu, M., Gama,Y.,Takagi.T.. Shrha rlsobe,T.,Ishikawa, T. IOC U.58-11r lgrn
Chloromethyl(dimethyl)silyl chloril N-Methylation of amides.l Tlur decompositionwith CsF.(9 examplcs.
ri\ ll
|
\NAo
il
/- s -
cl
cl
Bassindale, A.R.,Parker, D.J.,Patel.P. Ta l - Chloromethyl-4-fl uoro- 1,4-diazoot 2-Fluoro sugars.t Glycals un& thesesaltsfollowed by alcoholysis.
2-Chloro- 4,6-dimethoxy- 1,3,5-triazine. Esterification,r Activated estersderived from carboxylic acids with the title reagent react with alcohols (including tertiary alcohols) to give esters. rKaminski, J.E.,Kaminski,2.1.,Gora,J. S 593(1999).
+
F l
+
. rl) o.f&J tI? 4-oi7
2-Chloro-1,3-dimethylimidazolinium chloride. 20, 105 Ketenimines,t Elimination of hydrogen sulfide from secondaryN-arylthioamides is readily accomplishedwith the imidazolinium salt (and triethylamine).
2rto_ _c,
l-Chlorom€thyl-4-fluoro-1,4-diazoniabicyclo[2.2,2]octane salts
\\ +
l
l Ar
cl
S
o
I
tnY{*'o' A,'
A
129
-
\ - N ,,\
+
\
H
Ph
Et3N +
Fc=ruRr
cH2ct)
/
cl-
K
^
uthrnium(I). h :-, inpositionon exposureto the r .. :-'.rcrlonproductsare obtained
Assorted transformations.2 The function of this reagent includes the conversion of primary alcohols to chlorides, oxidation of secondary and primary arcohols in the presence of hexamethylenetetramine,chlorination of 1,3-diketones, reduction of sul_ foxides, preparation of ureas and carbamatesfrom hydroxamic acids, and of carbamides from oximes.
:::rcthvlsilyldiazomethane,the c u' . n c t r i c a1l 2 ; - e n o n e s .
IShimizu,M., Gama, Y.,Takagi,T., Shibakami, M., Shibuya, t. S 517(2000). rlsobe,T.,Ishikawa, T. JOC 64,5832(1999).
|:
Chloromethyl(dimethyl)silyl
.b
f.n
R-a(
COOET
,'\ are treated with the Ru . - , 'nc\ and a-thio ketones are
chloride. N-Methylation of amides.t This method involves formation of silaoxazolines and decompositionwith CsF.(9 examples,72_g5Vo).
ri\
ll
|
-NAo
/-.{cl cl
I
H
irr. reagent and triethylamine .rlr\r' workup leads to anti-o. -
(Me3Si)2NH / MeCN ;
+
-
CsF
r-
\ttAo Me
rBassindale, A.R., Parker, D.J., patel, p., Taylor, p.G. TL 41, 4933 e000\.
l'chloromethyl-4'fl uoro-1,4-diazoniabicy cro[2.2.2]octane sarts.r g, l 00; 20,r 06 2-Fluoro sugars't Glycals undergofluoroalkoxyrationby reactionwith one of thesesaltsfollowedby alcoholysis. rl-. ' . ire acidswith the title reagent F t
l .
i. :: .ceondaryN-arylthioamidesis t : : - : : : rl l t n i n e ) .
'-7-oi7 ff-r
4"6 OAc
+
+
rl) t \ l
\ r'i'' t -
2rfo - - c l
PhNO2;BnOH 90.
--T-o'T ,"oBn (1+' O"O OAc 75%(a:B1:1)
n-Chloroperoxybenzoicacid,MCPBA
Ffuortnation of aromatic compounds. The reaction of various indoles takes place at room temperature in aq MeCN to afford 3-fluoroxindoles.24-Substituted phenols are convertedto 4-fl uoro-2.5-cyclohexadienones.t rVincent,S.P.,Burkart,M.D.,Tsai,C.-Y.,Zhang,2., Wong,C.-H.JOC 64,5264(1999). 2Takeuchi, Y.,Tarui,T., Shibata,N. OL2,639 (2000). sStavber, S.,Jereb,M., Zupan,M. Sf 1375(1999).
Dithioestersare oxidized at the thron('t Benzylic oxidation,5 ATCH.R arc .'r in dichloromethaneat room temperaturc Baeyer-Villiger oxidations. Thc ..rr Sc(OTfl:.6 1,3-Dioxenesgive ring contrac applied.TThe rearrangementis causcdhr n A preparation of 3-hydroxyindolc-lVilsmeier-Haackformylation and thc Bacl
Chloromethyllithium. Allylamines.t N,N-Disubstituted ct-aminoaldehydesare transformed to the allylamines in one step without racemization.
Z\.-rr
R;
IConcellon, B., Riego,E.TL4l,4361 (2000). J.M.,Baragana,
ll
)-cooR'
\-,,,\N H
Chloromethylsulfonyl chloride. Sulfonates.t The sulfonates derived from alcohols and the title reagent are good electrophiles toward azide and cyanide ions. rshimizu,T.,Ohzeki,T.,Hiramoto,K., Hori,N., Nakata, T. S 1373(2000).
Chloromethyl trimethylsilylmethyl sulfide. Tetrahydrothiophenes.t Thiocarbonyl ylides are generatedfrom the title reagent on contact with CsF. Trapping with l,3-dipotarophiles leads to substituted tetrahydrothiophenes.Chiral adduct formation by this reaction is possible when the trapping agents contain a chiral auxiliary. rKarlsson, H.-F,.OL l, 1667(1999). S.,Hogberg,
m-Chloroperoxybenzoic acid, MCPBA.13,76-79;14,84-87;'15' 86; 16' 8G-83; L7' 76; 18, l0l; 19,94-95:20, 106-108 Oxidation of nitrogen and sulfur compound.s. These oxidations serve to complete transformation of amines to hydroxylamines,r hydrazonesto nitriles,2 and B-amino esters
H., Kuboyama, T.,Amano.A . \ en Trrkuyama, R., Martin-Zamora. [: I)icz. E.. Fernandcz, ( I 999). 't)avics, S.G.,Smethurst, C.A.P,Smith..\l) l 'Corbin,F.,Alayrac,C., Metzner, P.fL {0. :: l '\Ia. D . .X i a .C . .T i a n H . . T L 4 0 , 8 9 1{5l e ' r ' ) Kotsuki.H.,Arimura,K., Araki,T.. Shinr.hrn Wattenbach, ll r/ C., Maurer,M., F'rauenrath. 'Hickrnan, C.F-., Lachance. \ /1.I 2., Sturino, B.W.fL 41. l0li -1 .-\ndrus. M.8..Poehlein. Bickvall.J.-EJ()< K..Pict,J.J.N., Bergstail,
I Chloro(phenylthio)methylene]dimethrt Alkyl halides.' Primary alct'lx \le.N:C(C|)SPhlCl, to the chloridcr rn 'ccondaryhydroxyl groups.ln the prest-rx
to conjugatedesters.3
OTBS OTBS
a\
--V*,
Epoxidation.') Alkenes arc eFxr\rd catalyzedby (MeCN)+CuPFo. Dihydroxylation.t(t The conrentr,tn N-oxide (\\t()' and N-methylrnorpholine rs replaccdby substoichiomctricN-mr'thrlt
(iornez.L., Gellibert,F'.,Wagner. A.. l\lro.k,q'
MCPBA- NaHCO3
.-oMe
cH2ct2
/\ btt 63% (93% ee)
\'-Chlorosuccinimide NCS. 13, 79-tttt: l! (E)-Bromoalkenes.t (Z)- I -Dialkr ltt .tcrcoselectivelyby NCS. A specialsolrc' .rndis superiorto DMSO.
N-Chlorosuccinimide NCS
fI t::. -l
variousindolestakesPlace : l c ' r -l-Substituted Phenolsare
ll ,rl
t()c 64,5264(1999).
Dithioesters are oxidized at the thiono group'1 MCPBA_O: (NaHCo:) Benzylic oxidation,s ATCH,R are oxidized to ArCoR with in dichloromethaneat room temperature Baeyer-Villigerucidations.TheoxidationwithMCPBAiscatalyzedbyTfoHor (aldehydes)if direct distillation is Sc(oTf')..n1,3-Dioxenesgrve ring contractionproducts is causedby rn-chlorobenzoicacid' applied.TThe rearrangement Apreparationof3.hydroxyindole.2-carboxylicesters(yields80_907o)involves Vilsmeier-Haackfbrmylation and the Baeyer-Villiger reaction'N OH
u.r. .,.!' ransforrned to the allylamines
Z>r--f
R,
t
ll
) - COOR'
\-'l-N H
Pocr,-PhN(cHo)N/e- a)-\ ' Kll ll N / C P B A - T S O H /C H 2 C | ,
-
cooR'
\."-N H
80-90% .rnd the title reagent are good -:
tff)0).
::r'rat€dfrom the title reagenton lrto substituted tetrahydro:.iris tlr. '.'ihle when the traPPingagents B
) l { . . + - t i 7 r 1 5 , 8 6 ;1 6 , 8 0 - 8 3 ;L 7 ' , . .-.c' oxidationsserveto complete :r, -'- tr) nitriles,2and B-aminoesters
OTBS
I /\ Ct't 63% (93%ee)
(e'g'' -78') when Epoxidation.e Alkenes arc epoxidized at low temperatures catalyzcdby (MeCN )aCuPF6. with oso-, Dihydroxylation,l0 The conventionalmethod of alkenedihydroxylation reagent latter the that such modificd becn (NMO) has anclN-mcthylmorpholincN-oxide MCPBA' of equiv l 4 and N-methyhnorpholine is replaccclby substoichiometric T S 1299(2000)' T'' Fukuyarna' r1'okuyama, T.,Amano,A', Yamashita' tl., Kuboyama, J M IA l0' ll45 rDicz.Il.. Fernandcz, E, Pareja'C'' Prieto'A ' Lassaletta' R., Martin-Zamora, ( I 999). 'Davics. C.A.P,Smith'A'D ' Smyth'G'D' ?"A1l' 2437(2000)' S.G.,Smcthulst, rCtrrbin, P.'fL 40,23l9 ( 1999)' C.,Metzner, Fl,Alayrac, 'Ma. D..Xia.C..Tian,H. TL 40'8915( 1999)' "Kotsuki.H.,Arimura,K., Araki,T., Shinohara, T SL462( 1999)' 'Wattenbach, U' SL 303( 1999)' C., Maurer,M., Frauenrath' 'llickman,Z'.,Sturino'C.F-., N ?"L41' 8217(2000)' Lachance, 'Andrus. B.W.fL 41, l0l3 (2000)' M.8.,Poehlein, 'ucrgstad, J -E'JOC64.2s45( 1999)' Biickvall, K.. Piet'J.J.N., chloride' I Chloro(phenylthio)methylene]dimethylammonium reagcnt' this by converted are Alkyl halides.t Primary alcohols unprotected atl'ecting without yields in excellent lMc:N:C(Cl)sPhlcl, to the chlorides obtaincd' \ccondaryhydroxyl groups.In the presenceof BuaNBr' the bromidesare C' TL 4l' 6049(2000)' A., Mioskowski' Gomez,L., Gellibert,F'.,Wagncr, 19,95-96; 20' 108 .v-chlorosuccinimideNcs. 13, 79-80; 15, 86-88; 18' 101-102; induced to decompose are (E)-Bromoalkenes.t (Z)-l-Dialkylbora-l-bromoalkenes N, N-dimethyllbrmamide, by is exerted effect \rcreoselectivelyby NCS. A specialsolvent .rndis superiorto DMSO.
132
Chlorosulfonyl isocyanate
a f-a'\-
o
O=C=N-SO2C|
A 'n-cr
Ph
|
\,{
\7
\/
OMe
P
KoH - Na?so3
o THF - D[,,1F
'/-[
[3 + 2]Cycloaddition. l-Lactams arr particular interest is the formation of a I 1 precursorof peduncularine.
82o/o
Methylthiomethylation.2 The Corey-Kim reagent (NCS-dimethyl sulfide) induces cyclization of tryptamine derivatives while introducing a methylthiomethyl group at C-3. An efficientroute to physostigmineis basedon this process.
MeO
(
,!-o""t
\ '-1N) / / t
H
l
'cooMe i
NHCooMe
MeO 1F
Ncs- N/ezs
_SMe
'
(,, ,>.-f-^.
i - p r , N E t \ - - ( \ ) - C O O M e
'ufN
crrci, n
H
o/
H H boovr" Me.
o NH\O\
C,>l-\ -*t^. M6H
Me
physostigmine
Chlorination.s propanol.
>ie
O=C=N-SO2C|
Anilides and deactivated anilines are chlorinated with NCS*2-
Biaryls,a Homocouplingof ArZnI employs NCS as an oxidant in the presenceof a Pd(0) catalyst.Yields are good. lHoshi,M., Shirakawa, K.TL41,2595(2000). 2Kawahara, M., Nishida,A., Nakagawa, M. OL2,675 (2000). rZanka,A., Kubota,A. Sa 1984(1999). aHossain, K.M.,Shibata, T.,Takagi,K. Sa t 137(2000).
Chlorosulfonyl isocyanate. 13, 80-8 1; 18, 102 N-Allyl carbamates.t Preparation of the carbamates from allyl ethers may incur 1.3-transoosition.
iKim,J.D.,Lee,M.H.,Lee,M.J.,Jung,YH. IL I rlsaka,M., Williard,P.G.,Nakamura,E. 8CS/ 7l 'Roberson, C.W.,Woerpel, K.A. OL2,62l rlffi)
Chloro(triphenylphosphine)gold(I). Hexaalkylditins.' Oxidative dimenza (PhrP)AuCl.
Reductive silylations.: In the presen imines undergoreductive silylation b1 a h1 undertheseconditions.
'lto, H.,Yajima,T.,Tateiwa, J.,Hosomi,A. ft I rlto, H.,Yajima,T.,Tateiwa, J.,Hosomi,A. C(-9€
Chlorotris(triphenylphosphine)rhodiun I Allylic alkylations.t 3 Highly regros nucleophiles (phenolates,sulfonamides. and also possible with the Rh catalyst modrha
seems to play an important role in the dr branched allylic ethers; thus, reaction wirh I the product yields are low The best compru
Chlorotris(triphenylphosphine)rhodium(I)
O=C=N-SO,C|
Ph, y'., v
,OMe
'nn
:
> KOH - Na2SO3
\7
\./
NHCOOMe
(2.7 c"
1)
[3 + 2]Cycloaddition. ^y-Lactams are formed on reaction with allylsilanes.2 Of particular interest is the formation of a bridged ring representative that serves as a precursorof peduncularine.3
82Yo
: '\CS-dimethyl sulfide) induces ., nrc'thylthiomethylgroup at C-3.
Ph COOMe
\
/-\
rsiR3
O=C=N-SO2C|;
HN/\
,nlzt'a:)
oN 62To
!
booH,t"
peduncularine
l l,t,-
\\
..- ^ o \
Kim, J.D.,Lee,M.H.,Lee,M.J.,Jung,yH. fL 41,50:13 (2000). rlsaka,M., Williard,p.G., Nakamura, E. BCSJ72,2115(1ggg). tRoberson, C.W.,Woerpel,K.A. OL 2, 621(2000\.
I
/m \r-r-i-( M ; H
M e
physostigmine
. arc chlorinated with NCS-2g ' .
\
1. an oxidant in the presenceof a
!:- , r:ttcS from allyl ethers may incur
Chloro(triphenylphosphine)gold(I). Hexaalkylditins.t (PhrP)AuCl.
oxidative dimerization of RjSnH (e.g., BujsnH) is mediated by
Reductive silyrations.2 In the presence of (phjp)Aucl and Burp, aldehydes and imines undergo reductive silylation by a hydrosilane (phMe2SiH). Ketones do not react undertheseconditions. rlto,H.,yajima, T.,Tateiwa, J.,Hosomi,A. TL 40,7g07(lggg). rlto,H.,yajima, T.,Tateiwa, J.,Hosomi,A. CC 9S1(2000). Chlorotris(triphenylphosphine)rhodium(I). 19, 96_98; 20, 10g_l 09 Allylic alkylafions.t 3 Highly regioselective alkylation of both hard and soft nucleophiles (phenolates,sulfonamides, and phenylsulfonylacetic esters, respectively) is also possible with the Rh catalyst modified by the added (Meo\p. The countercation seems to play an important role in the displacement with alkali phenolates to afford branchedallylic ethers; thus, reaction with Li salts shows the highest regioselectrvity but the product yields are low The best compromise is to use Na phenolates.
Chlorotris(triptaf 134
Chlomtris(triphenylphosphine)rhodium(I)
'nlo)
'nY\ Ph.
ocooMe. a-)-/
(Ph3P)3RhCi
Y\ Mo'V
.t\t2
-^--J
--L/
(NIeO)3P THF
(97o/o)
M = Li
(11o/o)
Chlorotris(triphenylphosphine)rhodin mt I r Hydroacylation. ct-Cleavageof a phen (after elimination of styrene) to an alkene c
2 0 : 1 1 2 : 1 3 8 : 1
M = Na (97olo) M = K
o"\"'
switulski,B., Stengel, T. ACIEE3S'2426(lv)9t 6WendetP.A.,Dyckman,A.J., Husfeld,C.O.. Kid ( l e9e). TVogels, M.P, Westcc* C.M.,Hayes,P.G.,Shaver,
imine formation of the ketone with 2-amr speciescombines with the alkene and then un
Reformatsky-type reaction.a This procedure involves treatment of the ct-bromo esterswith Et2Zn and the Rh(I) complex. This mild and eflicient reaction is applicable to both inter- and intramolecular versions. Cycloadttitions. Substituted indolines are formed from N-functionalized l-alkynyl amides via a 12 +2 +2lcycloaddition process.5A study on the regioselectivityand stereoselectivityof the [5 + 2]cycloaddition promoted by the Wilkinson catalyst together
rY i
o Ph,/\-A
l
l
\"4n..
* R,\
(Ph3P)3RhC PhMe
.r
with AgOTf has beendelineated.6
||I "'
/--'r\ i l
(PhrP)3RhCl (
+ l l l + N-#I
S
'ru-\Z
Further extension of the method resullr r des and alkenes2and, in the case of an aro Imines of aryl ketones undergo o-alkylation
|
PhMe20'
TJ
TS
91Yo
1'\'/
Addition to vinyl aminopropyl ethers.l Boranes add to the double bond in the antiMarkovnikov sense under the influence of the Rh catalyst. However, intramolecular hydroamination to give tetrahydro-2-methyloxazine occurs in the presence of Pd or Pt complexes.
* nAH
\tR'
"t,
o (Ph3P)3Rhcr
H,Nvo-\
ll \*A
o
* f\-- tr J'-to'\ | to,,-
^\
PY-
H'NYo'\-d-o{
tto.,At l ll + \/
(
v.R'
NBn
1]X
lEvans, P A., Leahy, D.K. "/ACS122,5Ol2 (2000). 2Evans.P A., Robinson,J.E.,Nelson,J.D. .IACSl2l,6'761 (1999). 3Evans,P.A.,Kennedy,LJ. OL2,2213 (2000). lKanai, K., Wakabayashi,H., Honda, T. OL2,2549 (2OOO)-
* \-R' ri,^"1,,^\/
J u n ,C . - H . ,L e e ,H . J A C S1 2 1 ,8 8 0 ( 1 9 9 9 ) . Jun, C.-H., Lee, D.-Y., Lee, H., Hong' J.-8. ACri J u n .C . - H . ,H o n g ,J . - B . ,K i m , Y - H . ' C h u n g .K - l
Chlorotris(triphenylphosphine)rhodium(If 2-Amino-3-picoline
=^-.2-.,
Ph:Z\
,\-.l,J
.
l-z
,^-,,\,
-,
20
,
o^.,,lj
rl-:
5witulski,B., Stengel,T. ACIEE 38,2426(1999). 6Wender, P.A.,Dyckman,A.J., Husfeld,C.O.,Kadereit,D., Love,J.A., Rieck,H. IACS l2l, 10442 (1999). ?Vogels, C.M.,Hayes,P.G.,Shaver, M.P.,Westcott, S.A.CC 51 (2000). Chlorotris(triphenylphosphine)rhodium(I)-2-Amino-3-picoline. Hydroacylation. ct-Cleavageof a phenylethyl ketone and delivery of the acyl group (after elimination of styrene) to an alkene occurs around Rh. The reaction starts from
.. 'l
1 2 : 1 3 8 : 1
trl
imine formation of the ketone with 2-amino-3-picoline. After cleavage, the [Rh]-H speciescombines with the alkene and then undergoesreductive elimination.'
,,]\cs treatment of the a-bromo : jllicient reactionis applicableto
/Y i
(:
r rr()rnN-functionalizedl-alkynyl .:uJr on the regioselectivityand .r the Wilkinson catalysttogether
/--/\ i l ^,'\,/)
l
-S
*
a\a
?: , . :Jtl to the double bond in the anti-.rr]lvst. However, intramolecular i r., -,rrs in the presenceof Pd or Pt
(^A**,
(J
^,\.. K
H
+ \-R'
R=Bu 98%
o
R'Jl-.--^R'
PhcooH, PhNH2
z/-\Y/
ll
9Y
(Ph3P)3Rhcl
Phl\,le a
IJ
'o"\
--* n-\A
-,P6fi-
n\
Ph"\*
91%
-- ^rn
ltr. l L*^-Al
l
\rA"n,
o
Further extension of the method results in a direct synthesis of ketones from aldehydes and alkenes2and, in the case of an aromatic aldehyde, o-substituted aryl ketones.3 Imines of aryl ketones undergo o-alkylation.
l
1"- r.-ruYo-\-d.o{-
r35
/VH ll
v
|
+ \/,R'
i l t \*- *", (Ph3P)3RhCl '170' BUNH2
o ll
rr*a-
R'
\-7
-.-.AR,
o
f--A\z\.,.."rJun,C.-H., Lee,H. JACS 121, 880 (1999). 2Jun,C.-H., Lee, D.-Y., Lee, H., Hong, I.-8. ACIEE39,3070 (2000). rJun,C.-H., Hong, J.-B., Kim, Y.-H., Chung, K.-Y. ACIEE 39, 3440 (2000)
t(
136
Chromiurn-carbene
complexes
Chromium-carbenecomplexes.13, 82-83; 14,91-93: 15, 93-95; 16, 88-92;17, 80-84;L8,103-104; 19,98-101;20, I 10-l 11 RearrangemenL Allyloxy(aryl)carbenecomplexesare convertedto allyl aryl ketones on Pd(0)catalysis.l
/-\
\
(Ph3p)4pd
)
0
-Ecrrcot^
BuLi :
(
p \-
PhcHo BF3'OEI2
\-J
P
dienolates,respectivelY.o
co/cH2cr2
r
t-O
Reductive cyclization of chromrr the carbon chain leads to bicyclic b are assembled when conjugated c:
LO
Ic4co1u
(
. 71o/o
I
./"'
t
Cr(CO)
t l \oA *
Cycloadditions. Pyrolysis of O-alkynyl cyclopropylcarbene complexes generates fused cyclopentenones. This transformation has been exploited in a synthesis of a vitamin Dj synthon.2
OMe
. rc>Ac,tco): t t l \-/ OMe I
,Ac(co), tl vitaminD3 intermediate
*
L
R2
Highly functionalized diaryl etl 3-Substituted1,2-naphthoquinones are formed by an intramolecularreactionof o-alkenylarylcarbenecomplexes.With an electron-richaromaticnucleus,the photoinducedbenzannulation is sluggish.The useof r-butyl isocyanideinsteadof CO circumventssuchproblems.l
tutedFischercarbenecomplexesutt
ll\_x OMe
o !c4cor /
t-Bu-NC/ THF ; +
cAN
^t{
R
Meo
'
R
MeO 82Yo
A chromane synthesis is readily accomplished from pentacarbonyltetrahydropyranylidenechromium via alkylidenation and photoinduced cycloaddition.a
Dikctones. Pd(0)-catalyzed c and AII-CO give a-diketones.' '*h to furnish 1,4-diketones.'
Chmmium<arbene
137
complexes
| 15.e.1-95:16,88-92;17,
...................---.............*
rc. .lrc convertedto allyl ary1
hv / THF
OH Reductive cyclization of chromium-<arbene complexes that contain a triple bond in the carbon chain leads to bicyclic butenolides.5Five- and seven-memberedenol ethers are assembled when conjugated carbene complexes react with lithium enolates and
_J-)
dienolates,respectively.6
I -
c(co)s. r') -ilJ
a rl: t]
",,/(
z^'
1o/o
(oA*
..rrhene complexesgenerates '.nl,ritedin a synthesisof a
OMe
OMe
^
t
* a"y^"u co6 a( oli \-/
OMe
* ,1Ac.1co1u
. :aminD3intermediate
:r,\lccularreactionof o-alkenyn::.1: r . ... thc photoinducedbenzannuCl .:riumventssuchproblems.s
Lio<
tl R,.
\_-i
-J R
l:lttln.l
:
1
R
.
R
'
Highly functionalized diaryl ethers are accessible from reaction of aryloxy-substitutedFischercarbenecomplexeswith alkynes.T
>:,\R
l
tvteo"To
R'
o
,r rrbonyltetrahydropyranyli-
r"Yl --ffiot
(
l-\
l-\
82o/o
cH2c'2 10' /-Y?^ \o/"'*
'
!gr(691^
>:,\R
R-.......:R,
o\J*"
-{-ts
R R'
OH
Diketones. Pd(0)-catalyzed coupling reactions involving ArC(ONMe+):Cr(CO)s and AII-CO give a-diketones,Ewhereas a Pd(II) catalyst mediates diacylation of alkenes to furnish 1,4-diketones.e
138
Chromium(II) cNoride Me4NO
rc(co)s
/-\ , / \ \ / /
co
MeO
i l ^ .
nrlyHn o
in PhMe
84%
in CH2Cl2
28o/o
2-Chloro- l -alken--1 Homolngation with 1,1,1-trichloroethanein the presenc alcohols. Conversion of aldehydes to complished by the CCl2-catalyzed reacuc
(_, tl * ArA Pn
o
(Ph3P)4Pd
47Yo
R-CHO +
Cl- ,Cl FCI
C'4" *Lr
| (MeCN)4PdBF4
R
Me4NYR'
t".^Y^
CrC.-
R'
R-CHO + Me3SiCl [16
c(co)s
rSakurai,H., Tanabe,K., Narasaka, K. CL75,309 (1999). 2Yan,J., Herndon, J.W. JOC 63,2325 (1998). rMerlic, C.A., Aldrich, C.C., Albaneze-Walker, J., Saghatelian,A. ,/ACS 122,3224 (ZO0O). rWeyershausen,8., Dittz, K.-H. SI, 231 (1999). sRudler, H., Parlier, A., Certal, V., Vaissennann, l. ACIEE 39, 3411 (2OOO. "Barluenga,J., Alonso, J., Rodriguez, F., Fananas,F.I. ACIEE 39,2460 (2000). TPulley,S.R., Sen, S., Vorogushin, A., Swanson,8. OL l, l72l (lggg). nSakurai,H., Tanabe,K., Narasaka, K., Yamane,M., Ishibashi,Y CZ 168 (2000). ''Yamane, M., lshibashi,Y., Sakurai,H., Narasaka,K. CL l?4 (2000). Chromium(Il)
]'
c(co)s
chloride. 13, 84; 14, 94-97l'15,95-96;
16, 93_94;17,84_g5l
Reductive cyclimtinn.s Azide redu addition of the resulting amine to a cr assemblageof fused-bridged tricycles has synthesisof ( - )-cylindricine.
18. 104:
1 9 , 1 0 1 ; 2 10 1, 1 - 1 1 3 Alcohol synthesis. Halogenated allylchromiumreagentscan be preparedand used in a reactionwith carbonylcompounds.r
oH cl O il
C
ll
Ph
l
\-/
+
H
J
f c tcl
l crc,z ph{A
('ct
;i
I
2{ -Hydroxyalkyl)cyclopropanok." generatedfrom enoneson treatment'*'rth with aldehydes afforddiol producs.
) 73%
2-Tetrahydrofuranyl ethers.2 At room temperature alcohols are derivatized into the ethers with Crclr and cclu in THF under essentially neutral conditions.
tl 'rYpr'
RC<
tl
o crcl2-ccl4 ent\'to-YQ
Ph-\-'oH
--;;*
(/ 90o/o
\A
U;
C€
ChromiurnfiD chloride
-
o l
t Ar
Ph
c
Homologation 2-Chloro-l-alken-3-ols are obtained from aldehydes on treatment with 1,1,1-trichloroethanein the presence of CrCl2.r They are precursors of propargyl alcohols. Conversion of aldehydes to alkenylsilanes with one more carbon is accomplished by the CCl2-catalyzedreaction with MeI, Mn, and Me.SiCl in THF.a
1", P,
47Yo
R_cHo +
.{
r.- : rX)). t ::.' , ,1000).
+
*-Y'' + |
rHF
CrCl2- l\.4n
R-CHO+
i( \ 122.3224(2000).
oH
crclz
". r, . _ f -6C;l I
o tl --\rAn "-\*
139
M e- 3 S i C l +
N,lel/ THF
^,
oH
base
I
*\
D ''\Z\^... SiMeq
Reductive cyclization.s Azide reduction with CrCl2 is followed by intramolecular addition of the resulting amine to a cross-conjugated dienone system. This efficient assemblageof fused-bridged tricycles has been incorporated as the final and key step in a synthesisof ( - )-cylindricine.
t . J / .
I ..r,r(2000). !,,
t6. ,r 9-1:17,84-85;18,104;
"'l';-l'". p-" orBS (-)-cylindricine
andused !:J:r:. canbe prepared
oH cl I '\"t\ =-
' tcl
7 3'/o
rr .,...rhols are derivatized c..-:r.rlconditions.
H45'/.
2y'1-Hydroxyalkyl)cyclopropanols.6 2-Alkoxycyclopropylchromium(Ill) speciesare generatedfrom enoneson treatrnentwith CrCl2. The subsequentreaction of these reagents with aldehydesafford diol products.
{# -'t>i)^t'^ A"',^-" R = C6H17 93%
CrCl2/ DN,IF
cHo
:) Ph
j}-x' Ph' \_, 54Yo
ChromiumflIl) chloride
rBaati, R., Gouverneur,V., Mioskowski, C. JOC 65,1235 (2000). 2Baati,R., Valleix, A., Mioskowski, C., Barma, D.K., Falck, l.R. OL2' 485 (2000). 3Falck, J.R., Barma, D.K., Mioskowski, C. TL 40,2091 (1999). aTakai,K., Hikasa,S., Ichiguchi,T., Surnino,N. Sf 1769 (1999). sMolander.G.A.. Rtjnn. M. JOC 64,5183 (1999). 6Toratsu,C., Fujii, T., Suzuki, T., Takai, K. ACIEE 39,2'125 (2000).
ChromiumflI) chloride-nickel(Il) halide. 14,97-98;15,96-9"1;17,86; 18, 105; 19' 102:20.1l3-l 14 Alkenylation of aldehydes. Alkenylchromium(IlD species are generated by the electrochemical reaction of CClr-NiBr, with alkenyl bromides in DMF. Their reaction with ArCHO in the presenceof MerSiCl gives silyl ethers of allylic alcohols.r Instead of electrochemical reduction, aluminum can be employed as the electron source.2 An alternativepromoter is tetrakis(dimethylamino)ethylene.r IKuroboshi, H.' Torii'S.Sa 69 (1999). M., Kishimoto,S.,Tanaka, M., Tanaka, 2Kuroboshi, M., Tanaka,M., Kishimoto,S.,Goto,K., Tanaka'H., Torii, S. ?L 40' 2785(1999)' sKuroboshi. M.. Tanaka,M., Kishimoto,S.,Goto,K., Mochizuki,M., Tanaka'H. TL 4l' 81 (2000)'
Chromium(Ill) chloride. Benzhydrols and diaryI kctones.l Mediation of the ArZnI reaction with ArCHO by CrClr leads to benzhydrols. In the caseofo-zinciobenzoic esters,phthalides are formed. When PhCHO (or any other ArCHO) is added at the termination of the reaction as a hydrogen acceptor to the chromium(Ill) diarylmethanoates,an oppenauer oxidation oc-
'Takai, K., Ichiguchi. T.. Hika'a- S rTakai,K., Hikasa.S.. Ichigu.-hr-T ' ' A u g e , G i l , R . ' K a l s e l .S ' I L l . J..
Chromium(IV) oxide.20. I l{ D Reaction of acetaknamaldehyde) are hydrohzed aliphatic aldehYdesso generata
:Ko,K.-Y.,Park,S.T.IL {0. dll5 t
Chromium(Vl) oxideil-drc Aryliodin e(I I I ) dic h loridc CrO3-HCl in aq HOAc at roott
:Kazmierczak, P.,Skulski.L.. Oba
Chromium(Vl) oxidePeriod Benzylic oxidotion.: Th responding acids and dra4
temperaturein MeCN. Benzli phthalide and 3,4-dihYdrotsan S. OL 1' 2129tlV)9' Yamazaki,
curs and the products are diaryl ketones.
CrCl3
Ar-Znl
+ A/CHO
+
I
oc/il'l
PhCHO +
lo,"Aorl
? RrARr
Chromium Peroxide. Oxidation of alcohok. benzylicalcohols.
A ,lCl M.M., KeYvan. Lakouraj,
70-80o/o
Allylations.2 Allylating agents prepared from allyl halides, CrClr, NiBrz, and MerSiCl react with carbonyl compounds, provided that tetrakis(dimethylamino)ethylene is usedas electronsource. Zn, and (E)-Iodoalkenes. Aldehydes are homologated with iodoform, (thf)icclr' MerSiCl in dioxane to afford (E)-iodoalkenes3at room temperature. On replacing Zn with Mn the reactionproductsare (D-alkenylsilanes.o Conjugate additinns.s Organochromium reagents derived from halides such as BnBr and crClr-Mn add to acrylonitrile (water is an additive in the reaction medium). rOgawa, T.,Takagi,K. JOC 65,l03l (2000)' Y, Saiga,A., Mori,M., Shibata, 2Kuroboshi. M.. Goto.K., Mochizuki,M., Thnaka,H. SL 1930(1999).
Cobalt. Pauson-Khand reactb* rn refluxing toluene in the P heterogeneouscatalYst for th carbon,which can be usedat I
Kim, S.-W.,Son,S.U.,Lre. S I :Son,S.U.,Lee,S.I.,Chung. \' K Cobalt([) bromide. 19' l0r Coniugate additions. halides to activatedalkenes'
CobaltflI) bromide
rTakai, K., Ichiguchi, T., Hikasa, S. SL 1268 (1999). lTakai, K., Hikasa,S., Ichiguchi,T., Sumino, N. SI, 1769 (1999). sAuge, J., Gii, R., Kalsey, S. ZL 40, 6'1(1999).
I t, - . t t ) t . 2 . - 1 8 5( 2 0 0 0 ) . tr. t$... ! _ . .
9. I 5. q6-97; 17, 86; L8' 105;19, n i.. .pccies are generatedbY the tr. -: :nrdesin DMF. Their reaction cir -:. r,l allylic alcohols.rInsteadof p. .,.: .r: the electron source.2An lc:., r u. :l'
. '1.69( 1999). ii f,rnr.S. ZL40, 2'185(1999). .. \1..Tanaka, H. fL 41,8l (2000).
c: : - \rZnl reactionwith ArCHO bY ri.. - c':tcrS.phthalidesare formed' u ::.- :cnninationof the reactionas a !-1: .:1... an Oppenaueroxidation oc-
:-_ - H "^
rKo.K.-Y..Park,S.T.TL40,6025(1999). Chromium(Vl) oxide-hydrochloric acid. Arytiodine(Ill) dichlorides.t oxidative chlorination of ArI is completed by using CrO:-HCl in aq HOAc at room temperature' rKazmierczak, P, Skulski,L., Obeid,N.,/CR(S)64 (1999).
Chromium(Vl) oxide-periodic acid. BenzXlic oxidation.t This combination oxidizes substituted toluenes to the corresponding acids and diarylmethanes (including fluorene) into ketones at room temperature in MeCN. Benzyl ethers such as phthalan and isochroman are converted to phthalide and 3,4-dihydroisocoumarin in quantitative yield' rYamazaki, S. OL 1, 2129(1999).
Chromium peroxide. oxidation of alcohols.t benzylic alcohols.
- l ol Ar
A'
Chromium(IV) oxide. 20, ll4 Reaction of acetals.t Dimethyl acetals of aromatic aldehydes (including cinnamaldehyde) are hydrolyzed in aqueous chloroform with CrO, as catalyst. However, aliphatic aldehydesso generatedundergo oxidation to afford carboxylic acids.
Ar'
Polymer-supported cro.
selectively oxidizes allylic and
rLakouraj,M.M., Keyvan,A. JCR(S)206(1999).
70-80Yo
Ir: ,.r1 halides,CrCl., NiBrr, and I ::, r-'trakis(dimethylamino)ethylene r: .. ::'. r(xloforrn, (thf)',CrClr, Zn, and | : ::r (cmperature. On rePlacing Zn rg: . Jcnved from halides such as lr. .,.:.j:tl\!-in the reactionmedium). tr, n5 .'t.rlt1000). . .:
.199).
Cobalt. pauson-Khand reaction. Cobalt is depositedby decomposingdicobalt octacarbonyl in refluxing toluene in the presenceof mesoporous silica. The substanceis active as a heterogeneouscatalyst for the Pauson-Khand reaction.r A related catalyst is cobalt-oncarbon,which can be usedat least l0 times with yields maintaining at the 95Vo\evel.1 rKim,S.-W.,Son,S.U.,Lee,S.1.,Hyeon,T., Chung,Y.K.JACS122'1550(2000)' :Son,S.U.,Lee,S.1.,Chung,Y.K.ACIEE39,4158(2000). Cobalt([) bromide. 19, lO4 Conjugate additions.t Cobalt bromide catalyzes electrochemical addition of aryl halidesto activatedalkenes.
Copper(Il) acetate rGomes,P.,Gosmini, C., Nedelec,J.-Y.,Perichon, I. TL 41.3385 (2000).
Cobalt(fl) chloride. 14,99;15,97-98;18,107-108; 19, 104-105;20, I t5-t t6; Hydrosilylation.t A new catalyst for regioselective hydrosilylation of acrylonitrile is CoCl2. Only the B-silylated nitriles are obtained. a-Hydroxy-pketoesters.2 The hydroxylation of B-ketoesters with molecular oxygen is carried out under neutral conditions. rChauhan, M., Chauhan, B.P.S., Boudjouk ,P. TL 40,4127(1999). 2Baucherel, X., Levoirier, E.,Uziel,J.,Juge,S. TL 41,1385(2000). CobaltflID fluoride. Quinones,t Hydroquinone dimethyl ethers undergo oxidative demethylation on contact with CoF.. The reagentis comparable to AgO or CAN in efficiency. Fluorination,2 Fluorination of unsaturatedcompounds with CoF., is carried out in a stainless steel vessel from -196" to room temperature. The method transforms methyl trifluorovinyl ether to methyl pentafluoroethyl ether in 7O% yield. rTomatsu, A., Takemura, S., Hashimoto,K., Nakata,M. SL 1474(1999). 2Tamura, M., Takubo,S.,Quan,H., Sekiya,A. SL 343(2O}Ltt.
rKooti,M., Esm-Hosseini, M. SC30.651(2000). Copper(Il) acetate.18, 109-l l0; 19, 106; 20, ll'7 Arylations. Copper(Il) acetate catalyzes the reaction of arylboronic acids with thiolsr and of amineswith hypervalentarylsiloxanes.2 4-Substitutedimidazolesreactwith aryllead(IV) reagents (in dichloromethane at room temperature) to afford N-l arylated derivativesregioselectivelyundercatalysisof Cu(OAc)r.l Radical cyclizations. Copper(Il) acetate has a great influence on the Ni HOAc promoted5-endo and5-exocyclizations.a
o
i%*,3,yr.Aaiq" additive: NaOAc,i-PrOH Cu(OAc)2,t-BuOH
rHerradura, P.S.,Pendola, K.A.,Guy.R.K.OI2lam, P.Y. S.,Deudon,S.,Averell.K.tt.. t:. l (2000). 3Blliott,G.I.,Konopelski, I.P.OL 2,3055rlfi oCassayre, J.,Dauge,D.,Zard,S.Z.Sl {71 rl{l 5Nikal.1e, M.D.,Ali, I.s., Dewkar,G.K..Sudat 6Sammakia, T.,Jacobs, J.S.fZ 40,2685r 1999
Copper(I) bromide. Cyclizatian.t Cyclization of l'-allr room temperature involves atom transfer 2,2'-brpyrtdine.
Cobalt([I) halochromate, arnmine complexes. Oxidation.' The cobalt complexes are mild and efficient oxidants with which alcoholsare oxidized to carbonylcompounds.
o
Aroylfurmic aci .s l-Aryl-l-nrtn HOAc-MeOH at 90o to afford the ketomr only give the correspondingmethyl ether: Cleavage of picolinic acid esten.' protocol using picolinic acid as the nrx alcohols are readily recovered,that is. aric
rClark,A.J.,Duncalf,D.J.,Filik, R.P..Hadtlr ( I 999).
Copper(Il) bromide. 14, 100; 15, l0O: lt 4-H alo -5 -hy dro xypy rr ol- 2 (5H lonct. (slightly less efficiently, CuCl:) furnrsh followed by oxidation at C-5 when the all
P
,R'
R
:"{
'coruxn
R' CONHR"
Insertion into silacyclopropnct-' silacyclopropanes with methyl formate r selectivity is totally switched from one of r
Copper(Il) bromide
- rxtr.
lri
9. 1r-
- : I 0 5 : 2 0 , 1 1 5 - 11 6 ; . Jrosilylation of acrylonitrile
o:
.r-k!-toesterswith molecular
!'.
!r,,
, r i t l a t i v ed e m e t h Y l a t i oonn L'x | \\ rn efficiency. r .. :. \\ rth CoFsis carriedout in a ri I ::. rnethodtransformsmethYl . rr'ld.
Aroylfurmic acids.s l-Aryl-2-nitroethanols are oxidized by Cu(OAc)2 in HOAc-MeOH at 90" to afford the ketoacids.Nitroaldols derived from aliphatic aldehydes only give the correspondingmethyl ethers under theseconditions. Cleavage of picolinic acid esters.6 One advantage of the Mitsunobu reaction protocol using picolinic acid as the nucleophile is that the configurationally inverted alcohols are readily recovered,that is, after treatment with Cu(OAc)2-MeOH. rHenadura, K.A.,Guy,R.K. OL2,2019(2000). P.S.,Pendola, 2lam, P.Y. S.,Deudon,S.,Averell,K.M., Li, R., He,Y, DeShong, P.,Clark,C'G.JACS122'7600 (2000). rElliott,G.I.,Konopelski, J.P.oL2,3055 (2000). aCassayre, J.,Dauge,D.,Zad,S.Z. SL47l (2000). sNikalje,M.D.,Ali, I.S.,Dewkar,G.K.,Sudalai, A . rL 41,959(2000). 6Sammakia, J.S.fL40,2685 (1999). T.,Jacobs,
Copper(I) bromide. cyclization.t cyclization of N-atlyl cr-bromoamides induced by ligated cuBr at room temperature involves atom transfer. 2-Pyridylformaldimines are better ligands than 2,2' -bipyrrdrne. lClark,A.J.,Duncalf,D.J.,Filik, R.P.,Haddleton, D.M, Thomas,G.H.,Wongtap,H. TL 40' 3807 ( 1999).
licicnt oxidants with which
t.:-
.:\ f:'
t -
:r ol arylboronic acids with '..rrtutedimidazolesreactwith :.lturc) to afford N-l arYlated
Copper(Il) bromide. 14, 100;15, 100;18' 111;19, 106 Treatment of 2,3-alleneamides with CuBrt 4-Hala-5-hydroxypynol-2(5H)-ones.t (slightly less efficiently, CuCl2) furnishes the title compounds. Halolactamizationis followed by oxidation at C-5 when the allenyl moiety is not fully substituted.
X
R
R'
R
CONHR'
P
,R'
. rnUuenceon the Ni-HOAc
R
X=Cl,Br
X.,Ao
R ' ) R" X
:,-:Q+"
:C={
CONHR"
'
R>< R
'
R>< X=Cl,Br
,.oxfAo
'
\-,
c k
r-li ' 3uOH
Insertion into silacyclopropanes.2 Remarkably regioselective reactions of silacyclopropanes with methyl formate are mediated by CuBr2 and ZnBr2. The regioselectivity is totally switched from one ofthese two salts to the other.
144
Copper(I)chloride
\Z
CuBr2
!r,k
o * \or,t" H
t ||
-
L \4 I tnr,,,
\ / --FSi-O /
I
|
Yt
\
SnMe3
OMe
- -
70o/o
*p,_o,
-l*o""
Coupling of zirconacyclopentadter sults in cyclooclatetraenes.?
7$Yo
r--dx
O rMa.S..Xie,H. OL2,3801(2000). rFranz,A.K., Woerpel,K A. ACIEE39 4295(2000)' Copper(I) chloride. 13, 85; 15, 101; 18, ll2-ll3; 19, 107-108; 20, ll8-120 of alkyl halides Oxid.ations. Carbonyl compounds are obtained from autoxidation (15 8l-997o\'l examples' and tosylatespromotedby CuCt on Kieselguhr Sterically coupling reactions. The Stille coupling is accelerated by cuCl. cucl in (Phr)+Pd, Licl, of congested substrares are readily coupled in the presence DMSO.2 stannanes Allylfurans and allylthiophenes can be synthesizedfrom the corresponding to l-chloroalkynes and by coupling with allyl halides.r The coupling of alkynylsilanes Benas C--{'a such groups furnish conjugated diynes tolerates many sensitivefunctional zotropylidenes and benzotroponeszue accessiblefrom the reaction of zirconacyclopentadieneswith 2-iodobenzylhalide and 2-iodobenzoylhalide,respectively.5
5
I
ZrCp2
y=e;H,H
and
h
CuCI-DCC via pseudoureaintermedtar Aryl radicals.e A synthetic appl CuCl is radical generation at an c-pos aminobenzoyl) derivatives in the prer which the ct-position becomeschlorina the nascentaryl radicalsis evident.
'r\r^*/\
\4,
I
Silvlq
Tertiary
Dehydration.8
I
t\r-
I
SiMe3
NH2 O l l l
Y i R 'u''z .-.-A^, co,z,\''
SaMe
SiMe3
l--s -)
^
4\)
TBSO.,,/ -O
-U
Hc
'-''-
,
r-
2,2'-Bridgedbiaryls are readily obtained from short-chain 1,to-bis(2-trimethylstannylaryl)alkanesby treatment with CuCl in DMF at room temperature'6
Pinacolatoboration.tt) Hydrotrn effected with bis(pinacolato)diboron r borylcopper species is involved in t nucelophile toward allylic halides and I
Copper(I) chloride
Etooc .cooEt
\)Z
'fo'"
_-Fsi-o
SnMe3
-\
R
70%
Y
R
R = OMe
I
{
62%
by cuCl rewith (Z,Z)-1,4-diiodo-1,3-dienes coupling of zirconacyclopentadienes in cyclooctatetraenes.t sults
SiMe3
/v\
O
-
I
ZrCP2 + SiMe3
SiMe3
MesSi
,SiMe3
Aa" "'"'. ",l-h"
| ',t2--/
i rHF Dl\'lPU
/-\
|
Me3Si
SiMe3
SiMe3
56% ). . '- 108:20,118-120 t :: ::t rutoxidation of alkYl halides r : : : :: - . r . .8 | - 9 9 7 a ) . 1 i ,-,.'lcrated bY CuCl' StericallY R-r:r'e t)f (Phi)4Pd,LiCl, CuCl in N :: r1rthe corresPondingstannanes [, r:..rlanes and l-chloroalkynesto n.:. nll grouPssuch as C-0'4 Ben-
Dehydration.s
Tertiary
and
alcohols
benzylic
undergo dehydration
with
CuC1-DCC via pseudoureaintermediates. Aryl radicals,e A synthetic application of the arenediazonium ion reduction by CuCl is radical generation at an ct-position of amines. Thus, diazotization of the N-(2aminobenzoyl) derivatives in the presence of CuCl in MeOH leads to benzamides in which the ct-position becomeschlorinated and/or methoxylated. Hydrogen abstractionby the nascentaryl radicalsis evident.
n: :::. rcactionof zirconacyclopentau. :.::. rcspectivelY.5
o Hcr.NaNo2 'iO+-\
"*;;- \2;;.?" 2
3
-
r
|
X = C l 2 6 o / o+ X = O M e 3 0 %
h : .hein 1,to-bis(2-trimethylstanny)c'.:J:llPerature.6
Pinacolatoboration.to Hydroboration of 1-alkynesto give 2-pinacolato-l-alkenes is effected with bis(pinacolato)diboron in the presence of CuCl and KOAc. Perhaps a borylcopper species is involved in the reaction. The same reagent is useful as a nucelophile toward allylic halides and Michael acceptors.
Copper(Il) chloride
..-l-".^ .u",-Licr-KoAc
. --*;4-o'-'o-l--lll
-f
".
pf
|
,*
-1-o'\
rHashemi,M.M., Beni, YA. JCR(S).434(1999). 2Han,X., Stoltz,B.M., Corey,E.J.JACS 121' 7600 (1999). 3Nudelman,N.S., Cano, C. SL 1942 (1999). lNishihara, Y., Ikegashira, K., Hirabayashi' K., Ando, J'-I', Mori' A, Hiyama' T' JOC 65' l'780 (2000). 5Takahashi, T., Sun,W.-H., Duan'Z', Shen,B. OL2,ll9'7 (2000)' 6Piers.E.. Yee, J.G.K.,Gladstone,P.L.OL2,481 (2000). TYamamoto.Y., Ohno, T., Itoh, K. CC 1543 (1999)' 8Majetich, G., Hicks, R., Okha' F. NIC 23' 129 (1999)' eHan, G., LePorte, M.G., Folmer, J.J.,Wemer, K.M., Weinreb, S'M ACIEE 39,23'l (20O0): Han' G'' (1996)' LePorte.M.G., Mclntosh, M.C., Weinreb,S.M., Parvez,M' JOC 6l' 9483 r0Takahashi,K., Ishiyama, T., Miyaura, N. CL 982 (2000).
Copper(Il) chloride. 14, 100;18, 113-114;19' 108;20,120 Halolactonization.t Allenic acids give p-halo-^y-butenolideson reaction with cuX2 (X: Cl, Br). is Coupling of organometallics. The demetallative dimerization of RLi by CuCl2 give RSnBul Organostannanes by CuI.2 different from the conjugate addition catalyzed R-R when R is an alkynyl. alkenyl.or aryl group.' Hydrolysis of SAMP-hydrazones.a After asymmetric alkylation of the SAMPof the hydrazones,it is critical to generatethe chiral ketoneswithout racemization.Treatment a solution. provides ammonia productswith cuX2 in THF or MeCN followed by aqueous
Meo'-'"'a) N,NJ
--^y^-
aEnders,D., Hundertmark,T.,Lazny, R. SC 29. :5Takahashi,T., Sun, W.-H., Nakajima' K. CC l59J
l5: 19.I Copper(I)iodide.16,98;18' 11'1-1 oi l' reaction The Alkynyl ketones.t CuI-Et.N. Cyclization. Alkynesin which the tnp from a pronucleophlicsite undergoclchua Thetriplebondis actiral CuI andt-BuOK.2
lll x. cooMe tlt
v
|
|
? - : -
\,/
=
X = C N ,C O M e , . . .
Coupling between an imino chloride arx by cyclization.3This Pd-catalyzedprocer. r able decomposition occurs and the reactlon i
o THF ; NHg
#
tl
I (99% ee)
cyclooctatetraenes.5 (z,z)-1,3-Dienyl-1,4-dicopperspeciesare formed on treatment in the of zirconacyclopentadieneswith CuCl2. Further reaction with NBS results substitutedcyclooctatetraenes. IMa,S.,Wu,S.JOC 64,9314(1999). 2Pastor, I.M.,Yus, M. TL 4l' 1589(2000). 3Kang,S.-K.,Baik,T.-G.,Jiao'X.H.,Lee,Y-T.TL40,2383(1999)'
Either pyrroles or 3-pyrrolines are form formaldehyde and CuI.a
R
nf-\ Ar
i-Pr2NEt- HCrc . Cul
r
Copper(I) iodide
o. B-d
o'
!.'
,,R
147
aEnders,D., Hundertmark,T.,Lazny, R. SC 29, 27 (1999). 5Takahashi,T., Sun, W.-H., Nakajima, K. CC 1595 (1999).
\\
\lori. A., HiYama, T. JOC 65' 1780
19,109-110:'20,120-l2l Copper(I)iodide.L6,98;18,114-115; Alkynyl kptones.t The reactionof l-alkynes with acyl halides is promotedby CuI-EtN. by threeskeletalatoms Cyclization. Alkynesin which the triple bond is separated from a pronucleophlicsite undergocyclizationin the presenceof catalyticamountsof CuI andr-BuOK.2The triple bondis activatedon coordinationwith thecoppersalt.
rx)). l.
,
, \\. 'r. S \{ ACIEE39,237(2000);Han,G., r: \1 ./()C61,9483(1996). [t'
:0. I 20 '. hutenolideson reactionwith CuX2
I
d -
, L
-.
I.
: . c dimerizationof RLi bY CuCl2 is RSnBuj give t'ul.r Organostannanes :rrnctric alkylation of the SAMP.! rrhoutracemization.Treatmentof the .-','u:ammoniaprovidesa solution.
lll t \-,
xy.coottt" Cul - IBUOK l +
COOMe
THF
X = C N ,C O M e , . . .
is accompanied Coupling betweenan imino chloride and 2,2-dimethyl-4-alkynamide by cyclization.r This Pd-catalyzed process is aided by CuI, for without which considerable decomposition occurs and the reaction also becomessluggish.
.A ff-}
Cul - Pd
46%
F
(99% ee)
r::'
Either pyrroles or 3-pyrrolines are formed when N-propargylanilines are heated with formaldehyde and CuI.a
n1o-rspeciesare formed on treatment :cuction with NBS results in the
R
I
rT\
i-PrZNEt-HcHo aq +
cula
h\ ^'
nr-'JJ
>:\
n-N?
Ar It
_,.r 1999)
in dioxane in ethanediol
Copper(I)oxide
Desilylallylatian. 2-(1-Trimethylsilylalkenyl)thiopyridinesundergo allylation. Regioselectivity differences are noted for silylallyl- and silylvinyl-type substrates.s
(r
Cu;O- 3i
rtNqz
\____Z
DMSC .r:
Z"'att , + C u l- K F THF / lVle2CO
Me?Si
f"f\
rMoreno-Manas, M., Plexixata, R.,Villarrora. S
Copper(Il) tetrafluoroborate. pNitrostyrenes.t Styrenes undergr)r
)-,,"
.-2.-J.-)
Cul - KF
Cu(BFa)2and 12in MeCN.
THF / lVe2CO
78%
rChowdhury, C., Kundu,N.G.?55, 7011(1999).
2 Bouyssi,D., Monteiro, N., Balme, G. TL 40, 1297 (1999). 3Jacobi,P.A.,Liu, H. "/ACS121, 1958 (1999). alayaprakash,K., Venkatachalam, C.S., Balasubramanian, K.K. TL 40,6493 (1999). sTakeda,T., Uruga, T., Gohroku, K., Fujiwara, T. CL82l (1999).
Copper(Il) nitrate. 15, l0l; 18, 115-116; 19, I l0:20, l2l Biaryls.' Diarylstannanesincluding heteroaromaticanalogues(furan and thiophene series) undergo reductive elimination on treatment with copper(Il) nitrate trihydrate in THF at room temperature. Azidolysis of glycidic acids.2 In the presence of copper(Il) nitrate trihydrate, regioselectivering opening of the epoxide by sodium azide in water (pH 4) to provide 3azido-2-hydroxy carboxylic acids is observed. N-Nitro-1-methyluracil,\ l-Methyluracil undergoesN-nitration with a mixture of copper(Il) nitrate trihydrate and acetic anhydride, while nitration occurs at C-5 in fuming nitric acid.
rCampos, PJ.,Garcia,B., Rodriguez, M.A r1.I
Copper(I) 2-thiophenecarboxylate.19. t I Enami.des.t Enamides are prepartrJ NMP with Cs2CO.,asbase. lShen,R.,Porco, J.A.OL2, 1333(2M).
Copper(Il) triflate. 19, I 12;20, 122-l)] Cleavage of aziridines.t Coppenllr aziridinesby arylamines. Mukaiyama aldol reaction: With C cnol etherswith aldehydescan be carriedtr Acetylation. Alcohols, thiols. and ar reactionwith aceticanhydrideat room rem
are similarly transformedinto gem-diaceta N-Arylimidazoles.s Together *irh L as additives,Cu(OTf)2and cesiumcarbona
rHarada, G.,Yoshida, M., Iyoda,M. CL 160(2000). 2Fringuelli, F.,Pizzo,F.,Vaccaro, L. SZ311 (2000). 3Giziewicz, J.,Wnuk,S.F.,Robins,M.I. JOC 64,2149(1999).
lSekar, G.,Singh, (t999r. V.K.JOC 64,2537 rKobayashi, S.,Nagayama, S.,Busujima. T. (-/-I rsaravanan, P, Singh,V.K.TL40,26ll (lD99, rChandra, K.L.,Saravanan, P.,Singh,V.K.51,ri( sKiyomori,A., Marcoux,J.-F.,Buchwald. S.t- fl
Copper(I) oxide. 16, 99 Perfluoroallcylation,t By using Cu2O as the catalyst, anilines undergo perfluoroalkylation with RrI in DMSO at 130'. The perfluoroalkyl groups enter at ortho- and para-positions that are open. N,N-Dimethylaniline suffers demethylation in the
Copper(II) trifluoromethylthiolate. 19. I I Trifluoromethylthioarenes,t Arl laml in the presenceof the title reagent.
process.
'Adams,D.J.,Goddard, A., Clark,J.H.,Macqur
Copper(tr) trifluoromethylthiolate
allylationRegiorx. ..:rJcrgo t',:--.uhstrates.s
Cu2O - CsF17,
( \
/FNH2
/
---------------------_ ceFrzl Dr,,4soi3o'
_--'"u'u ,/-\ //-* , CeFrz
: r l \
^ . / Vl
l
I 5-/o
rMoreno-Manas, M., Plexixata, R.,Villarroya,S.Sa 1996(1999).
:: \\ I '. ''-Z
Copper(Il) tetrafl uoroborate. B-Nitrostyrenes,t Styrenesundergo nitration with sodium nitrite in the presenceof Cu(BF.), and I, in MeCN. rCampos,P.J.,Garcia,8., Rodriguez,M.A. TL 4l, 9'79 (2000).
e
Copper(I) 2-thiophenecarboxylate.19, I l2; 20, 122 Enamides.t Enamides are preparedby coupling alkenyl iodides with amides in N M P w i t h C s ; C O 1 a sb a s e . J r ' : , ) r( 1 9 9 9 ) .
lShen,R..Porco,J.A.OL2, 1333Q000).
Copper(Il) triflate. 19, l 12; 20, 122-123 r.: :Lrc:(furanand thioPhene tn r : - : ' . : l l t n i t r a t ct r i h Y d r a t e . ::.crrll) nitrate trihydrate, ....itcr(pH 4) to Provide3:
Cleavage of aziri.dines.t Copper(Il) triflate is a good catalyst for cleavage of aziridinesby arylamines. Mukaiyama aldol reaction r With CutOTf), as catalyst, the condensation of silyl enol etherswith aldehydescan be carriedout in aqueousethanol. Acetylation. Alcohols, thiols, and amines are acetylated by a Cu(OTf)2-catalyzed reactionwith acetic anhydrideat room temperature.rVariousaldehydes(but not ketones) aresimilarlytransformedinto 3erz-diacetates.a
.\ r-:
'r.rtlonwith a mixture of . rlccursat C-5 in fuming
N-Arylimidazoles.5 Together with 1,10-phenanthrolineand dibenzylideneacetone as additives,Cu(OTf), and cesiumcarbonatepromoteformation of N-arylimidazoles. rSekar, (1999). G., Singh,V.K.JOC 64,253'7 rKobayashi, S.,Nagayama, S.,Busujima, T. CL'11(1999). tsaravanan, P.,Singh,V.K.TL40,26ll(1999). +Chandra, K.L.,Saravanan, P.,Singh,VK. Sa 359(2000). 5Kiyomori, A., Marcoux,J.-F.,Buchwald, S.L.fL 40, 2657(1999).
.rnilines undergo Perr,.. li'.. :roups enter at ortho- and l::- . demethylationin the
Copper(Il) trifluoromethylthiolate. 19, I 12: 20, 122-123 Trifluoromethylthioarenes.t Arylamines are converted to ATSCFTby diazotization in the presenceof the title reagent. rAdams,D.J.,Goddard, A., Clark,J.H.,Macquarrie, D.J.CC 987(2000).
150
Cyanomethylenetriorganophosphoranes
1-Cyanobenzotriazole.
p-Cyclodextrin.
Aryl cyani.des.r Cyanation of ArLi by the title compound is expedient. rHughes, T.V.,Cava,M.P.JOC 64,313(1999). N-(2-Cyanoethoxycarbonyloxy)s-uccinimide. Amine protection.t Amino groups present in oligonucleotides are readily protected with this activatedcarbonate1 in the form of carbamates.
4 I
2-Amino alcohols. Epoxides are op trimethylsilyl azide2in the presenceof p-c1r Tbrephthalic acid. Benzene is selecrr yield) in a Cu mediatedreaction with CCl. r The C-{ bond formation occurs when benz
rReddy, L.R.,Reddy,M.A., Bhanumathi. N.. R.m 2Kamal, A., Arifuddin,M., Rao,M.V.IA 10.{:61 rShiraishi, Y.,Tashiro, S.,Toshima, N. Ct 8lE , -'{
,o
Carbonylhydridotris(triphenylphmphim I Hydroformylation I Wttig reactionaccomplished.
N-O
\ o otr",\
CN
(1)
>..,
H2tco.
rManoharan, M., Prakash, T.P.,Barber-Peoc'h, I., Bhat,8., Vasquez, G., Ross,B.S.,Cook,P.D.JOC 64.64681999\.
,nre^y'
1-Cyanoimidazole. Cyanation.t This reagent is prepared from imidazole and cyanogen bromide. It donates the cyano group to various nucelophilessuch as amines, thiols, and RMgX (or RLi). rWu,Y.,Limburg,D.C.,Wilkinson,D.8.,Hamilton,G.S.OL2,795 (2000). Cyanomethylenetriorganophosphoranes. Cyanomethylenation of carbonyl compounds. This powerful Wittig reagent MeIP--CHCN reacts with esters,lactones,and imides.r The reaction is valuable for synthesis of C-glycosides fiom glyconolactones and Phrh-{HCN. Microwave shorlensreactiontime to minutes.z assistance
rBreit,B.,Zahn,S.K.ACIEE38,969 (1999t ( 1,5-Cyclooctadiene)(1,3,5-cyclooctatrier
Isomerizatinn.r 2-Allylphenol is isom (cod)Ru(cot)in methanol at room tempera Triethylphosphineis also added. rSato,T., Komine,N., Hirano,M., Komiya.S. ('/. ( 1,5-Cyclooctadiene)cyclopentadien.r-lcnb
I * .'cN pnAoet [t",
"cN
This nrttr [2 +2 +2]Cycloaddition.t alkynesand a nitrile, has beenextendedro th
PhN.4e 100'
*{o=,
R
.lll lTsunoda,T., Takagi,H., Takaba,D., Kaku, H., Ito, S. TL41,235 (2000). rlakhrissi, Y, Taillefumier, C., Lakhrissi, M., Chapleur,Y. TA ll,4l7 (2000).
I
R
clrcr r,u.
l5l
(1,5-Cyclooctadiene)cyclopentadienylcobalt
p-Cyclodextrin. nr:. ..:-,Jts exPedient
" protected F, ..-lc'rrtidesare readily
2-Amino alcohols. Epoxides are opened regioselectively with arylaminesr and trimethylsilyl azidezin the presenceof B-cyclodextrin. Tbrephthalic acid. Benzene is selectively converted to tetrephthalic acid (46 mol%o yield) in a Cu mediatedreaction with CCla in the presenceof NaOH and B-cyclodextrin.r The C-{ bond formation occurswhen benzeneis trappedin the cavity of B-cyclodextrin. rReddy, N., Rao,K.R.S4 339(2000). L.R.,Reddy,M.A., Bhanumathi, 2Kamal,A., Arifuddin,M., Rao,M.V. fA rc, 4261(1999). sshiraishi, N. CZ 828(2000). S.,Toshima, Y, Tashiro, Carbonylhydridotris(triphenylphosphine)rhodium. Hydroformylation + Wittig reactian,t The
tandem process on
alkenes is
accomplished.
/'\'\-/"\ :
H2lCO- (PhrP)3Rh(CO)H
( i . . R o s s ,8 . S . , C o o k , P . D .J O C
enre^\o
phMe eo"
etoocv,,y,,Z{ :
!l .1.:
U.
.:
-
Ic
.:'
and cyanogenbromide. It rmines, thiols, and RMgX
- < l0fx)).
r. I :rr. powerful Wittig reagent fhe reactionis valuablefor u--r ,',1 PhIP-CHCN. Microwave
:
f
.cN
i
,nAoEt
I f!
.: l r x ) 0 ) . lr :1112000)
l
O
60% (syn : anti 9:1)
lBreit.8.. Zahn.S.K.ACIEE38,969(1999\. ( 1,5-CyclooctadieneX 1,3,5-cyclooctatriene)ruthenium(0). Isomerization.r 2-Allylphenol is isomerizedto 2-propenylphenolin 957oyield with 'the (Z/E) ratio of the products is 94:6. (cod)Ru(cot) in methanol at room temperature. Triethylphosphineis also added. rSato,T., Komine,N., Hirano,M., Komiya,S. CL44l (1999). ( 1,5-Cyclooctadiene)cyclopentadienylcobalt. [2 + 2 + 2]Cycloaddition.t This method of pyridine formation, which unites two alkynesand a nitrile, has beenextendedto the synthesisof spiroannulatedanalogues.
R'
. l Il l +#1*R' I
R
r52
Cyclopentadienylbis(ethylene)cobalt
rVarela, L., Saa,C. OLl,214I (1999). J.A.,Castedo, (1,5-Cyclooctadiene)(nu-naphthalene)rhodium(I) tetrafl uoroborate. This cationic rhodium complex is useful for inducing the [4 + 2]Cycloaddition. cycloaddition ofconjugated dienesto unactivatedalkynes in dichloromethane(15", 15 min), I forming I .4-cyclohexadienes.
4 6,I \.,^ru' o2"'V
rPaik,S.-J.,Son,S.U.,Chung,Y.K.OL1,2045(1999). (1,5-CyclooctadieneXr1o-tetraphenylborato)rhodium(I). Hydroformylation. Alkynes undergo hydroformylation to afford branched-chain aldehydeslor lactones.2
co-H2 (Pho)3P / cH2ct2
t 2Y
aY
tPerez,D., Siesel, B.A.,Malas r Eichberg, M.J.,Dorta,R.L..f2
Cyclopentadienylindium( I t Cy cIop en tad ie ny lc arbin ln water.
cHo 55%
/\ \ . / (
\t/
,)-e'
*Rh(cod)
\^ t'
7.
I
lYang.Y.. Chan.T.H. JACS 122.
91o/o rvandenHoven,B.G.,Alper,H.JOC 64,3964,9640 (1999). 2vandenHoven,B.G.,El Ali, B., Alper,H. JOC 65,4131(1999). Cyclopentadienylbis(ethylene)cobalt. [2 + 2 + 2]Cycloaddition. Extension ofthis cycloaddition method to annulation of benzofuran successfullyelaboratesfour rings of the morphinoids.' A strychnine synthesis2has beencompletedbasedon an analogouselaboration.
f<
siMe3
. rlt 1--\-\ 't' \ // \\ ""J-o-
CpCo(C2Ha)2
siMe3
,CoCp SiMe3 H SiMe3
Cyclopentadienylindium(I)
NHAc CpCo(C2Ha)2 + c2H4/ THF
luoroborate. il
o 47%
' ,,, afford branched-chain
,,
al
,v
.Y l
I Perez,D., Siesel,B.A.,Malaska, K.P.C.St 306(2000). M.J.,David,8., Vollhardt, I Eichberg, K.P.C.OL2,24'79(2000). K., Vollhardt, M.J.,Dorta,R.L.,Lamottke,
Cyclopentadienylindium(I). Cyclopentadienylcarbinols.t in water.
t
The title reagent reacts with carbonyl compounds
lHo HO
55%o
+ RCHO +
fA'
H2O/ rHF
L\X/ tn
lYang, Y., Chan, T.H. IACS 122, 402 (2000).
\
e . : . : ,,n methodto annulationof 1! :-
r n r r i d s .Ar s t r y c h n i n es y n -
:
(
n
.CoCp SiMe3
--\o SiMe3
,^2-^ \_/
rBose.D.S..Narsaiah, A.V.SC29,937(t999, 2Chaudhari, K.G.S 760( l99s S.S.,Akamanchi, 3Jenkins, N.E.,Ware,R.W.,Atkinson,R.N..Krn aNicolaou, K.C.,Zhong,Y-L., Baran,P.S..{C/
Decaborane. Reductive etherification.r Benzyl ethers are generatedfrom ArcHo with decaboranein an alcohol (e.g.,MeOH, EtOH). rLee.S.H..Park.Y.J.,Yoon,C.M. TL40'6049(1999)'
on treatment
Dialkylaluminum chloride. 20, 126-12,Addition to imines. The adducts l-mc the addition to N-sulfonylimines,which rr 1
cooEt I
Dess-Martin periodinane. Deoximation.t'2 A method for the regeneration of carbonyl compounds from oximes calls for oxidation with the Dess-Martin periodinane. A related application of the reagent is in the preparation of N-acyl nitroso compounds from hydroxamic acids.3 Heterocycle formation.a when o-iodination of acylanilines in which the acyl group contains a double bond at a proper distance is followed by several steps, benzomorpholines result. Unsaturated carbamates and amides form oxazolidinones and lactams undersuch reactionconditions.
o
,r\-{^
periodinane) DMP (Dess-Martin
\Zl;''in.
t-\_J
\ / - / r \ OD -M lN{ P h
o
P
/
W-ol
\ n CSHO \ - J ' N - \ / Pri
'
1/
\J
.o
\-4
Drl4P
Q"^,
I
(*
Propargylic alcohols.2 When catal stannanesto aldehydesis subjectto chelat substrate. 3-Acylindoles.r Friedel{rafts acrh catalyzedby R2AlCl (R : Me, Et). Michael
and. aldol reaction tandtt
o i
n-\'
l
r
l
l
90%
l
t oz-J
/ \ | '*, .*l \_/_l Ph
o
--'\^ru-\
---40
Ph
':
lot'D'N
n
83%
,/,-\
ill
dicarbonylcompoundsthat contain one (aldol reaction) if the second carbonrl g synthesisof 2-hydroxycyclohexanecarh The tarx step from 7-keto-2-alkenamides.a
A"o bn"
\
l,4e2cuL, E::.:
v f
)
r L i , G . , W e i , H . - X . , W h i t t l e s e yB, . R . , B a t n c e .\ r E v a n s ,D . A . , H a l s t e a dD, . P , A l l i s o n ,B . D . n - { r O k a u c h i ,T . , I t o n a g a M , . , M i n a m i ,T . , O u a . T . +schneider,C., Reese,O. ACIEE 39,29'18t lffl
DN,4P
(f\.to,?o r r + \ r , \ a^Y"E" ( coHo t*-rn ,pn \r' 83%
Dialkylaluminum
cyanide.
Cyanohydrins.r
Selective addition r
cyanohydrins en route to homologous nrtn
Dialkylaluminum bistrifl amides
rBose,D.S., Narsaiah,A.V SC 29,937 (1999). 2Chaudhari,S.S.,Akamanchi,K.G. S 760 (1999). rJenkins,N.E., Ware, R.W.,Atkinson, R.N., King, S.B. SC 30, 947 (2000). aNicolaou,K.C., Zhong, Y.-L., Baran,P.S.ACIEE 39,623, 625 (2000)-
r.-::irJ lrom ArCHO on treatment
Dialkylaluminum chloride. 20, 126-127 Addition to imines. The adducts from organocupratereagentscan be used in situ in the additionto N-sulfonylimines,which is promotedby Et2AlCl.r
oa.''
cooEr
rlr rll I
carbonyl compounds from t:
Me2CuLi/ Et2O
o"^a' Tot.--N
,,1',V-acylnitroso compounds
lfr
\,n
Et2Alcl
Tol'"-
NH
: Ph/\'cooEl tl -\ 77%
in which the acyl group a. . .:nrlines stePs,benzomor.. several t -.i hr s : ::r otazolidinones and lactams
lt: -
3eriodinane)
-c
Propargylic alcohols.2 When catalyzed by Me2AlCl, the addition of alkynylstannanesto aldehydesis subjectto chelationcontrol by a B-alkoxy or siloxy group in the substrate. 3-Acylindoles.r Friedel-Crafts acylation of indoles at C-3 with acid chlorides is catalyzedby RzAlCl (R - Me, Et). Michael and aldol reaction tandem. Michael reaction products arising from dicarbonyl compounds that contain one conjugated double bond undergo cyclization (aldol reaction) if the second carbonyl group is properly juxtaposed. For example, a acid derivativesis accomplishablein one synthesisof 2-hydroxycyclohexanecarboxylic The tandemreactionis promotedby Me2AlCl' stcp from 7-keto-2-alkenamides.a
'o 9-
-i-A.^;l-.f l;3:
,: a
02ph 9.
r L i , G . , W e i , H . - X . , W h i t t l e s e yB, . R . ,B a t r i c e ,N . N . " / O C6 4 , 1 0 6 1( 1 9 9 9 ) . r Evans,D.A., Halstead,D.P, Allison, 8.D. TL 40, 4461 (1999)' rOkauchi,T., Itonaga,M., Minami, T., Owa, T., Kitoh, K., Yoshino,H OL2' 1485 (2000). rschneider,C., Reese,O. ACIEE39,2948 (2000).
-O
-
\
Dialkylaluminum Ph
: r
Cyanohydrins.r
cyanide. Selective addition of Et2AlCN
to unhindered aldehydes gives o-
cyanohydrins en route to homologous nitriles. Ketones and enones are not homologated.
Diallylmercury
a-amino acids.2 Asymmetric addition to chiral sulfinilimines paves the way to the fluorinated amino acids. pFluoro
n '\a"''
lChan,T.H.,Yang,Y.,Li,C.I. JOC 61.t!:
o\^..''
-"N Tol
Et2AlCN
\_-
+
Ph
i-ProH
F
Tol
-bt
Diallyltin dibromide. Allylation. Formation of homor is possiblein aqueousmedia.r
N
:
,u".Yrn F 78%
Diaryliodonium salts. Arylations. Arylation of malo electron-rich aryl group is transferrcd of amines, amides, and lactams rs
undergoN-arylation using t-BuOK as
rNicolaou, ' S OL 2' G., Kranich,R., Baran,P.S, Zhong,Y-L., Natarajan K.C.,Vassllikogiannakis, 1895(2000). 2Davis,F.A.,Srirajan, V.,Titus,D.D.JOC 64,6931(1999)-
Tfo
,r'\r':'i\ \ ) \ o .
Dialkylaluminum trifl amides. Condensation reactions,t The title compounds (R2Al-NTft are excellent catalysts for Mukaiyama aldol reactions, Michael feactions, and allylation. The allylation is sensitive to steric environments of the substrates,enabling selective attack on a less
EtOOCvCOO
crowded formyl group.
\" 5 6e€
Biaryls.a
The coupling
of dia4
unsymmetrical biaryls is effected h1 obtained
rMarx.A.. Yamamoto, H. ACIEE39,178(2000).
Dialkyl c-nitroalkylphosphonates. very mild bases(e.g., K2CO3)are required for the Emmons-wadsworth reactionI synthesisof nitroalkenes using thesereagents. rFranklin. A.S.Sl, I I 54 (2000).
Diallylmercury. Allylations.
This reagent or allylmercury bromide react with aldehydes in aqueous
media.r rChan,T.H.,Yang,Y. TL40,3863(1999)-
from
the
reaction
oi
PhPb(OAc)j
O h , C . H . , K i m , J . S . ,J u n g ,H . H . J O C g . rKang, S.-K., Lee, S.-H., Lee, D. SL l0ll 'Jacobsen, S.A., Rodbotten,S., Bennechc ' K a n g , S . - K . ,C h o i , S . - C . ,B a i k , T . - G .S C j
DAE clol2.2.2loctane, 1,4-Diazabicy t28-129 Baylis-Hillman reaction.t Ofl fromsa synthesis of 3-acylchromenes Dechloroacetylation. Selectiv by transacl benzoates, andacetates.) L
1,4-Diazabicyclo[2.2.2]octane, DABCO
chiral sulfiniliminesPavesthe
157
Diallyltin dibromide. Allylation, Formation of homoallylic alcohols from aldehydesand the title reagent possible is in aqueousmedia.l I Chan,T.H.,vang,i, Lt, c.L Joc 64, 4452(lggg).
--
\, '.c--- -:/ :
Ph
F 7 8o/o
3'
Diaryliodonium salts. Arylations. Arylation of malonic esters is achieved in good yields. The less electron-rich aryl group is transferred from unsymmetrical iodonium salts.r N-Arylation of amines, amides, and lactams is under catalysis by CuI,2 whereas pyrimidinones undergoN-arylationusing r-BuOK as base(no copper salt.1.r
f ' s . Zhong, Y-L., Natarajan, S. OL 2'
Tfo /,,\,''.-t\
ll v I' e.
I
%
ll
o
DMF +Er ooc
|
Na*
.6X*
R \l-NTf2) are excellentcatalysts .rnil allylation. The allylation is :.,hlins selectiveattack on a less
74%
Biaryls.a
The coupling
of diaryliodonium
salts with aryllead triacetates to afford
unsymmetrical biaryls is effected by (dba).,Pdr.CHClr. For example,4-MeOC6HoPh is obtained
from
the
reaction
of
4-anisyl(phenyl)iodonium
tetrafluoroborate
with
PhPb(OAc)j
c g.. K:CO3) are requiredfor the
: . r c a c t w i t h a l d e h Y d e si n a q u e o u s
O h , C . H . , K i m , J . S . ,J u n g ,H . H . J O C 6 4 , 1 3 3 8( 1 9 9 9 ) . :Kang, S.-K., Lee, S.-H., Lee, D. SZ 1022(20OO). Jacobsen,S.A., Rodbotten,S., Benneche,T. JCS(P I ) 3265 (1999). 'Kang, S.-K., Choi, S.-C.,Baik, T.-G. SC 29,2493 (1999).
13,92;15,109;18, l2O;19,116-117;20, 1.4-Diazabicyclo[2.2.2]octane,DABCO. t28-129 Baylis-Hillman reaction.t One applicationof the reactionis for a convenient \vnthesis and1-alken-3-ones. from salicylaldehydes of 3-acylchromenes (e.g.,in the presenceof Dechloroacetylation. Selectivecleavageof chloroacetates to EIOHis readilyperformed.2 henzoates, andacetates.) by transacylation
r58
DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene,
lKaye, P.T.,Nocanda,X.W. JCS(P1) 1331 (2000). 2Lefeber, D.J., Kamerling, J.P.,Vliegenthart, J.F.G. OL 2, 70 1 (2000).
DBU. 13,92;14, 109;15,109-110;16' 105-106; L,8-Diazabicyclo[5.4.0]undec-7-ene, 18, 120-l2l; 19, 117;20, 129-130 17,99-lOO: 1,2,4There are reports on the alkylationof N-acylhydroxylamines,r Alkylations, last an a,N,N-triallyl glycine DBU as base. In the case, methyl esters using tnazole,2and rearrangement. of a [2.3]Stevens derivativeresultsbecause
f' -COOMe + 4::'u'Br
-K2CO3 \,^ru-\Z BuaNl +
ot'"f"t
|
y'-......'Acoou" B0o/o
Eliminations. Protected dehydro-ct-amino acids are formed from serinetype derivativesby eliminationaor from condensationofnitroalkaneswith ct-tosylglycines.s There is a similar processfor the transformationof enedionesto 2-alkylidene-1,4-
:'/
u-N
[o
l F c
Removal of protecting gt the removal of an Fmoc gru trichloroacetimidates is acco
involve acid-catalyzed hrd protected as trichloroacetimrd in acetonide,ester(acetate.tr
Ramberg-Biicklund ret. dienesis by treatmentof alll'l
diones.6
/\'t
\\ .,/ o
po
HN
\
* OrN-1 \
DBU/ THF
/-ts
v,,\
po
H
-
il I|
Y o
N
\ -./
/
Etooc/-\
Etooc
68%
Bay lis-Hillman
reactia
DMAP, etc.) because it signrfi adducts. Isocyanates,t3
An eliminationof toluenesulfinicacid is via doublebond misration.'
'ot'*'
DBUiTHF --;ZJ
rs&CooMe
y-Alkylidenation of I,3-dicarbonyl unsaturatedproducts with enals.
R.r..\.r\-COOMe R'tl OH
compounds.n The reaction gives rise to
InDl\lS(
Br) on treatmentwith DBL' ro
rJones,D.S., Hammaker,J.R.. Tc rBulger, P.G.,Cottrell, I.F.. Corr 'Arbore, A.PA., Cane-Honerscn iStohlmeyer,M.M., Tanaka.H I . iNagano,T., Kinoshita,H. SCs., "Ballini, R., Bosica,G., Petrelh.I TCaturla,F., Najera,C., Varea.\l Echaronnet,E., Filippini, M.-H.. 'Sheppeck,J.E.,Kar, H., Hong. I r"Yu, B., Yu, H., Hui. T.. Han. \ :
1,E-Diazabicycto[5,4.0]undec-7_ene. DBU
l - , .
//
-/
1 5 .l 0 9 - l l 0 : 1 6 , 1 0 5 - 1 0 6 ;
-/ r-N .'ir lhvdroxylamtnes,t 1,2,4. l3\t case.an o,N,N{riallyl
I
159
k--
[o t F o
/-N
Fo
U
.,)LH \
DBU / MeOH
l F o \ \
r 44o/o
^ntV *cootr,t" 8A%
t . , : lormed from serine-type O . : .
rar.su ith o-tosylglycines.s rJiones to 2-alkylidene-1,4-
AY i I
ll
Y o
V,\a-cct3 o7"--o
!o
HN'
::lOC
/a
Removal of protecting groups, A combination of DBU with a thiol can be used in the removal of an Fmoc groupe in a large scale process. Regenerationof alcohols from trichloroacetimidatesis accomprishedby treatmentwith DBU in MeoH (other methods involve acid-catalyzed hydrolysis and Zn dust reduction).r0Alcohols temporarily protected as trichloroacetimidatespermit their differentiation from others that are masked in acetonide,ester(acetate,benzoate,etc.), and ether (allyl, TBS, etc.) forms. Ramherg-Biicklund rea*angement.' An expedient accessto l,l-dichroro-1,3dienesis by treatmentof allylic trichloromethyl sulfoneswith DBU.
-
AY
DBU/cHcr3
-r}.'' i l / |
cl 92Yo
/
\
6BYo
.,-L.COOMe
)-
I'hc reaction gives rise to
Baylis-Hillman reaction,t2 DBU is an excelrent promoter (better than DBN, DMAP' etc.) becauseit significantlyenhances the reacrronrate, giving good yields of the adducts. Isocyanates.t3 In DMSo, trihaloacetamides undergoeriminationof cHX3 (x : cr, Br) on treatment with DBU to afford RN:C:O. rJones, D.S.,Hammaker, J.R.,Tedder, M.E.TL4l,1531(2000). rBulger,P.G.,Cottrell, I.F.,Cowden,C.J.,Davies,n.l.,Ooffing, u.-H.TL41,1297(200(tt. rArbore,A.PA , Cane-Honeysett, D.J.,Coldham, I., Middleton, M.L. SI 236(2000). 'Stohlmeyer, M.M., Tanaka,H., Wandless, T.J.JACStZJ, ArcO!SSS). 5Nagano, T., Kinoshita, H. BCSJ73,1605(2000). 6Ballini,R.,Bosica, perelli. petrini. G., L., M. .9I 236( t999). TCaturla, F.,Najera,C.,Varea,M. TL 40,5g5j(lggg). rCiaronnet, E.,Filippini,M.-H.,Rodrigue r, l. it tl5t USSgl. eSheppeck, J.8.,Kar,H., Hong,H. TL 41,5329(2000). ---" I ( ' y u8. . .y u . H . .H u i .T . .H a n i. . s L 7 5 3( 1 9 9 9 ) .
uoroethanol 1-Dibutylamino-2,2,2-trifl
I' Raj,C.P.,Pichnit,T., Braverman,S. TL 41, 1501 (2000). l2Agggarwal, V.K.,Mereu,A. CC 2311(1999). l3Braverman, S.,Cherkinsky,M., Kedrova,L. TL 40,3235(1999).
'Mispelaere,C., Roques, N. fZ !l{).611I r 19
N,N-Dibenzylformamide dimethyl acetal. Amine protection.l Primary amines are converted to N,N-dibenzylformamidines with this reagentor N,N-dibenzyl chloroformimidinium chloride.
Eto-\.,^r.-,.NHz
-#
Oxazolinyl epoxides.2 Condensa gives the epoxides.High stereoselecrir rr
OMe
N4eo NBn2 T
oEt
Dibutylboron triflate. 20, 132 Aldol reaction.t Predominanr sr phenylacetatewith aldehydesare obhrn
"tr-N
oEt Eto,,L--.,.-.r,,/N
:
NBn2
75Yo t99% l
Cl- ] Ior CICH=NBn2* cH2ct2
Bu2BOTf- Et3N
^,
........_
o"
pnaok
Pinheiro, S.,Lima,M.B.,Goncalves. C B Sl Florio,S.,Capriati, V.,Luisi,R. fZ 41.519!
rVincent, L., Mioskowski, C. SC29,16'1(1999) S.,Lebeau,
Di butylchlorostannane. Reductive amination,t
Diborane. Hydroborationr
Ph'
In chlorohydrocarbon solvents (dichloromethane, chloroform,
1,2-dichloroethane, etc), diboranehydroboratesunsaturatedcompoundsrapidly at -16".
The Bu-Sr
|ounds to secondaryamines. Hydrostannylation,2 The lraru-hri J ibutylchlorostannyl-3-hydroxy-I -alkeln
'Kanth,J.V.B.,Brown,H.C.TL4l,936l (2000).
,z R,r.? 'R ' '4
N,N' -Dibromo-N,N' -ethylenebis(2,5-xylenesulfonamide). Bromination.t Monobromination of arenesis achieved with this reagent.
OR.
Bu.^. * ^ '9' Bu
X=O B
I Ardeshir,K., Abbas,S. SC29, 40'79(1999).
1-Dibutylamin o-212,2-triflitoroethanol. Trifluoromethylatian.t The adduct of dibutylamine (or diethylamine) and trifluoroacetaldehydedecomposesin situ and transfers the CFr group to carbonyl compounds. (So far only PhCHO has been reported.)
iusa. T., Sugiyama,8., Shibata,I., Baba..\ \ l r t c h e l l ,T . N . ,M o s c h r e f ,S . - N .C C l 2 0 l r t 9
IXbutylchlorostannyl Esters.t
oxide.
The catalyst promotes rn
':,'m EtOAc to alcohols. Acetic anhr.dnd )nta.A., Sakamoto,K., Hamada,Y.. l\lrrrno
OH F3C-CHO+RzNH*F.C
NR, R=Et.Bu
PhCHO- t-BuONa
OH
I
F.c,^Ph 48%
l7-Di-t-butylfl uoren.9-ylmethor.r"ce Amine protection,t Comparedro r -:trl substituents make them more so
chloride 2,7-Di-r-butylfl uor€n-9-ylmethoxycarbonyl rMispelaere, C., Roques, N. ZL 40, 6411 (1999).
\ -Jrhenzylformamidines lu-
Dibutylboron triflate. 20, 132 Aldol reaction.l Predominant syn-aldol products from the reaction of methyl phenylacetatewith aldehydesare obtained, in contrast to that promoted by LDA. Oxazolinyl epoxides,2 Condensation of 2-chloromethyloxazolines with ketones gives the epoxides. High stereoselectivityis induced by a chiral oxazoline.
OMe ""1_ N
/'
/
NBnz .,- N \,.
pnAo-
\\
,wl
Bu2BOTf- Et3N + 0'
OMe /. "'y-N' BBu'
OMe ""1-N R2CO / NaOH
pn ot-vo
pn^oi cl
nAR
rPinheiro, S.,Lima,M.B.,Goncalves, C.B.S.S., Pedraza, S.F.,deFarias,F.M.C.ZL 41,4033(2000). 2Florio,S.,Capriati,V, Luisi,R. TL 41,5295(2000). Dibutylchlorostannane. Reductive amination.t
The Bu2Sn(H)CI-HMPA complex converts carbonyl com-
poundsto secondaryamines. The trans-hydrostannylationof propargyl ethers to give (Q-ldibutylchlorostannyl-3-hydroxy-l-alkenesis probably directedby the etherealoxygen atom. Hydrostannylation.l
h.
,r,,methane,chloroform' :.,,undsrapidlyat -16".
:42 oR"
L
F.: .. ih this reagent
.
Bu. ,H + ,Sn. B u X X=Cl,Br
Rtt'\
R'tl OR"
I SnBu2X
> 98%
rSuwa,T., Sugiyama,E., Shibata,I., Baba,A. S 789 (2000). rMitchell. T.N.. Moschref.S.-N. CC 1201 (1998).
ir.'th.vlamine)and trifl uotr) carbonyl comPounds.
Dibutylchlorostannyloxide. Esters.t The catalystpromotestransesterification, for example,the acetyl group fromEtOActo alcohols. Aceticanhydride canbe usedasacylatingagent. lOrita, A., Sakamoto,K., Hamada,Y, Mitsutome,A., Otera,A. T 55,2899 (1999).
OH
I
F.c 48o/o
Ph
2,7-Di-t-bu,tylfluoren-9-ylmethoxycarbonyl chloride. Amine protection.t Comparedto simpleO-(9-fluorenylmethyl) carbamates, the tbutyl substituentsmake them more soluble.On deprotectionby treatmentwith 20Vo
162
Di-l-butYlPYrocarbonate
enables its removal by piperidine in DMF, the formation of a highly lipophilic byproduct hexane extractton.
Carbamate exchange,2 Benzl l carh hydrogenolysis(Pd/C,polymethylhldrosrk
rStigers, M.R.,Chung'D'M'' Nowick'J'S'"IOC65' 3858(2000)' K.D.,Koutroulis,
Feneira,P.M.T.,Maia,H.L.S.,Monteiro.L S , :Chandrasekhar, S.,Chandraiah, L.. Reddr-C R
Dibutyliodostannane. Reductiveamination.AldehydesformsecondaryaminesontreatmentwithAINH'
Dibutyltin oxide. 13,95-96; 15, ll6-l l-. syn-Amino alcohols.t sln-l.l-DroL are converted to cyclic carbamateson rel-l
andBu2Sn(H)I.WhenaproximalMichaelacceptorispresent'cyclizationfollows'r the amine'2 However, a reduction-aldolization sequenceprevails without
ArNH2 / Bu2Sn(l)H
Monotosylation.2 1,2-Diolsundergo *hich yields are poor). In some caser O .toichiometricformation of the cyclic sran Cho,G.Y, Ko. S.Y.JOC 64.8745(19991 \lartinelli,M.J.,Vaidyanathan, R., Khau.\'\
i
Dicarbonylcyclopentadienylcoball Cycloisomerizatinn.t :ndergoene reaction. I Suwa,T., Shibata,I., Nishino, K.' Baba' A' OL l' 15'79(1999)' 2Suwa.T., Nishino, K.' Miyatake, M', Shibata,I', Baba' A'TL4l'
3403 (2000)'
Di-t-butyl pyrocarbonate.20' 133 with (Boc)zO Oriyiiadon.t Serineanaloguesundergodehydrationon treatment acid derivatives.Peptidescontainingserineresidues andDMAP to afforddehydroamino aresimilarlyaffected'
*-rot
o oA*A.oot" H
B-Keto esren r
3
:a
Renaud, J.-L.,Aubert,C., Malacna,N{.f 55. 5 (Boc)20- DMAP
,t"ia-\cooMe H 73-99o/o
Dichloroalane. 1,1-Diiodoalkanes.t Reactionof l-al .clr-dimetallic specieswith iodine leadr r
Dichloroalane
r:
i.r productenablesits removal bY
Carbamate hydrogenolysis
(2000). , rt 65.-3858
o:.--::r rntines on treatmentwith AINH, . lresent. cyclizationfollows'r L-: x . ..:ihrrutthe amine.2
exchange,2
Benzyl carbamates are converted to r-butyl carbamates on
(Pd/C, polymethylhydrosiloxane
in EIOH) in the presence of (Boc)20.
lFerreira, P.M.T., Maia, H.L.S., Monteiro, L.S., Sacramento,J. JCS(Pt ) 369i. (lggg). rChandrasekhar,S., Chandraiah, L., Reddy, C.R., Reddy, M.V CL 780 (2000).
Dibutyltinoxide.13,95-96;15,116-117; 16,ll2; 18, 125; 20, 133-134 syn-Aminoalcohols.t syn-1,2-Diols,after forming dibutylstannylene derivatives, areconvertedto cyclic carbamates on reactionwith BzN:{:S.
o
Y"
^-'\
I
Oty'O
eursnolcrcH2cH2ct
O
---....-----...-.-.---------------------* | ll PhcoNcs-Et3N: Bu4NBr
O-;.,AO : \
fNaz 81o/o
Monotosylation,2 1,2-Diolsundergoselectivetosylationwith this catalyst(without which yields are poor). [n some casesthe efficiency is comparableto that involving stoichiometricformation of the cyclic stannylenederivatives. ICho,C.Y..Ko. S.Y.JOC 64.8745,]1999). rMafiinelli,M.J.,Vaidyanathan, R.,Khau,V.V.TL 41,3773(2000).
: , Dicarbonylcyclopentadienylcobalt. Cycloisomerization.t undergoene reaction.
B-Keto esters that contain an alkynyl chain at the cr-position
{ t. tj0,r (2000).
CpCo(CO)2
i: ..
u:
lrrtion on treatment with (Boc)zO l'cptidcs containingserineresidues
I
.',
R-
iill
4o^ru^cooMe H 73-99%
benzene hvA
Renaud, J.-L.,Aubert,C., Malacria,M. f 55,5113(1999). Dichloroalane. 1,1-Diiodoalkanes.t
Reaction of l-alkynes with HAICI, followed by quenching the cen-dimetallic species with iodine leads to a twofold hydroiodination. The reagent is
ll"l-<
DDQ 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone,
prepared in situ from LiAlH4 and Alcls (ratio 1:3) in ether with subsequentexchange of OBn
the solvent.
HAtct2
Ph
\
;*
AlCl2
no: tn.Ao,",,
l2 THF
tn.A,i
OMe OMe
> 90% rAufauvre.L., Knochel,P.,Marek,l. CC 2207(1999). Dichloro(1,5-cyclooctadiene)ruthenium(Il). is Cyclization.l An efficient synthesis of methylenecyclopentanesfrom 1,6-dienes by Ru catalysis.
Xia,J.,Abbas, S.A.,Locke.R.D..Pirkorz(' Chandrasekhar, S.,Reddy,C.R..Reddr.\t \ Hungerhoff, B., Samanta, S.S..Rtlels.J . \lc 'Karimi,B..Ashtiani. A.M. Ca I199r llrr 'Xu, Y-C., Kohlman,D.T.,Liang.S.X . F_ni
rYamamoto, M., Itoh'K. JOCil'21'18 (1999)' Y.,Ohkoshi,N., Kameda, 19, 123-125; 20, 136-13-7 Dichlorobis(triphenylphosphine)ruthenium(Il). to ketones by this complex has alcohols allyl of The isomerization Isomerization way to acquire a-methyl-pa new therefore adducts, been applied to Baylis-Hillman ketoestersis develoPed.t 2-Thiazolines.2 Dehydrogenation of thiazolidines by l-BuooH is catalyzed by (PhjP)2RuCl2. Reduction of kztones.3 Extremely highly enantioselectivereduction by i-ProNa/ i(oxazolinylferProH is observed in the presence of the Ru complex and a chiral of racemic oxidation effects system rocenyl)phosphine ligand. The same catalytic '9Vo. 99 ee of with again secondaryalcohols with acetonevia kinetic resolution, IBasavaiah. K. .lC 29, 713(1999). D.. Muthukumaran, 2Fernandez, X., Fellous,R.,Dunach,E.TL4l' 3381(2000)' 3Nishibayashi, Y.,Takei,I., Uemura,S.,Hidai,M. OM 18'2291(1999)' 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, DDQ. 13, 1M-105; 14, 126-12'7:l15' 125-126; 16, 120; 18, I 30; 19, 121-122; 20, 137-138 Deprotection. Removal of the 2-naphthylmethyl group from 2-NpCH2OR' and oxidative cleavage of oximes and tosylhydrazones with DDQ proceed under mild room conditions.2 Smooth and selective transformation of RNBn2 to RNHBn at temperatureby DDQ in dichloromethanecontaining some water is observed.r Acetalizgtian, Diethyl acetals are formed from carbonyl compounds by functional group exchange with triethyl orthoformate (EIOH also present) under the influence of DDQ.a Benzylic activation. Hydride abstraction by DDQ from benzyl ethers, where the group)' benzylic position is also activated by a nuclear substitutent (e.g., methoxy an constitutes prepares such compounds to be attacked by nucleophiles. The reaction important step in a synthesisof deoxyfrenolicin.5
l. l -Dichloroethyllithium. 2,2-Dichloro-3-alkanones.r Thc 1 Jichloroethane.reactswith estersat l(,s 1.2-dichloro-3-alkanones. The dichlor, \tOM esters.
\ cr .cl
X,,
[.4e3SrCl
RcoOR 100
Me
Shiina, I., Imai,Y. Suzuki, M..Yanaqr.:ui!
I I -(2,5-Dichlorophenyl)-2,2-bismerhlld N-Acylation.t Reagent 1 is ohtarrx tophenone.It is a highly efficient acr ler rre formed from amino alcoholsand an rcactivity is observedtoward alipharrcOl
MeSa
(
benzoate [-(2,5-Dichlorophenyl)-2,2-bismethylthio]vinyl
OMe
11: .uhsequentexchangeof
OBn 4\/snPh3 I
'^.^,
CH2Cl2
OMe OMe
OMe OMe
94o/o
ts [r'r.trnes from 1,6-dienes
I Xia, J., Abbas, S.A., Locke, R.D., Piskorz, C.F.,Alderfer,J.L., Matta, K.L. TL 41, I 69 (2000). rChandrasekhar, S., Reddy,C.R., Reddy,M.V. CL 430 (2000). lHungerhoff, B., Samanta,S.S.,Roels,J., Metz, P. 51,77(2000). r K a r i m i , B . , A s h t i a n i ,A . M . C L 1 1 9 9( 1 9 9 9 ) . 'Xu, Y - C . , K o h l m a n ,D . T . ,L i a n g ,S . X . ,E r i k k s o n ,C . O L l , 1 5 9 9 ( 1 9 9 9 ) .
l^,. | . | -Dichloroethyllithium. 2,2-Dichloro-3-alkanones,r
10.136-137 lr:,,:rcs bY this comPlexhas
dichloroethane, reacts with esters at low temperatures to give mixed alkyl-silyl
ra.1r r() acquire ct-methyl-B-
2,2-dichloro-3-alkanones. The dichloroketones are obtained directly from reaction of
:r
Thc
title
reagent, which
is generated from
l,l-
acetals of
MOM esters.
,
iluOOH is catalyzed bY
t:r: :cductionbY i-PrONa/ir-: .r chiral (oxazolinYlferftr.:- oxidation of racemlc | ..::i, cc of - 99.9Va.
ct .cr 'X---'-R x . o
cr .cl
X.,
RCOOR' -1 00"
Me3SiO OR'
r
ct cl 'X',.,^ n O R'= CHzOMe
Shiina, 1.,Imai,Y.,Suzuki, M.,Yanagisawa, M., Mukaiyama, T. Ca 1062(2000). s
,f. 14,126-127:.15'
\.,. lrom 2-NPCH2ORTand | :)t)Q proceed under mild to RNHBn at room l\!l:r r r::: t. obseryed.3 r:r. eomPoundsbY functional I :nJcr the influenceof DDQ.a r, ::'. hcnzyl ethers, where the tutr:rl tc.g., methoxy grouP)' 5 Tf.!' reaction constitutes an
I I -(2,5-Dichlorophenyl)-2,2-bismethylthio]vinylbenzoate. N-Acylation.t Reagent1 is obtainedby enolbenzoylationof a,a-bismethylthioacetophenone.It is a highly efficient acylating agent fbr amines.Thus, only the benzamides ere formed from amino alcoholsand amino thiols, using limited amount of l. A higher reactivityis observedtoward aliphaticOH than phenolicOH.
A r O
""tYAoArn SMe (1)
Dicobalt octacarbonyl
rDegani, S.,Fochi,R., Serra,E. S 1200(1999). I., Dughera,
N, N-Dichloro-2-nitrobenzenesulfonamide. Aminochlorination.t The dichloro compoundeff'ectsaddition to cinnamic estersin combinationwith the sodium salt of 2-nitrobenzenesulfonamide.
oCo2(COr3
^.,.N._
OO'
NMO H:O MeCN
X cl I
N s N ( N a ) c-l N s N c 1 2 -.^t\ Ph-
v
-COOMe
cuort
cbH6/ MecN Na2SO3
pn-\..coottle = ^vr-e'N /.Y
H
2"-zNo'
t t l \-,/
76To ( s y n:
a n t i1 : 3 0 )
rLi. G..wei,H.-X.,Kim,s.H.oL2,2249(2000\.
Dichlorotin oxide. Alkene functionalizatian.t Vicinal addition of the [HOA,Jrl and IHO/RCOO] to alkenes is effected by MejSiX (X : N,, OCOR) in the presenceof bis(trimethylsilyl) peroxideand catalyzedby (Cl2SnO),,. l s a k u r a d a1, . ,Y a m a s a k iS, . , K a n a i ,M . , S h i b a s a k iM , T L 4 1 , 2 4 1 5( 2 0 0 0 ) '
D i c o b a l to c t a c a r b o n y l1. 3 , 9 9 - l 0 l ; 1 4 , l l 7 - 1 1 9 ; 1 5 , I l 7 - l l 8 ; 1 6 , I l 3 - l l 5 ; 1 7 ' 102-105;18, 132;19, 125-126',20, 139-141 Hydrosilylation.t The cohalr-catalyzedhydrosilylation of oxygen-containing alkeneshasbeenrePorted. Pauson-Khand reaction. Many modifications,particularly regarding the use of substoichiometricquantities of Coz(CO)s,have been studied. Addition of cyclohexylamine makescatalytic reactionpractical,and there is no needto purily Co2(CO)s,which r is somewhat air sensitive.z Various alkyne-Co2(CO),,complexes are usetul catalyst a Iinsteadof Co:(CO)ri]fbr carrying out the reactionundercarbonmonoxide Other reports include reactions in supercriticalethylene,5pfomotion by molecular sieves,"and the effect of a phosphine sulfide.7Clusters such as methylidynetricobalt nonacarbonylare also effective catalystof the Pauson-Khandreaction.nVinyl estersare idcntifiedas surrogatesfor ethylene.u ConventionalPauson-Khandreaction conditions are employed in annulatinga menthenederivativein an approachto t t-dendrobine.r"
Depropargylntion.tt The value c hols, carboxylic esters,and amines &
using Co2(CO)r and trifluoroacerrc Alcohols and amines can also be mar\:
esters.tl Regrorc B-Hydroxy ( methoxycarbonylation)of epoxrder
hydroxypyridine. plnctam*ti Insertion of CO synthesis.Regioselectivityfor such a n
v-orBs N
C o : , C C. DME':,:
Bn
'Chatani, N., Kodama, T., Kaiikau.a. \'. ! ( 2000). rKrafft, M.E., Bonaga,L.V.R., Hirosau:- ( 'kafft, M.8., Bonaga,L.V.R. SL 959 | :fl| rKrafft, M.8., Hirosawa,C., Bonaga. \ L I 'Jeong, N., Hwang, S.H. ACIEE 39. 6-16, l "Perez-Serrano, L., Blanco-Urgoiti.J.. Crs -35r 3 (2000). -Hayashi, M., Hashimoto,Y., Yamam<'ro.I 'Sugihara,T., Yamaguchi, M. "/ACSlZl. 1t 'Ken, W . J . ,M c l a u g h l i n , M . , P a u s o nP . L. 'Cassayre, I.,Zard, S.Z. JACS l2l. 60l: , I Fukase,Y., Fukase,K., Kusumoto.S. r/. { rHinterding,K., Jacobsen,E.N. "/OC 61. : I 'Davoli, P, Moretti, I., Prati, F.. Alxr. l.t /
Dicobalt octacarbonyl
N-
.rJditionto cinnamic estersin r lr d c .
C02(CO)8
^...N-.
OO'
Nt\,40. H20
X
H
"'oAc
l\.4eCN
(-)-dendrobine
cl
'
__ lr-.coov" : ^--'s'rln -
itn
y''-./,'", ll \-/ ^
antl 1 :30)
. llo,N,l and IHO/RCOO] to . nr!'\cnccof bis(trimethylsilyl)
Depropargylation.tt The value of propargyl derivatives as protected forms of alcohols, carboxylic esters, and amines depends on their facile reversal. It can be achieved using co2(co), and trifluoroacetic acid in dichloromethane at room temDerarure. Alcohols and aminescan also be maskedas RXCOOCH2CCH. esters.t2 Regioselective ring B-Hydroxy opening and homologation (methoxycarbonylation)of epoxides are achieved on treatment with co2(co), and 3hydroxypyridine. pl'actams.tl Insertion of co into aziridines is a new approach to BJactam synthesis.Regioselectivityfor such a reactionhas beenobservedin certainsubstrates.
r
I
t
f N
il
r:(XX)).
^r-OTBS
7
Co2(co)s
-
OTBS
TBSO
DME 100"
Bn (92 : 8)
l-i
-
llSr16,ll3-l15;17'
.l.rrr(ln()l oxygen-containing IC t
', I
U l.
( l\
n.
regardingthe use of .1:'11!ularly ',rJrc'd.Addition of cyclohexyl:rccdto purily Co2(CO)*,which i()nrplexes are useful catalyst ..rrhonmonoxide.a . rcnc-.ipromotion bY molecular :. .uch as methylidynetricobalt shend reaction.sVinyl estersare .'rnplovedin annulatinga men-
99.8%
lChatani, N., Kodama, T., Kajikawa, Y., Murakami, H., Kakiuchi, F., Ikeda, S.. Murai. S. CL 14 (2000). : Krafft, M. E., Bonaga, L.V.R., Hirosaw a, C. TL 40, g 1'7| (lggg). 'Krafft, M.8., Bonaga,L.V.R. SL 959 (2000). lKrafft, M.E., Hirosawa,C., Bonaga,L.V.R. Za 40,91i-7(lggg). 'Jeong, N., Hwang, S.H. ACIEE 39, 636 (2000). ''Perez-serrano, L., Blanco-urgoiti, J., casarrubios,L., Dominguez,G., perez-Castells, l. J[rc 65, - ] s 1 3( 2 0 0 0 ) . -Hayashi, M., Hashimoto,Y., yamamoto,y., Usuki, J., Saigo,K. ACIEE39,63l (2000). 'Sugihara, T., Yamaguchi,M. ,/ACS120, 10782(1998). 'Ken, W.J.,Mclaughlin, M., Pauson,pL., Robertson,S.M. CC 2l7l (1999). 'Cassayre, J., Zard, S.Z. JACS l2l, 6072 (1999). Fukase,Y, Fukase,K., Kusumoto,S. Za 40, I I 69 (1999). :Hinterding,K., Jacobsen, E.N. "/OC 64, 2164 (1ggg\. 'Davoli, P.,Moretti, I., Prati, F.,Alper. H. JOC 64,518 (1999).
Dicyclohexylboron chloride
Dicyanoketene ethyleneacetal. Mannich reaction.t This reagent and similar r-acids on polymer support effect chemoselective condensation between silyl enol ethers and imines in refluxing MeCN; aldehydesdo not participate in the reaction. Ether cleavage.2 The polymer-bound reagent catalyzes hydrolysis of TBS ether and acetals in aqueous acetonitrile. Methoxymethyl and tetrahydropyranyl ethers are stable under such conditions. rTanaka. N.. Masaki.Y SL406(2000). 2Tanaka. N.. Masaki.Y Sa 1960(1999).
1eo' Zt\/oH Me3NO
al_
Y l-*\ o ., K l o , - " - . o , 4)
60% rBatey,R.A.,Thadani, A.N.,Lough,A.J.CC 4'75(1999). Dicyclohexylboron chloride. Alkylation. Reaction of the reagent with ArCHO followed by oxidation delivers secondary alcohols. There are hints that other secondary R2BCI behave similarly, but the scope is severely limited to aldehydeswithout an c-hydrogen (otherwise enolization prevails).r Aldol reactions. In conjunction with an amine, dicyclohexylboron chloride is used to generate kinetic enolates from ketones. Some interesting and useful information concernsthe stereoselectivity of the aldol reactions.2
o o H
tl
* Cy2B-Cl
J"A + cyzB-ct
1--\_
(6
\,4/ T
Dicyclohexylboron trifl ate. Doable aldol reactions.t Thc. e compoundswith two aldehydesis hreh of Cj-symmetrictriols.
P h o
Dicyclohexylborane. 20, I4l-142 Hydroboration Hydroboration of alk-3-en-l-ynes provides conjugated dienylboranes that are reactive toward unactivated dienophiles. Cyclohexenols are readily acquiredfrom the cycloadducts.r
Cy2BH ; t\.4e3NO
Kabalka, G.W.,Wu,2., Trotman.S.E..Gr: rGalobardes, M., Gascon, M., Mena.\l _Ro
Abiko,A., Liu, J.-F.,Buske,D.C..Ilonr am
.\',N' -Dicyclohexylcarbodiimide. IX.C Nitroacetic esters.t Esterificatron conventionalmethods,but it can hr p \ervesto anchornitroacetylgroupsto hr 4-O-Allqtltetronic acids.) Preparar acidsundermild conditionsrelieson thec Sylvain,C.,Wagner, A., Mioskowskt. C. fL rSchobert, R.,Siegfried, S.51-686rl00l,
Diethylaluminum ethoxide. Aldol reaction l Enol estersare us at 0'. Productyields are in the 70e rang Diels-Alder reaction.2 Ar lou rc c'nonesand l-acetoxy-1,3-dienes rn O hydrolysisduring the condensarron.
ll
OAc
\
l l l . 'v
OR
RCHO
Diethvlaluminum ethoxide
i...:. ,,n polymer supporteffect .i: .: r:rlnes in refluxing MeCN; ti.. :. hrdrolYsisof TBS ether ethers are ,n.: :-'tr;rhvdroPYranYl
rKabalka, G.W.,Wu,Z.,Trotman, S.E.,Gao,X. OL2,255 (2000). rcalobardes,M., Gascon,M., Mena,M., Romea,P.,Urpi, F.,Vilarrasa,L OL2,2599 (2000). Dicyclohexylboron trifl ate. Double aldol reactions.t The consecutive (one-pot) aldol reaction of carbonyl compounds with two aldehydes is highly stereoselective.It is applicable to the synthesis of G-svmmetric triols.
P h o
P h O O H
--.f,o\+,,'
J"lle. ::,,\rdes conjugateddienYlbu :- Crclohexenols are readilY
-fr-ro,
Et3N; + CV2B-C| + i-PTCHO; PhCHO
\ +''Y -frrso, lIot
rAbiko, A., Liu, J.-F.,Buske,D.C., Moriyama, S., Masamune,S. "/ACS121,7168 (1999).
'V,N'-Dicyclohexylcarbodiimide,DCC. 14, 131-132; 16, 128; 18, 133-134 Nitroacetic esters.t Esterification of nitroacetic acid is not easy to achieve by conventionalmethods,but it can be performed with the aid of DCC. This procedure servesto anchornitroacetylgroupsto hydroxylatedMerrifield resin. 4-O-Alkyltetronir acids.2 Preparationof these compounds from the pa-renttetronic acidsunder mild conditionsrelies on the exchangereactionwith isoureasderived from DCC. .,scd by oxidationdelivers behavesimilarlY,but the IJC-I r. i r - ' , . : : , ' ! c n ( o t h e r w i s ee n o l i z a t i o n (i
l:, . - ,,hcrYlboronchlorideis used n:.' . .::'l! end useful inlormation
o o H
- . A , l .R
A., Mioskowski, Sylvain, C.,Wagner, C.TL40,875(1999) rSchobert, R.,Siegfried, S.SL 686(2000). Diethylaluminum ethoxide. AMol reactionr Enol estersare usedas donorsin the crossed-aldolreactionin THF at 0'. Productyields are intheT0Vo range. Diels-Alder reaction.2 At low temperatures, the cycloaddition occurs between enones and 1-acetoxy-1,3-dienesin the presence of Et2AlOEt. The acetate suffers hydrolysisduring the condensation.
I-Y
'
o o H
. . A ^R . Y Y o R l
A l l
o
OAc
\
l .z I
Et2AtoEt + hexane - PhMe
0.
2,6-Dihydroxypyridine
o
'Mukaiyama, T., Shibata, J., Shimamura, T., Shiina, I. CL951 (1999). 2shibata, J., Shiina, I., Mukaiyama, T. CL 313 (1999).
,.
S
\.r'^\.,"\ I
^^^i v v v r v r Er^
NHCOOBn
(Diethylamino)sulfurtrifluoride, DAST. 13, ll0-ll2;16, 128-129;18,135;19, 126-127:20.142 Cyclizations. Aone-stepcyclizationofN-hydroxyethylamidesto oxazolesand oxazolinesris mediatedby DAST. B-Hydroxycarbamates usuallyundergofluorination (OH - F), but theN-Bocderivativesaffordoxazolidin-2-ones.2
I I t
l
I
Z\f
DASr/ cH2cr2 78":
l 1,r"t'r.,-uH
6
Koco'-
H
+ Hor^-
Miller,S.J.,Collier, T.R.,Wu.W. Z- {1. :-!
Diiodomethane.13, 1l0-l I 5: 175-l-6. t13-t44 1,3-Diketones. Simmons-Smrrh r I . 3-diones.rBy addition of tetrahrdrrri
o-\
z\*,L-N/ tl o
\'latsubara, S.,Yamamoto, Y, Utimort. K -\
87To Diiodosilane. rPhillips,A.J.,Uto,Y.,Wipl P, Reno,M.J.,Williams,D.R.OL2,1165(2000). zzhao,H' Thurkauf, A. Sa t 280(1999).
Ureas.t Carbamatesare con\ r'na lsocyanatesto amines,unsymmetncalur
1,3-Dihydro- 1,3-diacetyl-2II-benzimidazol-2-one. Acetylation.t Selective acetylation of amines (primary amines ) secondaryamines, arylamines) is readily accomplished.
Ac
",*-l-\\:./
.fY*>o-r,*-l\ i,,n,
_\"
\:,/
,ruHn"
97Yo Ac
* fFU>o Ho,,-r--il.--,,"-NHz \.'^-Nf
h"
-------* gq,,-r-.-il**"o. 94Yo
'Chung, I.H., Cha, K.S., Seo,J.H., Kim, J.H., Chung, B.Y., Kim, C.S. H 53,529 (2000).
2,6-Dihydroxypyridine. Sulfuxidereduction.t By usingthis reagentto reducesulfoxides,many functional groups(e.g.,esters,carbamates) arenot affected.
Gastaldi, S.,Weireb, S.M.,Stien.D.,/(X a<
Diisobutylaluminum hydride, Dibd-H 123-125:18, 140-l4l ; 19, 128-l19: !l Conjugate reduction.t Thc douhk and tertiary amides are reduced b1 Drtul Debenzylation 2 Perbenzvlarc'dcrr
debenzylatedby Dibal-H in toluenc'rn a debenzylatedor AD-di-O, O-debenzrlarc Clnisen rearrangement.i Dihat-H rearrangement. Thus, allyl 4-l-but1lphcn rt room temperaturein 877cyield. \'h O
' Ikeno,T., Kimura,T., Ohtsuka. Y. \'ama&. Pearce, A.J.,Sinay,P.ACIEE39.-16l0rlfirl 'Sharma, G.V.M.,Ilangovan, A.. Sreenrr e.. P
Diisobutylaluminumhydride,Dibal_H
171
o ,-
:i J\.,-\a,,'\^^n I
NHCOOBn
1 6 . l 1 8 - 1 2 9 ;1 8 ,1 3 5 ;1 9 ,
l::
^r^ vvvrvrv
.
r'4ecN -S\-'\\-,"\^nn
f\ Ho
ttAoH
I
^
v v v r v t^,^ Y
NHCOOBn 90To
n \ . r:it\ | amidesto oxazolesand r,:::. r.uall) undergofluorination d::
Miller,S.J., Collier, T.R.,Wu,W IZ 41,3781(2000).
,nc'..:
-
I t
7>fru
o-\ t
Diiodomethane. 13,110_l15:2j5_276;16, lg4_1g5;17,155;lg,139_140; 19,12g:20, t43-144 1,3-Diketones,Simmons-Smith reagentreactswith acid chroridesto afford the l. 3-diones.r By additionof tetrahydrothiophene themonomeric formis stabirized.
/
tl
o
Matsubara, y, Utimoto,K. SL 14710lggg). S.,yamamoto,
87Yo Diiodosilane. .'
1
16.s(2000).
Ureas.t Carbamates
isocyanates roamines, "".rffi;il;::lJ:.r:i:rnates
F:
'- .,.\ lmines ) secondaryamines,
bv H,Sir,.on exposing the
H)siil
NH
i errer.re l c'2ct2
)-., o {
NH
Fryn B n
O
84%
HrNl
h
:
NHAC
97%
H -
H9-'-'-N*NHA. 94To
( s H 53, 529(2000).
| :..r-.1' sulfoxides,manv functional
castaldi,S.,Weireb,S.M.,Stien,D. JOC 65,3239(2000\ Diisobutylafuminumhydride, Dibal_H. 13, I l5_l l6; 15, 137_13 g;16, 134_135;17, 123-125; 18, 140-t4l: 1,9, t}g- t29; 20, 144*146 conjugate reduction..t The doubrebond of a,B-unsaturatedketones,esters,nitriles, and tertiary amidesare redlced by Dibal_H in the presenceof Co(acac)2. Debenzyratinn'2 perbenzyrated cyclodextrins10-, B-, ancr 1-forms) are partiary debenzylatedby Dibar-H in toluenein a regioserectivemannerto provide the mono-6-o_ dcbenzylatedor AD-di-O,O_debenzylated derivative. claisen rearrangement.3 Dibal-H serves as a Lewis acid catarystfor the craisen rearrangement. Thus, ailyr 4-l-butyrphenyrether is converted to the 2_alryrphenor product irt room temperaturein 87Toyield. yb(OTflr is a far lesseffectivecatalysi. lkeno,T., Kimura,T.,Ohtsuka, y., yamada, T. SL 96 (l9gg). . Pearce,A.J., Sinay,p ACIEE39,36l0(2000). 'Sharma, G.V.M.,Ilangovan, p. Mahalingam. A., Sreenivas. A.K. SZ615(2000).
172
Dilauroyl peroxide
tyor,
p-Diisocyanatobenzene. Nitrile oxide generation.t
Dehydration of nitroalkanes with a diisocyanatetriethylamine combination simplifies the product (of 1,3-dipolarcycloaddition) purification, becausethe urea byproduct is polymeric which can be filtered ofT.
5
rF
1Kantorowski, E.J.,Brown,S.P,Kurth,MJ. JOC 63,52'72(1998).
(.. /f\ xr-
Diisopropyl azodicarboxylate, DIAD. N-Debenzylation,t Benzyl ethers are unaffected when N-benzylamines undergo C-N bond scissionwith the title reasent.
X=NH,S Y = OAc, NPhth (
o
Boivin, J., Pothier,J., Zad,S.Z. Tl, $. ] r O l l i v i e r ,C . , R e n a u d P , .IACS122.6J%, 'Ly, T.-M., Quiclet-Sire,8., Sortair. B . /'Kaoudi, T., Quiclet-Sire,B.. Seeurn-S i
.o +
N=N
/)-o/
\ o / -
a
Dimanganese decacarbonyl. Radical reactions.
lnitiatron ,':
photochemical reaction in the prc..<-n
rKroutil, J.,Tmka,T.,Cemy,M. OL2, 1681(2000)
Dilauroyl peroxide. Radical addition,t The adductsof S-(ct-ketoalkyl)xanthatcsto allylamines (fiom by lauroyl peroxide)are useful precursorsof piperidines. reactioncatalyz.ed
t')
)
? ,\ , /
v
?u - s -^- o E^ t- + Il
l
3
+
Bz
svoEt
g
89o/o
Azidation.z On heating with EtSOrNr and dialuroyl peroxide in chlorobenzeneat 100', alkyl iodidesor xanthatesare translbrmedinto azides. Cyclizations. Indanes and indolines are readily tbrmed by treatment of 3butenylarenesand N-allylaniline derivativeswith a stoichiometricamount of dilauroyl ring adjoining an existing aromatic nucleus peroxide.:rFormation of a seven-membered by radical cyclization of xanthate precursorshas a useful scope.t Several different functionalgroupsinsidethe chain are tolerated.
>
(
3 l " J i : Jv: " " ' \ - - ) ( \ r u H a o c
|
V*rro.
-N'
Homocoupling and cross-coup Vn1(CO)'u.
Gilbefi,8.C.,Kalz,W., Lindsar.C.l . \k (2000). Gilbert, B.C.,Lindsay, C.I.,McCnrl.P T
.V,N' -Dimethoxy-N, N' -dimethl'lor.r Condensation I Reaction oi thr: l'unctionalizedbutenolides.
N,N'-Dimethoxy-N,N'-dimethyloxamide
173
syoer II !
[-
.,;lc: \\'ith a diisocYanate.,: e\ cloaddition)Purification, ll'
S
Y
il?JfJlv1
,->^\
"^"' F'H" ^ V*F
F'#" \-lrx)-
r. \'-hcnzylaminesundergo
35 - 54o/o
X=NH,S Y = OAc,NPhth,CN,
' Boivin,J.,Pothier, J.,Zard,S.Z.TL 40,31010999\. :Ollivier,C.,Renaud, P.JACS122,6496(2000). 'Ly,T.-M., B.,Zard,S.Z.TL 40,2533(lgg9). Quiclersire,8., Sortais, rKaoudi,T., B., Seguin,S.,Zard,S.Z.ACIEE39,73l (2000). Quiclet-Sire, HO Dimanganese decacarbonyl.
81%
Radical reactions. Initiation of the cyclization to fbrm five-membered rinssl D y a photochemicalreactionin the presenceof Mn2(CO)1qy is shown in the following.
u') lhltc\ to allylamincs(from 't piperidines.
\ (*)a
Mn2(CO)16
i-PrOH hv
Bz NHBoc
1J (*2
b. 43% (cisltrans1 :1)
o-'
t Tf S
B9o/o
:.croride in chlorobenzeneat ,rrncd by treatment of 3:,'rnctricamount of dilauroyl .rn cxisting aromatic nucleus rui scope.aSeveral different
Homocoupling and cross-coupling of bromides2 are efficiently achieved with Mn,(CO),,1. Gifbert,B.C.,Kalz,W.,Lindsay,C.I.,McGrail,PT.,parsons, A.F.,Whittaker, D.T.E.JCS(p1)llg7 (2000). Gilbert,B.C.,Lindsay, C.I.,McGrail,PT.,Parsons, A.F.,Whinaker, D.T.E.SC29,2ill (1ggg). .V,N' -Dimethoxy-N, N' -dimethyloxamide. condensation. r Reaction of this reagent functionalizedbutenolides.
with dilithiated B-ketoestersresults in
t74
chloride
N,N-Dimet\laminobenzotriazolylmethyleniminium
Heterocycles, Synthesis of su dienaminesand N-arylimines. r6pc(
,OH K
\
\
i-Pr2NLi / THF
78' ;
ofR'
R MeO-N
R
O
\ / /
/71 O
nru
C/i
N-OMe
ll R/)
l L a n g e r ,P , S t o l l ,M . A C I E E 3 8 , 1 8 0 3( 1 9 9 9 ) .
R'
N-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-N-methylmorpholiniumchloride. Activation of carboxylic acids. The coupling reagent 1, derived from Nreacts with RCOOH to methylmorpholine and 2-chloro-4,6-dimethoxy-1,3,5-triazine, form heteroaryl esters that are susceptibleto alcoholysisr and serve as transacylating agentsin peptidesynthesis.r The esterscan be convertedto aldehydesor alcohols on hydrogenationover Pd-C. Longer reactiontimes favor productionof the alcohols.:r
N,N-Dimethylfo rmamidnzp n, THF deliversR'NN:CHNMe, MeO
cl
\:ru / \ t N'r ')-,N1 F
N
(
\-o
nred
/
:Katritzky, A.R., Cheng, D., lrcmrng. (1996). rKatritzky, A.R., Denisenko, A.. Arend. ! 'Katritzky, A.R., Arend, M. JOC 8.98 'Katritzky, A.R., Huang, T.-B., Vomntor
(1)
I Kurishima.M., Morita, J., Kawachi, C., Iwasaki,F., Terao.K., Tani, S. SL 1255(2000). rFalchi. A.. Ciacomelli. G., Porcheddu.A., Taddei,M. SL 275 (2000). rFalorni, M., Giacomelli,C., Porcheddu,A., Taddei,M. JOC 64,8962 (1999).
chloride.
N,N-Dimethylbenzotriazol-1-ylmethyleniminium Preparation.l
2-Dimethylamino-2'-di-r-bu$dptc Diaryl ethers.r This elecrrm catalyzedsynthesisof diaryl ethen f
(
The stable salt I is obtained in92Vo yield by heating N-trimethylsi-
lylbenzotriazole with DMF and thionyl chloride in THF.
( \ N
"N
cl
N
Er(rvez (1)
br
rAranyos, A., Old, D.W.,Kiyomon ( 1999).
2-Dimethylamino-2'-di-/-butylphosphino-1,1'-binaphthyl 175
o "
Heterocycles. Synthesis of substituted pyridines2 and quinolines3 from ketones, via dienamines and N-arylimines, respectively, is by extraction of the [CH] unit from reagent 1.
\ Rn
:1"^R'
.g
R"
-
(l) THF A
-\ R' bolinium chloride. -.11!'nt l. derived from N! '1: : :ri. rcacts with RCOOH to l. . . .uid serve as transacylating :r hrdrogenationover Pd-C'
t
NC_./.r. ... NHz Y
a\ t \-,.-
*a>A
-r;;*
(ltcH2ct2,
t
t
ll
aY l
* I
\-,,'
N,N-Dimethylfurmamidrazones.a The reactionof hydrazineswith I in refluxing THF deliversR2NN:{HNMe2. lKatritzky, A.R., Cheng, D., Leeming, Ghiviriga, I., Hartshorn, C.M., Steel, P.l. JHC 33, 1935 (1996). rKatritzky, A.R., Denisenko, A., Arend,M. JOC 64,6076 (1999). rKatritzky,A.R., Arend, M. JOC 63,9989 (1998). lKatritzky, A.R., Huang, T.-B., Voronkov,M.V. JOC 65,2246 (20OO).
\ 5L 1255(2000).
\ '
6.t
I r1999).
hl,rri dt. :.')d by heatingN-trimethYlsit: l!
2-Dimethylamino-2'-di-f-butylphosphino1,1'-binaphthyl. Diaryl ethers.r This electron-richand bulky i?Nligand (1) facilitatesthe Pdcatalyzedsynthesisof diaryl ethersfrom phenolsandaryl halides.
r-ar \z\f rur,,r", .-*i-( \-\)J7
(1)
rAranyos, A., Old, D.W.,Kiyomori,A., Wolfe,J.P.,Sadighi,J.P.,Buchwald,S.L."/ACS121,4369 (1999).
2,7-Dimethyl-1,8-biphenylenedioxybis(dialkylaluminum)
4-Dimethylaminopyridine' DMAP. Esters. With promotion by DMAP the methanolysis of N-acyloxazolidinethionesr and N-acylthiazolidinethiones2is achieved at room temperature. DMAP has an ameliorating effect on the displacement of secondary alkyl sulfonates
A rapid Tishchenko
reacrion rr
propoxyal uminum.; analogue. : Ooi, T., Itagaki, Y., Miura, T.. l\tanx*r rOoi, T., Miura, T., Takaya, K.. \tantot
with inversion of configuration that employs CsOAc'' rSu,D.-W.,Wang,Y.-C.,Yan,T.-H. TL 40, 419'7(1999). 2Su,D.-W.,Wang,Y.-C.,Yan,T.-H.CC 545(1999). 3Hawryluk, N.A.,Snider,B.B.JOC 65,8379(2000).
hexachloroantimonate. N,N-Dimethyl-(l-benzotriazolyloxy)methyleneiminium Pepti.de coupling.t Excellent yields are obtained with the coupling reagent 1. Results are better than those of severalother reagents.
Dimethyl carbonate.18,l4.t: 20. lt Carbamates and ureas. Step carbonate by aminesleadsto carha
:Vauthey, I., Valot,F.,Gozzi,C.. Far-hr
.V,N-Dimethyl-2-(dimethylamioo I Carbonyl compounds.l .{n d halides to carbonyl products is empl Chandrasekhar, S.,Sridhar. M. ft {t- I
(1) ILi, P.,xu, t.c.TL40,3605(1999).
(lt)-3,3'-Dimethyl-1,1'-binaphthalene-2,2'-diamine. Asymmetric hydrogenationr The ligand enables the Ru-catalyzed hydrogenation ofketones to afford optically active alcohols(7 examples,-997o yield, ee9l-967o). IMikami, K., Korenaga, T., Ohkuma,T., Noyori,R. ACIEE39,3707(2O0O).
Dimethyldioxirane, DMD. 12. { l -1 144-146;19, 135-136; 20, l50- l Jl Epoxi.dation. A simple and cl acetone.rN,N'-Dialkylalloxansare I Trifluoromethyl ketones thar an with dioxiranes are subjecr to dc anchoringto silica.3 Iodohydrins.a A combinarroo convertsalkenesto iodohydrins.
Oxidation of aromatic contg arylisochromanesswhereas fl alanoo
2,7-Dimethyl- 1,8-biphenylenedioxybis(dialkylaluminum). 20' | 49 Redox reactions, Reversal of oxidation states in hydroxyaldehydes results when Oppenaur oxidation and Meerwein-Ponndorf-Verley reduction operate at the responsive functionalgroups.l
(5 mol%)
ts
I,2-Dicarbonyl compounds. o a-Bromo-arpenones." \\tFo of a bromineatom at the a-positionn
Dimethyldioxirane, DMD
f' ts].:
I \ -ec)loxazolidinethiones ..(lndan alkyl sulfonates
n ht rachloroantimonate. J ... ::. rhc coupling reagent
177
A rapid rishchenko reaction occurs when aldehydes are exposed to the bis(diiso_ propoxyaluminum) analogue.2 .9"i, I, Itagaki,Y, Miura,T.,Maruoka,K. TL 40,2137(lssg). iOoi, T., Miura,T., Takaya,K., Maruoka, X. ft n,iiSS f I)SSI. Dimethyl carbonate. lg, 144; 20, 150 carbamates and ureas. Stepwise displacementof.the methoxy groups of dimethyl carbonateby amines leads to carbamates and then ureas., lVauthey,I., Valot,F.,Gozzi,C., Fache,F.,Lemaire, M. TL 41,6347(Z0OO\. N,N-Dimethyl-2-(dimethylamino)anitine
N_oxide. carbonyr compounds.t An alternative to the Kornbrum method for conversron of halides to carbonyl products is employment of this reasent. 'Chandrasekhar, S.,Sridhar, M. TL 41,5423(2000.,. Dimethyldioxirane, DMD. 12,413;13, 120;14, l4g; lS, 143_144;16, 142_144; lg, 144-146; 19, 135_136:20, 150_152 Epoxidation' A simple and efficient protocol for alkene epoxidation uses DMD in acetone.rN,N,-Dialkylalloxansare now found to be effectivecatalysts.2 Trifluoromethyl ketones that are frequently used for mediating alkene epoxidation with dioxiranes are subject to degradation. A stabilized form is made by covalent anchoringto silica.l A. R.r-catalyzedhydrogenation r ield,ee 9l-9670). - -
I r{)).
Iodohydrins.a A combination of DMD and MeI generates HoI, which readily convertsalkenesto iodohydrins. oxidation of aromatic_ compounds, 3-Aryrisocoumarins are obtained from 3arylisochromanes5whereasflavanones *" o*yg"nur"d in the aromatic rins.6
El'.l{). I,l9 h . .:: ,rr aldehydesresults when u. :: ()perateat the responslve
OMe O _ 100%
78%
1,2-Dicarbonyr compounds. a-Diazoketones are readily oxidized.T a-Bromo-a,B-enones.8 when enonesare treated with DMD and NaBr, introduction of a bromine atom at the o_position results.
t78
Dimethyl(methylthio)sulfonium tetrafl uoroborate
rFerraz,H.M.C., Muzzi, R.M., de O.Vieira,T., Viertler,H.TL4l' 5021 (2000)' 2Camell, A.J., Johnstone,R.A.W., Parsy, C.C., Sanderson,W.R. TL 40,8029 (1999)' 3Song,C.8., Lim, J.S.,Kim, S.C.,Lee, K.-J., Chi, D.Y. CC 2415 (2000). aAsensio, G., Andreu, C., Boix-Bernardini, C., Mello, R., Gonzalez-Nunez,M.E. OL 2,2125 (1999). 5Bovicelli,P, Lupattelli, P, Crescenzi,B., Sanetti,A., Bemini, R' 255' 14719(1999)' 6Bernini, R., Mincioni, 8., Sanetti, A., Mezzett| M., Bovicelli, P. TL 41, 1087 (2000)' TDarkins, P., Groarke, M., McKervey, M.A', Moncrieff, H.M., Mccarthy, N., Nieuwenhuyzen, M' JCS(Pl) 381 (2000). sRighi, G., Boviclli, P.,Sperandio,A. ?I 40, 5889 (1999).
Dimethyl disulfide. (Jnsymmetrical
2,S-Dimethylphenacyl chloride. Photoreleasable esters.t .{ mc't}x obtained by O-alkylation of acrd. r th!' &rrd decompositionthat regenerates
1
0
,\-\-t'
l
l
l
Y Disproportionation
disulfides,t
between
a symmetrical
+
1
l
0
,\-^
l
Y
disulfide
Klan,P.,ZabadalM., Heger.D. 01-l. l:.,
with MeSSMe (NaOH) gives rise to RSSMe. rKamiyama, H., Noguchi, T., Onodera,A., Yokomori, S., Nakayama, I. CL755 (1999)'
Dimethyl 3,3'-dithiodipropionate. Methyt acrylilte precursor.t A heterocyclic NH is converted into the underbasicconditions' moietyby thereagent NCH2CH2COOMe
2,6-Dimethylphenylsulfi nyl chloridcKetimine radicals.' Ketorrmr'. chlorides via homolysis of thr' ,.ri
rccombination by steric hindrancc r. undergoother reactionssuchas intrenx
I Hamel, R., Girard, M. JOC 65,3123 (2000).
try.f
N,N-Dimethylformamide-phosphorylchloride. 18' 146;20, 153 Formylations. Direct conversionof silyl ethersto formic estersroccursat 0' with ketones.z DMF-POCl3.Silyl enolethersgivect-hydroxymethylene IKoeller.S..Lellouche,J.-P.TL 40,'1043(1999). 2Jameleddine, M. SC30' 2759(2000). K., Bechir,B.H.,Mustapha,
Dimethyl(methylthio)sulfonium tetrafl uoroborate. Furans.t The reagent activates thioacetal function by methylthiolation. Tt induces cyclization of thioacetals derived from carbonyl compounds (including lactones and lactams) and bis(methylthio)acetaldehydevia aldol reaction and acetylation.
+
\i,i
B
HONr'-S.M.Oi- l. ni' Lin.X., Stien,D.,Weinreb,
Dimethyl phosphite. Debromination.t l, | -Dibromt'al (McO):POH-EtrN of to lurnish thc , f-
S. fI- al ' Abbas,S.,Hayes,C.J.,Worden.
Dimethyl sulfonium ylide. 18, l-19 Allylic alcohols.' Epoxides arc constructpolyhydroxylatedcarboncha F
;
Q
OR
\q
rPadwa.A., Ginn, J.D., McClure, M.S. OL 1, 1559 (1999).
F
Me3Sl
BuLi THF
?* tl
Y
OH
Dimethyl sulfonium ylide
0: - . . I 9 9 9r .
{l
Lr, . \r F, oL 2.2t25 (t999) :-le r1999). L . t r- rl00O). .-_ I . \.. \ieuwenhuyzen, M
'..
l7g
2,S-Dimethylphenacyl chloride. Photoreleasable esters,t A method for carboxyl group protection is based on esters obtained by o-alkylation of acids with the phenacyl chloride. The photochemical decomposition that regeneratesthe acids does not requre photosensitizer. a
Ai.-. ?
+
hv.$"
Arfl-o** ?
A
?
+
R
C
O
O
H
., \\mmetrical disulfide
r,'
K I a n ,P , Z a t : a d a lM , . , H e g e r ,D . O L Z , 1 5 6 9 ( 2 0 0 0 ) .
.
r
{ t,
D. Tr.
-55t1999).
converted into
the
.
2,6-Dimethylphenytsulfi nyl chloride. Ketimine radicals-t Ketoximes are deoxygenated on treatment with sulfinyl chlorides via homolysis of the oxime surfinates. when suppression of diradical rccombination by steric hindrance is exploited, imine radical intermediatestend to undergoother reactionssuchas intramoleculzuaddition.
_A--
< l
o
/),-/
J.tr-rsloccurs at 0' with
tr'
i-P12NEl
a S cl
HoN/--
PhSe-SePh cH2cl2
Lin,X., Stien,D.,Weinreb, S.M.OL 1,6370999).
, ::..:hrlthiolation.It induces r-.:. rncluding lactones and a:..:.r!ctYlation.
-)-t"" -,-o
Dimethyl phosphite. Debromination.t l,r-Dibromoarkenesundergo monodebromination by the action ol' (MeO),POH-ErrN to lurnish the (E)_bromoalkenes. Abbas, S.,Hayes. C.J.,Worden, S. fL 41,3215(2000). Dimethyl sulfonium ylide. 18, 149 Allylic alcohols.r Epoxides are homorogatecr,and this reaction can be use
\q
?* ll BuLi THF
\./
I oH
+
?* Do \,..'
I 6n'
Mejs,o Buti rHF
R a
\rto' OH
Dimethyltitanium dichloride IDavoille, R.J., Rutherford,D T, Christie' S'D R' fL 41' 1255 (2000)'
149; 20' 154-155 Dimethyl sulfoxide. 13,124',16, 149;18' aldol and Michael reactions involving Spontaneous Al.dol and Michael reactions't temperaturein dry DMSO' silyl ketene acetalsare observedat room ---' to bromoalkenes bY (E\-Bromoalkenes.2 gem-Borylbromoalkenesare transformed DMSO, which actsas an oxidizing agent' alcohols are converted to l'3-dioxolanes Oxidative acetalization.l Secondary presenceof DMSO and 1'2-ethanediol' directly in a Re-catalyzedoxidation in the rGenisson, Y.,Gonichon,L TL 4l' 4881(2000)' K ' Arase'A' CC62'7(1999\' tH"rii, fnl.,f-"ta, H', Shirakawa, (1999)' 3Arterbum, OLl,'769 Mr'C' Perry, J.B.,
rDuncan, D., Livinghouse. T' OV ll
DimethYltitanocene. Alkl-r Hydroamination. presenceof CP2TiMe2.r':Imrr< sis results in ketones. An intramolecular version u lactam.3
chloride' Dimethyl sulfoxide-2-chloro- l,3-dimethylimidazolinium to the Swern is comparable EtrN with Oxid.ation.r This combinationtogether reagent.
a*"' \-----Ph
I lsobe,T., Ishikawa, T. JOC 64,5832( 1999)'
Dimethyl sulfoxide+xalyl chloride' of a primary silyl ether to an Desilylative oxidation.t Selective transtormation ethersis achieved' aldehydewithout afTectingsecondarysilyl
OSiEt3
*m:''-"',,:-f-^#; OSiEt3 " :
Lactones' MethYlenauo bear a vinYl grouP at a carbn give lactones.a
DMSO-(COCI)r:
^
(.L]O
:
z< :
l
r \ n tl
o rRodrisuez,A.'Nomen,M,Spur'BW'Godfroid'J'J'TL40'5161(1999)'
DimethYltin dichloride' MonobenzoYlation.l
with BzCl and I.2-Diols form monobenzoateson reaction
2-M ethYleneazetidincs' whenthe substratebearsa str
Me2SnClz. Y' JOC 65' 996(2000)' W'' Matsumura' rlwasaki,F.,Maki,T., (Jnomura, O'' Nakashima'
DimethYltitanium dichloride' cyclization to pyrrolines under the influence Cyclization'r 4-Alkynylamines undergo ofMe2TiCl2.lnsome.u,"t,"huinextensionatthealkyneterminalcanbeefl'ected'
rHaak,8., BYtschkov,I.' Do1-e-S rHaak, E., Siebeneicher,H'. Do!' 'Fairfax, D., Stein, M.' Livinglr lDavidson, J.E.P., Anderson. E R.H., Holmes,A.B. CC 629 { l0 5Martinez,I., Howetl, A.M' IL {
Dimethyltitanocene
5 _ . .
+
SiMe3
\
T
i
/
o" - 25"
,cl
'Cl /\/"^ tl n
L < i
,: .j \lichael reactionsinvolving r. :: . I)\lSO. r- ,::.lirrrnedto bromoalkenesby
181
)cVL87%
|
.,rnrcrted to 1,3-dioxolanes l ' \ 1 . r t . r n d1 , 2 - e t h a n e d i o l .
lDuncan. D.. Livinghouse.T. OM 18.4421 (1999).
Dimethyltitanocene. Hydroamination. Alkynes are converted to enamines on addition of amines in the presenceof Cp2TiMe2.r'2Immediate reduction provides stable products, whereashydrolysis results in ketones. An intramolecular version in which an acyl cyanide is added leads to the vinylogous lactam.3
1."
niunr ehloride. \ . - ,ntparableto the Swern
/_NH, ':-Hn
+
Cp. ,z rHF 2s" Ti 'ct +
/
/\/",
tl o
,/-NH
\,UI
O
Ph
87% , prinrary silyl ether to an
Lactones, Methylenation (Cp2TiMe2in refluxing toluene) of cyclic carbonatesthat bear a vinyl group at a carbinolated carbon is followed by a Claisen rearrangement to sive lactones.a
1artrt^
: -- -cHo Y
OBn
I
osiEt3
:
o
A
-\r'
Cp2Til\,,|e2 PhMe A
n
ll
I 9 9 9) .
o
o 52%
. {,n rcaction with BzCl and
2-Methyleneazetidines. Methylenation of B-lactams by the title reagent is efficient when the substratebears a strongly deactivating N-substituent (e.g., N-Boc derivative).5
: t()('65.996(2000).
rHaak,E'.,Bytschkov, I., Doye,S.ACIEE38,3389(1999). :Haak,E., Siebeneicher H., Doye,S. OL2,1935(2000). rFairfax,D., Stein,M., Livinghouse,T., Jensen, M. OM L6,1523(1997). aDavidson,J.E.P.,Anderson,E.A., Buhr, W., Harrison,J.R., O'Sullivan,P.T.,Collins, I., Green, R.H.,Holmes,A.B. CC 629(2OO0). sMartinez,I., Howell,A.M. TL 41,5607(2O0O).
pr rrolinesunderthe influence : ltlinal can be effected.
Diphenylphosphorazidate
Diphenylammonium trifl ate. Esterifi.cation.r Heating carboxylic acids with alcohols in toluene at 80' in the presence of Ph2NH2OTi (l molzo) furnishes esters (12 examples, 78-96Vo). The same catalyst can be used in transesterification. Improved yields are obtained by adding MerSiCl as cocatalyst.
{+R
rWakasugi, Y TL 4l' 5249(2000). K., Misaki,T., Yamada,K., Tanabe, Diphenyl diselenide. 13, 125; 18, 15 1-l 52; 19, 140-141; 20, 157-158 Coupling reaction.t Photoinduced three-component coupling combines an alkene (enol ether, silyl enol ether, l,3-diene, etc.) and ethyl propiolate to form a carbon chain in which the two PhSe groups from PhSeSePhare separately located. The reaction starts from B-addition of PhSe radical to the ester.
Bna oz * ,.o"Z
PhSe-SePh
:Evans.D.A.,Wu, L.-D.,Wiener.JJ . ( 1999).
2,6-Diphenyl-4ll-thiopyran4d reactio ttBaylis-Hillman thiopyranone is combined rrith T(
tno)t^r'"'n
Ph
SePhCOOET
oAo
a\ *rn$
rOgawa,A., Doi, M., Ogawa,L, Hiao,T. ACIEE38,2021 (1999).
perchlorate. of E-cyclopropyl-1,6-unsaturated hydroacylation Intramolecular Cyclooctenones.t is carried out under ethylene to (dppe)RhClOa. reaction This by is effected aldehydes
(Diphenylphosphinoethane)rhodium(I)
suppressthe decarbonylationpathway.
+"r
R
o (dppe)RhclOa H2C = CH2
cr'\zc|
\
t
oH
rlwama.T.. Kinoshita, H., Katao\l.T
t
P?\--y' 65Yo
rAloise,A.D.,Layton,M.8., Shair,M.D.JACS122,12610(2000).
Dodecylbenzenesulfonic acidMannich reaction. The su proves to be a most effective cate aldehydesand o-anisidine.'Actru
rManabe, S K., Mori,Y.,KobaYashr. rManabe, S. OL l. lc K., Kobayashi, Diphenyl phosphorazidate. pAmino acids,l A method involving asymmetric alkylation of chiral Nacyloxazolidin-2-ones with l-butyl bromoacetateand saponification furnishes substituted succinic monoesters.On submission to degradation by (PhO)zPONj, properly protected B-amino acids are obtained.
Dysprosium. Propargylntion of carbonyl promotes formation of homoProP
Dysprosium
l8J
o*,oBn rn toluene at 80" in the ilc:. 78-967o).The same .rrc obtained by adding
t
I -\r-NH
gPn Et3N / PhMe ; * Pho-i-Ns BnOH A
YcooH \,-oV
I
I \,,o.-"/ l l 1 r- ' n
[.,
76Vo
20. i--158 t . ..nlrngcombines an alkene r, : . r,, torm a carbonchainin :1. ,i.rtcd. The reaction starts
rEvans,D.A.,Wu, L.-D.,Wiener,J.J.M.,JohnsonJ.S., Ripin, D.H.B., Tedrow,J.S. JOC g,64ll ( 1999).
2,6-Diphenyl-4II-thiopyran-4-thione. Baylis-Hillman reaction.t A useful catalvtic svstem is formed when the thiopyranoneis combinedwith TiClo.
' -lz-s"Pn
Ph
>::r COOET
o-\"
*
s\ l
!
+
cl
ricr4
Ph'l\,As
s^\zLoricrs / /
r
Ph
. i lopropyl-1,0-unsaturated
(-"'
:rtl out under ethylene to
-
+eZ\ v
t
*
i
l
i
pn'\.Ast\fo
RCHO
|
l
l I
R
oricr,
Ilwama,T., Kinoshita,H., Kataoka,T. TL 40,3741(1999).
Dodecylbenzenesulfonic acid. Mannich reaction. The sulfonic acid is both a Bronsted acid and a surfactant. It proves to be a most effective catalyst for promoting condensationof silyl enol ethers with aldehydesand o-anisidine.r Actually, other arylamines and ketonescan be used.2 lManabe, K., Mori,Y.,Kobayashi, S. SL 1401(1999). 2Manabe, K., Kobayashi, 5.OL1,1965(1999). :i:. .rlkylation of chiral No:- :.-.1tlonfurnishessubstituted P:., r PON., properly protected
Dysprosium. Propargylation of carbonyl compounds.r promotes formation of homopropagyl alcohols.
This metal in the presence of HgCl2
Dysprosium(Ill) trifl ate tLi,Z.,Jta,
r84
Y , Z h o u ,J . S C 3 0 , 2 5 1 5 ( 2 0 0 0 ) .
Dysprosium(Il) iodide. Alkylation of carbonyr compounds.t The Barbier-type reaction is mediated by DyI2 in THF. The reagent, possessinga reactivity pattern similar to that of (thf )JmIr, must be preparedjust before use. Reductinns') The complex (dme)iDyl2 is a reducing agent whose reactrvity lies between Birch reducing agents and Sm(II) and rm(II) salts. It can be used to convert tolane to (Z)-stilbene and naphthaleneto the r,4-dihydro derivative. rEvans,W.J.,Allen, N.T.,Ziller, J.W.JACS122,Il74g (2000).
Dysprosium(Ill)
trifl ate. cycloadditionr In the presence of Dy(orf)q aromatic aldehydes and arylamines form aldimines in situ, and then react as heterodienestoward enecarbamates.
Ethanesulfonyl azide. Azidoalkanes.r A prep peroxide to add a carbon r decomposesby extrusionof r chain reaction on.
o.o-$, rOllivier,
C., Renaud,P r{(i
,
ll:
BnOOC. BnOOC
j"r1
\
\,/
.,')2
Dy(OT03
iR'
IVeCN
')7
R+ \
2-Ethoxy-1-ethoxycarbong I Activation of *hydrot temperature. Whenan aminer n v
lBatey,R.A., Simoncic,pD., Lin, D., Smyj, R.p., Lough, A.J. CC 651(19gg)
tl \ , \ 'ot * HzN\ Y OH
rHyun,M.H.,Kang, M.H..Han.S
Ethylaluminum sesquichlorN Frtedel-Crafts alblab chloroformate acts as an alkrle
11 ( / * o rBiermann. U . . M e t z g e rJ. . O .. . 1 ( 7
Irrsprosium(Ill)triflate
lM
r-:.rc rcaction is mediatedbY r. ':nrilar to that of (thf ).TmI2' r:.- .11!-ntwhose reactivity lies r..r- lt can be used to convert -rltve.
d;:.
Ethanesulfonyl azide. Azid.oalkanes.r A preparation of RNj from RI involves initiation by dilauroyl peroxide to add a carbon radical to a nitrogen atom of the reagent. The adduct decomposesby extrusion of sulfur dioxide and an ethyl radical, the latter then carries the chain reaction on.
*o$r
. ?uri'
dilauroylperoxide PhCl/ heptane
o.o$*.
a
, .rldehydesand arylamines -'nccarbamates.
84To lOllivier,C., Renaud,P.JACS122,6496(2000).
BnOOC. 2-Ethoxy- 1-ethoxycarbonyl- 1,2-dihydroquinoline. Activation of u-hydroxy acids.t The derivatization is complete at room temperature.When an amine is present,the carboxyl group is transformed into an amide.
,
l()qg)
o tl \ ,/\. / 'on + HzN'v Y
e).\ t
\,
OH
i
l
tl \ ,/\ ,'^\. ./ Y
l
ru oet cooEt
N
V
5HH 97Yo
lHyun,M.H.,Kang,M.H.,Han,S.C.TL40,3435(1999). Ethylaluminum sesquichloride. alkylation.t Under the influence Friedel-Crafts chloroformate acts as an alkylating agent for alkenes.
O. ",io! rBiermann, J.O.ACIEE38,3675(1999). U., Metzger,
of
EtiAl2cli
isopropyl
186
Ethyl diphenylphosphonoacetate
N-Ethyl-2-bromo-4-methylthiazolium tetrafl uoroborate. Peptide couplings,t This reagent is particularly useful for coupling of hindered amino acid derivatives. rLi,P.,Xu,J.C.TL 40,8301 (1999).
rAndo,K., Oishi,T.,Hirama.\l .
Ethylenebis(triphenylphospl Alkylation.t Displacenr nucleophiles occurs in the pre
Ethyl N-benzyloxycarbonyloxamide. Gabriel synthesis.t Following N-alkylation of the oxamide, selective saponification removes the ethyl ester to afford RNHCOOBn. The N-Boc derivative is similarly transformed.
o o *oot.f\cooEt Rooc.N&cooEr'B"oIlDMF,
LioH
o
4A','oec'
H
ROOC.
R ' O
H I I
cl
N K
R = t B u .B n
Hydroboration and bon lato)diboron is mediated h1 r ketones(a net regioselecrrreI undergoborativecoupling *rd
'Berree,F.,Bazureau, J.-P,Michelot,G.,Le Corre,M. SC29. 2685,1999). Ethyl cr-chloro.or-phenylselenoacetate.
* Ph7\,
,n{
Pictet-Spengler cyclization.t Ethyl tetrahydroquinoline-1-carboxylatesare readily preparedfrom a reaction (catalyzed by SnClo) of phenethylaminesand the ester. lSilveira,C.C.,Bemardi,C.R.,Braga,A.L.,Kaufman, T.S.T4 40, 4969(1999). f -Ethyl-3-(3-dimethylaminopropyl)carbodiimide. Dehydration.t a-Substituted cinnamic esters are obtained stereoselectively from the benzylic alcohols[anli-alcohols-> (E)-alkenes;syn-alcohols-> (Z)-alkenesl.
N,-\
OH
tl
tn"^lrCooMe I L
F unctionalization of aILl thio groups to alkynes.Disulf is regioselectiveand stereo,.,e lc
+
tl
r,'N
nreq
Me2NJ
I
cucr2
'*;:
Cl
pht\y'COOM"
(,.oras 99lo
' S a iH . . ,O h m i z uH. . T L 4 0 . 5 0 1(91 9 9 9 ) . Ethyl diphenylphosphonoacetate. Emmons-Wadworth reaction.t (Z)-2-Alkenoic esters are the overwhelmingly major products. The reaction is carried out in the presenceof DBU and NaI.
( \ ) CoH +
S $
+
\ \ / cl
rKadota,J., Katsuragi, H.. Fu\unx rLawson,YG., Lesley, M.J.G.. \L 'suginome, M., Nakamura.H.. \L 'Han, L.-B., Tanaka.M. JACS lll
Ethylenebis(triphenylphosphine)platinum(0)
rAndo. K., Oishi, T., Hirama, M., Ohno, H., Ibuka, T. JOC 65' 4'745(20oo).
l.
!.:.r. l()r coupling of hindered
Ethylenebis(triphenylphosphine)platinum(0). acetateby of thevinylic chlorineof 2-chloropropen-2-yl Alkylation.l Displacement of thePt complex. occursin thepresence nucleophiles
tr:: .,lc.'elective saponification \ . lJ,'e derivative is similarlY
lc : =:
R O O C . - . ,H N l,
LroH
K
i' ' 4)--,,-,oAc
I
--J
.a.oo=, v\
ll-ereena,
Na*
! I
.,1999).
r'^..../.OPh 53%
Hydroboration and borative coupling. O,C-Diboration of enones by bis(pinacolato)diboron is mediated by the Pt-complex.2 Hydrolysis of the adducts gives B-boryl ketones (a net regioselective hydroboration of the conjugated double bond). 1,3-Dienes undergo borative coupling with B-silylpinacolatoborane in the presenceof aldehydes'1
qlk ,, Ph<
/ / \ p +
I -carboxylatesare readilY nc'ralld the ester.
t
cooEt \-cooEt
PhoNa
COOET
ph-<
\
+ P h - S i - B'^zt. I /
E
t
V
\
||
,zB-o
-
etteen.t,
octane
..p{
'120"
pn-si...
Ph 79To
from nc.l stcreoselectivelY '1. -> (Z)-alkenesl.
u.
Functionalization of alkynes.a The Pt-complex catalyzes the addition of silyl and thio groups to alkynes. Disulfides and disilanes are sources of the addends.The reaction is regioselectiveand stereoselective.
cl
., Ph"\acooMe (-.ores ;
C1
CoHrs +
99To
\ \\ cl
c.r.:. cr
ilfc the overwhelmingly
: [)BU and Nal.
S -5
//
CoHrs
ll - ptrpptr.t,
tl . "'tt'rr,",. +
P h l \ , l e1 1 0 ' ; Et3N/ EIOH
ct<
/,----\ ):.. 'si(oEl3 )-d 83To
I Kadota, J., Katsuragi, H., Fukumoto, Y., Murai, S. OM 19' 9'19(2000)' rLawson,Y.G., Lesley,M.J.G., Marder,T.B., Norman, N.C., Rice, C'P.'CC 2051 (1997) rSuginome, M., Nakamura, H., Matsuda, T., Ito, Y. JACS 120' 4248 (1998)' lHan. L.-B.. Tanaka.M. JACS 120,8249 (1998).
'Chambers, R.D.,Spink,R.C.H.C(- ril rBowden,R.D.,Comina,P.J.,GreenhalI
Ferrocene. ferroceneconvertssulfoxides Reductionof sulfuxides.l Togetherwith (cF3CO)2O, into sulfidesat roomtemperature. rKobayashi, K., Kubota, Y, Furukawa' N. CL 400 (2000)'
9-Fluorenylmethylchloroformate. to 99-Fluorenylmethylesters,l The title reagentconvertsN-protectedaminoacids (10 molTo)' DMAP (1 and equiv) i-Pr2NEt of estersat 0' in thepresence fluorenylmethyl
N-Fluorobenzenesulfonimide. Il. N-Fluorosulfunamides.: Flu fonamides(as K salts)is facile. rTaylor,D.M.,Meier,G.P.Il 41. l:91
Fluoroboric acid. pAmino carbonYl comprr silyl acetalsis promoted b.r-HBF. t a surfactant2). 2,3-Dihydro-yPYridones.' water alone or aq MeOH.
.t
rMerette,S.A.M., Burd, A.P.,Deadman,J.J.TL40' 753 (1999)'
Me3SiO Fluorine. 13, I 35; 14, 167; 15, 160; 18, 16I ; 19, 146: 20, 165 Fluorination of pyridine, quinoline, and quinoxaline Heteroaromatic fluorination,t when an systems occurs with fluorine-iodine mixtures. Pyridine is alkoxylated appropriate alcohol is Present. nitrogen) Fluorination at unactivated.carbon sites. With fluorine gas (diluted with Thus' quite efflcient'2 be can such a reaction in MeCN at the temperature of ice fluorinated is decalin that yield. Note fluorocyclohexane has been obtained in 63Vo by lexclusively at an angular position whereas the secondarycarbon sites are attacked bis(tetrafluoroborate)' chloromethyl-4- fluoro-1,4-diazoniabicyclo[2.2.2)octane A microreactor has been designedfor use with elemental fluorine'r Arylsulfur pentafluorides.a Diaryl disulfi des undergo this transformation.
OMe
iAkiyama,T.,TakaYa, J.,KagoshrnnI :Akiyama,T., Takaya,J., KagoshrnnI 'Akiyama,T., Takaya,J., Kagoshrrna|
l -Fluoro-3,5-dichloropyridiniul Phenol oxidation't The trtk mild conditions.When a MO\l ed fluorination at the central methl la
,No'
1/ \\ S_5
r\
V
/ F2-N2/MeCN +
SFc
-
\ / ozN 41%
ozN
rChambers, R.D., Parsons, M., Sandford, G.' Skinner, C'J', Atherton' M'J" Moilliet' J'S' "/CS(P1) 803 (1999). 2Chambers,R.D., Parsons,M., Sandford, G., Bowden, R' CC 959 (2000)' 18E
OMe
1-Fluoro-3,5-dichloropyridinium trifl ate rChambers,R.D., Spink, R.C.H. CC 883 (1999). lBowden, R.D., Comina, P.J.,Greenhall,M.P., Kaduki, B.M., l-oveday,A., Philip, D. ? 56, 3399 (20m)
20, 165-166 N-Fluorobenzenesulfonimide. N-Fluorosulfonamides.t Fluorine transferfrom the reagent(PhSO)2NFto sulfonamides(asK salts)is facile. ) ( ) :.rrocene converts sulfoxides
rTaylor,D.M.,Meier,G.P TL4l,329l (20OO). Fluoroboric acid. pAmino carbonyl compounds. Condensation of aldehydes, amines, and ketene silyl acetalsis promotedby HBFa in an aqueousmedia (aq i-PrOHr or in the presenceof
rr:. \ -protectedamino acidsto 9I . .-urv ) and DMAP (10 mol7o).
a surfactant2). 2,3-Dihydro-ypyridones,s water alone or aq MeOH.
rtteasioT !). . h:
'r..r.r.. quinoline,and quinoxaline rt.j::'i ls alkoxylated when an !u ::::.' gas (diluted with nitrogen) x -.,:: he quite efflcient.2 Thus, \ :r rhat decalin is fluorinated l^r-.-.rrht)nsitesare attackedby lr - . :r-trafluoroborate). r:.:-,. lluonne.S lc:; lhrs transformation.
/
-
OMe
A facile hetero-Diels-Alder reaction takes place in
.tPh ll r'\
H B F 4/ H 2 O + MeOH
H2N- Ph
opPh \/,NPh 95%
rAkiyama, T.,Takaya, H. SZ 1045(1999) J.,Kagoshima, 2Akiyama, T.,Takaya, H. SL 1426(1999) J.,Kagoshima, rAkiyama,T.,Takaya, J.,Kagoshima, H. TL 40,7831( 1999) 1-Fluoro-3,5-dichloropyridinium trifl ate. Phenol oxidation.' The title reagentoxidizes substitutedphenols to quinones under mild conditions. When a MOM ether is present,it is concomitantly transformed (likely by fluorination at the central methylene group) and hydrolyzed on workup.
OMe OMe
I
\r/ t-N 41%
ct"1'ct |J-i,/ rro
i cH2ct2 0o
:,,n. \'1.J.,Moilliet,J.S.JCS(P1) : xx)).
o
HN/O
I oz\ 697o
Fluorotris(trimethylsilyl)methane
'Martinez,E.J.,Corey,E.J.OLl,'75(1999).
1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate). Fluorination.t This new reagent, which that needs no special caution or glassware in handling, can be used for fluorination of aromatic rings, alkenes, enol ethers, and dienol acetates.In the presenceof ZnCl2, either mono- or difluoro derivatives of active methylene compounds can be isolated from its reactions. Preparation of the reagent is simple. It involves passing a stream of fluorine (l\vo in nitrogen) to a mixture of DABCO-N-oxide, boron trifluoride. and tetrafluoroboric acid at 0o.On evaporation,the solid is collected and washedwith DME (157a yield). rPoss, A.J.,Shia,G.A. TL40.2673,19994.
Fluorous reagents and ligrnd Improvement of organrc r liquids has beenthe subjecrof natedchain (fluorousionic lrqr
tional ionic liquids. Thus emu facilitated.r
Hydroxyl protection. Fl sulfoxide 2 is available t'or Cp2ZrCl2-AgClOa. The flucr stability.aA method for selerrr by organotin oxides is also mq
tl
cr-Fluoromalonaldehyde. (Z )- p Acy loxy - e-fluo roacry lalde hydes. I
After generation from the fluorinated enol sulfonate the sodium salt of this aldehyde reacts with acid chlorides to orovide the substitutedacroleins.
ol
cur,r*C (1)
F
I
Fl2CHoTs I F
NaoH
;r.-*o*
I
oHc__ cHo
t
r
9
"n"o"'-
pnAo-\f
|
J
F Na*
cHo
i
92To
lFunabiki, K., Fukushima, Y., Matsui, M., Shibata, K. JOC 65.606 (2000).
Fluorotris(trimethylsilyl)methane. Fluoroallyl alcohols.t The reagent,obtainedby silylationof lithio derivarives from tribromofluoromethane, servesas a fluorinatedC1 nucleophile.Thus, its reactionwith aldehydes in thepresence of KF-l 8-crown-6leadsto fluoroallylalcohols.
Br I
Br-f-gr F
OH
SiMe3 Me3SiCl
+
I
Me3SitSiMe3 BuLi
F
pncrn
----!
KF - 18-crown-6 DMF
97%
Silyl enol ethers.6 The ro media has operational advanr2t
Reductions, The reducu fluorous BINOL (chiraly denrr The use of fluorous tin hldndc dehalogenation.6 Fluorous-phasesoluble h1< acryloxysuccinimide-contarnrn henceWilkinson catalyst analo!
M iscellan eous reac tio ns. solvents while employing a 0
diaryl diselenide used to a-islsrr A multicomponentcouphnt and rapid Stille couplings are with microwaveirradiation. '
o*-\---Cnen
t.
F
q
72Yo
CN CuH'trtl + C O + /
rShimizu,M., Hata, T., Hiyama, T. BCSJ 73,1635 (2000).
Fluorous reagentsand ligands
llrt rafluoroborate). l .:rirel caution or glassware Lg:-.,lkcnes,enol ethers, and J::r.r,)r()derivativesof active | : -irCdr.llof fluorine (lOVoin t . .,rJ tctrafluoroboricacid at -rqr yield). ,\1i.
tr()m the fluorinatedenol .hlorides to Provide the
a\
Fluorous reagents and ligands. Improvement of organic reactions by the use of fluorous components and ionic liquids has been the subject of intense research.Imidazolium salts that carry a polyfluorinated chain (fluorous ionic liquids) are found to act as surfactantswhen added to conventional ionic liquids. Thus emulsification of fluoroalkanes with the ionic liquid phase is facilitated.' Hydroxyl protection. Enol ether I has been developed.2 A tetrahydropyranyl sulfoxide 2 is available for the formation of mixed acetalsr upon activation with Cp2ZrCl2-AgClOa. The fluorous bromosilane 3 form siloxanes with improved acid stability.4A method for selective tosylation of diol systemsthat is known to be catalyzed by organotin oxides is also modifiable in terms of fluorinated catalysts.s
Cf;Till.-*,,,
o) I CsF17,,,,,,"...#CsF17 (1)
o
-
il o^An'\.t"' -
^,,^ l F
92%
b
r':
:r of lithio derivativesfrom .e Thus, its reaction with
n . r .I :rlcohols.
OH I
: =..
>
Silyl enol ethers.6 The reductive silylation ofenones with hydrosilanesin fluorous media has operational advantages. Red.uctions. The reduction of a-alkoxyketones with SmI2 in the presence of fluorous BINOL (chiral) derivative shows that the protonation step is enantioselective.T The use of fluorous tin hydrides that are highly soluble in fluorinated solvents facilitates dehalogenation.n Fluorous-phase soluble hydrogenation catalysts are obtained by conversion of Nacryloxysuccinimide-containing fluoroacrylate polymers into phosphine ligands and
- ' r t r
'l::
(3)
(2)
henceWilkinson catalyst analogues.' Miscellaneous reactions. The Heck reaction is accomplishable in perfluorinated solvents while employing a fluorous triarylphosphine ligand.r') A minimally fluorous I diaryl diselenide used to assisttin hydride mediated cyclization can be recovered.r A multicomponentcoupling involving fluorous allyltin reagentshas been reported,r2 and rapid Stille couplings are completed employing aryltris(polylfluoroalkyl)stannanes with microwaveirradiation.Ir
^-)-'-//CHP\ Trr f F
CoFr:--f
72Yo
CN C u l r r t ' * C O * )
*
o Lf_Sn '3
\
CN
A'BN> c8H17J\-l--,o
--\
68% ll
192
o-Fluorovinyltriphenylphosphoniumsalts
when
ketones are converted to enones by reaction with p-perfluorohexylbenzene-
\\
selenenyl chloride and subsequentoxidative elimination, the spent reagent can be recovered in the form of the diselenide by reduction and continuous fluorous extraction.la Products from hydroboration with catecholboranein fluorous solvents are extractable by THfl while the catalyst [(c6Fr3cH2cH2)3P]rRhcl (0.04 molvo) remains in the fluorous phase.r5 Fluorous-soluble polymer ligands obtained from copolymerization of p-dipenytphosphinostyrene and (heptadecylfluoro)decyl acrylate are suitable for the preparation of a Rh-basedhydroformylationcatalyst.r6 There is dramatic acceleration of certain Diels-Alder reactions in fluorous solventsrT (enhancementapproachingthose observedin water).
'Hanamoto, T., Shindo,K., MaLsuo\
Formaldehyde.20, 167 N-Methylation. By using m amines are methylated with HCH(
Reagentsinvolved in the oxidation of alcohols to aldehydes-ketonesby oxygen under fluorous biphasic conditions are TEMPo, cuBr.sMe2, and 4,4'-bis[heptadecafluoro)dodecyll-2,2'-bipyridyl.rsThe Mn(salen) complexesthat mediateepoxidationof alkenes have beenmodified to bear polyfluoroalkyl substituentsin the aromaticrings.reoxyfunc-
hydrolyzablegroups.r
tionalization of unactivatedC-H 2') propyloxaziridine.
Formic acid. 13, 137; lE, 16-1:lt N-Formylation r Diphenl lar weakJynucleophilicanilinesare io
sites is achieved with perfluorinatedcis-2-butvl-3-
rMerrigan, T.L.,Bates,8.D.,Dorman,S.C.,Davis,Jr.,J.H.CC2051(2000). rwipf, P, Reeves, J.T.TL 40,5139(1999). rwipf, P.,Reeves, J.T.TL 40,4649(1999). +Rover,S.,Wipf, P.1"240, 5661(1999). 5Bucher,B., Curran,D.P.TL 41,9617(2000\. "Dinh,L.V.,Gladysz, J.A.TL 40,8995(1999). TNakamura, Y.,Takeuchi, S.,Ohgo,Y.,Cunan,D.P.256, 351(2000). sCurran, D.P.,Hadida,S.,Kim, S.-Y,Luo,Z. JACSl2l.66Oi (1ggg\. eBergbreiter, D.E.,Franchina, J.G.,Case,B.L. OL2,3g3 (2000). l"Moineau, J.,Pozzi, G.,Quici,S.,Sinou,D.TL40,7683(1999). rlCrich,D., Hao,X., Lucas,M. T SS,14261 Oggg). lrRyu,f ., Niguma,T.,Minakata, S.,Komatsu, M., Luo,2., Cunan,D.p.TL40,236:-(lggg). rrOloi.sson, K., Kim, S.-Y.,Larhed,M., Cunan,D.P.,Hallberg, A. JOC 64,4539(lggg). 'tCrich,D., Barba,G.R.OL2,989 (2000). l5Juliette, J.J.J., Rutherford, D., Horvath,I.T.,Gladysz, J.A JACS121,2696(19gg). '"Chen,W, Xu, L., Xiao,J. CC 839(2000). lTMyers,K.E., Kumar,K. JACS122,12025(2000). rsBetzemeier, B., Cavazzini, M., Quici,S.,Knochel,p. TL 41,4343(2000). "'Cavazzini, M., Manfredi, A., Montanari, F.,Pozzi,G.CC 2lj1 (2OOU. roAmone, A., Foletto,S.,Metrangolo, P, Pregnolato, M., Resnati, G. OL 1,281(1ggg).
o-Fluorovinyltriphenylphosphonium
salts. Fluoroallyl ethers.t The ethers are accessible from the wittig reaction by using these salts in the presence of NaoR. Monofluorochromenes are obtained from salicyladehvdederivatives.
h-
)-Ph F Tfo
rDavis,B.A.,Durden, D.A. SC30. .rit
rChakrabarty, M., Khasnobis. S.. Hang
Formic pivalic anhydride. Deoxygenation.t Remor.al oi anhydride at the temperature of rc and used in situ from HCOONa arr
rRosenau, T.,Potthast, A., Ebner.G . Kr
Fullerenes (C6o/C7o). [3 + 2]Cycloaddition.l Lnda cycloadditionof dimethyl iminodrt
rShi,Y.,Gan,L., Wei, X., Jin,S..i4haa
Fullerenes (C6/C7s)
n .\ .:r /)-perfluorohexylbenzeneal: :t. the spent reagent can be l\: :t and continuous fluorous
+ FPPh3 _' T \\
EtoNa + PhcHo
Tfo
Eto-\ FCHPh F 75o/o(E + Z)
[::.- ,r,russolventsare extractable .r-: ",,1'i ) remainsin the fluorous rHanamoto,T.,Shindo,K.,Matsuoka,M.,Kiguchi,Y.,Kondo,M. JCS(P1) 103(2000). rF". . :nr'rizationof p-dipenylphos..-::.r'Flcfor the preparationof a Formaldehyde.20,167 k: :,.1!tlonsin fluoroussolventslT drr ..tc. ketonesby oxygenunder -1.-1'-bis[heptadecafluoro)r,'r.i 'r.-Jratc epoxidationof alkenes 13 i .' ::r aromaticrings.leOxyfuncu': rcrfluorinatedcls-2-butyl-3-
N-Methylation By using monosodium phosphite as the reducing agent, secondary amines are methylated with HCHO. This method perrnits the presenceof other reducible, hydrolyzablegroups.r rDavis,B.A.,Durden,D.A. SC30,3353(2000).
Formic acid. 13, I 37; 18, 163; 19, 148-1491, 20, 168 N-Formylationr Diphenylamine, carbazoles, 3-alkylindoles, and moderately weakly nucleophilic anilines are formylated in neat formic acid.
( - i. l(X)o).
Formic pivalic anhydride. Deoxygenation,t Removal of the oxygen atom from amine oxides with the mixed anhydride at the temperature of ice is quite convenient. The mixed anhydride is formed and used in situ from HCOONa and pivaloyl chloride.
i " Ir
rRosenau, T., Potthast, A., Ebner,G., Kosma,P.SL 623 (1999).
F
I
rChakrabarty, M., Khasnobis, S.,Harigaya,Y., Konda,Y. SC30, 187(2000).
) I' 7Z 40,2367(1999). , / ( 6 { . . 1 5 3(91 9 9 9 ) . r:l 1696(1999).
: : x)t)). - ' r t t
| )1,l. 281 (1999\.
fr :' :hc Wittig reaction bY using r .-:r:,,lncnes are obtained from
Fullerenes (C6olc7i. [3 + 2]Cycloaddition.t Under photochemical conditions, fullerenes catalyze the cycloaddition of dimethyl iminodiacetate to maleic anhydride. rShi,Y.,Gan,L., Wei,X., Jin,S.,Zhang,S.,Meng,F.,Wang,Z.,Yan,C.OL2,66'1(2OOO).
Gallium0ll) halides. 20. l6+ Vinylation. Introductirn aromatic ringsr and the c-Fxrt with silylalkynes. If the reac-u is obtained,due to bromolr sri
GadoliniumflID chloride. 20, 169 Diels-Al.der type reactionr The reaction of imines with dihydropyran or is catalyzedby GdClr. dihydrofuranto givetricyclicheterocycles
OSiMe
rY I I
r\
i l l
ao\ t
t
-$r' --n
l
+
Y
NHz
Gdcl3 N4eCN
OSiMe-.
cHo
Ph
I
Ph
Ph.lV
n = 0 ,1
rMa,Y, Qian,C.,Xie, M., Sun,J. "/oC64,6462(1999). Gadolinium(Ill) isopropoxide. Reductive acylation.t Acetates are generated from carbonyl compounds in a Meerwein-Ponndorf-Verley reduction in the presence of isopropenyl acetate. Beside gadolinium(Ill) isopropoxide, samarium isopropoxide can also be used to induce the reaction. rNakano,Y., S.,Ishii,Y.TL4l,1565 (2000). Sakaguchi, Gallium. Allytation and propargtlation.t
# ,"fi
I \\tn oH 94Yo
, , \ + c a { j } t n PhcHo ) \
THF A
OH 90%
I Han, Y., Chi, 2., Huang, Y -2. SC 29, 1287 (1999). t94
Directed reduction.s Srr a donor (such as triple bondr hydride reagent.
Aldehydes are attacked by the organogallium species.
+ca
a,.M
Mannich-type reaction-' CFTCHOcondensewith silrl c 1,3-Diketones.4 Dehdol with GaIr provides a ne\l \r a\
\
3-AIkoxy-3-pyrrolines. additionin the presenceoi ( pattern(trans-cisratio in tlr t
otar":
(OC).Cr \ /R"O
Galliurn(Ill) halides
Gallium(Ilf halides. 20, 169-170 vinylation. Introduction of vinyl groups to an ortho-posrtion of substituted aromatic ringst and the ct-position of a ketone2is accomplishedby the catalyzedreaction with silylalkynes. If the reaction is quenched with NBS, an a-(2,2-dibromovinyl) ketone is obtained, due to bromolysis of the gem-digalliumspecles. ::--irneswith dihydropyran br (iJCl..
OSiMe3
*
A-
O
t"tt'\
Gacr3: Ah HrO'
\..,'
/\
i .a v)\/2
l
\_,/
l
65To I
!,YNH
siMe3
OSiMe3 +
Ph
t
,l
Ph'\."
- = 0 .1
l
t
g
cacrj: + l l
l
Hro- errf
l
rl
n
R 76-970/"
carbonyl compounds in a i'opropenyl acetate.Beside elso be used to induce the
t: :
Mannich-type reaction.3 carbinolamines formally derived from amines and CFTCHOcondensewith silyl enol etherswhen catalyzedby GaCl. 1,3-Diketones.a Dehalogenative coupling of a-bromoketones and acid chlorides with GaI. provides a new way to the diketones. Directed reduction.s Simultaneouscomplexation of Gacl., to a carbonyl group and a donor (such as triple bond) activated the former toward regioselective attack by a tin hydride reagent.
GaCl3/ CH2C|2 78
l. r.r'.1hr the organogalliumspecies.
x^------* 35n'
oHc
Ph i
^.,,Ph
T OH l'1eb F'
-
,^\
3H 30%
r
\
3-Alkoxy-3-pynolines.6 Fischer carbene complexes and aldimines undergo cycloaddition in the presenceof Gaclr. The major products have a trans-2,5-disubstitution pattern (tans-cis ratio in the 8:2 range).
o'-*1
R GaCl3
(oc)5cr.
I_
R'O
ctcH2cH2cl
/aR'
Rr-.n,N
,,
R'
F
R"O
\ans.irs-\.1\
GoldoID cHoride
Graphite. 20, 170 Acetalization,t In reflur pentaerythritol serves as rhc expansivegraphite as the catalr
lYonehara, F., Kido, Y., Yamaguchi, M. CC 1189 (2000). 2Yamaguchi,M., Tsukagoshi, T., Arisawa' M. ./ACS I21,40'74 (1999)' 3Takaya,J., Kagoshima, H., Akiyama, T. OL2,1577 (2000). 4chen, R., wu, H., Zhang, Y. JCR(S) 666 (1999). 5Asao. N., Asano, T., Ohishi, T.,Yamamoto,Y' JACS 122' 4817 (2000) 6Kagoshima,H., Akiyama, T. ./ACS 122' ll74l (2000).
HO--r Gallium(IlD nonafluorobutanesulfonate. Friedel-Crafts acylation.t The effectiveness of the salt in catalytic quantities to promote acylation is indicated by the excellent yields of ketones obtained from fluorobenzene,chlorobenzene,and dichlorobenzenes.
\ /r-OH X
gg-J
I
\-6s
rJin,T.-S.,Li, T.-S.,Zhang.Z.-H .
lMatsuo,J., Odashima, K., Kobayashi,S. St 403 (2000).
Gold[ID chloride. cyclizatian. 3-Alkynones cyclize to afford furan derivatives in the presence of gold(Ilf chloride.r Furans bearing an alkynyl chain undergo intramolecular cycloaddition further. Transformation into bicyclic phenols is noteworthy becausethe hydroxy group rs at aperi-position.
/-:r'^x
o"'t, -{A tJ
MeCN 20'
-:J
w : J
+ G
l
o\# "
l
l
G
Grignard reagents. 13, 138- 1 167-17l; 19, 151-154;20. I ?0
Reagent formation by t related heteroarylmagnesiumr l-PrMgBr or l-Pr2Mg in THF i functionalized alkenyl and all preparationof RCOOCH.\I$
cosolvent becauseit solubihz not).7 Lithium trialkylmagnesa alkenylmagnesiumreagents.'
l OH
G = O, NTs,CHz
o )^o^
1,2-Alkadien-4-onesbehavedifferently toward Au(IID and Pd(II) species'z
t'oYoY* Auct"
I
I MecN2o. I /:w-
R--d
l
lr---l o
'
l \t
\
l
q#=-.,1h\"
A method for generatingrc:
ct
Ph.-rAt 'Hashmi,A.S.K.,Frost,T.M.,Bats,J.W.IACS122'11553(2000). 2Hashmi. A.S.K.,Schwarz,L., Choi,J.-H.,Frost'T.M- ACIEE39' 2285(2000)'
'
CtMgt--l
I
Griglard rragents
Graphite. 20, l7O Acetalizatian,t In refluxing benzene or toluene, spirodiacetals are formed when pentaerythritol serves as the condensation partner with carbonyl compounds and expansivegraphite as the catalyst.
t -: l9g9) ll t: t:: - . r l 0 O 0 ) . )
HO-1
sraphite + R-CHO +
7-OH Y
.r the salt in catalytic quantltres to r rclds of ketones obtained from
f.i'
a . -
O--r r-O
R-{
bJ
HO--J \-OH
X\-o }-n
1Jin, T.-S.,Li, T.-S.,Zhang, Z.-H., Yuan,Y.-J. SC 29, 1601 (1999).
U.:' fr
: rriln derivatives in the presence of : ndergo intramolecular cycloaddition .r,,nfiv becausethe hydroxy group is
I ci
2-v\
(l
+.\,5 '
l '
l
l
G
Grignard reagents.13, 138- 140; 14, 11l-17 2; 16, 172-173; 17, l4l -142; 18, 167-17 l: 19, 151-l 54; 20, 170-173 Reagent formation by exchange reactions. Pyridylmagnesium bromides and related heteroarylmagnesium reagents can be prepared by an exchange process (with l-PrMgBr or l-Pr2Mg in THF at-25" to -40o).r-3 The accessto Grignard reagents from functionalized alkenyl and alkyl halides also benefit by this technique,a{ and in the preparation of RCOOCH2MgCI by this procedure, N-butylpyrrolidone is added as a cosolvent because it solubilizes magnesium reagents at low temperatures (NMP does not).7Lithium trialkylmagnesateshave also been employed in the preparation of aryl- and alkenylmagnesiumreagents.'
l OH
o
>fAo^' r.:: : \u, tll t and Pd(II) sPecies'2
)
I
l
+
)
THF
f-\ o4"Ao
o^vscr
I
Bu
t'oYoY* , - r JL-l
o tl
i-PrN,lgCl
\r
R
EtMgBr/ DIVIE
e,o1o7R -\rnB."
\
A method for generatingrearrangedreagentsinvolves carbenoid insertion''
\ .\o ^
R
ct
Ph'-Ar .. i l00O). ! T r1 lr /[f39.2285 (2000)'
*
ctMg-_R
|
MgX EI,U
I
*
Ph.v\,R -78--20
tn---X*
1 I
(94-97 : 6-3)
'
MgX
198
Grignard reagents
Nonstabilized aziridinylmagnesium bromides are similarly prepared from the exchange of an arenesulfinyl group, with retention of configuration.r0 Another way to prepare RMgBr from RX is to use a mixture of Mg' 12' BrCH2CH2Br.rrOn this protocol, suitablesubstratesundergoBarbier reaction.12
A process involving addition io hand, furan ring opening is featured
t "n-''
drab ./\.A
-,^. 'cl
- Ho"\\.,,o/-l
BrcH2cH2Br Et2o
l
ll
,/\-)
* /uge,
\-N
N/'
-4
ril
rir
l-\
67%
p-",r5-tnt, ( Chiral ct-chloroalkylmagnesiumreagentsprepared from C-S I3 sulfoxides maintain their steric integrity.
i'r,^ cl
EtlvlgBr BrMO -.-,1 THF -78'
bond cleavageof chiral
OH I
phcHo
o*
t - - - - - - - - Me2Alcl - - - - - - -enfen -
Ct
cl
'O/-r/
l
ll
Ts. -r
+
N
H
Addition to muhiple CC b 1-hydroxy ct,p-unsaturatednitnlcs
substrateswith 1 equiv of t-Bu\lg( Propargyl alcohols are carbomagrr be functionalized.22
bond. Several useful preparations relating to this type Addition to the C:N mention: to SAMP-hydrazones,r4to chiral bisiminesr5and of are worthy of addition and to thosegeneratedin N-(diethoxyphosphoryl)atdimines,rT to N-sulfinylimino esters,r6 n I amides. lbnyl )alkyl situ from N-(cr-benzenesul
to)
lrMo' .
lli I
!--\
!--r\
X'" _A:
N.4eMgBr N
.-OMe i-
X
PhN.4e 0 :
lA-*"
l\,4eOH
-'
.-oMe Ni
I
\2
Nitrogen compounds. Senl carbonylbisben zotriazole sequentre reagent to furnish an amide product
N.
62Yo
\
'r{n"4 Ph
t-BuMgCl/ THF ;
.................--.-*. Ph
PhlvgCl
Ph
)-NRR
y P h '._J
rJ, i*{ 89%
o Ph
Displacement reactians. :-l propane derivatives2son reaction ' aryl sulfoxides readily undergo S-
Grignard rtagents
lr: I,-
-.:lrlarly prepared from the ex: Jration.r(r r , use a mixture of Mg, 12' ::rgo Barbierreaction.l2
A process involving addition followed by cyclization is remarkable.reOn the other hand, furan ring opening is featured in another reaction.20
t N)
ir
/-\
l
* Aviga,
\-*
/l
il
I Xor
;r l/'
+
-
]
XI
-
-
X
L'' A
67Yo
p-r-\7Mgat :n C-S
bond cleavage of chiral
\"\)
T". -N
.
l-\
,o-=,;\f'\.'\,.cHo
il'so/+(oJV 80%
OH I pn-'\rt-pn \4e2AlCl
I
cl
Addition to multiple cc bonds. conjugate addition of Grignard reagents to 1-hydroxy cr,B-unsaturatednitriles is facilitated by chelation.2rThus, pretreatmentof the substrateswith I equiv of l-BuMgCl followed by a secondRMgX completes the reaction. Propargyl alcohols are carbomagnesiatedand the ensuing alkenylmagneium halides can be functionalized.22
i, ::rparations relating to this type r.r-.,. hcs.ir to chiral bisiminesl5and I : . :lnc'S.r'and to those generatedin
"o-l
1 r r ' r o c. t
to)
'l'
oH
+oHC-ph+=l-^r^ 80%
) 7.\-*t
'
.-oMe
l-\
-N
\/
-N
62%
{-
/ \ t -NH HN< Ph 89%
,N
\
v '._J P h ='
Nitrogen compound.s. Serving as a doubly electrophilic carbon monoxide' I'l'carbonylbisbenzotriazolesequentially reacts with an amine and then with a Grignard reagentto furnish an amide product.23Grignard reaction of ArNr deliversN-alkylanilines.2a
+ R"MgX
+
R,,_./,NRR, tl
NRR'
Displacement reactians, 2-Substituted dioxolanes are converted to l,3-disilylpropane derivatives2son reaction with MerSiCHrMgCl. Rather surprisingly, substituted aryl sulfoxides readily undergo S-{a. bond cleavage.26
Grignard
reagents
Me3si\/N.4scl
p1
o)
-
Ph'^+o/
r-oH
Me.si ' \ , / Mocl -;hM"
pn-\-.\.-,.
^-
ph,-\-/-.-,-sives
,,,SiMes SiMeg
68%
(
..,,SJa-.-+ ll
|
o."..., RMgX ___:*
rHF
./"\^
Br*
Benzylthiols.3z Reaction of A reduction with LiAlHo furnishes .\r(
B-Aminoketones,3r Aqueousr amides,morpholino amides)and ru B-aminoketones. Tetrahydrophthalides.rt Th€ |
estersis renderedregioselectivebr the combinationof the alkoxy'magn H omo lo gatio n-c onden satio n-
K
Tetrahydrofuran derivatives. With the EtMgBr-neopentyl iodide system in THfl the solvent becomesiodinated atC-2 (free radical process)and 2-aryltetrahydrofuransare obtained on addition of EtI and EtMgBr to arylmagnesium halides in THF.27 Radical cyclizationof allyl B-iodoacetalsis inducedby EtMgBr in DME.6 1-Bromo-l-chloroalkenes are obtained from dibromochloroElimination. on exposure to EtMgBr.28 Dehydration of B-hydroxy nitriles acetates methylcarbinyl A occurs when they are treated with MeMgCl at -78' and warmed to room temperature.2'r
vinylmagnesiumhalide also triggen Bridged ring compounds can be pref
Z\,4. COOMe
Mg&;
methodof allenesynthesisalso involvesan analogouseliminationstep.r0
Go-*%J#O<* 93% Ph
SOPh THF _78'
Ph 88%
A modified Julia olefination involves reaction of sulfonylcarbanionswith ct-haloalkylmagnesiumhalides3rinsteadof aldehydes.Elimination of halomagnesiumphenylsulfinate immediately follows the C-{ bond-forming step.
f ot\u"'
,2
TIPS
oaes
t l .,..\.,,\so2ph
oaes
f n1""'
i
lvleCH(Cl)N/gcl
,2
l
.r'\\-AcHMe
TIPS
91Yo
ht
rAbarbri. M.. Dehmel. F.. Knochel. P fl rTrecourt.F.. Breton. G.. Bonnet.\'.. \lc 'Felding, J., Kristensen,J., BjerregaarrL r T h i b o n n e tJ, . , K n o c h e l ,P Z a 4 1 . - r - 1 1 -Avolio, S., Malan, C., Marek. I.. Krxrch G., Knochel,P.JOC 64, 1080( I 999 , "lnoue. A.. Shinokubo.H.. Oshima. K ( 'Avolio, S., Malan, C., Marek. I.. Kmr-h nKrtagawa,K., Inoue,A., Shinokutn. H "Hoflmann, R.W., Knopff, O., Kuschc.J roSatoh,T., Matsue,R., Fujii, T., Mon\.rr " L i , J . ,L i a o ,X . , L i u , H . , X i e , Q . . L r u .Z r r H u a n g J, . - W . ,C h e n ,C . - D . ,L e u n g .\ l - l IHoffmann. R.W.. Nell. P.G.ACIEE 3t. ''Enders. D., Diez. 8.. Femandez.R . \k
t.M. JOC 64,6329 (1999). r5Roland,S., Mangeney,P. EIOC 5ll t\ r{'Davis,F.A., McCoull, W. ,/OC 6{. -r-r* rtZwierzak,A., Napieraj,A. S 930 t l99q rsMecozzi,T., Petrini,M. JOC 64.Eg'(.tI NKim, S., Oh, D.H., Yoon, J.-Y..Cbemg. r')Chandrasekhar,S., Reddy, M.V.. Reddr rrFleming,F.F.,Wang, Q., Steward.O.\t. rrForgione,P.,Fallis,A.G. 7L 41. I I r ltl rtKatritzky,A.R., Monteux, D.A.. Trrrn! :rKumar, H.M.S., Reddy,B.V.S..An;arrr
Grignard reagents
aSiMee pnl-.-,r]'\,.
SiMeg
68%
Benzylthiols.3z Reaction of ArMgX with chlorothionoformate esters followed by reduction with LiAlH. furnishes ATCH2SH. pAminoketones.s3 Aqueousquenchof the reactionbetweenamides(e.g.,Weinreb amides, morpholino amides) and vinylmagnesium bromide at room temperature leads to B-aminoketones. Tetrahydrophthalides.3a The Diels-Alder reaction of 2,4-alkadienols with acrylic esters is rendered regioselective by pretreatment with MeMgBr so that chelation directs the combinationof the alkoxymagnesiumspecieswith the dienophiles. The reaction of cyclic B-keto esters with a Homologation-condensation vinylmagnesiumhalide also triggers oxy-Cope rearrangementand Claisen condensation.
: R
:'-'nrrl iodide sYstemin THF, .,:1J l-ary'ltetrahYdrofuransare S\ r . . rr halides in THF.27Radical r \ l F _"
Bridged ring compoundscan be preparedby this method.rs
n.i
l:-
h : . . ' .'J
dibromochloro-
from
r : .:r.1tronof B-hYdroxYnitriles A ::rcd to room temperature'2e steP.30 h : : ::.rtron
r'-
:
- (
cl
/1
Br
93%
8:
ll: ': . lcarbanionswith cr-haloalkyl:..r1()magnesiumPhenYlsulfinate I
:^oePs ^/.\.."'
Y
,2
I
...'\.Acul,le 95To
63%
rAbarbri, M., Dehmel,F., Knochel,P. TL 40,7449 (1999). :Trecourt,F., Breton,G., Bonnet,V, Mongin, F., Marsais,F., Queguiner,G- T 56, I 349 (2000). 'Felding, J., Kristensen,J., Bjenegaard,T., Sander,L., Vedso,P, Begtrup,M. JOC 64,4196 (1999). rThibonnet,J., Knochel,P. TL 41, 33 I 9 (2000). 5Avolio, S., Malan, C., Marek, I., Knochel,P. Sat820 (1999); Rottlender,M., Boymond, L.' Cahiez, G . , K n o c h e l ,P .I O C 6 4 , 1 0 8 0( 1 9 9 9 ) . 6 l n o u eA , . , S h i n o k u b oH , . , O s h i m a ,K . O L 2 , 6 5 1 ( 2 0 0 0 ) . rAvolio. S., Malan, C., Marek, I., Knochel,P. SL 1820 (1999). sKitagawa,K., Inoue,A., Shinokubo,H., Oshima,K. ACIEE 39,2481 (2000). "Hoffmann, R.W., Knopff, O., Kusche,A. ACIEE 39,1462 (2000). rosatoh,T., Matsue,R., Fujii, T., Morikawa, S. TL 41,6495 (2000). l r L i , J . ,L i a o , X . , L i u , H . , X i e , Q . , L i u , Z . , H e , X . S C 2 9 , 1 0 3 1( 1 9 9 9 ) . rrHuang,J.-W.,Chen, C.-D., Leung, M.-K. fL 40, 864"7(1999)r r H o f f m a n nR , . W . ,N e l l , P . G .A C I E E 3 8 , 3 3 8 ( 1 9 9 9 ) . 'lEnders,D., Diez, E., Femandez,R., Martin-Zamora,8., Munoz, J.M., Papparlardo,R.R.,Lassaletta, J.M. JOC 64,6329 (1999). rsRoland,S., Mangeney,P. EJOC 5ll (2000). r('Davis,FA., McCoull, W. JOC 64'3396 (1999). t'Zwierzak, A., Napieraj,A. S 930 (1999). I'Mecozzi, T., Petrini,M. JOC 64,8970 (1999). r " K i m , S . , O h , D . H . ,Y o o n ,J . - Y . ,C h e o n g I, . H . J A C S1 2 1 ,5 3 3 0 ( 1 9 9 9 ) . r"Chandrasekhar, S., Reddy,M.V., Reddy,K.S., Ramarao,C.TL41,2667 (2000). ItFleming, F.F.,Wang, Q., Steward,O.W. OL2, 1417 (2000)' rrForgione,P, Fallis,A.G. TL 41, l1 (2000). }Katritzky, A.R., Monteux, D.A., Tymoshenko,D.O., Belyakov,S.A. JCR(S)230 (1999). r r K u m a r ,H . M . S . ,R e d d y ,B . V . S . , A n j a n e y u l uS,. , Y a d a vJ, . 5 . T L 4 0 , 8 3 0 5 ( 1 9 9 9 ) .
Grignard reagents{opper salts 25Hsieh,y-T., Luh, T.-y H s2, tr2s (2000). 26Capozzi,M.A.M., Cardellicchio, C., Naso, F., Tortorella, P. JOC 65,2843 (2000.). 27lnoue,A., Shinokubo,H., Oshima,K. Sl, 1582 (1999). 28Rezaei, H., Normant, J.F.S 109 (2000). 2eFleming,F.F.,Shook,B.C. TL 41, 8847 (2000). 30satoh,T., Kuramochi, Y., Inoue, Y. ZI, 40, 8815 (1999). 3 r S m i t h I I I , A . B . , M i n b i o l e , K . P , V e r h o e s r , P . R . , B e a u c h a m p , T . I . O Lgl ,l 3 ( 1 9 9 9 ) . 32Nakamura,T., Matsumoto, M. SC 29, 201 (1999). 33Gomtsyan, A. OL 2, 11 (2000). r4ward, D.8., Abaee,M.S. OL2,3937 (2000). 3sSheehan, S.M., Lalic, G., Chen,J.S.,Shair,M.D. ACIEE 39,2714 (2000).
Grignard reagents-cerium(Ill) chloride. L8, 17 1; 19, 154;20, 173 y,yDisubstiluted a-alkylidene-y-butyrohctones.)These compounds can be synthesizedin two stepsfrom 1-keto-ct,B-unsaturated esters,the secondstep being a Grignardreactionin thepresence of CeClr.
Primary amines.3 A preparau with Grignard reagents(Cu-catalr za
FiC __z
Phr - cect3; PrMsBr
// 1
._ COOMe
HoAc
o 53To
Ketone synthesis.a N-Atk1l-l-r presenceof BF1.OEtr.The metalloe by electrophiles.
lBallini, R., Marcantoni,F., Perella,S. JOC 64,2954 (199q.
Grignard reagents{oppersalts.18,171-173;19, 154-156;20, 174-175 Transpositionaldisplacements. Basedon the displacement of allylic carbamates, alkenes containing bothallylicandhomoallylicsilyl substituents areaccessible.r
OCONHPh
,.,,,.,%siMerpn
BULTiTHF:Cul-2LiCl: Me3SiVMgCl
Ivsittterpn at'""'
Ytn
Rrrt
N
\
'Smitrovich, J.H.,Woerpel, K.A. ./OCa,4 )Wan,Z.,Nelson,S.G.JACS122,lolio r 'Tsutsui,H., lchikawa, T.,Narasaka. K.B( rHayes,J.F.,Shipman, M., Twin,H. CC'l'
82%
Stereoselectivereaction of B-alkynyl-B-lactones gives rise to 3,4-alkadienoic acids. A product of this type has been recognized as a suitable precursor of malyngolide.2
D
Grignard reagents-iron(Ill) chlorN Carbometallntion. Grignard ru of an iron catalyst.r When the all-r-1 bicyclo[2.2.1]octanesystema ner S\:
Grignard reagents-iron(Itr) chloride
CeHleMgBr- CuBr
t 6 5 . 2 8 4 3( 2 0 0 0 ) .
l :
.CoH.o " '" LoBn
/:C{ (
THF -78"
Ag'
cooH ( )r, t, 913(1999).
lc.
H2
OBn + I -r,l
/--\
-CgHrg
\_A-o* //
o
rI (1000).
I le. .:-l:20,173 These compounds can be t)nf.. li:i-.r i'rtcfs, the secondstep being a
'
(-)-malyngolide
Primary amines.r A preparation of RNH2 is via the reaction of oxime mesylate I with Grignard reagents(Cu-catalyzed) to give imines that are easily hydrolyzed.
F3c* t
i
l
VYV
/.\7cr. i l l
N -OSOrMe
c
(1)
53o/o
Ketone slnthesis.4 N-Alkyl-2-methyleneaziridines react with RMgX (CuI) in the presenceof BF3'OEt2. The metalloenaminesthus generatedcan be hydrolyzed or trapped by electrophiles.
F., -._a- ph
t. ': I 56:20,174-175 of allyliccarbamates, f.r :.-rlacement areaccessible.l lr ...-.tiruents
,,
aSiMes Ssitr,t"rpn
I N
R M g B-rC u l- B F 3 ' O E I 2R
,
Y
O LR'
\ 'Smitrovich, J.H.,Woerpel, K.A. JOC 65, l60l (2000). )Wan,Z.,Nelson,S.G.JACS122,10470(2000). rTsutsui,H., Ichikawa, T., Narasaka, K.BCSJ72,1869(1999). iHayes,J.F.,Shipman, M., Twin,H. CC l'/91 (2000).
82Yo
.:. rise to 3,4-alkadienoicacids.A : t h . , :.!ursor of malYngolide.2 c.
Grignard reagents-iron(Ill) chloride. Carbometallation. Grignard reagents add to strained cycloalkenes in the presence of an iron catalyst.rWhen the allylic position bears a leaving group (such as the 7-oxabicyclo[2.2.1]octanesystema net Sp2' reactiontakesplace.
Grignard reagents-nickelcomplexes
><
Alkenyl halides are transfornra 2-Substituted 1,3-dienesare genera
PhMoBr-Fecr.
oxo -G--;
oxo
,{96%
PhlVgBr- FeCl3
P-V
ph
t-l
b-l\
55%
rShatayev,K.V, Ten'kovtsev, A.!'.. Brhb 2Bohm, V.PW., Weskamp, T., Gsrotrmes rUenishi, J., Kawahama. R.. Izaki. \'. \b lKarlstrom, A.S.E., Itami, K., Backvall.I
Grignard
lNakamura, M., Hirai,A., Nakamura, E. JACS122,978(2000).
reagents-palladinrn
cq
Cross couplings. Biphenrl 11 complexes in the presenceof l.-l-d Grignard reagents-manganese(Il) chloride. 20, I7 5-17 6 Coupling reactions.t The coupling of RMgX with ArX (including ArF), which is activated by an electron-withdrawing substituent, proceeds readily with MnCl2 as catalyst. Allylmanganese reagents,2 These reagents are formed from allyl ethers by a fragmentativepathway.When 2-allyloxytetrahydropyranis treated with RjMnMgX, the ensuingfragmentsrecombineto give 7-octene-1,5-diol.
ligand enablesthe selectiverep|rcrr
rHuang,J.,Nolan,S.P.JACSl2l. 9EtI)I 2Kamikawa, T., Hayashi, T. 755. 3{55r I Grignard reagents/silver salL Allylamines.t a-Amino nirnh
OH
*
I
BulMnMsBr ,rA
Z.-.oyo)
\]i
HMPA *
oH
v
,%
N-{ 'cr.r
v
n=0.1
rAgami,C.,Couty,F.,Evano,G. OL 2. ! tCahiez,G., Lepifre, F., Ramiandrasoa, P. S 2138 (1999). 2Nishikawa,T., Nakamura,T., Kakiya, H., Yorimitsu, H., Shinokubo,H., Oshima, K. TL 40, 6613 ( l 999).
Grignard reagents-nickelcomplexes.18, I 73; 19, 156-157;20, 176-177 biphenylsis easilyachieved,includCrosscouplings. Formationof unsymmetrical ing thosefrom iodophenols.r By addingthe highlyhindered1,3-dimesitylimidazolinium well.2 saltto thereactionmedia,couplingwithArCl proceeds
Grignard reagents-titanium( IV I cr 20.177-180
F unc tia nalize d cyclopropa*containsan ct-hydroxyl,ra p-ester. the precursoral esters. These are rz when the n-ligand of propeneriraniu is exchangedby vinyltrimethylsilar: generated.a
Grignard reagents-titanium(IV) compounds
Alkenyl halides are transformed into alkenes while retaining their configurations.3 2-substituted 1,3-dienesare generaredfrom the readily available dienyl phosphites.a
Ph
l-i
*r
78o/o
l H \ro :-./
'4 1.
O
s5%
!'
.. .
.\rX (including ArF), which is - ..c'ds readily with MnCl, as
:nrcd fiom allyl ethers by a tr::- :. rreatedwith R]MnMgX, the
IShatayev, K.V.,Ten'kovtsev, A.V.,Bilibin,A .y. RJOC35,30g(1999). rBohm,V.PW.,Weskamp, T., Gsrottmayr, C.W.K.,Herrman n,W.A. ACIEE 39, 1602(Z0OO). 'Uenishi, J., Kawahama, R., Izaki,y., yonemitsu,O. T 56,3493(20M). rKarlstrom,A.S.E., Itami,K., Backvall,I.-F..JOC 64, 1745Oggg). Grignard reagents-palladium complexes. cross couplings' Biphenyl synthesis by cross-coupling can be promoted by pd complexes in the presence of l,3-dimesitylimidazolinium chloride.r A chiral phosphine ligand enablesthe selectivereplacementof one of two triflyloxy groupson an arenenucleus.2 rHuang,J.,Nolan, S.P.JACS121,98g9(1999). jKamikawa. T..Hayashi, T. f SS,3455( t999).
rh
Grignard reagents/silver salt. Allylamines.t s-Amino nitriles suffer attack by alkenyrmagnesium halides.
OH
I \r/
,Ph N-{ tCN
BtMsV
A}BF4
I
N-<
'Ph
v \ :
91To lAgami,C.,Couty, F.,Evano,G. OL2,2Og5e}OU. s'
, :ho. H.. Oshima, K. TL 40, 6613
.5r: 20, 1'76-177 r:nrls is easily achieved,includ. :rtl 1.3-dimesitylimidazolinium .'ll.l
Grignard reagents-titanium(Iv) compounds. 14, 121_122;lg, 174;19, l5g_l6l; 20,177-t8O Functionalized cycropropanors. cyclopropanors in which the geminal side chain contains an a-hydroxyr'r a B-ester,2or a B-phosphono group3 have been prepared from the precursoral esters. These are valuable synthetic intermediates. On the other hand, when the n-ligand of propenetitanium diisopropoxide [from r-prMgCl and (r-pro)..Ticr] is exchangedby vinyltrimethyrsilane, cyclopropanols containing a nucrear silyl group are generated.a
Grignard reagents-titanium(IV)compounds
-J Me3si
- (i-Pro)3Ticl i-Prr\4scr
Me3Si\
\ -
=b
l
ll-----------------.-.--------------tt'.^ | I / ) \ v
,"r,>r;:
phcooEt
-
l
A propargylic carbonate or phosp via the allenyltitanatespecies.e
Certain 2-alkylidenecycloalkano lar processinitiatedby cyclotitanarro
88% (trans j cls 93 : 7)
4\\(n
Reaction with alkenes and aWnes. In the carbosilylation of alkenes and dienes with carbon fragment that comes from a secondary or tertiary alkyl halide, promotion by BuMgBr/Cp2TiCl2 is efficient. Primary alkyl halides are less suitable contributors unless the reaction is intramolecular. The regioselectvity of this process is such that the silyl group is branched out.5
ph,,/ -
ll
ti l ll r o
't
I
K
-cp2ricr2>tn7f4BuMscr tBuBr. Et3SiCl
I
c+^ii
94%
tn6A.Ar,.
I
BuMgCl- Cp2TiCl2 MetSiCl
,,.YO Me3Si
Reductive cleavages. Dia4l dl BuMgBr/Cp2TiCl2 system. Alkl.-lar respectively.
Both the removal of the ester gru (alsoArBr, ArI)ra are accomplishedar Allyl ethersand allylaminesun&r rcgioselectivelyaccordingto the rrtan
87% /-)
o.
Hydrotitanation of l-silyl- and l-stannyl-l-alkynes leads to B-silyl (or Bstannyl)alkenyltitanates,6 thus showingoppositeregioselectivityto other relatedprocesses (hydroboration,hydroalumination,hydromagnesiation,hydrotitanation,hydrozincation, hydrozirconation).Well-defined alkenes are obtained on further reaction of the alkenyltitanates,for example,with allylic carbonatesan Sx2' displacementoccursto afford 1,4-dienes.7If another alkyne is added before protonation of the titanacyclopropenes(to give the alkenyltitanates),then the intermediates are transformed into titanacyclopentadienes, and henceto conjugateddienes.n
\_-2
XY o-
rll R
R^Tix3 Me3Si..".-[Ml
*.iJ
I
Er--C
+ Cp:T + EBT
t"rt') SiMe3
t-\
f).* \-J
ll -------.---.-(i.Pro.-
M= B,Ms,At,zn,zr
Cyclization. If a proper learrng ,liene,an opportunity for eliminarionc resultingalkyltitanium speciesmar hc hasbeendevelopedaccordingly.
Grignard reagents-titanium{IVlcompounds
Measirt-Ph - ,oH
i:-
A propargylic carbonate or phosphonatemay be converted to a hydrazino derivative via the allenyltitanatespecies.e Certain 2-alkylidenecycloalkanols are synthesizedfrom alkynones by an intramolecular processinitiated by cyclotitanationof the triple bond.r0
88%(trans:cis 93 : 7)
.di.n
r- .rlrlation of alkenesand dienes o: ::1ritn' alkyl halide, promotion by r tr:- ..\s suitablecontributorsunless r,' ''i- processis such that the silyl
-,
Y
c
'h,
Y/\ l Et.si
-,/ l I
94%
:- ^ltn
flf 'l'
3
.L{* -(tsPro)ari i-PrN'4scr ; Ytot ll R'^x
R'
X = H ,l n=1,2
Reductive cleavages. Diaryl disulfidesrrand ditelluridesr2are cleaved with the rBuMgBr/Cp2TiC12system. Alkylation results in alkyl aryl sulfides and tellurides, respectively. Both the removal of the ester group from a B-ketoesterrrand dechlorinationof ArCl (alsoArBr, ArI)ra are accomplishedat room temperature. Allyl ethersand allylaminesundergodimerization,rswhereas 1,6-dienesare cyclized regioselectivelyaccordingto the titanium complexesused.ro
Me3Si 87Yo
1-},o,,
.:rc\ leads to B-silYl (or Pprocesses t ' ' r.tl\ ity to other related 'i hydrozincation. r tlrotitanation. 1: '' iunher reactionof the alkenyltit\: .:-l.rccmentoccursto afford 1,4-di(to give : thc titanacycloProPenes
r-
: :Ic'd into titanacyclopentadienes,
\-J ,/-\ o ll \_-,
(i.pro)ari
H HOJ
\_OH
( d l: m e s o > 9 6 : 4 ) 51%
)")<#-.{)c(xfl + cp2Ticl2 92% + EBTHI-TiClz-
a
M = B, Mg,Al,Zn,Zr
49%
Cyclization. If a proper leaving group is present at an allylic position of a 1,6diene, an opportunity for elimination exists after formation of a bicyclic titanacycle.The A synthesisof (-)-o-kainic acid resulting alkyltitanium speciesmay be functionalized.rT has beendevelooedaccordinslv.
Grignard reagents-titanium(IV) compounds
Pho
/
5 (*)""aot" (
:1..
(i-PrO)aTi
-
l
:a,.
a'
IE n
--cooH
/
Vi=--/
\*AcooH
I OMe
H
ri
*"r
(-)-kainicacid
Cyclization with 1,5-chirality transfer is related to the abover8
R!.
R
^ F o -o
K,,r(
R i-PrMsBr-(FPro)ari> *,,,,Fo,
\
?
f1o
a'
B fJ,,,,-OME -N.
t2
OMe
Bn
/
6 \
UIJ
,,R, \_1
to-\-42t"
| \o/^ ),,,r'-,,-lt"
n=1,2
Bicyclization involving an intramolecularacylation is further extendedto include an aldolization.reA route to bicyclic enoneis basedon controlledprotonolysisof the titanacycle and subsequentcyclization.This synthesisis amenableto asymmetricinduction.20
Homoenolate and homoalleayl cnolate speciesare basedon the actrq titanatesgeneratedfrom acetalsof rm
iicetals are similarly cleaved to a.f carbonates are transformed into r l compoundswith ^y-selectivity.rr
rO. t F o
ior-^ | /-w
a)
.Y ................"'..".'................'"."'..................................* "\
\-\'o '
i-PrN,lgBr-(i-PrO)aTi ; s-BUOH
l-42:-siMe.
I SiMe3
T t
-\_/ /
-q .a n 17
\-/
54Yo The possibility of forming a bridged tricyclic system by an intramolecular reaction of an imide2ris of syntheticsignificance.
.v
I
I
H 1 9
\.,N : H
N
Z
U
R
G"n"'
.........................................._ (i-PrO)3TiCl ;
X
O2
The Cp2TiPh species generatedfrom addition of PhMgBr to the l-PrMgBr-Cp2TiCl2 system is able to induce cyclization of D-ketonitriles to cyclopentanolones.22The vinylogues afford 2-hydroxycyclopentaneacetonitriles.
t"-.
Following activation of conjugared c rmines gives products with multiple srer
Me?Si _P2 '-icl2
\\
..--_ [cornpt i_prMscl
\ '\2. R'
a,a-Dimethylamines.26 Reductnt reaction with MeMgBr in the presenceol
Grignard reagents-titanium(IV)compounds
J
--cooH
l "'te
/--(o
\-f,
\..r\cooH N
H
c
OH rP
r-4, t
Cp2TiCl2
(
i-PrMgCl; PhMgBr
\-f-J
H
H
77%
(-)-kainicacid
r h o te l
)
CN Cp2f i0l2
x
i-PrN,lgCl PhMgBr
^
K
R
/
' 64Yo
\o-\.,42t" H
i. lurther extendedto include an [. '::r()llcd protonolysisof the titanan 'r.rhlc to asymmetricinduction'2o a::'-
Homoenolate and homoallenyl carbanion equivalents. Two routes to homoenolate species are based on the action of (propene)titanium diisopropoxide. Trialkoxytitanatesgeneratedfrom acetalsofacrolein react with aldehydesand imines. Chiral cyclic acetals are similarly cleaved to afford the nucleophiles.zr3-Alkoxy-2-propyn-l-yl carbonates are transformed into (l-alkoxyallen)-1-yltitanatesthat add to carbonyl compoundswith T-selectivity.2l
n ./v,
.^)
l F o
).'
/-+/I \ ^
'>J
\
o
I SiMe3
Cp2TiCl2 i-Pr[rgcl I
*-*4*'
a) -
ron ,,-)""'\-o,,r1n' NHR" \_,/
54% ;r . - :: hr an intramolecularreactionof
Following activationof conjugatedenynes,the reactionwith carbonylcompoundsand iminesgivesproductswith multiplestereocenters.z5
:
:
N^Ph
Me"Si
^-ict2 vP2l
\
\ '\2. '
R
'
+ [complex] i-PrMscl :
tl
HN^Pn Me?Si -
l,/zv
r' tr
r : t'!\leBr to the i-PrMgBr{P2TiClt The vinyr: :- :,, cvclopentanolones.22
.4{a,' R'
a"a-Dimethylamines.26 Reductive methylation of tertiary amides occurs on reaction with MeMgBr in the presenceof TiClo @r ZrCl) in THF.
Grignard reagents-zirconiumcompounds 'Cho, S.Y.,Cha, J.K. OL2, 133'7(2000). 2Raiman,M.V, il'ina, N.A., Kulinkovich, O.G. Sa 1053 (1999). 3Winsel, H., Gazizova,Y., Kulinkovich, O.G., Pavlov, V., de Meijers, A. SL 1999 (1999). lMizojiri, R., Urabe,H., Sato,F.TL40,2557 (1999). 5Nii, S., Terao,J., Kambe, N. ,/oC 65, 5291 (2000). 6Urabe,H., Hamada, T., Sato, F. JACS 121,2931 (1999). TOkamoto, S., Takayama,Y., Gao, Y, Sato, F. S 975 (2000). 8Hamada,T., Suzuki, D., Urabe, H., Sato, F. JACS l2l,'1342 (1999). ' An, D.K., Hirakawa,K., Okamoto,S., Sato,F. TL 40,3'137(1999). r0Morlender-Vais, N., Solodovnikova,N., Marek, I. CC 1849 (2000). I lHuang, X., Zheng, W.-X . SC 29, 1297 (1999). r2Huang,X., Zheng,W.-X. SC 30, 1365 (2000). r3Yu,Y., Zhang,Y. SC 29,243 (1999). raHara,R., Sato, K., Sun, W.-H., Takahashi,T. CC 845 (1999). rsdeMeijere, A., Stecker,B., Kourdioukov,A., Williams, C.M. S 929 (2000). 'oOkamoto, S., Livinghouse, T. OM 19,1449 (2000). rTCampbell,A.D., Raynham,T.M., Taylor,RJ.K. CC 245 (1999). rsTakayama, Y, Okamoto,S., Sato,P. JACS l2l,3559 (1999). reOkamoto,S., Subburaj, K., Sato, F. JACS 122, 11244 (2000). 20Urabe,H., Hideura,D., Sato,F. OL2,38l (2000). 2 r S u n gM , . J . ,L e e ,C . - W , C h a ,J . K . S L 5 6 l ( 1 9 9 9 ) . 22Yamamoto, Y., Matsumi, D., Hattori, R., Itoh, K. JOC 64,3224 (1999). 2iTeng,X., Takayama,Y, Okamoto,S., Sato,F. JACS l2l,11916 (1999). 24Hanazawa,T., Okamoto, S., Sato, F. OL2,2369 (2000). zsHamada,T., Mizojiri, R., Urabe, H., Sato,F. JACS 122,7138 (2000). 26Denton,S.M., Wood, A. Sa 55 (1999).
Grignard
reagents-zinc
Reductive
alkylation.
*/
lvlgB
l,S-Dienes and l,S-envnttnentenes(derived from alkr.rrs. rre treated with alkynylmetals. h s ith iodine gives 1,5-enynes.
Cp2ZrCt2 K:K
R
EtMsBr
Cp-Z)
Alkenylcyclopropanes.a
Th
borohydride. Esters
are converted
to
secondary
alcohols
where
the
F.tMgBr and Cp2ZrCl2 converr-s r}r
G r i g n a r d r e a g e n tc o n t r i b u t e s o n e a l k y l g r o u p . l
R'MgBr
R.
R_COOEI +
Zn(BHiz
FOH R,'
rHallouis,S., Saluzzo,C., Amouroux, R. SC 30, 313 (2000).
Grignard reagents-zirconium compounds. 18, 174; 19, 1611,20, 180-1 8 I Organozincation.t On reaction with EtMgBr-Cp2Z{12, 1-alkenesgive 2-substituted dialkylzincs that can be usedin coupling reactions. Alkylsilanes.2 Grignard reagents are isomerized by Cp2ZrCl2.Subsequentreaction with hydrosilanes in the presenceof an alkyl bromide leads to silanes bearing a primary alkyl group.
Gagneur,S., Montchamp,J.-L.. \egu t'ra, Y., Hara, R., Takahashi.T. CC tl Dumond,Y.,Negishi,E. JACS l2l. l' 'Bertus, P, Gandon,V, Szymonral-J
ztl
Grignard reagents-zirconium compounds
R \
: , \ l e r l e r sA. SL 1999(1999).
i [r, -:r_ 1999). . :-:- rq99).
. ._.:rxn).
Cp2ZrCl2
t
Y MgBr
R. z'\ v siHPh2
B(CH2)3Br Ph2siH2
7,S-Dicnes and 1,S-enynes,3 Insertion reaction takes place when zirconacyclopentenes(derived from alkynes, ethylmagnesium bromide, and zirconocene dichloride) are treated with alkynylmetals. Protodemetallation leads to l,5-dienes, whereas oxidation with iodine gives 1,5-enynes.
R \: \ 919(2000).
!.
cp2ztct2
*t-J*
R'---€-rvi
CpZr
':t
D--E-D
R
/\
EtMsBr Cp2ZrJ
/
)
-
I i - , ,
*<
R
r.'{ ,llJ(1999). , 1 6( 1 9 9 9 ) . t:l
) l:
f(
MeOH:
R/.
t
- i' ,1(n0).
/'
R
)
t R
H
)
R
t,,
1,
//
HCI
\
R
// K
\ /
K--:-
R'
.L'condary alcohols where the
.f
a
-oH
t
1
r: , ,
-:
1 9 .l 6 l ; 2 0 , 1 8 0 - 1 8 1 lgh: t p-ZCl., 1-alkenesgive 2-substituted n. reaction n-.' .J h1 CplZrCl2.Subsequent " primary a bearing silanes ..j.' leadsto tr t.
Alkenylcyclopropanes. EtMgBr
The
zirconocene-+thylene
complex
generated
and Cp2Zr{12 converts the carbonyl group of enones to a cyclopropane ring.
Gagneur,S., Montchamp,J.-L., Negishi,E. OM 19,2417 (20OO). rUra,Y., Hara, R., Takahashi,T. CC 875 (2000). 'Dumond, Y, Negishi,E. JACS l2l, 11223(1999). 'Bertus, P., Gandon, V., Szymoniak, J. CC 171 (2000).
from
Hafnium0V) chloride. 20, 182 trans-Carbosilylationof allqnes.t Splitting of propargyl- and allenyltrimethylsilanesandadditionof thecomponents to alkynesis effectedby hafnium(IV)chloride.
Hexaalkylditin, 13, 142: 14, I 7-1-I 162-163:20. 182-184 Aldols.t Treatment of a mrrru Bu,SnF2,and HMPA in aq THF lealr Oxyfluoroalkylation.2 Ben,,r lx s hen styrenesare subjectedto phot.r
C6F13-l
Ph Ph......:
+
r
\ t^ \\
cH2ct2 0"
\-
/SiMe:r
\
Me3Si
*
50Yo
rYoshikawa, E., Kasahara, M., Asao,N., Yamamoto, Y. TL 41, 4499(2OOO).
Addition to propargylic alcoh R.MnLi, and (BujSn)2effect /rrrnr-a :husproducedbear an R group ar C-l
Additio n-e liminatio n sequ. nc c. :.rdicalto an electron-deficientdouh ,n the structural featuresof the .ut
- r eloalkanone oxime ethersidem()n 4-Halobenzyl bromides. Protection of alcohols.t Ether formation from ROH and 4-XC6HaCH2Brmediated by NaH in DMF is easily achieved. Such ethers are cleaved by Pd-catalyzed processes. 4-Bromobenzyl ethers can be cleaved by treatment with (dba)jPd2, l-BuONa, PhNHMe,
phO._.,,\,At
and then SnCla.4-Chlorobenzyl ethers are stable to these conditions but they are cleaved on changing (dba)rPdzto Pd(OAc)2. rPlante,O.J.,Buchwald,S.L.,Seeberger, P.H."/AC.S 122,7148(2000).
Ph,
/
/-D
LicH?cr i Ph,
,o-L |
b1-
lRen, L., Crudden,C.M.CC72l (2OO0).
2r2
-
ro1
/
.oH
*
o'\--o \-l
NOBz
,-^ Halomethyllithiums. Homologationr When alkylboranes are treated with LiCHTX before oxidative workup, insertion of a methylene group to the C-B bond is accomplished. Double homologation to some degree occurs with bromo- and iodomethyllithiums but nol chloromethyllithium.
Ph
l-
/
ll
so2Me
* //6-COOEI
\ h i b a t a ,I . , K a w a s a k i M , . , Y a s u d a\.t . l t r \ i r s h i d a ,M . , O h k o s h i ,M . , A o k i . \ . l r , r l t : u g i , S . ,T a n g ,J . , S h i n o k u b oH . .. O.hrn K i m . S . ,Y o o n ,J . - Y . ,L i m , C . J .5 1 -I l i I : K i m , S . , K i m , N . , Y o o n ,J . - Y . O h . D l l \
l. l, 1,3,3,3-Hexafl uoro-2-propano Epoxi"deopening. The reacrr .rlcohols is facilitated usingthe rrrlc RSH-H2O2 in thesamemediumre.u
I,1,1,3,3,3-Hexafl uoro-2-propanol
213
Hexaalkylditin. 13, 142; 14, l'73-11 4; 16, 114; 17, 143-144; 18, 115-17 6; 19, t62-163:20. 182-184 Aldols.l Treatment of a mixture of a-iodoketones and aldehydes with (BurSn)2, Bu2SnF2,and HMPA in aq THF leadsto aldols. Good diastereoselectivityis also observed. chain are formed Oxyfl.uoroalkylation.2 Benzylic alcohols containing a CH2C,,F2,,*1 when styrenesare subjectedto photooxygenationin the presenceof (Bu.Sn)2. ni ,,i propargyl- and allenyltrimethyls :. .llL'ctedby hafnium(IV) chloride. C6F13-l
*
hv (Bu1sn),CoFrg-1
N \-ph
"r,*;*
'.,o/-tn
tnr.-/t'""' 58%o
-_\ \\ 50%
:. 1l .rJ99(2000).
fr :: ROH and 4-XC6HaCH2Brmediated ! i:, .lcaved by Pd-catalyzedprocesses. p- .rrth tdba)rPdz,l-BuONa, PhNHMe' . : ::,c\e conditionsbut they are cleaved
2;
Addition to propargylic alcohols.t Tributylmanganate reagents generated fiom (BujSn)2 effect trans-addition to proparglylic alcohols. The allylic alcohols R.,MnLi,'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''and produced thus bear an R group at C-3 and are stannylatedat C-2. Addition-elimination sequence. Addition of a photochemically generatedfiee radical to an electron-deficientdouble bond engendersdifl'erentconsequencedepending on the structuralf'eaturesof the substrates.Routes to f'unctionalizednitroalkanestand cvcloalkanoneoxime ethers5demonstratethe versatilemethod.
o ph-\--O
PhO..-,2-r-r^:,
,)
-
So2Me
NO2
62Yo NOBz
NOBz
A
l:-
P hO...,rr\-...r^-...,r.
,ilOTBS
-:,rr1000).
::r,:r'il with LiCH2X before oxidative t ( -B bond is accomplished.Double x :--:,' and iodomethyllithiums but not
+
hv (t\,4e3Sn)2 ,
O
\-51'*
+ //2-cooEr
hv
(Me3Sn)2
|
\-ar\r\trl
83Yo 'Shibata, M.,Yasuda, M., Baba.A. CI.689( 1999). I., Kawasaki, I Yoshida, M.,Ohkoshi, M.,Aoki,N.,Iyoda.M. TL 40,573I ( 1999). 'LJsugi, H.,Oshima, K. Sa l4l7 ( 1999). S.,Tang,J.,Shinokubo, 'Kim,S.,Yoon,J.-Y,Lim,C.J..tL I l5l (2000). 'Kim, S.,Kim,N..Yoon,J.-Y.,Oh,D.H.51-ll48 (2000).
onr.
/ro,
uoro-2-propanol. 1,1,1,3,3,3-Hexafl Epoxide opening. The reaction of epoxides with arylamines to afford B-amino alcoholsis facilitatedusing the title compound as solvent.rTreatmentof epoxideswith RSH-HrO: in the samemedium result in B-hydroxy sultbxides.r
Hvdrazoic acid
IDas, U., Crousse,B., Kesavan,V., Bonnet-Delpon,D., Begue,I -P.JOC 65,6'749(2000). r Kesavan,V., Bonnet-Delpon,D., Begue,J.-P.TL 4l, 2895 (2000).
Hexamethyldisilane. Deoxygenation. Nitroalkanes, nitrones, and heterocyclic N-oxides submit their oxygen atoms to hexamethyldisilane.Nitroalkanes(via nitronate anions) are converted into oximes.l lHwu.J.R..Tseng, H.V, Wong,F.F.,Horng,D.-N.,Liaw,B.R.'Lin' L.C.JOC64,2211 W.N.,Patel, ( I 999)
Hydrogen fluoride-amine. 16, 286-187. I Oxidative fluorination, 1.6-Difl ucro enoder when dienoic esters are subjected tr A chemicalprocessemploying 3HF-EI,\ , -r-halotetrahydropyrans2and allyl alcohol
.ase study,only with NBS). The combination of HF-pyridine rrrth Jithiocarbonatesinto trifl uoromethvl ethers Nazarov clclization.s Cross
Hexamethyldisilazane,HMDS.13, l4l;18, 171 I78; 19' 163-164:20' I84-l85 Amide formation. HMDS promotescondensationof acidsand amines.r
F
\___
rChou.W.-C..Chou,M.-C.,Lu,Y.-Y,Chen,S.-F.TL 40,3419(1999).
'9
Hydrazine hydrate. 13, 144;18' I 79; 20, I 85 Reductive cleavageof diaryl diselenides.t.2 Gencrationof arylselenideanions by hydrazinehydrateis most convenientunderbasicconditions. Arylamines.r Reductionof ArNo. can be carriedout with hydrazinehydrateover a
Desilylation. Desilylationpromded accessof o-azido \a rn an enantioselective
cerium(lV)-tin(lV)oxidecatalyst. 'ev.A.A..Engman, I Vasif Andersson, C.-M.OM t8' l3l 8 ( I 999). L..Storm,J.P., :llenriksen, N. "ICS(Pi L., Stuhr-Hansen, ) l9l-5(1999). rJyothi,T.M., Rajagopal, S., Rao.B.S./CR(S)674 K.. Talawar,M.B.' Sungunan' R., Sreekumar, ( I 9S9).
o
,-Y/\-,^..T
j:Si-4
: N3
:. I
I Hydrazoic acid. x-Amino-z,y-Pyrandiones.r Introduction ol an amino group to pyrandioncsis by thcir direct exposure to NaNr-HOAc at pH 4--5. The adductswith HN. eliminate dinitroscnin situ.
: I-Aryl-3-hexenopyranosiduloses.an anl in a reactionthatintroduces erenes
,NHZ NaN, NaOAc
o<
_\_d 1
Ph
Fo
A
.-----------------*oa Fo "91: __\_ct .""on
1pn +-5;
\
"
Ph 94%
rKoulocchcri, S.D., Haroutounian,S.A., Apostolopoulos,C.D., Chada, R.K., Couladouros,E.A. Eloc 1449(t999).
Dinoiu, V., Fukuhara,T., Hara, S.. Yonede B.J. Pc D.F, Horney,M.J.,Pettus. Shellhamer, Dobrolsky,J.M.JOC 64, 1094(1999). Lubke,M., Skupin,R., Haufe,G. ./FC102.I lJ
Hydrogen fl uoride-amine
rt tt' 65. 6'749 (2000).
E
r< \
-re lic N-oxides submit their lr()natcanions) are converted
,u 8.R..Lin.L.C.JOC64,2211
Hydrogen fluoride-amine. 16, 286-287 ; 18, 18 I ; 19, 164-165 ; 20' I 85 Oxidative fluorination. 1,6-Difluoro-ct,B-unsaturated esters are produced at a Pt anoder when dienoic esters are subjected to electrolysis in MeCN containing 3HF-Et3N. A chemical process employing 3HF-Et.rN and NXS converts dihydropyran into 2-fluoro3-halotetrahydropyrans2and allyl alcohol into 3-bromo-2-fluoropropanolr (in the latter casestudy,only with NBS). The combination of HF-pyridine with 1,3-dibromo-5,5-dimethylhydantoin converts dithiocarbonatesinto trifl uoromethyiethers.a Nazarov cJclization.s Cross-conjugateddienonescontaining methylthio substituents give rise to fluorocyclopentenones.
t r
t e . I 6 . 1 -1 6 4 ;2 0 , l 8 4 - 1 8 5 ' .,eids and amines.l
MeS \
/,>-{.
MeS _. / P
t
/:\
(,
,/
\\
\ FO
/ \
h
//
N
6HF
+ \
Hs(OTf)z cH.cr2 67o/o
(
r,)n ot' arylselenideanionsbY
rj
s ith hydrazinchYdrateover a
t." t\
Desilylation. Desilylation promoted by 3HF-EtiN in THF constitutes the key step accessof a-azido ketones.6 in an enantioselective
rls(1999).
-^rtl
: , t n a n . S . . R a o , B . S . J C R ( S )6 7 4
tl
);)si.-
I
!rroup to pyrandionesis bY rtltluctswith HN1 eliminate
NHz \-n
----.-o Dh
THF O"
86To
l-Aryl-3-hexenopyranosiduloses.r 2-Acetoxyglycals serve as electrophiles toward arenesin a reaction that introduces an aryl group to C- I of the sugar moiety.
o"o\,_., / \ /
_
N3
Et3N-3 HF
nco"
AcO
\
v
/ OAc
94lo
( h a d a . R . K . , C o u l a d o u r o sE , .A.
rDinoiu, V., Fukuhara,T., Hara, S., Yoneda,N. JFC 103, 75 (2000). rShellhamer, V.L.,Syvret,R.G., J.M.,Heasley, T.L.,Stringer, B.J.,Pettus, D.F.,Horney,M.J.,Pettus, Dobrolsky,J.M.JOC 64, 1094(1999). 'Lubke,M., Skupin,R.,Haufe,G. JFC 102,125(1999).
216
Hydrogen peroxide, acidic
aKanie, K., Tanaka,Y., Suzuki, K., Kuroboshi, M., Hiyama, T. BCSJ 73,471 (1999). 5Hara,S., Okamoto, S., Narahara,M., Fukuhara,T., Yoneda,N. SL 411 (1999). 6Enders,D., Klein, D. SL719 (1999). THayashi,M., Nakayama, S., Kawabata, H. CC 1329 (2000).
Hydrogen
Rov,A., Reddy,K.R.,Mohanta. P_K.. ll
iodide.
Hydrodechlorination,
salts are dechlorinated
B-Chlorovinamidinium
by
HI
in
dioxane.r
*'f '*'
Y"' \*-*' R
PFo
* - *' l'l- rru
"'' \,
dioxane
Hp'drogen peroxide, basic. 13. I J5 Oxidations. Mildly basic co rlkenes.rFor epoxidationof,*ater u rcry similar system is useful for r srfluoroalkyl group to furnish alcol c-Formylpyrroles yield 2-p1'rroh
MeOOC
\
\r-*' R
/-coolte
(L""o
IDavies,I.W.,Taylol M., Hughes, D., Reider,PL OL2,3385(2000). Hydrogen peroxide. Activation, Catalystsfor alkene epoxidation with H202 include perfluoroheptadecan7-one,r butyl 2,4-bis(perfluorooctyl)phenyl selenide,2phenyldibutylarsine,3and HReOatriphenylarsine.aFor ring contraction of cycloalkanones,an oligomeric 9,1O-bis(diseleno)anthraceneeffectively promotes the action of hydrogen peroxide.sPolyfluorinated alcohols such as hexafluoroisopropanolalso activate hydrogen peroxide toward epoxidation and Baeyer-Mlliger oxidation.6 Oxidations. Alkene formation from alkyl aryl selenidesvia oxidation is cleanerwhen the aryl group is ort o-substituted(vs. para-substitution), for example, with a nitro group.T In the presenceof a phase-transfercatalyst,oxidation of aldehydesto carboxylic acids8with H2O2is successfullycarried out without an organic solvent,halide, or metal ion. rvanVliet,M.C.A.,Arends,LW.C.E.,Sheldon, R.A. CC 263( 1999). 2Betzemeier, 8., Lhermitte, F.,Knochel,P.SL489(1999). rvanVliet,M.C.A.,Arends,I.W.C.E., R.A. 7L 40, 5239(1999). Sheldon, avanVliet,M.C.A.,Arends,LW.C.E.,Sheldon, R.A.JCS(P/)3'17(20W). 5Giurg,M., Mlochowski, J. SC29,2281(1999). 6Neimann, K., Neumann, R. OL2,2861(2000). TSayama, S.,Onami,T. TL 41,5557(2000). nSato, K., Hyodo,M., Takagi,J.,Aoki,M., Noyori,R. TL 41,1439(2000). Hydrogen peroxide, acidic. 14, l'16; 15, 167-168; 16, 177-778; 17, 145; 18, I 82-l 83; 19,1661'20,187 Degradation of acylarenes,r Such carbonyl compounds are readily converted to phenols with hydrogen peroxide-boric acid.
Yao,H., Richardson,D.E. JACS 122. .r: Falck,J.R., Lai, J.-Y.,Ramana,D.\'.. tr Pichon-Santander, C., Scon,A.l. fL {1.
H1'drogen peroxide,
metal catalp
: Bf l 85; 19, 166-167; 20, I 88 Nitrones. N-Alkyl a-amino r nrtrones.l
Ph'^Nlrcoo
Oxidative esterification.: Thc nethyl estersin methanol (perchlorx Bromination,t Brominating ag .rtu from tetrabutylammoniumbromt
Oxidation,a In the presenceof 'ridized by H2O2-Na2W0. to affm rnd secondary alcohols, respecrtr
Hydrogen peroxide, metal catalysts
8('s"/73. 471(1999). .1 ll l (1999).
a
&
Roy,A., Reddy,K.R., Mohanta,P.K.,Ila, H., Junjappa,H. SC 29,3781 (1999).
Hydrogen peroxide, basic. 13, 145;14,156; L5, 167;18,183-184; 20, 187-188 Oxidations. Mildly basic conditions (NaHCOl) have been used to epoxidize r. are dechlorinated by HI in
:
rlkenes.r For epoxidation of water insoluble substrates,aq MeCN is a suitable medium. A very similar system is useful for oxidative cleavage of organostannanescontaining a perfluoroalkylgroup to furnish alcohols.2 a-Formylpyrrolesyield 2-pyrrolinones.r
- _R'
\
MeOOC
)r\ * ' * '
\
ll
fcooMe
COOMe H2O2- NaHCO3
\N'/.-cHo H
I f(
85%
t:.{ : r|()).
s::: ll O; includeperfluoroheptadecanand HReOaIr :'rcnvldibutylarsine,3 r -.. .rn oligomeric9,10-bis(diseleno)rs: ' :.t rorid€.5 Polyfluorinated alcohols x-
;r:roxide toward epoxidation and
I r -:::ticsvia oxidationis cleanerwhen tirr example,with a nitro group.T u:. to carboxylicacidsowith r ' .,.Jc'hydes , r m e t a li o n . r . . : . t .h r l i d e o :.
'")c)
).
Yao, H., Richardson, D.E. JACS 122,3220 (2000). -Falck,J.R., Lai, J.-Y, Ramana,D.V., Lee, S.-c. fa 40, 2715 (1999). ' Pichon-Santander,C., Scott, A.I. TL 41,2825 (2000).
Hydrogenperoxide,metalcatalysts . 13, 145;14, 177;15,294;17,146-148;18, I 84-185;19, 166-167 ; 20, I 88 Nitrones, N-Alkyl o-amino acids undergooxidative decarboxylationto afford nitrones.l
pnAruAcoon]11';1ll ph,'\iz\ EtaNUl- K2UU3 | { H2o
S'-:.tr1999). :-- i1000). i;
-.ll
::9 r1000).
. 1 6 ..
-r-178; 1 7 ,1 4 5 1 ; 8,
are readilyconvertedto | - 'r)p()unds
cH2ct2
O-
70%
Oxidative esterification,2 The H2O2-V2O5reagent converts aromatic aldehydes to methyl estersin methanol (perchloric acid is also present). Bromination.3 Brominating agent for activated arenes (e.g., phenols) is formed in situ from tetrabutylammonium bromide (oxidation by H2O2-V2O5). Oxidation.a In the presenceof a phase-transfercatalyst (BuaNHSOa),alcohols are oxidized by H2O2-Na2WOato afford either carboxylic acids or ketones (from primary and secondary alcohols, respectively). Because of its easiness in separation and
Ilydrosilanes
regeneration the heterogeneouscatalyst WOFSiO2 is useful for cleaving cyclopentene with H2O2to glutaraldehyde.s Nitriles.b Copper powder and various copper salts catalyze the conversion of aldehydesto nitriles by ammonia and H2O2in isopropanol. ' Ohtake,H., Imada,Y., Murahashi,S.-I.BCSJ 72, 2'137 (1999). 2Gopinath, R.,Patel,B.K. OL2,577 (20M). 3Bora,U., Bose,G., Chaudhuri, M.K., Dhar,S.S.,Gopinath, R., Khan,A.T.,Patel,B.K. OL 2,247
:nterestingly,direct deoxygenarr( rossiblewith Et.SiH and a caralrrrc Regioselectivity is imponanritr rtion of the two hydroxyl group\ rn :hat the combinationof Et.SiH *rrt :.0-O-benzylidenesugars' i: r.'n
rr drosilaneis catalyzedby PdtOAc r
(2000). 4Bogdal,D., Lukasiewicz,M. SZ 143(2000). 5Jin,R.,Xia, X., Xue,D., Deng,I.-F.CL3'71(1999). 6Erman, M.B.,SnowJ.W.,Williams,MJ.TL41,6749 (2O0O).
Dh---\-n-1 \ v /-\n
Bno'
/
/\;/ --OBn BnO
\
^ \
NHAc
Hydrogen sulfide. Alkyl poxoalkanedithioates.t The combination of H2S-BFj.OEI2 dealkylate one of the S-substituentsof acyl ketene dithioacetals in refluxing dioxane.
Thiono estersand lactones;rc c t:t,B.s Partial dechlorinationof Fr.lr
Ph
\\ )-SMe MeS
Rh-phosphinecatalystproceed.rn h
o
H2S- BF3.OEt2 dioxane A
S MeS
Cl
"'J'o
67Yo
\v a-Silyl enethiols.2 Acylsilanes react with hydrogen sulfide to provide a-silylated enethiols.A route to thiolactones passesthrough such intermediates.
Symmetricaltetraaryldisilanerrp :rrcly perlbrms hydrodehalogenarr rdductswith activatedalkenes.
r\
o ll tn-r,\.^aoo" /
\
s
H r S- H C I ;
- NaHCO3
H tn-si'\,^"oort I
,i\
tl S/\ t tn'a,'\r/
al
l
/ \
rNair,S.K.,Asokan,C.V.SC29,'191(1999). 2Bonini,B.F.,Comes-Franchini, M., Fochi,M., Mazzanti, G.,Ricci,A. 54 486(1999).
Hydrosilanes. 19, 167-169; 20, 188-192 Defunctionalizatinn, Hydrosilanes are better reagents than hydrostannanes for deoxygenation of alcohols via their xanthates.Thus, reasonablygood results are obtained by using the symmetrical tetraphenyldisilane under free radical conditions.l More
/" P-",*
X = SOzPh,COOEI
Reductions. Ketones are rcdtrc -()mplex(Ph,P)AuClcatalyzeshrdrr :. a precatalystin the reduction of
Hydrosilanes
f)
:- useful for cleaving cyclopentene
of Di!: .alts catalyze the conversion p{ l-rn,rl.
|.*,' ;r:,:
R..Khan,A.T.,Patel,B.K. OL2'247
interestingly, direct deoxygenation of primary alcohols and cleavage of ethers are possiblewith EtrSiH and a catalyticamountof (CoFs)rB.r Regioselectivityis important for reductivering opening of cyclic acetalsas differentiation of the two hydroxyl groups in a diol systemis often desiredin synthesis.The fact that the combinationof Et.SiH with TfOH and PhBCl2 operatein the oppositesenseon -1.6-O-benzylidene sugarsr is very valuable. Note that cleavageof benzyl esters with hydrosilaneis catalyzedby PdtOAcl'.i
t{-\$3-"'"'ruHn"
:: :-
enoy'"'N2"--OBn BnO
Thiono estersand lactonesare convertedto ethersby Ph2SiH2and catalytic PhrSnH, FlrrB.sPartial dechlorinationof polychloroareneswith triethylsilaneand a homogencous Rh-phosphinecatalystproceedsin high yields.6
Ph
\o )-t MeS t'
o -cooH
cl I \a\
cl
,\
Y
96%
Symmetricaltetraaryldisilanes(preparedtiom Ar2SiH2and Cp.TiPh2 at 120') efl'ecrivcly perfonns hydrodehalogenation.iHowevcr, the radical intermediatesreadily form .rdductswith activatedalkenes.
,il'.-.; /
-7-\
l(
I
t4'*
i**:::r reagents than hydrostannanes for Tl-.-.. rcasonablygood results are obtained re -rrJ!'r free radical conditions'l More
\/
lRhl
cl
Ph.si,\,/
r!:: (; . Rrcci.A. SL486(1999)'
t'Y\
Et?siH- Ph3P
i l l
I r...r:rr!eo sulfide to provide o-silylated t.,-r rntermediates.
\
NHAc
87%
,r of H2S-BFj.OEI2 dealkYlate one :lu\ing dioxane.
67Yo
?-
Hor5Si\.ov"
..:.r-:,r:: r\'4s4A7cH2cr2
eno-A9y'rn
la:
Bno-\
Er.siH- roH
+
'/ x ./\u
Ph
\
Ph>
.-7---
l(
|
AtsN/;;i LHlx
X = SOzPh,COOEI,PO(OE02
47-887o
A gold Reductions. Ketonesare reducedwith trialkoxysilane-histidinecomplexes.n .omplex (Ph,P)AuCl catalyzeshydrosilylationof the C:O group." Dibenzenechromium :. a precatalystin the reductionof aryl carbonyl compounds."'A systemcomprising
Hvdrosilanes
hydrosilaneand a copper salt has selectivereducingpower for ketonesand double bonds conjugatedto an aromaticring.r1For saturationof the enonedoublebond, a choicecan be made of PhMezSiH with the tris(triphenylphosphine)copper(I)fluoride-bisethanol adductrr or PhSiHj and Mn(dpm)..l:rReduction of esters to alcohols can use either diphenylsilanein the presenceof the [(cod)RhCl], complexraor trimethoxysilaneand t l MeOLi in THFr5 c a t a l y t i ca m o u n o Benzyl ethers can be prepared from THP ethers by the MejSiOTf'-catalyzed reaction with PhCHO and EtrSiH.r6Analogously,amides.carbamates,and ureasare N-alkylated with aldehydesfollowedby in situ reductionwith Et,SiH.r7The aldevia condensation hyde may be replacedby a thioesterthat is subjectto reductionin situ. Thus, a mixture of sodium triacetoxyborohydride, tricthylsilane,and Pd-C catalystis employed.rx
N
o H z
P hvv[\ o / v \ '
n '
o-r,,^"[r,o H o 5 s = ,
MeOOC r--Z X MeOOC \'
+ Me3si-o-si{H
Cyclization and hydrosrlrlatr :' process. Cp*.Y Me-catalyzed
o-l s* , l M e 3 S i O '- f Sl i - H
o
,-\
mainlr crc able.rl5,7-Alkadienals
Pd/c NaBH(OAc)3
-yo
\2
When the Pd-inducedclclrratr drosilane,the productsbecomt-h properhydrosilanes(e.g.. pentanx
W"^i'ovMl,n r^) F) - Y o ' n - ^ y o l O )< 93%
to oxcpancsis ellected A regioselective conversionof6,8-dioxabicyclo[3.2.1]octanes by a TiCla-catalyzed reductionwith EtrSiH.r') Benzyl azides undergo rearrangement-reductiontandem to allbrd N-methylarylamincsr0on treatmentwith Et.rSiH-Sncl1. Hydrosilylation. Allyl alcohols form cyclic structurcs in a Rh-catalyzedhydro-
n = 33-35
Dehydrogenative silylatioasrth r derivatives by hydrosilanes catalyst,respectively. Peptide synthesis.:" An \.
deblockedby a combination
silylationreactionwith Ph.SiH..rrRing openingoccursduring reaction of alkylidenecyclopropancs.l2
u
Ph + EtrSiH
(phrp)rRhcr ---;Ph. 20"
\:,/
SiEt3 f-J
/-// G = O , N s, T C(C@{
Hydrosilanes
k F: t-:
t'
l r
- r li)r ketonesand double bonds rc doublebond, a choicecan be . .opper(I) fluoride-bisethanol -r\ t0 alcohols can use either :r.lcr ' or t.rimethoxysilaneand :r \lc.SiOTf-catalyzed reaction :.rtcr. clndureasare N-alkylated ...rion with EtrSiH.rTThe alde..tr()nin situ.Thus,a mixtureof : i . r l s\ t i s c m p l o y e dr .E
22r
when the Pd-inducedcyclization of 1,6-dienesis carried out in the presenceof a hy_ drosilane,the productsbecomehydrosilyrated.23 primary alcoholscan be prepared with properhydrosilanes(e.g., pentamethyldisiloxane) to render the silylmethyl group oxidizable.21 5,7-Alkadienarsmainly cyclize to r:rs-2-alkenylcycropentyl silyl ethers.2s
FrC
MeOOC /--Z .MeooC . ^^^X, ^.
( H-tr" '4
Pd
):r FrC
+ Me3Si-O-Si(H)Me2
;
KF / ACOOH
tvteooc"^-f\oH MeOOC
\--2",,,
859o
. i o - /\
Et3siH
SEt
cyclization and hydrosilyration of nitrogen-containingenynes are achieve
Pd/c NaBH(OAc)3
I O-F - nS i M e : ,
' ?#t't"'
pd(oAc)2
|
Me3SiOJSi-H ' I
HoAc70,,
Me3SiO-f Si-OAc
n = 33-35
L
,,etancsto oxepanesis effected :r.icnr to allirrd N-methylary-
l -
Dehydrogenative silyration. l-Alkynes and amines are converred to sityl dcrivativesby hydrosilaneswith iridium carbonylrTand ytterbium-imine complexesrEas catalyst.rcspectively. Peptide synthesis.z') An N-alryroxycarbonyl derivative of an o-amino acid is dcblocked hy a combination ol'phsiHr and a pd catalyst. when an activatedestcr olanotheramino acid is present,it will be attackedby the released amine. cyclocarbonylation.rt) when cataryzed by a Rh-carbonyr speciesand under a co atmosphere,certain enediynesyield tricyclic ketones.Also involved in this reactronis PhMezSiH.
.rrr\ in a Rh-catalyzedhydro.luring rcactionof alkylidene-
"a--:---.^ + PhMe2siH G
SiEtr
,J" //
G = O, NTs,C(COOE|2
Rh4(co)12 1\
fl
t-n-J
)t1
{li I
Hydroxylamine
lTogo, H., Matsubayashi,S.,Yamazaki,O.,Yokoyama, M. JOC 65,2816 (2000). rGevorgyan,V, Liu, J.-X., Rubin, M., Benson,S., Yamamoro,Y. TL 40,8g1g (lggg). rSakagami,M., Hamana,H. TL 41,55.{7 (2000). a C o l e m a nR, . S . ,S h a h ,J . A . S 1 3 9 9( 1 9 9 9 ) . s J a n gD , . O . , S o n g ,S . H . S r 8 1 1 ( 2 0 0 0 ) . 6Esteruelas, M.A., Henero, J., Lopez, F.M., Martin, M., Oro, L.A. OM f8, 1110 (1999). TYamazaki,O., Togo, H., Matsubayashi,S.,Yokoyama,M. f 55, 3735 (1999). ELaRonde,F.J.,Brook, M.A. TL 40, 3507 (1999). eIto, H., Yaiima,T., Tateiwa,J., Hosomi, A. CC 981 (2000). r0LeBideau,F., Henrique,J., Samuel, E., Elschenbroich,C. CC 1397 (1999). " Ito, H., Yamanaka,H., Ishizuka,T., Tateiwa, J., Hosomi, A. SL 479 (2000). l2Mori, A., Fujita, A., Kajiro, H., Nishihara,Y, Hiyama, T. T 55,4573 (1999). r3Magnus,P, Waring, M.J., Scott,D.A. TL 41,9731 (2000). laOhta,T., Kamiya, M., Kusui, K., Michibata, T., Nobutomo,M., Furukawa,l. TL 40,6963 (1999). l5Ho.|o,M., Murakami, C., Fujii, A., Hosomi, A. TL 40,911 ( 1999). " ' S u z u k i ,T . . O h a s h i ,K . , O r i y a m a ,T . l - 5 6 1( 1 9 9 9 ) . S l i D u b e ,D . . S c h o l t eA . . A . T L 1 0 . 2 2 9 5, l 9 9 q ) . nHan,Y, Chorev,M. JOC 64. 1912(1999). reFujiwara,K., Amano, A., Tokiwano, T., Murai, A. 256, 1065(2000). r0|-opez,F.J.,Nitzan, D. TL 40,2071 (1999). r r W a n g ,X . , E l l i s ,W . W , B o s n r c hB , . C C 2 - 5 6 1( 1 9 9 6 ) . rrBessmertnykh.A.G.. Bilnov, K.A., Grishin, Y.K., Donskaya,N.A., Tveritinova, 8.V., Beletskaya, t.P.RJOC 34.799 ( | 998). r I Widenhoefer,R.A., Vadehla,A. TL 40, 8499 ( I 999). rrPei, T., Widenhoefer,R.A. OL2. 1469(2000). :5Sato,Y., Saito,N., Mori, M. JACS 122,2371 (2000). r6Molander,G.A.. Corrette,C.P. JOC 64,9691 (1999). rTShrmrzu,R., Fuchikami,T. TL 41,907 (2000). rtTakaki, K., Kamata,T., Miura, Y., Shishido,T., Takehira,K. JOC 64.3891 ( l9S9). r')Thicriet,N., Gomez-Martinez,P, Guibe, F. TL40,2505 (1999). 'oOjima, I., Lee, S.-Y.JACS 122,23t15(2000).
Hydroxylamine. Tricyclic lbllowing
isoxazolidines.r
The possibility
exists for an intramolecular
reaction
oximation of certain ketones that contain double bonds at proper distances.
Based on this concept, a potential precursor of histrionicotoxin has been assembled.
,/,CN 'a
NH2OH. HCI + NaOAc N.4eOH
N n
\ t
/
\-"iV I
CN
r S t o c k m a nR , .A. fZ4l.9l63
(2000).
\
H 1'droxy(tosyloxy)iodobenzem- | t0. 193 Cleavage of N',N'4iaItvILl - leavagemethod. The furan ring ra Alkynyl tosylates.z Tosl lorl eund-assisted,AgoTf-catalyzed n
\\'uts,P.G.M.,Goble,M.P.OL 2. ll!9 Tuncay,A., Anaclerio,B.M.. Zllcdz- .
H 1-pofluorous acid-acetonitrila I N-Oxides.t This compler rs r Dayan,S.,Kol, M., Rozen,S.S l{l?,
Hypophosphorous acid. Radical rcactions.t The rx Bu,SnH but without the many prob
Graham,S.R.,Murphy,J.A.,Coarcs"I
Hypophosphorous acidiodiDe Reductions.t Diaryl kerom f'enzaldehydeand aliphatic kerorn Joublebond only. Hicks,L.D.,Han,J.K.,Fry A.J.IL .|l
Hypophosphorousacid-iodine , y
i .::
r , fi5
h: l\lf'rl(X)0r. { r . \ 9 1 9 ( 1 9 9 9) .
,. ,/r/ lE.lll0(1999). -rtrlt)991.
cleavage of N',N'-dialkylhydrazides.t Mild conditions are involved in this cleavagemethod. The furan ring in a substrateis not degradedby the oxidant. Allcynyl tosylates,2 Tosyloxy group transfer to l-alkynes is effected in an ultrasound-assisted,AgOTf-catalyzed reaction. iWuts,P.G.M.,Goble, M.p.OL2,Zt3g (200C.l. rTuncay, A., Anaclerio, B.M., Zolodz,M.,Suslick, K.S. TL40,5gg 1ggg).
' .- l()(19). -- :rNX)). -'-r 1999).
r ' . ' : . : ' . r k a n r1. . T L 1 0 , 6 9 6 3 ( 1 9 9 9 J
Hypofluorous acid-acetonitrile. lg, lgg; 19, l7O;20,193 N'oxides.t This complex is a new reagentfor oxidation of tertiary amines. r Dayan,S.,Kol, M., Rozen,S. S 1427i1 ggg\.
Hypophosphorous acid. Radical reactions.t The acid mediates c-{ bond formation in a simirar way to BujSnH but without the many problems associatedwith the tin reagent.
t '
t.
Hydroxy(tosyloxy)iodobenzene.14,179_lg0; 16,179;17,150;1g, lg7; 19,170; 20, lg3
r
frc'ritinova, 8.V., Beletskaya.
lGraham, S.R.,Murphy,J.A.,Coates, D. TL 40,2415(1999).
Hypophosphorous acid-iodine. Reductions.t Diaryl ketones are deoxygenated by this reagent system while benzaldehydeand aliphatic ketones are not affected. Chalcone undergoessaturation at the double bond only.
6J. ittgl ( 1999).
:Hicks,L.D.,Han, J.K.,Fry A.J.TL4l,78t7 ?OOU.
: un intramolecular reaction '.r honds at proper distances. '.rn hasbeenassembled.
,,CN N
o\
\-t-Y
\
t
./ CN
r I
Imidazole. 20. 194 Thioethers.I Alkylation of thiols with alcohols under the Mitsunobu reaction
In the presence of ar compoundsare reduced b Aroyl cyanides undeq Allylatian of carbt toward aldehydesenable \\'stem in ring A.e Alll \ln-MejSiCl in THF.;'
Fluorinated homoall;. honyl compoundsrror tlx
conditions is catalyzed by imidazole. rFalck,J.R.,Lai, J.-y.,Cho,S.-D.,yu,J.TL40,2903(1999).
2-Imidazolylidenepalladium
fli tI
complexes. bis(imidazolylidene.)r and mixed imidazolylidene-phsophine complexes2ofpalladium (1,2) aregood catalystsfor promoting Suzuki and Stille coupling Couplings.
Both
*;
reactions.
Y Y
P "'P
/N
.N\ -<( )F tl lt -N
Pd
N-
-\
/r (1)
h
I
/
\
P
h
N.v/ N -/
I
t-Pd- |
\
PR:
(2)
Allylation of acylsrh .-diketones16is also easr Jiene-4,5-diol.However end then allylindium reag
Carbonyl compounds
r'tals (e.g., trifluoroacet :hesecaseshomoallylic a The employment of fl .ompoundsin one step.:'
rBohm, V.P.W.,Gstottmayr, C.W.K., Westkamp, T., Herrmann, W.A. IOMC 595, 186 (2000). 2Westkamp,T., Bohm, V.PW., Herrmann, W.A. JOMC 585, 348 (1999).
\ Indium. 14, 8l; 16, 18 l-l 82; 18, I 89; 19, 17l-17 3; 20, 194-197 Reductions, Reports of rather simple reductions by indium keep appearing: of ct-halocarbonyl compounds in water with ultrasound assistance,' of p-nitrobenzyl ethers and esters,2disulfides,3 amine N-oxides,a and organic azides5 in alcoholic solventsin the presenceof NHaCl. When the azide reduction is carried out in DMF the products can be directly converted to carbamatesby having a chloroformate ester in the reaction vessel.6
cl
Fo*
MeO
In / DMF PhNS PhN3 + FO MeO 90To
o a 8 OH
The organoindium rc: -rrbon atom,22whereas I .r the presenceof indium
Br \
In the presence of an electron acceptor (e.g., 2-bromo-2-nitropropane), 2-nitroaroyl compounds are reduced by indium to [c]benzoisoxazoles.T Aroyl cyanidesundergo reductive coupling to furnish a-diketones in moderate yields.s Allylation of carbonyl compounds. The chemoselectivity of allylindium reagents toward aldehydesenableselaboration of the steroid side chain without affecting the enone system in ring A.e Allylation is also viable using a catalytic amount of indium and ,. under the Mitsunobu reaction
Mn-MerSiCl inTHF.ro Fluorinated homoallylic alcohols are readily prepared from fluorine-containing carbonyl compoundsrror the allylic halides.r2'r3
imidazolylidene-phsophine f, : :-:,'ntotingSuzukiand Stille coupling :rrred
nj
{x:,."X^;; $?..^ OH
57To
-- \.-.N-7
Y
-ld-l
\
PRg
(2)
Allylation of acylsilanesraand a-ketoesters15proceeds normally. Monoallylation of a-diketonesrbis also easilyrealized,whereasglyoxal N,N-monohydrazonegives I,7-octadiene-4,5-diol. However, sequential reactions of the glyoxal monohydrazone with RLi and then allylindium reagentlead to unsymmetricaldiols.r7 and hemiacCarbonyt compounds in certain protected forms such as gem-diacetatesrs etals (e.g., trifluoroacetaldehydeethyl hemiacetalre)also undergo allylation, giving in thesecaseshomoallylic acetatesand homoallyl alcohols, respectively. The employment of functionalized allylic bromides servesto construct more elaborate compoundsin one step.2(r2l
r:-' : \\'.A.JOMC595,186(2000). sli.r : : r r 1 9 9 9 ) .
2I. t94-197 d u .: :,,n' by indium keep aPPearing:of li.: . ,und assistance,rof p-nitrobenzyl i
L.
'
.rnd organic azides5 in alcoholic :!'duction is carried out in DMF the nrr ing a chloroformateesterin the
PhNH
-
F \ a^
MeO 90o/o
"+,,.^aA ;H;"by X=O,NPh
The organoindium reagent derived from 5-bromo-1,3-pentadienereacts at the central agent behavesas a 1,3-butadien-2-ylating carbon atom,22whereas 1,4-dibromo-2-butyne in the presenceof indium in aqueousmedia.23
.
""'o"o\4. ,I* tl O
In/H2o
OH
Different regioselectivities for the addition to azetidine-2,3-dionesby organometallic reagentsprepared from propargylic bromides and zn or In are observed.2a Allenyl derivatives are produced exclusively with In in a mixture of THF and saturatedNH4C1. 4-Ally\-2-azetidinones are synthesizedby displacement of the corresponding acetoxy derivatives.25A preparation of homoallylic amines can take advantageof the reactivity of allylindium reagentson iminium speciesthat are formed in situ.26 n-Allylpalladium speciesfrom the Pd-catalyzedcoupling of ArI with allene undergo Pd/[n exchangeand subsequentreaction with aldehydes,enabling a three-componentassemblage of homoallylic alcohols.2T The reactioncan be further extendedwith an alkyne relay.28
,,R
Ar-l +
tl
a
tl
Pd(OAc)2 / 2-Fu3P
+ R'CHO + I n/ D M F 8 0 .
(Y'
RCH.
-,+
\-r\r-.-O.-ZC-
Ar
(Ph3P)4Pd "t\'lIn/DN.4F
\,,)\.=-O
OH
ll ten.e1.eo f +ArcHo+i ,# <\
z\r.l
QI-.'"-r,
-
an
X = o, NR, CR2
\-\-X
1,4-Dienes.2e Allylation of functionalized hydroxylated alkynes leads to 1,4-dienes. Regioselectivity dependson the distance between the hydroxyl group and the triple bond: Propargylic alcohols give linear products due to chelation control, but branched 1,4-dienes are obtained from 4-pentynol and higher homologues. when quenched with an N-halosuccinimide, halogen-containingproducts are obtained.
Allylarenes,3o
C-Allr larrt'n
carbonate and molecular siere. J
Ranu,B.C., Dutta, P., Sarkar..\ ./(' : \ , l o o d y ,C . J . , P i t t s ,M . R . 5L l:-: R e d d y ,G . V S . , R a o ,G . V . .I r e n s r I 'Yadav, J . S . ,R e d d y ,B . V . S . .R c ' d r i r!. 'Reddy, G . V S . , R a o ,G . V . I r e n g u I \hdav, J.S.,Reddy,B.VS.. Reddr (
K i m , 8 . H . , J i n ,Y , J u n ,Y M . . t l a n . I 'Baek, H . S . ,L e e , S . J . Y , o o .B . \ \ ' . X r 'Loh, T.P, Hu, Q.-Y.,Virtal. J.J il. 5 ..\uge,J., Lubin-Germain.N.. Thrn Loh, T.-P.,Zhou, J.-R.,Li. X -R A. Loh, T.-P.,Zhou, J.-R.,Li. X.-R IJ Percy,J.M., Pintat,S. CC 607 r:r I r, 'Bonini, B . F ' .C , o m e s - F r a n c h i n\rt . . 6 4 , 8 0 0 8( 1 9 9 9 ) . 'Loh, T . P , H u a n g ,J . - M . .X u . K . - ( . r Nair, V., Jayan,C.N. IL 41. l()91 : Ccre.V., Peri. F., Potlicino. S.. Rr..r 'Yadav, J.S.,Reddy.B.V.S..Reddr ( 'Loh. T . - P ,L i , X . - R .2 5 5 . 5 6 1 I , l q
Choudhury,PK., Foubelo.F..\'u.. I Paquette,L.A., Kem, 8.8.. \ten&z-t rMclekhov,A.. Fallis,A.G. 11{0. 'Lu, W . . M a , J . ,Y a n g ,Y . C h a n .T l l '.\lcaide, 8., Almendros,P. Arason'Kang, S . K . ,B a i k ,T . - C . ,J i a o .\ - t . t. C h o u c a i rB , . , L e o n ,H . , M i r e . \ l - . \
A n w a r ,U . , G r i g g ,R . , R a s p a n n r\.l '.{nwar, U., Grigg, R., Sridharan.\ ( 'Klaps, -::' 8 . , S c h m i d ,W . J O C 6 1 . 'Lrm, H . J . ,K e u m ,G . , K a n g .S t s . t r r
Indium-Indium(III)
chloride.
5-Aryl-4-penten-2-ones.
l
OH
:_l._ \
OH
+
e e Br
Br
H:o'
ln/THFI
H:o-
R
nrcthyl vinyl ketone and ArCH() t
C
-\o"
Y\
+ oHc'--/
o
l
--a OH
Kang, S., Jang,T.-S.,Keum. G.. Kanr
Indium-Indium(III) chloride
,11
by organometallic r::.:::rr'-1.-J-diones Allenyl deriva| : i:', :rre observed.2a NH4CI. I I l{i .rndsaturated ic:t.r'irl t)f the correspondingacetoxy a:. :.ri,. advantageof the reactivity of
c-Allylation of arenes is catalyzed by indium (0.1 equiv). calcium sieves 4A are also present in the reaction system. and molecular carbonate
nr.::n ritu.l6 c. .::lrng of ArI with allene undergo t. r::.rhllng a three-componentassemr.:.-: c'\tendedwith an alkyne relay.28
rYadav,J.S.,Reddy,B.V.S.,Reddy,M.M. fL 41,2663 (2000). sReddy,G.V.S.,Rao, G.V, Iyengar,D.S. ZL 40, 3931 (1999). "Yadav,J.S.,Reddy,B.V.S.,Reddy,G.S.K.K. NJC 24,571 (2000) 'Kim. B.H., Jin, Y., Jun,Y.M., Han, R., Baik, W., Lee' B.M. TL 4l'2137 (2000)' ! B a e k ,H . S . ,L e e , S . J . , Y o o 8 , . W . , K o , J . J . ,K i m , S . H . ,K i m , J . H . T L 4 l ' 8 0 9 7( 2 0 0 0 ) ' ')Loh, Vittal, J.J.5Z 523 (2000). T.P, Hu, Q.-Y., r"Auge,J., Lubin-Germain,N.. Thiaw-Woaye,A. TL 4O,9215(1999). I I Loh, T.-P, Zhou, J.-R., Li, X.-R. TL 40,9333 (1999). rLoh, T.-P, Zhou, J.-R.,Li, x.-R. EJOC 1893 (1999). ; ' P e r c y J, . M . , P i n t a t ,S . C C 6 0 7 ( 2 0 0 0 ) . rrBonini, B.F., comcs-Franchini,M., Fochi, M., Laboroi, F'.,Mazzanti,G., Ricci. A., varchi, c. "/oc
"
;RoH
l r l xrVR'
).t:
: .Pd :.'lF
d: ' ...rtcdalkynesleadsto l,4-dienes' i^- : .JrorYl Sroupand the triple bond: ili:. :r !()ntrol, but branched1,4-dienes 1.;:. \\'hen quenchedwith an N-halo-
Allylnrenes.lt)
lRanu, B.C., Dutta, P.,Sarkar,A. JCS(Pl) 1139 (1999). rMoody, C. J., Pitts, M. R. ^tl, 1575(1999). 'Reddy, G.VS., Rao, G.V., Iyengar,D.S. SC 30, 859 (2000).
6 4 . 8 0 0 8d 9 9 9 ) . ' L o h , T . P , H u a n g ,J . - M . ,X u , K . - C . ,G o h , S . - H . ,V i t t a l ,J . J .7 L 4 l ' 6 5 1 1 ( 2 0 0 0 ) . "Nair',V., Jayan,C.N. ZL 41, l09l (2000). -Cere. V . . P e r i .F . . P o l l i c i n o ,S . , R i c c i ,A . S L 1 5 8 5( 1 9 9 9 ) . ' Y a d a v ,J . S . .R e d d y ,B . V . S . ,R e d d y ,G . S . K . K .f L 4 1 ' 3 3 7 6( 2 0 0 0 ) . ''Loh. T.-P.Li, X.-R.255, 56l l (1999). r"Choudhury,P.K.,Foubelo,F., Yus, M. T 55 10119(1999):JOC 64,8008 (1999)' :l Paquette,L.A., Kcrn, 8.E., Mendez-Andino,J. TL 40. 4\29 (1999). rr Melekhov,A., Fallis,A.G.'l L 40, 7867 ( 1999\. r' Lu, W., Ma, J., Yang,Y., Chan,T.H. O L 2, 3469 (2000). r r A l c a i c l e8, . , A l m e n d r o sP , . OL 2, l4l I (2000). , , A r a g o n c i l l oC r ' K a n g , S . K . ,B a i k ,T . - G . ,J i a o ,X . - H . , L e e , K . - K . ' L e e ,C . H . S L 4 4 7 ( 1 9 9 9 ) ' r " C h o u c a i rB, . , L e o n ,H . , M i r e , M . - A . , L e b r e t o nC , . , M o s s c t ,P O L 2 ' l 8 5 l ( 2 0 0 0 ) ' r- Anwar, U., Grigg, R., Rasparini,M., Savic,V., Sridharan'V.CIC645 (2000)' I ' A n w a r , U . , G r i g g ,R . , S r i d h a r a nV, . C C9 3 3 ( 2 0 0 0 ) . r''Klaps,h,.,Schmid,W. JOC 64,753'7(1999). '"Lim, H . J . ,K e u m ,G . . K a n g ,S . B . ,K i m , Y . . C h u n g ,B . Y f L 4 0 ' 1 5 4 7( 1 9 9 9 ) '
Indium-Indium(Ill)
chloride.
5-Aryl-{-penten-2-ones,t
Reductive
homoaldol
reactions are ef'fectecl between
nrethyl vinyl kctone and ArCHO by In powder (200 molTo) and lnCll in aq THF
=
\--oH
\r\
o
+ oHc
I n- I n C l 3 H2O - THF
Kang,S., Jang,T.-S.,Keum, G., Kang, S.B Han.S.-Y. Kim.Y. OL 2, 3615(2000).
Indium(III)
chloride
Indiumfl) bromide. Bromocyanomethylation,t The organoindium species that are formed by insertion of InBr into a C-Br bond of dibromoacetonitrile reacts with carbonyl compounds. Generation of the antlbromohydrin is favored in the case of a bulky aliphatic aldehyde. Such productsserveas precursorsof glycidonitriles.
Br
I
InBr :
Sf I
h
Fo
* crA.
*.-rron
*.Fo*',.-(cN;:n,)-c^r
Sp2' Displacement- .l: produced from acetylglycals u'ith proper nucleophiles.t'
rNobrega,J.A., Goncalves,S.M.C., Peppe,C. TL 41,5ii9 (2000).
Cyclization reactions. { unsaturated alcohols and th natternsafter the Prins reactrq
("' chloride. 19, l'l 3-174; 20, 197-198 Aldol reactions. Aldol products are obtained in good yields from reaction of ketones with glyoxylic acid monohydrate with assistanceof ultrasound irradiation.r substrate-control(by 1,3- * 1,5-asymmetricinduction) of the aldol reaction involving Indium(Il! 1i
P
H
1-amino-ct-ketoestersunder solvent-free conditions is very effective.2 With lithium dicyclohexylamideand InCl. the reaction of esterswith aldehydesfurnishesB-hydroxy esters, and that of a-bromo esters affords ct,p-epoxy esters.s These are typical Reformatskyand Darzensreactionproducts,respectively.
C y 2 N L.i l n c l 3
Br_ cooMe *ffi
pnAo
'
-r)
,nl\i_coove 80To
Reductions. The lnCl.,-BujSnFVPhjPcombination (catalytic in indium) reduces acid chlorides to aldehydes.aAryl ketones and secondary benzyl alcohols are deoxygenatedwith hydrosilanesusing Inclj as catalyst.sDeoxygenativeallylation of aryl ketonesoccurswhen allyltrimethylsilaneis added.6
A one-step synthesis of c glyoxylate is mediated by InCl
Ph
(
.
uo^qi-J
/-
lnCl. NIe2Si(Cl)H
*'\_
cH2cl2
R 67%
Propargylation.l An approach to epoxyalkynes involves indium-mediated reaction of ct-chloropropargylsulfides with carbonyl compounds.Interestingly,opposite stereoselectivityis shown by a reactionusing In and InCl..
*
u*7 oHc
N ilro gen heterocy clcs. various InClj-catalyzed cych skeleton,characteristicof scrc
Indium(Itr) chlorlde
ll: ll: I
.rc'cles that are formed by insertion rcacts with carbonyl compounds. -.r\c of a bulky aliphatic aldehyde.
SPh
Ph
Fo*
cr\.
H
Sph
\gnlt /
Br
_
20
:
8
0
88
:
1
2
Incl3 + ( cHzcr2
-|
\ |
|
pnAoApn 81Yo
oO.'rl+*G{
COOMe
,'n (catalyticin indium) reduces .ccondary benzyl alcohols are ' Deoxygenativeallylation of aryl
37To
A one-step synthesis of ct-amino-1-lactones from arylamines, alkenes, and methyl glyoxylateis mediatedby InCl or Sc(OTf).1.14
I
R'
67%
t'
ln InCl3
\1 * pnAo ,oArn
E0%
tr'
K\
r\|
z-\
:h aldchydesfurnishes B-hydroxy e:. (r. -:.\\\\ esters.rThese are typical - \ r.
ir
:
Sr2' Displacement. A2-Glycosides of both the normal and carbon-series are produced from acetylglycals (Ferrier rearrangement) by Incl-catalyzed glycosylation q with propernucleophiles.8 cyclizltion reactions. 4-chlorotetrahydropyrans and -thiopyrans are formed from unsaturated alcohols and thiols on condensation with carbonyl compounds, which patternsafter the Prins reaction.lLl2 chlorinated oxepanesare similarly accessible.l3
L . :rl s(x)d yields from reaction of h ,.-.rrncc of ultrasoundirradiation.r l of the aldol reactioninvolving d.r: . . i. icry effective.2With lithium
t:
Sph
' a X. O H <
n^
prr
I
H2._DMF x\.
\
lc
E
Ph
_
nr olvcs indium-mediatedreaction .i'. lntcrestingly,opposite stereo-
R-
MeO-
oHC
R'
' ^, rY,,2 ,tl,dri{
/'\
* Hrr^"
Nitrogen heterocycles. Aziridines,15oxazoles,16and quinolinesrT are formed from various InCl-catalyzed cycloadditions and cyclization reactions. The pyrroloquinoline skeleton,characteristicof severalalkaloids, can be assembledin one step.r8
Indium(trI) hydride
o o
A VruAn
+ -.-/( N_
\)
R = Ar, COOMe
Diels-Alder
reaction,te
lndiumfl) iodide. Ally lation and p ropatgrb :ndium(I) iodide form organo
l *'^lu1
MecN /,>a\/ (/._I.
nesylates2that react with cartr Homoallylalcohols.: lry .r allylstannanes.
H
The
cycloalkenones is enhanced by InCl
ll'
l Incr3 +
dienophilic
reactivity
of
ethyleneacetals
of
rLoh, T.-P.,Wei, L.-L., Feng, L.-C. SZ 1059 (1999). 2l-oh, T.P., Huang, J.-M., Goh, S.-H., Viual, I .J. OL 2, l2gl (2000). 3Hirashita, T., Kinoshita, K., Yamamura, H., Kawai, M., tuaki, S. "/CS(p1) S25 (2000). alnoue,K., Yasuda, M., Shibata,I., Baba,A. TL 41,113 (2000). sMiyai, T., Ueba, M., Baba, A. SL 182 (Iggg). 6Yasuda,M., Onishi, Y., Iro, T., Baba, A. TL 41,2425 (2000). TEngstrom,G., Morelli, M., Palomo, C., Mitzel, T. TL 40,596i. (lggg). 8Babu,B.S., Balasubramanian,K.K. TL 41, lZ71 (200U. " G h o s h ,R . , D e , D . , S h o w n ,B . , M a i t i , S . B . C R 3 2 l , l ( 1 9 9 9 ) . roYang,J., Viswanathan, G.S.,Li, C.-J. TL 40, l62j (lg9g). "Yang, J., Li, C.-J. 5L717 (1999). r2Yang,X.-F., c.S., Li, C.-1. TL4t, 1321(2OOO). r3Li, J., Li, c.-J. 1153, t69l (2ooo). 'oHuang, T., Li, C.-J. TL 41,9747 (2O0O). rssengupta,S., Mondal, S. TL 41, 6245 (2000). 'nSengupta,S., Mondal, S. 24 40, 8685 (1999). rTRanu,B.C., Hajra, A., Jana,U. TL 41,531 (2OOO). 'nHadden,M., Stevenson, P.J.TL 40, 1215 ,1r99q. leReddy,B.G., Kumareswaran, R., Vankar,y.D. ZL 41, 10333 (2000).
Indium(Ilf hydride. Reductions.t The InHs@cyi)i complexreducesketonesand epoxidesto alcohols. Enonesand ct-bromoketonesafford allylic alcoholsand bromohydrins,respectively. Estersarenot reduced.
OH ll
OH
(Cy3P)3lnH3
|
tn-t,Aou ,"
P h M e7 8 " - 0 "
tnrrn OH
100vo
'Abemethy, C.D., Cole,
ffi
through complexation.
M.L., Davies,A.J., Jones,C.TL41.7567 eO00\.
\ou'.
\rakr, S.,Kamei,T., Hirashita,T.. \tarshall,J.A.,Grant,C.M.JOCa
Indium(Il!
iodide. Transacylationr Alcohol .rtalyst. Selectiveacylationof p rmlnes (vs. secondaryaminesar
Ranu,8.C.,Dutta,p.,Sarkar..{../C
Indium(Ilf
triflate. Acylation.t Catalyzed br rnhydride.
H etero- Die I s-A lder reacti rminesto generateN-substitutc rtfected by this salt. A mixrure .'mployedinsteadof imines.
Chauhan, K.K.,Frost,C.C.,L-ove. L .{li, T.,Chauhan, K.K.,Frost,C.C.i
Iodine.13, 148-149;14, l8l-lt t99-200
Iodohydrins. Iodohydnns rodine-manganese(salen) compk irom iodine and AcSH.2
237
Indium(I) iodide. Allyration and propargyration reactions. In the presence of the (phjp)opd catalyst, rndium(I) iodide form organoindium(Ill) reagents with allylic haridesr and propargylic mesylates2that react with carbonyl compounds in vanous solvents. Homoallyr arcohors.2 Indium(III) iodide catalyzesalrylation of carbonyl compounds bv allylstannanes.
:..1.tr\l[\ ,.:::.rn.
X
of
ethyleneacetalsof
\*.o*"r)
hl - (dppf)PdCl2
THF - HMPA
- . r t r
:,r(-SrP1/825(2000).
-,
fi.
..- 1999).
ll I
760/o (anti: syn 95 : 5)
.taki, S., Kamei, T., Hirashita, T., yamamura, H., Kawar, M. OL 2, g47(2000). :Marshall, J.A., Grant, C.M. JOC 64, A2lS OSgSli.
j.
9.
Indium(III)
iodide. Transacyrationr Arcohols and amines are acylated with an ester usrng InIs as caralyst' selective acylation of primary alcohols (vs. secondaryalcohols and phenols) and amines (vs. secondaryamines and primary alcohols) is possible. Ranu,B.C.,Dutta,p.,Sarkar,A. JCS(Pl ) 2223(2000\.
Indium(III)
triflate. Acylation.t Cataryzed by this sart, alcohols and amines are acyrated wrth acetic anhydride. |,.:. \.rones and epoxidesto alcohols. o.: .rndbromohydrins,respectively.
-
YI
9H -Ptr
Hetero-Diers-Alder reaction.z The condensation of Danishefsky,s diene with rmines to generateN-substituted 2-aryr-2,3-dihydro-4-pyridonesat room temperature is effected by this salt. A mixture of aldehydes, amines, and the dehydrant MgSoa can be employedinsteadof imines. ,F::,-Lc:c .Love,r., waite,D. sL 1743(lsss). lil.**.r.. Lhauhan, 'Al. : K.K.,Frosr, C.C.TL 40.5621 ( 1999).
OH 100o/o
tt
- . r - r( 2 0 0 0 ) .
[ll;}att'
r48-r4e;14,18r-182;15,172-173; 16,182;18, 18e-1e1; re,t74-175;20,
Iodohydrins' Iodohydrins are. formed by opening of epoxides using either iodine-manganese(saren)complexesr or anhydrous HI, which is conveniently generated from iodine and AcSH.2
Protection and deprotection offunctianal groups. Alcohols and their tetrahydropyranyl ethers are interconverted with iodine as catalyst.3.aEtherfication is done in a nonhydroxylic solvent, whereasthe ether cleavageis achievedin MeOH. Regeneration of carbonyl compounds from oximes is accomplished by heating with iodine in MecN,s and a mild workup of the products from reduction of amides with borane involves treatment with iodine.6 Iodinations. Arenes undergo iodination with iodine and an oxidant (e.g., potassium permanganate or manganese dioxide.i sodiumiodateor periodate.8 or tetrabutyl-ammonium peroxydisulfatee). One method for the a-iodination of ketonescalls for the assistanceof seleniumdioxide.r0 Heterocyclization. A new route to a-iodo boronic acids consists of iodoetherification.rr B-Iodobutenolidesthat are useful for carbon chain extension at the B-position (via Pd-catalyzedcoupling) are readily accessibleby iodolactonizationof allenic acidsr2
lll' 12-THF;
-u1 cooH
-#"
Unusual results are obtained from the treatment of O-(3-cyclohexenyl)thiocarbamidate esterswith iodine.ls
1-\o \_/
t2- THF
)_snr"
EtN
Na2SO3
, / \ t""( )",I \ . / t-
Et_N
Iodine(I) bromide. 20, 2M Cleavage of TBS ethen. \ r-butyldimethylsilyl ethers are clear Iodoetherification.z Regro.cl eccomplished through iodolacrom rnd hydrolysis.This procedurerr rr
__vo < o- \ /
o/t
Kartha. K. P R. Field. R. A. SL -1I I , I { '\Iarshall, J. A., Yanik, M.M. ./OC 61. !
Iodine(I) chloride. 20, 2m Iododesilylation.t The silr I , rcactionwith 2 equiv of ICI and I o Iodination. The stereoseletrcaction of ICI and then NaI is in*r
Ph
)-su" o 69%
rSharghi,H., Naeimi, H. BCSJ 72,1525 (1999);./CR(S)310 (1999). 2Chervin,S.M., Abada,P., Koreeda,M. OL2,369 (2000). rKumar, H.M.S., Reddy,B.V.S., Reddy,E.J.,yadav,J.S. CL 857 (1999). aRamasamy,K.S., Bandaru, R., Averett,D. SC 29,2881 (1999). sYadav,J.S.,Sasmal,P.K.,Chand, PK. SC 29,366i ,1 ggg). 6Hall, D.G., Laplante, C., Manku, S., Nagendran,L JOC 64,698 (1999). TLulinskr,P, Skulski, L. BCSJ72, lt5 (1999). 8Lulinski,P., Skulski, L. BCSJ 73,951 (2000). 'Yang, S.G., Kim, YH. TL 40, 6051 (1999). r0Bekaert,A., Barberan,O., Gervais,M., Brion, J.-D. TL 41,2903 (2000). rlBaba, S., Leroy, F., Le Goaster,C., Jegou,A., Carboni,B. SC 29,1133 (1g99). I2Ma, S., Shi, 2., Yu, Z. TL 40,2393 (1999\. rrSabate,M., Llebaria,A., Molins, 8., Miravitlles, C., Delgado,A. JOC 65,4g26 (2000)
The ICI-AgSOa is a superacur zeneto form n-iodonitrobenzener')
Alimardanov, A., Negishi,E. fL.O. 3t :Henaff,N., Whiting,A. "/CS(P1) 395ri 'Chaikovski. V.K.,Kharlova. T.S..Frhu
Iodomethyl pivalate. Hydroxymethyl anion.t Ttrc i-PrMgCl in N-butylpynolidinoneAvolio,S.,Malan,C.,Marek.I.. Krrlt
Iodomethylpivatate lrttup\. .\lcohols and their tetrahydro_ s -: :.r.t. ' Etherficationis done in a B . . : - : l : r ' \ ! 'idn M e O H . rr::r.. .. rccomplishedby heatingwith h:. . :: ,rrtrc'ductionof amideswith boh .. : .. :rndan oxidant (e.g.,potassium k' - :''..:r, date.' or tetrabutyl-ammonium ! : - : -'.i\\l\tanceofseleniumdioxide.l0 o -. :.r. acids consistsof iodoethe_ trl'.
, nlln extensionat the B-position r 'l:rctonization of allenicacidsl2
\.:a a
\ :
.-.a
o
Iodine(I) bromide. 20, 204 cleavage of rBS ethers.t Many other protecting groups :ue not affected when t-butyldimethylsilyl ethers are cleaved with IBr in MeOH. Iodoetherification.2 Regioselective hydration of a homopropargyl alcohor is accomplished through iodolactonization of its carbonate with subsequent deiodination and hydrolysis. This procedure is valuable for preservrng epimerizable stereocenters.
It 1
p_(
o-\
,CuH,',
o tl )
"" -_
69%
1999).
ta
,r r 1999).
ll -. I 11000). I :e I183(1999). F=i
,CaH,,
Lr
Kartha,K. P.R, Fietd,R. A..ta 3110999). rMarshall. J.A.,yanik.M.t/1.JOC 64,3798 ( t999). Iodine(I) chloride. 20, 2OO Iododesilylation.t The silyl group of an ct-s'yl enone is replaced by iodine reactronwith 2 equiv of ICI and I equiv each of ICI and AlClj. Iodination. The stereoserectiveformation of r,2-diiodoarkenes2from alkynes reaction of ICI and then NaI is instrumental to a route to highly substitutedalkenes.
lCl:Nal
rlr
6r
p<
o={ ),,,,, o<\
r//
Ph
-
Br/cl2ct2
,An
r -c) clohexenyl)thiocarbamidate
(, : ,
233
\ J)C 65,4826(2000).
l./. Ph
l\ l, 86%
The ICI-AgSoo is a superactiveiodinating agent that is capabreof attacking nitrobenzene to form z-iodonitrobenzene (74vo yield) at room temperaturein 5 min.:l rAlimardanov, A., Negishi,E. TL 4O,3g39 (1999). rHenaff,N., Whiting, A. JCS(pI)395(2000). 'Chaikovski, V.K.,Kharlova,T.S.,Filimonov,V.D.,Saryucheva, .LA. .! 74g0999). Iodomethyl pivalate. Hydroxymethyl anion.t The title compound undergoes I-Mg exchange with i-PrMgcl in N-burylpyrrolidinone-THF to afford a usefur nucreophilic ieagent. rAvolio,S.,Malan, C.,Marek,1.,Knochel,p. SZ 1g20(1999).
234
N-Iodosuccinimide
Iodomethylzinc 2,4,6-trichlorophenoxide' AIOH' Et2Zr'' ar.rdCH2I2' is a Ttre tiite compound' prepared from Cyclopropanation" modifledSimmons-Smitr'."ug"nt'wittrwhichalkenesaretransformedintocyclopropanes inexcellentyields(6examples'90-987o)'Intermsofreactivity'thezincphenoxideis comparabletobis(chloromethyl)zinc,butmorereactivethanbis(iodomethyl)zincand Furukawa'sreagent' lCharette,A.B.,Francoeur,S.,Martel,J.'wilb'N.ACIEE39,4539(2000).
Iodosylbenzene.13, 151: 16 I Oxidations. BY using F oxidized to acids and ketorrs
poly(4-vinylpyridine )-supp
N-Iodosaccharin' Iodinations,|Thisreagentispreparedfromiodineandthesilversaltofsaccaharin. are formed when alkenes and activated arenes.Iodohydrins It is effective ro. ioolnation Jr in aqueousacetone' alkenesare treated with N-iodosaccharin
.l;,
l
N
bc
rDolenc,D. SL 544(2000)'
,} ,11
N-Iodosuccinimide,Nls'16'185-186;18'193-194;19'177-L78 Iodohyilrins'|,l.ni.p.u"osynthesisofiodohydrinsfromalkenesinvolvestheuse
*.ti#r1?lYfu,rn"rr
in thefollowing'2 asexemprified is observed, rrnrrr, Selectivity
HO
\ (-^
NIS / MeNo2
B0,.oNi\
( \ \ /
Pn-vo:.--r \n--r_Le B;b_-+\
n
84o/o
Radical cyclization'3
Medium-sized rings are formed
F"\=cHoMe
1
\_r
uoH
_
\
\ ^\
a^n--\--]zY
/>-o
O X/ "
$n-o--r-t\ anb lrn
rtsrcszcu /\-n t
- Et3B | Bu3snH
I
|
\-,/-'--J
Y
Tohma, H., Takizawa' S ' \le I-riedrich,H.B.' Singh' \ IL .\dam, W., Gelalcha,FG ' Sr ' . \ d a m , W . ,S t e g m a n n , V R' 5 Boto, A., Hernandez.R ' Sur Wakao, M., Fukase, K" Kusr
5S% p -Iodotoluene (2000)' rsmietana, M., Gouverneur,V' Mioskowski 'C' TL 41.'193
,;;-d*" j., viur,c., Bols,M. cEJ6, 1140(2000)' r' sr1le3(2000)' :.'*;;;;I *1.,ruau,A.,lsobe,Y',Yajima'
./
Flo_ Bi'o
by NlS-induced cyclization'
OMe I
):(
/ v \
BnOO*"
BnOo*.
GlYcosYlation'6 Oxrda Me,SiOTf furnishes actrsatc s hen such a thioglYcoside ts
difl uorkla
FluorocYclization' HF-pYridine.
p-Iodotoluenedifluoride
re.r ::,'rn.ArOH,EtzZn,and CH2I2,is a r. .:c rransformedinto cyclopropanes r ' : :ractivity, the zinc phenoxide is ,}.:.\. than bis(iodomethyl)zincand
!n
-. :./ , rfxYll
Iodosylbenzene.13, 15I ; 16, 186; 18, 194; 19, 17g; 20, 2Ol oxidations. By using phl:o (in presence of KBr) as an oxidant, alcohols are oxidized to acids and ketones in water in excellent yields.rwhen catalyzed by either poly(4-vinylpyridine)-supported sodium ruthenate2 or a (salen)chromium complex3 chemoselective oxidation of alcohols (e.g., allylic alcohols to alkenoic acids) occurs. which is contrary to the effect of (salen)manganeseand (porphyrin)iron complexes (giving epoxy alcohols).a oxidative decarboxylatinn,s o-Amino acid derivatives undergo degradation by PhI:O/Iz.
:l;:.: .rndthe silver salt of saccaharin. a:.:.e.. Iodohydrinsare formed when
\/ I
N--(
v . b
Phl=O- lz cH2ct2
cooH 82o/o I te. 177-178 hr.::.r. l'rom alkenesinvolvesthe use n r..: .t\ cxemplifiedin the following.z
Glycosylation.6 oxidation of phenylthioglycosides with phl:o in the presenceof MqSiOTf furnishes activated glycosyl donors. Stereoselectiveglycosylation is achieved when such a thioglycoside is clamped to another sugar component.
(-\
._o)<
-""ffi:^4*Iil""
Me3SiOTf MS4A CH2C|2
u%
f,,:r:rcdbv NlS-inducedcyclization. 86%
OMe
'-"
.
;,:1
\.-\ l o )--/ 59%
lTohma,H., Takizawa, S., Maegawa,T.,Kjt^,y. ACIEE 39, 1306 (2000). rFriedrich, H.B., Singh, N. Za 4l, 3971 (2000). rAdam, W., Gelalcha, F.G., Saha-Mtiller,C.R., Stegmann,VR. JOC 65, l9l5 (2000). rAdam, W., Stegmann, VR., Saha-Mijller,C.R. ,/ACS l2l, tSTg (1ggg). 5Boto,A., Hernandez, .lggg). R., Suarez,E. TL 40,5g4S 6Wakao,M., Fukase,K., Kusumoto,S. SZ 1912 (1999).
p-Iodotoluene
difluoride.
Fluorocyclization.t HF-pvridine.
19, 17 8 This reagent promotes cyclization
of unsaturated alcohols with
Ion exchangeresins
\ /
+-<
\
l\
\:,/
)-CsH1 HO
Cyclizations. An rnr hy Amberlyst 15 is apph Dowex-50X2-200, couma
HF
. > - l'F -Pyridine \F
cH2cl2-45'
\o/\c5H11 600/o
HO
OH
rSawaguchi, M., Hara,S.,Fukuhara, T.,Yoneda,N. ,/FC 104,277 (2000). o-Iodoxybenzoic acid. 19, 119 Coniugated carbonyl compounds.l The title reagent converts saturatedalcohols or carbonyl compounds to the conjugated carbonyl compounds.
2\A
,t
I ' l
FoH + l-
ll ;o =-?,'lo,
\__/
Desulfinyhtion.: Su the presenceof an ion ercl Deoxygenation of 4 capableof removing the q rnsteadof LiI, also bromtn
,rr_orio 74To
Heterocyclizntion.2 cyclization of allylic carbamates to oxazolidin-2-ones vla oxidative radical cyclization. Hydrogen comes from THF.
1
oYo "il-r--l ( ) \z\
(
.
ar)i, p
rHF-Ol\,lSO; ACO
\)L
o'l'-o*
o
po
N H
OMe
Epoxi.dation.3 The tetrabutylammonium salt, prepared on admixture with BuoNF, transfersits iodine-bound oxygen atom to enones. rNicolaou,K.C.,Zhong,Y.-L.,Baran, PS. JACS122,i.596(ZOOO). 2Nicolaou, K.C.,Baran,P.S.,Zhong,Y-L.,yega,I.A.ACIEE39,2525(2000). rOchiai,M., Nakanishi,A., Suefuji,T. OL2,2923 (2000). Ion exchange resins. Esterification. At room temperature, saturated carboxylic acids are selectively esterified with an alcohol in the presence of Amberlyst-I5 resin.r Alkenoic and aroic acids are left unreacted. Transesterification of alkyl formate to a dicarboxylic acid forrning the monocarboxylic ester is catalyzed by Dowex-50WX2.2
. \ n a n d .R . C . .V i m a l ,A . \ 1 . . / ( l \ishiguchi, T., Ishii, y. Fulv \ i t u n g . 1 . .J u n g ,L . . C h e n g .K 'Je la Hoz, A., Moreno. A.. \ei L i . G . , K i m , S . H . ,W e i . H . - \ tsovicelli, P, Righi, G.. Spere tsovicelli,P.,Righi, G., Sperl
Iridium complexes, Isomertzation. Carro unsymmetrical diallyl erlre rncludingan accessto ]1s .'thersto ^y,E-unsaturated ca
Iridium complexes
tr-
-_
C.
:.
F.
Cyclizatians. An intramolecular S,r12'processto form an oxaspirocycle as mediated by Amberlyst 15 is applicable to the synthesis of theaspirone.3under the influence of Dowex-50X2-200, coumarin derivativesare obtained from phenol and propynoic acid.a
h
\o/-c5H11 60Yo
HO\4\,>,/.OH I
x.:--
Y
:000).
ll
I OH
HO
*4
---;-
50x2-200 _COOH Dowex
98o/o
itJirnt convertssaturatedalcoholsor tg..r.J.
F
- ,.'_io
//:\ | \:/
Desulfinylation.s Sulfinamides are methanolyzed to the corresponding amines in the presenceof an ion exchangeresin. Deoxygenation of epoxy ketones. An alkali metal halide on Amberlyst 15 is capable of removing the epoxide group from epoxy ketones.6Interestingly, LiBr or NaBr, insteadof LiI, also brominatesthe enonesat the o-position.T
\- /.\ 74%
Irn:nr:rtes to oxazOlidin-2-onesvla TI,]I
o
po
N H
o
A
xo
ffi6
l - \ lt
t 15> lAmberlvsr LiBr
ol lt>rr, \
-1//
72%
a::nercd on admixture with Bu+NF,
|:.., ti .re t5t5 (2000).
.arhoxylic acids are selectively x:. r .r- I 5 resin.r Alkenoic and aroic ll:. rrrrmdt€ to a dicarboxylic acid t.:
ou:'.-5(JWX2.2
'Anand,R.C.,Vimal,A.M. JCR(S) (1999). 378 rNishiguchi,T., Ishii,Y., Fujisaki, S. ,/CS(p1)3023(tggg). rYoung, J.,Jung,L., Cheng, K. TL4l,34lt,34l5 (2000). {dela Hoz,A., Moreno,A., Yazquez,E. Sl, 608(1999). :Li, G.,Kim,S.H.,Wei,H.-X.756,719(2000). "Bovicelli,P.,Righi,G., Sperandio, A. T 56,1733(2000). -Bovicelli, P.,Righi,G.,Sperandio, A,.TL40,5889(1999).
Iridium complexes. Isomerization. cationic iridium complex effects selective isomerization of unsymmetrical diallyl ethersr and conjugated boronatescontaining an allylic ether group, including an accessto "y-(siloxy)allylboronicesters.2The conversionof allyl homoallyl ethersto ^y,6-unsaturated carbonyl compounds3is promoted by [(cod)IrCl]r.
238
Iridium complexes
*y*'gto [(cod)rrcr]?
*>-o.--r\ R' ' l
+
\r,r'
Cy3P-cs2co3
Il
I
\r/\
I j{#I|l
Ph'v2'-..,.o.v,\
Ph\t2'...-,.o.-Z\ 78%
(
\J
F
O-\-1/
+ \
Iron. 19, 179-180;20,20-1-: y-Lactones.t In the pre halogenated esters.
[(Ph2MeP)21(cod)]PF6
(
F
O
H2trHF
6
8
"\:1
\J %
'Suda, K., Baba,K., Nakajima. S 'Adams, R.D., Bamard,T.S.. Bnx ^Matsuda, I., Hasegawa,y.. \tahl -Petra, D.G.I., Kamer, PC.J.. Spl (2000). 'Takeuchi, R., Tanabe,K. ACIEE : "Matsumoto, T., Taube,D.J.. penr
\
(i,;
/-l
I , ll rl
(Tetraphenylporphyrin)iridium(Ill) triflate isomerizes terminal epoxides to aldehydes in refluxing dioxane.a 1,3-Diaxolanes.s Epoxides and ketones combine under the influence of [Cp*Ir(MeCN)rl@Fe)2. Aldol reaction 6 A new catalyst for the Mukaiyama version of an aldol reaction is [Ir(cod)(PPhj)2]OTf. Actually, after activation by hydrogen, it promotes a Michael reaction of enones with silyl enol ethers and the svstem can be modified to continue an aldol reaction. Reduction. Certain successhas been achieved in transfer hydrogenation of ketones (from HCOOH, Et.N) using [Ir(cod)Cl]2 and a chiral ligand.? Sp2' dhplacement.s Employment of an iridium complex instead of the more commonly used palladium catalysts successfully mediates regioselective allylic displacement.
1^fcoou" I I ----Acr
Somech,L, Shvo,Y. JOMC f{ l. I
Iron(II) chloride. 20,2U Chloroamination.t Deco by iron(Il) chlorideleadsto lar n tl
q Na*
*
Etooc^cooEt
I(cod)lrCll2
,\
.N3
t
\"^\-
E
//--\
R
\
'e: -
\
(Pho)3Pl rHF ETOOC"\COOEt
OAc 94Yo
Friedel-Crafis allqlation,e A straighrchain alkyl group can be introduced into an aromatic nucleus by reaction with an alkene, using the binuclear Ir(III) complex, as caralyst.The result is remarkablydifferent [Ir(p-acac-O,O,C3)-(acac-O.O)(acac-Cr)]r, from the commonly known reaction pathway. rYamamoto, Y., Fujikawa,R., Miyaura,N. SC30, 2383(2000). 2Yamamoto, Y., Miyairi, T., Ohmura,T., Miyaura,N. JOC &,296 (2000). 3Higashino,T., Sakaguchi, S.,Ishii,Y. OL 2, 4193(2OOO).
Alky lativ e r earran gemcnL : diazo compounds(particularll tropic rearrangement:ue induce<
*v* ll
\-sR"
.
Iron(II) chloride
,R
rSuda,K., Baba, K., Nakajima, S. TL 40,7243 (1999). iAdams, R.D., Bamard,T.S.,Brosius,K. JOMC 582,358 (1999). "Matsuda,I., Hasegawa,Y., Makino, T., Itoh,K. TL 41,1405, 1409 (2000). -Petra, D.G.I., Kamer, P.C.J.,Spek,A.L., Schoemaker,H.E., van Leeuwen,P.W.N.M.JOC 65,3010 (2000). *Takeuchi,R., Tanabe,K. ACIEE 39,1975 (2000). eMatsumoto,T., Taube, D.J., Periana, R.A., Taube, H., Yoshida, H. "/ACS122,^74I4 (2000).
l.O
t-F:
78Yo
Iron. 1.9.179-180;20,203-204 y-Inctones.t In the presenceof CuCl, iron mediatesa reductivecyclizationof halogenated esters.
- /-"r-/ 680/"-_\
cl ,.. terminal epoxidesto aldehYdes
Fe - CuCl
(^t-;.^cooure ---.Acl
0:.
-
:c under the influence of [CP*lr-
[ii.r.rrlra versionof an aldol reactionis t'. :rrJrogen, it promotes a Michael ' .. -:i.'lncan be modified to continue an r.,.i .:: lransferhydrogenationof ketones tl::
H2O- NreCN 140
.:!Jrid.r
r..-:...::r complex instead of the more mediates regioselective allylic s! -
].PITHF
\.,^O
\.,'
5lYo
50Yo
lSomech,I., Shvo,Y JOMC 601, 153 (2000).
Iron(II) chloride. 20, 204 Chloroamination.t Decomposition of properlyconstitutedunsaturated acyl azides by iron(Il)chlorideleadsto lactams.
o
\"r
ar>" . a)^cooMe
oAl.r"
n FeCl2- Me3siCl + EtoH 0 - 25'
tl on tttt
tl +
1'.-",
\
EIOOC"'\COOEt
oANH
R
cl
( 9 : 1 )
94Yo
tr .:.rr I group can be introducedinto an i. ...r:rs the binuclear Ir(IlI) complex, r:. . -: The result is remarkably different
Alkylntive rearrangement.2 Sulfonium ylide formation from allylic sulfides and diazo compounds(particularly trimethylsilyldiazomethane)and subsequent[2.3]sigmatropic rearrangementare induced by (dppe)FeCl2in 1,2-dichloroethane.
R,..'..R t _ " ' (r .,{ tq6 (2000). I
Il \-SR"
* f r-siMe3 N2
(dppe)Fect2 *;
; n - K \ s-f'i H , r e g
clcH2cH2cl \
Iron(III) chloride rBach, T., Schlummet B., Harms, K. CC 28'7(2000). rCarter. D.S.. Van Vranken. D.L. OL 2. 1303 (2000).
Iron(IID chloride. 13,133-134;14,164-165;15, 158-159; 16,167-169, 190-l9l;17, 138-139; 18, I97 ; 19, 180-18I ; 20, 204-205 Acetylation. Either alcoholsr or methoxymethyl ethers2 are transformed into acetatesin the FeCl3 -catalyzedacetylation, using HOAc and Ac2O, respectively. Michael reactions. 2-Alkylidene derivatives of 1,3-dicarbonyl compounds behave as donors in Michael reactions. Of particular interest is the formation of biaryl precursors with quinones.l
b
Cyclopentenonesare formed t at the ct-position.TCommon lrrr this cyclization.
, i
'I
39%
Benzils.a Benzoinsare readily oxidized by FeClj'6H2O without solventat - 80". Cyclobutenediones and p-benzoquinones.5 Iron carbonyl species are formed by reaction of the FeClr-NaBH4 system with carbon monoxide. When alkynes are present,
pyridines in the presence of FeCl,
thev are converted to cvclobutenedionesor benzoouinonesin situ.
with r-butyl hydroperoxide.
*.'--/o CO / HOAC Mel / THF 25"
\
R
ill
o |
,"",.-r,r".
-ffi-
rHF 7s'
-"\
R
\r
+
f^*
o
(65 : 35)
B-Keto esters condense *rrh t-Butylation.u
FeCl, is an c
rSharma,G.V.M., Mahalingham. .{ I ( I 999). rBosch,M.P., Petschen,I., Guerrcn . 'Christoffers, J., Mann, A. EJOC :5ll rZhou, Y.-M., Ye, X.-R., Xin. X.-Q 5( 'Rameshkumar, C., Periasamy.\t ()-\ "Wang, Y., Arif, A.M., West, F.G ./.{(: -Kuroda, C., Koshio. H. CL 961 r:m 'Chibiryaev, A.M., De Kimpe. \ . Tllr "Liguori. L.. Bjorsvik. H.-R., Fonram
Iron(IID nitrate. 20, 205-206 Dehydrogenation.t Hy'draz ArN:NCONHNHAT
Cyclization. The oxyallyl intermediate derived from treatment of a crossconjugated dienone with FeClr is trapped by an intramolecular [4 + 3]cycloaddition if one of the a-positions of the dienone is connectedto a diene. Interesting tricyclic systems can be producedin this Nazarovcyclization.6
by grindrng Oxidative alcoholysis.: Ac1 the presenceof iron(III) nirrare
Oxidation.3 Oxidation of ak is accomplished by mixing *'irh I and crushedtogether) and wirh mx
Iron(III) nitrate
l'.
R' .
I 59: 16, 167-169,190-79I; 17,
tl
FeCl3
'\*
cH2ct2 -30'
/.:l H / o\.j
/-1
.
\,\fl \,y' ."'\ /\'/ .""\ x2 --\
--\
R mr'::.,,I ethersz are transformed into H( ) \. .rndAc2O,respectively. l : ...r-dicarbonylcompoundsbehave t.' .. rhr' tormationof biaryl precursors
H
, oy_^
R=Me R = Ph
R 65% 72Yo
Cyclopentenonesare formed by treatment of dienals bearing a silylmethyl substituent at the a-position.T Common Lewis acids other than FeClj are not effective for mediatins this cyclization.
R = Me
t : :
r,H:O without solventat - 80o. : earbonyl speciesare formed by 'r,'ride. When alkynes are present,
lL::
:rl' in sttu.
ix t -
78To
B-Keto esterscondensewith conjugatedoximes at 150.-160" to afford substituted pyridinesin the presenceof FeClj.8 t-Butylation.e FeCl is an effective catalyst for electrophilic aromatic substitution with t-butyl hydroperoxide. rSharma, G.V.M',Mahalingham, A.K., Nagarajan, M., Ilangovan, A., Radhakrishnan, B. sll200 ( 1999). rBosch,M.P.,Petschen, I., Guerrero, A. S 300(2000). 'Chrisroffers. J.. Mann,A. EJOC251I{ 1999t. 'Zhou.Y-M.. Ye.X.-R..Xin.X.-e. SC 29,2229tts99t. 'Ramesh,kumar. C.. Periasamy. M. OM lg, 2400e0001. "Wang,Y.,Arif, A.M., West,F.c. JACS121.876 ,1ggg). Kuroda.C.. Koshio.H. CL 962(2000). *Chibiryaev, A.M., De Kimpe,N., Tkachev,A.V. TL 41,80l l (2000). "Liguori,L., Bjorsvik, H.-R.,Fontana, F.,Bosco,D., Galimberti, L., Minisci,F.Joc 64,g8r20999).
t
Iron(II!
35)
lc::.:J trom treatment of a cross::'.r:,,nr()lecular [4 + 3]cycloadditionif I :, .' Jrcne.Interestingtricyclic systems
nitrate. 20, 205-206 Dehydrogenation.t Hydrazides (fuNHNH)2co are dehydrogenated to afford AIN:NCONHNHAT by grinding with Fe(NO.)..9H2O. Oxidative alcoholysis.2 Acylsilanes are converted to esters in alcoholic solvent in the presenceof iron(III) nirrate. Oxidation.3 Oxidation of alcohols to carbonyl compoundsin solvent-freeconditions is accomplished by mixing with Fe(Nor).'9H2o-HZSM-5 zeolite (in equivalent weight and crushedtogether)and with microwave assistance.
Iron pentacarbonyl
Radical cyclization. Internal trapping of the radical generated during cleavage of a siloxycyclopropane with Fe(NOr)q leads to a new cyclic array.aVarious radical terminators can be used to functionalize a remote oosition.
/
BnO
(65-7s%o\
lRl / DMF
"(il. A dramatic change in the fate of the first radical intermediates is observed when Cu(OAc)2 is also presentin the reaction media.5
,|:, Fe(NO3)3
f;*-* I
Me3SiO
;
R = H , C l ,S P h
Fe(NO3)3
,,;,
s
-lI I
rn
t t \-,\,,/
Terent'ev,A.B., Vasil'eva.TT _ Belokon,Yu.N.RCB 48. I lll r I :Taber,D.F., Kanai, K., Jiang.e.
Iron(III) perchlorate.20. :O Transetherification. A differentethers. Rilter reaction 2 Ironrll arnidesfrom nitrilesandbenz
Salehi,P.,Irandoost,M.. Seddrg 'Salehi,P, Motlagh,A.R. .tCJ0. I
l
41Yo
Iron(Il) sulfate. Acetalizafion.t Spir<x1
Fe(Nos):_
'oLon
"'ffi:"'
HO--J \-oH 48Yo
rWang,H., Wang,Y.-L.,Zhang, G., Li, J.-P.,Wang,X.-Y.SC30, 1425(2000). 2Patrocinio, A.F.,Moran,P.J.S. SC30, 1419(2000). rHeravi,M.M.,Ajami,D.,Aghapoor, K., Ghassemzadeh, M. CC 833(1999). 4Blake, A.J.,Highton,A.J.,Majid,T.N.,Simpkins, N.S.OZ l,1787 (1999). 5Booker-Milbum, K.I., Cox,B., Grady,M., Halley,F.,Marrison,S. TL 41, 4651(2000).
Iron pentacarbonyl. 13, | 52; 18, 196; 20, 206-207 Reformatsky reaction.t The Fe(CO)5-I2 combination promotes Reformatsky reactlons. Cyclohexenones,2 Carbonylation and cyclization of alkenylcyclopropanes leading to cyclohexenones with Fe(CO)5 under carbon monoxide constitute an enantioselective process.
Hydrochlortnation.: Ad FeSOois stereoselective. rhe p t O-P-chlorovinyl ketones.
,"oo-
Jin, T.-S.,Ma, Y-R., Li, T.-S..\\'a! -Conde,J.J., Martucci, M.. Olsrn, I
Iron(II) sulfate
tr
:.,::.el senerated during cleavageof a r^ . .,.:e arrar.' \'arious radical terminao:
o
(
V
Fe(CO)s/ CO i-PrOH
BnO
A.'"o"^t"(
ano.,,.-,1'-r!j
(/
c 59%
R = H, Cl, SPh
. :
(65-757o)
15%
**' NA' Mvsov, EI.,rkonnikov, NS,Kuzne,sov, Nyu.,
#ii]i;l,i;#l
ffi:;l'3' -Taber, D.F.,Kanai, K.,Jiang, e., Bui,G..)ACS 122,6807 (2000\. Iron(IIf perchlorate.20, 207 :i.:.-:l
rnterrnediatesis observedwhen
oru"!!X!tJr#ii!"o"".,
Allyticandbenzylic ethers reactwith an alcoholto sive
Ritter reaction'2 Iron(III) perchlorate supported on silica can be used ro prepare amides from nitriles and benzylic alcohols.
Y: ;.
n "\-h -
l
\-\-, 41o/o
FK,rhhmasebi, ,:liili,l, il11i"111;T Dpsc30,1743 (2000) 31"1i?lii;ff;l"n-| Iron(II) sulfate. Acetalization.t Spirocyclicdiacetals arereadilyprepared.
r F
48To
'] .t -1{).1425(2000).
74_99% Hydrochrorinatioz.2 ,
r \1 ('C833(1999). ' . t.t787 Q999). Ii.,- .,,n.S.TL 41,4651(2000).
,Hffi;*:;;ff;:..'
Addition of hydrochroric acld to ynones in the presence of products
*"In t -*f,-i-propynI -ones beingpredominantly
l',,'nrbination promotes Reformatsky t-r:rr,,oof alkenylcyclopropanes leading m.,':.,,rrdeconstitutean enantioselective
Y.-R., Li, r.-s.,
wang,J.-X.JCR(S) ll",T.{:,Ma, 26s(lsss). -Conde, J.J.,Marrucci,M., Olsen, M. TL 41,4709(2000\.
N-Isocyanotriphenyliminophosphorane
Iron(III) sulfate. Nitriles.t Dehydration of aldoximes with iron(Ilf sulfate occurs in refluxing benzene. Esterificatian.2 Aroic acids and mandelic acid can be esterified in the presenceof iron(ID sulfate.
Lanthanum(Ill) trifl uorw Aziridines.t The highl lcetatesin protic media uscs
rDesai,D.G.,Swami,S.S.,Mahale,G.D.SC30' 1623(2000). 2Zrang,G.S.,Gong,H. SC 29,154'7(1999).
N-Isocyanotriphenyliminophosphorane. a-Diazokctones.l Reaction of acid chlorides with this reagent provides chlorohydrazones,which on treatment with EtrN delivers the diazoketones'
,;,;;
veol>.)
o -cN
...
* l]-- cH2cl2 ;^: ;\'*-*', I itpn.
Cyclizatinn of epoxy aL rnfluencedby molecularsierr
2,J I
Ct
7SYo
rAller. E., Molina, P., Lorenzo, A. SL 526 (2O0O).
\ie. W.,Fang,J.,Li, J.,Wang.P Tokiwano, T., Fujiwara.K.. \lru
Lead(IV) acetate.13, 155-l t09-2 I 0 a-Siloxy acetates. o-S Ph(OAc)avia a radical Brmt Acetoxylation 2 p-t-rr
Oxidative dearonotit lactonizationis critical touar need.l
OH
I
a.ir^r \.\oire
.ulfate occurs in refluxing l.tc'nfied in the presenceof Lanthanum(Ill)
l:'
:rr. reagent provides chloro. . kc'to0es.
^reolY^\
: !
trifl uoromethanesulfona te. 20, 209 Aziridines't The highly cls-selective cycloaddition between imines and diazoacetatesin protic media useslanthanum triflate as catalyst. crclization of epoxy alcohors.2 The regioselectivity of this cyclization is greatly influencedby molecularsieves.
-{
\ , N 'NH2 Y/
/
, Ho-
oH La(orr): - na"o-"',f.-\
MeoH-cH?crz
Meo
.
.,,..(o)
cl
* rot..i"u".
i
,
9 88
*, o"lr, J.,Li, J.,wang,p.G.r ss,12s2s (tgsg). I':: Tokiwano, T., Fujiwara,K., Murai, A. CL272 (2000).
Lead(IV) acetate.13, 155_156;14, t8g; 16,193_194; lg,2Ol_202;19, 184_185; 20, 209-2t0 a'silaxy acetates. cr-Silyl alcohors are transformed into a-siloxy acehte with Pb(OAc)ovia a radical Brook rearrangement.r Acetoxylation 2 B-Lactams undergo acetoxylation at the B_position. oxidative dearomatization. The modification of a naphthol by oxidative lactonization is criticar toward a synthesis of lactonamycin. Lead(IV) acetatefulfills this need.3
OH
,-cooH Pb(OAc)4
cH2ct2
OMe 74Yo
Lipases
Cleavage
of catechols,a
Lead(IV)
acetate is much
superior
to CuCl-pyridine-
methanol in the ring cleavage. rParedes.M.D.. Alonso. R. JOC 65,2292 (2000). zciang, L.T., Fetter, J., Kajtar-Peredy,M., Lempert, K., Czira, G. 255, 13741 (1999). 3Cox,C., Danishefsky,S.J.OL2,3493 (2000). lwalsh, J.G., Furlong, P.J.,Byrne, L.A., Gilheany,D.G. 255, 11519(1999).
Lipases. 17, 133- 134: 18, 202-204; 19' I 85- I 88 ; 20, 2l l-212 Resolutions. The following types of substrates have been resolved via lipasemediatedenantioselectiveesterification:malic and asparticesters,r3-hydroxyalken-1-yl p-tolyl sulfoxides,2 B-hydroxy sulfoxides.3 A practical method involves sequential transacetylationand sulfation, followed by extraction and treatment of the aqueouslayer with methanolic HCI to recover the alcohol (the organic layer yields the acetate).4The use of 1-ethoxyvinylacetateas acetyldonor in thesereactionshas beenproposed.s Coupled with in situ racemization of the unacetylated enantiomer by a ruthenium complex, the complete conversion of a secondaryalcohol to the chiral acetateis efficient.6 An alternative method involves hydrogenation of alkenyl acetatesin the presenceof both l i p a s ea n da R u l l l ) c a t a l y s t . T Simultaneousresolutionof both acetateand amine with lipasehas beencarriedout.n Alcoholysis of B-lactonesprovidesoptically active B-hydroxy estersin one-halfof the original quantities.' Kinetic resolution.t(r Allylic alcoholsare resolvedwith a combinationof lipaseand a (p-cymene)rutheniumcomplex. Ammonolysis.rr A preparationof primary amides catalyzedby lipase proceedsin ionic liquids at leastas well as in organicmedia. Partial hydrolysis and esterifi.catinn. Aryl esters are hydrolyzed in the presenceof alkyf esters (e.g., methyl salicylate from the O-benzoyl derivative), and esters of from vinyl acetateto o-dihydroxyarenesundergopartial hydrolysis.12'r:rTransacetylation hydroxymethylphenolsoccursat the primary alcohol sites.ra Cleavage of N,N-dimethylhydrazones.ts Ketones are recovered from the lipasecatalyzedreactionin good yields exceptthe highly hinderedmembers(e'g', menthone). lLiljeblad,A., Kanerva, L.T.TA 10,4405(1999). rdela Rosa.V.G..Ordonez, M., Llera,J.M.TA ll, 2991(2000). rMedio-Simon. T.,Asensio, G. TA 10,561(1999). M.. Gil. J..Aleman,P.,Varea, aYamano, S.,Miwa,K., Kawada,M., Ito,T., Ikemoto,T., Tomimatsu, T., Kikumoto,F.,Yamamoto, K.. Mizuno.Y. CL 448(2000). sKita,Y.,Takebe, Y.,Murata,K., Nata,T.,Akai,S../OC65,83 (2000). 6Koh,J.H.,Jung,H.M.,Kim,M.-J.,Pak,1.TL40,6281 (1999). 7Jung, H.M.,Koh,J.H.,Kim, M.-J.,Park,J. OL2,248'7(2000). 8Garcia-Urdiales, F.,Gotor,V. TA ll, 1459(2000). E.,Rebolledo, eNelson, K.L. JOC 65,1227(2OO0). S.G.,Spencer, l{)Lee, D., Huh,E.A.,Kim, M.-J.,Jung,H.M.,Koh,J.H.,Park,J. OL 2,2371(2000).
' 'Lau, R.M., van Rantwijk. F.. ::Nair, R.V., Shukta,M.R.. Prr rrCiuffreda,P.,Casati,S.. Sar 'Parmar, V.S., Prasad, A-K-.
( 1999). :iMino, T., Matsuda,T.. Hiran
Lithium. 13, 157-158:15. Deaminatian.t Th€ lines ani suffersdetachmen a-Silylamines.2 THF.
Red
Azzena. U., Dessanti, F..Ilcll -Bolourtchian, M., Badnan.A
I-ithium-liquid ammonir (E)-Alkenes.) The sc with LilNH.,. Reduction of hetcrwt
Brandsma, L., Nieuwenhurz '\lcComas,C.C.,VanVrantc
l.ithium aluminum hydri Reductian of amidctreduction of morpholine I room temperaturetakespl. rlo not behavesimilarly.
A
H N _
>-Y F
O
a-Ketols,3 Reduction r with standardhydrolytic w l-alkanones. Hydrogenation ol aI raturatedby LiAlHo{eC|..
Lithium aluminum hydride r " ...h \uperior to CuCl-pyridine-
/ 5 5 . 1 3 7 4 1( 1 9 9 9 ) .
71: !:
rrLau, R.M., van Rantwijk, F., Seddon,K.R., Sheldon,R.A. OL2,4189 (2000). r2Nair,R.V., Shukla, M.R., Patil, p.N., Salunkhe, M.M. SC 29, 167t (1999). rsCiuffreda, P., Casati, S., Santaniello, E. T 56,317 (2000). 'uParmar,V.S., Prasad, A.K., Pati, H.N., Kumar, R., Azim, A., Roy, S., Errington, W. BC 27, llg ( 1999). r5Mino, T., Matsuda, T., Hiramatsu, D., Yamashita,M. TL 41,1461 (2000).
I
f l l
:r.t\e been resolved via liPase-yl 11rc esters,r3-hydroxyalken-1 ,.rl method involves sequential ..i rreatmentof the aqueouslayer The use .i\ !'r yields the acetate).4 '. hasbeenproposed.5 ;c'...rtr'denantiomerby a ruthenium ,.,rthe chiral acetateis efficient'6 L " . . .rcctatesin the presenceof both lln- .. :h lipasehasbeencarriedout.n 1r- .: irr droxy estersin one-halfof the
Lithium. 13, 157-158; 15, I84; 18,205-206;19, l9O-19|;20,212 Deamination.t The dimethylamino group of phenyl-substituted N,N-dimethylanilines suffers detachmentfrom the aromatic ring. a-Silylamines.2 Reductive silylation of imines is accomplishedwith Li-MejSiCl in THF. tAzzena, U., Dessanti, F.,Melloni,G.,Pisano, L.TL40,8291(199r. :Bolourtchian,M., Badrian,A. PSS152, 129,]r999D.
Lithium-liquid ammonia. 13, 158; 17, 16l ; 18, 206; 20, 213 (E)-Alkenes.t The scope was defined for the formation from alkynes by reduction with LiAIH.. Reduction of heteroaromatics,2 Indoles are reduced to cyclohexanopyrroles. rBrandsma, L., Nieuwenhuizen, W.F.,Zwikker,J.W.,Maeorg,U. EJOC775(1999). :McComas, C.C.,VanVranken, D.L. TL40,8039,1999D.
r. . , .r ',irth a combinationof lipaseand r. :.- irtalyzed by lipaseproceedsin [,:. .,.c hvdrolyzedin the presenceof 1,f^,'z,,rl derivative),and esters of T:.:- -.tic'tvlationfrom vinyl acetateto 0 _.
-\
i( :'. . rrc recovered from the lipaseh ' ::rcd members(e.g.,menthone)'
Lithium aluminum hydride. 14, 190-l9l ; 18, 207; 19, 19I ; 20, 213-214 Reduction of amides. A synthesis of N-protected a-amino aldehydes involves reduction of morpholine amides.r Defluorination of secondary o-fluorobenzamides at room temperaturetakes place before carbonyl group reduction.2However, tertiary amides do not behavesimilarly.
z\ l l
\-\N-"^*"-'t
I F
'\ 1 0 . 5 6 (11 9 9 9 ) . : l:..: r: \1.. Ito,T., lkemoto,T., Tomimatsu, l:
t(x)0).
I
rl
(2000). ?.-. i ()t.2.237'7
z\
H
l ll O
I ' \._,O
THF 25'
H
l l l \,,\N.-.^
f-)
tl
!.o
77o/o
a-Ketols,3 Reduction of the silyl enol ether derivatives of ct-ketoestersby LiAlHo (with standardhydrolytic ryorkup) constitutes a method for the preparation of l-hydroxy2-alkanones. Hydrogenation of allylic alcohols.a The lithium salt of an allylic alcohol is saturatedby LiAlHo-CeClj.
Lithium chloride
2-Nitroalkanols,s Various aldehydesreact with nitroalkanes to produce nitroaldols (syn * anti isomers) in THF with catalytic amount of LiAlHa at 0'. rDouat,C.,Heitz,A., Martinez, J.,Fehrentz, J.-A.TL 41,37(2000). 2Hendrix,J.A., Stefany,D.W. TL 40,6749(1999). rDalla,V.,Catteau, J.P 255, &97 (1999). 4Bartoli,G., Bellucci,M.C.,Bosco,M., Dalpozzo, R., De Nino,A., Sambri,L., Tagarelli, A. EIOC 99 (2000). 5Youn,S.W.,Kim,Y.H.SL 880(2000).
Lithium amide. PKeto nitriles.t The chirality center is not disturbed in the condensation of an cr-amino ester with acetonitrile when lithium amide is employed as the base. t '
rChang,S.-J.,Stuk,T.L.SC30,955(2000).
I
Lithium chromium(I) dihydri
Ph. /l'., ,ZZ', v v
,n,r/,
Ph
\
^
\
COOMe
Lithium bromide. 18, 209-210; 19, 192; 20, 215 Ethylene carbonates.t Epoxides are transformed into cyclic carbonateswith carbon dioxide (1 atm) at 100" in the presenceof LiBr in NMP.
,a' poly(methylmethacrylate)
rlwasaki, T., Kihara,N., Endo,'1.BCSJ73,7l3(2000).
F-rsch, J.J.,Alila, J.R. OM 19. I I I I r f,
Lithium l-butoxide. 18, 210; 20,215 t-Boc amines.r N-Substituted ureas are converted to f-Boc amines by t-BuOLi in the presenceof copper(Il) bromide. rYamaguchi, Y, Suyama, J.,Shusa, T. TL 40,8251(1999).
L ithiurn N,N-dialkylaminoborot Benzyldialkylamine-boranc t rnTHF to form the amine-borane r Collins, C.J.,Lanz, M., Goralskr.G T
Lithium alkyl(trityl)amides. Enol silylations. With the superhindered lithium ,-butyl(trityl)amide (and related tritylamides) ketones give more (E)-siloxyalkenes than lithium 2,2,6,6-tetramethylpiperidide.rAsymmetric enolizationis possibleusing chiral N-(1-phenethyl)analogue.2 IBusch-Petersen, J.,Corey,EJ. TL 41,2515 (2000). 2Busch-Petersen, J.,Corey,EJ. TL 41,6941(2000).
Lithium chloride. 18, 2l l; 20,218-219 Acetylation.' The acetylationof alcohols(including phenols),thiols, and aminesby acetic anhydride is catalyzed by LiCl. a-Methoxyacetophenones.2 LiCl mediates Ph.,P:CHOMe to give ATCOCH2OMe.
the
reaction
of
lSabitha, G.,Reddy,B.V.S.,Srividya,R.,Yadav, J.S.SC29,2311(1999). 2Camuzat-Dedenis, B., Provot,O.,Moskowitz, H., Mayrargue, J. S 1558(1999).
ArCN
with
l.ithium 4,4' -di-t-butylbiphenlti I I 0-2 1| ; 19, 192-193; 20, 2t6-21
Cl-Li exchange. a-Chlorol Jilithio derivatives and their rer c'rplored.I N-(Chloromethyl rcarhe .ire similarly lithiatedby Li-DTTB 3-Chloropropyl and 4-chloroh sith Li-DTTB, reductive clea\a! Jilithiopropaneand 1,4-dilithiobuu
The systemcontaining nickekl. tonates(mesylates,triflates)6to hrr C-S bond scission. Othcr hisphenylthiopropaneand I
thiums are generated from l-ph
Lithium 4,4'-di-r-butylbiphenylide
h '::::,,alkanesto producenitroaldols rf I \lH. at 0". t - - . . , .
Lithium chromium(I) dihydride. Multiple reactions,t The reagent is prepared from chromium(Ill) chloride and 4 equiv of BuLi in THF. It can be isolated as a dark red-brown LiCTH2.THF complex, free lrom LiCl. As shown in the following diagram, it can perform hydrodehalogenation,aryl ether cleavage,coupling reactions,and polymerization.
A. EJOC \.. Sambri,L., Tagarelli,
;\
'n6rh .::.:.:rhed in the condensationof an t. - :rtplovedas the base.
A(CHrnH n = o. 1...
I
;\rf'
,Ph
t-icrHz I
../
/t r.,.: ;tt()cyclic carbonateswith carbon
1.z-t-\"
\-\^,"-^"^ ''"'""'' z-Y< + \A*htn lo<""4"'
pn. z^ 16''\ \coo"" /
Ph
phcN
\
lo"o
poty(methytmethacrytate) | Ar-OH
ph '")-*
\ pn-(ru\pn H
Iiisch, J.J.,Alila, J.R. OM 19,12ll (2000).
ri--,1 t() I-Boc aminesby r-BuOLi in
Lithium N, N-dialkylaminoborohydrides. Benzyldialkylamine-borane complexes.'
These reagentsreact with benzyl halides in THF to form the amine-borane complexes that are useful in certain synthetic purposes. Collins,C.J.,Lanz,M.,Goralski,G.T.,Singaram, B. JOC 64,2574(1999).
l} n!'
r.:
:-butyl(trityl)amide(and related h;rn lithium 2,2,6,6-tetramethYlanalogue'2 rrel.V-tI -phenethYl;
: :r,: phenols),thiols, and aminesbY :hr'
:9
reaction of
- i . 1r 1 9 9 9 ) . . r s lssS(1999).
ArCN
with
Lithium 4,4'-di-t-butylbiphenylide. 13, 162-163; 16, 195-196: 17, 164; 18, 2 lL2l 1; 19, 192-193; 20, 21 6-217 Cl-Li exchange. ct-Chloroacetic and B-chloropropionic acids are converted to dilithio derivatives and their respective reactions with many substrates have been cxplored.r N-(Chloromethyl)carbamates2 and N-(ct-chloroalkoxy)carbonylpyrrolidines3 are similarly lithiatedby Li-DTTB. 3-Chloropropyl and 4-chlorobutyl phenyl ethers not only undergo Cl-Li exchange with Li-DTTB, reductive cleavageof the C--{ bond also occurs. Accordingly, 1,3dilithiopropaneand 1.4-dilithiobutane are formed.a The system containing nickel(If chloride dihydrate reduces alkyl chloridess and sullbnates(mesylates.tri flates)6to hydrocarbons. C-S bond scissian. Other convenient precursors of 1,3-dilithiopropane are 1,3As expected, B-oxyalkyllibisphenylthiopropaneand 1-chloro-3-phenylthiopropane.i thiums are generated from l-phenylthio-2-alkanols.6By virtue of its tendency of
Lithium diisopropylamide, LDA
deprotonation at the a-carbon, phenyl vinyl sulfide can be considered as a l,l-dianion equivalent of ethylene.eAt the second stage, a C-S bond cleavage with Li-DTTB generatesthe required nucleophile.
R R I -\ SPh
+
--J
)-oH
BuLi ; Li - DTTB ;
Z\/c
(A
*fR o*
.................."...........,......................*
sPh
R'2c=o
+o'., R'
(
Cleavage of 2-methylene-3,3-dimethyl-4-phenyloxetane.ttt Reductive lithiation of this compound apparently leads to an O,C-dianion. However, only the enolate reacts with electrophiles(e.g., carbonyl compounds).Steric hindranceof the benzylic position may be the reason.
Alkylation of ct-tetralone in D I . I ,4,7,10,10-hexamethyltriethl lcr Directed lithiations.
3.-tr \l
t-DA.7
Tandem cyclization. Deprorr evclizationvia an cycloalkylidenc
,^1h
LDTTB |,I'$
RR'c=o
o ll pn-^XMn ,/\
OH
L n,
rPastor,I.M., Yus,M. TL 41,5335 (2000). 2Ortiz,I., Guijano, A., Yus, M. T55,4831 (1999). rOrtiz, J., Guijarro, A., Yus, M. EJOC 3OO5(1999). aFoubelo,F., Saleh,S.A.,Yus, M. JOC 65,34'78(2000). 5Alonso,F., Radivoy,G., Yus, M. T 55,4441 (1999). 6Radivoy, G., Alonso, F., Yus, M. f 55, 14479 (1999). TFoubelo,F.,Yus,M. TL41,5047 (2000). nFoubelo,F., Gutienez,A., Yus, M. S 503 (1999). 'Foubelo, F., Gutierrez, A., Yus, M. TL 40,8173 (1999\. loHashemzadeh, M., Howell, A.R. TL 41,1855 (2000).
/
r"Jtll
Kataoka,K., Tsuboi, S. S452 t2ffi, :Nishiyama, Y., Kishimoto,y., Iroh. K . 'Murai, T., Suzuki,A., Ezaka.T.. Kero. 'Vurai, T., Endo, H., Ozaki, M.. Karo. I 'Brun, E. M., Gil, S., Mestres,R.. hrn 'Goto, M., Akimoto, K., Aoki. K.. Shru Mattson,R.J.,Sloan,C.P.,Lockhan. C 'Harada, T., Fujiwara,T., Iwazaki. K . C
Lithiumdiisopropylamide,LDA.
13, 163-164:15, 188-189; 16, 196-191;17,165-16'7: 18, 212-214; 19, 193-197; 20,218-220
Eliminations. l-Fluoroalkenes afford l-alkynyllithiums. which can be used to form propargylic alcohols.I Deprotonation Organolithium speciesare obtained from 1-alkoxy-3-phenylseleno1-alkenes (subsequentregioselectivealkylation occurs at C-3),2 selenoamides,iand selenono-thioesters.4When those derived from cr,B-unsaturatedacids condense with nitriles 2-pyridones are obtained.5
Lithium
hexamethyldisilazide.
LI
20,221-222
4-Jodooxazoles.t After lirhra treatmentwith iodine effects iodinr Eliminations, Double elimrn alkynes,2while propargylic bromrd flrnish enediynes.3
Lithium
t ,.:
bc consideredas a l,l-dianron ^()nd cleavasewith Li-DTTB
o Z:...\,,COOH Et2NLiZ>A**
\A R R I --3
7-o,
-' R'-TOH
hexamethyldisilazlde
;**t\.Jlt-z^*
o ll
(^r ,/'-.ZZZ.Z\
Et2NLi i-PrCN
K
.tht.tetane.ttt Reductivelithiation of ll .,.:r cr. only the enolatereactswith ri-r-.:'rscof the benzylic position may
Alkylation of ct-tetralonein DME using LDA as base shows rate enhancement when I'l'4'7'10'l0-hexamethyltriethylenetetramine is present.Dialkylation is also lessserious.o Directed lithiatians. 3,4-(Methylenedioxy)halobenzenesare lithiated at c_2 with LDA.7 Thndem cyclization. Deprotonation ofan alkyne such as that shown below initiates cyclizationvia an cycloalkylidenecarbeneintermediate.s
(o)-1.-,6
/ tlt
-'** tY'" i'PrzNLi (ol']-pn
'Kataoka, K., Tsuboi, S. S 452 (2000). rNishiyama,Y., Kishimoto,y., Itoh, K., Sonoda,N. SL611 .lgggJ. 'Murai, T., Suzuki,A., Ezaka,T.,Kato, S. Ot 2, 311 (2000). lMurai, T., Endo, H., Ozaki, M., Kato. S. "/OC 64, 2130 ( 1999). 'Brun, E. M., Gil, S., Mestres,R., parra,M. SL 10gg (1999). "Goto, M., Akimoto, K., Aoki, K., Shindo,M., Koga, K. TL 40,8129 (1ggg'). -Mattson, R.J.,Sloan,C.P.,Lockhart, C.C., Catt, J.D., Gao, e., Huang, S. JOC 64,g004 (1999). 'Harada, T., Fujiwara, T., Iwazaki, K., Oku, A. OL 2. lg55 O00O .
. ..
l rt9:16, 196-197;17,165-167:
t1 ::trums.which can be usedto form xi. :..J lrom 1-alkoxy-3-phenylselenoand s.--:. at C-3),2 selenoamides,3 ! .',..:n\aluratedacids condense with
Lithiumhexamethyldisilazide,LHMDS. 13, 165;14,lg4;lg,215-216;lg, 197_lgg; 20,221-222 4-Iodooxazoles.rAfter lithiation of oxazoleswith LHMDS at C-2, subsequent treatmentwith iodineeffectsiodinationat C-4. Eliminations. Double eliminationof B-hydroxysulfoneswith LHMDS leadsto alkynes,2 while propargylicbromidesareunitedvia an alkylation-elimination processto furnishenediynes.s
Lithium naphthalenide, LN
o
<''*"'
A
(Me3Si)2NLi
HMPA _ THF
SiMe3 9 6 0 / (oZ : E
Alkylations.
2.2:1)
Glycine derivatives are readily alkylated at C-2 by using a combina-
tion of LHMDS and LiCl.' rVede.ls, E., Luchetta,L.M. JOC 64,1011 (1999). 2orita, A., Yoshioka,N., Struwe,P, Braier,A., Beckmann,A., Otera' J. CEJ 5' 1355 (1999). iJones, G.B., Wright, J.M., Plourde,G.W., Hynd, G., Huber, R.S., Mathews, J.E. JACS 122' 1937
(:
(2000). aMyers,A.G., Schnider,P., Kwon, S., Kung, D.W. JOC 64,3322 (1999)'"1
H alo gen-lithium exchan gctchlorinated nitrogen aromatic hcta Reductrq Partialreduction. is obsened. Birch reduction the as liquid ammoniars advantageous
a.4'
Y b +\ o*ot
Lithium iodide.20,223 Ring expansion. Cyclohexanonesare formed by isomerizationof methylepoxideswith LiI.r Apparently,iodohydrinsaretheintermediates. enecyclopentane Diailcllphos phine-boranc ca accessiblethrough reductiveclearl
o ll
&:::n.* a\ [
_ tcoottte COOMe
96%
Deoxygenation.2 Amberlysrl5
-)r/. ."^, ( zP..J
Conjugated epoxy ketones are converted into enones with LiI and
resin in acetone (12 examples, 85-98Vo).
Cyclization." A related reag used to form cyclopropyl- and clcl
rBouyssi,D., Cavicchioli, M., Large, S., Monteiro, N., Balme, G. SL'749 (2000). ' Righi, G., Bovicelli, C., Sperandio,A. T 56, 1733 (2000).
Lithium naphthalenide,LN. 15, 190- 19 1; 18,217-218; 19, 199-200;20,224-225 O-C bond cleavage. p-Ketols result from epoxy ketoneson exposureto LN'l Variousbenzyllithiumsare formed by reductivelithiation, for example,of 4-aryl-1,3andbenzylpivalates.a 2-aryloxazolidines.r N-substituted dioxanes.2
r
-^-) PhS
CHSPh
LitNum naphthalenide,LN
,--
o
SiMe3
A
I €',
o tl
Li-napthalenide THF _78" Hzo
siMe3
Z:E
r\
-T-\ot 68Yo
2.2:1) Halogen-lithium
;.r . ..ttcd^L C-2 bY using a combina-
exchanges. Aryllithiums are generated from fluoroarenes5and chlorinated nitrogen aromatic heterocycles.6 Partial reductian. Reduction of certain heterocyclesby LN in the same pattern as the Birch reduction is observed.? Using this method in a large scale preparation is advantageousas liquid ammonia is not required.
J. CEl5, 1355(1999). r ! rrcra. J.E."IACS122, 193'7 1-.-- R S.. Mathews,
: ,r999).
ZZ\N--{,P
I
Y
X
Li-napthalenide
\ \
nh?
R 2 N H / T H F- 7 8 " ; Mel
hv isomerization of methylinns are the intermediates.
c d
f^'/
7 b +\ o2-\
62Yo
Diallcylphosphine-borane complexes. Chiral secondaryRR'PH-BH1 complexesare accessiblethrough reductivecleavageof thiophosphineswith retentionof configuration.8
_.'COOMe COOMe
-Y,
/'../y %"r {;:
96%
i.:
Li-naptharenide-Y ," ,
o,rrr 6S
.r,nveftedinto enoneswith LiI and Cyclizatinn.e A related reagent from Li and l-dimethylaminonaphthalene has been usedto form cyclopropyl- and cyclobutylcarbinyllithiums.
f\
t.
(; .s1749(2000).
j
Li+ _ It", -
I I r. 19, 199-200; 20,224-225 B-.J:'"\] ketones on exposureto LN.' for example,of 4-aryl-1'3: ..::r:.rtron. " , h. .I pivalates.a t
r t
4\/ PhS
CHSPh t
ZY\ l l l t \,'\Z
l
rHF -78" i MeoH
Li
\ )-spr' /v 87%
Lithium
perchlorate-diethyl
ether
rJankowska,R., Mhehe, G.L., Liu, H.-1. CC 1581 (1999). 2 Azzena,U., Pilo, L. S 664 (1999). 3 Azzena,U., Pilo, L, Piras, E. T 56,3'775 (2000). aAlonso,E., Guijano, D., Martinez, P.,Ramon, D.J.,Yus,M. 255, 11027(1999). 5Guijarro,D., Yus, M. f 56, 1135 (2000). 6Gomez,I., Alonso, E., Ramon, D. J., Yus, M. 256, 4043 Q000). TDonohoe,T.J.,Harji, R.R., Cousins,R.PC. Za 4l, 133I (2000). 8Miura, T., Yamada, H., Kikuchi, S., Imamoto, T. JOC 65,1877 (2000). eChen, F., Mudryk, B., Cohen, T. T 55,3291 0999).
Baylis- H illrnan reaction.' by DABCO.
rTietze,L.F., Weigand,8., Wulff. C 5 2Naimi-Jamal,M.R., Mojtahedi. \l \l rMasanori,M., Shioiri, T. TL &- 7|.ff alanger, P., Freifeld, I., Holtz. E. St- i 5Saidi, M.R., Javanshir, S., Mojrahcd. 6Heydari, A., Larijani, H., Emami. J . l TKawamura,M., Kobayashi, S. ft a.
Lithium perchlorate{iethyl ether.18,218-219;19,2OO-2O|;20,224-225 from Carbonyl masking, Dithioacetalizationrand formation of cr-silylamines2 exploittheLewis acidityof LiClOo-EtrO. aldehydes
Lithium
tetrachloropalladate
Oxidative
desilylation.
.fu
Li2PdCla-CuClr. Thus, cycliz:rru - LiClOa; Me3SiNl\4e2 t
Dosition.
Ph 5l
PhMe2SiLi &
NMe2
lnot\
74%
The products from reaction of epoxides with diphenyl azidophosphate assisted by LiClOa are P-azido phosphates. 2-Azido-2-alkenones are Epoxide opening.
obtainedfrom epoxy ketones.' In the presenceof LiClOo the alkylation of the ethyl acetoacetatedianion with epibromohydrin leads to 2-ethoxycarbonylmethylene-5-hydroxymethyltetrahydrofuran.a
NaH , BuLi - LiClOa;
COOET -.-.-.-.---.-------..----._ n'-1 '9 " \,/ \{
THF
/t o \ \\.\,cooEt
Tetrahydropyranylethen.: promotedby LiBFa in MeCN.
I
74o/o
R'_NHOH+
LicroaEt2o M E 3 S i _ C N+
I
rBabu, 8.S.,Balasubramanian. K-K iC rBabu,8.S.,Balasubramanian. K.K SI
Amines,5 In situ transformationof the Grignard reaction products of carbonyl compoundsinto aminesis accomplishedby the addition of lithium hexamethyldisilazide and LiClOa. u-Cyanohydroxylamines.6 The three-component condensation of aldehydes N-alkylhydroxylaminesand MejSiCN is convenientlyaccomplishedat room temperature (yields in 9OVorange) with the aid of LiClOo-EtrO.
R-CHO+
IMacsari,L, Szabo,K.J.7L 41. I I l9 r.
Lithium tetrafl uoroborate. S7y2'displacements.t Gllcal thioglycosidesin the LiBF.-catal1
Ho-t
o )-,.-
R"
cN
Lithium tetrakis(pentafl uoropba Benzylations. Arenes undcr presenceof LiB(CoF.)4.Addition
increasingthe catalystturnover., The LiB (C6F5)o-LiOTf/MgO cc hols (10 examples,72-lW%\ Th taining basesensitivefunctionalirr
NAru.R' I
OH
rMukaiyama, T.,Nakano,M., Kikuchr 2Nakano, M., Matsuo,J.,Mukaiyama1
Lithium tetrakis(pentafluorophenyl)borat€
,, otf{t;|t"*an 7ii
l-,1999r
,I::,:: ,!
reaction'. Liclo4-Et2o accelerates thereacrion rhatrspromored
o. *:lcjnl. B. Wurff. c. s 6e(2000).
;Jl'T'Iffi T',hJfi:t r'' M.R rcs(pr)37 0s(tess ) )'iX?ll*l-';' saidi, Freifeld,r., Holrz,
) I
t . : 1.20.221_225 r' n ()f o-silylamines2 from
/t --rrr-
e. SZSOiIZOOO;. .:"lg"t,p., )Saidi, M.R.,Javanshir, S..Mojtahedi, lfn4.]ZnO 330(1999). nHeydari, A., Larijani,H.. Emami,J., Karami, n. iiiI,")qtt 'Kawamura, -'' ". tzoool. M., Kobayashi,S. rL 40, tiig'riisstl Lithium,tetrachloropalladate-copper(Il) chloride. -allylrifu""--_i desilylation.l e" - . _Oxidative
ffi
ph I
'"""r,'rn""' .v.rzation occurs *;.";;;3"Jr"::Tfi::Jf:f:ifi:"#
-'a
I NMe2
_^1.-cooEr
.:-lr()nproductsof carbonyl : hi um hexamethyldisilazide rJ!'nsation of aldehydes ' :'ir'hed at room temperature
x:- :. I
lMacsari, I . , S z a b o ,K . J . T L 4 l , t I l 9 ( 2 0 0 0 ) .
Lithium tetrafluoroborate. S7y2'displacements.t Glycal
--3
cN
nAru'R' OH
,.
lo
jtr:{)-z--
: !.poxides with diphenyl , -. l-Azido-2-alkenonesare F: ' .:gcr?t€ dianion with epibro_ .' :r ltetrahydrofuran.a
)t
tr: rl
*-a\ !7-or).,'",
)t'
a.
2Ss
acetatesare coj thiogrycos ides intr,"i inno-. ut aty ze d'"".,,"; ;J::[li: Tetrahydropyranyl
ethers.2 promoted by LiBFa in MecN.
p.ot".tio;
'l.*Jffi'.f -. 1l i",:tf
;; ;;; rhols by reaction with dihydropyran is
rBabu, B . S . ,B a l a s u b r a m a n i a n ,:: S : _ 1 g , 4 2 9 9( 1 9 9 9 ) :r . L 4 0 , rBabu, 5j77(tggg). B.S., Balasubramanian, K.K. SI 1261(lggg\.
Lithium tetrakis(pentafluorophenyl)borate. Benzllations. Aren
j**n:'J'?iT"Tlff TIi";;i,""#;?,JtT; r,."nmhl,,l
TheLiB(c6F5)rt-iorvjgo_l0mbination caralyzes benzyretherformarionfiom hols (10 exampres, arco_ 72-ro0vo).The methodt. l.i*,. -'' for dealingwirh subsrrates tainingbasesensitive con_ functionalities., rMukaiyama, T., Nakano,M.. Kikuchi, W., Matsuo,J. CL ,I()IO 'Nakano. . (2000). M . . M a t s u o .J . . M u k a i y a m a . r ' aa , jrjl)oool.
Lithium tri-r-butoxyaluminum hydride
Lithium 2,2,6,6-tetramethylpiperidide, LTMP. 13, 167; 14, 194-195;17, 17I-172; 18,220-221;19,202;20, 226-227 Conjugateddienes, Alkenylchloridesandalkenylzirconocene chloridesarecoupled with LTMP.
caHrcsA7,l"' a^"n^ vv
, * ",-z.l-.-
f*,,,, =^ '-
-
Frrouzabadi, H., Karimi,B.. Eslamr \uge,J.,Gil, R., Kalsey,S..Luhrn-
cantz,,y',,-)---
vv
73Yo
('
Unprotected pyridinecarboxylic acids are readily lithiated.
Directed lithiatian.
lil
';
cooH I
cooH
BuLi
r^ \rr'
6\cootr i
l
\N-'
l
65%
Benryne formation.3 Iodobenzenesuffersdehydroiodinationat -40' in the presence of LIMP. Trapping of the benzyne by ester enolates is followed by iodination, therefore 2-substitutediodobenzenesare generated. rKasatkin, A., Whitby,R.J.JACS121,7039(1999). 2Mongin,F.,Trecourt, F.,Queginer, G. TL 40,5483( 1999). rTripathy,S.,LeBlanc,R., Durst,T. OL l, 19'73(1999).
Lithium tri-f-butoxyaluminum hydride. Reductinn,' One of the ester groups in a disubstitued malonic ester is reduced to a primary alcohol by this reagent.
Ph
.cooEt
X"oo=,
LiAl(t-BuO)3H
Ph
cooEt
,-\--on 85Yo
rAyers,T.A. TL 40, 5467(1999).
| -ithium trifl uoromethanesulfq Dithioacetalimtion.t LiOT r-rformed without solvent. Diels-Alder reactions.: l-rr rctivities are comparable.
Lithium trifl uoromethanesulfonate
t"
l{. I 94-195;17,171-172:'
n;
arecouPled chlorides !()nocene
Lithium trifl uoromethanesulfonate. Dithioacetalization.t Liorf is a highly efficient catalyst. The reaction can be performedwithoutsolvent. Diels-Alder reactions.2 LiOTf is a suitable substitute for LiClOa as their catalytic activities are comparable. Firouzabadi, H., Karimi,B., Eslami,5.TL40,4055(1999). :.{uge,J.,Gil, R., Kalsey,S.,Lubin-Germain, (2000). N.,!L 8':-7
- coH,s -tL 73To
.rcrdsare readily lithiated.
looH
=1
65%
fa
)
i
=:2 't,
I
\.-'cooH
*
)r
rE: rl
.irnationat -40" in the presence ,llrrwedby iodination,therefore
l.l malonic esteris reducedto a
e- cooEt --"-oH 35%o
EA
r{
w
COOlYl.
Magnesium. 13, 11O; 15, 194 ; 16, I 98- I 99; 18, 224-225 ; 19, 205; 20, 229-230 sitylations. A method for silylation of tertiary alcohols employs Mg and Mersicl in DMF at room temperature (12 examples, TT-99Vo).t Under similar conditions, thermodynamic silyl enol ethers are formed.2 Interestingly, trifluoromethyl ketones provide 2.2-difluoroalkenylsilyl ethers.l
Mo/THF
(:l -.:l
F
H
+ Me3sicl
,}{n F
O
,
Ph
OSiMe3 91To
Magnesiumservesto re( rg a free radical cyclizaticx Reductions. Carbonrl .)\'lF at room temperature in THF : \1g-SnC12'2H2O
Barbier reactions. Al ..'lutionusinga combinatr -r. been demonstrated.
i{,rrrever,conjugateadditro Deoxygenation.
Cyclic thionocarbonatesare reductively openedby Mg-MeOH'a
S
tl oAo
Mg / NIeoH
R o H \
l-f
R
COOMe
COOMe R=Ph 79%
Eliminations. Unsaturatedoximes are obtained from 5-bromomethylisoxazolidines that are the cycloadducts of nitrile oxides with allyl bromide. At temperature )0o, the double bond moves to conjugation with the oxime.5
Mg / N,lsoH
,|-q R-\./--J
NOH
*4.,^\
Br
\ t agnesium bis(diisoprop5
Silyl enol ethers.t Kr -.rng this baseand Et,N. H:
i-essene, G.,Tripoli,R..Cazc NOH
*42""Cyclizttions, D,e-Unsaturatedcarbonyl compounds undergo cyclization with Mg.o The reaction can be carried out electrochemically on a magnesium electrode and its application to a synthesisof musconehas been demonstrated.? 258
\r.higuchi.I., Kita.Y. \latan l.hino,Y., Kita,Y., Maekas r999). T..Hau \mri.H.. Kobayashi. Rho,H.-S.,Ko,B.-S.SC29.. 1fu.S.J.,Lee.G.H.,Yoon.I K t.ce.G.H.,Ha,S.J.,Yoon.I K S.,Murai.\'.. lsh Kashimura, s-l.949(r999). H.. Ostr Tang,J.,Shinokubo, \*ami, S.S..Desai,D.G..Bb R.P. Bordoloi,M., Sharmaq. lhang.W.-C..Li. C.-J.JOCa D.P.,Geraghq.\ $ Costello,
\lagnesium bis(hexametb Aldol reactions.t Th -.cxamethyldisilazane. can . :r drocarbonsolvents.
K-\[ . i \llan. J.F.,Henderson.
Magnesiumbis(hexamethyldisilazide)
acqsPh
oH __-sPh
Mg/MeOH-EIOH HgCl2
l---' 19.105:20, 229-230 r :.. ,holsemploysMg and MesSiCl ; r., L nder similar conditions. n:f 'r.:rnsl\'. trifluoromethyl ketones
Ph OSiMe3 91%
trr,. :rr r'lv openedby Mg-MeOH.a
F
o
H IOOMe
F. = 36
79o/o
I :: ::r -5-bromomethylisoxazolidines | ': ;nide. At temperature)0o, the
NOH ' i/-'tt'\
NOH
,-+^ ( | )
w
COOMe 96To
Magnesium servesto reduce Li2Mncro to active Mn(0), with the latter speciesmediat_ rng a free radical cyclization of unsaturated iodo compounds.8 Reductions' Carbonyl group reduction is achieved with Mg-Fecrj.6H2o in aq DMF at room temperature.eFor chemoselective reduction of aldehydes,the combination ,ri Mg-SnCl2.2H2Oin THF suffices.r0 Barbier reactions- Allylation of aromatic aldehydes in 0.r N ammonium chroride 'olution using a combinarionof Mg and an alryl bromide or iodide (bur not allyr chloride) has been demonstrated.r Unfortunatery, ariphatic aldehydes give complex mixtures. Howeveqconjugateadditionto enonesi2 can be achievedwith mediationuy cut. Nishiguchi, I., Kita,y, Watanabe, M., Ishino,y., Ohno,T.,Maekawa, H. SZ 1025(2000). : Ishino,Y, Kita,y, Maekawa, H., Ohno,T., yamasaki, y, Miyata,T., Nishiguchi, I. T.L 40,l34g r I 999). .{mii,H., Kobayashi, y, Uneyama, T., Hatamoro, K. CC t3Z3(1g9g). 'Rho,H.-S., Ko,B.-S.SC29,2875(1ggg.'. 'Ha, S.J.,Lee,G.H.,yoon,I.K.,pak.C.S.SC29,3165( 1999). Lee,G.H.,Ha,S.J.,yoon,I.K.,pak,C.S.ZZ40, 25gl ilggg). Kashimura, y., S.,Murai, Ishifune,M., Masuda,H., Shomomura, M., Murase,H., Shono,.,-AC,S s3,949(1999). 'Tang, J.,Shinokubo, H., Oshima,K. ?.55,lg93 (1999). .Swami, S.S.,Desai,D.G.,Bhosale, D.G.SC30, 3Og7'(2000). Bordoloi,M., Sharmaq, R.p.,Chakraborry,V. SC 29,ZiOtllVf;. Zhang,W.-C.,Li, C.-J.JOC 64,3230(tggg\. :Costello, D.P.,Geraghty, N.W.A.SC29,3083(1999). \Iagnesium bis(diisopropylamide). silyl enol ethers.t Kinetic enolsilylation of ketoneswith Mersicl is observedby usrngthis baseand Et3N,HMPA in ether _7g". at Lessene, G.,Tripoli,R.,Cazeau, p, Biran,C.,Bordeau, M. TL 40,4037Oggg\.
'a-'1.-2"..-
rn.:. undergocyclization with Mg.6 o. .1 ntagnesiumelectrode and its St:r lad.
\ Iagnesium bis(hexamethyldisilazide). Aldol reactions.t This base, prepared in heptane from dibutylmagnesium and hexamethyldisilazane,can be isolated in crystalline form. It mediatesaldol reactions in hvdrocarbonsolvents. .{llan,J.F.,Henderson, K.W.,Kennedy, A.R. CC 1325(lggg).
)r
tr:
rl
,. lr
7; < t-
I
Magnesium chloride-triethylamine
Magnesium bromide. 15, 194-19 6 ; 16, 199; 17, l7 4 ; 18, 226-227 ; 19, 206-207 ; 20, 230-232 Deprotection.t Trimethylsilylethoxymethyl ethers are cleaved on exposure to MgBr2.OEt2. Solvent plays a critical role, with the most effective being a mixture of ether and nitromethane. Cyclization.2 A remarkable formation of the skeleton of saframycin A has been reported.
MeO
I
C
\
'*1-t"-
(::
\-^
OEt2 l\,'lgB12.
/
THF ^
a
-Cl
OH
R H N -1
to/
.:
:r'c similarly obtained.
>> Z'>.'< l l l F o \-,^r'r 'an
Ho\4 N
\lagnesium iodide. 20, 232 Pynolidines.t Pyrrolidrn<'. 'caction with aldimines. are cau
OMe
P\-ove OMe
llofslokken. N.U..Skattebol. L. ..1( Corbel,B., L'Hostis-Kervella. I.. lla Krm,D.Y.,Lee,Y.M.,Choi.\'.J. f 5!
)
R = Fmoc CONPh:
Cyanohydrination.3 Cyanohydrination of ct-alkoxy aldehydes with MerSiCN in dichloromethane at 0o requires an excess (5 equiv) of MgBr2'OEtr for high diastereoselectivity (syn-selective).Note that EtaNAg(CN)2 is a more powerful cyanohydrinating reagentthan MerSiCN.
\ tanganese.20, 233-234
rVakalopoulos, A., Hoffmann,H.M.R.Oa 2, 144'7(2000). 2Myers,A.G.,Kung,D.W.OL2,3019(2000). 3Ward,D.8.,Hrapchak, M. OL2,57 (2000). M.J.,Sales,
Active manganese.t A cc -.'ductionof Li2MnClowith Lr ,'1 reanohalogencompoundsrntrrr -.ters, and alkenyl halides.
Magnesium chloride-triethylamine. Salicylaldehydes.t o-Formylation of phenols with paraformaldehyde takes place under the influenceof MgCl2'EtjN. pKeto phosphonates. A transformation of diethylphosphonoaceticacid to B-keto phosphonates2 is achievedwith N-acylimidazolesin the presenceof MgClr'EtqN. However, is also effectedafter C-acylation.r dephosphorylationof ct-fluorophosphonoacetates
n vr\ ,
D/
ntrt vEi
P
h Mgcl2 / Et3N
-r-1 ,/'-oEt + PhCoCl -+ . cooEt
PhMe 25'
\lper, P.8., Meyers,C., Lerchner.\
r
B enzylmangane se su lfo nata i tosylatesand mesylatesurtlr 'chave similarly to Grignard rcae
t'rhiez,G.,Martin,A., Delacrorr. T i.rm.S.-H.,Rieke,R. D. Za {0. Jqil \langanese(Ill) acetate.13. l I le. 209-210; 20, 234-235
L
-X
FO
/
\-^
Perfluoroalkylation.l Intrq -r'actionof sodiumperfluoroalka u' -Functionalization of crro , -position of 3-alkoxy-2-ctcltra
31To
'J--rationby reactionwith \tnrC).
ETOOC /-" Ph
Manganese(Ill)acetate
-.: 1 18. 226-227:19,206_207;20, l:il.::. are cleaved on exposure to c ::: .: r-ilectivebeing a mixture of ether
Hofslokken,N.U., Skartebol,L. ACS 53, 255 (1gg9). rCorbel, 8., L'Hostis-Kervella,L, Haelters,J.-p.,!C 30, 609 (2000). 'Kim, D.Y., Lee, y.M., Choi, yJ. T SS,12983(tggg). Ilagnesium
frr .,.rlcton of saframycinA has been
261
iodide. 20, 232 pyrroridines,
Pyrrolidines't
via ring expansion of an activated cyclopropane nng on reactron with ardimines, are cataTyzed by magnesium iodide. spiroannurated oxrndores are similarly obtained.
OMe
N
O +
-Ts
tl
Nrgl2/ THF
o
A
)
N
E
Bn
r aI
90%
, =
Ts . coNPh2 r-: , .rr aldehydeswith MerSiCN in : \lgBr,.OEt2 for high diastereo_ ir , :. : :l()re powerful cyanohydrinating
r .1:ih paraformaldehyde takes place lr*::r lphosphonoacetic acid to B-keto lhi :-rc.enceof MgClr.Et.N. However, il' :rlc'ctedafter C-acylation.3
Ph i:'. 1
' > (F O r
,/ \-^
ETOOC rv
Pri
31Yo
N-T'
Mgl2 / THF
Pn)l
t
.'N
I Fpr, \
I
a a
coNPh2
t c
'\lper,P.B.,Meyers,c., Lerchner, A., Siegel,D.R.,carrerra,E.M. ACIEE3g,3rg6 (1999). \langanese. 20, 233_234 Active manganese.t A convenient procedure lbr the preparation consists of r-t'duction of Li2Mncl, with Li /2-phenylpyridinein 'fHF at room temperature.lt converts ''rganohalogencompoundsinto species reactivetoward phCocr, enonesand conJugated r'st€rs,and alkenyl halides. Benzylmanganesesurfonates.2 A preparation of these reagentsis by direct reaction ''i tosylatesand mesyrateswith Rieke manganesein THF at room temperature. They :-*havesimilarly to Grignardreagents. Cahiez, G., Martin,A., Delacroix, T. TL 40,6107(lggg). Kim,S.-H.,Rieke,R. D. TL 40,4931 (1gg9). \langanese(Ill)acetate.13,.l7l;14,197_199;16,200;17,175_176;1g,229_230; 19. 209-2 | 0 : 20, 234_235 Perfluoroalkyration.t Introduction of a perfluoroarkyr group to c-3 of coumarrns by :eactionof sodiumperfluoroalkanesulfinates is mediatedby Mn(OAc)j.2H2O. a'-Functionalization of enones. Introduction of phenyr and acetoxy groups to the o'-position of 3-alkoxy-2-cycloalkenones (five- and six-membered)is carried our ln one ()perationby reactionwith Mn(oAc). in benzeneor a halobenzene.2
-{<
a
Manganese(Ill) acetate
o -'#...,
o R'\Af"^ Ny'n(oAc)3
*o{/
Liu, J.-T.,Huang,W.-Y.JFC 95, l3l I lE}r, :Tanyeli,C.,Sezen, B. TL 41,7973eXn, Wu,Y.-L.,Chuang, C.-P,Lin, P.-Y f 55..'-. 'Cossy,J.,Bouzide, A., Leblanc.C. JOC6.< 'Cossy, J.,Bouzide,A. f55,6483(1999,
*o{/
--:h
n = 0 ,1
Radical cyclizations. When the acyl group of an anilide bears an alkylthio alkylsulfonyl group, cyclizationonto the Ar ring is initiatedby Mn(OAc).,in HOAc.r
(.--
fl
Oxi.dativechain extension.. Re.rr hydes and the Wittig reaction '*.irh .ral cordingly, three-carbonhomologarron,r
o\-
rs
Mn{oAc)r \Z*\ \,.Z\ /-.\1. l l l l l l - - - - - - - - - - - - - - * l l l l
\A*Ao
o
HoAc 80
\ArAo
$l
Manganesedioxide. 14, 200-201: 15. t Nitrile oxides.r An alternatir.errrr oximesis by oxidation with MnO-.
ably,the transformationis successful* rt
\
(
A
AH+Ph3Vc
62Yo
B-Keto amidespossessingunsaturationin the side chain undergooxidativecyclization in the presenceof the Mn(OAc)r-Cu(OAc)ucombination.a
\Iercury(Il) acetate.15, 198-199:17. I Oxymercuration. Homoallylic alo .rt an aldehyde,giving rise to l._1-dr I unctionalized.
o
#<'J
Niln(OAc)3- Cu(OAc)2
EtoH
Kiegiel,J., Poplawska,M., Jozwik. J.. Krxr.r :Blackbum, L., Wei, X., Taylor, R.J.K. ('(- I r
25.
55To OH | Oxi.dation.5 B-Enamino carboxamides derived from cyclic B-keto amides are oxidized by Mn(OAc)1-Cu(OAc)2to give enones, dienamines,or aniline derivatives, dependingon the ring size.
q)" A^ _,,l--
o
- Cu(OAc)z N.4n(OAc)3
v
o
By the conventionalprocedure($rth I ;ohols.2It shows chemoselectivit\.such I :. retained.
/\-J'.,',\
K2CO3/ EIOH 80" HCI
t
+ ETCHO
C8H17tt---'\
)
"
H 57o/o
.,oMe /,4,v nv Nv nv n\ v
') --
_*
Mercury(Il) acetate lLiu, J.-T.,Huang,W.-Y. JFC 95, 131 (1999). :Tanyeli,C., Sezen,B.TL4l,79'73 (2000). 'Wu,Y.-L., Chuang, C.-P.,Lin, P-Y 256,6209 (2000). rCossy,J., Bouzide,A., Leblanc,C. JOC 65,7257 (1999). 'Cossy, J., Bouzide,A. r55, 6483 (1999).
:r .rnilide bears an alkYlthio -J b1'Mn(OAc)j in HOAc.l
Manganese dioxide. 14, 200-201 ; 15, 197-1 98 ; 18, 230-23 1; 19, 210 ; 20, 237 -238 Nitrile oxides.' An alternative method for generation of these reactive speciesfrom oximes is by oxidationwith MnO2. Oxidative chain extension.2 Reaction conditions for oxidation of alcohols to aldehydes and the Wittig reaction with stabilized phosphoniumylides are compatible.Accordingly, three-carbon homologation of alcohols is feasible in one operation. Remarkably,the transformationis successfulwith unactivatedalcoholssuchas nonanol.
lVn02
N
\
A
"n+PhaP"cooet
\
WWVCOOET
PhMe
80Yo
62%
d
.rrnundergooxidativecyclization
K i e g i e l ,J . , P o p l a w s k aM , . , J o z w i k ,J . , K o s i o r ,M . , J u r c z a kl,. T L 4 0 , 5 6 0 5 ( 1 9 9 9 ) . :Blackburn,L., Wei, X., Taylor,R.J.K. CC 1337(1999).
=
!
, { I
B.
\lercury(Il) acetate.15, 198-199; 17, 176-177; 18,232;19,2l l Oxymercuration.Homoallylicalcoholsundergooxymercuration in the presence ,rt'an aldehyde,giving rise to 1,3-dioxan-4-ylmethylmercury derivativesr that can be iunctionalized.
o 55o/o
O
O
I
-,"-
-HgCl
By the conventionalprocedure(with NaBHa work up), enol ethersare convertedto al;ohols.2It showschemoselectivitysuch that a simple double bond in the same molecule :\ retained.
OMc
'
57To
^ ,. .-tt,.H.,
77%
r\A*\H
;- j"
EtcHo -l;-
CaHrz
:r()m cyclic P-keto amides are 'nJrnines,or aniline derivatives.
-/ : ^,,,\^ U U : :
Hg(OAc)2
OH
.
:
,^.v n v An A\z-"'" v v v
Hg(OAc)2 / H2O - THF ,
NaBH4.K2coriH2o
Al\AAl"' 81%
I
tr r, Ia a a
Methanesulfonic
acid
7,2-Diketones.3 a-Substituentsof ketones such as o-sulfenyl derivatives are readily replacedby alkoxy groups in the presenceof mercury(I) acetate.1,2-Diketonesare accessibletherefrom. Biaryls.a Homocoupling of substituted arenes to biphenyls occurs on treatment with Hg(II)-Ce(IV) salts, for example, Hg(OAc)2 and Ce(OTf)4.
Aziridine opening. .A,zr openedwith MsOH and the pro
Hg(OAc)2- Ce(OTf)a
'Sarraf,S.T.,Leighton, J.L.OL2,403 (2000). 2Crouch, R.D.,Mehlmann, J.F.,Herb,B.R.,Mitten,J.V.,Dai,H.G.S 559(1999). 3Tehrani, K.A.,Boeykens, M., Tyvorskii, V.I.,Kulinkovich, O.,De Kimpe,N. 256, 6541(2000). alranpoor,N., Shekarriz,M. JCR(S)442 (lggg). Mercury(I) fluoride. Decarboxylation.t
Photodecarboxylationof arylacetic acids is induced with HgrF2.
Ph
--
hv Ho,F,
)-cooH n{
;
MecN
Tl
rWang,M.W, Chen,y.J., Wang.D I rTamamura, H., Yamashita. l\t.. \el JCS(P1)2983 (1999). jKaboudin, B. I55, 12865( 1999r
Ph H Ph
Fries reatangement.' rearTangement.
Ph 83o/o
Methoxyamine.
Amination. Conjugated dr via an addition-+liminationprcrr
'Habibi, M.H., Farhadi, S. fz 40, 2821 Qggg).
Mercury(Il) tosylate. oxazoles.t under microwaveirradiation,Hg(ors)2 effectscondensation of ketones with nitriles.
l{;'"J
( tht.'t-X-'J tl
R
R
.
N
F o* /
\
R'
P
\\
+
h
);ru // \\
R'--\^/-Ph U
R=Ph,R'=H
Nitroarenes undergo amlnatro 51%
rLee,J.C.,Song,I.-G.TL 41,5891(2000). Methanesulfonic acid. 20, 240 Allylation.t Allylation of aldehydes with allyltrimethylsilane is catalyzed by MsOH (actually MejSiOMs thar is generatedin situ).
r S e k oS , . ,M i y a k e , K. SC29,2-187, rSeko,S., Miyake, K., Kawamura-\
O-(4-Methoxybenzyl) S-(2-p1ri 4-Methoxybenzyl ethen. derivatizedunderneutralcondiu dichloromethane.
O-(4-Methoxybenzyt)S-(2-pyridyt)thiocarbonate
s r'.ult-enylderivativesare readily II .:.r'tate.1,2-Diketonesare
265
Aziridine opening. Aziridines containing electronically biased substituents are openedwith MsoH and the products may be transformed into vicinal amino alcohols.2
t,' ^lphenyls occurs on treatment 6-.'r )Ti)r.
-Y, \")a ""'ff t
OMs t
r I
COOMe
(
;fz\cooMe
-a'r \-NH
MSOH / CHCI3 ..+
o--i
Y
. f: ( ' .\ 559(1999). ) i )e KrmPe,N. T 56,6541(2000)'
-1O0To I
rt b
lr.ilrc acidsis inducedwith Hg2F2'
Ph
P.
Ph
Methoxyamine. Amination, conjugated dicarbonyl compounds are aminated with methoxyamine I via an addition-eliminationDrocess.
ctfectscondensationof ketones
o
il On-n,,z\,,Arn O
. . , ,^ NH2olvre: tn\r'\rApn Naol\re
R
i
o
l
U
tl
l
NHz
83o/o
) , N
// \\
R'--\^/.-Ph '\J
-
r, I
t
t t J
I
a3 ' ;
.
combination is useful for inducing the
rWang,M.W.,Chen,YJ.,Wang,D. S4 385(2000). rTamamura, H., Yamashita, M., Nakajima, Y, Sakano,K., Otaka,A., Ohno,H., Ibuka,T., Fuiii, N. JCS(PI)2983(1999). rKaboudin, B. 255, 12865 (t999).
Pr
)T.
Fries rearrangement.3 The MsoH-poclj reiuTangement.
R=Ph'R'=H 51o/o
a...llrimethylsilaneis catalyzedby
Nitroarenes undergo amination, but the reaction is promoted by r-BuoK and cucl.2 rSeko,S.,Miyake,K. SC29,2487(1999). rSeko,S.,Miyake,K., Kawamura, N.,/CS(pl) 143'I(1ggg).
O-(4-Methoxybenzyl) S-(2-pyridyl) thiocarbonate. 4-Methoxybenzyl ethers.t Alcohols (primary, secondary, and terriary) are derivatized under neutral conditions with the title reagent in the presenceof Agorf in dichloromethane.
a a
I i :
a
Methylaluminoxane,
MAO
rHanessian, S.,Huynh,H.K. TL 40,6'71 (1999).
Ring formation.2 Homoallylzircont-rcyclopentenes under the influenceof \lAO
N-Methoxycarbonylsulfamoyl triethylammonium hydroxide. (Burgess reagent). Dehydration. Dehydration of aldoximesr'2 and a-amido ketones3 with Burgess reagent afford nitriles and oxazoles,respectively.
r--/\"'-\.
cpzzi I
ai
ll
.
R
\
rJose, B., Sulatha, M.S.,Pillai,P.M.,Prathapan, S. SC30, 1509(2000). ' Miller.C.P..Kaufman.D.H.Sa 1169(2000). 3Brain.C.T..Paul.J.M.SL 1642i199q.
.'flr
N-Methoxy-N-methylformamide. Formylation.t This Weinreb amide is prepared from methyl formate and N,O-dimethylhydroxylamine in the presenceof NaOMe. It reacts with Grignard reagents, organolithium compounds,and enolatesto furnish aldehydes. rLipshutz, B.H.,Pfeiffer,S.S.,Chrisman, W TL40,'7889(1999).
D a s h ,A . K . , E i s e n ,M . S . O L 2 , ' 7 3 1 ( 2 ( W ) t . jKotora, M . , G a o ,G . , L i , Z . , X i , 2 . , T a k a h a r h rT.
Methylaluminumbis(2,6-di-t-butyl-l-rnt0 15,204-205;16,212:17,l 87-l 88:18.:-r-. Allylation.l MAD is anefficienrcaral with allylstannanes. Marx,A., Yamamoto, H.SL584(1999).
2-(Methoxymethylthio)pyridine. Methoxymethyl ethers.t
Etherification of alcohols with this reagent is mediated by
AgOTf-NaOAc. This method is suitable for derivatizing acid-sensitivealcohols. Primary, secondary,and tertiary alcohols react at comparablerates,phenols slower. rMarcune,8.F., Karady,S.,Dolling,U.-H.,Novak,TJ. JOC 64,2446(1999).
Methoxymethyltrimethylsilane. Trtmethylsilylmethyl ethers.r After radical bromination of MejSiCH2OMe with NBS, reaction with an alcohol results in the mixed acetal of trimethylsilylacetaldehyde. Reduction with Dibal-H selectively removes the methoxy group. rSuga,S.,Miyamoto,K., Watanabe, M.,Yoshida, J.AOMC13,469(1999).
Methylalurninoxane, MAO. 20, 242-243 Alkyne dimerization.t 1-Alkynes are dimerized in the head-to-tail fashion by MAO in refluxing benzeneto provide 2-substituted 1-alken-3-ynes.
D
-
!
lll
MAo
l l l
I
R
PhH^
/ \ R R = i-Pr 99To
Methylaluminum bis(ditrifl amide). Ethers from alcohols.t Allylic and hcn
rt room temperatureunder the influence of \l is possibleusingexcessbenzyl alcohol. This reagent is prepared from : r'qur d ichIoromethane.
Ooi,T., Ichikawa, H.,ltagaki, Y.,Maruoka.K l/ 5
\Iethylammonium chloroformate. Carbonyl regeneration.t With this ..xh compoundsfrom oximes, semicarbazonc-.: rqueousconditionsis established. Zhang,G.-S.,Chai,B. SC30,2507t2000r.
\tethyl cyanoformate. Carbonyl group protection.t A C--{) cyanohydrin carbonate at room temFrrrrr ketonesare less reactive.The adductsarc.re rn MeOH. Berthiaume, D., Poirier,D. 256,5995t1000,
Methyl cyanoformat€
Ring formation.z Homoallylzirconocene chlorides couple with alkynes to form cyclopentenesunder the influenceof MAO. h1d nxide. (Burgess reagent). xj r ernido ketones3 with Burgess
"yl')..-r._-. \ --;;* --\+,.!-__Zf*
R.
NrAo/PhMe;
r--l^\2.^\
! - I r)0). 56-71% ' D a s h ,A . K . , E i s e n , M.S. OL2, j3j (Z0OO). rKotora, M., Gao, G.,Li,Z., Xi, 2., Takahashi,T.TL 41,7905 (2000).
pq:rJ
irom
methyl formate and
U: Ii reactswith Grignard reagents, le:i,c.. 9i..
Methylaluminumbis(2,6-di-/-butyl-4-methyrphenoxide), MAD. 13, 203;14,206-207; 15,204-205; 16, 212;17, 187- I 88; 18,237; 2U Zt3_Z| 4 Allylation.I MAD is an efficientcatalystfor chemoselective allylationof aldehydes with allylstannanes. rMarx, A., Yamamoto, H..!L 584 0 999).
r .. .rrth this reagentis mediatedby r:. : .'ird-sensitivealcohols.Primary, a:i. lhcnols slower. : br _-!6 ( 1999).
n:--r:r.ttronof MejSiCH2OMe with r. :r.ri Lrftrimethylsilylacetaldehyde. |( \ . :r()up. l-r :.q, 1999).
Methylaluminum bis(ditrifl amide). Ethersfrom alcohols.t Allylic and benzylicalcoholsfbrm ethersin dichloromethane at room temperatureunderthe influenceof MeAl(NTfr),. Catalyticbenzylationof alcohols is possibleusingexcessbenzyl alcohol. This reagent is prepared from 2 equiv of AgNTt) and r equiv of MeArcr, in dichloromethane. rOoi,T., Ichikawa, H.,ltagaki, Y.,Maruoka,K. H 52,575(2000). Methylammonium chloroformate. Carbonyl regeneration.t With this salt adsorbedon silica, regenerationof carbonyl compoundsfrom oximes, semicarbazones, and 2,4-dinitrophenylhydrazones under nonaqueousconditionsis established. rZhang, G.-S.,Chai,B. SC30.2507 (2000).
I :: ::.' head-to-tailfashionby MAO '-: ,:rc..
// K
= -)'
99%
Methyl cyanoformate. carbonyl group protection.t A c:o group is masked on conversion into the ctcyanohydrin carbonate at room temperature with NCCooMe-r-pr,NEt. conjugate ketones are less reactive. The adducts are revefted to ketones by treatment with NaoMe in MeOH. Berthiaume, D., Poirier,D. Z56,5995(2000).
- , I a
r, Ia b
a
a , , {
s
268
2-Methylene-1,3,3-trimethylindoline
2-(Methr-.lsulfor}'-
Methyl 2,3-dichloropropanoate. Two rinss are formed when the kinetic enolate of an enone reacts Bisannulationr with this ester.
+
oHc \/ i HO--<'
\
E
cr-..
. crlcoov"
"rl-(Me3Si)2NLi
Cho,Y.J.,Lee,S.H.,Bae,J.W.,$un. H 'J
THF _70'
Y
COOMe 82Yo
rSakai,H., Hagiwara, H., Hoshi,T., Suzuki,T.,Ando,M. SC29,2035(1999).
(-
::m 'ii: :.t
i
\
I -(Methyldithiocarbonyl)imidazole. Thioureas.t Symmetricaland unsymmetricalthioureascan be preparedby reaction of amineswith this reagent. rMohanta, H. T 56,629(2000). P.K.,Dhar,S.,Samal,S.K.,Ila,H., Junjappa,
\ lethyl fl uorosulfonyldifl uoroacetrtcTrffiuoromethylation.t The allen rcplacedby a CFj group in a Cul-catalr
Zhang,X.,Qing,F.-L.,Yang,Y. \'u. J . Fu l
.Y-Methyl-3-( p-methoxyphenl'l )isdod Aldol reactions.' Compound I u .ilyl enol etherswith aldehydesat l()$ tl
3,3' -Methylenebis[1,1'-bi(2-naphthol]. Mannich-type reaction.l The zirconium(IV) complex I of this tetrol is an effective catalystfor the condensationof silyl enolateswith aldimines.
..--\ MeO-417
o o-l -o .1'-, o r -
(1)
rlshitani,H., Kitazawa, T., Kobayashi, S. 7L 40,2161(1999,.
2-Methylene-1,3,3-trimethylindoline. Protectinn of salicylaldehydes.t This reagent forms spirocyclic N,O-acetals with Recoveryof the latter compoundsis by ozonolysis. salicylaldehydes.
T.,Yanagisawa, M.. Iida.D . }l \{ukaiyama,
V-Methylmorpholine N-oxide. 20. :{J Pauson-Khand reactions. Ttx' q componentmethyl acrylaterand rrnll cthylene.l
.\hmar,M., Antras,F.,Cazes, B. Il {0. ilJ :Ken,W.J.,Mclaughlin,M., Pauson. PL . R
2-(Methylsulfonyl-3-phenyl- l -prop2. Amino group protection.t Reaga
orotectionis removedbv thiols and a ca
2-(Methylsulfonyl-3-phenyl-1-prop-2-enyl succinirnid-N-oxy carbonate
oHc
n r - r.in!-tic enolate of an enone reacts +
/
\_ /
HO-
EtoH \
\)
+
\-\n
lCho,Y.J., Lee,S.H.,Bae,J.W.,Pyun,H.-J.,yoon,C.M.TL4l,3915 (2000). COOMe 82%
:e lrll5 ( 1999).
.rrcascan be preparedby reaction
s6 r)19(2000).
Methyl fl uorosulfonyldifl uoroacetate. Trifluoromethylation.t The alkenyl bromine atom of an ct-bromoalkenolc ester is replacedby a cF., group in a cul-catalyzed reaction with the title fluorinated ester. tzhang,X., Qing,F.-L.,Yang,y., yu, J.,Fu,X.-K. TL 41,2953(Z0OO).
N-Methyl-3-(p-methoxyphenyl)isoindolo-l-one
tetrakis(pentafluorophenyl)borate. Aldol reactions,t Compound I is a new catalyst for the condensation of various silyl enol etherswith aldehydesat low temperature. t{
:.lcr I of this tetrol is an effective :lr'\.
o (c6F5)48
MeO
. \,
(1)
?
rMukaiyama, T.,Yanagisawa, M., Iida,D., Hachiya,I. CC606(2000).
aa)
N-Methylmorpholine N-oxi de. 20, 245 -246 Pauson-Khand reactions, The scope of this reaction now includes as the alkene component methyl acrylater and vinyl benzoate,the latter serving as an equivalentof ethylene.r rAhmar,M., Antras,F-.,Cazes, B. TL 40,5503(1999). rKen,W.J.,Mclaughlin,M., Pauson, pL., Robertson, S.M.CC 2171(19gg).
:Jil\ spirocyclic MO-acetals with . ()ronolysis.
2-(Methylsulfonyl-3-phenyt-l-prop-2-enyt succinimid-N-oxy carbonate. Amino group protection.t Reagent I reacts with amines to form carbamates.The protectionis removedby thiols and a catalyticamountof base.
l-Methyl-l -vinylsilacyclobutane
o Il
/
\
N-O
o
\
f o
q
,sozMe \
)
Ph' (1)
rCarpino,L.A., Mansour,E.M.E. JOC 64,8399 (1999).
st .-it ..:;
Methyltrioxorhenium-hydrogen peroxide. 19, 217; 20, 248 Epoxi.dations. Epoxidation of alkenes in the NaY zeolite host have been studied.r Instead of hydrogen peroxide, sodium percarbonatecan be used as the
Denmark, S.E.,Wang,Z. S 999(2m,
Ilischmetal. SmI2 supplement.t This inerp \d l2%o,Pr 47o, others l7c) can bc reactions(e.g., Barbier reaction) rh.r
Helion,F.,Namy,J.-L.JOC 6. ?91! t I'
oxygensource.2 Excellent conversion and selectivity are attained when the epoxidation is performed in an ionic liquid.r Oxidations. MTO and bromide ion serve as cocatalystsin the oxidation of alcohols by hydrogenperoxide.aAldehydes are further transformedinto methyl estersand ethers into ketones.
\Iolybdenum carbene complercs. l 219-251 Alkene metathesis, Notablc Schrock catalyst (1) include the stcrt
On the other hand, selectiveformation of aldehydesis observedon oxidationswith a systemcomposedof MTO, TEMPO, HBr, and HrOr. Desulfurization.b Episulfides are desulfurized with a chemical system containing triphenylphosphine, hydrogensulfide,and catalyticamountof MTO. IAdam,W.,Saha-Mtjller, C.R.,Weichold, O. JOC 65,2897(2000). 2vaino,A.R.JOC 65,4210(2000). 3Owens, G.S.,Abu-Omar, M.M. CC1165(2000). aEspenson, J. H., Zhu,2., Zauche, T.H.JOC 64,I I 9 I ( I 999). sHerrmann, W. A., Zoller,J.P,Fischer, R.W.JOMC 579,404(1999). oJacob, J.,Espenson, J. H. CCl003(1999).
\ R.*'si'o /'
-:* cH9:
I
//n--/-R' i l
Y'Y^ , N
F3C. ,O,',,'lto Methyltrioxorhenium-urea-hydrogen peroxide. 19, 2l'7 -218: 20, 248 Epoxidation.t Procedure modification includes the use of an ionic liquid as reactionmedium. rOwens, G.S.,Abu-Omar, M.M. CC I165(2000).
1-Methyl- 1-vinylsilacyclobutane. Cross-coupling.t Pd-catalyzedcoupling of silane I with haloarenesgives styrenes
Frcl d
F"C-\-" CFr (1)
Tandem asymmetric ring-openrq with the aid of 2.2
Molybdenum carbene complexes
o Si
/\:
: -- ','e
(1)
:Denmark,S.E.,Wang,Z. S 999(2000).
Mischmetal.
lr u:l
:0. llti - \aY zeolite host have been -:..rrhonatecan be used as the
sml2 supplement.t This inexpensive alloy of light lanthanides (La 33vo, ce 5ova, Nd l2vo,Pr 4vo, others l7o) can be used to replace large portion of sml2 in mediating reactions(e.g., Barbier reaction) that require stoichiometric quantities. IHelion,F.,Namy,J.-L.JOC&,2gM (l9gg).
' -:r the epoxidationis performed in
Lr.
'. , .rir.ts in the oxidationof alcohols '':.rJ rnto methyl estersand ethers
Molybdenum carbene complexes. 17, 194-195; 18,242-243; 19,219-221; 20, 249-251 Alkpne metathesis, Notable applications of the metathesis catalyzed by the schrock catalyst (1) include the stereoselectivesynthesisof alkenylsilanes.r
rf r.. :. ()bservcdon oxidation5with a (1 f(
. :ir e chemical system containing . . : r ot l ' M T O .
-?.1, *i *-,a.-i*.
*
cH2ct2
t,.
\-l*,
R,
ffi
siue3
r-
,
N
I
F3C.,O""'ilo=\
:-lq. ll' 218;20,248 li :.. rhc use of an ionic liquid as
rscl d F"C-\-
tsrn
CFg
(1)
I ri ith haloarenesgives styrenes.
Tandem asymmetric ring-opening metathesisand cross-metathesishas been effected, with the aid of 2.2
Molybdenum carbenecomplexes
-at
OR t
^,
K
/=11
(t+=J
R-Li
+ / fu r
BF3.OEt2 + Mo(CO)6 + Et2o
o*
R FuBO
ry"i/:x^+^&*, V I r i - L ,Y (2\
The application of [Ru] and [Mo] catalysts in consecutive steps to convert a bridged ring ether to a fused heterocycler that retains all the atoms servesto illustrate the power of modern synthetic design and methodology.
),,"psr5= fi_,,,- jXoY The tris[N-aryl-N-(r-butyl)amino]molybdenum(0) complexes (3) are good catalyst precursorsreadily activatedin situ for metathesisof alkynes and diynes.a
o tl I
)ro
w
^/ o "\
) Y
)fY*'' d*f
Yx-rrY
Y
+
)-.t-\
l
l
l
,{hmed, M., Barrett,A.G.M., Beall, J.C.. Bred Salter, M.M. T 55,3219 (1999). :La, D.S., Ford, J.G., Sattely,8.S.,Borurarchri I (t999). 'Weatherhead, G.S., Ford, J.G., Alexanran. EJ (2000). rFurstner,A., Mathes, C., Lehmann, C.\l'. ./ACS l 'Barluenga, J., Rodriguez, F., Fananas,FJ.. Rnh
Molybdenumhexacarbonyl. 13, lll-195. 20,251-252 Metathesis. Diarylalkynesare prcg Mo(CO)oand p-chlorophenolat l{O' ynyl)phenylsiloxanes form cyclotrimersar
l
\--o...-J 91%
(3)
Michael-aldol reaction tandem. Fischer carbene Mo complexes containing a difluoroboroxy group, that is R-{(OBFr):Mo(CO)s, donate R to enones.The adducts may be trapped with aldehydes.s
-{r-fF
Llq CO i
Molybdenum hexacarbonyl
BF3.oEt2 R. R-Li + Mo(CO)6--: "* FMo(CO)s Etzo F2Bo'
\.
l* PF, I | )_UrofCOf. I | {
+
I
l-
sn
+
| R'cHo
/
(
L--
l
R
'
V
"'oH
R
D . :..1'cutivestepsto convert a bridged ln...,: 'nrs servesto illustrate the power of
-t r I
rAhmed, M., Banett, A.G.M., Beall, J.C., Braddock,D.C., Flack, K., Gibson,VC., Procopiou,P.A., Salter,M.M. T 55,3219 (1999). rLa, D.S., Ford, J.G., Sattely,8.S., Bonitatebus,P.J.,Schrock,R.S., Hoveyda,A.H. "/ACSl2l, 11603 (1999). rWeatherhead, G.S., Ford, J.G., Alexanian, E.J., Schrock, R.S., Hoveyda, A.H. "/ACS 122, 1828
,/--=
n'
(2000).
Y
lFurstner, A., Mathes, C., Lehmann, C.W. JACS 121,9453 (1999). 5Barluenga,J., Rodriguez,F., Fananas,F.J.,Rubio, E. ACIEE3E,3084 (1999).
j\)mplexes (3) are good catalYst
Molybdenumhexacarbonyl.13, 194-195; 15,225-226;18,243-244;19,221-222; 20,251-252 Metathesis. Diarylalkynesare preparedfrom l-arylpropyneson heating with at 140'.r Under the same conditions,bis[4-(prop-1Mo(CO)oand p-chlorophenol ynyl)phenylsiloxanes form cyclotrimersandcyclotetramers.2
,.xr flcSirnddiYnes.a
*
':-/ . .// ' '-a-
k I l :- s, r. . . ,.'7
I
o lt
+
a-o l l
,/--\ l
r)r l
\-"...-J o
-( !o'
Si'q
+ "tetramer"
91o/o
3 O
r ..::^cne Mo complexescontaining a cr( ( ) .. donateR to enones.The adducts
\i-"6n--p' "trimer"
l
.,-bi^
I a a
I
, a : tf -
c-Morpholinyltrifluoroethyl
trimethylsilyl ether
rPschirer, N.G.,Bunz,U .H.F.TL40,2481(1999). 2Pschirer, N.G.,Fu,W.,Adams,R.D.,Bunz,U.H.F.CC37 (2000).
a-Morpholinyltrifl uoroethyl trimethylsilyl ether. Trifluoromethylation. This reagent is prepared from N-formylmorpholine and trifluoromethane. It reacts with carbonyl compounds to deliver trifluoromethylcarbinyl silyl ethers.
Ph
)-o
Ph
.
Me35iO F N O \-J Fri
csF
{ -:1 t
,tf
rOSiMeo
;". # prlcr,
GL.*.,
75o/o
:xt r
Phr
Nafion-H.14,213;18,246:20,15-1-:5{ u-Hydroxy-B,y-unsaturated estcr unsaturated hvdroxvesters
rBillard, (2000). T.,Bruns,S.,Langlois, 8.R.OL2,2101 Hachoumy, M., Mathew,T., Tongco.F,C { I 999).
I If -Naphtho[ 1,8-d e]-1,2,3 -triazine 2-Amino alcohols.t The l-chltxt Barbier reaction with carbonyl comFrrr
hydrogenation. Those derived from r hvdrogenolyzedalso.
a-Amino acids.' Compound I r. n cstersof o-amino acids on treatment\alo
N ,,N--\ N COOEI
(1)
btr. f:.: .::rJ tiom N-formylmorpholine and F .. .:. to deliver trifluoromethylcarbinyl
.=
": r1
Ph
Nafion-H. 14,213; 18, 246;20, 253-254 a-Hydroxy-B,y-unsaturated esters.l Glycidic unsaturated hydroxyesters.
esters are isomerized to the
OSiMeq
\1 pnl\cF.
Ool"oo=,# O<.:"=,
75%
99%
rHachoumy, M., (1999).
Mathew, T., Tongco, E.C., Vankar, y.D., Prakash, G.K.S.,Olah, G.A. Sf 363
I II- Naphtho[ 1,8-del - 1,2,3-triazine. 2-Amino alcohols.t The 2-chloromethyl derivative of the triazine undergoes Barbier reaction with carbonyl compounds.The products release2-amino alcohols on hydrogenation. Those derived from activated aromatic ketones-aldehydes can be hydrogenolyzedalso.
N. *
(t1",
N.4g/RR,c=o,HrN-1
r,*;*
*;/-o
a-Amino acids,2 compound I is readily alkylated and its products are converted to estersof o-amino acidson treatmentwith aluminum amalgamin THF.
N. * .N--r tcooE, N' (1)
i-Pr2NLi /RX; ,R -...1-.-------* HzN{ 'cooet Al (Flg)
)- ar
!i
t I
Nickel, Raney
IChandrasekhar, S., Sridhar,M.TL 41,4685(2000). 2Anilkumar,R., Chandrasekhar, S.,Sridhar,M.TL 41,6665(2000).
2-Naphthylmethanol. Functional group protection, 2-Naphthylmethyl ethersr and esters2(formation by the DCC method) are more readily hydrogenolyzedthan benzyl analogues,thus permitting their differentiation. 2-Naphthylmethyl carbamatesundergo selectivehydrogenolysisin the presenceof the 4-trifluoromethylbenzyl carbamategroup.s
I
rGaunt,M.J.,Yu,J.,Spencer, J.B.JOC 63,4172(lgg8). 2Gaunt, M.J.,Boschetti, C.E.,Yu, J.,Spencer, I.B.TL40,1g03(1999). rPapageorgiou, E.A.,Gaunt,M.J.,Yu,J.,Spencer, J.B.OLZ,l049 (2000).
Nascent Raney nickel fro diamineto the 5,6,7,8,5'.6'. afford products with 97.5-99{
{1 . -l[
:.-fl
F*
Nickel. 12, 355: 13, 197; 14,213; 18, 246; 19,224; 20, 253-254 Reduction of nitrogen compounds. Arylamines are produced by electrogenerated nickel (suspensionfrom a nickel anode)to reducenitroarenes.r Deallylatian.2
using
Allyl aryl ethers are converted to phenols using electrogenerated
nickel. rYasuhara, A., Kasano, A., Sakamoro, T. JOC 64,2301(1999). 2Yasuhara, A., Kasano, A., Sakamoto, T. JOC 64,4211(lggg).
Nickel, Raney. 13, 265-266; 14, 270 ; 15, 218; 17, 296; 18, 246; 20, 254 Reductions. chemoselective reduction of aldehydes in the presenceof ketones is quite general,exceptfor very highly hinderedaldehydes.l
c>" _\-"*o
IBarrero,A.F.,Alvarez-Manza.n I Barrero,A.F.,Alvarez-Manzan 'Wang, X., Xu, M., Lian,H.. Pao 'Wang,X., Xu, M., Lian,H.. hn 'Gowda, D.C.,Gowda,A.S.P.Bd 'Tsukinoki, T., Kanda,T., Liu. G -Guo, H., Ding,K. ZL 41, 10o6lr
\lickekarbon.
Cross-coupling. Ni{ u metallicreagents(e.g.,RZnl r
Lrpshutz, B.H.,Blomgren. PA. .C :Lipshutz,B.H.,Ueda,H. ACIEE RaneyNi
\ F O
THF 25"
OH 98%
Nickel acetatr2,2'-bipyridit Biaryls.' The bipyridir aryl halides with LiH-r-BuOl-r
Massicot, F.,Schneider, R..FGL' Selectivehydrogenationof enones,rparticularlyassistedby ultrasonicirradiation,ris a syntheticallyvaluableprocess.Ultrasonicallyactivatednickel reducesnitroarenesto the azoxyarenestage.aon the other hand, with formic acid or ammonium formate as the hydrogen source,the reduction results in arylamines.5 The aromatic ring of a phenol is saturatedunder alkaline conditions (lzo KoH. no organic solvent).6Interestingly, 4-methoxybiphenyl is reduced to phenylcyclohexane (69% yield).
Nickel(ID acetylacetonate. l7 Cross-couplings. The N
lodonium reagents is also extr coupling between functional performed in the presenceof B
Nickel(Il)
RaneYN-Ar 1-\-a\ KoH-H2o
l-\-{:)-o"" \:,/
\:,/
\___/
acetylacetonate
\_J
69To lr:r- . .I cthersrand esters2(formation by ': rc.: .1nbcnzyl analogues,thus permitting . .:crgoselectivehydrogenolysisin the e. k
I ti ,
:: a
(
,/r----\
\-oH
\:,/
Ranev Ni-Al KoH-H2o
: 1999). ; lrr_{r)12000).
I0. t5-t-254 .1:nlnes are produced by using .ic r to reducenitroarenes.l I l() phenols using electrogenerated
.
FoH
\--J
93%
.lF.'
-:
(
.
l - . - , , . .1 8 , 2 4 6 ; 2 0 , 2 5 4 of ketones is :.:rrdcsin thepresence i k"'t''
alloy reduces BINOL and the analogous diamine to the 5,6,7,8,5',6',7',8'-octahydroderivativesin good yields.TChiral substrates afford products with97.5-99Vo ee. Nascent Raney nickel from the Ni-Al
rBanero,A.F.,Alvarez-Manzaneda, R. SZ 197(2000). R., Meneses, 8.J.,Chahboun, :Barrero, R. SI, 1663(1999). R.,Meneses, A.F.,Alvarez-Manzaneda, E.J.,Chahboun, rWang,X., Xu, M., Lian,H., Pan,Y., Shi,Y. SC29, 129(1999). lWang,X., Xu, M., Lian,H., Pan,Y.,Shi,Y. SC29,303I ( 1999). 5Gowda, D.C.,Gowda,A.S.P,Baba,A.R.,Gowda,S.SC30,2889(2000). 6Tsukinoki,T., Kanda,T., Liu, G.-B.,Tsuzuki,H., Tashiro,M. fZ 41, 5865(2000). rGuo,H., Ding,K. IZ 41, 10061(2000).
Nickel-carbon. Cross-coupling. Ni-C is an inexpensive reagent for coupling ofArCl with organometallic reagents(e.g..RZnl)r and arylation of secondaryamines.2 rLipshutz, P.A../ACS 121,5819(1999). B.H.,Blomgren, rlipshutz, B.H.,Ueda,H. ACIEE39,4492(2ON).
98%
Nickel acetate2,2'-bipyridine. 20, 255 Biaryls.t The bipyridine complex of Ni(OAc)2 has catalytic activity in coupling of aryl halides with LiH-l-BuOLi. IMassicot,F.,Schneider, R., Fort,Y. "/CR(S) 664(1999).
li: N t:
.:..rstedby ultrasonicirradiation,ris a ,:lJ nickel reducesnitroarenesto the :-rJ or ammonium formate as the hy-
E .
n.:-: .,lLalineconditions(l7o KOH, no orn: . :r.tluccdto phenylcyclohexane(69%
Nicket(Il) acetylacetonate. 17, 201; 18, 247-248; 19, 225-226; 20, 255-256 Cross-couplings. The Ni-catalyzed coupling of organostannaneswith hypervalent iodonium reagents is also extendable to a carbonylative process, yielding ketones.rThe coupling between functionalized benzylzinc reagents and primary haloalkanes2 is performed in the presenceof BuaNI in addition to Ni(acac)2.
lr l ,
ii
l 1
r- {7
r1
.1 :! :l
:t =- 1t
Nickel(Il)
acetylacetonate
,-l (rxrnrr.
+ PhztBF+
Ni(acac)2
C1
(\,^
"nA*' 79Yo
The coupling between two tetrahedral carbon centers from functionalized diorganozinc reagentsand alkyl iodides is efficiently catalyzedby Ni(acac)2 while adding p-trifluoromethylstyreneas promoter.l N-arylation,a Secondary amines undergo arylation with ArCl in the presence of NaH, bipyridine, and Ni(acac)2. Homoallylation, Carbonyl compounds afford 4-alkenols from a Ni-catalyzed con-
"l*
or\
II
\4
O.
-l
I + Ni(acac)2
flf
l^n
r|e:^' r
densation with 1,3-dienesthat is promoted by dialkylzinc (as alternative to the previously reported triethylborane). With diethylzinc there is an overall reductive alkylation but dimethylzinc also donatesa methyl group to the product.s,6
{ OH
Pentasubstitutedbenzenederivatives arc c tivity indicates the possible developmenrof I ' process.'
+ phcHolf:% A.pn Me2Zn I THF
\..\
99o/o
I
\.\
to-'l
Ni(acac)2
+ PhcHo
'l'. ,l'
*;;;
Cyclization of aldehydesbearing a distant diene unitT is synthetically valuable. HOt'
osiEt3 Ni(cod)2 - Ph3P
OMe
Et3siH / Pht\.4e
OBn
[2 + 2 + 2]Cyclnaddition. Enones and alkynes combine to furnish indanones.The catalytic system consists of Ni(acac)r-PPhr, MerAl, and phenol.8 There is a change in regioselectivity when the reaction is promoted by Ni(acac)2and an oxazole ligand.e (Note a different reaction pathway that proceeds by carbozincation of alkynes and conjugate addition.ro)
=-=-rz-9 N{4.; r€uzAl-
.I i
Ac.€ -t
Nickel(Il)
acetlacetonate
,[l
\.Atn ,n-(t"\rn Tgok
r. rl .
rr. irom functionalizeddiorgano^r \iracac). while addingp{riflu,n *ith ArCl in the presenceof
I
or\
\4
O.
II
+ Ni(acac)2 -[=-
flf
b: : : .'tkcnolsfrom a Ni-catalyzedconr-i. , .,.re ras alternativeto the previously ! . ::t ,r\etall reductive alkylation but
67o/o
Me3Al - PhOH
Fr,.:...:
o.rY
bo-T
o \L
(11 : 89) 4504
OH
99%
I
)
a a
, oI I
Pentasubstituted benzene derivatives are expediently formed. The observed regioserec_ tivity indicates the possible development of a synthetic route for taiwanin C based on this D r o c e s s . Il
/
I a
l 9 '
to)
#pr'
':
ill
63%
,1,.
rr syntheticallyvaluable
,o) lS !t,
,
I
/\.t\-oMe .OBn 67o/o
rr.r. .{)rnbineto furnish indanones.The ,--\. .tnd phenol.sThere is a changein \: .r.rc). and an oxazoleligand.e(Note r}' zrncationof alkynes and conjugate
Ni(acac)z-Ph:P;
RO ..................""....._ i-Bu2AlH/ THF ; ActO - py
t
Nickel bromide-amine complexes
1,4-Silaboration.t2 B-silylpinacolatoboranes are split and add to 1,3-dienesby the Ni(acac)2-r-BurAlH combination. The major products possessa (Q-configuration, and cyclic dienesfurnish adductswith cis-B,Si substituents.
',\ l
I Kang,S.-K.,Ryu,H.-C.,Lee,S.-W.JCS(PI 2661(1999) ) 2Piber,M., Jensen, A.8., Rottlander, M., Knochel,P.OL l, 1323(lggg). rGiovannini,R., Stqdemann, T., Devasagayaraj, A., Dussin,G., Knochel,P.JOC 64,3544(l9gg). tBrenner,8., Schneider, R., Fort,Y. T 55,12829(1999). 5Kimura,M., Fujimatsu, H., Ezoe,A., Shibata, K., Shimizu,M., Matsumoto, S.,Tamaru, YACIEE 38,397(1999). oKimura,M., Matsuo,S.,Shibata, K., Tamaru, Y ACIEE38,3386(1999). 7Sato,Y., Takimoto,M., Mori, N. ./ACSI22, 1624(2000). nMori,N., Ikeda,S.,Sato,Y "/ACS121,2722(1999). 'Ikeda,S.,Kondo,H., Mori,N. CC 8l 5 (2000). rOlkeda, s., cui, D.-M.,Saro,y. "/ACSl2l,4l12 (1999\. ''Sato,Y, Ohashi,K., Mori,M. TL 40,5231(1999). l2Suginome, M., Matsuda, T.,Yoshimoto, T., Ito,Y. OL l, 1561(lggg).
3Budnikova, Y., Kargin,Y., Nedelec.J.-\'..Fa aOlivero, S.,Dunach,E. EJOC1885( 1999' 5Kuroboshi. M.. Goto.K.. Mochizuki.\t 51 Nickel bromidedppe. Diarylmethanols.l
Zinc in combrr reaction between aryl bromides and artr groups such as ketone, ester,arnide. and
rMajumdar, K.K.,Cheng,C.-H.OL 2.:leJ , Nickel chloride. Claisen rearrangemenf. Alll I ev with LDA and NiCl". Such chelatesund
{
;-11 a
o \z\
Nickel boride.
i
Reductive amination,t Secondarybenzylamines are rapidly formed when aromatic aldehydesand ketones are treated with RNH2 and nickel boride.
l
nA1rt^'rrto
H
--
3
rSaxena, f ., Borah,R., Sarma, J.C.JCS(PI ) 503(2000). 3-Hexenedinic esters. 3-Halofrn? Nickel bromide-amine complexes. Coupling reactions. Electrochemical coupling reactions with (bpy)NiBr2 catalysis include those betweenalkenyl bromidesand cr-haloesters,raryl and pyridyt halides,2as well as aryl and chlorophosphines.l Cyclization-carboxylation.a Cyclization of o-haloarylalkenes is induced by (cyclam)NiBrr. Under a carbon dioxide atmosphere,carboxylation occurs. However. yieldsin mostcasesare nol impressive.
Z"t'cl
(A"^_6
e
NiCl2 as catalyst.2
I
ETOOC \w
Cl ./
Nicl2.6H2oI O | ETOOC' zntH2o pyridine
| L
Cross-coupling. Suzuki couphne r free complex (Et.rN)2NiCl2rA soluhle o NiCl2 with BuLi effects the coupling of R
CO2
Ni(cyclam)B12
Bu4NBF4 / DN.4F
70%
Allylation.5 Formation of homoallylic alcohols by reaction of aldehydes with allyl bromide under the influence of NiBrr-CrClj also requires an electron source. Tetrakis(dimethylamino)ethylene is a suitable candidate. lCannes, C.,Condon,S.,Durandetti, M., Perichon, J.,Nedelec, J.-Y.JOC 65,4575(2000) 2Gosmini, C.,Nedelec, J.-Y.,Perichon, I. TL 41,5039(2000).
1Kazmaier, U., Maier,S.JOCU,.157Jr 199 2Kotora,M., Matsumura,H., Takaha-shr. T (l rLeadbeater, N.E.,Resouly, S.M.f 55. llLi! alipshutz,B.H.,Blomgren, P.A.,Kim. S K I
Nickel chloridephosphine complercrr 22'7-228;20,258-259 Couplings. A nickel catalyst grepr been employed to synthesizearylalkerrs t
Nickel chloride_phosphine complexes > : :
[._,
.:lrr and add to l.3-dienesby the 11)\\!:\\ a (Z)-configuration,and
Ui:
281
rBudnikova, Y., Kargin, y., Nedelec, J._y., perichon, J. JOMC 57S, 63 (l9gg). aOlivero, S., Dunach,E. EJOC 1gg5 (1999). sKuroboshi, M., Goto, K., Mochizuki, M. Sl, 1930 (1999).
ar.
.1.
-:
le99)
\n(\hel. P.JOC9,3544 (1999). tr
'.: \lf,r\umoto. S..Tamaru, YACIEE
t.\
'.^ 19991
I
Nickel bromide-dppe. Diarylmethanors.t Zinc in combination with the (dppe)NiBr2 complex mediatesthe reaction between aryl bromides and aromatic aldehydes.This processtolerates l'unctional groups such as ketone, ester,amide, and nitrile. rMajumdar, K.K.,Cheng,C.-H.OL2,Z2g5(2000\. Nickel chloride. claisen reaftangemenL Allyl esters of N-acylglycine form chelates on treatment with LDA and NiCl2. Such chelatesundergo stereoselectrverearrangement.r
o \Z\
ir.-. ::. rapidly formed when aromatrc r. . . -,,rrde.
l
l
l
nArrr---'-o H I I o
i
l
t
l
R-\N"'VoH H r l o
/
T a
.:r()nswith (bpy)NiBr2catalysis :.. aryl and pyridyl halides,2as
c:
l,,arylalkenes is induced b1 .trhoxylation occurs. However.
_\-^cooH -o ) 70%
rcactionof aldehydeswith allyl .'' an electron source.Tetrakis-
k
\ JOC 65,4s75(2000).
,-Hexenedioic esters. 3-Halopropenoic estersare reductively dimerized by zn with NiCl2 as catalyst.2
N i c r 2 6 H 2 |o I ", Etooc Ervvv\-/w' c r -;;; etoocr"''rui-", 'cooetf * f p
y
'
d
i
n
e
L
:
j
-^--
=too"\__/-\_-
I a a
F a I a
o\,\.
i-Pr2NLi- NiCt2
)
c
o o E t 66%(E:23:1\
cross-coupling. suzuki coupling tolerable to water is achievedusing the phosphinefree comprex (EtrN)2Nicl2 3 A soluble nickel speciesprepared from treatment of phjp and NiCl, with BuLi effectsthe coupling of RZnI with ArCl.a rKazmaier, U., Maier,S.JOC 64,45:14 (lggg). 2Kotora,M., Matsumura, H., Takahashi, T. CL236(2000). sleadbeater, N.E.,Resouly, S.M.255, I1889(1999). tlipshutz,B.H., p.A.,Kim, S.K.2140, Blomgren, tSl (tS9r)1. Nickel chloride-phosphine complexes. 14, 125; lS, 122; 16, 124; 1g,250; 19, 227-228; 20, 258-259 couplings. A nickel caralyst prepared from reduction of (dppf)Nicl, with BuLi has beenemployedto synthesizearylalkenes by coupling aryrboronicacidswith enolphosphates.l
-
Nickel perchloratc
A water-soluble Ni catalyst is obtained2 when (dppe)NiCl2 is treated with Zn and sodium triphenylphosphinotrimetasulfonate. AlkyldesuWrization.3 Thioglycolic is the leaving group in the Ni-catalyzed reaction with organozinc reagents.
\\
(MePh2P)?NiCl2
\-669H
\-J
80%
Nickel iodide. [2 + 2 + 2]cycloaddition.
conjugated carbonyl compounds are benzannulated with alkynes.r Different reaction patterns may emergeon varying the substrates.
.: l
I \_/
-
\
ll * :_r/
AC
o
(ph3p)2Nitz
l + /zn'znt2 ,^v,\,.^\ rHF ^
|
from allyl carbamatesby rhrs pn When the propargyl ether mor group transfer occurs to a large r
2'\,. cHo R-j- ll
ll
| ll \-r\2\,
Reduction,2 For transfcr which the cation is complexed rr
Nickel tetrafl uoroboratebipy Deallylation and deprop propargyl aroates are cleaved cl
.-il
i
*
rSaito,T., Takekawa, K., Takaha*u 2Phukan, P.,Sudalai,A. SC30. :Jr't
lNan,Y, Yang,Z. TL 40,3321(1999). 2Galf and,J.-C.,Savignac, M., Genet,I.-p.TL 40,2323(lggg). rSrogl,J.,Liu, W.,Marshall, D., Liebeskind, L.S../ACS121,9449(lgg9.).
il
l
prrAs
O
//
THF A
.I
v
O
MezZn
n r.
//-
Ph
\.,,\
)
o"\
80%
r | |:/ . cooEr
Carboxylation The eletrr when the molecule is appendedr
(Ph3P)2NiCt2 Zn I CH2CI2
R
R
R R = Pr R = Bu
62Yo 71o/o
rSambaiah, T., Li, L.-P, Huang,D.-J.,Lin, C.-H.,Rayabarapu, D.K., Cheng,C.-H.JOC 64,3663 ( I 999).
\
Cfl".,
VBr Nickel perchlorate. Hetero-Diels-Alder reaction. when catalyzed by nickel perchlorate the condensation of N-acrylyloxazolidinone with thiabutadienesgives dihydrothiapyrans.r
^
Nickeltetrafluoroborate-bipyridinecomplex
lS i:()up in the Ni-catalyzed
v l
prrAs
80Yo
o
Ph
r \:(-l- is treated with Zn and
9
P
AS"r y ' " f i Ni(cto4)2
*
h
o
o
,#rAo\J
",,roi(.-l-V
,nAr)
AH
H}r'\
\_/
\_/
90%
Reduction,z For transfer hydrogenation of aryl ketones, nickel perchlorate, in which the cation is complexed to a macrocyclic ligand, may serve as catalyst. rSaito,T.,Takekawa, K., Takahashi, T. CC 1001(1999). 2Phukan. P..Sudalai.A. SC30. 2401Q00U.
)t Nickel tetrafl uoroborate-bipyridine
complex.
'l
Deallylation and depropargylation. Allyl and proparyl ethers of phenols and propargyl aroates are cleaved electrolytically with the Ni-catalyst.r Amines are released c, ::n()unds are benzannulated \:i, 10! the substrates.
-Y) -4"\..'
from allyl carbamatesby this procedure.2 When the propargyl ether moiety is ortho to an aldehyde, an intramolecular propargyl group transferoccursto a largeextent.r
Z"{
R, tl \.,,\
e
CHO
R DMF
o\
-1
rt l7 :E
./
(bipy)3Ni(BFaD
ua )) /,
;r
:e :t
\
- 1
cooEr -
The electrochemical carboxylation is followed by lactonization Carboxylation when the moleculeis appendedwith a neighboringepoxide.a
R F. B-
(bipy)3Ni(BFa)2
I
. . \
\roH
62% 71%
Cheng,C.-H.JOC 64,3663
a)-\" ve.
+ co2-lI I r"v"r",itNie,, _
n:.r.:l perchloratethe condensad::. Jrothiapyrans.r
o 73To
2-Nitrobenzenesulfonamide 'Olivero, S., Rolland, J.-P., Dunach, E., Labbe, E. OM 19,2798 (2000); Olivero, S., Dunach, E. 38.6193 (1997\. 2Franco,D., Dunach, E. TL 41,7333 QO}OD. 3Franco,D., Dunach,E. TL 40,2951 (l9gg). aTascedda, P.,Dunach,E.5L245 (2000):
Nitric oxide. 19, 229; 20, 259-260 Alkyl nitrites.r Alcohols react with No in organic solvent (air is present) ro grve RONO directly. oxidation.2 under the influence of N-hydroxyphthalimide, No is used as an oxidizing agent for benzyl ethers (ro aldehydes).
oYo +
l-;t-*'*
hY" v rFukuyama, T.,Cheung, M., Kan,T. St lV
2-Nitrobenzenesulfonyl chloride. Sulfunamides.r The reagenr s polyamine.
r'fl -:txl[
o--zNro
:. -' :.ri
f,,^
d-Y\
I
l l
,/-\
\-/ O - l
z\-:/'cHo l l
\..'--J
Vcno
+
a>A
l l l \-,)-Z
,o o
12o/o
lFavre-Reguillon, A., Segat-Diour_r'. F. \t sL 868(2000).
Nitrogen dioxide. 15,219: 18, 2-s1-'r Decarbamoylation.t Prima4 an ment with NO2.
rCollet,H., Boiteau,L., Taillades. J..Coma
Nitrolic acids. Nitrile oxides.r Nitrolic acids u DMSO containing HOAc and Na-\O. nitrile oxides.
I
Y)r\'^o-< \.,,\Z 85%
HO-.*.-O NN-(1-Adamantyl) amides.z Adamantyl radical is formed by hydrogen absrraction. In situ interception with a nitrile results in the generationof the amide. 'Grossi,L., Strazzari, S.IOC g,8076 (1999). 2Eikawa, M., Sakaguchi, S.,Ishii,Y. JOC9,4676 (lggg).
2-Nitrobenzenesulfonamide. Primary amines.t After N-alkoxycarbonylation (Boc, cbz, etc.) of the sulfonamide, alkylation at the nitrogen atom and treatment with a thiolate anion complete the preparationof a protectedprimary amine.
HO' INo'
ll------*
Rt"
R"
rMatt,C.,Gissot,A., Wagner, A., Mios\or
4-Nitrophenyl formate. N-Formylationr Protectionoi a amines are selectively formylated.
'Orelli,L.R.,Garcia,M.B.,Niemevz. F. Fe
4-Nitrophenyl formate
: :- .. 1000)l Olivero, S., Dunach, E. Zl
oYof
oYot'
\
\
o-r^-N.^
,.t;:-*t
- 5 O'l
7Y*o, \r'
o1-o\f R.sNa +"-il-*\
K
cF3cooH --.--..-.---.----RNHz
i\t'lo' i l l
v
Er:.:. .()lvent (air is present)to give rFukuyama, T.,Cheung, M., Kan,T. Sa 1301(1999). o\.:-rlhalimide, NO is used as an 2-Nitrobenzenesulfonyl chloride. Sulfonamides.r The reagent sulfonylates the primary amino group(s) of a polyamine.
o v .' e._'
--ru * l - -lu
Z-'r_-\ l l \.,2-J
o
120/o
rFavre-Reguillon, A., Segat-Dioury, F.,Nait-Bouda, L., Cosma,C., Siaugue, J.-M.,Foos,J.,Guy,A. sz 868(2000).
Nitrogen dioxide. 15, 219; 18, 252-253 Decarbamoylation.t Primary amines are recovered from monoalkylureas on treatment with NO2. lCollet,H., Boiteau,L., Taillades,J.,Comrneyras, A . TL 40,3355(1999).
I a a
I
F o I a
, {
'a
7 t
ra
-
c f
r /
?
;21''a'cuo
\-,V
Nitrolic acids. Nitrile oxi.des,r Nitrolic acids are prepared from nitroalkanes or alkyl bromides in DMSO containing HOAc and NaNO2. They decomposeunder neutral conditions to afford nitrile oxides.
no-;-o ll
| :. :,'nned by hydrogen abstraction lt: :: ,'l the amide.
R)
to-,| rNozr
+
2'a'
ll
R
N.,
THF A
N-O
n{2-n'
rMatt,C.,Gissot,A., Wagner, A., Mioskowski, C. TL 41,1191(2000).
n li t. Cbz, etc.) of the sulfonamide, rr::. .1 thiolate anion complete the
4-Nitrophenyl formate. N-FormylationI Protection of amino group takes place by transacylation. Primary amines are selectively formylated. rOrelli,L.R.,Garcia,M.B.,Niemevz, F.,Perillo,l.A. SC29, 1819(1999).
9 , -
Nitrosonium tetrafluoroborat€
4-Nitrophenyl trifl ate. Transtriflationr The title compound transfer its Tfgroup to various alcohols under mild conditions (K2COq-DMfl room temperature). rNeuville,L., Bigot,A., Dau,M.E.T.H.,Zh'.t,J.JOC 64,7638(tggg).
Nitrosonium tetrafl uorobor ate.| 4, 2 | 5 ; 19, 230; 20, 262 Oxidation of dienes.t The conjugated diene unit at the terminus of certain carboxylic acids is subject to oxidation via the tricarbonyliron complexes. Activation by ligand exchange from a carbonyl to a nitrosyl group precipitates an electrophilic attack and subsequenttransformations.
Organoaluminumreagents. Allyl alcohols. Stereoselec enablescreationof quaternan'cartw Sp2'displacement with cuprares.
Y
* -ArA
r--+c{o
-tr1"o" ( )
-l\-1-"oo,.
NOBFa; Et3N
\
HON
........................* MeCN
I, I, I - Trifluoro-3-alkyn-2-ok. trifluoroethyltosylatewith lithium d theprecursors of theseuniquealcoh
n =1 , 2
'Yeh, M.-C.P.,Chuang,L.-W., Hsieh,Y.-S.,Tsai,
M.-S. CC 805 (1999). a,\
CFe +
\
,nolor.
'Spino,C.,Beaulieu, C. ACIEE39. tgt{r ' 2Matsutani, H., Kusumoto, T..Hivama.T
Organocopper reagents. 13, :07-:0 2O1-218; 18, 25'l-262: 19, 232-: -15
Silylcuprations. Alkynes and I further applications.Thus, a synrherr
tfdf- *Yo
"r
rr
I: rroup to variousalcoholsunder
,ri)g ).
:0.:b:
?:.- ..nlt at the terminus of certain f,i.-- 1\liron complexes.Activation by o:: :-r.'cipitatesan electrophilic attack
Organoaluminum reagents. Atlyl alcohots. Stereoselectiveaddition of alkenylaluminums to chiral aldehydes enablescreation of quaternarycarbon centersat the allylic position after esterification and with cuprates.r Sx2' displacement
I,l 'l - a
76To
s a 1,1,1-Trifluoro-3-alkyn-2-ols. Substitution of optically active 1-benzyloxy-2,2,2trifluoroethyl tosylate with lithium alkynylaluminates is an excellent method for accessto of theseuniquealcohols.2 the precursors
2z
il
tQt
- a
ft'
*
9r,
t'\
Bno^ors
-R
Et3Ar i Et2o BnO\.
-R 77To
I Spino, C., Beaulieu,C. ACIEE 39, 1930 (2000). 2Matsutani, H., Kusumoto, T., Hiyama, T. CL 529 (1999).
Organocopperreagents.13,207-209; 14,218-219;15,221-221; 16,232-238;17, 207-218; 18,257-262; 19' 232-235; 20,264-267 Silylcuprations. Alkynes and allenesare readily convertedto usefulreagentsfor is readilyachived.' Thus,a synthesisof B-silyl alaninederivatives furtherapplications.
*Yo tfdt'-
"r
(Me3Si)2Cu(CN)Li2 IHF -78'
*Yo tfoft'""'
"r
79Yo
:::7 :t
'"" - 1
Organocopperreagents
To direct a ring formation2 following the silylcupration is also synthetically sisnificant.
vl" /\:
t ^
-1^tc'l
-N-
oAo
_*
o4o
(PhMe2Si)2Cu(CN)Li2 THF -78. - 25"
Addition of organocuprat€Sro rT Dimethyl sulfide stabilizes the cupca reaction medium.s
SiMe2Ph 6SVo
A route to 3-silylmethyl-1,4-alkadienesrinvolves silylcupration of allenesand trapping of the ensuing organocopperspecieswith allyl phosphate. The 3-silyl-propen-2-ylcopper reagentderived from allene is used to react with enones and the products can be cyclized to give 3-methylenecyclopentanols.a
The conjugate addition-trapping p nates.Under CO carbonylationoccun formed.e
R2Cu(CN)L|2 * A i
'nvtl( o
* nnu"rsi -(
-40'
n
tn)t'-Ja
BF3/ THF
PhMezSi...,,\
o'O -(
O
89%
Many methods have been derelq cloalkanones.A clever designincorpo treatment with organocopperreagenLl
Stannylcuprationis analogousto silylcupration.Such a reaction on 1,4-diyn-3-olsis regioselectiveand stereoselective.5
OH (Bu3Sn)2Cu(CN)Lrz
*-r,,o ;: SiMe3
Lijx
\_/
-\
-[ Bu3Sn- \
-----
r
a
\r,""" 83To
Conjugate additions. Methoxyallylcopper reagentsare formed from the allyl ethers via lithiation (with s-Buli) and they give monoenol ethers of 1,6-dicarbonyl compounds on conjugate addition to enones. N-(/-Butoxycarbonyl)dimethylamine is lithiated at one of the N-methyl groups. A route to B-alkylidenepyrrolidinones is developed on further conversion to the cuprate reagentsand subsequentaddition to 2,3-alkadienoic esters.6
Sy2' displacements. 1-Bromo-1 to give l-alkynes. The chirality of rhc entrant group.' I (Note the Zn-based cr4
\^,'\^ I
J |
\-"\-,'\ZU
Br
U
I ^t/
+ l/b
Organocopper reagents
ilr., -:nration is also synthetically
-N-
oAo
(
-tt^1cr1 ----*
c
oAo
-i-F +
-cooet
oAo =(
,roo"/
82o/o
r
-\
) Addition of organocuprates to cross-conjugated enynones leads to the dienones.T Dimethyl sulfide stabilizes the cuprate adduct intermediates when it is employed as a reaction medium.s The conjugate addition-trapping protocol has been applied to preparation of phosphonates. Under CO carbonylation occurs prior to the addition and 1-ketophosphonatesare
LSiMezPh 65%
sr.r.. uprationof allenesand trapping
t
formed.e
rc'..:.lc'neis usedto reactwith enones r. ,.,,pcntanols.a
:,
o
R2cu(cN)Li2 . ^il::, o
tn)''Y errMersi...-\
7h
J
-
*UX-o#, o
Many methods have been developed for the synthesis of chiral 3-substituted cycloalkanones.A clever design incorporatesa neomenthol moiety at the ct-position prior to treatment with organocopperreagents.r0
I
r\
's---*#d
tl
t-
R
-siMe3
.- ,nA 83%
Sp2' displacements. 1-Bromo-1,2-alkadienes undergo transpositional substitution to give l-alkynes. The chirality of the allene moiety determines the configuration of the entrantgroup.rr(Note the Zn-basedcupratereagentscan be usedr2)'
. .ire formed from the allYl ethers comPounds I : ' i : :r' of 1,6-dicarbonYl E_
| .: ,nc of the N-methYl grouPs.A or :.;nher conversionto the cuprate c.: J:.
E f
P
t J
R2Cu(CN)Li2
OH
r -
b
.t reactionon 1,4-diYn-3-olsis
I
t
t a 7
a
80%
89%
)
a a
Ll: i
95%
Organolithim reagents
Olefination.t3 Under the influence of BFr.OEt , acetalsare convertedto 2-substituted 1-alkeneson reactionwith MerSiCH2Cu(PBuj).LiI. Furans and pyrroles.ta Of 2-alkynyl-1.3-dithiolanes, the consecutive reactions with cuprate reagentsand aldehydesor aldimines lead to the five-memberedheterocycles.
Bu2cuLi/ THF P h C H O ;C F 3 C O O H
.J // \
Ph
Ph--\O/^Ph 60Yo
<--;'; .L.,, -T ::il '- .t
:"; . l
,'.
rReginato,G., Mordini,A., Valacchi,M., Grandini,E. JOC 64,9211(1999). 2Fleming, I., deMarigorta, M.E.JCS(PI)S89(1999). 3liepins,V.,Karlstrom, A.S.E.,Backvall,I.E. OL2,123'1(2000). aBarbero, A., Garcia,C., Pulido,F.L TL 40,6649(1999). sBetzer.J.-F.,Pancrazi. A. S 629 0999\. 6Dieter, R.K.,Lu,K. TL 40,4011(1999). 7lee, P.H.,Park,J.,Lee,K., Kim, H.-C. TL 40,'1109(1999). 8KingsburyC.L., Sharp.K.S.,Smith,R.A.J.f 55, 14693(1999). el-i,N.-S.,yu, S.,Kabalka, c.w. oM lg,181l (1999). roFunk,R.L.,Yang,G. TL 40, 10739(1999). I rBernard,N., Chemla,F.,Normant,J.F.TL 40, 1649(1999). r2Caporusso, A.M., Filippi, S.,Barontini,F.,Salvadori,P.TL 41, 1227(2000). r3Suzuki, T., Oriyama,T. Sl, 859 (2000). ral-ee, C.-F.,Yang,L.-M.,Hwu,T.-Y, Feng,A.-S.,Tseng,J.-C.,Luh,T.-Y.JACS122,4992(2ffi0).
Ketones, including chiral o-an organolithium reaction with morph Addition reactions. A routc with quinones derivatives.r
Pr
(t-Bu)2Si
B€'r FO
b1 ,\-r,* HY
o"
TIPSO
Addition of RLi ro cinname containing a chirality center al rhc therefore optically active a-amrrrc : of the doublebond).4
( Ph'V2\tN.O^s
:
The adducts derived from a brc ring expansion on reduction u.itl Lr
Organogallium neagents, Conjugate additions. Both triallylgallium' suitable addendsfor electron-deficient alkenes.
and lithium tetraorganogallates2are
rAraki,S.,Horie,T., Kato,M., Hirashita,T.,Yamamura, H., Kawai,M. TL 40,233I (1999r. 2Han,Y.,Huang,Y.-2.,Fang,L., Tao,W.T.SC 29,867(1999).
'n
Ph,,. NC\ l
N-wrO + RLi F u
\-, Organolithium reagents. 20, 268-269 Ketones. At low temperatures,3,4-dihydropyranonesreact with RLi. The adducts can be properly manipulated to afford the 1,5-diketones.r
Li
oMe
o\-o>a-
U
THF, _75'; N,le3SiCl ;
H:o.
Sulfines provide dithioaceral nx tion can avoid attack on the carbonv
Organolithiumreagents
-- i,(t.11: are convertedto 2-substituted it:. ..,nc.. the consecutivereactions a.: : rlhcfive-memberedheterocycles'
,.
-/
Ketones, including chiral a-amino ketone derivatives,2are also produced from the organolithium reaction with morpholine amides. Addition reactions. A route to C-arylglycosides involves reaction of lithioglycals with quinones derivatives.3
Ph
I \ =-'-\or^ph
/lll (1999).
Bno-r4;'"v:o
Pf
(tBu)2Si. Fo b{ ,}-ti
I o^Y
*
I.
(t-Bu)rSi
+
H TIPSO
(orn
tPSJ-
60%
f( ril
297
Addition of RLi to cinnamaldehyde oxime ethers gives allylic amines. Those containing a chirality center at the carbinyl site are subject to l,4-asymmetric induction, therefore optically active a-amino acid derivatives are readily synthesized(upon cleavage of the doublebond).4
I J I
7 F MeLi- BF3.OEt2
................................- H PhMe -78" tn=*.o^ph
: Ph,t/\t F r. {l .
NrO
ph
\
1 TA
:
a
I
9 f
9SYo
l.uh.T.-Y JACSl22,4992(2000).
The adducts derived from a bicyclic oxazolidine bearing an o-cyano group undergo ring expansion on reduction with LiAlHo.5 are lrthium tetraorganogallatesz
R
Ph,,.
oH
R H \ :,r rt. )1. TL 40,233I (1999) F-
c:. I
I
a a -
=
117(2000).
l : . , ,ncs react with RLi. The adducts
). a
NC\'N-wrO
I \-/
L,A'H..
+
+ RLi +
Fr-r
)-*t (
ph
)
;l-*.V \ H OH
Sulfines provide dithioacetal monoxides in the addition reaction.6A controlled reaction can avoid attack on the carbonyl group.
o
1?1 t
'Y \,
(
l
s )-.""
' ror R + 'V \,
(
i !r""
I l
H
r
oJ-\MeLi:
+ o
'
A/ \-J
(
l
9
t
-
Organolithium reagents
Butenolides and 7-isoindolinones. Reaction of enals containing an iron substitutent with RLi results in the formation of "y-substituted(with R) butenolides.TThus, the addition
f
g^lV.u"
also induces cyclocarbonylation.
a
Fe(CO)2CP
snBu3
Ph
l\4eLi / rHF
50To
CI; -:,
t:t-
St -
3-Substituted I -isoindolinones are synthesized from MN-dimethylaminophthalimide via reaction with organolithiums (or Grignard reagents), deoxygenation with Et.,SiHCF3COOH, and N-N bond cleavagewith Zn in HOAc.8
Zirconacycles - a zirconacyclesis achieve
:..'j
-11
/Y' I
\rv
N-NMeu +
ll
\\
o
o
.o
U RLi
dt I \r,^{
- cF3cooH Et3siH : a< ll .N-NMe2 +
Jt1
'OH
l
/-'-/
Cp2ZrCl2 b
N_H
zn-HoAc
^
BuLi
I
R
85-g2o/o
Eliminations, Thionocarbonatesderived from l,2-diols are transformed into iodo thiocarbonateswith RI, which decomposeinto alkeneson treatment with RLi.'The threestep processrepresentsa reductive deoxygenation. Alkynes are formed when trichloromethylcarbinyl tosylates react with MeLi. This reaction is suitable for the synthesisof ethynylcyclopropane.r0 Organoiodine compounds.tt Iodoarenes,iodoalkenes,and iodoalkynes are prepared from organolithiumsby reaction with 2,2,2-trrfluoroethyliodide. Homopropargylic ahohols. In the opening of hetero-substituted epoxides with alkynyllithiums, trimethylgallium shows good catalytic reactivity.I2 u-Amino acids.t3 Chiral amino acids (l-alanine, r--methionine, L-leucine, L-homocysteine) have been prepared via carboxylation of the proper N-(a-lithioalkyl)-4phenyloxazolidin-2-ones.The configuration of the chelated organolithium speciesis such that the side chain would not sterically interact with the phenyl group. Regardlessof the original configuration in the precursorial stannane,rapid equilibration to the more stable isomer after Sn-Li exchangeensuresthe generation of the predicted (desired) product in each instance.
I Harrowven,D.C.. Hannaa rsengupta,S., Mondal. S. rParker,K.A., Georges..{ 1 rMoody, C.J.,Gallagher. P 5 C u t r i ,S . , B o n i n , M.. \trcc r'Corbin,F., Alayrac. C.. \tr TMollerC , .,Mikulas. \t.. x 8Deniau,E., Enders.D. Il"Adiyaman, M . , J u n g .) ' - . 1 4019 (1999). " ' W a n g ,2 . , C a m p a g n a . S .l r 889 (2000). r r B l a c k m o r e1, . J . B , o a .A . \ rrOoi, T., Morikawa, J.. lchr lrJeanjean,F., Fournet.G.. L '"Vicart, N., Whitby. R,J. (-(
Organotellurium Organocopper
Feagc! reagt
reagents for conjugate ad
both alkyl and alkenr'l gnr
Organotellurium reagents
o : , ..'1. containing an iron substitutent Thus, the addition l : : l - i{ hutenolides.T
o ll
t
BULi
g^lVrr"
a
9----r-i
9----r-i
snBue 5
t
!^f -\
i
t ''^rr"
/
9^fY.r" '1 \
Ph
Ph
Ph
l
| "o,
I
f
cooH
I
l l t qA.r/r^o^r 50%
H'
I : : ::r .\'.N-dimethylaminoPhthalimide :1r.r. deoxygenationwith Et3SiH-
ti:
l()\
Birchred
sMe +
Ph
la ro Zirconacycles - carbocycles.ta Replacement of the zirconium atom by carbon in zirconacyclesis achievedby reaction with cr,a-dihaloalkyllithiums.
H
H
o : | . cF3cooH
N-H
Z. . HOAC
/cooH
H'ru/ZAsM"
/'--/ ^
cp2ztct2
-
BuLi
Rcx2Li --
^-{--\
G
|
\---.:-:/
:
H
.zrcp2
/-{--\
c..ry I
H
H rR
,)\
ZrCPz
i
/--l-r.2R + nt-!/" MeoH NaHCo3
H
R
t r:. ta:..
l-diols are transformed into iodo . ,ln rreatmentwith RLi.e The three-
I
r.: :l :'
. tosylatesreact with MeLi. This nrne.
d. ., r..rrr's.illd iodoalkynes are prepared
\\: : .. rrvjide. epoxides with : hr'tero-substituted u-.
h'l E . : l::i: X
:
Ll, :-.
. rcactivity.r2 i. r -methionine,Lleucine, L-homor the proper N-(ctJithioalkyl)-4-i.rtcd organolithiumspeciesis such :rL' phenyl group. Regardlessof the ':rJ equilibrationto the more stable l the predicted (desired) product in
I Harrowven,D.C., Hannam,J.C. ? 55, 9333 (1999). rSengupta,S., Mondal, S., Das, D. TL40,4107 (1999). iParker,K.A., Georges,A.T. OL2,497 (2OOO). aMoody,C.J.,Gallagher,PT., Lightfoot, A.P.,Slawin,A.M.Z. JOC U,4419 (1999)' 5 C u t r i ,S . , B o n i n ,M . , M i c o u i n ,L . , F r o e l i c h O , .-P TL4l,1179 (2000). , . , Q u i r i o n ,J . - C . ,H u s s o n H 6Corbin, F., Alayrac, C., Metzner, P. EJOC 2859 (1999). TMoller,C., Mikulas, M., Wierschem,F., Riick-Braun,K. SL 182 (2000). sDeniau, 8., Enders,D. TL 41, 234'7(2000). eAdiyaman,M., Jung,Y.-J., Kim, S., Saha,G., Powell, W.S., FitzGerald,G.A., Rokach, I. TL 40' 4 0 1 9d 9 9 9 ) . r()Wang,2., Campagna,S., Yang, K., Xu, G., Pierce,M.8., Fortunak,J.M., Confalone,P.N."/OC 65' l 889 (2000). I I Blackmore,LJ., Boa, A.N., Munay, 8.J., Dennis,M., Woodward,S. TL 40, 6671 (1999). |2Ooi,T., Morikawa, J., lchikawa, H., Maruoka, K. TL 40,588I (1999). lrJeanjean,F., Fournet, G., Le Bars, D., Gore, l. EJOC 1297 (2000). laVicart,N., Whitby, R.I. CC l24l (1999).
Organotelluriumreagents.19,237-239 Organocopperreagents.t Dialkenyltelluridesare readilytransformedinto copper reagentsfor conjugateaddition,on reactionwith CuCN-RLi. Whenthe telluridescontain into alkenylcuprates. bothalkyl andalkenylgroupstheyarealsotransformed
ti f a I t
'-7
t2 r - l -
tlrl
:cl
:rl
i.p,
iti
Organotin reagents
(Z)-Alkenyl
Enynes,'
butyl tellurides couple with l-alkynes at room temperature in
the presence of PdCl2-CuI. 'Araujo, M.A., Barrientos-Astigarraga, R.E., Ellensohn,R.M., Comasseto,I.Y.TL40,5115 (1999). 2Zeni, G., Comasseto,J.V. TL 40, 4619 (1999).
Organotin reagents. 19) 239-240 Preparation. Aryltributylstannanes are available from coupling of ArI with BujSnH using a catalyst system containing PdClr/(PMePh2)2and KOAc.r Reaction of potassium triphenylstannate (from PhlSnH and r-BuOK) with haloarenes (and halo-
c-ll
heteroarenes ) provides PhrSnAr.2 When alkenyl selenides are available, they can be converted to the alkenylstannanes by reactionwith Bu,SnH in the presence of AIBN.T
:il i-T
.a*
,..4, -,it
SEPh
(
-r* """r,f':: ""o5;(,.,,
Bu35nH- AIBN PhN.4eA
,"of;"/-r.rHa,
Metal exchange.a Allenyltributylstannane is transformed into propargylmetal halides by reaction at low temperatureswith MX,,, where 14 : P, As, Sb, Ge, B. The allenyl isomers are favored at higher temperatures.
Organotitanium neatcr 3-Hydroxy aAchyl ethers of aldehydes fo should be emphasizedrlr In this method, the dono pAlkcnyl kctoncs. alkynes with l-hMgCl Li2Cu(CN)C12.
rYachi,K., Shinokubo. H .r rUrabe,H., Hamada. T.. Sl
Organozinc reagents. l. 228-234;18,264-265. I Preparations. Fun via stereoselectiveand n
synthesisof carboxr'lic , prior attachmentto a res
OBn
#*: \-,
Conjugate addition,5 Contrasting diastereoselectivities are observed for the additionof R.Snl-i and R.,Sn(Etr)ZnLito 1-alkoxy-ct,B-unsaturated esters.
d1 )f
o
78'
COOMe
Bu"Sn
/:\ 'cooM" ttt.
/
Bu3Sn_
fooue
{{
+
\"
\o
Bu3SnLi
58Yo
Bu35nZnEt2Li
84Yo
100
:
0
0
:
100
rMurata,M., Watanabe,S., Masuda,Y. Sa 1043 (2000). 2lockhart, M.T., Chopa,A.B., Rossi,R.A. JOMC 582,229 (1999). rBerkowitz, D.B., McFadden,J.M., Chisowa,E., Semerad,C.L. JACS 122, 11031(2000) aGuiltemin,J.-C., Malagu, K. OM 18,5259 (1999). 5Kdef, A., Provins,L., Dumont, W. ACIEE 38, 1946 ,l99q).
An accessto unslmm enones relies on succe ketones.3 Lithiation and, Li-Zn propargyl chlorides. Ttrs
lenylzinc reagentsprepat size ant i-homopropargl h
, AC(J\,-/,-/'
.4
ows
Organozinc
it::' . '.rlklnes at room temperatureln
\l
: r r s \ e t oJ,. V . T L 4 0 , 5 1 1 5 ( 1 9 9 9 ) .
Irr)m coupling of ArI with ll'\1,1)h:): and KOAc.l Reactionof qith haloarenes(and halo6-l[, h^ -
rtagents
Organotitanium reagents. 3-Hydroxy aldehyiles.t On treatment with MeLi and then (BuO)aTi, silyl enol ethers of aldehydes form enoxytitanates that condense with carbonyl compounds. It should be emphasizedthat in conventional aldol reactions aldehydesbehave as acceptors. In this method, the donor role is established. pAlkcnyl ketones.z l-Silyl-l-alken-2-yltitanium reagents generated from l-silylalkynes with i-PrMgCU(i-PrO)+Ti are used as Michael donors in the presence of Li2Cu(CN)Clr. rYachi,K., Shinokubo, H., Oshima,K.,/ACS121,9465(1999). 2Urabe,H., Hamada,T., Sato,F.JACSl2l,2931 (1999).
- rrcned to the alkenylstannanes i=.., Organozinc reagents. 13, 220-222; 14, 233-235 ; 15, 238-240; 16, 246-248; 17, 228-23 4 ; 18, 264-265 ; 19, 24V24 | ; 20, 270-27 5 Preparations.
€-
.
z
+
l-/-Nna= MeOOC
F:--
T l. a
Functionalized organozinc reagentshave been prepared from alkenes
via stereoselectiveand regioselective hydroboration andB-Zn exchange.rAn interesting synthesis of carboxylic acids by chain extension from (to-l)-unsaturated acids involves prior attachmentto a resin (in the form of polymeric esters).2
I I
a
rl
oBn ,:r.iirrmed into propargYlmetal . r'c \{ : P, As, Sb, Ge, B. The
k' t
.'l
,,,-..-f:^
EtzBH-Me2s; aY^t^
'Phzn -?
(/
Bu3Sn-_ ,COOMe
. { { \" 0
=
cucN.2Licr a{lr,
^\,.8,\4-.o 6SYo
An accessto unsymmetrical 1,6-diketonesby conjugate addition of 1-keto zincatesto enones relies on successfulenolization and a Sn-Zn exchanse reaction of B-stannvl l ketones. Lithiation and LiJn exchange make 3-chloroallenylzinc bromides available from propargyl chlorides. These reagentsreact with aldimines to form 2-alkynylaziridines.aAllenylzinc reagentsprepared from chiral propargylic mesylateshave been used to synthesize antlhomopropargylic alcohols.5
100
: / 1('s 122,1103I (2000)
'.Z/\oMs AcO-v 7/
Pd(OAc)2- Ph3P
+ OHC
-
o OgBnn
H t
: I\ lties are observed for the esters. .:r.Jturated
C l'.':
a
ta
OBn
!
I
a
AcO 75o/o(anti : syn 95:5)
E f
P
t
Organozinc reagents
Electrogeneratedzinc (Zn anode) reacts rapidly with functionalized alkyl iodides and cross-couplingreactionscan be eflectedin situ.6 Mixed diorganozinc reagentscontaining a nontransferableneopentyl or neophyl group are obtained by a metathetic reaction between dineopentylzinc and another R2Zn, or by reaction of neopentyllithium with RZnX. Neophyl analogues are similarly prepared. These reagentshave been used in asymmetric alkylation of aldehydes.T Addition to C:X bond. Allylzinc reagents add to the carbonyl group of B-keto phosphonates.8With respect to a catalytic enantioselectivesynthesis of chiral pyrimidyl carbinols, an automultiplication phenomenonis elucidated.v
N-\CHO
-il :T
+
\r)
'7
iP.2zn I
N
The addition of allylzinc h ums gives rise to gem-bimeta setsup a Fritsch-Buttenberg-\
+
R:Li
HCt - H2O
' . { l
...",
7a\si^%
\,
U
(catalyst)
€
,il
RL'-2
Addition of organozincsto iminium saltsr0and oxime ethersrrfurnish amines. Diethylzinc used in the latter processis a chain-transferagent. cr-Selenozinc reagents such as ArSeCH2ZnCl have been developed.r2Their addition to aldehydesis mediatedby CuCN-LiCl and promotedby BF1'OEtr. Conjugate additions. Allylzinc halides add to B-nitrostyrenes in DMF at room temperature(12 examples,76-90Vo).t3This result is contraryto the report on substitution of the nitro group under microwave irradiation,rathereforethe situation needsclarification. An enyne group that is introduced to the B-position of an enone in the nickelcatalyzed addition is generatedfrom alkynylzincation. Is
o '
1\
\--A
1 N
i
(
a
. [n-:jzn
c
\ a c + R-:
/ )
2
*sil;;
\
/
/ / -\J'
electron-deficientalkenyl ha.h substitutionpatternsof the lan result.2l
I
Hn-
* /
-* R = Bu
Coupling reactions. Cr triflates need the presenceof, are catalyzed by Pd(0) compl
\ R + H
670/o
due Air facilitatesthe addition ofdiethylzinc to 6-alkoxy- and 6-acyloxypyran-3-ones, to formation of EZnOOEI, which is a catalyst.ro Addition to aWnes and dienes. Organozincation of alkynes and dienes generates new organozinc speciesthat are exploited synthetically.For example, alkenylzincs derived from propargyltrimethylsilaneare useful for the synthesisof 1,3-disubstituted1,3-dienes.rT
Other coupling partners r methylthiobenzothiazole,:: alk thesisof trisubstitutedalkencs cross-coupling conditions betr zinc iodidesin solutionand in r
Organozincreagents
:-nctronalized alkyl iodidesand a--.' r. 1..,
l] il
k - -
:rlc' neopentll or neophylgroup :,zrnc and anotherR2Zn,or by .,'gues are similarly prepared. : .rldehvdes.' , rhe carbonyl group of B-keto . \\ nthesisof chiral pyrimidyl
Cr - : . , '
-a
RLi - ZnCt,
-siMes
R
>
4/
Ni(cod)2 ._ PhcHoirHF
The addition of allyrzinc bromide (allyrmagnesium bromide * znBr) to arkynyilithi_ ums gives rise to gez-bimetalloalkenes. chlorination of the latter species with phso,cl setsup a Fritsch-Buttenberg-Wiechell rearrangement.I8
l(:Lt
N
-
T t Ph^
R f
297
+
M
ZnBr2
Vrnr,.
Phso2cl
(-"' \:
E
!1 i r
, , , r.i' c'therslrfumish amines.Di-
d
rr. - -r.n developed.r2 Their addition rr:^.llF,.OEt.. t . :rrr()\tvrenesin DMF at room ':.rn to the report L on substitution '. :hc :ituationneedsclarification. rL: t r ' ' n of-an enone in the nickelE
coupling reactions. cross-coupling reactions of organozincs with actrvated triflates need the presenceofcuprates.reThose involving teilurium compoundsand cul are catalyzed by Pd(0) comprexes.2'Regioselectivity in the pd(0)-catalyzed coupling of electron-deficient alkenyl halides with ailenic/propargyric zinc reagents depends on the substitutionpatternsof the latter speciestherefore either alkenynoicor alkatrienorcesrers result.''
B u L i , H-' q C t , :Z n B r ,
;
r'n------:-\
\-./
COOET
cooEt
I
66% Ph
B u L i , H g C t 2 iZ n B r 2
R R = Bu 67Yo
t r .
l:
:'
ll:
I
k'. .
.rnd6-acyloxypyran-3-ones, due 't alkynes and dienes generates ,r cxample,alkenylzincsderived r7 ,i I .3-disubstituted 1,3-dienes.
,
4 t: 7
r.t -
-
E
r
P , Ph_-- -
R
iz
R + H
/:\ I
cooEl
F"r \ EIOOc
R
other coupling partners to organozinc reagents incrude heterocyres such as 2methylthiobenzothiazore,22 arkenyl aryr iodonium triflates (arkenyl group transfer fbr syn_ thesisof trisubstitutedarkenes),23 and aryl heteroarylethers.2a Imp.ou"d nicker_cataryzed cross-coupling conditions between orlfta-substituted aryl iodides_nonaflatesand alkyl_ zinc iodidesin solution and in the solid phasehave beendefined.r5
J
Organozinc reagents
e(:""='
* ''n""-'^''cooEt
(\'cooEt
Bu4Nl- 4-fluorostyrene NMP THF
\.r'\-,-.-COOEt 83To
SMe
-ti'^l
+BrZn*Ph
\NASM"
SMe (Ph3P)4Pd> #* rHF^ ll I \N/tA=-'Ph
Alkylatinns. With Pd-catalyst to open all allylic oxabridge diorganozincs intercept the tr-allylpalladium speciesby donating their o-ligands.26
-'("
:'T*
OH
=!d ----$
lve2zn- (dppOPdC12
.']
I
Z'>//V t i l \."^'.-Z
.rl
l
Organozirconium Alkylations.
B0%
' . I
" Bertrand, M.P., Feray, L.. \ousu r r D u a n ,D . - H . ,H u a n g , X. JCR:S, rrKumar,H.M.S., Reddy, B.\,S . t ''Hu, Y, Yu, J., Yang, S., Wang.J r5Ikeda,S., Kondo, K., Sato.\ ('/_ 'nvander Deen,H., Kellogg. R \l . 'tQi, X., Montgomery I.IOC 6l.l rNRezael, H., Yamanoi,S.. Chemtr reLipshutz,8.H., Vivian, R.V. ff, { roDabdoub,M.J., Dabdoub. \lB - \ rrMa, S., Zhang,A., yu, y.. Xra- \A :rAngiolelli, M.8., Casalnuoro. .\.1 ]Hinkle, R.J., Leri, A.C., Dar rd_G lBrigas, A.F., Johnstone, R.A.!* J r5Jensen, A.8., Dohle, W.. Knahrl :('Lautens,M., Renaud, J.-L.. Hrctr rTOhno,H., Toda,A., Oishi. S.. Tar riVarghese,J.P.,Knochel, P..\larcl
reagents. Acylzirconc
ketones.r In the latter ca\e. mechanism.
Elimination. Chiral terminal alleneshave been preparedfrom 2-bromo-2-alken-1-yl mesylatesbearing a protected amino group by treatment with diethylzinc.2TAn alternative way to set up the elimination is by alkylation of alkenylcopperspeciescontaining an ct-sulfonylalkenyl(or sulfinylalkenyt)group with o-iodoalkylzinc reagents.2s The latter protocol allows preparationof trisubstitutedallenes. Ph ..../.--..../,^-..',,. ZrCh R"
R'2cu- lvgBr2 n-----ee,n,
,r,
Ri /:\ R
r-1 ,Cu SOlnlTol
ZnR
R' R
rBoudier, A., Hupe, E., Knochel, P.ACIEE 39,2294 (2000). 2Jackson,R.F.W.,Oates,L.J., Block, M.H. CC l40l (2000). rRyu, I., Ikebe,M., Sonoda,N., Yamamoto,S., Yamamura,G., Komatsu,M. TL 41,5639 (2000). oChemla,F., Hebbe,V., Normant,I.F.TL40,8093 (1999). sMarshall,J.A., Adams, N.D..rOC 64, 5201 (1999). 6Kurono,N., Sugita,K., Takasugi,S., Tokuda,M. f 55, 6097 (1999). 7Lutz,C., Jones,P.,Knochel, P S 312 (1999). nl-entsch,L.M., Wiemer, D.F. JOC 64,5205 (1999). eShibata,T., Morioka, H., Hayase,T., Choji, K., Soai, K. JACS ll8,4'11 (1996). roMillot, N., Piazza,C., Avolio, S., Knochel, P. S 941 (2000).
Under the influenceof ( Ph,p the reactionof alkenylzirconiu Acylations. Alkenylzircm of alkynes readily undergo copl selenium substituents are arz respectively.Alkenyl alkyn;"Ikc carbon monoxide with alkvnr.ho
Organozirconium reagents
z
/\,'cooEl
-
;
\-\--cooEt 83% S'.!e
\,
--\ ..
l.
---\,.Ph
' .:\ndg!- diorganozincsintercept
N.
OH
I --^\/ \i.. -\v
I
1lBertrand,M.P, Feray, L., Nouguier,R., perfetti, p. JOC il,91 g9 (1999). t2Duan,D.-H., Huang, X. JCR(S)26 (1999). lrKumar, H.M.S., Reddy, B.V.S.,Reddy,pT., yadav,I.S. TL 40, 53g7(lggg'). raHu,Y., Yu, J., Yang, S., Wang,J.-X., Yin, y. SC 29,1151.(Iggg). r5Ikeda,S., Kondo, K., Sato,y. CZ 122j (lggg). lovander Deen, H., Kellogg, R.M., Feringa,B.L. OL2,1593 (2000). 'tQi, X., Montgomery, J. JOC @,9310 (tggg). lERezael,H., Yamanoi, S., Chemla,F., Normant, l.F. OL2,4lg (2000). l'Lipshutz, B.H., Vivian, R.V. ZZ 40, 2gi1 0999\. 20Dabdoub,M.J., Dabdoub, V.B., Marino, J.p. TL 41, 433, 437 (ZOO0). 2rMa, S., Zhang,A., yu, y., Xia, W. JOC 65,Z2g7 (ZCf,,O). r2Angiolelli,M.E., Casalnuovo, A.L., Selby,T.p. SZ 905 (2000). rrHinkle, R.J., Leri, A.C., David, G.A., Erwin, W.M. OL2, l52l (Z0OO'). 2aBrigas, A.F., Johnstone,R.A.W. "/CS(p/) 1735 (2000). r5Jensen, A.8., Dohle, W., Knochel, p. T 56,4lg7 e0O0\. 26Lautens, M., Renaud,J.-L., Hiebert,S. JACS 122, lg04 (2000). 27Ohno,H., Toda,A., Oishi, S., Tanaka,T., Takemoto,y., Fujii, N., Ibuka,T. TL 4l,5l3l 2sVarghese, J.P.,Knochel,P, Marek, I. OL Z,2g4g (2000\.
Organozirconium reagents, Alkylations. Acylzirconocenes react with allyl and propargyl halides to give ketones.r In the latter case, allenyl ketones are obtained, as a result of the s"2, mechanism.
300,b -.: .:ird irom 2-bromo-2-alken-1-yl f An alternative r-' . :h,licthylzinc.2T i l . - . . r ) p n c rs p e c i e sc o n t a i n i n ga n -: '.r .,ilrlzinc reagents.28 The latter
ZrCOz
cu*
| t |
\\ - n : /
9'lYo
" * l
tn-^-f.o
/
o
Br
R 61%
(
\ ,nrf,tsu.M. TL 41,5689 (2000)
{ , . l i l i 1 7 r( 1 9 9 6 ) .
,!
iz
t ta :rf
nrt I
"u
*t\y' -
U
R'
a
;f P
'nuff Ph...-,^-,..-1
ZnR
lr i r
:E
cl
J
(2000).
Under the influence of (Ph.1P)aNi, a,ct-difluoro-B,"y-unsaturatedestersare formed from the reaction of alkenylzirconium reagentswith bromodifluoroacetic esters.2 Acylations. Alkenylzirconocene chlorides that are generatedfrom hydrozirconation of alkynes readily undergo copper-catalyzedacylations. Thus, enones containing tin and selenium substituents are available from alkynylstannanes3 and alkynylselenides,a respectively.Alkenyl alkynyl ketones are obtained when the reaction is carried out under carbon monoxide with alkynyliodonium salts.5
Organozirconium reagents
R
SeEt
R
SeEt
CuBr.SlVe2
+
R:SeE1
Cp2Zr(H)Cl +
ZrCoc t
Carbocycles.t8 Either fiu zirconacyclopentanesand alklrr
F N
-
Ph
CI
After hydrozirconation withCp2ZrEtz and reaction with an chloroformic ester,alkynes directly (requiring no catalyst) afford conjugatedesters.6 Heterofunctionalizations. Practically all the substrates are alkenylzirconocene chlorides. They behave well in halogenation,Tphosphorylation,s sulfenylation,e sulfinylation,r0selenenylationrr'r2 and selenoacylation,r3 as well as tellurylation,rr'rawhich gives
H
^-+--\
Ph2Si.
\z}:/
I
ZrCh
: H
rise to the substitutedalkenes. a-Cyanoalkenylation.ts
-il
Lithiated epoxynitriles give 2-cyano-1,3-dieneson reaction
with alkenylzirconocenechlorides.
:.I*
s '{"
*..2.. ,fi
1'"0' r/r
I
*
i-Pr2NLi/ THF
/<"7-
t
CN
Nc
'
R = Hx 64To
Homoallylic alcohols and l,3-dienes. Insertion of carbenoids to the C-Zr bond of alkenylzirconocenechlorides by gez-chloroalkyllithium generatesreactive reagentsthat can be exploited in a carbon chain extension.Thus, consecutivereactions of the zirconocene species with Me.rSiCH(C1)Liand aldehydes lead to homoallylic alcohols.roSimilar insertion with 1-chloro-l-lithioalkenesgives rise to conjugated dienes.rTThis method is adaptable to the synthesis of more extended conjugated
rHanzawa,Y., Narita, K., Taguchr. 1 2Schwaebe,M.K., McCarthy.J.R t . t Zhong P., Xiong, Z.-X., Huang. X. aSun,A., Huang, X. ,9775 (20Or 5SunA , . , H u a n g ,X . I 5 5 , 1 3 2 0 1r t ! 6Takahashi, T., Xi, C., Ura, Y.. \& THuang,X.,Zhong, P.SC 29. -l{ls r sZhong,P.,Huang, X., Xiong. Z-.-X '/Huang, X., Xu, X.-H., Zheng.\t'-l loHuang,X.,Zhong, P.,Guo. I{.-P .f I IPark,C.P, Sung,J.W.,Oh, D,Y. St r2Ma,Y., Huang, X. SC 29,429 tl9g] r3zhong,P.,Xiong, Z.-X., Huang. )r 'oHuang,X., Liang, C.-G. SC 30. l?: r5Kasatkin,A.N., Whitby, R.J. ft {l 'nKasatkin,A.N., Whitby, R.J. fL I rTKasatkin,A.N., Whitby, R.J. ./.{Cs rELiu,Y., Shen,B., Kotora, M.. TaLl
systems.
Osmium tetroxide. 13, 222-225 18, 265-267 ; 19, 241-242: 2fi, J'
*..2.. 4rcp, r /
cl
*l4,
* -
'f,,""'
Li
!siu",
l
Li
cr'v\
--------*f
*yr\rt'""r1
Lcp2zrcl
*
^"y''€lZ
--.r-( R.cHo> .l
BF3 oEt? S,r"i
Modifications. A recoverr acrylonitrile-butadiene-sryrene t Dihydroxylations. Bv usrn efficiency is attained.2 A nes
analogue1,3-dimethyl-5-erh1 l-5. An allylic trichloroaceramin OsOa and quinuclidine N-oxidc
diastereoselectivity by variation<
Osmiumtetroxide Carbocycles.t8 Either five- or six-membered carbocycles are obtained from zirconacyclopentanesand alkynes in the presenceof CuCl.
SeEt
R
Se:'
CuBr'Slr4e2 Phcocl
\--
n
Ph CuCl/ THF
t+ r .t. :r'.rn chloroformic ester,alkynes
H
^-l--1
: . .^-lrrte\ are alkenYlzirconocene rp: -r lltion.8 sulfenylation,esulfiny,.i-' .r. tellurylation,rr'rawhich gives r : .- l-cvano-1,3-dieneson reaction
CN R = Hx 64Yo
t:' :r ,rf carbenoids to the C-Zr . , l k i l l i t h i u m g e n e r a t e sr e a c t l v e h . , n .T h u s ,c o n s e c u t i vree a c t i o n s r:.: r ..' .rldehydeslead to homoallylic h. .: rr'Ilc'Sgives rise to conjugated i.:. . ,rl more extended conjugated
..
\
S Me31
]
OH R'CHO> BF3.OEI2
:
K
SiMe3
.r'
Phzsi--L.-. ,zrcoz : H
I
Ph---:-Br
Ph2Si. I \--|\/
l
H
I
H
I
):\
'ph
.u.,,r+r+ r-1."-o}zen |----------------------Ph2si. I ll Pn--E
4/,/
H rHanzawa,Y., Narita, K., Taguchi,T. TL 41, 109 (2000). 2Schwaebe,M.K., Mccarthy, J.R.,Whitten, J.P.TL 41,791 (2000). 1Zhon1, P., Xiong, Z.-X., Huang, X. SC 30, 3245 (2000). aSun,A., Huang, X. S 775 (2000). sSun,A., Huang, X. T 55,13201 (1999). 6Takahashi,T., Xi, C., Ura, Y., Nakajima, K. JACS 122,3228 (2O0O). THuang,X., Zhong, P.SC 29,3425 (1999). 8zhong,P, Huang, X., Xiong, Z.-X. 5L721 (1999). eHuang,X., Xu, X.-H., Zheng,W-X. SC 29,2399 (1999). r{)Huang,X., Zhong, P., Guo, M.-P. JOMC 603,249 (20W). "Park, C.P.,Sung,J.W.,Oh, D.Y. Sf 1055 (1999). I2Ma,Y, Huang, X. SC 29,429 (1999). lrzhong, P.,Xiong, Z.-X.,Huang, X. SC30,887 (2000). 'oHuang,X., Liang, C.-G. SC 30, 1737 (ZOOO). rsKasatkin,A.N., Whitby, R.l. TL 41,6201 (2000). 'nKasatkin,A.N., Whitby, R.J. IL 40, 9353 (1999). rTKasatkin,A.N., Whitby, R.J. JACS 121,7039 (1999). rEl-iu,Y., Shen, B., Kotora, M., Takahashi,T. ACIEE 38,949 (1999).
Osmium tetroxide. 13,222-225; 14,233-239; 15,240-241; 16,249-253; 17,236-240; 18, 265-267 ; 19, 24 | -242; 20, 275-27 6 Modifications. A recoverable and reusable catalyst has been prepared from an acrylonitrile-butadiene-styrene polymer and Os04. I Dihydroxylations. By using molecular oxygen to sustain the oxidation, high atomefficiency is attained.2 A new cocatalyst duet is N-methylmorpholine and the flavin analogue1,3-dimethyl-5-ethyl-5, l0-dihydrobenzopteridine-2,4-dione.r An allylic trichloroacetamino group in cycloalkenes directs dihydroxylation with OsOa and quinuclidine N-oxide as the oxidizing system.4An interestingchange in the diastereoselectivityby variation of the oxidant composition has been observed.5
lr
12
i2 :1 :2 , l
i9
;i Pr ', J
302
Osmiumtetroxide NHCOCCt3
r'\ t t
+ osoa+
l
\-,/
NHCOCCt3
NHCOCCI3
+ /t ^ ' , ' ol H
aYot \_-,AOH
NMO / H2O- Me2CO 25' TMEDA lCH2CI2-78'
t l ----/',,OH
2 4 : 76 >95
98Yo 99o/o
Amino-substituted heterocyclesre. sulfonamider3,and primary amides h reactions.raThe untenable siruadoo prepared) as cooxidant in indusrrial sc r5 5,5-dimethylhydantoin.
Aryl 2-alkenoatesshow a revers.( lation.r6
Stereoselectivity in the catalytic dihydroxylation of acyclic allylic alcohols can be enhanced.6 Functional alkanes bearing a 2,3-dihydroxylated pattern are readily obtained, for example, aldehydes from 1-acetoxy-2-alkenyl phenyl sulfonesTand esters from ketene acetals.n I OAc
OAc
r pn-#onc
l
-
+
*
l p6t\,^so2en
"
osoa-NMo
.rrc,;#
1
OH |
OAc |
enl)7^soren . 'oH
NHZ
4 o H 'ro-r^ o V
89%
In situ oxidation of the diols derived from terminal alkenes results in ct-hydroxy carboxylic acids."
Ph.,.a
q AD-mix
Ph<,/
revpo
ll
HO'
'COOH
rL4r,3209(2000).
NaCIO- NaClO2 60% (>98o/o ee) tBuOH - H2O
Aminohydroxylations, Baylis-Hillman alkenes give predominantly syn-diols,r0 whereas the reaction with a,B-unsaturated phsophonates gives rise to cr-hydroxy-paminophosphonates.rr
-r
9" COOMe +
OH
K2OsO2(OH)a
tl
TsN(Cl)Na MeCN - H2O
2"ooMe'oH ( NHTs
rKobayashi,S., Endo, M., Nagayama-S .& 2Dobler,C., Mehltretter, G., Beller. l\l..{O rBergstad,K., Jonsson,S.Y., Beckvall.J -E aBlades,K., Donohoe,T.J., Winter. JJ.G . I 5Donohoe,T.J.,Blades, K., Helliwell. \1.. V 6Donohoe,T.J.,Waring, M.J., Newcombc. TTrost,B.M., Crawley,M.L., tre, C.B .rA EMonenschein, H., Drager,G., Jung..{.. Kr 'Aladro, F.J., Guerra, F.M.. Moreno-Dq-r
OH
* v)Tcoott'l" Ho' 'l NHTs
r0Pringle,W., Shalpless, K.B. ?L 2(). 5 l5 I r ' 'Thomas,A.A., Sharpless, K.B. "/OC 61. tj IrGoossen,L.J., Liu, H., Dress, K.R.. ShlrC rsGontcharov, A.V., Liu, H., Sharpless.K B 'uDemko,2.P.,Bartsch,M., Sharpless.K B r 5 B a r t aN , . S . ,S i d l e r ,D . R . , S o m e r v i l l eK . B (2000). 'nMorgan,A.J., Masse, C.E., Panek.J.S.()l
Osmium trichloride-potassiumferrl Dihydroxylations. An efficienrr couplesandquinuclidine methanesul rEames,J., Mitchell, H.J., Nelson.A.. O'Bn
Osmiumtrichloride-potassiumferricyanide
f'l*.- -uli
NHCOCCI3
^l
\Y,
. -,'\,"oH I t
l
\,/,,,on
,a
: 7 6
Amino-substituted heterocycles(e.g., 2-aminopyrimidine),r2 sodium N-chloro-t-butylsulfonamider3,and primary amides have been developed as a nitrogen source for these reactions.ra The untenable situation in using t-butyl hypochlorite (3 equiv, freshly prepared) as cooxidant in industrial settings is amendedby replacing it with 1,3-dichloroIs 5,5-dimethylhydantoin. Aryl 2-alkenoatesshow a reversed regioselectvity in the asymmetric aminohydroxy-
>95
lation.r6
.rcrclic allYlic alcohols can be
)r
K2OSO2(OH)a
I
(DHo)?-AoN>
a\/-\(o.-r\ il O
.rrt!-rn are readilY obtained, for ullonesr and estersfrom ketene
Fnl
,. \MO + ..,. H2o
|
OAc
en\*so,en
z-NH2/ t-Buocl n-ProHiH2o
I
%Br
tl ; f
r OH
ll
N
H
Z
4Aro)oH o
.
I
?
aYo)-
NHZO
%Br (7
|\ ,,
H 9e|.
1)
89%
r.1l alkenesresults in a-hydroxy
c:"
F-
.,/
F]
COOH
6.
-38% ee)
r-, . irvc predominantly syn-diols,rO o.: 'r.tt.s gives rise to a-hydroxy-p-
_ : loN4e a
a1..-s
Ho
COOMe 'l NHTS
t t
',,-
trl
"2 , .
rKobayashi,S., Endo, M., Nagayama,S. ./ACSl2l, 11229(1999). 2Dobler.C.. Mehltretter.G., Beller. M. ACIEE38,3026 (1999). rBergstad,K., Jonsson,S.Y.,Biickvall, J.-E.../ACSl2l, 10424(1999). aBlades,K., Donohoe,T.J.,Winter, J.J.G.,Stemp,G. TL 41,4701 (2000). sDonohoe,T.J., Blades,K., Helliwell, M., Moore, PR., Winter, J.J.G.,Stemp,G. JOC 64' 2980 ( 1999). 6Donohoe,T.J., Waring, M.J., Newcombe, N.J. SL 149 (2000)TTrost,B.M., Crawley,M.L., Lee, C.B. ./ACS122,6120 (2000). sMonenschein,H., Drager,G., Jung,A., Kirschning,A. CEJ 5,2270 (1999). eAladro, F.J., Guena, F.M., Moreno-Dorado,F.J.,Bustamante,J.M., Jorge, 2.D., Massanet'G.M. TL41,3209 (2000\. rOPringle, W., Sharpless,K.B. 7a 40, 5151 ( 1999). llThomas,A.A., Sharpless,K.B. JOC 64,8379 (1999). l2Goossen,L.J., Liu, H., Dress,K.R., Sharpless,K.B. ACIEE 38, 1080( 1999). l3Gontcharov,A.V., Liu, H., Sharpless,K.B. OLl,783 (1999). raDemko,Z.P, Bartsch,M., Sharpless,K.B. OL2,2221 (2000). rsBarta,N.S., Sidler,D.R., Somerville,K.B., Weissman,S.A., Larsen,R.D., Reider,P-J.OL 2' 2821 (2000). r6Morgan,A.J., Masse,C.8., Panek,J.S.OL 1, 1949 (1999)'
9H
, l
Osmium trichloride-potassiumferricyanide. Dihydroxylations. An efficient dihydroxylationprotocol employs theseoxidant /-butanol.r in aqueous methanesulfonamide couplesandquinuclidine rEames,J., Mitchell, H.J., Nelson,A., O'Brien, P, Wanen, S., Wyaa, P.JCS(PI ) 1095( 1999).
'g ts i P
t J
304
l-Oxo'2,2'6,6't$ramethylpiperidine chloride
-268; 19' 243;20,277 Oxalyl chloride. 17,241-242;18,26'l the following Diaryl kctones.t A Friedel-crafts acylationmethod is shown in eouation:
rTakata,T., Tsujino,Y., Nr\an.
Oxygen. 18. 268-269: 19. . Epoxidations. In thc hydrogenperoxidegenemk
without a metal catal) sr hydroxyphthalimide, Mol O Oxidations. Benzllrc the presenceof many differ
ctco-cocl i Alc13 PhOMe / CH2C|2
OsOais needed).rRu-on-h under fluorous biphasic coo A remarkableeffect of q
CJ :I::
:-r
s-!^ ,.{
catalyzedbenzylicoxidatro
rTaber,D.F.,Sethuraman, M.R. .IOC65' 254(2000)' S-(1-Oxido-2'pyridyl)- 1,1,3,3-tetramethyluronium salts' temperature by a Amides.t carboxylic acids are converted to amides at room tetrafluouronium combination of NH4CI and i-Pr2NEt in DMF using the substituted roborate or hexafluorophospahate(1) as condensingagent'
..n
Aromatic aldehydes thc liquid underthe influence< tcristic of the VOCIr-catalr; honyl compounds).e
B-Ketoesters are oxidrz rnanganese(Il) acetate)"or r c.p-unsaturatedphosphoru
PdCl, and isopentylnitnte trons,that is. 02, Fe;O,.and Oxidation of organonr cleavagewith Zn-HOAc cr the oxidative captureof a p rnd the reductiveDath$a\r
*!!M", ,f\ x il t tl \ fr'As^ Ntt't", o I
(1)
rBailen.M.A.,Chinchilla, D'J',Najera,C'TL4l'9809 (2000)' R.,Dodsworth,
| -Oxo-2,2,6,6-tetramethylpiperidine chloride' pAminoxychlorides'|Thetitlecompoundbehavesasanelectrophilicagent used to form the chlorotoward activated alkenes. Allied oxoammonium salts can be
o l i l
o'"\'/ :
hydrin derivatives.
r-\ t
;\;{
t
-
t
l
cr * \*
R = Ph, OEt,.
.*;
I o) I R^cl
Alkyl halides and tosll CuCl-Kieseelguhr as catalv Sulfoxidation of saturarc
Oxygen rTakata,T., Tsujino, Y., Nakanishi, S., Nakamura, K., Yoshida, E. CL937 (199q.
r
- 'no*n in the following Oxygen. 18, 268-269; 19, 243-244; 20, 277-27 9 Epoxi^dations. In the presence of perfluoroacetone and N-hydroxyphthalimide, hydrogen peroxide generatedin situ from oxygen and l-phenylethanol epoxidizes alkenes without a metal catalyst,t although there is also an alternative2 in using Nhydroxyphthalimide, Mo(CO)6, and Co(OAc)2.
i- ' ' ''^'o M "
Oxidations. Benzylic alcohols undergo aerial oxidation to aromatic aldehydes in the presenceof many different catalysts: OsOo/CuCl-pyridine (for benzylic alcohols only OsOais needed),3Ru-on-hydroxyapatite,4hydrotalcite-supportedPd(ID,5 and CuBr'SMe, under fl uorous biphasic conditions.6
5. k'
.rl IOOfiI
temperature bY a
tetrafluo: . . . ^ - t i t u t euronium d
A remarkable effect of quaternary ammonium bromides in the N-hydroxyphthalimidecatalyzedbenzylic oxidation has been noted.T Aromatic aldehydesthemselvesare oxidizedto acid 8 by molecularoxygen in ionic liquid under the influence of Ni(acac)2. Excellent yields and mild conditions are charac:
lf
teristic of the VOClj-catalyzed oxidation of ct-hydroxy carbonyl compounds (to the dicarbonyl compounds).Y
t ) ' . J
B-Ketoesters are oxidized at the a-position with oxygen in the presence of either manganese(Il)acetatel0or cobalt(Il) chloride.rrCyclic allyl phosphonates give 1-acetoxy o,B-unsaturatedphosphonateswhen they are exposedto oxygen in HOAc containing PdCl2and isopentyl nitrite.12Tertiary amine oxides are formed undercooxidation conditions, that is, 02, Fe2Oj,and isovaleraldehyde.r3 Oxidation of organomercury compounds via formation of TEMPO derivatives and cleavagewith Zn-HOAc completesthe functionalizationof alkenes.laWithout TEMPO the oxidative capture of a primary radical generatedfrom organomercurial is inefficient, and the reductivepathway(lossof functionality)becomescompetitive.
,1000). O i l
Itr
.r\ an electrophilic agent used to form the chloro-
l l
o'\-\ : 02 - NaBHaTEMPO/ DMF ZnlHOAC-H2O 100.
,-_\ '-*{ I
o-l R^cl
50%
Alkyl halides and tosylatesare oxidized to carbonyl compoundsby oxygen using CuCl-Kieseelguhras catalyst.r5 Sulfoxidationof saturatedhydrocarbons'6with O2-SO2is catalyzedby VO(acac)2.
a
a
t
7
"j
1/a E
I
i
fr t
P ,
Oxygen
cooH I
.r\ t f
rF4 /,./\./
I
cooH 02 - SO2 VO(acac)2 / HOAC
SO3H
A catalyst prepared cleavageof enaminestc A formal hydrauo PhSiHj-Mn(dpm). in rs
oxidation of unsaturated compounds. Methyl ketonesare producedfrom l-alkenes using molecular oxygen as oxidant [catalyst: Pd(OAc)2-pyridine].r7 on the other hand' methyl 3,3-dimethoxypropanoateis formed when eth1il acrylate is oxidized on activated and Pd(oAc)2 in acidic ethanol.r8Treatmentof carbon-supportedmolybdovanadophosphate enoneswith LiAlH4 under dry oxygen gives l,3-diols.re
Cl :T:
Ph
;-t-
)
7.
02 - LiArHa + THF
Ph \_nu ./ \
roH ,P hroH
Ph
90% (syn : anti 1 ;1)
.,{
Oxidation of phc dihydroxybiaryls in the1 a-Hydroxy-ybut-m combinedin an oxidat phthalimide, Co(acao,;
. i
Cyclization of diarylamines are also effected although an analogous process for the and Sn(OAc)2.2() lessreactivediphenytetherrequiresPd(OCOCFT)2 o-benzoquinone,which forms Dielsphenol into of Tyrosinaseinitiates conversion other cooxidants in the oxidative instead of of oxygen Alder adducts.2tEmployment ether and alkenyl side chain is silyl enol a cyclization of compounds containing
Go"
desirable.22
o
OH
02 / Tyrosinase
\o=, 'A. v
cHct3
ov rl-t>
I oEt
Acetyladamantancs. of adamantanewhen thc IO1-Co(OAc),in HOAc.
70% OSiMe2(t-Bu)
6.Y
02 / Me2SO Pd(OAc)2
BlYo
Oxygen , _:-l
-1-so,n
A catalyst prepared by encapsulation of cucl, in zeolite X is useful for oxidative cleavageof enaminesto afford amides.23 A formal hydration of enones and dienones is achieved by reactron with PhSiHvMn(dpm)i in isopropanol under oxygen followed by work up with (Eto)3p.24
I i.- ::c. are producedfrom l-alkenes ;-rndine].r-On the other hand. Ais oxidized on activated .,-^latc li. ethanol.rsTreatmentof .:r .rcidic )-r-
-
iox
[.4n(dpm)3
r1.'"\-\ t l
n
ii
-t--f
PhsiH3
51%
,, F l -
r
1: 1 )
oxidation of phenors. phenors including 2-naphthol are oxidized to 2,2,dihydroxybiarylsin the presenceofVO(acac)2.25 Hydroquinonesgive quinones.26 a-Hydroxy-y-butyroractones.zi secondary alcohors and meihyr acrylate are combined in an oxidative fashion when they are subject to oxidation with N-hydroxy_ phthalimide,Co(acac)j,and Co(OAc)2 under oxygen.
a
I
, ) t
_ t
a
It: .::r ,rn analogousProcessfor the lr : .': O.\c)r.10 , -.-'l,lquinone,which forms Diels':r..r cooxidants in the oxidative r - :rc'r and alkenYl side chain is I
=
E
O2 Co(OAc)2 Co(acac)3
2\-4
I
\,,\
ll
s
P
o NoH NrecN
t 83%
Acetyladamantanes.2s Acetyl groups are introduced into the bridgehead positions of adamantanewhen the hydrocarbon and biacetyl are submitted to oxidation conditions [O2-Co(OAc)2in HOAc, 60.i.
47Yo
20yo
l"
Orygen
Alkylation of carbonyl compounds and derivatives. The O2lCo(OAc)2-Mn(OAc)2 Acetals also add system is useful to accomplish ct-alkylation of ketones with 1-alkenes.2e to acrylic esters under 02 in the presence of catalytic amounts of Co(OAc)2 and N-hydroxyphthalimide to afford ct-hydroxy-"y-oxoester acetals.30The adducts of methyl vinyl ketone suffer oxidative degradationin situ.
O..rO R^H
+ Z\COOMe
Oxygen,singlet.13,22g-229:ll. 2a 269-270;19,244 Allylic alcohols. Accesslo r. photooxygenation with reductir.e * trj Alkoxydioxines.2 Dienolerhen
02/ co(oAc)2 -1--l- On --------l* O..rO R"-'-'/\coptr,le A ,-.4 I
\,-\
ll
,aR )
NoH
l-oR' l
o
*
Cleavage of 1,3-oxathiolanes.rt
F FI
F--rr
(J I
};*.
Carbonyl
compounds are regenerated on heating
2-substituted oxathiolanes with VOCIr in CF.CH2OH under 02. rlwahama, T., Sakaguchi,S., Ishii, Y. H 52, 693 (2000). 2Iwahama,T., Hatta, G., Sakaguchi,S., Ishii, Y. CC 163 (2000). 3Coleman,K.S., Coppe,M., Thomas,C., Osbom, J.A.TL40,3723 (1999). aYamaguchi,K., Mori, K., Mizugaki, T., Ebitani, K., Kaneda, K. JACS 122,'7144 (2000). sNishimura,T., Kakiuchi, N., Inoue, M., Uemura,S. CC 1245 (2000). bBetzmeier,B., Cavazzini, M., Quici, S., Knochel, P. TL 41, 4343 (2000). TMatsunaka,K., Iwahama, T., Sakaguchi, S., Ishii, Y. TL 40,2165 (1999). bHowarth, J. TL 41, 662'7(2000). eKirihara, M., Ochiai, Y., Takizawa, S., Takahata,H., Nemoto, H. CC 1387 (1999). roChristoffers. J. JOC U.7668 (1999). IIBaucherel,X., Levoirier,8., Uziel, J., Juge,S. TL 41, 1385(2000). I2Attolini, M., Peiffer, G., Maffei, M. I56, 2693 (2000). r3Wang,F., Zhang,H., Song,G., Lu, X. SC 29, 11 (1999). r a H a y e sP, , S u t h e r s8, . D . , K i t c h i n g ,W . T L 4 l , 6 1 7 5 ( 2 0 0 0 ) . rsHashemi,M.M., Beni, Y.A . JCR(S) 434 (1999). 16lshii,Y., Matsunaka, K., Sakaguchi, S. ,/ACS 122,'7390 (2OO0). rTNishimura,T., Kakiuchi, N., Onoue,T., Ohe, K., Uemura,S. JCS(P1) 1915 (2000). r8Kishi,A., Sakaguchi,S., Ishii, Y. oL2,523 (2000). 'ecsaL:),,A.G., Maximo, N., Plumet, J., Ramila, A. TL 40,6485 (1999). 20Hagelin,H., Oslob,J.D., Akermark, B. CEJ 5,2413 (1999). 2 r M u l l e r ,G . H . , I - a n g ,A . , S e i t h e lD , . R . ,W a l d m a n n , H .C E J 4 , 2 5 1 3 ( 1 9 9 8 ) . 22Toyota,M., Odashima, T., Wada, T., Ihara, M. JACS 122,9036 (2O0O). z3Bbitani,K., Nagashima,K., Mizugaki, T., Kaneda,K. CC 869 (2000). 2aMagnus,P., Payne,A.H., Waring, M.J., Scott, D.A., Lynch, V. TL 41,9725 (2000). 2sHwang,D.-R., Chen, C.-P.,Uang, B.-J. CC 1207(1999). 26Hwang,D.-R., Chen, C.-P.,Wang, S.-K., Uang, B.-J. SL77 (1999). 2?Iwahama,T., Sakaguchi, S., Ishii, Y. CC 613 (2000). 28Kishi,A., Kato, S., Sakaguchi,S., Ishii, Y. CC 1421 (1999). 2elwahama,T.,Sakaguchi,S., Ishii,Y. CC2317 (2000). 30Hirano,K., Iwahama, T., Sakaguchi, S., Ishii, Y. CC 245'7(2ON). 3rKirihara,M., Ochiai,Y, Arai, N., Takizawa,S., Momose,T., Nemoto, H. TL 40,9055 (1999).
Oxidative cleavage,t The .\.-an undergoring fission to afford ranlr c'xcludedfrom the reactionmedia.rhc the presenceof Me.SiCN).
(\'* \:'/
o: -'€-{
tr--
t)
\b3\
Helesbeux, J.-J.,Guilet,D., Seraphrn. D. ':000). Dussault, P.H.,Han,e., Sloss,D.G..Srrnu C()cquer. G.. Ferroud. C..Guy.n. f SO.:C-:
Oxygen,singlet
ldre s. The O2lCo(OAc)z-Mn(OAc)z Acetals also add 96.;. $ rth l-alkenes.2e Co(OAc)z and of amounts r::.:.rllc of methyl adducts The rcetals.ro ..:J:
^-1 g* I{A"oo""
c
Oxygen,singlet.13,228-229; 14, 247; 15, 243; 16,257-258; 17,251-253; 18, 269-270:19.244 Allylic alcohols. Accessto o-(2-hydroxy-3-methylbut-3-enyl)phenols is through photooxygenation with reductiveworkup.I Alkoxydioxines.2 Dienolethersform suchcycloadducts with singletoxygen.
tr*
'
g-oY* ...............'.........'..'.,.'"............-...............*
( -oR'
02 | cH2ct2
tetraphenylporphyrin
.
*-oD R = Bu
630A
,, heating c " :",unds are regeneratedon ,()li ,indcrO1.
3 ,,,' It {r rll-l (1999)' (2000)' b;, :, K JACS122,'7144 '( -ir l(DO). .l rt :rrl (2000). r : . l l r - 1 6 5( 1 9 9 9 ) . I l C C 1 3 8 7( 1 9 9 9 ) '
\r'.
. :.. lrn0).
Oxidative cleavage.3 The N-arylamino derivatives of piperidine and pynolidine undergo ring fission to afford (aryl)diazenylalkanals or their acetals. When water is excludedfrom the reactionmedia, the o-carbon can be functionalized(e.g., cyanationin the presenceof MejSiCN).
_
r r r r
r. .
. - / ( ' s / P / l)9 l 5 ( 2 0 0 0 ) .
{Jr '.1\i ( 1999). ,: r 15l3(1998)' ; l :: '' ' 16(2000). .r,9 i2000). ; r . \ TL41.9725(2O0O)' (+,' . -, ..
1999).
I
0 ":.6
.
l(X)O). I .\emoto,H'TL40,9055(1999)'
a -
, a
NH
\.... ( )
02 / methyleneblue MeCN - H2O
-
l-v* \-/
a
\\ *-\
*\c"o
7SYo
F
F a
It
7
) ),.
a
rHelesbeux,J.-J., Guilet, D., Seraphin, D., Duval, O., Richomme, P., Bruneton, J. TL 41,4559 (2000). rDussault,PH., Han, D.J. T 55,11437 (1999). Q., Sloss,D.G., Symonsbergen, 'Cocquet, G., Ferroud,C., Guy, A. f 56,2975 (2OOO).
I f
P , I
I
|
/---r
o{r-p
Palladacycles for Many palladacycles,besidesthosederivedfrom bidenatephosphines'are available P'N-"BCligated N'C-' N,N-, O,N-, include varieties These catalyzingorganic reactions. as well as species.In the following, a selectionof palladacyclecatalystsbearing such presented' are diphosphines moreexoticbidentate
r!_p6_eso( ( | \_,/
--1..,-f-Ta
o v (2)
Reductions.Acenaphthoquinonediimineligatedpalladiumcomplexesanda of polymer-boundpalladaisoindolinehave tbund use as catalystsfor semihydrogenation nitro (including the compounds unsaturated common alkynesl and reduction of several group),2respectivelY.
E -T', =t:
Couplingreactions.Various(Heck'stille,suzuki,sonogashira'andUllmann) r coupling reactionsare mediatedby a stablepalladacycle1
activespecies.ll Sulfur-containingpallad< show excellent utility in 0r I ,850,000)|2 and Suzuki coup
tt,
Ph \ nr.r /AN'""
t;., {rli
l-\pi-t \ . / \_/
r ct_
Other stableand efficienrr zole-basedpalladacycles."Th that palladacyclesderived in
Aromatic ketones are a.l RCOS(CHr)4X.Palladac.v-c!
l Iz
(1) that is Accelerationof the intramolecularcoupling of phenol and aryl halide moieties etfectedwith a 4C-palladacycleby a baseis realized'ao-Aminophenyldiphenylphosphine is a ligand that forms effectivePd complexesfbr the Heck reaction's
.,\ O -"4*"i
- z+d3!"lfi-:::^]J"' ^.4 \/-''\o16^[# '.oAfo)
Displacements. A ratho nucleophileshas been reponed
BjYo
in contrastto other Note that palladacyclestypified by 2 arepoisonedby 1,4-dienes,6 pd(0) catalystsystems.Accordingly,the Heck reactioncannotemploy thesecatalysts.on (aryl the other hand, 3 has a high thermal stability and broad scope of application (3 examples, 4 is also a highly activecatalystfor the Heck reaction couplings).TComplex 95-100%)." 310
t N"'
*9
*r* \
0
Palladacycles
? _ ---.-b-<) ( availablefor r- * :-:r.itcphosphines,are l.r- ' \' ,V.N-,N,C-, flN-' 4C-ligated as well as t\ - '.rttlvsts bearing such
)-ri,-"cocF3
a,f-r-> o v
and Ullmann) e . ..,Liki.Sonogashira, 1 . .- . l '
l
/
.---<'"-P1 / / \\FPd-cl \ r ( | \-./ a^-flv
(2)
and a r!., - .r Palladium comPlexes of e ,- -.,t.rlvstsfor semihydrogenation nitro the t.,' . -.1 cornpounds(including
Y.
^
311
l
l
(3)
(4)
Other stable and efficient catalysts for the Heck reaction are pyrazole- and benzothiazole-basedpalladacycles.e They are capableof promoting Barbier{ype reactions.r0Note that palladacycles derived from aromatic imines decompose to form metallic Pd as the activespecies.rr Sulfur-containing palladacycles such as 5, which are stable to air, water, and heat, show excellent utility in the phosphine-free Heck reaction (turnover number up to I3 I ,850,000)I2 and Suzukicouplingsat room temperature. Aromatic ketones are also accessible by coupling of AIB(OH), with thioesters RCOS(CHJ4X.Palladacycle5 and NaI are presentin the reactionmilieu.ra
that is .:irrl and aryl halide moieties il . :,,-.\minophenyldiphenylphosphine ll-ik rcaction's r' r'
S-R
's-I Cl-lz
(5)
Cs2CO3
Displacements. A rather unusual displacement of alkenyl chlorides with carbon nucleophileshas beenreported.rs
AcNMe2
e5'
HO B0%
\on' P
Q
al::
in contrastto other J hr 1.4-dienes,6 On ,,n cannotemploy thesecatalysts' (aryl application of rJ hroad scope .r ior the Heck reaction(3 examples'
-N rY\J \,,/ \./ P
1
Nt'
*
COOMe
*"* \"oo""
DMF
D
12O"
COOMe
1--cool,r" aa\
76%
312
Palladium-+arbon
Addition the ligands)
to muhiplc is applicable
bonils.
A water-soluble
carbonylation.'u
\ -rl -r:,1
--I-1 ?s' -:!t
'7, t , ai
Pd catalyst (picolinic
to the synthesis of 2-arylpropanoic
acid as one of
acids from
styrenes by
\-.'\,,,\-,,<
.
Ivan Laren, M.W., Elsevier,C.J.ACIEE38,3715 (1999). 2lslam,M., Bose,A., Mal, D., Saha,C.R. JCR(S)44 (1998). 3Alonso,D.A., Najera,C., Pacheco,M.C. OL2, 1823 (2000). aHennings,D.D., Iwasa,S., Rawal, Y.H. JOC 62,2 (199'1)sReddy,K.R., Surekha,K., Lee, G.-H., Peng,S.-M., Liu, S.-T. OM 19,263'7(2000)6Kiewel, K., Liu, Y., Bergbreiter, D.8., Sulikowski , G.A. TL 40,8945 (1999). TMorales-Morales, D., Redon,R., Yung, C., Jensen,C.M. CC 1619 (2000). 8Miyazaki,F., Yamaguchi,K., Shibasaki,M. TL 40,'13'79(1999). ecai, X., Grigg, R., Ramzan,M.I., Sridharan,V, Collard, S., Muir, J.E. CC 2053 (2000). r0Gai,X., Grigg, R., Collard, S., Muir, J.E. CC 1765 (2000). rrNowotny, M., Hanefeld, U., van Koningsveld, H., Maschmeyer,T. CC 1877 (2000). r2cruber,A.S., Zim, D., Eberling,G., Monteiro, A.L., Dupont,J. OL2, 1287(2000). \3Zim,D., Gruber,A.S., Eberling,G., Dupont, J., Monteiro,A.L. OL2,2881 (2000). IaSavarin,C., Srogl,J., Liebeskind,L.S. OL2,3229 (2000). rsReetz,M.T., Wanninger, K., Hermes, M. CC 535 (1997). r6Jayasree, S., Seayad,A., Chaudhari,R.V. CC 1239 (2000).
Palladium-carbon. 13, 230-232; | 5, 245 ; 18, 273 ; 19' 247; 20, 280-28 | Hydrogenolysis. 2-Naphthylmethyl esters are more readily hydrogenolyzed in the presenceof Pd-C than benzyl analogues,therefore two such esterspresent in a molecule are easily differentiated.r'2Quinolin-4-ylmethyl estersincluding carbamatesand mixed
It is possible to retain a hc unsaturated esters.l0
NHBoc
tno-_-r\Z-coa
Trimethylsilyl ethers of Bar genation.ll
Catalytic reduction in merharr \aturatesalkenesand alkr.ner: \'-alkylation to afford tuNHCHX present.l't
Dehydrogenation. Under a undergohydrogen transfer and arc
carbonateshave the sameselectivitiesin transferhydrogenolysis.r A practical synthesisof polysubstitutedpyrrole-2-carboxylicestersis via the corresponding benzyl esters,the other functional groups are not affected under hydrogenolysis conditions.4 P-Aryl-glactams undergoring fission in a transferhydrogenolysisthat is also assisted by microwave irradiation.5Regioselectivetransacetylationafter hydrogenolysisof certain C-arylglycosideshas beenobserved.n
Bno--,
Bno--O1-oBn
e^o;$it\\zo
Biaryls. Homocoupling of a media (PEG-400,NaOH, H.Or un
H2ipd-c
.;*-
crown-6.r7The considerableimpm rntriguing. 98To
Hydrogenolysis of terminal epoxides to afford secondary alcohols is best accomplishedwith the Pd-C(en)catalystin methanol.T Hydrogenation. The Pd-C(en) catalyst shows selectivity in hydrogenation such that an epoxide group is retained.s The same system provides a means for the hydrogenation of alkenesthat also contain an acid-labile TBS ether.'
Amidocarbonylation.
A u-fu
o
nAlrHn, + R"-
Palladium-+arbon
l -.,:.:lrtt (picolinicacid as one of styrenesby ['- :'.,Ir()icacids from
\-',\-,/^\-.,
313
r\
\,/-\-,-\..<J" 96%
It is possible to retain a benzyloxy group during hydrogenation of ^y-amino-ct,punsaturatedesters.lo . - , 1 11 9 .2 6 3 7( 2 0 0 0 ) . J 1 r . . r - t 5t 1 9 9 9 ) . ' l00O). ( i , '.1 : J r-..cc2053 (2000) t s . . : ( ' C 1 8 7 7( 2 0 0 0 ) ' ' ' t 2 . 1 2 8 7( 2 0 0 0 ) ' c \ . ,,/ 2. 2881(2000).
NHBoc
H2t Pd-c
:
trnu.v/^\12\COOMe
EtOAc
NHBoc
BnO=-,^r..,,,''.
COOMe
94%
I Catalytic reduction in methanol using decaboraneas the hydrogen source successfully saturates alkenes and alkynesr2 and converts nitroarenes to arylamines.r3Concurrent
le. i:-.20,280-281 in the r '- rcadily hYdrogenolYzed molecule a in ....h estersPresent \r and mixed c:- ' .luding carbamates
N-alkylation to afford ATNHCHRR' occurs when a carbonyl compound (RR,c:o) present.I4
.
C2Hal\,lecN
I
-q
Ho"'(
)
Y
o
Biaryls. Homocoupling of aryr harides has been effected by pd_C in an aqueous media (PEG-400,NaoH, H2o) under hydrogenr6or in air in the presenceof Zn and lgcrown-6.17The considerableimprovementin yield observedwith added crown ether is intriguing. Amidocarbonylation, A useful procedurefor the Pd-catalyzedreaction is available.rs
O ll
+ R"-cHo RAtlHR'
O co/pd_C
",.";; NMP
c t
HO_\ H2tpd-c
,
C e
c .-.(,ndary alcoholsis best accom-
l-,- : I'BS ether.''
n
:
97o/o
rh .,.- \electivity in hydrogenation r1'- -\\tem provides a means for the
a
,
Dehydrogenation. Under an ethylene atmosphere, allylic and benzylic alcohols undergo hydrogen transfer and are thereby transformed into ketones.t5
.irogenolysisthat is also assisted ', .rltcrhydrogenolysis of certain
98%
o
A
l
I,
is
P ;-'-r.'lrsis.l l.rrrylic estersis via the corre,r underhydrogenolysis el't'ected i!! e:
t
Trimethylsilyl ethers of Baylis-Hillmann adducts undergo syn-selective hydrogenation.ll
il
|
nAruAcooH I,
t(
Palladium(Il)
Enolsilylation triethylsilane
acetate
The conversion
of carbonyl
compounds
to silyl enol ethers with
in toluene at 100" is performed by Pd-C while adding an amine and halide
as cocatalysts.le
) J ' D-' >a -,
l-r- ti F 'l >--rl
ni
rGaunt,M.J., Boschetti,C.E., Yu, J., Spencer,J.B. TL 40, 1803 ( 1999). 2Papageorgiou, E.A., Gaunt,M.J., Yu, J.-Q.,Spencer,I.B. OL2,1049 (2000). 3Boutros,A., Legros,J.-Y.,Fiaud, J.-C TL 40,7329 (1999), aNarkunan, K., Ciufolini, M.A. S 673 (2000). sBanik, B.K., Barakat,K.J., Wagle,P.R.,Manhas,M.S., Bose,A.K. JOC 64,5746 (1999). 6Kumazawa, T., Akutsu, Y., Matsuba, S., Sato, S., Onodera, J. CR 320, 129 (1999). Tsajiki, H., Hattori, K., Hirota, K. CC 1041 (1999). 8Sajiki, H., Hattori, K., Hirota, K. CEJ 6,2200 (2000). vHattori,K., Sajiki, H., Hirota, K. TL 41,5711 (2000). r0Misiti,D.,Zappia, G., Delle Monache,G. S 873 (1999). rrMateus, C.R., Almeida, W.P.,Coelho, F. TL 41,2533 (2000). r2Bae,J.W.,Cho, Y.J.,Lee, S.H., Yoon, C.M. TL 41,175 (2000). r3lee, S.H., Park,Y.J.,Yoon, C.M. TL41,887 (2000). raBae,J.W.,Cho, Y.J.,Lee, S.H., Yoon, C.-O.M., Yoon, C.M. CC 1857(2000). rsHayashi,M., Yamada,K., Nakayama,S. S 1869 (1999);JCS(PI) 1501 (2000). roMukhopadhyay,S., Rothenberg,G., Wiener, H., Sasson,Y. T 55,14763 (1999). rTVenkatraman,S., Li, C.-J. TL 41,4831 (2000). lsBeller,M., Moradi, W.A., Eckert,M., Neumann,H. TL 40,4523 ,1'999D. relgarashi,M., Sugihara,Y., Fuchikami,T. TL40,'1ll (1999).
Complexation of pd with a bisimidarc coupling.3
Aromatic alkylation and Suzukr o properdesignof a catalytics\srem. o-alkylation.
,,,T\
(\_7 r F r * l l ) 1 . \1.,,
R //
(
ArB(oH .
\\
)-Ar=
(
R
Ar=ph,R=pr 95%
"il
Palladium-various supports. Semihydrogenation. Alkynes are hydrogenatedto (Z)-alkenes with Pd on pumice.l C-C Bond couplings. Different supported Pd catalysts have been tried. For example, Suzuki coupling based on Pd-thiourea resin2 and nanosize Pd on poly(Nvinylpynolidone),3 Heck reactions using Pd-CaCOj,a or Pd-SiO2.5 Colloidal Pd stabilized by tetraoctylammonium formate that is generatedin situ from simple palldium saltsis effectivein catalyzingSuzuki and Heck reactions(phosphine-freeconditions.l.6 Hydrogenolysis. Palladium nanoparticles show excellent activity for hydrogenolysis of benzylatedcarbohydratesthat are attachedto solid supports.T 'Gruttadauria, M., Noto,R.,Deganello, G.,Liotta,L.F.TL 40,2857(1999). 2Zhang,T.Y., Allen, M.J. rL 40,5813(1999). 3Li,Y.,Hong,X.M.,Collard,D.M.,El-Sayed, M.A. OL2,2385(2000). aBrunner, H., Le Cousturier deCourcy,N., Genet,I .-P.TL 40,4815( 1999). sZhao,F., Bhanage, B.M.,Shirai,M., Arai,M. CEJ6,843(2000). 6Reetz, M.T.,Westermann, E.ACIEE39,165(2000). TKanie,O., Grotenbreg, G., Wong,C.-H.ACIEE 39,4545(2000).
Palladium(Il) acetate. 13,232-233; 14, 248; 15, 245-247; 16,259-263; 17,255-259; 18, 274=277; 19, 248-251; 20,281-283 Coupling reactians. Microwave assiststhe Suzuki coupling in aqueous media.r A route to biaryl-2-carboxylic acids is via coupling of l-hydroxy-I,2-benziodoxo-3(ll1)-one.2
Other variationsof the biaryl sr nrhc arenediazoniumsalts.T Heck reactionswith arenediazonru \alts are more soluble in organic rolr.
1-butyrolactonesare successfuilyprepe rlazonium saltseor ArI.r0 The couplu rno other solvents)can be catalyzed hr moderate.rl Arylsilanols,I2 aryltributylstannarc
coupling partners.When a hypen.alenr coupling,an aryl iodide is left behindrh.
HSOt
"",N)r,t.-1'ffi"t", *\ \-t\-.,\Z
(
Palladium(Il) acetate
ethers with F -:rJ\ to silYl enol r:..: rdding an amine and halide
'q r 1000).
r r /t)C 9.5746(1999) ( :' .U0.129(1999).
3r5
complexation of Pd with a bisimidazol-2-ylideneunit is favorable to catalyzins the Suzuki coupling.r Aromatic alkylation and Suzuki or Heck coupling are combined in one operation by proper design of a catalytic system.a'sNorbornene acts as a platform for regioselective o-alkylation.
o_.ro.**##fdo] ti
V
(, ; i
r::
.
t:
.e 9 9 ) .
/R
I
n
,*t'Tti:
,,
.1
q^,ArB'H2 l++',.-Qr2] Ar=Ph,R=Pr 95%
r, ,/ -alkeneswith Pd on Pumice'' )c ,.,t.ilvsts have been tned' For i.'' .1nd nanosizePd on PolY(N(| ,,r Pd-Sio2.5 colloidal Pd c:-, :J in situ from simPlePalldium r - :.ho:phine-freeconditions)'6 )s :r.cllent activity for hYdroC ' ., ,lrd suPPorts'7 I -.'
-
lq99).
I Xl). r ,1999).
Other variationsof the biaryl synthesisinvolve K[ArBFr] and diaryliodoniumsalts6or arenediazoniumsalts.T Heck reactionswith arenediazoniumtrifluoroacetates8 are more efficientbecausethese salts are more soluble in organic solvents than the tetrafluoroborates. o-Benzylidene1-butyrolactonesare successfullypreparedfrom ct-methylene-1-butyrolactone and arenediazonium saltseor ArLr0 The coupling of cycloalkenes with ArI in water at 225" (no other solvents)can be catalyzedby pd(oAc)r-NaoAc alone, but yields are low to moderate.rl Arylsilanols,r2 aryltributylstannanes,r3 and arylantimony chloridesra are suitable coupling partners.when a hypervalentiodine heterocycleundergoesring opening upon coupling,an aryl iodide is left behind that can be further manipulated.15
HSOt
|6. 259-263;17,255-259; z-f. .()uPlingin aqueousmedia'' A lH)-one'r .l'. :',rr - 1.2-benziodoxo-3(
""'"YYYY""'* \
-
\..\-.\Z
cHo
Me2N Pd(OAc)2
Na2CO3 / Dl\.4F
90%
I
I,
) , n t
-
c t,
r) , I
316
Palladium(Il)
acetate
18 Ring formation is observedfrom reaction of aryl halides with alkynes.16 N t ' h R
I
I
.lll
fiao" ve.
I
I
Pd(OAc)zi KOAc + Dt\4F100'
Z\XOH
U\^_R
R
Carbonyl compounds as catalyst.2aA more cc oxidation.2sUnder such c<
cooEt
A i
l
t
P
COOMe
h
\z\, I l ' . l l l+ ..ri'\ tii: -T'11 >rl
--]vr tt
-
ri: {rlll
i.iir :l
i
l
t
YcooEt
P
|
A ll
Pd(OAc)2/ K2COr
I
cleaved (further transfornu
K2CO3- BuaNl
oztt,,.,%t,toz
h
Me
Dt\.4F100"
Triarylbismuthinesare decomposedto give biaryls in the presenceof Pd(OAc)2 at in the air.r" room temperature Reactions of alkynes. Hydroarylation,20carbonylation,2rand the formation of are some of the reactionsmediatedby Pd(OAc)r. While an a-substitutedacrylamides22 intramolecular version of the former completes a synthesis of coumarins and quin-
H
/-+ tQ" I \-f
R
olinones,the lattertwo incorporateCO group(s)from carbonmonoxide. H
a-f Y
, n - * r ,l l l # r n - i l / r n Ph "ffj::,
^'?o
d--f i
\.,/
l
l
lll
,;
pd(oAc)2 cFlcooH-cH-cr-
a),\I
R .
\
I
R' X=o,NH
Suzuki coupling un<J Pd(OAc)2also catalyzesrhc Carbonyl compounds an tin(II) chloride.2e M iscellan eous reac tiot as a result of the participarr
50-91%
A method for the preparation of isoindolo[2,]-a]indoles prescribes treatment of N-(o-iodoaryl)aldiminesand arylalkynes with Pd(OAc)2 and a base. The coupling is followedhy an annulationevent.21
-?w
Palladium0l)
acetate
317
, . ir t h a l k Y n e s . l 6l 8
*
OH
Pd(OAc)2
G'.--'n */'n
Na2C03 - LiCl Dt\,4F 100"
R=Ph 85%
-
-
-^.
Carbonyl compounds. Allylic alcohols are oxidized under ethylene with Pd(OAc), as catalyst.2aA more conventional hydrogen acceptor is molecular oxygen in such oxidation.2sUnder such conditions, cyclobutanols that are gem-vinylatedor arylated are cleaved (further transformationsare also possible).26 hlo
o
OH
1-H--
Pd(OAc)2 py
^v 2 t 4\^^^_. LvvEr PhN/lE
.,lron.lr and the formation of lr bY Pd(OAc)r'While an n. :Jrate<J quinr . . :lrc:is of coumarinsand ' , , n monoxide' r.,..
D
-
J
or,
"ooa,
E,t
PhN,4E
c,t) tt
H O H
I
Pd(OAc)2 py;
or,
h
"oor,
Suzuki coupling under carbon monoxide leads to diaryl ketones.2TLigandless Pd(OAc)2also catalyzesthe reactionof ATCOCI with NaBAro to afford ketones.2s Carbonyl compounds are regeneratedfrom hydrazonesby Pd-catalyzedreaction with tin(lI) chloride.2') Miscellaneousreactions. Cyclization accompaniesoxidation of an allenemoiety as a result of the paticipation of an internalnitrogennucleophile.r0 50-91%
^')
, rrlll()lesprescribestreatment of I and a base.The couPlingis !, ,\-
, { I
Pd(OAc)2 py;
PhMe
x:
D
J
/--$pn t-t-'f t l \
\.\
t
at ': thc Presenceof Pd(OAc)z
r
r]-
:
Ia
=W
,)
HN'
i.
Pd(OAc)2- LiBr Cu(OAc)2 K2CO3 MeCN
) \--(. t r ) Br +^ t 5
69%
318
Palladium(Il)acetate
Chromenes are formed by dehalogenative coupling of o-haloaryl ethers that bear a haloalkenesidechain.3r
OMe
|
z->/o-t)\.8' 11 tr
-,,^^-. ,,^,d- ,-(o\ tot'^"''-''l
I ll '-Pr2NEti DN'4F\-"\Z\OV" 5o'
ctr
MeO
I
61%
afford 1,3-transAllylic N-tosylcarbamates (from allylic alcohols and TsN{:O) decarboxylation, DMF, in Pd(OAc)2-LiBr with posed allylic N-tosylamines via ionization - J "
^*, -r'ul -.:rrl
.
,.1 ,
and substitution.32 Silyl esters are formed by oxidative functionalization of hydrosilanes with Pd(oAc), and carboxylic acids.rr Bisphosphinesare oxidized to the monooxides,3athus bidentate phosphorusligands of mixed oxidation statesare readily accessible.
Conjugate addition. T}r is catalyzed by Pd(OAc)1. Fr lidinones)that bear a 4-oxoalhl't
availableby a Pd-catalyzedrntrr R
I+*
04.
o
dl
ph2p.*r,
,;i
pph2
L rn
- NaoH Pd(oAc)1 ph2p-F-U''i'Ph2 BTCH2CH2BT
L rn
clcH2cH2cl
IN
Hydroarylation. Catalytic Ar-H bond activation is observedwith a complexed Pd speciesand the delivery of the aryl group to alkenesshowssome asymmetricinduction'ts activation by For heterocycles such as methylfuran, pyrroles, and indoles, Ar-H pd(OAc)2is adequatein their addition to 2-alkynoicestersin a rrans-fashion.16
Pd(oAc)z- -): Ar-H
+ R:cooa,
c'zctz
Ai
t"oor,
Many arenes are converted to carboxylic acids in good yields pressure of co under the influence of Pd(oAc), but without under atmospheric phosphine ligands. Potassium peroxysulfate and trifluoroacetic acid tue present in the carboxylation.sl
reaction media. Rearrangement-coupling.ls This effective synthetic process involving an alkene and allylic alcohol in juxtapositionis applicableto the synthesisof (+)-equilenin.Solvent determinesthe diastereoselectivity.
t
\
,NH'\
rs
'r:
\r
h,
rBlettner,C.G., Konig, W.A.. Srco rXia, M., Chen,Z. SC 30, 63 (2U rZhang,C., Trudell, M.L. TL 11.1 lCatellani, M., Moni, 8.. Minan. t 5Catellani,M., Cugini, F. f 55.65{ 6xia, M., Chen,Z. SC 29,2457 rl\ tDarses, Michaud, S., G., Gencr.J. EColas,C., Goeldner,M.E JOC ll. 'Brunner, H., Le Cousturier de Ccr "'Arcadi, A., Chiarini, M., Marirrlt "Gron, L.U., Tinsley,A.S. TL 4. = rrHirabayashi,K., Ando, J., Kas'ash rrHirabayashi,K., Ando, J.. Nishh HMatoba,K., Motofusa,S., Cho. C r5Liang,Y., Luo, S., Liu, C., \*'u. X. 'nQuan,L.G., Gevorgyan, V.. \'anp r r M a n d a lA , . B . , L e e ,G . - H . .L i u . . t ' [Larock, R.C., Doty, M.J., Han. X. reOhe,T., Tanaka,T., Kuroda. Il . ( roJia,C., Lu, W., Oyamada.J.. Krt (2000);Jia, C., Piao, D., Krtamun rrSakurai,Y., Sakaguchi,S., Ishl. t r:Ali, B.E., El-Ghanam,A., Fenouh :rRoesch,K.R., Larock, R.C. Ot l. rlHayashi, M., Yamada, K., Anhrr. :sNishimura, T., Onoue, T., Ohc. lL. roNishimura. T.. Ohe. K.. Uemura- !
PalladiumflI) acetate
r.-
1,-haloarylethers that bear a Pd(OAc)z
MeO HMPA- THF ctcH2cH2ct
OMe
27 100
73 0
61Yo afford l,3-trans:-.r f.N{:O) t-rBr in DMF, decarboxYlation.
A-
lu: : ,\l hydrosilaneswith Pd(OAc), tl-.-. ^rdcntatephosphorusligandsof
Conjugate addition. The addition of MerSiCN to enones derivatives of glycals3e is catalyzed by Pd(oAc)2. Five-membered azacycles (lactams, imidazolinones, oxazolidinones) that bear a 4-oxoalkylidene group adjacent to the nuclear nitrogen atom are readily availableby a Pd-catalyzedintramolecularaddition and conjugateaddition tandem.ao t
R
I a
X_VR
..4N ,NH'\ Ts )-, t1
t
, I
IS
R
'
I ,
J
n
.-:
'bpn"
\r
r, : :. ()hservedwith a complexedPd \: .\. \ome asymmetricinduction.ri j:r.: :ndoles. Ar-H activation b;c-'.:. ln a lrans-fashion.36
, '. -
R\
Ar
'cooet
: ..rrboxylic acids in good Yields n:: ...':r.!- of Pd(OAc)2 but without 'r::.. ,:,,eccticacid are present in the ir.::r-:r! processinvolving an alkene hr . .:rthesisof (+)-equilenin.Solvent
'Blettner,C.G., Konig, WA., Stenzel,W., Schotten,T. JOC 64,3885 (1999). 2xia, M., Chen,Z. SC 30. 63 (2000). 3zhang, C., Trudell, M.L. rL 41,595 (2000). aCatellani, M., Motti, E., Minari, M. CC 151.(2000). 5Catellani,M., Cugini, F. 255,6595 (1999). 6xia, M., Chen,Z. SC 29,245i (1999\. TDarses,S., Michaud, G., Genet,I.-P. EJOC 1875 (1999). 8Colas,C., Goeldner, M.E JOC 1357 (1999). 'Brunner, H., Le Cousturier de Courcy,N., Genet,J.-P.TL 40,4815 (1999). I0Arcadi,A., Chiarini, M., Marinelli, F., Berente,Z.,KollalL. OL2,69 (2000). " Gron, L.U., Tinsley,A.S. TL 40,227 (1999). r2Hirabayashi,K.,Ando,J.,Kawashima,J.,Nishihara,Y.,Mori,A.,Hiyama,T. BCSJ73,1409(2000). IrHirabayashi,K., Ando, J., Nishihara, Y., Mori, A., Hiyama, T. SLgg (19gg). raMatoba,K., Motofusa,S., Cho, C.S., Ohe, K., Uemura,S. JOMC 574,3 (1999). r5l-iang,Y., Luo, S., Liu, C., Wu, X., Ma, Y. 256, 296l (2000). r6Quan,L.G., Gevorgyan, V., Yamamoto, Y. JACS 121,3545 (lggg). rTMandal,A.B., Lee, G.-H., Liu, Y.-H., Peng,S.-M., Leung, M.-K. JOC 65,332 (2N0). rsl-arock,R.C., Doty, M.J., Han, X. JOC 64,8i.70 (1ggg). IeOhe,T., Tanaka,T., Kuroda, M., Cho, C.S., Ohe, K., Uemura,S. BCSJ 72,1851 (1999). :OJia,C., Lu, W., Oyamada, J., Kitamura, T., Matsuda, K., Irie, M., Fujiwara, y. JACS 122,7252 (2000); Jia, C., Piao, D., Kitamura, T., Fujiwara, Y. JOC 65,'1.516(2000); :rSakurai,Y., Sakaguchi, S., Ishii, Y. TL 40,1701 (1999). 22Ali, B.8., El-Ghanam, A., Fettouhi, M., Tijani, J. TL 41,5761 (2000). :3Roesch,K.R., Larock, R.C. Ot 1, 1551 (1999). raHayashi,M., Yamada,K., Arikita, O. 255, 8331 (1999). 2sNishimura,T., Onoue,T., Ohe, K., Uemura,S. JOC 64,6750 (lggg). r6Nishimura, T., Ohe, K., Uemura, S. JACS 121,2645 Ogg9i.
t
-
:
c t, ca t ,a I
Palladium(Il)
acetate-phase-transfer
catalysl
2?Xia, M., Chen,Z. JCR(S) 400 (1999). 2sBumagin,N.A., Korolev, D.N. fZ 40, 3057 (1999). 2eMino, T., Hirota, T., Fujita, N., Yamashita,M.S 2024 (1999). 3oJonasson, C., Karstens,W.F.J.,Hiemstra,H., Blickvall, l.E. TL 41,1619 (2000). 3rEdvardsen,K.R., Benneche,T., Tius, M.A,. JOC 65,3085 (2000). 32lei, A., Lu-X. OL2,2357 (2000). 33chauhan,M., Chauhan,B.PS., Boudjouk,P. OL2,1027 (2000). 3aGrushin,V.V../ACS121, 5831 (1999). 35Mikami,K., Hatano,M., Terada,M. CZ 55 (1999). i6lu, W, Jia, C., Kitamura, T., Fujiwara, Y. OL2,292'7 (2000). 37Lu,W., Yamaoka,Y., Taniguchi, Y., Kitamura, T., Takaki, K., Fujiwara, Y. JOMC 580,290 (1999). 38Nemoto,H., Yoshida, M., Fukumoto, K., Ihara, M. TL 40,9O'7(1999). 3eHayashi,M., Kawabata, H., Shimono, S., Kakehi, A. TL 41,2591 (2000). ml-ei, A., Lu,X.OL2,2699 (2W0).
Palladium(Il) acetate{cr 247-248; 16, 264-268: t7, Aryl coupling reacti contains Pd(OAc)1, KF. catalyst to date is the co which is effective to ccru mol%o)yet showing turnor in good yields.
Allylatinns. Allylauc presenceof Pd(OAc):_ph.I leading to bridged ring srr active methylenecomprrund
\ J '
--T-'lfl ,;
=! -!
Palladium(Il) acetate-phase-transfer catalyst.20, 284-286 Heck reaction Heck reaction of 2,5-dimethoxy-2,5-dihydrofuran leads to Barylbutenolides. It only requiresa reductionstepto furnish3-arylfurans.r
r^
.;l ..arI
h\6\
\z\, i *$t 'i
Pd(oAc)2-R4Nct
* M"o-/toAou" -A".J: -
>\ ->-, \
/
\oAo
,i 66% An aryl group can be introduced to a substituted B-posittion of an a,B-unsaturated ketone2 or other electron-deficient alkenesl by the Heck reaction in the presence of a phase-transfercatalyst. Deallylation.a Water-insoluble allyl substrates are cleaved by Pd(OAc)2 using water-soluble phosphine ligand and per(2,6-di-O-nethyl)-B-cyclodextrin. Unsymmetrical biaryls. Coupling of ArI with Ar'Br proceedswith good selectivity employing electron-deficient Ar'Br under specified conditions: A catalytic system composedof Pd(OAc)2,Bu+NBr,iPrrNEt in refluxingp-xylene.s A simple procedurefor Suzuki coupling involves heating the substrateswith Pd(OAc)1 and KsPOa in DMF. A beneficial additive is BuaNBr.6 When (EtS)2PdCl, is used. the quaternaryammonium salt is not required. rTaniguchi, T., Nagata,H., Kanada,R.M.,Kadota,K., Takeuchi,M., Ogasawara, K. H 52,67 (2000). 2xia,M., Chen,Z.SC30,l28l (2000). rGurtler,C., Buchwald,S.L. CEl 5, 3107(1999). 4Widehem, R., Lacroix,T., Bricout,H., Monflier,E. 5L722(2000). 5Hassan, J.,Hathroubi, C.,Gozzi,C.,Lemaire,M.TL4l,8791 (2000). 6Zim,D' Monteiro,A.L.,Dupont,J. TL 41,8199(2000).
L--o
Arylamines undergo .\.contains titanium tefai sop( the amino group is unhindcr Homoallyl alcohok. homoallylic alcoholsin rhc three-component condensa
moiety from allene and ant indium. A relayed processd intricacyof sucha reaclion
-$"ro.
:
Palladium(Il) acetate-tertiary phosphine
1s... j : . ' r ' { 1 . 1 6 1 9( 2 0 0 0 ) . -'rtt. F' !- -.,,,
Palladium(Il) acetatFtertiary phosphine. t3,91, 233-234; 14, 249, 250_253: lS, 247-248; 16, 264-268; 17, 259-269 ; 18, 277 -281; 19, 252-256; 20, 286-289 Aryl coupling reactions, A highly active catalytic system for Suzuki coupling contains Pd(oAc)2, KF, and di-r-butyl-2-biphenylphosphine,t but the most efficient catalyst to date is the combination of Pd(oAc)2 and bis(l-adamantyl)butylphosphine, which is effective to couple deactivated Arcl on very low pd loading (down to 0.001 molvo) yet showing turnover number in the 10,000-20,000 range.2products are obtained in good yields.
t: ,. rr r tjujrwara,Y. JOMC 580' 290 (1999)' +r . r1999). t'i {l :591 (2000).
Allylations. Allylation of enamineswith l-allylbenzotriazoles3is accomplishedin the presenceof Pd(OAc)2-Ph.P andZnBr2. The stepwisetwofold allylation of cycloalkanones leading to bridged ring systemsauses 2-methylene-1,3-propylenediacetate.Allylation of active methylenecompoundswith allylic alcohols is promoted by triethylborane.5
1
20. l.fl86
OAc Pd(oAc)2- Ph3P
\
leads to Brn.:: ,\\ -2.5-dihydrofuran t(':..:nl\h3-arylfurans.r
|\\/
/-v
MecN a0
I
\
rTf\-
l=\Z_/ rv
OAc
r:
tr
> ..-
. RINCI
lr,1F 80' -3-
66% ir-:,.r 1,i-posittionof an ct,B-unsaturated r:.- llc'ck reaction in the presenceof a lr:r-'. ilrc cleaved by Pd(OAc)2 using -r:. : :rr I r-P-cyclodextrin' r::: \r Br proceedswith good selectivit)'
--_ trn0). L at .-.rl r1000). t
)
t I
77%
Arylamines undergo N-allylation with allylic alcohols.6 The reaction system also contains titanium tetraisopropoxideand molecular sieves. Some dialkylation occurs when the amino group is unhindered. Homoallyl alcohols. Benzaldehyde reacts with various allylic alcohols to give homoallylic alcohols in the Pd-catalyzed reaction that is promoted by triethylborane.TA three-componentcondensationthat producesarylated homoallyl alcohols derives the allyl moiety from allene and aryl iodides.sThis Pd-catalyzedreaction is mediated by metallic indium. A relayed process that forms an isochromane systemeillustrates the power and intricacyof sucha reaction.
-S.no.-c-*l.ph
In - Pd(OAc)2
tq\,
c..: r.i conditions: A catalytic system | u . . . : :i.t - r y l e n e . 5 lr:. ::tating the substrateswith Pd(OAc); ; fi ...\Br.h When (EtS)2PdCl2is usedK. H 52'67 (2000)' lr. - .-hr.\1.,Ogasawara,
Ia
/--
Ph
l-\ (,
\:./
\F-l ' .
\ - v!
ph
-
+ :Q:
* H< ' o
OH
In - Pd(OAc)2
tq\, 52To
J
J
(
s
,.
a
Palladium(Il)acetatFtertiaryphosphine
322
Cyclizations.lnacatalyticprocess2.aryl-3-alkenylindolesalegenefatedfrom cyclization reactions of enynes and dienynes aldimines derived fiom o-alkynylanilines.t0 in the presenceof aryl iodidesr2to participate under reductive conditions (HCOOH)II or in a coupling Processare useful'
or\
o )---B o r rn - N
+r-ph+
-\_
\
|
pd(oAc)2 - ' B n - N>Y
v
HNJ
|
.&'
)-rn I
a)
\-12\
Ph3PiNIecN
(--("'* .yorf
Y*71o/o
ir.
x,i TI =[ 't:r
Cyclizationthataccompaniescouplingefficientlydeliversa.benzylidene-1-lactones " from homopropargylic chloroformates''
Triarylphosphines. .t bromides or triflates * ith Pt groupslTsuch as a ketoneart rE accessible.
oTf
R
;: -rll
NaBH4-Pd(OAc)2
>
x-,}_ -T,
}> o l -).\..R'
Ph,Pi rHF
\
u I o P h
r-- [l
J
'i ,rl leads to dihydropyran derivattves' An alkyne/5-hydroxy-2-pentynoic ester coupling ethyl 6-hydroxy-2-hexynoate proceedsin Formation of the homologoo' h"t"'otytle from Pd(OCOCFTI:''a two stages,the secondstageis promotedby
*
R--
/-P)^
HO
Pd(OAc)2 / PhH
OMe
J
o \ 'T
):\
r,/1
l-
'nnncr vvvLl
f( )+-P LYI: ON4e
Annulation,
tosylate tsenzyne rs probably generated from o-trimethylsilylphenyl
t1 "U::l-.1^n:*"nthrene is by CsF.Aunion of two benzvnemolecules1d.the f]
ffi"o
;**
;;;";
and or paiol'i,' tri-o-tolvlphosphine'
from A synthesis of 9-alkylidene-9H-fluorenones reiurangementstep.l6
displacements.'
lWolfe, J.P.,Singer,R.A.. \'en3 )Zapf, A., Ehrentraut,A.. Bcltre l K a t n t z k y .A . R . . H u a n g .1 - . .F r
R /-:-COOET
Allylic
liquid has been used for elfcr
ArI and alkynylarenes involves
4Buono,F., Tenaglia,A. JOC t 5Tamaru,Y., Horino, Y.. AraL. f'Yang,S.-C.,Hung, C.-$'. .Sl; TKimura,M., Tomizawa.T.. llc sAnwar, U., Grigg, R., Raspar "Anwar, U., Grigg, R.. Sndhan It)Takeda, A., Kamijo, S.. \'ama r l O h ,C . H . ,J u n g ,H . H . , K i m . J ! lrXie. X.. Lu. X. ZL 2(). 8J | 5 , I rrGrigg, R., Savic,V. CC l-1.91r rrTrost,B.M., Frontier,A.J. ./..1 r5Saito,S.,Tsuboya,N.. Chouru 8.TL40.7s33(1999).
Palladium(Il)
Lr:.'lrndoles are generatedfrom I :-.:-lr(rnsof enynesand dienynes n,- 'l rryl iodidesr2to participate
le
pd(oAc)2 i A .I, \Ao' t"t# \A/--,
. frY' \v I
8n-N
R Pd(OAc)2- Ph3P Bu4NCl - NaOAc Di,4F t00'
R=Ph 55%
71Yo
, .r! .:\ !'rs cr-benzylidene-^y-Iactones
phosphine
y'-1,.SiMe,
CFa
'.
acetatFtertiary
Triarylphosphines, ArPPh2 are synthesized by a Pd-catalyzed reaction of aryl bromidesor triflates with PhrP in DMF at 110'. Thus, phosphinescontaining functional groupsrTsuch as a ketoneare obtainedby this method.Useful fN-ligands are also readily r8 accessible.
=
PPh2
1f 1l 1f,
ID
,I ,, t
-
Pd(OAc)2 - Ph3P
' ^ - R ' - \Y-
i
Dt\.4F110'
, P h
7 687o
derivatives' ! -.:.:: tt) dihydropyran 't ^ :,Jroxy-2-hexynoateproceedsin
x i
;
I
l :: ::r r,-trimethylsilylphenyltosylate is hr .: \\ne to afford a Phenanthrene and an alkyne.l5 1-.:-:r.nc. involvesa n:' \rl and alkYnYlarenes
Allylic
displacements.t')
The Pd(OAc)z-Ph.rP-K2COr
catalyst system in an ionic
liquid has been used for effecting allylic displacements. r w o l f e ,J . P . S , ingerR , . A . , Y a n g , 8 . H . ,B u c h w a l d ,S . L . " / A C S1 2 1 , 9 5 5 0( 1 9 9 9 ) . 2Zapf A., Ehrentraut,A., Beller, M. ACIEE39,4l53 (2000). , rKatritzky, A.R., Huang,Z.,Fang,Y. JOC 64,'7625(1999). aBuono,F., Tenaglia,A. JOC 65,3869 (2000). sTamaru,Y., Horino, Y., A-raki,M., Tanaka,S., Kimura, M'TL4l,5705 (2000). 6Yang,S.-C.,Hung, C.-W. S 1747 (1999). TKimura.M., Tomizawa,T., Horino, Y, Tanaka,S., Tamaru,Y. TL 41,3627 (2000)sAnwar, U., Grigg, R., Rasparini,M., Savic,V, Sridharan,V. CC 645 (2000). eAnwar, U., Grigg, R., Sridharan,V CC 933 (2000). r()Takeda,A., Kamijo, S., Yamamoto, Y. "/ACS122,5662 (2000). l l O h , C . H . ,J u n g ,H . H . , K i m , J . S . ,C h o , S . W .A C I E E 3 9 , 7 5 2 ( 2 0 0 0 ) . r 2 X i e ,X . , L u , X . T L 4 0 , 8 4 1 5 ( 1 9 9 9 ) . rsGrigg,R., Savic,V CC 238 I (2000). laTrost. B.M., Frontier, A.J. JACS 122, 11127 (2OOO). rsSaito,S.,Tsuboya,N., Chounan,Y, Nogami, T., Yamamoto,Y., Radhakrishnan,K.V., Yoshikawa, E. TL 40.1533 (1999't.
r I
t ) t
Palladium(Il) acetate-tertiary phosphine-base 'oTian,C., Larock, R.C. OL2,3329 (2000). r?Kwong,F.Y, Chan, K.S. CC 1069 (2000). r8Kwong,F.Y.,Chan, K.S. OM 19,2058 (2000). reChen,W, Xu, L., Chatterton, C., Xiao, I. CC 1247 (1999).
A route to 2-aryl-2l'-u (o-halobenzyl)hydrazines
'-4r"^-"
Palladium(Il) acetate-tertiaryphosphine-base. 20, 289-292 Aryl coupling reactions. A new catalystfor Heck and Sonogashira couplingsand (1) thatcany allylic displacements is madefrom glassbeadscoatedwith triarylphosphine groupin eachbenzenering.r a dimethylguanidinyl
A new route to biarll-! o-arylation (and o,o'-diaryl zanilides must contain N-l
NHrCI
vte"n4 \
l( L
x-r-l l r
fll = : ll 't 1,, ;:
i-.|
ttl ..
,li
9*.ilt'
\t-p ls
\:,/
(1)
(
.o /X
+ Ph-
NHPh
By taking advantage of o-alkylation to precede a Heck reaction, ct-alkylidene cycloaromatic compounds are synthesizedin one step.2
I A(,. I
\."
ll
Etooc\ l( grJ
I
, /"ooa, Pd(oAc)z-(2-Fu)3P AA n o r b o r n e nC e s,COj l-
NrecN^
ll
A synthesisof arylamidrr Pd(OAc) or PdCl, in combr
I
\-\-, 90%o
Alkynylsilanes can be used to couple with aryl iodides, and the process is useful for the preparationof arylalkynylamides.' In promoting the Suzuki coupling of aryl chlorides and bromides with arylboronic acids,the Pd(OAc)z-(t-PrO)jPsystemis adequate.a Arylation. For N-arylation of lactams with ArBr, a catalytic system composed of Pd(OAc)2, l,l'-bis(diphenylphosphino)ferrocene, and r-BuONa has been employed.sFor arylationof amides,6and amines,T'8 Xantphos(L) appearsto be the ligand of chorce.
Ar-Br
+ P'r11
P-C bond formotiot alkylated with enol triflates accomplishingP-arylationof
Cyclizations. A grear studied, including those lead pyrroles.r5IntramolecularHc useful for the synthesisof crr
Palladium(Il)
acetatFtertiary
phosphine-base
A route to 2-aryl-2H-indazoles involves intramolecular N'-arvlation of N-arvl-N(o-halobenzyl)hydrazines.e
tY-if^N-\-/
). I .', l9l H:.r. .rnd Sonogashiracouplings and r: ..::h rriarylphosphine(1) that carry
\Ae.
aYo'"
Pd(OAc)2- dppf
F
-vz^"tzr |
t-BuONa/ PhN,1e 90"
NH'
|
N-{r
\.,\-1r'
\---l
zFOMe
51Yo
A new route to biaryl-2-carboxylic acid derivatives is found through regioselective o-arylation (and o,o'-diarylation)ro of benzanilides with ArBr or ArOTf. Reactive benzanilides must contain N-H.
\r \--l
rfl
,P 'NHph
+
Ph-OTf
cr.:- .r Heck reaction, a-alkylidene
pd(oAc)2- phrp + cs2co1/ DMF 11 0 "
J
Ph
Ph . l
( ,Y"
,1
. ( / Y.o
48To
"'cooEt
: . . l l l --
i l'
lll
a F
t
Ph
I
37To
, )a ra : O
A synthesisof arylamidinesrr from ArBr, t-butyl isonitrile, and amines is promoted by Pd(OAc)2 or PdCl2 in combination with dppf and CszCOr.
t t
It
a
\..,^\,.,90%
Ar-Br
+ R,2NH + -f*" I
r:..:-. rnd bromideswith arylboronic .\:ii:. .r catalytic system composedof a:..: - BuONa has been emPloYed'5For ofchoice' {'::-.::\ to be the ligand
Pd(oAc)' -dppr-'l-*...-**, -J Cs2COr/PhMe | 109'
| . .:.J.'.. and the processis useful for
Ar
P-C bond formation. Alkenyldiarylphosphines are formed when AI2PH are alkylated with enol triflates.r2 Cocatalysis by Pd(O) and Cu(I) species is effective for accomplishing P-arylation of ArP(H)Me-borane complexes.I3 Cyclizations. A great number of substrates designed for cyclization have been studied,including thoseleadingto l-sulfinylmethylene-2-methylenecycloalkanesra and to pyrroles.r5Intramolecular Heck reaction involving enol triflate and allylsilane moieties is useful for the synthesisof cyclic compounds.16
P.
osa-Tol (
F-
NHPh
-,
NHPh
I
h-l //
Pd(OAc)? - Ph3P
\-----
S=O
A o , c o 1 /N , t e c N
Tol
78Yo
rt a
326
Palladium(Il)acetatFtertiaryphosphine-base
t
N-Allylbenzotriazoles in which a remote halogen atom is also present in the a-position of the allyl group undergo stepwise substitution reactions with primary amines.rTIntramolecular allylic displacementof the benzotriazoleoccurring in the second stageis induced by a Pd-catalyst. Formation of a bridged ring skeleton by an intramolecular Heck reaction is the key featurein a synthesisofcvtisine.l8
(
l-\Tfo-\z\ l
l
l
P
\--.\/Nl
d
(
o A c ---1-1
)
Alkenylation. Alkenvlatrcn dienes(or enones).2a 2 -Alky lid en ecyclop enta no na
alkynyl)cyclobutanols proceedsu difficult to prepareby other merho
,
;* 6 r)/-^'"'f tl
\y''ppn,
g2Yo
i-Pr2NEt/ PhN,te
ri" - ^- 111 -r-
lll
=,ri ilt
Intramolecular addition to a carbonyl group (to afford l-indanols and l-tetralols) through activation of an o-bromoarene by Pd(oAc)r-phosphinere is chemoselectively superior to that relying on Br-Li exchange. However, different reaction patterns are revealed in the following,20'2rin which o-arylation of ketones22must be involved.
rPh
(
tl - l
+
o
.Y,, VBr
a* |
ll
\,,,^-o
)-Ph
)-Ph
100To
,,,......--)."^o
+
)
,t%cuo
\,,1LJ\.9SYo
ri\cuo 9r,.
+
Ph
a'n ........."......."-...._
I
fo
Pd(OAc)2- Ph3P K2CO3/ xylene
OH
rLeese,M.P, Williams, J.M.J. SL l6r rl-autens, M., Piguel,S. .4C1EEJ9. l0 'Koseki, Y., Omino, K., Anzai. S.. \q lZapf , A., Beller, M. CE"/ 6, l8_10r lfi 5shakespeare, W.C. TL40,20-15r 199 nYin, J . , B u c h w a l d ,S . L . O L 2 . I I 0 t , : tHarris, M.C., Geis, O., Buch*.ald_S I "Guari, Y., van Es, D.S., Reek.J.\.H . eSong, J.J.,Yee,N.K. OL 2, 519 r2U\ I'JKametani, Y., Satoh,T., Miura. Il . \ 'rSaluste, C.G., Whitby, R.J., Furber.V rrGilbertson, S.R., Fu,2., Srarker.G \l 'Al-Masum, M . . L i v i n g h o u s.ei r t l 'uSegorbe, M.M., Adrio, J., Carrercm.J r5Grigg,R., Savic, V. CC 873 (20m, loTietze,L.F., Modi, A. EJOC 1959, _rO rTKatritzky, A.R., Yao, J., yang. B. ./r)C ' " C o e ,J . W . OL2,4205 (zOC{. r"Quan,L.G., Lamrani, M., yamanrxo. r0Terao,Y., Satoh, T., Miura, M.. \onrr rrTerao,Y, Satoh,T., Miura, M.. .\onr IFox, J.M., Huang, X., Chieffi. A.. grrt :rRousset, S., Abarbri, M., Thrbonncr.J :rValin, K.S.A., Larhed,M., Johans,.r,o rsl-arock,R.C., Reddy,C.K. OL 2. _l.r:5 Palladium(Il)
Ph
acetatFtertiary.
Thiocarbonylation.
pL
Extensrm
thiol to 1,3-dienes produces g.f-unsi
72Yo
and there is further deviation of rert
Sequentialstille coupling and cyclization to give ct-pyronesis readily achieved.2l
*J^too' I
*
snBu3
n'AcvrR"
2'\.. | l l l \AsH
"YYo pd(oAc)2-ph3p
-".*;ffi Dt\rF 2s"
*'\o t_ R,,
| + )
Palladium(Il)
€r. .:t,rnl is also Present in the b. .'..t',,1 reactionswith primary n., :.r.Iroleoccuring in the second n. .-.ular Heck reaction is the keY
acetatetertiary
phosphine+arbon
monoxide
Alkenylation. Alkenylation ofenol ethers at the a-position furnishes 2-alkoxy-1,3dienes(or enones).24 2-Alkylidenecyclopentanones.2s Coupling-induced ring expansion of 1-(lalkynyl)cyclobutanols proceedsin moderate yields. Some of theseproducts are relatively difficult to prepareby other methods.
60%
52% r :: ,rJ l-indanols and l-tetralols) ,. ;'1,''phinereis chemoselectively rr:: Jrtterent reaction patterns are \,.: :rl.ll mustbe involvec.
lLeese,M.P, Williams, J.M.J.SL 1645 (1999). 2l-autens,M., Piguel,S. ACIEE 39,1045 (2000). sKoseki,Y., Omino, K., Anzai, S., Nagasaka,T. TL 41,2377 (2000). aZapf A., Beller, M. CEl 6, 1830 (2000). , 5Shakespeare,W.C. TL 40,2035 (1999). 6 Y i n .J . . B u c h w a l d . S . L .O L 2 . 1 1 0 1 ( 2 0 0 0 ) . THanis,M.C., Geis, O., Buchwald, S.L. JOC 64,6019 (1999). 8Guari,Y., van Es, D.S., Reek,J.N.H., Kamer, PC.J., van Leeuwen,P.W.N.M.TL 40,3789 (I999t. eSong,J.J.,Yee, N.K. OL2,519 (2000). r{}Kametani, Y, Satoh,T., Miura, M., Nomura, M. TL 41,2655 (2000). ll Saluste,C.G., Whitby, R.J.,Furber,M. ACIEE 39,4156 (2000). r2Gilbertson,S.R., Fu, 2., Starkey,G.W. TL 40,8509 (1999) II Al-Masum, M., Livinghouse,T. TL 40, 7'l3l (1999). 'oSegorbe,M.M., Adrio, J., Carretero,I.C. TL 41, 1983 (2000). rscrigg, R., Savic,V. CC 873 (2000). 'nTietze,L.F., Modi, A. EJOC 1959(2000). rTKatritzky,A.R., Yao, J., Yang,B. JOC g,6066 (1999). 'nCoe,J.W. OL2,4205 (2000). reQuan,L.G., Lamrani, M., Yamamoto, Y. JACS 122,4827 (2000). 2oTerao, Y., Satoh,T., Miura, M., Nomura, M. 256, 1315 (2000). rlTerao, Y, Satoh,T., Miura, M., Nomura, M. BCSJ 72, 2345 (1999). 22Fox,J.M., Huang, X., Chieffi, A., Buchwald, S.L. JACS 122, 1360 (2000). rrRousset,S., Abarbri, M., Thibonnet,J., Duchene,A., Panain, J.-L. CC 1987 (2000). rlvalin, K.S.A., Larhed,M., Johansson,K., Hallberg,A. JOC 65,453'7(2000). 25larock,R.C., Reddy,C.K. OL2,3325 Q00O). Palladium(Il)
acetate-tertiary
Thiocarbonylation.
phosphinFcarbon
monoxide,
20, 292
Extension of the method of carbonylation
in the presence of a
thiol to 1,3-dienes produces p,^y-unsaturated thioesters.r Enynes fumish branched products2 72o/o f r:
and there is further deviation of reaction pattern by using o-iodothiophenol
:',.' is readilY achieved'23
*YYo
*'Yo -R'
Z-'rlt
11
\A.".j(
Pd(OAc)2- dppf i-Pr2NEt- CO PhH 100"
in the reaction.r
I I
i )
I , -
t , a
= )
,t
! r a a 1 -
328
Palladium(Il) acetylacetonate-2,6-xylylisocyanide
Heterocycles. 5-Vinyloxazolidin-2-ones expel carbon dioxide and then incorporate co to form dihydropyridones.a 3.4-cycloindoles are accessible from peri-nitro l-methylenetetralin and analoguesby a reductive cyclization process.sInterestingly, the simplest way to prepare the substratesis by an intramolecular Heck reaction.
o
,o //
HN-1
t
-T')
Pd(OAc)2- Ph3P
o
\,."v | \-
Palladium(Il) chloride. 13. l_r 257-258:20.293-394
Coupling reactions. A o PhoPBr intercalated in moo bis(trimethylstannyl)alkenesr I with retention of configuratroo
equiv of the coupling reagenrs
co / EtoH
)....\z
Ph-,
87Yo
-TF_-)l, *
utt ttl
jtr
r; r l l
r"^
r
/14'
\4n"".
^-'t
rn
Pd(OAc)2 - (o-Tol)3P
\A*o,
SnMe:
/X\
A^ \Ani"
Pd(OAc)z- dppp
co/DMF 120.
V*o,
X=O,NAc
I
Coupling of organoshnnarx affordsketones.3Either pdCl. cr Arylation of salicylaldcl salicylaldehydesand dianliod
samereaction had been reahzed
rXiao,W.-J.,Vasapollo, G.,Alper,H. JOC 65,4138(2000). 2xiao,W.-J.,Vasapollo, G.,Alper,H. JOC 65,2080(2000). rxiao, W.-J.,Alper,H. JOC 64,9646(t999). 4Knight,J.G.,Ainge,S.W.,Harm,A.M., Harwood,S.J.,Maughan, H.I.,Armour,D.R.,Hollinshead, D.M., Jaxa-Charniec, A.A. JACS122,2944(2000). sSiiderberg, B., Rector,S.R.,O'Neil,S.N.fZ 40, 3657,1ggg). Palladium(II) acetylacetonate-2,6-xylyl isocyanide. Silaboration,t Regioselective silaboration of monosubstitutedallenes at the internal double bond is observedwith this catalyst system. However, perfluoroalkylallenes show a different reaction profile.
^-/
R
R
I
Si_Ph
:UJ I
o.
d
l
B-Si-Ph
I
I
l
I O
)'{
O
'Suginome, M., Ohmori, Y., Ito, Y SL 1567 (1999\
r-Si-Ph
|
'CHC6F13
[' ry"'" OH
Deallylation.s Allyl anl o is the catalyst.Under such cond hydestakesplace.
Halosilanes.6 Hydrosrlarr suchas CCla and CHrBr, in the 1 Hydrogenation.T The don subjecting it to PdCl, in HCOOF reducesbenzoylformicacid ro m
rVarma, R.S.,Naicker,K.P. Lre.cn.I 2Kang,S.-K.,Lee,Y-T., Lee.S -ll I rKang,S.-K.,Lee,S.-W., Ryu.H -C aXia,M., Chen,Z.-C. SC30.5.rl r_. sFranco,D., Panyella,D., Rocanrrz 5685(r999). 6Ferreri,C., Constantino, C.. Rorrro TArterbum, J.8.,Pannala, M.. Gonzr
Palladium0D chloride
[. -.::htxl dioxide and then incorporate I . - .rrc accessible from peri-nitro i . . -.:/rtion process.5Interestingly,the |3::: ..'eular Heck reaction.
329
Palladium(Il) chloride. 13, 234-235 ; 15, 248-249; 16, 268-269 ; 18, 282; 19, 257-258:20,293-394 Coupling reactions. A new catalyst for the Heck reaction consists of PdCl2 and PhaPBr intercalated in montmorillonite Kl0 clay.r Stille coupling of (Z)-1,2bis(trimethylstannyl)alkeneswith hypervalent iodonium salts takes place initially at C-1 with retentionof configuration.2Replacementof both stannyl groups is completewith 2 equiv of the couplingreagents.
Ph
SnMee ,
:r(oAc)2-dppp
\
f-)
"-o*-r** an \"^-NH
{C
ll
pdcrr -
']il"J' -snM". -.-::*
Ph
Ph
SnMea ,
-------*
ll
- pn
y ll
Ph
- Ph
Coupling of organostannanesand organotellurium chlorides under a CO atmosphere affords ketones.i Either PdCl2 or CuI is used as catalyst. Arylation of salicylaldehydes.a o-Hydroxybenzophenones are obtained when salicylaldehydes and diaryliodonium salts are brought together with PdClr-LiCl. This samereaction had been realized before usine ArI instead of the iodonium salts.
I I
) a
a a l l
OH I
l l
rY \2
t . " '
o H o
cHo
f^, l\r,. \
/ r ' B r
Pdct2- Licl
du" 89%
ildr. rt : ::,rrubstitutedallenesat the intemal show a r li .rlrer, perfluoroalkylallenes
R
I
Si-Ph
Deallylation.s Allyl aryl ethers suffer cleavageelectrochemically. PdCl2-bipyridine is the catalyst.Under such conditions O C allyl transferwithin 2-allyloxybenzaldehydestakesplace. Halosilanes.6 Hydrosilanes are converted to halosilanes in halocarbon solvents such as CClo and CH2Br2in the presenceof catalytic amounts of PdCl2. Hydrogenation T The double bond of cinnamic acid derivatives is saturated by subjecting it to PdCl2 in HCOOH in an alkaline medium. This transfer hydrogenation also reducesbenzoylformic acid to mandelic acid in 80Vayield.
O ,b-\
O
/
7-Si-Ph l
|
'CHCc Frg
rVarma, R.S.,Naicker,K.P, Liesen,P.J.TL40,20750999). zKang,S.-K.,Lee,Y.-T.,Lee,S.-H.TL 40,3513(1999). rKang,S.-K.,Lee,S.-W.,Ryu,H.-C.CC 2117(1999). aXia.M.. Chen.Z.-C.SC30.531(2000). sFranco, D., Panyella, D., Rocamora, M., Gomez,M., Clinet,J.C.,Muller,G., Dunach,E. TL 40, s685(1999). 6Ferreri,C., Constantino, C., Romeo,R., Chatgilialoglu,C. TL 40, 1197(1999). TArterburn, J.B.,Pannala, M., Gonzalez, A.M., Chamberlin,R.M. ?|L41, 7847(2000).
J
i ,
a
Palladium(II) chloride-+oppcr(Il)
chloride-oxygen
Palladium(Il) chloride-copper(Il) chloridecarbon monox ide. 20, 294 Carbonylation By changing reaction conditions, l-alkynes are converted to either B-chloro-ct,B-unsaturatedestersror 2-substituteddialkyl maleates.2 PdCl2- CuCl2
PhYcooEr \cooEt
NaOAc / PhH (R = Et)
Ph
3,3-Dimethoxyprop:rnorc oxidation with oxygen-merh dioxide is useful.3
rDuan,H.D.,Gore,J.,Vatele. -t J ' White,J.D.,Hong, J.,RobarycL rJia,L., Jiang,H., Li, J. CC 9t5 r
+co+RoH lll
tnY"' (R = Nre)
\cooM"
Palladium(Il) chloride
alcohols arising therefrom car can further react with guanrdu
Propargylic acetatesform B-alkoxy-cr,B-unsaturatedesters3when acetals are added to the carbonylation media. cleavage of cycloalkanones. Diesters are the major products. The cleavage preferentially occurs at the less highly substitutedC-{ bond.
..\
t t l a<
pdc,2.cuc,z a<
(,_,F" ;;;il
L#fiy"
.
a1",
(-"oo'"
(88 : 12)
o^n .\"
78%
\.,\l
lLi, J., Jiang,H., Feng, A., Jia, L. JOC 64,5984 (1999). : L i . J . . J i a n g .H . . J i a . L. SC29. J733( t999). rOkumoto, H., Nishihara, S., Nakagawa,H., Suzuki,A. 5L217 (2OOO). aHamed,O., El-Qisairi, A., Henry p.M. TL 41,3021 (2000).
Palladium(Il) chloride
CO i MeOH
The I -alkyne-acetoneaddrrc reaction conditions (e.g., presco
fu.
PdCl2- Cucl2
TIPSO -COOMe
oH
331
Palladium(tr) chloride-copper(I) iodide-triphenylphosphine
rtxrn monoxide,20r294 !:. :.-. l-alkynes are convertedto either r:..'.r.rI maleates.2 Ph-_ cooEt ll
ll -cooEt
].
PhYcl
-
.'
\"oo""
esters are subjected to
esters are generated when acrylic
3,3-Dimethoxypropanoic oxidation
with oxygen-methanol.
A reaction medium
composing
carbon
supercritical
dioxide is useful.3 rDuan, H.D., Gore, J., Vatele, J.-M. fL 40, 6'165(1999). 2white, J.D., Hong, J., Robarge, L.A. TL 40, 1463 (1999). 3Jia,L., Jiang,H., Li, J. CC985 (1999).
Palladium(Il) chloride
lI-:.,:rJ cstersrwhen acetalsare addedto
o tl
xr rhc major products. The cleavage d t {- bond.
,\
a ) +
\
-l. -O,. I
oH
9Br
I
l l l
--)r
(Ph3P)2Pdclz =......_ Cul - Et3N
rHF ^
,
I
Yo' o
, , f,
o
ozN.-Z\
)l','e
12\
38
78%
o'*Y).\'n. \.,\l
\ ..
oH
t t l
t'*;4*t
| r/\
l1,,S
"
{Ph.P},Pdcr,
VYY
;
*Y*
o
I
cul - EtlN
trr
Ph
?e l - /
r1000). 57Yo
nrgrn. lE,283; 19' 261-262;20,294 svnthesisfrom l-trimethylsilylr.'r: rr r.. -.rrhonylamino derivatives give the rtt- - . of substitutedtetrahydropyransis
The l-alkyne-acetone adductscan be used instead ofthe alkynes in the coupling, when reaction conditions (e.g., presenceof NaOH) are conducive to their decompositionin situ.r MeO
MeO
(Ph3P)2PdCt2 + Cul - (Et3NPh)Cl NaOH/ H2O
-
PSO
100.
t 4
Palladium(Il) chloride-tertiary phosphine 'Miiller, T.J.J.,Ansorge, M., Aktah,D. ACIEE 39, 1253 e}OOt. 2Miillet T.J.J., Braun, R., Ansorge, M. OL 2, lg 6'l (zcf/Oi). 3choi, .-K., Tomita, I., Endo, T. CL 1253 flggg).
Ketones. 2-Alk1.noo l-alkynylstibines and acr l Generation of the cot surprising.
Palladium(Il) chloride-tertiary phosphine . 19, 26L; ZO,295-2gg coupling rcactions. with a ligand based on gluconamide in which a 4(diphenylphosphino)benzyl group is attached to the nitrogen atom, the Suzuki coupling can be carried out in water.rln the synthesis ofalkenylarenes by this coupling method, it is not necessaryto employ alkenyl triflates as the correspondingmesylates,tosylates, and phosphatesappearto be adequate.2 The Heck reaction of allenyl carbinols under carbon dioxide leadsto cvclic carbonates.3
Ph
1-
lll;
<:ii --:l J a
// r . C \ / / --T-HO
. \ _
(Ph3P)2PdCt2
+ Ph-l
+
co2- K2co3
N,leCONMe2100.
-il\ r o..,/o tl
o
t;,'i :_ 11
1,4-Diol monoacetale beenusedin a synthesisof
B-(2-Alkenyl)pinacolatoboranesare now readily preparedfrom bis(pinacolato)diboron and l-alkenyl halides or triflates.a Closure of the unsaturatedmacrocycle representing access to a potential precursor of phomactin D by an intramolecular Suzuki coupling5 is remarkable,despitelow yielding of this step at the presentstageof development.
- Ph3As (dpp0PdCl2
(
N-Arylamines.t(t .{D when the catalyst is suppoo reaction by filtration. Hydrostannylatiott a-stannylated styrenesn tx the p-position or o-substrtu
CS2CO3/H2O-DMF
a,; Telomerization The Pd-catalyzed head-to-head telomerization of isoDrene with amines provides 3,6-dimethyl-2,7 -octadienylamines.6
78To
rUeda,M., Nishimura, M_. \t 2Huffman, M.A., Yasuda.\. j 3Uemura, K., Shiraishi. D.. \< 4Takahashi,K., Takagi, J.. lslu sKallan,N.C., Halcomb. R.L. 6Maddock,S.M., Finn. M.G (
Palladium(Il) chloride-tertiary phosphine
Ketones. 2-Alkynones can be prepared from Pd-catalyzed reaction between -alkynylstibines and acyl chlorides.? | Generation of the cobalt complexes of 4,5-didehydro-2,3-benzotroponessis rather surprising. O .l " : - 1 9 8 Co(CO)4dppm
r:.rconamide in which a 4tr, :r'n lltom, the Suzuki couPling uc:r.'- h) this coupling method' it ig. :.irng mesylates,tosYlates,and
oppm; (PhsP)zPdCl: EI2NH/ DMF 80'
a\/\ l i l o
h. r..ir'L-adsto cyclic carbonates.3
Ph
, rL_-
>
.'
-+-< i
t
n
=-/
1,4-Diol monoacetatesundergo Pd-catalyzed elimination of HOAc. This method has beenusedin a synthesisof (-)-shikimic acid.'
,,
\
o'.,1o l
(Ph3P)2PdCt2
n
HCOONH4 IVeCNA
rcat
I
- v Y
,
t ,
o
4.i:.1 lrom bis(pinacolato)diboron s:r..:.rtc'dmacrocyclerepresenting Suzuki couplings n .:.:r.rnrolecular N :.: .trse of develoPment.
I
a
80% N-Arylamines,ttr Arylation of secondaryamines in good regioselectivity is observed when the catalyst is supportedon NaY zeolite. Such catalystsare easily separatedafter the reaction by filtration. Hydrostannylation.tt Regiochemical syn-addition of BujSnH to arylalkynes affords ct-stannylatedstyreneswhen the aromatic ring contains an electron-withdrawing group in the p-position or o-substituentof any electronic nature.
F
: r.':
(Ph3P)2PdCt2 Bu3SnH/ THF
( \{ R=H
R=Br
71Yo
*\
/f
R
,'merization of isoPrene with
r-,-----\.,"t-*r,,
// rH. 'snBr.
38 '. 100 :
rUeda,M., Nishimura,M., Miyaura, N. Sf 856 (2000). 2Huffman,M.A., Yasuda,N. SL 471 (1999). rUemura, K., Shiraishi,D., Noziri, M., Inoue, Y. BCSJ 72, 1063 (1999). aTakahashi,K., Takagi, J., Ishiyama, T., Miyaura, N. CL 126 (2000). sKallan,N.C., Halcomb,R.L. OL2,2687 (2000). 6Maddock, S.M., Finn, M.G. OM 19,2684 (2O0O).
oz
0
7J-SnBuz
, , , , ,-)
7 t n-t ( -
Palladium(tr) chloride-triphenylphosphine-carbon monoxide TKakusawa,N., Yamaguchi, K., Kurita, J., Tsuchiya, T. TL 41, 4143 e}ACii. slwasawa, N., Satoh, H. JACS l2l,':.95t (lggg). eYoshida,N., Ogasawara,K. OL2, 146l (2OOO). 'ODjakovitch, L., Wagner, M., Kohler, K. JOMC 592,225 (lg9g). rrLiron, F., Le Garrec, P.,Alarni, M. 5L246 (1999).
Thiocarbamates,6 The Pd-catalysisavoids using pho Aromatic aldehydes.- | with this catalytic system urxl
Palladium(Il) chloridetriphenylphosphinmarbon monoxide.20, 298-299 Lactams. Dependingon the nature of the imines and their reaction partners, Iactamsarisingfrom the Pd-catalyzed reactionundercarbonmonoxidevary.r.2
3-Alkenamides.E Thesc under the carbonylation reaL-
*
4'-'.o-oet r.! o
H:N F(
(i ' nl
3 -I-
\r.\,-N
Ph..,
(Ph3P)2Pdcr2 +
clvPh ;;,.^,* MecN 1oo"
!1,
4g%
<: - -l: 1i ,,
,r-\
f.u
I:i
,sPh
---,,,^...-il-\.o
fl:* \ J \
\
(Ph3P)2PdCr2
)
|
cl
co/Et3N
\ ,AO
rCho, C.S., Jiang,L.H., Shim. S C :cho, c.s., w u , X . , J i a n g .L . H S rBeller, M., Eckert, M.. Moradr. I 4Miao, H., Yang,Z. OL2. l':'65,: iLiao, 8., Negishi, E.-1.It 52. l:{ bJones,WD., Reynolds,K.A.. Sp TCarelli, I., Chiarotto,I., Cacchr.S ELoh,T.-P, Cao, G.-Q., yin.Z TL
MeCN 1oo
Palladium(Il)
chloridetertir
Cyclopropanes.
- Itr]ri
Couphn
halides, for example, benzllx
92%
-'l
Heterocycles. Many different heterocycles are synthesized via a carbonylation process: hydantoins from aldehydes and urea,3 flavones from ethynylarenes and oiodophenol acetates,aand ct-substitutedct,B-unsaturatedlactonesfrom iodoalkenols.5
. tll aY' YoR" in
- dppp (Ph3P)2PdC12 co/EI2NH,DBU thiourea 40'
NHz
* H,N\
,,-..-,2\l-B(oxr:
IChen,H., Deng,M.-2. JCS:p t , ll rChen,H., Deng,M.-2. IOC 6:\.u rChen,H., Deng,M.-2. OL 2. t6!9
zJ$oI"n
Palladium(Il) hydroxide-cert Hydrogenolysis.t N'..\"-l Removal of the :CHNRI grou
92To
(---r!crc
propanes.
t"oJrYn
(Ph3P)2PdB12
CO / LiBr H2SO4- HC(OE03 '100"
\/ 9lYo
Palladium(Il) hydroxide-carbon
|t
Thiocarbamates.6 The carbonylative condensation of amines and thiols by Pd-catalysisavoids using phosgene. Aromatic aldehydes.l Electrochemical deiodoformylation of ArI is accomplished with this catalytic system under carbon monoxide and in the presenceof formic acid.
ilri lrxxl).
3-Alkenami.des,s These amides are prepared from ally1 carbonates and amines under the carbonylation reaction conditions. pn(f \ide. 20,298-299 t'. .,1d their reaction partners, t : :ntrnoxidevary.l'2
*
*oyo=t
- CO (dppp)PdCl2
,,*lcooMe
i-Pr2NEt/ DMF
,=--L-lcooMe H
HCI 52% Ph .Ph \----r' r l -.-,---^..--. N\O 48%
rCho,C.S.,Jiang,L.H.,Shim,S.C.SC 29,2695(1999). 2cho,C.S.,Wu,X., Jiang,L.H.,Shim,S.C.,Kim, H.R"/HC36, 297(1999). 3Beller, M., Eckert,M., Moradi,W.A.,Neumann, H ACIEE38,1455(1999). 4Miao,H., Yang,Z.OLz, 1'765 (2000). 5l-iao,B., Negishi,E.-1.H 52,l24l (2000). 6Jones, W.D.,Reynolds, K.A.,Sperry,C.K.,Lachicotte,R.J. OM 19, 1661(2000). TCarelli, I., Chiarotto, I., Cacchi,S.,Pace,P.,Amatore,C.,Jutand, A., Meyer,G EJOCl47l (1999). "Loh,T.-P.,Cao,G.-Q.,Yin,Z. TL 40,2649(1999).
I \ 92o/o
(,-:':r.\lzed via a carbonylation xr. Ir()tn ethYnYlarenesand ol:. ,DCsliom iodoalkenols.s
Palladium(Il) chloride-tertiary phosphine+ilver(I) oxide. Cyclopropanes. Coupling of cyclopropylboronic acids with various activated halides, for example, benzylic,rallylic,2 and acyl halides,3leads to substitutedcyclopropanes.
.,.--r,,.t
-Zf-
\
B(OH)2 .
cl
Ph
Y o
(dppf)PdCl, Ag2O - K2CO3
tl 'o^Ph
PhN.4e 80"
7$Yo
Palladium(Il)
hydroxide--carbon.
19, 262: 20, 299-300
Hydrogenolysis,t N',N'-Dialkylformamidines serve as protected primary Removal of the :CHNR2 group is readily achieved by hydrogenolysis. U
: ..
\
A '--J
utl n I HN-\o 90%
""o-:,N!
NMe2
n2
.....".........* Pd(oH)2- c I-BUOH- H2O
tueorl.ruuz v 98%
t
ti , , i o
it G -
_Qfrn
lChen, H., Deng, M.-2. JCS(Pl) 1609 (2000). 2Chen,H., Deng, M.-2. JOC 65,4444 (2000). rChen, H., Deng, M.-2. OL2, 1649(2000).
c ^)
, , , a
N-
(
;
I
amines
Palladium(Il)
iodidethiourea
N'Methylatian 2 Monoalkyl amino acids are further methylated on hydrogenation using formaldehyde as the carbon donor. IVincent,S.,Mioskowski, C.,Lebeau, L. JOCg,9gl (lggg). 2Song, Y.,Sercel, A.D.,Johnson, D.R.,Colbry,N.L.,Sun,K.L., Roth,B.D. TL4I,8225 (2000\.
Palladium(Il) iodide-potassium iodide. Heterocyclizations. Cyclization of 5-hydroxylated 3-en-l-ynes leads to furans.r The analogous thiols afford thiophenes.2In methanol and under a carbon monoxide atmosphere(CO/air: 9:l) 5-hydroxy-l-alkynes are transformed into 2(E)-(methoxycarbonyl)methylenetetrahydrofurans.3
I l o H
H., yang.L
Pentamethylcyclopentr
AAol reaction.t Tl are active in promounl cyanoacetlcesters.
Pdt2- Kl + C O +
-\.--S
'Nan, Y., Miao,
rMurahashi, S.-I.,Take.K.. i
N4eOH
COOMe oxidative cyclocarbonylationof 2-amino alcoholsis achieved.aA convenientsynthesis of oxaolidin-2-onesis therebydeveloped. substituted maleic anhydri.des,s The catalyzed formation of butenolides from alkynes and co is changed to maleic anhydridesby adding carbon dioxide in the system.
Pdt2- Kl
.'o l||
Aziri.dination.l Buh cis-aziridine derivatir.es
-,Y
R'\r1l l
ll .o
|;;;;; I
R
3,3-Pentamethylenedieri
I
p H2O- dioxane coz
o
o
l l \.1 i l o
rHori,K., Sugihara, H.. lro.l'
Y
'Gabriele,B., Salerno,G., Lauria, E. JOC 64,7687 (1999). rGabriele,B., Salerno,G., Fazio, A. OL2,35l (2000\. rcabriele, B., Salerno, G., de Pascali, F., Costa, M., Chiusoli, G.p. JOMC Sg3l1g4,4Og e0O0\. rGabriele,B., Salemo,G., Brindisi, D., Costa,M., Chiusoli, G.P.OL2,625 (2000). 5Gabriele,B., Salemo,G., Costa,M., Chiusoli. G.P.CC 1381 (1999).
1,2,21616-P entamethyl pi g Base.t Hindered seo amine as basecan avoid re
QOoMe PalladiumflI)
iodide-thiourea.
Benzo[b]furan-3-carborylic
esters,t
Cyclization and alkoxycarbonylation
when 2-alkynylphenols are exposed to Pdl2-thiourea{Bra
under co
Cs2CO1. Carbon tetrabromide serves as the reoxidant of Pd(0) species.
is observed
and in the presence of
!,,NH
I
COOMe
+ Ts
-Pentamethylpiperidine I Q,,2,6,6
h;::.. : niethYlatedon hydrogenation
COOMe
4
Pdt2- cs(NH2)2
.+
+CO
CBra- CS2CO3
fa
(:
:r 'rh.B.D.rL4l'8225 (2000)'
N,teOH
2>A
R; ll )-n' \.,/-o 79-85o/o
il:rr.: .1-en-l-ynesleads to furans.l u-. .rnd under a carbon monoxide B r:.:n'li)rmed into 2(E)-(methoxy-
(' r
rNan,Y.,Miao,H.,Yang,Z. OL2,297 (2000).
Pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium complexes. Aldol reactiont The Rh-complexes that also contain the ethyl cyanoacetateanion are active in promoting both aldol and Michael reactions, for example, involving cyanoacetlcesters.
l
rMurahashi, S.-I.,Take,K., Naota,T.,Takaya, H. SZ 1016(2000).
- COOMe ri. .. .,ehieved.lA convenientsynthe-
3,3-Pentamethylenediaziridine.
:
Aziridination.r Both cis- and trans-u,g-unsaturated amides are transformed into cls-aziridine derivatives.
,
,/J.: :')rmationof butenolidesfrom r-.:.:rr carbondioxide in the system.
-.-^Yo+
HN-NH ,\
l
l
BuLi
-
u-t,.o r 3
rHori,K., Sugihara, (1999). H.,Ito,Y.N.,Karsuki, T. TL 40,520'7
o L,2,2,6,6-Pentamethylpiperidine. Base.t Hinderedsecondaryaminesthat undergoN-alkylationby usingthis tertiary amineasbasecanavoidracemization of chiralitycenters.
(2000). t' loMC 5931594,409 i' ( )t, 2. 625(2000).
t \
COOMe
\r()9).
COOMe
= ,^.
\,,NH c. .r::.i rlkoxycarbonylation is observed rt lj:. underCO and in the presenceof ,
. L,-,r)t SpeCleS.
I
COOMe
+ Tso-J
cooMe
. 7-OTs PhN,le A
,\
aN-'/-*."2
coottte
Y
COOMe 93o/o
I o '
,i
1' i o L t
r1 3 -
82To
--(
I
338
Phase.transfercatalysts
'Insaf, S.S.,Witiak, D.T. S 435 (1999).
Perfluoroarenes. N-Arylation.t Amines are perfluoroarylated with perfluoroarenes in THF. The amino group is attached to the p-position in the reaction involving perfluorotoluene or pentafluoropyridine. Generally, primary amines are more reactive but secondary amines also undergo perfluoroarylation at a higher temperatureand with added triethylamine.
/-NHz
(
-T. }a -\ \
LNH,
+F{r
><
/>-F
X
tri
DMF rNHz
( 1oo" \__NHC.F, 42Yo
ltr. r/{' r," l:,
+
Wittig reaction The pro precursor of Wittig reagenrs.'t 'Beletskaya, I.P.,Artamkina, G.A.,Ivushkin,V.A.,Guilard,R. TL 4I,313(2000).
r-l Phase-transfer catalysts. 13,239-240; 15, 252-253; 18,286-289; 19,264-267 ; 20, 302-303
lI - ti:
Alkylations. For alkylation and Michael reactions involving enolates a new phasetransfer catalyst is the Ru-complex l..l
z
P h l 'Pt\
Pri
,I
2 PF; (1)
Phenols undergo o-alkylation in the presenceof PEG-400 without solvent.22-Methallyloxyphenol is preparedfrom catechol by a microwave-assistedmonoalkylation.3 Alkylation ofN-sulfonyl derivatives ofct-amino acid derivatives proceedswell under solid-liquid phase-transfer catalytic conditions,a whereas imines from a-amino acid /-butyl estersundergo asymmetric alkylation5 with activated halides in the presenceof the chiral quaternary ammonium salt (2).
Cyclocondensations. Th sulfoxonium methylide geru employing the r-BuOK-D\lS( propanationis the formation of
The asymmetric Darzens rs chona alkaloids as phase-rr-ans is usuallyhigh yielding. Ho,* er
Oxidations. Oxidation o benzyltriethylammonium chlqr and under similar conditions. .\'. Degradation of aldehydes r cleavagewith hydrogen perorrd Epoxidation of enones*rrh DABCO and Merrifieldresinrr,
Phase-trmsfer
catalysts
| .r ::. perfluoroarenes in THF. The rJ,:: 'n involving perfluorotolueneor ! :. :r' reactivebut secondaryamines tu:: .rndwith addedtriethYlamine.
:,,,. l -
/-NH, \ LNHC6F5 42o/o
(2\
(3) is Winig reaction The poly(ethyleneglycol)-linkedbis(triphenylphosphine) precursor Wittig phosphonium of reagents.6 UponP-alkylation. the saltsareusec.
11.{r. 313(2000). Ph I
< : I !t. 186-289; 19, 264-267 ; 20,
(1
:'. rnvolving enolatesa new phase-
P
4-yP'en o.--+o.\./ ,^J h t t l
'P'^\r/
Ph (3)
2 PF6
Cyclncondensations. The cyclopropanation of conjugated sulfones with dimethylsulfoxonium methylide generated under PTC conditions is higher yielding than employing the r-BuOK-DMSO system.TRelated to the the well-known dichlorocyclopropanation is the formation of 2,2-dichloroepisulfidesfrom thioketones.6 The asymmetric Darzens reaction of ct-chlorocycloalkanoneseusing quaternized cinchona alkaloids as phase-transfercatalyst and LiOH as base in Bu2O at room temperature is usually high yielding. However, the moderateee is disappointing.
o: ['[:Cl-J00without solvent.22-Methalmonoalkylation.' tu :. r'-.r:siSt€d p. .,. rJ derivatives proceedswell under ' .r r.'rcas imines from cr-amino acid r :.::'.:rted halidesin the presenceof the
Oxidations. Oxidation of benzyl ethers with KMnOo in the presence of benzyltriethylammonium chloride gives alkyl benzoatesin refluxing dichloromethane,r{) and under similar conditions, N-phenyl azacyclesafford lactams." Degradation of aldehydes is accomplished via their silyl enol ethers by oxidative cleavagewith hydrogen peroxide in a two-phase system with added PTC.r2 Epoxidation of enones with HrOr-LiOH in water and a solid catalyst prepared from DABCO and Merrifield resin is essentiallv ooeratedin a triohase situation.13
Phase-transfercatalysts
Isomerizatians. Under PTC conditions (presenceof tetrahexylammonium bromide) 1,3-diarylpropynescan be isomerized to diarylallenes by KOH at room temperature.iaA Brook rearrangementof acylsilanesoccurs upon addition of cyanide ion.15
,X
-si
O
KCN / BuaNBr H2O tCH2Ct2
n 5l
NC
/ 1 95To
Hydrolysis. Hydrolytic cleavage of silyl ethers under PTC conditions shows selectivity. Phenolic TBS ethers are preferentially removed.r6
OTBS
:-T- Jt, OTBS
= {
roMarkgraf, J.H., Choi, B.y. SC t. "Markgraf, J.H., Stickney. C..\ tH lrSakaguchi,S., Yamamoto.\'.. Su3 rrAnand,R.V, Singh, V.K. SL 8O- i ''Oku, M., Arai, S., Katayama.K . : r5Takeda,K., Ohnishi,Y. ft {1. rl( roCrouch,R.D., Steiff, M.. Fne. J L rTThorpe,T., Brown, S.M.. Cr6ta.
(2000). 'nAlbanese, D., Landini,D.. \tan . ''Masaki,Y.,Arasaki,H., Shrro.\l l -( 1-Phenoxyalkyl)benzotrirrr
Diketones.t These reagcn or-dihaloalkanes followed br rr NaOH(solid)/ dioxane
BuaNHSoa
d-\/oH t t l \,'\-orBS
':fr
)rN.. i l . N ^N
76To
,ft
r
L
Heck reaction
1,r
I ' ti':; , T .if
The sodium salt of a disulfonated triphenylphosphine serves as ligand for the Pd-catalyzed Heck reaction when the latter is conducted in a mixture of tolueneand ethyleneglycol.rT Hydroboration,ts Controlled generation ofborane in the organic phase is critical to the successof hydroboration under PTC conditions that consist of stirring mixtures of the alkenes,bromobutane,an onium salt, and aq NaBH4. Dichloromethylatian. Insertion of dichlorocarbene into tertiary C-H bonds geminal to alkoxy and siloxy groups proceeds with retention of configuration.re This reaction is synthetically valuable.
O-\H.T O
NaoH- cHcr3 C16HsN(l\,,|e3)Cl
Ph-
80"
ct2Hc')-Jo Ph' 86Yo
l T z a l i s ,D . , K n o c h e l ,P . T L & , 3 6 8 5 ( 1 9 9 9 ) . 2Cao,Y.-Q., Pei, B.-G. SC 30, 1759 (2000). 3Li, J., Pang,J., Cao, G., Xi,Z. SC 30,1337 (2000). aAlbanese,D., Landini, D., Lupi, V., Penso,M. EJOC 1443 (2000). 5Ooi, T., Takeuchi, M., Kameda, M., Maruoka, K. JACS 122,5228 (2O0O). 6Sieber,F., Wentworth, P., Toker, J.D., Wentworth, A.D., Metz, W.A., Reed, N.N., Janda, K.D. JOC 6 4 , 5 1 8 8( 1 9 9 9 ) . TPadmaja,A., Reddy, K.R., Reddy, N.S., Reddy, D.B. PSS 152,91 (1999). sMloston,G., Romanski,J., Swiatek,A., Heimgartner,H. HCA82,946 (1999). eArai, S., Shirai, Y., Ishida, T., Shioiri, T. CC 49 (1999).
X
Pho 'Katritzky, A.R.,
Huang, 2.. Fane.l'
O-(Phenylcarbamoyl)hyd ror-rt Nitriles.t Direct conversr PhNHCOONH2.TsOH in THF r I
Coskun, N.,Arikan,N. 255. Il9{_r
Phenyl chloro(thionoformal. ). Dealkylation.t Unhindered secondaryamines on reactron r'l S-methylation(with Me,SO. r an fbrmate reagentis superior to CK
N,.
rl\' "7 AcO
Phenyl chlom(thionoformate)
bromide) ( : i J:r.rhexylalnmonium A )H temPerature.L4 room at b: fr( ion.ls .. anide r. :
* 1
-
-
^
"i
/
a,-J/'
\
15', n
.,:',Jcr PTC conditions shows
)\:-;
"'Markgraf, J.H., Choi, B.Y. SC 29,2405 (1999). " Markgraf, J.H., Stickney, C.A. JHC 37 109 (2000). , I2Sakaguchi, S., Yamamoto,Y., Sugimoto,T., Yamamoto,H., Ishii, Y JOC fu,5954 (1999). rrAnand,R.V., Singh,V.K. SZ 807 (2000). 'uOku, M., Arai, S., Katayama, K., Shioiri, T. SL 493 (2000). lsTakeda,K., ohnishi, y. TL 41,4169 (20oo). 'nCrouch,R.D., Steiff, M., Frie, J.L., Cadwaller,A.B., Beris, D.C. TL 40,3133 (1999). rTThorpe,T., Brown, S.M., CrosbS J., Fitzjohn, S., Muxworthy, J.P.,Williams, l.M.J. TL 41, 4503 (2000). rEAlbanese, D., Landini, D., Maia, A., Penso,M. 5L997 (2000). reMasaki,Y., Arasaki,H., Shiro, M. Ca I 180 (2000).
I -( l -Phenoxyalkyl)benzotriazoles. Diketones.t
These reagents are acyl anion equivalents.
Thus, alkylation
with
1,
to-dihaloalkanes followed by acid hydrolysis leads to diketones.
--'-'-.,.oH \:-.^\-.OTBS 76% servesas a:-.: :rrphenYlPhosPhine la::-.: L. conductedin a mixture of
N ,N N
fn Pho
BuLi/ BrvA
---;;l*
Br
?
*'fi*
it
aq. HCI , IVeOH
t , t
rKatritzky, A.R.,Huang,Z.,Fang,Y.,Prakash, I. JOC 64,2124(1999). oc . r :irc organic phase is critical to u - :r.r\t of stirring mixturesof the bonds rt '- rnto tertiary C-H ', This configuration.le of :rll()n ::
"-\: LJo
O-(Phenylcarbamoyl)hydroxylamine. Nitriles.t Direct conversion of aldehydes to nitriles is completed on heating with PhNHCOONH2.TsOHin THF (11 examples,87-97Vo). rCoskun, N., Arikan,N. 755, 11943099q.
Phenyl chloro(thionoformate). Dealkylation,' Unhindered aliphatic tertiary amines afford thionocarbamates of secondary amines on reaction with the title compound at room temperature. Subsequent S-methylation (with Me2SOo)and hydrolysis accomplishes N-dealkylation. The thionoformate reagentis superior to CICOOPh in terms of its efficiency.
N,L ': -. l()00). .:- ,\ \ . Reed,N.N., Janda,K.D..IOC -(: . 1999). t t : r , t l . r J 6( 1 9 9 9 ) .
.l\. "1 AcO
s tl
q
tl
crAopn
-
un2ur2
*-
N,,^OPh
"--> | \
rl-]' AcO
96Yo
I
|:1 =', i t L t
Phenyliodine(Ill)
bis(trifluomacetate)
Dehydration.2 Alkanamides are dehydrated to nitriles by this reagent, but formamides give isonitriles. 'Millan,D.S.,Prager, R.H.AJC 52,841(1999). 2Bose, D.S.,Goud,PR. TL 40,747(1999'). Phenyl(fluoro)iodine triflate. 20, 304-305 Oxidative rearrangement,t (PhIF)OTf induces reiurangement of nonterminal alkynes in an alcohol to give a-branchedesters.
rll + Pn-r-r -il.* pnlcoov" I Ph
rTohma, H., Watanabe, H., Takisag.a-S. rKita, Y., Egi, M., Ohtsubo,M.. Sarh. T 'Kita, Y., Egi, M., Tohma,H. CC l.l_r, l, rVarma, R.S., Kumar, D. "/CS(p/ r I ?J5 i squideau,S., Looney, M.A., pouvscgu-I
Phenyliodine(III)
diacetate.
13. l{
280-281 ; 18, 290-29 | ; 19, 268-: -C Diaryliodonium sulfu natcsadmixture with PhI(OAc)2.2TfOH u
Oxidations, 4-Hydoxy-2-crcl with PhI(OAc)r. 2-Methoxyphenols adducts.3'a
Tfo-
rPirguliyev,N. Sh., Brel, V. K., Zefirov, N. S., Stang,P.J. MC 189 (1999).
Phenyliodine(Ill) bis(trifluoroacetate).13,241,242;14,257; 15,257-258; 16, 274-275: 18, 289-290:19,267-268: 20, 305 Cyclizations,Annulationaccompanies oxidationof N-sulfonyl-4-methoxyanilines with PhI(OCOCFj)2 in the presence of 1-alkenes.r5-Methoxyindoles or indolinesare producedin this one-potreaction.Cyclizationof 3-arylpropylazideswherethe aromatic ring is activated(e.g.,3-methoxylated) to fusedquinoneiminesis observed.2
Meo--4 I ll
* A "rln
Pht(ococF3)2
o€[3'n
9xHr.
MeOOC...,,,1.-.OMe
-l ll\v\oH
+ rt,t€
Acylnitroso compounds gerrre alkenesin situ. O-Acetylationand rc 2-(B-Indolylethyl)oxazolines arc
Ts 65%
2-(m-Methoxyaryl)ethyl benzyl sulfides are similarly cyclized to S-benzyl-2,3dihydrobenzothiophenes.3 Dehydrogenation.a 1, 4-Dihydropyridines are rapidly aromatized on exposure to PhI(OCOCFI)2 although addition of sulfur and microwave irradiation of the mixtures has the sameeffect. Dearomatization.s 2-Substituted l-naphthols are allylated at C-2 when they are exposedto PhI(OCOCF3),and an allylsilane. 1-Trimethylsiloxy-1,3-butadiene also react with the naphthoxyiodonium species.
Pht(ococF3)2
05*."".''o\
cH2ct2
With a (salen)CrCl complex as with PhI(OAc)2is chemoselecrir.e Ring contraction. A facile srr is by oxidationof 2-alkylideneclclo
o tl
(Y^
Phenyliodine(tfl) diacetate
rnles by this reagent, but for-
}, :;.:::rh9€lTl€ntof nonterminalalkynes
=-.lcooMe
l: I
rTohma, H., Watanabe,H., Takisawa, S., Maegawa, T., Kita, y. H Sl, l7g5 (lg9g). 2Kita, Y., Egi, M., ohtsubo, M., Saiki, T., okajima, A., rutuou, r., Tohma, H. cpB 47,24r (rggg). rKita, Y, Egi, M., Tohma, H. CC 143 .:Igg9\. rVarma. R.S.. Kumar. D. JCS(pt ) l7S5 (lgggt. sQuideau, S., Looney,M.A., pouysegu. L. OL l,I651 (1999).
Phenyliodine(Ill)diacetate.13,242_243;14,25g_259;15,25g;16,275_276;17, 280-281;18,290-291;19,268_270;20, 305_307 Diaryliodonium surfonates. These salts are prepared from ArB(oH), upon admixrurewith phI(OAc)2.zTfOHin dichloromethane. I oxidations' 4-Hydoxy-2-cyclobutenones are oxidized to -y-acetoxybutenorides2 with PhI(oAc)r. 2-Methoxyphenols give o-quinonesthat can be ffappedu, Di"lr-Ald". adducts.3'a
.q, 1999).
l/
t . '
I J. 157; 15, 257-258; 16,
Meooc)i'lYo'" * ""o$ ffi \V\oH
''i
.\'-sulfonyl-4-methoxyanilines ' \lc-thoxyindolesor indolines are
OMe
#ffi"""
rsoH_H2c
\_/
a(
' , .:rlnesis observed.2
.
\{eo:y';-1
-
|
ll
\An'\
) <-en
.oMe
o
i - ,:. :r()pyl azideswhere the aromatic
-c,
343
89To Acylnitroso compounds generated by oxidation of hydroxamic acids react with alkenesin situ. O-Acetylation and reduction afford N_allyl amides.5 2-(B-Indolylethyl)oxazolines are transformed into a tetracyclic system.6
Ts
Phl(OAc)2
.'rlr cyclized to S-benzyl-2,3-
Bn
-4
I i"{ 'Z-\X )
\AJ-"
r- -.:prtlh aromatized on exposure r' -: \\ rve irradiationof the mixtures
H
with a (salen)crcl complex as catalyst, the oxidation of alryric alcohols to with PhI(OAc)2is chemoselective.T Ring contraction. A fac'e synthesis of 2-alkylidenecycroarkanecarboxylic esterso is by oxidation of 2-alkylidenecycloalkanones phI(OAc),. with
o
Etooc \
tl
/Yrn | \-,"
Phr(oAc)2 |
HC(OEI), Hcto4"
/-a\
\,
72%
Ph
t, ,"' io
:,,7 3,r
.tJ
65%
r .::- .rll\latedat C-2 when they are tr: , ::: . l.i loxy- I ,3-butadienealso react
I I,
Phenyliodine(Il!
diacetate-bromine
Benryne precursors. Cyclic siloxanes such as 1 are readily prepared from o-dibromoarenes via Grignard reaction with dimethylchlorosilane. o-Silylaryliodonium triflates that are obtained from oxidation decomposeto benzyneson exposureto fluoride ion.e
()
-s{
\,/ 'o' \
Phr(oAc)2
(l
trorrcHrct, ,n-,/
rfJ
(1)
./\,.ot \
B,4NF
()
.,o\
4o)
\__/
\:,/
Camps,P, Lukach,A.8.. Pulol.\
Phenyliodine(III) diacetate-ir Iodination.t An acid-ca combination.An oxidatire &i introductionof an iodine atom i
oto\
r. I
87%
v
N-COO|/
boox
c -T r' r,' =t -:r
.',
j:n _
-'t . 4
t -l
Only the n-silyl group of methyl 3,4-bis(trimethylsilyl)benzoate is replaced by the [PhI] residueon reactionwith PhI(OAc)2.r0 N-Sulfonylamine activation, Iminoiodine(Ill) compounds (which can serve as nitrene sources)are produced when sulfonamides are combined with PhI(OAc)r.rr In the presenceof sulfides,N-sulfonylsulfilimines (RrS:NSOTR' ) are formed.I2 Amination.t3 A combinationof PhI(OAc)2and RNH2 (R : Ts, Ns, Ms, CF3CO)
Phthali.des. o-Alkylbenrr phthalideswith a hydroxr'l gnxr
in the presenceof Mn(porphyrin) or Ru(porphyrin) are effective in aminating a variety of hydrocarbons.
a ' , n
,'": t,. . .,f
ICanoll,M.A., Pike,V.W.,Widdowson, D.A. TL 41,5393(2000). 2Ohno,M., Oguri,I., Eguchi,S.JOC 64,8995(1999). 3Rao,P.D.,Chen,C.-H.,Liao,C.-C.CC 7130999). 4Kurti,L., Szilagyi,L., Antus,S.,Nogradi,M. EJOC2579(1999). 5Adam,W., Bottke,N., Krebs,O., Saha-Mtjller, C.R.EIOC 1963(1999). 6Braun, N.A.,Bray,J.D.,Ciufolini, M.A.TL40,4985(1999). 7Adam,W.,Hajra,S.,Herderich, (2000). M., Saha-M6ller,C. OL2,2'7'73 nVarma, R.S.,Kumar,D. S 1288(1999). eKitamura,T., Meng,2., Fujiwara,Y. TL 41,6611 (2000). r0Kitamura, T.,Wasai,K., Todaka, Y. SL731(1999). M., Fujiwara, rrDauben, P, Dodd,R.H.OL2,2327(2000). r2Ou,W, Chen,Z.-C. SC29,4443(1999). r3Yu, X.-q.,Huang, J.-S., Zhou,X.-G.,Che,C.-M.OL2,2233(2000).
MeO
Remote functionalizltion' hypoioditefor subsequent iodrna
Phenyliodine(Ill) diacetate-bromine. Hunsdieckcr reaction.' Decarboxylative bromination is achieved photochemically by this reagentcombination.
y'-azcooa
\A*o,
phr(oAc)2 /-;a''
%.1* \A*o, 51%
AcO OH
Phenyliodine(III)
r: .:\ I are readily prepared from n::.:: . Ichlorosilane. o-Silylaryliodonium r. -.-' ,/\ neson exposureto fluorideion.e
rCamps,
P, Lukach, A.E., Pujol, X.,yazquez,S.
256, 2703 (2000).
Phenyliodine(Ill) diacetate-iodine. 20, 307 Iodination.t An acid-catalyzed iodination of activated arenes uses the oxrdant combination.An oxidative decarboxylationof o-amino acid derivatives results in the introductionof an iodine atom at the B-position.2
AcO^ Phl(oAc)2 -t2 / MecN ; " , [ ,r'l-coolt'te TSOH - l\4eOH
I
AcO
N-COOMe
1
I
COOH rrl:r...ilvl)benzoateis replacedby the .()mpounds (which can serve as i ::- .rrmbinedwith PhI(OAc)r.r1 In the - \ \ ( ) . R ' ) a r ef o r m e d . r 2 :: r R\H. (R : Ts, Ns, Ms, CF3CO) lll
r ,:-' rlt'ectivein aminatinga variety of
diacetate-iodine
OMe
Phthalides. o-Alkylbenzoic acids are transformedinto phthalides.s 3-substituted phthalideswith a hydroxyl group in the side chain give spiroacetals.a
4-N.4eC6Hal(OAc)2
I
I
91yo !-
t, , t ,
);:
, n . rr 1 9 9 9 ) . --.r
i:.
MeO
{1000).
Phl(OAc)2
":,
,12
lr,-
t
MeO OH r l(xlO).
Remote functionalization.s The combined reagenr changes an alcohol into hypoiodite fbr subsequentiodination of an unactivatedC-H bond.Ultrasoundis helpful. (
.rlrr,nis achievedphotochemically
.Yt' *ro , 51o/o
:ll; ,:,,
Phl(OAc)2 -12
)))) AcO
Phenyliodine( III.) diacetate-iodine
Dealkylation. The alkyl group of an N-alkylsulfonamide is detachedby the reagent couple with ultrasound assistance.6Howeveq arylethylsulfonamides undergo iodinative heterocyclization.T
an
Phl(OAc)2 -12
ora-rrr"
\-/
clcH2cH2cl
Y)a) \A*-so'
Phenyliodine(Ill) diacetate-trimerhgtd Oxidation. 3-O-Silylatedglycals r ethersarenot affected.
Me 89o/o Cycloaddition, The following reaction is a most unusual oxidative 1,3-dipolar cycloaddition involving a benzenering as the dipolarophile.8 Ph
/\.\ i l
\" rT t
l
ctcH2cH2cl
aorBs Et3sio-< b \:,/
hromoazidation of alkenes.
Fragmentation Angular alcohols suffer fragmentation on treatment with PhI(oAc)2-I2, therebycreatingmedium-sizedrings.eHowever,the regioselectivitycan be subvertedby placing an azido group in a subangularcarbonatom.r0
o /'-\U---\
Phl(oAc)2 t,
=t;;-
I
FCOOMe
reso"'---f-\ AcO
rKirschning, A., Hary,U., plumerer, C.. Rrcs.\l zChen,D.-J.,Chen, Z.-C.TL 41,7 361t2UI.t, 3Kirschning, A., Abdul Hashem,M.. \lm 6s22(1999)
Phenyliodine(Ill) dicyanide. Alkene functionalizations.t This rct reagents(e.g.,phSeSeph)to initiate a rc{r nucleophiles presentin the reaction medrar
COOBn
Ph(C\.. <
72o/o
1
N"" o H
R
|
-\--\
| | FCOOMeTBSO/-'-try H booan
>r
Note that the PhI(OAc)2-NaN, combrn pBromoalkyl azides.3 Bromide r,x 77o/o
booan
Et3sio
Phl(OAc)2 -12
HO-N
COOMe
5Costa,S.C.P., Moreno, M.J.S.M., Sa e llclo. 6Katohgi, M., yokoyama, M., Togo, H. SL IrI 7Togo, H. , Harada, y., yokoyama, M. JOC 6 8Barnes,J.C., Horspool,W.H., Hynd. G. CC { 'Wipf, P, L|W. JOC 64,4576 ,lgggt. r0wipf, P., Mareska,D.A. ZL 41, 4.:.23euin,,
Phr(oAc)r ,,
cH2ctt
NC\
PhSeS€F
I
o\-^
| | FcOOttte TBSO/-rv.,i-N H booen
rMargarita, R.,Mercanti,C.,parlanti,L., pran-r
59% a-(Phenylseleno)acrylic esters. rKryska,A., Skulski,L. JCR(S)590(1999). 2Boto,A., Hernandez, R., Suarez,E. TL 41,2494(2000). 3Muraki,T.,Togo,H., Yokoyama, M. JCS(Pt) t7l3 (1999). aBrimble, M.A., Caprio,V.E.,Johnston, A.D.,Sidford,M.H. IL 41,3955(2000).
furrolidine-3-carboxylic esters.t Th adducts of PhSeCl and acrylic esters br Michael addition of allylic amines to the scl abstractionstarts the free radical cyclizatioc
c-(Phenylseleno)acrylicesters
::rrde is detachedby the reagent n . ...rirnamidesundergo iodinative l,
_r"n i
l
l
v,\N'so2
Phenyliodine(III) diacetate-trimethylsilyl azide. Oxidatian. 3-O-Silylated glycals are oxidized to afford the enones.l Other silyl ethers are not affected.
Me 89Yo r.- . : unusual oxidative 1,3-dipolar ( \ :
5Costa,S.C.P.,Moreno, M.J.S.M., Sa e Melo, M.L., Neves,A.S.C. ZZ 40, 8711 (1999). 6Katohgi,M., Yokoyama,M., Togo, H. SZ 1055 (2000). 7Togo, H. Harada, Y., Yokoyama, M. JOC 65,926 (2000). , sBarnes,J.C., Horspool, W.H., Hynd, G. CC 425 (lg9g). ewipf, P., L|w. Joc 64,45i6 (1999). '0wipf, P., Mareska, D.A. TL 41,4723 (2000).
j '
Ehsio aorBs
,
Ehsiol_/o
/
:
Ph
\
EtsSio''7-orBS Phl(oAc)2-Me3siNt
.
-
PhN4e 25"
ro1:/o H
I
gEYo
\r\ H
I
- .<','r
..
r
Note that the PhI(OAc)2-NaNj combination converts ArcHO into aroyl azides.z B-Bromoalkyl azdes.3 Bromide ion is oxidized in situ by PhI(OAc)2 ro induce bromoazidation of alkenes.
).\
-
"
t\
ir.:- ' r'ntation on treatment with li .,.. r cr. the regioselectivitycan be C.:-'-
rKirschning, A., Hary,U., Plumeier, C.,Ries,M., Rose,L. JCS(PI)519(1999). 2Chen, D.-J.,Chen,Z.-C.TL 41,7361(2000). rKirschning,A., Abdul Hashem,M., Monenschein, H., Rose,L., Schoning,K.-U. JOC 64, 6522(1999\
:l lttOfil."'
COOMe
Phenyliodine(III) dicyanide. Alkene functionalizations.t This reagent can be used for oxidative activation of reagents(e.g., PhSeSePh)to initiate a reaction with alkenes.With participation of proper nucleophilespresentin the reactionmedia additionreactionscompleted.
COOBn Phi(cN)2- KscN
PhSe
\,J .............................."* h
PhSeSePh/ MecN
R R=Hx
COOMe
H booen 5go/o
J l 1 9 5 5( 2 0 0 0 )
SC N
80%
rMargarita, R., Mercanti, C.,Parlanti, L., Piancatelli, G. EJOC1865(2000)
c-(Phenylseleno)acrylic esters. Pyrroli.dine-3-carboxylic esters.t The selenoacrylic esters are obtained from adducts of PhSeCl and acrylic esters by base-promoted dehydrochlorination. After Michael addition of allylic amines to the selenoacrylates,radical generation via selenium abstractionstartsthe free radical cyclization.
Phenyl
(^
PhSeCl- ZnC12
Phseyx
cH2ct2
R2'
Phserx Et3N
+
\*
nAcr
X = CHO,Ac, COOMe,CONH2
I ou*
V
x. / \__J / o-{. ''
r,^e
PhSe, X
+ (i'4e3si)3siH
\ - N)
I R^N H
H
r
rBerlin,S.,Engman, L.TL41,3701(2000).
rBillard, T.,
Langlois,B.R. f 5!
Phenyltrifluorosilane. Azomethineylides.; T ethersby treatmentwith phC agentsfor theirusein ring fo
3-Phenylthio-2-(N-cyanoimino)thiazolidine. Sulfenylation.r This reagent (1) readily transfers its PhS group to amines and enolates.
-lb -/" \ + .
Ph
Fu,n
N
- . !
.-s. LFN -N
- - l J', <
rsc-sozsen + (
i
1 l
- t i
Ph
SPh
-'- r " f:
-oM.
PN
rWashizuka, K.-1.,Minakara S.
(1) rTanaka, T.,Azuma,T.,Fang,X., Uchida,S.,lwata,C., Ishida,T., In,Y.,Maezaki,N. SL 33 (2000).
rit
Phenyl trifl uoroacethioate. Trifluoromethylation.t Photochemicalreaction of CF.C{(gPh) (also CFjSO2SPh) with alkenes gives alkanesbearing a trifluoromethyl group, although in rather low yields.
2-Phenyl-2-(trimethylsilflX Carboxyl protection. lntoesters. Rapidregenera
rWagner, M., Kunz,H. Sl .l0 rl
The trifluoromethyl radical generatedon decompositionof the reagentis the addend. Phosgene.
Y
l
l
F3C SPh _ + l l o
hv l
cq2ct2
\ ^-Vr", .,\
39Yo rBillard,T., Roques, N., Langlois,B.R.24 41,3069(2000).
Phenyl trifl uoromethanesulfonethiolate. Alkenyl triflones.t This reagent, CF3SO2SPh,as well as CFjSO2SePh,react with alkenesat 80', and the adductsundergo elimination on oxidation.
Phosphonothiaformic t (in the presence of trierhr.h RSC(:O)PO(OR')2. rSalomon, C.J.,Breuer,E. Sa tt:
Phosphazene bases.
Diaryl sulfides.' Th. p reaction between fuSH ard hindered, they generatehighll carbonacids).
Phosphazene bases
r ..
rhse-
x
Y
F3c-So2sPh+(
l\ lR
\-'
Bo. )-
\
+
/
Iol
=
pns'asorcr,
I o"u*"'
V
,n""Y^
so2cF 63%
rBillard,T.,Langlois,B.R.r55, 8665(1999).
(
*A*/
H
Phenyltrifl uorosilane. Azomethine ylides.t
These reactive dipoles are generatedfrom N-(a-silylalkyl)imino ethersby treatmentwith PhSiF.. It is necessaryto provide proper dipolarophilesas trapping agentsfor their use in ring formation.
Ph
rts PhS group to amines and
!siv".
N
f_ oMe
P
lt
phsiF3 ,i-1 + ll N .NPh + '--1
Ph
h
\
O
l
I
t N
P
h
CH>Clt
o
)-\ P h
o
99% rWashizuka, K.-I., Minakata,S.,Ryu,I., Komatsu,M. f 55, 12969(1999). N. SL 33 (2000). r;., . In.Y, Maezaki,
(alsoCFTSO2SPh) , : t l'C{(SPh) i: .;p. althoughin ratherlow yields. o: : thc reagentis the addend.
2-Phenyl-2-(trimethylsilyl)ethanol. Carboxyl protection,t DCC-mediated esterification transforms carboxylic acids into esters.Rapid regenerationof the acid (as salts) is achievedby treatment with BuoNF. rWagner,M., Kunz,H. SI 400 (2000).
Phosgene. Phosphonothioformic esters.t Consecutive reaction of phosgene with a thiol (in the presence of triethylamine) at low temperature and trialkyl phosphite furnishes RSC(:o)Po(OR')2. 39Yo
( : l
rSalomon, C.J.,Breuer,E. SL 815(2000).
*cll as CFrSO2SePh,react with
Phosphazene bases. Diaryl sulfides.' The phosphazenebase P2-Et (1) is useful in the CuBr-promoted reaction between ArSH and Ar'I in toluene. Bases of this class are very strong and hindered, they generatehighly nucleophilic "naked" anions from various acids (including
r rdation.
carbon acids).
Phosphines
NR N M e- ,- l l t P-NMe2 MezN-P=Nlr", NMe2
Copp er(I ) hydrfule comphx ct the use of such complexesto redrn
(1) rPalombo, C.,Oiarbide, M., Lopez,R., Gomez-Bengoa,E.TL4l,1283 (2000). Phosphinic acid. Radical cyclization.t of haloalkenes.
..\ \,, /
9o)
HrPo2-NaHco, a*{
;^;.-,7
(dba.:P
-+f t l
tl
I
tl
PhMe 5:
87%
,fl ' !
n l
6
c
(
I o'B'o
\-ll-J
D
,
different regioisomeric adoucr-scar
Phosphinic acid has been used to induce reductive cyclization
aY'
.,
Mitsunobu reactions.s .{n r phosphine and di-r-butyl azodicart Hydroboration.e The narure hydroboration of allenes with prr
+ Cy:p + t_Buf
rYorimitsu,H., Shinokubo,H., Oshima,K. Ca 104 (2000).
Phosphines. Preparation. 2-Hydroxyethylphosphines are conveniently prepared from red phosphorus, via reduction with Na in t-BuoH and reaction of the resulting NaPHr with e p o x i d e isn l i q u i da m m o n i a . r Carbamates2 Reaction of organic azides with MejP, treatment of the ensuing iminophosphoraneswith chloroformic esters,and hydrolytic cleavage of the aminophosphoniumsaltscompletethe conversion. Transesterificatinn.s Activation of 2,2,2-trihaloethyl esters by phosphines enables exchangeof the alkoxy residues. Furfurylidenetrialkylphosphoranes,a These Wittig reagents are generated from conjugated 2-alken-4-ynonesby the addition of RrP. In situ reaction with carbonyl compoundsleadsto 2-alkenylfurans.
\
-Y*
-
Bu3P/ R"CHO
OMe
+ ueoehF Otle
rArbuzova, S.N., Brandsma,L.. Gusaro Trofimov, B.A. S 65 (2000). :Aiza,X., Urpi, F., Vilarrasa,I. Tl.{.. rHans,J.J., Driver, R.W., Burke. S.D .l( rKuroda, H., Hanaki, E., Kawakamr.\l 5Yamada, Y.M.A., Ikegami,S. fL {1. : I 6Matsukawa, S., Okano, N., lmamolo. T. 7Chen, J.-X., Daeuble,J.F.,Bresrenskr_ I 'Kiankarimi. M.. Lowe.R..McCanir I "Yamamoto, Y. Fujikawa.R.. yam-t, f Phthalic
R
anhydride.
Hydrolysis cH2ct2
o
of amides.r
pnmr
heating in the dry state with phrhrl pivalic acid in9l%o yield (rhe side pr lChematF , .
Baylis-Hillman reactions.s BINOL and a reriary phosphine (e.g., Bujp) constirure a cooperative catalytic system to promote the reaction (higher rates and yields). Application to catalyticasymmetricsynthesisis indicated.
Picoline hydrochloride.
Mukaiyama aldol reactians,6 Silyl keteneacetals undergo condensation with aldehydesunder the influenceof tris(2,4,6-trimethoxyphenyl)phosphine. Triphenylphosphine is slightly lessefficient and aliphatic phosphinessuchas /-Bu.P are much inferrior.
Chlorination.t Aliphatic aldct chlorine using picoline hydrochtan carboxylic acids are formed.
T L 4 0 , 3 8 5 5( 1 9 9 9 ) .
351
Picoline hydrochloride
Copper(I) hydride complexes. Stabilization of CuH with various phosphinesenables the use of such complexesto reducecarbonyl groups (in the presenceof a double bond).7 Mitsunobu reactions,R An improved reagent pair consists of diphenyl(2-pyridyl)phosphine and di-t-butyl azodicarboxylate. Hydroboration e The nature of the phosphine additive plays a critical role in the
V:i
r; {l ll8-l (2000).
L-r.r l() inducereductivecyclization
- ^ -\.--1. l
r-
t ) >'nO
hydroboration of allenes with pinacolatoborane under the catalysis of (dba)2Pt. Thus, different regioisomeric adductscan be preparedby variation of such additive.
r-\ t l
Y a
tl
.)
H (dba)2Pt
R
o,- - o -|_ft
PhN.4e 50'
Y
l
+ cy3P + t-Bu3P OMe
d- \l- P trealmentof the ensuing r;: . . irc cleavageof the aminoPhosh('. .1 cstersby phosphinesenables f, r'.- rcagents are generatedfrom R i' In situ reaction with carbonYl
_ - 5 o ^ l-\ R' = ' rr:. :'hosphine(e.g.,Bu3P)constitute r..:,:rr)n (higher rates and yields).
..l
4o-o
6--x
+
87%
- 'r',cnientlY Prepared from red r j- ,,n of the resulting NaPHr with
) o'B-o
o Y .^"X.
+ ueo{LP -Otvte
/\
56 1
0 0
0
100
44 99
0
rArbuzova, S.N.,Brandsma, L., Gusarova, N.K.,vanderKerk,A.H.T.M.,vanHooiidonk,M.C.J.M., Trofimov,B.A. S 65 (2000). )Aiza,X., Urpi,F.,Vilarrasa, 1.TL40,7515(1999). jHans, J.J.,Driver,R.W, Burke,S.D.JOC 64,1430(1999). aKuroda, H., Hanaki,E.,Kawakami, M. TL 40,3753(1999). 5Yamada, Y.M.A.,Ikegam i, S. TL 41,2165 (2000). 6Matsukawa, S.,Okano,N., Imamoto,T. TL 41, 103(2000). iChen,J.-X.,Daeuble, J.F.,Brestensky, D.M.,Stryker, J.M. f 56,2153(2000). 8Kiankarimi, (1999). M., Lowe,R., McCarthy, J.R.,Whitten,J.P.TL40,4497 ''Yamamoto, Y.,Fujikawa, R.,Yamada, A., Miyaura,N. CL 1069(1999). Phthalic anhydride. Hydrolysis of amides,t Primary amides are 'hydrolyzed' to carboxylic acids by heating in the dry state with phthalic anhydride at24O-250". Thus, pivalamide affords pivalic acid in9lVo yield (the sideproduct is phthalimide). rChemat, F. TL 40,3855(1999).
[:i-.i
Picoline hydrochloride.
L;i.,.. undergo condensation with pr:: :rr I rphosphine.Triphenylphosphine a. I-t.r.P are much inferrior.
Chlorination.t Aliphatic aldehydes are converted to ct,cr-dichloroderivatives with chlorine using picoline hydrochloride as catalyst. On further'reaction, the dichlorocarboxylic acids are formed.
l
Platinum(Il) chloride
rBellesia, F.,deBuyck,L., Ghelfi,F.SZ 146(2000).
When the ene portion of rhc ucts are still 1,4-dienes.r
x / ^x-\
Platinum/montmorillonite. Deorygenation.l A method for the reductive removal of the oxygen atom from a carbonyl group consists of high+emperature hydrogenation with a Pfon-KlO montmoril-
x \--\
r
lonite clay catalyst in diglyme. rTorok,B., London,G.,Bartok,M. St 631(2000).
X = SOzph Platinum(Il) chloride. 19, 272 Cyclization. Novel cyclization patterns of 1,6-enynes induced by PtCl, are revealed.l2
X
t
f--€
X
F --b -l
/"
5-.
-., r. '. , ,11
.
a"n
il \--/ il;;
\,.^-_,
COOMe
(siMe3
Ptcrr, Tr-Ntry
rs-rui LsrM",
t 'r'l
Allylation.a Allylic chloro residuesto aldehydes.Such rca
70To
-4
,:
X = SO:ph
Ptc,zu"ooc'.-{\
)q''V
. o
cr I
PhN,le8o'
E
Y
a) tlt ol^ t
\
Ptclz
Fiirstner, A., Szillat,H., Stelzer. F .fl rMendez, M., Munoz,M.p.,Echarlrn 'Fernandez-Rivas, C.,Mendez.Il.. Fr 'Fiirstner,A., Voigtlander, D. S 959rf,
MeOOC
PhMe 80'
COOMe
X
PtCt2
x
X
R'OH
X
OR'
X = COOMe,SO2Ph... E
E. E
X
PtCt?
/ \--{
.
/ \\
E = COOMe
+N,leoH
).Y t r l
I
X""
Platinum(IV) oxide. partial sar! Hydrogenation, constitutes a key step in a sl.nrlx catalyst.r
Platinum(Moxide
353
When the ene portion of the substratesis allylically silylated or stannylated,the products are still 1,4-dienes.3 i,,- -,"lroral of the oxygen atom trom a r -- ".rlr()nwith a Pt-on-Kl0 montmoril-
^{Y -"l=
X lVe2CO
X
A
94To Ptct2
(r-cnynes induced bY PtCl2
* X
MeOH A
y=SnBug Y = SiMeo
Y X = SOzPh
79% 48%
Allylation.a Allylic chlorosilanes are activated by PtCl2 and submit their allyl residuesto aldehydes.Such reactions are syn-selective.
70%
,.
,siMes
-s-N
r\7
.-
\^ )q''V c(l
| + PhcHo
Ptcr2 ;il
/
:
92o/o (syn : anti
\j::_/
73Yo
73To -<= '.rr=r9p' - , 1 i
t
=-L.",,rn | oH 99: 1)
'], ',/
lFiirstner,A., Szillat,H., Stelzer,F.JACS122,6785(2000). rMendez,M., Munoz,M.P.,Echavarren, A.M. JACS122, 11549(2000). 'Femandez-Rivas, C., Mendez,M., Echavarren, A.M. JACS122, 1221(2000). 'Fiirstner,A., Voigtlander, D. S 959(2000).
7
Platinum(IV) oxide. Hydrogenation. Partial saturation of a 2,3-bipyridyl after selective quaternization constitutes a key step in a synthesis of cytisine. PtO, serves well as the hydrogenation catalyst.r
l
R
MeO
/^ ..///
H2 | PlO2
:N
Et3N- MeOH
\ / /
It t al t
Bn ( frans: cls 85: 15) 1O0Yo
Poly(methylhydrosiloxane), PMHS
'O'Neill,B.T.,Yohannes, D., Bundesmann, M.W.,Arnold,E.P.OL2,42Ol (2000).
Poly(methylhydrosiloxane), PMHS. 20, 371 Reductions, The reduction of carbonyl compounds with PMHS requires promoters. and These include 2,8,9-trimethyl-l-phospha-2,5,8,9-tetraazabicyclo[3.3.3]undecaner zinc compounds.2'3Conjugated aldehydesare converted to allylic alcohols.2 Imines are similarly saturatedin the presenceof zinc chloridea or a chiral titanocene difluoride,s the latter reaction on ketimines proceeds with excellent enantioselectivity (up to 997o ee). Hydrogenolysis. PMHS is a useful hydrogen source in the Pd-C-catalyzed hydrogenolysis of aziridines6 and organic azides.l The amine products can be converted to ,-butyl carbamatesin situ by (Boc)2O. Benzylidene acetals are cleaved reductively with PMHS in the presenceof AlClr. A lesshyghly substitutedhydroxy group is exposed.n
'Maleczka,R.E.,Terrell,L.R.. Clz 5958(1999). tA.P.T Maleczka,R.E.,Gallagher.
Potassium. Deoxygenation l
Ultra-vm azoarenesat room temperature Wang,X., Xu, M., Chen,J..Pan \'.
Potassium /-butoxide. 13, l5:-: 273-275; 20, 11-313 Eliminations. A neu preg .'limination of quaternaryamnror
t,
?' ---- ' : -
a t
Ph
N
PMHS
---t;,-*
It . ,t.
Et2O- CH2C|2
7n I
ph
I-o
*
OSitvle.
Ho$rua l"
G,, .v 1
Hydrostannylation and Stille coupling. In situ reduction of triorganochlorostannaneswith PMHS during Pd-catalyzedhydrostannylatione is convenient.Modification of reactionconditionsenablesan efficient synthesisof dienes(Stille coupling).I')
1,3-Eliminationof phosphrrr l .rctivecyclopropylketones.
o
'n:,t,,,a Ph'
NIe3snCl- (2-Fu)3P - (dba)3Pd2 (Ph3P)2PdCl2
-/t
R---,'7/ R' tl OH
*
o..\-Ph PN,IHS/ NaHCO3 H2O - Et2O
\
Ph+-o :
OS'Mc
Jz*" OH
tWang,Z., Wroblewski,A.E., Verkade,J.G. IOC 64,8021 (1999). 2Mimoun, H. JOC 64,2582 (1999). 3Mimoun, H., de Saint Laumier, J.Y., Giannini, L., Scopelliti, R., Floriani, C JACSl2l. 6ts8 ( 1999). aChandrasekhar, S., Reddy,M.V., Chandraiah,L.SC 29,3981 (1999). 5HansenM.C., Buchwald, S.L. OL2,713 (2000). 6Chandrasekhar,S., Ahmed, M. TL 40,9325 (1999). TChandrasekhar, S., Chandraiah,L., Reddy,C.R., Reddy,M.V. CL 780 (2000). sChandrasekhar,S., Reddy, Y.R., Reddy, C.R. CL 1273 (1999).
Double eliminationof [PhSO rr the laststepin an alkylatir.earc
Ph-so2
Go.
Potassium/-butoxide .i
, t! 2. .1201(2000).
eMaleczka' R.E., Tenell,
s9s8(1999).
3Ss
L.R., clark, D.H., whitehead, S.L., Gallagher, w.p, Terstiege, r. Joc g,
Ir)Maleczka,R.E., Galtaghel W.P.,Terstiege,l. JACS 122,3g4 (2000).
o-:-.:. \\ ith PMHS requirespromoters. -rJ::.r.r,/abicyclo[3.3.3]undecaner and r:r.: :Lrallylic alcohols.2 rt ::, chlorideaor a chiral titanocene it.:. rirth excellent enantioselectivity Err!'r \()urce in the Pd-C-catalyzed T'.- .rrrine productscan be converted f l'\lHS in the presenceof AlCl3. A
Potassium. Deoxygenation.) Ultrasonically dispersed potassium reduces azoxyarenesto azozfenes at roomtemperature. rWang,X., Xu, M., Chen,J., Pan.y, Shi, y. SC 30, 2253(2000).
Potassiumf-butoxide.13,252-254.,15,2'll-2:12.,1?,299-290; 1g,296_297;19, 2'13-2'75;20, 11-313 Eliminations.
Anew
preparafion of o-substituted
acrylonitriles involves a twofold
elimination of quaternary ammonium salts.l
lM", ..rN r
Met/ tvte2co : l*'o;^*.-----*
';,,,/-r,-NMez l
+
CN I
OSiMe3
;
OSiMe3 57o/o
It
rl-:i dr-
:,:Juction of triorganochlorostanr rs convenient.Modification of - . r S t i l l ec o u p l i n g ) . r 0
- Jz*"
1,3-Eliminationof phosphineoxide with stereocontrolenablessynthesisof optically activecyclopropyl ketones.2
o
,n:1,,,/,.._Bu P h ' \ / Ph-+--O : OSiMe3
-
phrA,,. t-BuoK/t-BuoH l -\?l B
u
r\ 83To
OH
Double eliminationof [PhSOrH] and benzoicacid, which resultsin substitutedarenes. is the last stepin an alkylative aromatizationofcyclohexone.3 I
, .'l
r:'i
: : . R . . F l o r i a n i ,C . J A C S 1 2 1 , 6 1 5 8
i".
Ie99).
BuLi ; PhCOCI/ THF ;
-\ \r
r 1.780(2000), 7SYo
"l '., 1)
',
Potassiumt-butoxide
Wittig and Emmons-Wadsworth reactions. An alkyne synthesis by chain extension of aldehydes uses dihalomethyltriphenylphosphonium salts as Wittig reagent precursors.aNote that temperature is important in determining whether the products are 1,l-diiodoalkenes,l-iodoalkynes,or l-alkynes.
Aromatic substitutions. l-\ru,r nucleophilic substitution on nitroarene
I
6u"
I
cHo
'n"-"T )|v^ t-euox 6vr"
t-BuoK Ar '-----5""
|
78
-50.
80%o
| R=r
+25o R=H
I r)
)."
ai
t."
\^
R
97% 81Yo
For polyvinylogation, 4-diethoxyphosphonyl-1,3-dienolatesand their O-acylated and O-silylatedderivatives are efficient reagents.5
o Ph-J ,n)'vYcHo
+ PhcHo
> . t
aziridineesters.la
t-BuoK/rHF Ph"\,\-cHo
-'0"
|
I
j.,
t ' 4
o
71Yo
,oMe \-o
a ' r
iti = f'-
Amides. Conversionof ".te.. r.l heating with solid t-BuOK.i: Orrd.rr aldehydeswith t-BuOK in DMSO alro Hydrolysis. Amino esters ro- a (r-BuOK-THF) at 0' or belor,r'.Thrr
2-Alkylideneglutaronitriles are readily formed by consecutive Michael and Wittig reactions.6 The process involves addition of the cyanomethylphosphonate anion to acrylonitrile and quenching the homologated anion with aldehydes.
IBUOK / THF . HN,IPA ;
ot l
ffiP;.cru
.
\
\
J
on"'-*t
Y / \
t-BuOK
--f
2a
Ph,,\.CN
PhCHO;HCl-H2O
I )
CN
CN
Claisen rearrangement Allrl d propargyl ethers with l-BuOK are rc.( o-substitutedacroleinsis established
72o/o Cyclizntians. Synthesis of substituted indoles from o-haloanilines by condensation with ketones?or nitriless is promoted by t-BuOK in DMSO. Furansare formed from a-propargyl ketones.qAlkynyl benzyl sulfidescyclize to give 2-aryl-2,3-dihydrothiophenes.r0 Deprotonation at the benzylic position initiates the cyclization.
l--\
( \:
./
,r-s
\
N
\}-r \\ / \ \
t ? \
(YY '
I-BUOK/ THF
,)'\?-.'
I-BUOK/MeCN
Al.dol reactions. A reagentconur Addition to styrenes. A caralrrr additionof ketonesand iminesto sgl6
o. 7SYo
at room temperaturein either DITISOtr
Potassium,-butoxide
-\n alkyne synthesis bY chain rh, -rhonium salts as Wittig reagent r:l:lrning whether the products are
Aromatic substitutions. 2-Nitroaryl-1,3-dithianes are assembled by the vicarious II nucleoohilicsubstitution on nitroarenes.
/ _r:il^N. -50'
R=l
+25o R=H
95Yo
97Yo |'lYo
f-i:fi()lates and their O-acylatedand
Amides. Conversionof estersto amides in a solvent-freeprocessuses mrcrowave heating with solid t-BuOK.12Oxidative decyanationof ct-aminonitrilesderived from aldehydeswith r-BuOK in DMSO also afford amides.rl Hydrolysis. Amino esters (ct- and B-) are cleaved under nonaqueous conditions (I-BuOK-THB at 0o or below. This method proves valuable for kinetic resolution of aziridineesters.ra
Ph\cHo ;_
o ,oMe \_o
75% t^. ,,)n\ecutive Michael and Wittig anion to i -r.1nr)methylphosphonate
o
L-{ K
Phs
\
I B U O K/ T H F
20"
r ::: .!lJehydes.
c - ,
(""fv. /\
,^...!_*X 42%
PhryCN I \ I CN
o
(o""-.\.o^ ,n.!tX 58To
Clnisen rearrangemenf. Allyl allenyl ethers resulting from isomerizationof allyl A route to propargyl etherswith l-BuOK are ready to undergoClaisen rearrangement.l5 o-substitutedacroleinsis established.
72Yo ; :: nr o-haloanilinesby condensation
[ ) \ 1\ o \:i.::rr I benzyl sulfidescyclize to give r:.. hcnzylic position initiates the
| ?-\
(YY a'.O"-
IBUOK / THF
\
| ?^cs I o*,, /'<,/--/ | rl | ;-)'v\/sls6actto 93%
l
Aldol reactions. A reagentcontainingt-BuOK and (BuO),rTiis highly effective.'n Addition to styrenes. A catalytic amount of r-BuOK in DMSO promotes the addition of ketonesand imines to styrenesat 40'. Clean addition of nitriles is conducted in eitherDMSO or NMP.r' at room temperature
: ,
t ) ,
Potassium chlorate-hydrochloric
acid
CN I
-r\ K R
+ \,/Ar '
rBuoK/ NIVP ---;zc-
Potassium /rans -dichlorotetrac!'enog Disulfides.l Rapid and quantrta! dithiols is effected by this reagent.
CN I
nf*nr '. / R'
rShi,T.,Rabenstein, D.L. JOCg. Ji9O, l9
74-910/o
X
X
II R ' ,\ '
+ \ l
v
-Ar
K
I - B U O/KD M S O II + o-tr--.rt-r--Af ' ' 40" I K
X=O,NPh
Potassium fluoride. 13,256-251 . 13. ln t Irifl.uoromethylthiolation.' fluoride salts) servesto introduce a SCI
64-76%
s ozNl
I, ,v, )/ /:.,
!:r a ' ,
). , a
a
)
it i:, ,{> t
r
2- <
iTsvetkov,N.P, Vakhmistrov,V.8., Koldobsky,A.B., Kalinin, V.N. RCB 48,1685 (1999). 2Nelson,A., Warren, S. ICS(PI) 3425 (1999). rOrita, A., Yaruva,J., Otera,J. ACIEE38,226'7 (1999). lMichel, P, Gennet,D., Rassat,A. TL 40,8575,8579 (1999). 5Mohamed-Hachi,A., About-Jaudet,E., Combret,J.-C.,Collignon, N.S 1188(1999). 6Shen,Y, Zhang,Z. SC 30,445 (2000). TBaumgartner, M.T., Nazareno,M.A., Murguia, M.C., Pierini,A.B., Rossi,R.A. S 2053 (1999). EMoskalev,N., Makosza,M. H 52,533 (2000). 'rMaGee, D . I . , L e a c h ,J . D . ,S e t i a d j i S , . 755,2847 (1999). r{)McConachie, L.K., Schwan,A.L. TL 41,5637 (2000). l rK i m , w . - K . , P a i k ,s . - c . , L e e , H . , c h o , c . - G . T L 4 1 , 5 1I I ( 2 0 0 0 ) . rrvarma, R.S., Naicker,K.P. TL 40,61'11(1999). rrEnders,D., Amaya, A.S., Piene, F. NJC 23,261 (1999). '' Alezza,V., Bouchet,C., Micouin, L., Bonin, M., Husson,H.-P.TL 41,655 (2000). r5Parsons, P.J.,Thomson,P.,Taylor,A., Sparks,T. OL2,571 (2000). l 6 H a n , Z . , Y o r i m i t s uH, . , S h i n o k u b oH . . , O s h i m a ,K . T L 4 l , 4 4 l 5 ( 2 0 0 0 ) . rTRodriguez, A.L., Bunlaksananusorn, T., Knochel, P. OL2,3285 (2000).
Potassium bromide--oxidant. N-Bromosaccharin.t
N-Bromination
and sulfuric acid in aq HOAc
of saccharin by the KBr-KBrO.,
combination
at room temperature yields 74Vo of the product that is a
sourceof electrophilic bromine. Bromination
of anilines.2
Good selectivity (p-bromination)
is observed with KBr
and sodium perborate in HOAc at room temperature.
Aryliodine(Ill)
dichloride.'
f_, Noi
Allylation.2 Desilylativeallllarx SiMea
")',>
* cl'--A
rTavener, S.J.,Adams,D.J.,Clark.l.H Jf ( rTakeda, T.,Uruga,T., Gohroku,K.. Fuyrr
Potassium fluoride-alumina. 20. -1I -r Alkylations, KF-AI2O: is a ctn' poundsin DMF.r'2 Azlactones.3 Formation oi tlrr acetic anhydride in the presenceof Kf Desulfunylation.a Sulfonates an dry stateon microwaveirradiation.
rBlass,B.E.,Drowns,M., Harris.C.L . t-ru 2Blass. 8.8., Burt,T.M.,Liu, S.,Ponlct- | rWang,Y, Shi,D., Lu, Z.,Da| G. SC30.? aSabitha, S.,Reddy.B.\'.S. 1 G.,Abraham,
t Z a j c , B . S C 2 9 , l ' 7 7 9( 1 9 9 9 ) . rRoche, D., Prasad,K., Repic, O., Blacklock,T.J. TL41,2083 (2000).
Potassium chlorate-hydrochloric
\
acid. When
used in
a two-phase
system
chlorine generated from the reagent combination converts ArI to ArICl2. I Krassowska-Swiebocka, B., Prokopienko,G., Skulski, L. SZ 1409(1999).
(H2O-CCI4),
Potassium hexamethyldisilazide. Cyclopentenes.r Ondehydrohro KHMDS carbenes of the RR'C:( abstrationand cyclizationfollou.
Potassium hexamethyldisilazide
Potassium trazs-dichlorotetracyanoplatinate(IV). Disuffides.l Rapid and quantitative intramolecular disulfide bond formation from dithiols is effected by this reagent.
CN
I o'N./\4. R'
(
1Shi,T.,Rabenstein, D.L.JOC 64,4590(1999).
74-91% X i l A.-rrr-r.r.a o ' ' l
-
. Af
R'
\ Potassium fluoride. 13,256-257 ; 15,272; 18,297-298; 19,275-276; 20,313 In combination with thiophosgene, KF (or other Trifluoromethylthinlation.t fluoride salts) servesto introduce a SCFj group to aromatic substrates.
64-760/o
- KF Cl2c=S
ozN{r
-
,l-r / /
+ 1
s
"
ozN{r \
/
.NOz
\' N. RCB48, I 685(1999).
Allylation.2
Desilylative allylation is promoted by KF and CuI.
- : r . \ . 8 . . R o s s i ,R . A . S 2 0 5 3 ( 1 9 9 9 ) .
:
SiMeq 1..'_
J\r'
t <
' i P T L 4 1 . 6 5 5t 2 0 0 0 t .
r\
: : '- :(n0). I . r l r - 1 5( 1 0 0 0 ) . ' : r t s 5( 2 0 0 0 ) .
.1nnby the KBr-KBrOj combination r: .., 1 'cl
'r:. : hromination)is observedwith KBr
.r r1000).
tl
c )l'
tr
* cr-"\
KF- Cul THF - DMSO
'fAr.r \
: rx X ) ) .
tJ
'
.i two-phase system (H2O-CCI4)' - :'.\L'r1sArI to ArICl2. r1.l-109(1999).
^rCFs
85Yo
) ..., l r s n o nN . . S I 1 8 8( 1 9 9 9 ) .
/fs
NOz
I t
/
st\.'^\r'\'
67Yo ( E : Z 9 0 : 1 0 ) rTavener, S.J.,Adams,D.J.,Clark,J.H.JFC 95,l'71(1999). rTakeda,T., Uruga,T., Gohroku,K., Fujiwara,T. CL821 (1999).
l
t t
,a Potassium fluoride-alumina. 20, 3 13 Alkylations. KF-AI2O3 is a convenient base for N-alkylation of lactam-type compoundsin DMF.r'2 Azlactones.3 Formation of these products from N-acylglycine and aldehydes in acetic anhydride in the presenceof KF-Al2Oj apparently requires a lower temperature. Desulfunylation.a Sulfonates and sulfonamides suffer X-S bond cleavage in the dry stateon microwave irradiation. lBlass,B.8.,Drowns,M., Hanis,C.L.,Liu, S.,Portlock,D.8.TL40,6545(1999). rBlass,8.8., Burt,T.M.,Liu, S.,Portlock,D.8.,Swing,E.M. TL 41,2063(2000). rWang, Y.,Shi,D.,Lu,Z.,Da|G. SC30,707(2000). rsabitha,G.,Abraham, J.S.S21745(1999). S.,Reddy,B.VS.,Yadav,
Potassium hexamethyldisilazide. Cyclapentenes.r On dehydrobromination of 2-substituted 1,2-dibromoalkaneswith type are generated. Intramolecular hydrogen KHMDS carbenes of the RR'C:C: abstrationand cyclization follow.
Potassium hydroxide
(Me3Si)2NK
iT+
,o+ X"
Prima4 dr RNHt + Pgg.r glycol at lll by KOH in diethylene
\ / /
Y
d:*1
72% Benzyl nitrilcs.2 Tertiary benzyl nitriles are preparedby substitutionof aryl fluorides. rTaber, T.E.,Neubert, T.D.,Batra,D. JOC 64,9673(1999). D.F.,Christos, 2Caron,S.,Yazquez, E., Wojcik,J.M. "/ACS122,712(2000)
Potassium hydride.
1,, :
Indoles.t o-Alkynylanilines undergocyclization (S-endo-digprocess)on treatment with KH in NMP. Sodium hydride is largely ineffective (<5% yield) in bringing about the reaction.
'l
Ph
. ,,
KH/ Nr,4P rZ\-\ + | ll 2s \.,^-N
)-Ph H
l - l
72-79o/.
{:.:,
Pn*M
Zabjek,A., Petric,A. TL 40. Q7- ,lc rBallini, R., Bosica,G., Parrini.\l ('1'Rahman, S . M . A . ,O h n o ,H . . \ t a e r e \ ' .
Potassium monoperoxysulfate.
C
-i00; 19, 2'l'l ; 20, 313-3 I 5 Epoxidations. Combinatron l idine and o-trifl uoromethylbenra caseof an active alkene(e.g.. tns Other types of mediatorsinclu& and the N,N'-dialkylalloxans l.'
t
;
Ring expansion,2 2-Cyano-l-vinylcycloalkanolsare induced to expand by two carbonunits on heatingwith KH and 18-crown-6in THF.
o \
OH
f-"1:) Js
KH - 18-crown-6 THF A
/-) I L-CN \___,/\ . - P h 72o/o
rRodriguez, A.L., Koradin,C., Dohle,W.,Knochel,P.ACIEE39,2488(2000). 2Shia,K.-S.,Jan,N.-W.,Zhu,J.-L.,Ly,T.W.,Liu, H.-J.TL40,6753(1999).
Potassium hydroxide. Ketone cleavage,t Enolizable ketones are cleaved to furnish carboxylic acids with KOH in DMF. Nitro aldols.2 Condensation of nitroalkanes with aldehvdes can be performed in dry media (powdered KOH as condensationagent).
Oxidations. Oxidation oi d conditionshas been reported.'Ao the constituent alcohols.6Accordu The double bond of an enol ts arylaceticestersvia hydroxlnrrl
steps.T Basedon the facile oxidatlon( (a multipurposesyntheticreagcn that is, displacementwith PhSH.c Cyclopropyl aryl ethers are co last two steps involve sulfide o group.
Potassium monoperoxysulfate,
: ' -,"+ x \__\t l
OBn NHz
KoH diethylene glycol 210"
d'-:' 50%
.r substitutionof aryl fluorides. ^on 1999).
361
RNHt + p6p,3 Primary aliphatic amines are converted to alcohols in good yields by KOH in diethyleneglycol at 210'.
72To
-r
Oxone@
pn,'\.r"t...NHz
-
dieth'lenegl'col
pn*OH 59%
r
' ,,tdo-tlig process)on treatment 57c yield) in bringing about
tZabjek, A., Petric, A. fL 40,607'7 (1999). rBallini, R., Bosica,G., Panini, M. CL 1105(1999). 'Rahman,S.M.A., Ohno, H., Maezaki,N., Iwata, C., Tanaka,T. OL2,2893 (2000).
:r. , -
'/z/
\\..
-)-rn --N n
-.79%
o.- .,:.' induced to exPandbY two flri
Potassiummonoperoxysulfate,[email protected],259;14,26'7;15,274-275;16, 285; 18, 300; 19, 277: 20, 3 l3-315 Epoxidations. Combination of Oxone and the iminium salt derived from pyrrolidine and o-trifluoromethylbenzaldehyde is effective for epoxidation of alkenes.r In the case of an active alkene (e.g., trisubstituted alkene), pynolidine is an adequatecatalyst.2 Other types of mediatorsinclude ct-functionalizedketones (e.g., ct-acetaminoacetone)r l.a and the N,N'-dialkylalloxans
N
po
N
c
(1)
t-r -r9 :]lllt (2000)
l\ -
,, l'urnishcarboxylic acids with rl,ichydescan be performed in
Oxidations. Oxidation of alcohols to aldehydes with Oxone-TEMPO under mild conditions has been reported.5Acetals are oxidized to esters,with releaseof one mole of the constituentalcohols.6Accordingly,this oxidation can be usedto cleaveTHP ethers. The double bond of an enol is readily cleaved, therefore a route to cr-keto estersfrom arylaceticestersvia hydroxymethylenationis viable becauseof the high yields in both steps.T Based on the facile oxidation of sulfides to sulfones with Oxone, phenyl vinyl sulfone (a multipurpose synthetic reagent) can be obtained in three steps from 2-bromoethanol, that is, displacementwith PhSH, oxidation,and dehydration(via mesylation).n Cyclopropyl aryl ethers are conveniently prepared' from phenols in a manner that the last two steps involve sulfide oxidation and reductive removal of a benzenesulfonyl group.
:
I t
, ,
Potassium permanganate
o"on"'l cHcr3on
Ph's-t o-l\"oo*"
\:,/
"r[f
Ketones are also Produced fron copper(Il) sulfatepentahydratern dr are cleaved with the same reagent T Aromatization l I,4-Cvclohe r
,o$coour" 100%
Oxone in water oxidizes o-iodobenzoic
acid to 2-iodoxybenzoic
lcetone at 0o. acid at 70' (yield
19-817o).to It also can be used in the workup of hydroboration.rl Chlorination.
Amides
and carbamates
undergo
N-chlorinationr2
by Nacl-Oxone.
S.E..lm.rn A.R.,Mallakpour. Hajipour, : \oureldin,N.A.,Bellegarde. J.\\' .! 'r :9 'Goksu, Altundas, \ S( R., Sutbelaz. S., '\,lcBride,c.M., chrisman,w.. Ham.. c
Under the same conditions, oximes afford a-chloro nitroalkanes.rs When the chlorine source is absent, regeneration of carbonyl compounds from oximes and hydrazones occurs.ra Desilylatinn.ts primary
A solution
and aromatic
of Oxone in 50Vo aq MeOH
t-butyldimethylsilyl
is effective
ethers at room temperature.
for cleaving
In a molecule
containing both types of ethers, the aliphatic silyl group can be selectively removed by
Potassium selenocyanate. Dialkyl diselenides.t A conr o KSeCN in aq DMF in the presencc and the resultingalkyl selenideronr
virtue of the faster rates of hydrolysis.
I t
t .,'|
(.". <^
rArmstrong,A., Ahmed, G., Gamett, I., Goacolou,K., Wailes,J.S. Z 55, 2341 (1999). 2Adamo,M.F.A., Aggarwal, V.K., Sage,M.A. JACS 122,8317 (2000). rArmstrong,A., Hayter,B.R. 255, 11119(1999). aCarnell, A.J., Johnstone,R.A.W., Parsy, C.C., Sanderson,W.R. TL 40,8029 (1999). 5Bolm, C., Magnus,A.S., Hildebrand,I.P.OL2,1173 (2000). 6Curini,M., Epifano, F., Marcotullio, M.C., Rosati,O. SL'177 (1999). TMahmood, S.J., Mclaughlin, M., Hossain, M.M. SC 29, 2957 (1999). 6l-ee,J.W., Lee, C.-W., Jung,J.H., Oh, D.Y. SC 30, 2897 (2000). eHollingsworth, G.J., Dinnell, K., Dickinson, L.C., Elliott, J.M., Kulagowski, J.J., Swain, C.J.,Thomson,C.G. TL 40,2633 (1999). r0Frigerio,M., Santagostino,M., Sputore,S. JOC @,4532 (1999). l ' R i p i n , D . H . B . ,C a i , W , B r e n e k ,S . J . T L 4 l , 5 8 1 7 ( 2 0 0 0 ) . r2Curini,M., Epifano, F., Marcotullio, M.C., Rosati,O., Tsadjout,A. 54 813 (2000). rrCurini, M., Epifano, F, Marcotullio, M.C., Rosati,O., Rossi,M. I55, 6211(2OO0). raBose,D.S., Narsaiah,A.V, Lakshminarayana, V. SC30,3121 (2000). rssabitha,G., Syamala,M., Yadav,J.S. OL 1, l70l (1999). Potassium organotrifl Alkylations.
uoroborates.
Allylation
of aldehydes with
proceeds at low temperatures by using BFj.OEt2 analogously.'
In the presence of (acac)Rh(Co)2
aryltrifluoroborates
C {(' Krief,A., Dumont,W.,Delmotte.
Potassium superoxide. Hydrosilylation and the Trsl .{cH2osiEh and ACOOCH-Ar
THF at 40".r Sulfuxides. Sulfides are ortdr: rs mediatedby the trimethylsilllgwo
T.,Gouner.[) . Le Bideau,F.,Coradin, rChen, Y-P fL 41.5:.:: ,: Huang, Y.-J.,
Potassium trimethylsilanolate. Nitrile hydrolysis.t Reflurrnt amides.At least in the case oi Ph dramatic elf'ecton the product rrcl with MejSiOK, 837o.
the stable allyltrifluoroborate as catalyst. Crotylation and a phosphine
reagent
is performed
the alkenyl-
K.L TL 41.37.17 {lOfir ' Merchant.
and
add to aldehydes and enones, the latter in a conjugate fashion.2
rBatey,R.A., Thadani,A.N., Smil, D.V, Lough, A.J. S 990 (2000). zBatey,R.A., Thadani,A.N., Smil, D.V. OL 1, 1683 (2000).
Potassiumpermanganate.13,258-259;14,267;15,273-214;18, 301;19,277-278; 20,315-316 Oxidations. The oxidation of alcoholsto carbonyl compoundsusing KMnOaAl2Oj (no solvent)ris very rapid.
Pyridinium fluorochromate. Oxidation.t Trimethl IsrlrI cd {6. 6:e Ho.T.-L..Jana.G.H../CCSrf/
(2-Pyridyldimethylsilyl )methr..llirl Hydroxymethylation.l Tht' t 2-trimethylsilylpyridine.Its alkyb RCH2OH are quite strightforn ard
(2-Pyridyldim€thylsilyl)methyllithium
Ketones are also produced from amines2 by oxidation with KMnOo supported on copper(Il) sulfate pentahydratein dichloromethane. Bridged alkenes such as norbornene are cleavedwith the samereagent.This methodis an alternativeto ozonolysis.r Aromatization 4 1,4-Cyclohexadienesare dehydrogenated with KMnOa-Al2Oj in 100% r i' ,'Joxybenzoic acid at 70" (yield f,'a
:.rtion.l1
g,, \-chlorinationr2by NaCl-Oxone. ru' ., kanes.lrWhen the chlorinesource l4 r\: :itr'. ruld hydrazonesoccurs. ,- \lcOH is effective for cleaving r'. r,'r)m temperature.In a molecule g: jp can be selectivelyremoved bY
acetoneat 0o. rHajipour, G. CL 99 (1999). S.E.,Imanzadeh, A.R.,Mallakpour, rNoureldin, J.W.S 939(1999). N.A.,Bellegarde, rGoksu,S.,Altundas, R.,Sutbeyaz, Y SC30, 1615(2000). rMcBride,C.M.,Chrisman, B. TL 40,45(1999). W, Harris,C.E.,Singaram, Potassium selenocyanate. Dialkyl diseknides.t A convenientaccessto RSe-SeRliom RBr is by reactionwith are hydrolyzedin situ KSeCN in aq DMF in the presenceof K2COj. Alkyl selenocyanates and the resultingalkyl selenideions undergoaerialoxidation. IKrief,A., Dumont,W.,Delmotte, C. ACIEE39, 1669(2000).
r : : - J S .1 " S S , 2 3 4 I ( 1 9 9 9 ) . l()00). r: rr. $.8029 (1999).
Potassium superoxide. Hydrosilylation and the Tishchenko reaction. Aromatic aldehydes give both ArCH2OSiEt3and ATCOOCH2ATon treatment with KO,-18-crown-6 in benzene or
q99). Iq99).
THF at 40".r
J.M., Kulagowski, J.J., Swain,
Sulfuxides. Sulfides are oxidized to sulfoxides with KO2 and MerSiCl. This reaction radical.r is mediatedby the trimethylsilylperoxy lLe Bideau, E.TL4l,5215(2000). D.,Henique, J.,Samuel, T.,Gourier, F.,Coradin, rChen,Y.-J.,Huang,Y-P TL41,5233(2000).
. !-: ..r.\. SL813(2000). , i . . r l r 5 5 , 6 2 1 1( 2 0 0 0 ) . : - l(Xn). I
Potassium trimethylsilanolate. Nitrile hydrolysis.t Refluxing with MerSiOK in THF converts RCN to primary amides.At least in the case of PhCN, the counterion of different alkaline salts has a dramatic effect on the product yields: with Me,SiOLi, 57o, with MejSiONa, 40Vo, and withMerSiOK,83%.
f..; .r.rble allyltrifluoroborate reagent :. ,:talyst. Crotylation is performed .::.: e phosPhinethe alkenYl- and ts ..:i:.r in a conjugatefashion.2 [
IMerchant,K.L TL 47,314'1(2000). Pyridinium fluorochromate. Oxidation.t Trimethylsilyl ethersare directly oxidized to carbonylproducts.
- . r r l
,
rHo,T.-L.,Jana,G.H.JCCS(T)46,639(1999).
15.l-.t 274;18'301;19,277-278;
(2-Pyridyldimethylsilyl)methyllithium.
ci:\,,n)l compoundsusing KMnO4-
Hydroxymethylation,t The organolithium reagent is obtained by lithiation of 2-trimethylsilylpyridine.Its alkylation with RX and oxidative desilylation to provide RCH2OH are quite strightforward.
I
t t
,
a
a-
2-Pyridyl methoxymethyl sulfi de
r-
)siAruo
('\
t-BuLi )s,Ar/
t*
n -
oH
+
\E
)r,A*y'
(ri"
\=
rltami.K.. Mitsudu.K.. Yoshida.J. TL 40. 553'7(1999).
2-Pyridyl N-methoxy-N-methylcarbamate. Ketone synthesis.t It is not necessaryto prepare individual Weinreb reagents for the preparation of ketones. Sequential exposure of the title pyridyl carbamate to two different organometallic compounds is the most expedient procedure.
'
:t ,
/ l ' t I
' ;
o d^\ M"o-NAoAN, I
RM
o M"O-rA*
THF
+ THF
pn-si-o
o
R,M
il
Quinoline-2-thiol. Alknnethials.t The reageu releasedfrom the mixed sultidcs can be consideredas a sourceoi I
Ph
II ^,-\^ f(
K
I
+
'(
.\
s
I Lee, N.R., Lee, J.l. SC 29, 1249 0999).
2-Pyridyl methoxymethyl sulfide. O-Methoxymethylation.r The MOM ethers are formed by reaction of the title reagentwith alcoholsin the presenceof AgOTf.
M.D. fL {l. I Zhang,I.,Matteucci,
lMarcune, B.F.,Karady,S.,Dolling,U.-H.,Novak,T.J.JOC 64,2446(1999).
Quinuclidine N-Oxide. Alkylatinns.t Quinuclidrn lation reactionsthat typicalll rc< W1nn.D O'Neil,I.A.,Lai,J.Y.Q..
; \ o H . i l r l -t-_-r,A*y'+\E (_ E
Quinoline-2-thiol. Alkanethiols.t The reagent is converted to mixed sulfides by alkylation. Thiols are releasedfrom tJremixed sulfides on reduction with NaBH.CN. Accordingly, this reagent can be consideredas a source of hydrosulfide. f :J:-.rrcindividual Weinreb reagentsfor r. : ihc title pyridyl carbamateto two e. :-.-.irc'nt Drocedure.
o
c c.
- -jF n'-Ln
r
pn-siro
O
\-( ( )**
.
- t H
^'N--(
P h K ) b NaBH3CN / HOAC
O
\ ( . ' NN -{ H Ph-si-o ", 'b
Ph v"v
\__J
HS 9SYo
r:
r lirrmed by reaction of the title tZhang,1.,Matteucci,MD. TL 40, 146'7(1999). f'J. ll'16 (1999). Quinuclidine N-Oxide. Alkylations.t Quinuclidine N-oxide offers an alternative choice to HMPA in alkylation reactionsthat typically require suchan additive. rO'Neil,I.A.,Lai,J.Y.Q., Wynn,D. CC59 (1999).
) I I , ,t
Matsuda. L. Takeuchi, K.. Itotl K :Matsuda, I., Niikawa, N., Kuszh 'Fukuta, Y, Matsuda,I., Itoh. K. I
Rhodium. Hydrogenation.t Rhodium in nanosize(from reduction ofrhodium trichloride with NaBHa and stabilized with water-soluble alkylammonium salts) is effective for hydrogenation of arenes at atmospheric pressure and room temperature under biphasic conditions.
Rhodiumcarboxylats. 13.! 19.281-285:20.-1I I 306-3071 Carbenoidinsertions. . lormation of dehydropep 1,4-dro retrahydrofuranones,r
'n-Yo
lSchulz, J.,Roucoux, A., Patin,H. CEJ6.618(2000).
\
MeooCAH2
t.
Rhodium carbonyl clusters.13,288; 15,334;18,305-306;19,280-281;20,317-318
a/ b-
t'-l -'l
Hydroformylation. A phosphine plays a crucial role to suppress hydrogenation during hydxoformylationof 4-vinylpyridine.rThe N-vinyl group of a divinylpynole can be retainedto achieve selectivehydroformylation of a carbon-linked vinyl residue.2 1-Indanone-3-carboxylic esters.l Carbonylation of ethynylarenes in the presence of alcoholsleadsto the indanoneesters.
' tii\ t-,
+ CO + R'OH -
/cooR'
Rholco)ro
ZV,
*-\,,\1 \
(
o
o
1
\/
The insertion at C-2 and C gives rise to Cr-symmetric co the catalyst, the reaction leads
<
'Caiazzo, A., Settambolo, R.,Pontorno, L.,Lazzaroni,R. JOMC599,298(2000). 2Lazzaront, R., Settambolo, R., Mariani,M., Caiazzo, A. JOMC 592,69(199q. rYoneda, 8., Kaneko,T.,Zhang,S.-W.,Onitsuka, K., Takahashi, S. ZL 40,7811(1999).
Rhodium carbonyl clusters-hydrosilanes. Silylfunctionalizations. The reaction of alkynes with this reagent combination can give B-silylacrylamides,rc-silylmethyl cr,B-unsaturated aldehydes,2 or cyclization products,r dependingon reactionconditions(additives)and substratestructures.
/--\
(
\--J
lr
/'
X OH
-- "'--". + H-si-Ph ( PhH1oo' /
\
co tRh4(co)12
\--J
C*-ro" . A key building block fr taking advantageof the prefa
OTB
cHo
>< \-st_Ph /
Y
.,Jo-\-/ \
MeoocAN2 81%
\
Rhodium carborylates I 'Matsuda,I.,Takeuchi,K.,ltoh, K.TL40,2553 (lggg). 2Matsuda,I., Niikawa, N., Kuwabara, R., Inoue, H., Nagashima, H., Itoh, K' JOMC 574' 133 (1999). rFukuta, Y., Matsuda, I., Itoh, K. TL 40,4703 (1999).
l-,
r.
.rrr)n of rhodium trichloride with r,,nium salts) is effective for ,,rnrtemperatureunder biphasic
Rhodium carboxylates.13,266;15, 2'18-286;16,289-292;17,298-302; 18, 306-307; 19, 281-285; 20, 318-320 Carbenoidinsertions. Advantagehas beentaken of the insertionreactionin the o-silyl a-amino acid derivatives,2functionalized formation of dehydropeptides,l andspiranesystems.5 1,4-dioxenes,a tetrahydrofuranones,3
Ph,,zyo ' '
ro) Ho2
MeoocANz
Rh2(oAc)4
t'*;i
Ph'4\'O
rraeoocAo
ri 16:19,280-281;20,317-318
42Yo
u...,. rrrlc to suppresshydrogenation -. : . I rroup of a divinylpynole can be : r - - . ' r - l r n k e vdi n y l r e s i d u e . 2 lr :
*
Nz\
"{_I}" /zN,
,t c'thynylarenesin the presence
oil,zRh2(oAc)4
lA{"
#
27Yo
4Y,|
- R - -
\-\
/
cooR'
)
o , ,.1 599.198(2000). l, "' 5e2.69( 1999). a - : . : 1 1 - , 1 0 , 7 8(1119 9 9 ) .
The insertion at C-2 and C-5 of N-Boc-pynolidine in the presenceof Rhz[(S)-DOSP]r gives rise to C2-symmetriccompounds.6On the other hand, by using Rh2[(R)-DOSP]aas the catalyst, the reaction leads to mixtures of diastereomersand regioisomers.
N2
|\v
ru-Aoc +
FCOOMe Ar
Rh?(s-DosP)4
---..----------.----.--N - B o c COOMe
lc..i
...:rhthis reagentcombinationcan or cyclizationproducts,r ,..i.'hvdes,r
1l' .
.:ir-':tfUCtUf€S.
fK..'
A key building block for synthesis of eburnamonine was assembledby the reaction taking advantageof the preferred insertion into a tertiary C-H bond by Rh-carbenoids.T
cHo
us1_en 81%
o MeOOC
(-)-eburnamonine
I
I
, ,
368
Rhodiumcarboxylates
o
An exceptionally reactive and selective chiral dirhodiumlll.l carboxJmides, Rh2[(4S)MEAZI4, has the potential to significantly broaden the applicability of asymmetric synthesisusing diazocarbonyl compounds.8 Rearrangements. A variety of reactions catalyzed by Rh(II) carboxylates, including Wolff reanangement of 3-diazo-2,4-dioxo-1,2,3,4-tetrahydroquinolinesleading to oxindoles due to in situ decarboxylation,einsertion followed by [2,3]sigmatropic
/h tl o
reilrangementr0and Claisen rearangement,lr serve to affirm their synthetic potential.
o I
Y\-.sen * ?'""' \N,
SiMe3 Rh2(OAc)a
sen
)
/--,.
ll ct'Y
o
\
I
86%
) / 2
Four-membered rings.t2 Rearrangement of a-diazo thiol esters to substituted ketenes and cycloaddition of the latter to alkenes lead to cyclobutanones. A similar addition to imines gives BJactams.
tI rl .-/ , '
7--
, - '
t=
Wolff rearrangement. Srlrl I on exposureto rhodrurwI diazoketones Nr
||-
R' Y A - s i E b
t i.' l.llr i
o o
ll *, pns'tr'rzN'.
Rhz(oAc)4
\-1
(i
.""il-
b^
Phs?-)
1
73-78o/.
Diheterobicycloalkanes.tt Hydroformylation of l-alkenes that contain in-chain heteroatomsis terminated by cyclization.
a^---1 a*r \.,^-/ \-NH,
H 2 tc o Rh2(OAc)a phosphine
-." Rh2(OCCJ4 PhH
?]
o
\---l
.
*
a-r*€ \-t'tH
80To
rBuck, R.T., Clarke, PA., Coe. D.\l . Iln N . D . . S w a n n .E . C E J 6 , 2 1 6 0 ( 2 0 0 O ' :Bolm, C., Kasyan,A., Drauz, K.. Gunrlrr 'Lacrampe, Leost, F., Doutheau.A Il, F., rHilgenkamp,R., Brogan,J.B.. Zerctrr- C 5Aburel.P.S..Undheim. K. JCS(P1r lt9l r ('Davies, H.M.L., Hansen,T., Hopper.D rt ' W e e ,A . G . H . ,Y u , Q. fL 41,587(lm, rDoyle, M.P., Davies,S.B., Hu. W. Ol !. I 'Lee, Y.R., Suk, J.Y.,Kim, B.S. fL {1. 8:l r{' Carter. D.S.. Van Vranken.D.L. fL {0. l6 rrWood, J.L., Moniz, G.A., Pflum. D .{ . Se
( 1999). rrLawlor, M.D., Lee, T.W., Danheiser.R L 'tBergmann,D.J., Campi, E.M.. Jac\soo"u rrPimrng, M.C., Kaliappan,K.P OL 2. 353 I 5 M a r s d e nS, . P , P a n g ,W . - K . C C I 1 9 9 r l s Rhodium
Carbonyl ylides generated from 6- and 8-carbonyl-c[3*2]Cycloadditions.ta diazoketones undergo cycloaddition with quinones. Chemoselectivity (C:C vs. C:O) of the reaction is dependenton the solvent and catalyst.
perfl uorocarboxylates.
Alkoxy c arb o ny lm ethy I en o I c{., from carbonyl
compounds
is b1 a R
ester. The enol etherification is applrcd
Rhodium perfluorocarboxylates
o tl
rc:.-::r,il ) carboxamides,Rhz[(a,S)::: rpplicability of asymmetric
.r-Yo
a-..,tJ hy Rh(II) carboxYlates, l. : j tctrahydroquinolinesleading t : :, 'lltrwed by [2,3]sigmatroPic
Rh2(ocoA04
[].::: their syntheticPotential.
Rhz(OCOAT)r
SiMeg
I
)fsen - I \
\
N2
860/o
.
64Yo
c . , , . , t h i o l e s t e r st o s u b s t i t u t e d A similar ei.: r,' cvclobutanones.
Wolff rearrangement. Silyl ketenes are readily on exposureto rhodium(Ilt octanoate.rs diazoketones
R
73-78o/o
L c n e s t h a t contain in-chain
,"'rrrry
/
-J
80o/o
R'NH2 -+ cH2cr/
from
ct-silyl-ct-
_ t -2\.l R
' ' Y ' r u 'r\ iiet. H
IBuck, R.T., Clarke, P.A., Coe, D.M., Drysdale,M.J., Ferris, L', Haigh, D.' Moody' C'J', Pearson, N . D . . S w a n n .E . C E I 6 . 2 1 6 0 ( 2 0 0 0 ) . rBolm, C., Kasyan, A., Drauz, K., Gunther, K., Raabe,G. ACIEE 39' 2288 (2000). rlacrampe, F., Leost, F., Doutheau, A. TL 41,4773 (2000)aHilgenkamp,R., Brogan,J.B.,Zercher,C.K. H51, 1073 (1999). 5Aburel,P.S.,Undheim, K. JCS(PI) 1891 (2000). 6Davies,H.M.L., Hansen,T., Hopper,D.W., Panaro,S.A. "/ACSl2l' 6509 (1999). 7Wee,A.G.H., Yu, Q. ZL 41, 587 (2000). sDoyle,M.P, Davies,S.B., Hu',W. OL2, 1145(2000) elee, Y.R., Suk, J.Y.,Kim, B.S. TL40,8219 (1999). l{)Carter.D.S.. Van Vranken, D.L. TL 40,161'7 (1999). lrWood,J.L., Moniz, G.A., Pflum, D.A., Stoltz, B.M., Holubec'A.A.' Dietrich, H.-J. ,/ACSl2l' l'748 ( l 999). lrLawlor. M.D., Lee, T.W., Danheiser,R.L. JOC 65,4375 (2000)' lrBergmann,D.J., Campi, E.M., Jackson,W.R., Patti,A.F. CC 12'19(1999). raPimrng,M.C., Kaliappan,K.P. OL 2, 353 (2000). r5Marsden,S.P.,Pang,W.-K. CC 1199(1999). Rhodium
a:-.: Ir()m 6- and E-carbonYl-c}.::::,'.clcctivity(C:C vs. C:O)
RVsiEt3 Rh2(ococ7Hls)4 llz ,j\ -SiEt3 ll PhH 20' C Y O O
formed
perfl uorocarboxylates.
Alkoxycarbonylmethyl from carbonyl
compounds
enol ethers.t
A convenient preparation of these enol ethers
is by a Rhr(OCOCF.T) 4-catalyzed reaction of a diazoacetic
ester. The enol etherification is applicable to ct-pyridone.
I
I ) ,
Ruthenim-+arbene complexes
. ,,,,,,,,,,,,,,,,Hr,_o {_cooEt
Rh2(ococFj)4
\
/-COOEt
/-\
,-\
,. |
clcHzcH2ct o
//-
v
I
PCys
\___!
ct"..] 69%
/Ph oc,r ct
c r . lI' J
PCYg rBusch-Petersen, J.,Corey,EJ. OL2,1641(2000).
I
(1)
Rhodium(Ilf
chloride. Aryl ketones.l Benzyl alcohols and alkenes are united by a catalytic reaction using polymeric phosphine ligated RhCl3hydrate.
/
{
n l
\ \
z)-N..rN{-)-
t
I "^ "r '. : R u =r
CI. I
\J
PCve RhCl3 x H2O
I
,
r \
(4)
Ph3P r.f PhMe
o-N
NH,
rJun,C.-H., Hong, H.-S., Huh, C.-W. TL40,8897 Oggg).
i1"i'-1"q -X--
o
R = Me, CF: Ruthenium-<arbene complexes. 18, 308; 19, 285-289; 20, 320_323 The prevalentcatalystsfor metatheticreactionsof alkenesor alkynes are 1,2,3, 4, and 5. Those containing imidazol-2-ylidene ligands are readily prepared from 1 by ligand exchange.' complex 6 is a precatalyst for various ring-closing metathesis (RCM) reactions.2 Its counterion affects reactivity and selectivity. The immobilization of the Ru complexes to polymer yields a series of RCM catalysts that are recyclable and possess comparable or better reactivity than their homogeneouscounterparts,particularly in dealing with highly hindered substrates.3-5 The four-coordinate complexes 7, which possesstrigonal pyramidal geometnes, zue moderately effective RCM catalysts, but reactions involving them are greatly accelerated by the addition of HCl.6 Also prepared from I and allyl 2-bromo-2-methylpropanaoteis a multifunctional catalyst 8 that is capable of mediating three mechanistically distinct reactionsT:ring-opening metathetic polymerization, atom-transferradical polymerization, and hydrogenation. The use of tris(hydroxymethyl)phosphine is recommended for removal of the ruthenium residue from the products.8Addition of a modest amount of pb(oAc)a (1.5 equiv relative to the Grubbs catalyst) at the end of the reaction rids all the colored imnurities.e
(7)
Metathetic rtng closure. ( tbr RCM and the scope of ru the elaboration of cyclic srruc those containing phosphine o I -(Dialkoxyboryl)vinylcycloal\a Formation of a /rcns-cycloct the metathesis(using either I cr r undergocyclization.I8
/-cooEt
/
./-\ ---J
PCys
cr,,.| .,tlui
,Ph
BF; h
?"t' ""1:lo:r:,,
I
PCys (1)
pCvr
5
4
I
\
371
comPlexes
Ruthenium-carbene
\
// \\ F-
z)-N..,,N-L-)-
t
r
I UI" RU:r 'Ph cl' | ' PCy:'
\
(3s) C+-Cssaturated (3u) C+-Csunsaturated
(2)
-. r:\ \_ir\r,i!_>
.J by a catalytic reaction using
Bn,, 1,,_ Ph
,'._,1"
rLi-\", (5)
(4)
PCYg R ,O,,. I ,Ph RuJ X R \ ^ I t ( n
^">(-R K ' R
ct,,...,1 * ,*'--^ "--a**,
RsP-
X
I
K
,
(6)
o / PCYg )-F Br c1,,. I ro ^ , r l Iu i
i I
PCYs
D
R = Me, CFs r. l(1..120-323 fr .:-rcncSor alkynesarc l, 2, 3, 4, rf :r.iJrlv preparedfrom I by ligand rr.--..,'singmetathesis(RCM) reac-r:, Ihc immobilization of the Ru r.:. lhat are recyclableand possess L. - 'unrerparts,particularlyin deal, ': -.'nrl pyramidalgeometries.are r ..::rg them are greatly accelerated 11 -'rromo-2-methylpropanaoteis a distinctreacg ':' . r' mechanistically -:: j::.1dr radical polymerization,and nr::.cndedfor removal of the rutheIr.: .unountof Pb(OAc)a(1.5 equiv r, :. ::J' rll the coloredimpurities.q
(7)
(e)
(8) PCvr - -rSePh Ct,,. |
^,rlui I
PCYs (10) Metathetic rtng closure. Catalyst 1 pan be regarded as the standard workhorse for RCM and the scope of its applications continues to expand. Thus, its use in and 3-pyrrolines,rr'12 the elaboration of cyclic structures including azaspirocycles,l0 sulfonamides.r6 dioxasilanes,rs those containing phosphine oxides,lr phosphinates,ra l-(Dialkoxyboryl)vinylcycloalkenesare obtainedfromx-alken-1-ynyl boronates.rT Formation of a tans-cyclooctene system reveals a profound stereochemicaleffect of the metathesis(using either I or the Schrock catalyst). The other diastereoisomerdoes not undergocyclization.r8
It
Ruthenium-carbene
complexes
Structural modifications such el high efficiency. (1)
,,,rr--a '
n,,T--
o-t/o tl
o-t/o tl
I
e$!€.
oTBS
uh:_.:
on elaboration of 1,5-hexadiene-3,4-diolthrough a l,3-dioxolane derivative, the RCM delivers a precursor of either e-ro-brevicomin or endo-brevicomin.reA route to ( + )malyngolidealso exploits the RCM process.20A successfulcyclization-fragmenrauonapproach to medium-sized rings is based on the RCM reaction of 2-hydroxycycloalkanones that are substitutedwith proper alkenyl groupsat both ct- and ct,_positions.2r
)ro1." o i! A"\z ,
exo-brevicomin
)r-, "o
2
Higher activity of catalysts eo RCM has been observed.r{Such cr tuted cycloalkenes,25'26 and vanotrs highly active catalyst 9 is recover{
ETOOC r
t
: llt,t '- lti'
OTBS
/\
'.. p;
(1)
AJ,,,,r'
/J,
+H2
'
endo-brevicomin
ETOOC\
Cross-metathesis. Funcumrl using catalyst I has been well esrl gives to-silylstyrenes,2e bet*eto butenonitriles.30Alternativell. ho 1,4-diaryl-2-buteneis first camed < is the homo-metathesisof monosub
\
o +
q^*ottt
+
r
{z |
\
l
Rz\'c\ I
q^#""'n -ro
l-o
92%
(+)-malyngolide
Both catalysts I and 2 are effcr conjugateddienes from alkenesand is obtained from (R)-3-acetoxr-Furthermore,the reaction of 1.6{rv
COOMe (1)
osiMe3
\ --\ f
Pb(OAc)a
o n = 0 ,1
11 \ l t >-+4" o
Ts R--N-..,
rlrr
Ruthenium-carbene
complexes
are pleasing becauseof their Structural modifications such as those shown below22'23 high efficiency.
i")
o
(1)
o
ethylene cH2cl2
OTBS
a . ' . t..:. 'r_.:. t
,
** a$,", t
tl
l.l-dioxolane derivative, the ,-brevicomin.re A routeto (+)I er clization-fragmentationap,,n of 2-hydroxycycloalkanones ':r,1o'-positions.2l
t
u
bn
OTBS
Higher activity of catalysts embodying imidazolin-2-ylidene ligands (e.g., 3u) for RCM has been observed.2aSuch complexes as 3u and 5 allow formation of tetrasubstiThe and various functionalized analogues(e.g., 1-cyanoalkenes2T). tuted cycloalkenes,25'26 highly active catalyst 9 is recoverableand recyclable.28
ETOOC\f-/ x + Etooc'
exo-brevicomin
(3u) ETOOCV^I / \ r l \"/ Etooc-
,
100Yo Cross-metathesis. Functionalization of terminal alkenes by the metathetic method using catalyst L has been well established.The reaction between styrene and vinylsilanes gives co-silylstyrenes,2ebetween allylarenes and acrylonitrile leads to 4-aryl-2butenonitriles.3oAlternatively, homo-metathesis of two allylarene molecules to give 1,4-diaryl-2-buteneis first carried out and the cross-metathesisfollows.rr Also of interest
- -l-.,-1 6 - | endo-brevicomin
is the homo-metathesisof monosubstitutedallenes to symmetrical allenes.r2
s
tt'
RAc-
-
RAn
"cgHrg I
CgHrs
[
(+)-malyngolide
Both catalysts I and 2 are effective in promoting cross-metathesisleading to vanous conjugateddienes from alkenesand alkynes.13s4Chiral2-(ct-acetoxybenzyl)-1,3-butadiene is obtained from (R)-3-acetoxy-3-phenylpropynevia cross-metathesiswith ethylene.rs Furthermore,the reaction of 1,6-diyneswith alkenesis even more intriguing:r6
COOMe
.
-: .*
/ -)--.- \ / \
\
\-+/f Il o
ll
-n
Ts R -,.
I
N.r
-\
l*
ilt ill
(1)
'R'------*
I a
Ia
Ruthenium--carbenecomplexes
The scope is further expandedby using catalysts 3s37.38 and 4.3eFor example, it allows the preparation of trisubstituted alkenes by an intermolecular reaction for the first time,a0 and 1,5-cyclooctadienes(e.g., a precursor of aristeriscanolidear).The intramolecular version is a useful preparation of some other interesting molecules.a2
74Yo
aristeriscanolide
Technically significant is the finding that 4 can be generated in situ from I and 1,3-dimesityl-4,5-dihydroimidazolium tetrafluoroborate (treatment of the salt with I-BUOK in THF at room temperaturefor < I min). The RCM is performed in the presence of etherealHCl.a3 Complex 10 is a very active catalyst for ring-opening cross-metathesisof norbornene derivatives.aa [2 + 2 + 2]Cycloaddition. Formation of benzene derivatives from three alkyne units is catalyzed by several transition metal reagents. 1,2,4-Trisubstitutedbenzenesare the major products from reactions using the Grubbs catalyst containing Ph.P ligands.as Differences in regioselectivty for reactions promoted by the Grubbs and Wilkinson catalystshave been noted.ab
*or. (1)
RO-\ cH2ct2
Ro. ,:Co"
lf*.Y maJor
*T.li -,,*35*.r.*d* (1) 5-6 (Ph3P)3RhCl 1 Radical addition.aj (PhjP)2Ru(:CHPh)C12.
'l 1. 5 - 1 0
Carbon tetrachloride adds to alkenes in the presence of
Scholl,M., Ding, S., Lee, C.W.. Grubtr :Fiirstner, A., Liebl, M., t-ehmann. C Dixneuf, P.H. CEJ 1847 (20001. 'Jafarpour, L., Nolan, S.P OZ 2. JO-: ': 'Yao, 39, 3896 (2000t ACIEE Q. 'schiirer, S.C.,Gessler,S., Buschmann ''Sanford, M.S., Henling, L.M.. Da1. \l' -Bielawski, C.W., Louie, J., Grubbs.R I 'Maynard, H.D., Grubbs,R.H. Il {l. J 'Paquette,L.A., Schloss,J.D.. Efrenx-r
l 259 (2000). Wright, D.L., Schulte,J.P, Page.\l .\ Evans,P.,Gngg, R., Monteith. It rl I :Bujard, M., Briot, A., Gouverneur.\ . ! 'Trevitt. M.. Gouverneur,V.. Mios\orr 'Bujard, M., Gouverneur,V., Mioskorr 'Hoye, T.R., Promo, M.A. IL 40. lr-'9 ^Hanson, P.R.,Probst,D'A.. Robrn
Ruthenium-<arbenecomplexes
" .::rJJ. '' For example,it allows r..r: rL-actionfor the first time,ao 1...::- r. The intramolecularverr.---'.'-
o
.
= H . l
o\
aristeriscanolide ir:::ratcd in situ from I and ::-'.1rtnentof the salt with l\1 . pcrformedin the presence !: ..'nretathesisof norbomene if:r..rlrVes from three alkyne .l: Irr:ubstitutedbenzenesare rir.: iontainingPhsPligands.a5 f,. :r, Grubbs and Wilkinson
I
1. 5 - 1 0 i.r.,ncs in the presenceof
375
'Scholl, M., Ding, S., Lee, C.W., Grubbs,R.H. OL 1,953 (1999). 2Fiirstner, A., Liebt, M., Lehmann, C.W., Picquet, M., Kunz, R., Bruneau, C., Touchard, D., Dixneuf, P.H. CEJ 1847 (2000). rJafarpour, L., Nolan, S.P.OL2,4075 (2000). aYao, ACIEE 39, 3896 (2000). Q. 5Schiirer,S.C., Gessler,S., Buschmann,N., Blechert,S. ACIEE 39,3898 (2000). 6Sanford,M.S., Henling, L.M., Day, M.W., Grubbs,R.H. ACIEE 39,3451 (2000). TBielawski, C.W., Louie, J., Grubbs, R.H. "IACS 122, 12872 (2000). uMaynard, H.D., Grubbs, R.H. Zt 40, 4137 (1999). ePaquette, L.A., Schloss,J.D., Efremov,I., Fabris,F., Gallou, F., Mendez-Andino,J., Yang,Y. OL2, 1259 (2000). rOwright,D.L., Schulte,J.P.,Page,M.A. OL2, 1847 (2000). rrEvans,P.,Grigg, R., Monteith, M.TL40,5247 (1999). r2Bujard,M., Briot, A., Gouverneur,V, Mioskowski, C. TL40,8785 (1999). rrTrevitt,M., Gouverneur,V., Mioskowski, C. TL 40,7333 (1999). raBujard,M., Gouverneur,V, Mioskowski, C. JOC g,2119 (1999). r5Hoye,T.R., Promo, M.A. TL 40, 1429 (1999). lt'Hanson,P.R.,Probst,D.A., Robinson,R.E., Yau, M. TL 40,4'76I (1999). rTRenaud, J., Graf, C.-D., Oberer,L. ACIEE 39,3101 (2000). lilBourgeois, D., Pancrazi,A., Ricard, L., Prunet, J. ACIEE 39,726 (2000). r"Burke,S.D., Miiller, N., Beaudry,C.M. OLl, 1827 (1999). r{rCarda,M., Castillo, E., Rodriguez,S., Marco, J.A.TL4l,5511 (2000). rrRodriguez,J.R., Castedo,L., Mascarenas,J.L. OL2,3209 (2000). r2Ovaa,H., Stragies,R., van der Marel, G.A., van Boom, J., Blechert,S. CC1501(2000). 2tVoigtmann,U., Blechert,S. OL2,3971 (2000). raScholl, M., Trnka, T.M., Morgan, J.P.,Grubbs, R.H. IL 40, 2247 (1999). r5Fijrstner,A., Thiel, O.R., Ackermann, L., Schanz,H.-J., Nolan, S.P.JOC 65, 2204 (2000). roAckermann, L., Ftirstner,A., Westkamp, T., Kohl, F.J., Herrmann, W.A. TL 40,4787 (1999). rTGessler,S., Randl, S., Blechert, S. TL 41,9973 (2000). :8Garber,S.B., Kingsbury,J.S.,Gray, B.L., Hoveyda,A.H.,IACS 122, 8168 (2000). }rPietraszuk,C., Marciniec,B., Fischer,H. OM 19,913 (2000). roBlanco,O.M., Castedo,L. SL 55'1(1999). rrBlackwell, H.E., O'Leary, D.J., Chatterjee,A.K., Washenfelder,R.A., Bussmann,D.A., Grubbs, R.H. JACS 122, s8 (2000). 32Ahmed,M., Amauld, T., Barrett, A.G.M., iraddock, D.C., Flack, K., Procopiou,P.A. OL 2, 551 (2000). 'rSchiirer.S.C., Blechen, S. ft 40, 18'77(1999). rlYi, C.S., Lee, D.W., Chen,Y. OM 18,2043 (1999). 15Smulik,J.A., Diver, S.T."/OC 65, 1788 (2000). 16Stragies, R., Schuster,M., Blechert,S. CC 237 (1999). rrsmulik, J.A., Diver, S.T. OL2,2271 (2000). 3sStragies, R., Voightmann,U., Blechert,S.TL4l,5465 (2000). 3eChatterjee, A.K., Morgan, J.P.,Scholl, M., Grubbs,R.H../ACS 122,3'183(2000). a()Chatterjee, A.K., Grubbs,R.H. Oa I, l75l (1999). I 1Limanto, J., Snapper,M. L.,IACS 122, 807 1 (2OOO). a2Mori,M., Kitamura,T., Sakakibara,N., Sato,Y. oL2,543 (2000). a3Morgan,J.P.,Grubbs,R.H. OL2,3153 (2000). aaKatayama,H., Urushima, H., Nishioka, T., Wada, C., Nagao, M., Ozawa, F. ACIEE 39, 4513 (2000). a s D a sS, . K . ,R o y , R . Z L 4 0 , 4 0 1 5 ( 1 9 9 9 ) .
I
Ia
--
Ruthenium(Ill) chloride-*odiumperiodate aoWitulski, B., Stengel, T., Femandez-Hemarde4 J.M. CC 1965 (2000). aTSimal,F., Demonceau,A., Noels, A.F. fL 40, 5659 (lggg).
Alken Dihydroxylation. of th by replacement cleavage rn derivati\.es tetrahydropyran
Ruthenium(Ill)
chloride. 13, 2681,14,27 l-272; 19, 289-290; 20, 324 Quinolines. Quinolines are obtained by following the procedure of an indole synthesisfrom arylamines by changing the reaction partners to 3-aminopropanol.lyields are moderate(11 examples,2946Vo). lcho, c. s., oh,8.H., Shim,S.c. JHC 36. t1i5 o9g7\.
Ruthenium(Ill)
chloride-sodium periodate. 18, 3 I 0; 19, 290; 20, 324 a-Acetox!-N-acetyl amides.t The availability of chiral pyrimidylalkanols is the impetus for the oxidative cleavagereaction. No racemization occurs.
v' _ ' . 1
RuCl3- NalOa [,leCN
- t ,
\
\--/- './/
O
Hzo
- t
,t:!\ (:::i
CCla
AcNH
OAc B0To
Oxidation. Primary alcohols are converted to carboxylic acids using EtOAc to replace carbon tetrachloride as solvent.2 Bicyclo[2.2.1]heptane-2,3-dionesare obtained from the Diels-Alder adductsof a 5,5-dimethoxy-I,2,3,4-tetrahalocyclopentadiene.3
MeO-_ OMe
X=-N{
RuCl3. 3H20 NalO4 MeCN - H2O
x-Lfl\R X R X=Cl,Br
A RuClt complex (1) in combination with NaIOa has been used to oxidize trifluoromethylcarbinols.a
^i-}' oY*\ cr r/ \-/" R
^,,\ \__,*
u
' l,t*Ao \-r tJ (1)
l
rTanji, S., Kodaka,Y, Shibata-T . rPrashad,M., Lu, Y., Kim. H.-\'. 'Khan, F.A., Prabhudas,8.. Dasb
rKesavan,V, Bonnet-Delpon.D . 5Shing,T.K.M., Tam, E.K.\r' rl, 6Piccialli,v. TL 41, 3731 (lm)'
Ruthenium(Ill) chloride-sodiumperiodate
Dihydroxylation. Alkenes afford cis-|,2-diols instead of suffering oxidative cleavageby replacementof the solvent EtOAc with acetone.sHowever, 1,6-dienesafford tetrahydropyranderivatives in a mixture of EtOAc, MeCN. and H2O.6
t i . , n 51 2 0 0 0 ) . F,
t9.l\9 290;20,324 f .. rrns the procedureof an indole Yields Ir,:.:.rnnersto 3-aminopropanol.t )
''a
|
|
\
Rucr33H2or . I | .oH -;;;* )t'''o't""2-
""!h!'o
oH
63Yo
L : : . 19,290;20,324 is the f , : 1 . ,'l chiral pyrimidylalkanols N . : :i/lition occurs.
AcN.H a
-
\ )-
//V '.
rTanji, S., Kodaka,Y., Shibata,T., Soai,K. H 52, 151 (2000) rPrashad,M., Lu, Y., Kim, H.-Y., Hu, B., Repic, O., Blacklock, T.J. SC 29,2931 (1999). rKhan, F.A., Prabhudas,B., Dash, J., Sahu, N. /ACS 122,9558 (2000). rKesavan,V., BonnetDelpon, D., Begue,J.-P.,Srikanth,A., Chandrasekaran,S.TL4l,3327 (1999). 5Shing,T.K.M., Tam, E.K.W. TL40,2l'19 (1999). nPiccialli,V. TL 4l, 3731 (2000).
OAc
O
80%
carboxylic acids using EtOAc to iare obtained [,i i I]heptane-2,3-diones ,- I :.J-tetrahalocyclopentadiene.r
,
t MeO.-.,,,OMe
o\-l\<{ .- - 1 | x
('a R
1-,1tt has been used to oxidize trifluo-
h
j
a-
I
4^
.t
S
("
Samarium.14,275; 17, 305-307; 18,3 I I ; 19,291; 20, 325-326 Reductive dimerimtion. Alkenes, which are geminally substitutedwith two activators,undergodimerizationat the B-position.Cyclizationfollows.r
Ph
_
CN
s
m
+
CN
r H F- H 2 o NH4cl
/
cr\ Ph \_J \ \ -NHz
.,(
ph.")( NC-
Ph
:Banik,B.K.,Zegrocka, O.. Baru\rYamada, R.,Negoro,N.. Okarurr
'CN
80%
Cleavage of diaryl diselenides. With Sm-Me.SiCl the cleavage is accelerated by water.2 lWang,L.. Zhang,Y.255,10695(1999). rWang,L., Zhang,Y.SC 29,310'7(1999).
Samarium(Il) iodide. 13. l;o307-311;18, 312-316:19. :9:Reductions. B-Ketols ari
monoethers,respectivel)'. Fcx tl fectively with Sm, however.thr The N--O bond in hydroryl However, a bridged oxazine ha temperature.a
Samarium-metal halides.
a'l 'i
Samarium selenides. Reductive cleavage of ArSeSoAr by samarium is catalyzed by a great number of metal halides: bismuth(Ilf chloride,r cadmium chloride,2cfuomium(Ill) chloride,r cobalt(If chloride,apotassium iodide,5and titanium(IV) chloride.6The resulting samarium arylselenidesreadily react with various organic halides. Reductive desulfunylation,T p-Keto sulfones gives ketones on treatment with Sm-HgCl2 in THF containing water. Cleavage of diaryl ditellurides, Michael donors are generatedfrom ArTeTeAr on reaction with Sm-ZrCla.n tZhan,Z.,Lu, G.,Zhang.Y.JCR(S)280(1999). zZheng,Y.,Bao,W., Zhang,Y.SC30, l73l (2000). 'Liu, Y.,Zhang,Y. SC29,4043(1999). rChen,R.,Zhang,Y.SC30,l33l (2000). 5Lu,G.,Zhang,Y. SC29,219(1999). 6Zhou,L.-H.,Zhang,Y.SC29,533(1999):"/CR(S) 28 (1999). 7Guo,H., Zhang,Y.SC30,2559(2000). 8Zhang,S., Zhang,Y.SC30, 285 (2000).
xpr. j pn-\o
Desulfonylationof N-sulior ods using either tin hydnde c higher yields. The carbon-bou readily removed.6Under shghtl
Resolutionof trans-2.5{rsl mandelateester is enabled hr tl
"'l\N'2""..-\' r l
n
Samarium-iodine. 19, 292 Reduction and reductive dimerizatians, ArN:CH2 are reduced to ATNHMe in methanol.I N-Alkyl aldimines undergo reductive dimerization.2 378
nv-o
I rn\' o
Samarium(Il)
-l\^ /\.^
OMe
Sm-12
OMe
PhYNH Ph"'\ NH
(*
L 10. rl-5-326 a:. .:cminally substituted with two C . . . : z a t i o nf o l l o w s . '
iodide
Ph
1""-ot" 78o/o
?>
CN
NHz CN
rBanik, B.K., Zegrocka, O., Banik, I., Hackfeld, L., Becker, F.F. TL 40, 5731 (1999). 2Yamada,R., Negoro, N., Okaniwa, M., Miwa, Y., Taga, T., Yanada,K., Fujita, T. SL 53'7(lggg).
Samarium(Il) iodide. 13, 270-27 2; 14, 27 6-28 1; 15, 282-284 ; 16, 29 4-300 ; 17, 307-3ll; 18, 312-316; 19, 292-296: 20, 327 -335
80% h \:('l the cleavageis acceleratedby
Reductions, B-Ketolsr and 3-alkoxy ketones2are reduced to anti-1,3-diols and the monoethers,respectively. For the directed reduction, the alkoxy group must complex effectively with Sm, however, this is not observedwith TBS and benzyl ethers. The N--{ bond in hydroxylamines and hydroxamic acids is rapidly cleaved by SmI2.3 However, a bridged oxazine has been found to undergo ring contraction at or above room temperature.a
t:\- \..{r by samariumis catalyzedby ]rj: ..rdmium chloride,2chromium(Il! N '.:.rnrum(lV)chloride.6 The resulting x-.':r:. halides. 5 :: \ .\ ketones On treatment with
---a.o
,^-o2/ l
Sm12
,\-9 N
( t ) 'a /'->/w,
\--'-d
HN
Ph-\o
.{:.lk PhAO
Ph
x. .,:J !!'neratedfrom ArTeTeAr on re-
Desulfonylation of N-sulfonylamidesswith SmI2 is found to be superior to the methods using either tin hydride or Zn-:fiClo, because of lower reaction temperature and higher yields. The carbon-bound sulfonyl group at the a-position of cinnamonitriles is readily removed.6Underslightly different conditions, the double bond is also saturated.T Resolution of trans-2,5-disbstitutedpyrrolidinesE via the carbamatesthat constitute a mandelateester is enabled by the facile reductive cleavageof O-acylmandelic esters.
f_\ o,4|7,,,,\-4r n2-o reduced to ATNHMe in
\:{'H.are l f : ' i. : : / . l t l 0 n .
-
"'^\"J-
f-\ MeOH - THF
^ar-4tNl""'\\-Ar r H
92%
I
Samarium(Il) iodide
Deamination of ct-amino carbonyl compoundseoccurs when they are treated with SmI2 in the presenceof HMPA and a sufficient amount of MeOH as a proton source. By this reaction, proline esters are converted to piperidones [and thence application to a synthesis of (- )-adalininel.r0Pyridinemethanolsare deoxygenated.rl
r--1 .-1 etooc,,.(ru\.ur,,ottt
+
smr2
a^) )oras oA*,{^'
*/(h*
H CsHtt
H
Enolates are generated from a-cyanoketones. Such species undergo regioselective alkylation.r2 Reductive couplings. A synthesis of tartaric acid derivatives containing quaternary carbon centersis by reductive coupling ofct-ketoamides.r3
""")*V )ao
Condensationreactions r*rth stituted carbonyl compounds r yalkyl)-B-ketols is quite stragt derived from ct-(pyridylthio rglr r ural peptides by reaction * ith r r
An accessto optically acurc ral oxazolidin-2-ones to reacl r.l of a-haloketones with acyl cran Dimerization of enonesis ta hydroxy ketone is formed b1 a n chain. The net result is that of al
|BUOH - THF HMPA
\--,
Sml:
.{-\ 61Yo
The diastereoselectivityfor the reductive coupling of PhCHO in THF is increased(favoring the anti-syn isomer to 6:l) by addingtetraglyme.ra 2-Substituted cyclopropane-1,1-dicarboxylic esters undergoes ring opening and dimerization.15Efficient coupling of two aldimine molecules or aldimines with carbonyl compounds (imine slowly added to the ketone and reagents) has been carried out with
4.
,o /t\/t\A oHc/
two metaliodides:SmI2-Ni12.r6 AAol and Reformatsky reactions, readily promoted by SmI2.
I-BUOH- T* HMPA -78
| i =vl )
The cross-aldol reaction exemplified belowri is
d."j
MS.4A / THF
As expected, bromoacetoru nitriles.25 6-Lactones.26 The SmI;-rclization of 6-keto aldehydesto the catalvtic cvcle.
Samarium(Il) iodide
c.-:. \\'hen they are treated with rr : \teOH as a Proton source.BY r. ind thenceapplicationto a syni!ill,ttc-d.ll
-)
Condensationreactions with donor speciesgeneratedby reductive cleavage of ct-substituted carbonyl compounds are regioselective. Thus, the synthesis of a-(l-hydroxyalkyl)-B-ketols is quite straightforward from a,B-epoxy ketones.rESamarium enolates derived from cr-(pyridylthio)glycyl peptides are also applicable to the synthesisof unnatural peptides by reaction with various carbonyl compounds.ro
ores
f
o'
^,, l ' ' * 4\-5n1 1 Fl
r:
o o H Sml2
1-1
+ R"-cHo
*,\[).-*'
,.\r\^. ,. I
;;
n,,/,,,oH 70-95%
-rccies undergo regioselective
| :.'::r atives containing quaternary
r(
An accessto optically active p-hydroxy acids usesthe bromoacetyl derivatives ofchiral oxazolidin-2-ones to react with aldehydes.2O 1,3-Diketones are obtained from reaction of ct-haloketoneswith acyl cyanides.2r Dimerization of enonesis terminated by an intramolecular aldol reaction.22A bridged hydroxy ketone is formed by a reduttive coupling between an enone and an aldehyde side chain. The net result is that of an aldol reaction involvins a homoenolate.2r'24
OMe
a
>q. .|^,
\-61%
r--l{-rn I-BUOH - THF HMPA
78'
o H +
Yal
I
/' o cyclomyltaylan5o-ol
, : i'hCHO in THF is increased(fa0<'
.:- :ndergoes ring oPening and o-r...1c.or aldimineswith carbonyl ri-i-rnt\l has been carried out with
/\.t\-4 oHc/
t i -vl )
|j . ::rction exemPlifiedbelowrTis
' ".
/-- - \\ /
B6%
rl
,o
o
/""a-'-.< l
l
\-.^-/
:
)
_
H , 9
*+
/"'.av, t t vtJ
)
OH
l H cooH
60%
coronafacicacid
As expected, bromoacetonitrile reacts with carbonyl compounds to give B-hydroxy nitriles.25 &Inctones,26 The SmI2-l-PrSH or SmI2-MeSSMe combination induces redox cyclization of 6-keto aldehydesto furnish lactone products. The thiol facilitates operation of the catalyticcycle.
Samarium0l) iodide
cHoo l \ -
R
smrr-i-PrSH
-
Ketones bearing a remo(e I exposureto SmI2and (Ph.Pr.Pd
O\-O'r-n
-
l
rHF 25'
l \-.\
\ \.
Barbicr reactions. Allylic alcohols are produced from alkenyt halides and carbonyl compounds2?on mediation by SmI2. This process includes the preparation of the Baylis-Hillman adducts from ct-bromoacrylamides and carbonyl compounds.28Barbier reaction involving l-chloromethylbenzotriazole2eaffords alcohols that are valuable synthetic intermediates.N-(co-Iodoalkyl)-O,O'-bis(r-butyldimethylsilyl)tartrimide undergoes cyclization quite efficiently and the reaction has been applied to a synthesis of (+)-
Sml2- Fe(dbm)3 THF 25'
rBSo,,'\N
EtOOi u
A tfuee-step protocol for d volves two (first and third t rcr heterocyclewith ketones is foll Cyclizations. Reductive r-
lentiginosine.3o
TBSO\-d
Y"\)-ot
-x
resolfi'ru/ I
are remarkably efficient.
TBSO.''\
o
I ,
77Yo
t"wct
A route that leadscarbohydratesto carbocyclesinvolves an intramolecular alkylation'tl '-
cHo
tt
BnQ
1:
Smr2 -'-
(
Bno{
THF-MeOH
BnO
2s
\-J
BnO.
pH
Y
//
+Bnoa
'.oH
-
Bno-'
Bnoj
9H
./wo //
)"'" ,oH
(75 : 25) 83Yo The condensation of alkyl halides with nitriles, tertiary amides, and esters afford ketone products with SmI2-NiI2.32'33 Reaction of ketyts. The coupling between ketones and nitriles to afford ct-ketols3a likely involves ketyl intermediates.Conjugate addition ofthe ketyl derived from ct-ketols owing to chelationeffects'r5 showsstereoselectivity
cyclization.
/
/ *--A i'. )-/
( i \*'\.4 \
OH
O^"Y.#o#
2,3-Disubstitutedpyrroltdt amines that bear an alkenll another chain. The far tern
+
Bn
71%
An activated o-methoxl' grr
Samarium(Il) iodide
'! a , /
Ketones bearing a remote propargyl ester group afford 2-alkynylcycloalkanols36on exposureto SmI2 and (PhjP)aPd.
-
":/K
I
..-,,\
:: ::r elkenyl halidesand carbonYl :.,,udes the PreParationof the Barbier n.: ..rrhonyl compounds.28 r.:. .rliohols that are valuable syn-
\,
Y"\loac
sml2-(Ph3P)4Pd
-X
rHF 2s"
ETOOC
,<' ) , ' , ' -- R ,/ ETOOC' \_J
b
R= H 68%
k:::rrrhr lsilyl)tartrimide undergoes r: .,rplicd to a sYnthesisof (+)-
A three-step protocol for alkylation of l,l0-phenanthroline(at C-2 and C-2-C-9) involves two (first and third) reactions mediated by SmI2. Thus, condensationof the parent heterocyclewith ketones is followed by O-methylation and reduction.rT Cyclizations.
Reductive cyclization that leads to cyclopropanes38and cyclobutanes3e
are remarkably efficient.
- V\rcooBn __tll fHF - N.4eOH
r.-\,,\-cootn
25
rn intramolecularalkYlation.''
cHo
|.,\-cooBn +I -l
99%
-A|
..oF
6SYo
BnO (75 : 25) 83%
. rJ::i.rr\ amides, and esters afford r'.r- .r:rdnitriles to afford ct-ketolsra rc : thu'ketyl derived from ct-ketols
2,3-Disubstitutedpyrrolidinesaoand piperidinesarare readily obtained from tertiary amines that bear an alkenyl chain and a benzotriazolyl group at the ct-position of another chain. The far terminus of the double bond becomes nucleophilic upon cyclization.
N-l\
"i 1r"-x). /
\r-(^
I Bn
THF - HI\,4PA
)
51o/o(trans ; cls 4.3 : 1)
An activated o-methoxy group is replaced via ketyl attack and elimination.a2
I
Samarium(II) iodide
COOMe Sml2
Q-"oot" /--f
.oH
A very interesting and highly useful synthetic process is that which dearomatizes a benzene residue through addition of a ketyl in the side chain and thereby a fused ring system is created.a3If an ethynyl group is present at an o-position cyclization gives an eighlmembered ring.
-a
\J
COOMe :R
yJ
Sml2
'..-..-"............"..........-..* THF - HN,4PA t-BUOH
.--l
R = CHzOMe 67Yo R = SiMes 52%
a-,
(
Sml2
COOMe
THF. HN,IPA rBUOH
cooMe ,
\
\-Y
*
t
|'oH
F -,.{o
Y
I"'
\lY
61Yo
13Yo
Fulfy substituted sym-tiazines are formed from cyclotrimerization of nitriles,aawhich reactionis catalyzedby SmI2and an amine. Eliminations and cycloadditions. I,l-Dihalo-2-alkyl acetatesare transformed into (Z)-alkenyl halidesason treatment with SmIt. Azomethine ylides are generated from bis(tosylmethyl)aminesRN(CH2Ts)2.Trapping of these 1,3-dipolarspecieswith alkenes or alkynes furnishes pyrrolidines and 3-pyrrolines, respectively.16 By a cycloaddition process, oxazolidines are formed from epoxides and imines.aT Contact of epoxides with SmI2 apparently results in their activation (ring opening).
A*-r, . ")-
Sml2
"V
>(
Bn
93Yo
'Keck, G.E., Wager,C.A.. ScU :Keck, G.E., Wager, C.A. Ot, rKeck, G.8., Wager, C.A.. \lcl rMcAuley, B.J., Nieuwenhure 'Knowles. H . S . ,p a r s o n sA. i . 6Guo, H., Zhang,Y. "/CRIS, .1 -Guo, H., Zhang,y. SC3{). lt' EHanamoto, T., Shimomoto. \ eHonda, T., Ishikawa, F. CC l( l"Honda,T., Kimura, M. OL Z. " Kato, Y, Mase, T. ZL 40. tS:_ r)Zhu, J.-L., Shia,K.S.. Lru. H I'Krm, S.M., B y u n , I . S . .K r n . I )rPedersen, H.L., Chrisrenscn (1999). iiYamashita, M., Okiyama. K. s. cPB 47,1439 Q99q roMachrouhi, F., Namy. J.-L Il ' Lu, L., Chang, H.-Y., Fang.J '"Mukaiyama, T., fuai. H.. Shru ''Ricci, M., Madariaga.L.. S\n l"Fukuzawa, S., Matiuzau.a-H r r B a e k ,H . S . , Y o o ,B . W . K e u n rrZhou, L., Zhang,y. SC J). 5E rrSakai,H., Hagiwara,H.. lro. )' ]Sono, M., Hashimoto,A.. \.L :sCaracoti,A., Flowers II. R.A I rnHsu,J.-L., Chen,C.-T.. Fang.J rrKunishima, M., yoshimura-K_ }Youn, S.W., Park, H.S.. Krm..t :'Huang, Z.-2., Jin,H.-W.. Drea '''Ha, D.-C., Yun, C.-S.,tre. \' . ''Kan, T., Nara, S., Ozawa.T. S 'rKang, H.Y., Song,S.E. fL al. r "Molander, G.A., Machroulu.F 'rZhou, L., Zhang,y. Shl. D S g "Matsuda, F., Kawatsura.\t.. ll '6Aunecoechea, J.M., Fanana.. ( I999). '-O'Neill, D.J., Helquisr.p Ot I '8David, H., Alfonso, C.. Borun, l "'Johnston, D., McCusker.C.F. ! '"Aurrecoechea, J.M., Feman&r_ '' Katritzky, A.R., Luo, 2.. Fang., lrTanaka, T., Wakayama, R.. \h "Nandanan,8., Dinesh,C.U.. Ra " X u , F . ,S u n , J . - H . ,y a n , H . - 8 . . S 15Concellon, J.M., Bernad.pL. p *oKatritzky, A.R., Feng, D.. Fang. rrNishitani, T., Shiraishi, H.. Satr
Samarium(Il) iodide
: --COOMe OH
a rr.. r- tha( which dearomatizes ring fused dr ,r.rin and therebYa cYclizationgives an 3: pori116n
_K
)U:
67%
1
52o/o
c, ,, . ' t {
+ ]H
13To )..
which of nitriles,44 ::rlrcrization
'a.r... ecetatesare transformedinto rr..::'.rn!'1-lidesare generatedfrom rr ...r-dipolarspecieswith alkenes rp:, ::r r'l\'.'n r::::.: lrttm epoxides and imines'al tc:: .1.tl\ ation (ring opening).
o>( \
l
>-N
/
Bn 93Yo
'Keck, G.E., Wager, C.A., Sell, T., Wager, T.T. JOC 64,2172 (1999). 2Keck,G.E., Wager,C.A. OL2,230'1 (2000). 3Keck, G.E., Wager, C.A., McHardy, S.F. 255, 11755 (1999). aMcAuley, B.J., Nieuwenhuyzen, M., Sheldrake,G.N. Ot 2, 1457 (2O0O). 5Knowles,H.S., Parsons,A.F., Pettifer,R.M., Rickling, S. f 56, 979 (2000). 6Guo, H., Zhang,Y. JCR(S) 342 (1999). 7Guo,H., Zhang,Y. SC30, 1879 (2000). oHanamoto,T., Shimomoto, N., Kikukawa, T., Inanaga, J.TAl0,295l (1999). eHonda,T.. Ishikawa.F. CC 1065 (1999). r0Honda,T., Kimura, M. OL2,3925 (200U. rrKato, Y., Mase, T. fL 40, 8823 (1999). 12zhv,I.-L., Shia,K.S., Liu. H.-J. TL40.'7055 ,]l99q). I3Kim, S.M., Byun, I.S., KLm,Y.H.ACIEE 39,725 (2000). raPedersen,H.L., Christensen, T.B., Enemaerke, R.J., Daasbjerg, K., Skrypdstrup,T. EJOC 565 ( 1999). rsYamashita,M., Okiyama, K., Ohhara, T., Kawasaki, I., Michihiro, Y, Sakamaki, K., Ito, S., Ohta, ,:Iggg\. s. cPB 47. 1439 'nMachrouhi,F., Namy, J.-L. TL 40, 1315 (1999). r7Lu,L., Chang,H.-Y., Fang,J.-M. JOC 64,843 (1999). r8Mukaiyama,T., tuai, H., Shiina,I. Cf 580 (2000). reRicci, M., Madariaga, L., Skrydstrup, T. ACIEE 39,243 (2000). 20Fukuzawa,S., Matsuzawa, H., Yoshimitsu, S. ./OC 65, l7O2 (20OO). 2rBaek,H.S., Yoo, B.W., Keum, S.R.,Yoon, C.M., Kim, S.H., Kim, J.H. SC30,31 (2000). 22zhou,L., Zhang, Y - SC 30, 597 (2000). 2rsakai,H., Hagiwara,H., Ito, Y, Hoshi, T., Suzuki,T., Ando, M. TL40,2965 (1999). 2aSono,M., Hashimoto,A., Nakashima,K., Tori, M. TL 41,5115 (2000). 25Caracoti, A., Flowers II, R.A. TL 41, 3039 (2000). r6Hsu,J.-L., Chen, C.-T., Fang,J.-M. OL2,1989 (2000). zTKunishima,M., Yoshimura,K., Nakata,D., Hioki, K., Tani, S. CPB 47,1196 (1999). 28Youn,S.W.,Park, H.S., Kim, Y.H. CC 2005 (2000). reHuang,Z.-2, Jin, H.-W, Duan, D.-H., Huang, X. JCR(S) 564 (1999). r0Ha,D.-C., Yun, C.-S.,Lee,Y. JOC 65,621 (2000). rrKan, T., Nara, S., Ozawa,T.,Shirahama,H., Matsuda,F. ACIEE 39,355 (2000). r2Kang,H.Y, Song,S.E. TL41,937 (2000). rrMolander, G.A., Machrouhi F. JOC 64, 4119 (1999). , taZhor,L.,Zhang,Y., Shi, D. S 9l (2000). r5Matsuda,F., Kawatsura,M., Hosaka,K., Shirahama,H. CEJ 5,3252 (1999). r6Aurrecoechea, J.M., Fananas, R., Arrate, M., Gorgojo, J.M., Aurrekoetxea, N. JOC 64, 1893 (1999\. r7O'Neill, D.J., Helquist,P. OL l, 1659(1999). rsDavid,H., Alfonso, C., Bonin, M., Doisneau,G., Guillerez,M.-G., Guibe,F. TL 40,8557 (1999). reJohnston,D., McCusker,C.F.,Muir, K., Procter,D.J. JCS(Pl) 681 (2000). r(rAurrecoechea, J.M., Fernandez,A., Gorgojo,J.M., Saornil,C. f 55,7345 (1999). llKatritzky, A.R.,Luo,Z-, Fang,Y, Feng,D., Ghiviriga, l. JCS(P2) 1375(2000). l2Tanaka,T., Wakayama, R., Maeda, S., Mikamiyama, H., Maezaki, N., Ohno, H. CC 1287 (2000). rrNandanan,8.,Dinesh,C.U., Reissig,H.-U.256, 4267(2000). 'oXu, F., Sun, J.-H., Yan, H.-B., Shen, SC 30, 1017 (2000). Q. asConcellon,J.M., Bernad, PL., Perez-Andres,J.A. ACIEE 38,2384 (1999). 'oKatritzky,A.R., Feng,D., Fang,Y. SZ 590 (1999). rTNishitani,T., Shiraishi,H., Sakaguchi,S., Ishii, Y. TL 41,3389 (2000).
F
Samarium(Ill) triflate
SamariumflIl) iodide. pAmino esters,l Promotedby SmIj the condensation of silyl ketene acetals with aldiminesis highly anti-selective.
on"* OSiMe3
ErO
Sml3
*
(*,,tn THF : OTBS An- p-anisyl
H N
NHAn I EtOOCv&.Ph
e{
: OTBS
)-sa6 ,
thioglycosides that are not acu valuable feature. rChang, G.X.,Lowary,T.L.OL 2.
Samarium(Il) trifl ate-nickdt Alkylations.l Samariumrtl taining catalytic amounts of H.
with NiI, for condensationof h
Go.=
rHayakawa,R., Shimizu, M. Cl,59l (1999).
triflate. Samarium(Il) iodidesamarium(IlD Reduction.t With this combination of reagents,methanol and base (KOH), reduction of carboxylic acids to primary alcohols is observed.Aldehydes are hardly affected.
Various reactions.t The b reaction, Mukaiyarna-aldol ra reaction, as well as the reductrr
rKamochi, Y.,Kudo,T.TL4l,341 (2000).
rCollin,J.,Giuseppone, N., l\lrtrr
isopropoxide. and nitroalkenes undergo condensation to afford 1,3,4+risubsti Imines firroleil tuted pyrroles. For the promotion of this reaction, samarium(Ill) isopropoxide is better than severalother Sm compounds and isopropoxides of lanthanum and ytterbium.
Scandium(Ill) triflate. lt. -1I i Allylation. When tetra.lllll pounds, the presenceof water I
Samarium(Ill)
(i-PrO)3Sm
.,]--r^*-
*
r',,/\r'*o'
IHF A
Aldol reactions. To condr water, the presenceof a surfat employed as surfactants.' ..\ h enol ethers,thereby increasing r
Vinylogous aldol reactrcxr alkenyloxiranes and aldehl dcs teric charactersin that thev beh
{ */:*\ 70To
o 'Shiraishi, S.,Ishii,Y f55, 13957(1999). T.,Nishihara, T., Sakaguchi, H., Nishitani,
Samarium(Ill) triflate. Glycosylation.r Samarium(Ill) triflate catalyzes the reaction of glycosyl 2-pyndyl sulfones with alcohols. This method is applicable to the preparation of di- and trisaccharides containing both furanose and pyranose residues. The difference in reactivity from
*\^*
I
Mannich reactions. F-.fu Sc(OTf)r-catalyzed condensarx taining a surfactant.5Under rlx imines in MeCN to provide p-e
ScandiumflIl)
rr..:!:r..rtionof silyl ketene acetalswith
triflate
thioglycosides that are not activated by the hard Lewis acid Sm(OTf)r is a synthetically valuable feature. rChang,G.X.,Lowary,T.L.OL2,1505(2000).
H N
\HAN
l o ^ : OTBS
- -'t-,/ -
o{
"'
Fonc :
Samarium(Il) triflate-nickel(Il) iodide. Alkylations.t Samarium(Il) triflate is prepared by reduction with Sm in DME containing catalytic amounts of Hg.'The solvated product is freed of solvent and combined with NiI2 for condensationofketones and acrylic estersto afford ylactones.
( F o L-J
nr. :Icthanol and base(KOH), reduction a.- \ldchydes are hardlY affected.
COOMe
Sm(OT02- Nil2 EtOH
\
f--t,ro-(o \-/\
Various reactions,t The binary salt is a very useful reagent for promoting Barbier reaction, Mukaiyama-aldol reaction, Michael reaction, Mannich reaction, Diels-Alder reaction,as well as the reductivecoupling ofcarbonyl compoundsand ofimines. rCollin,J.,Giuseppone, N., Machrouhi, F.,Namy,J.-L.,Nief,F. TL 40,3161(1999).
o . rJcnsation to afford 1,3,4-trisubstio:. ..rnrarium(lll) isopropoxideis better rc:. ,t lrnthanumand Ytterbium.
{
Scandium(Ill) triflate. 18, 3 I 7-3 I 8 ; 19, 3OO-302;20, 335-337 Allylation. When tetrallylgermane is used as the allylating agent for carbonyl compounds,the presenceof water in the reactionmedium is indispensable.r Aldol reactions. To conduct the Sc(OTf);catalyzed Mukaiyama aldol reaction in water, the presenceof a surfactantis very advantageous.2Calixarenesulfonatesalts can be employed as surfactants.i A hydrophobic microenvironment is created to protect silyl enol ethers,thereby increasing the yields of the products. Vinylogous aldol reactions leading to D-hydroxy-cr,P-unsaturatedaldehydesa from
I
alkenyloxiranes and aldehydesare promoted by Sc(OTf):. Such oxiranes possessamphoteric charactersin that they behaveas acceptorstoward allylborate reagents.
N--r
Ph/=/
\ 7lYo
tl S ..::rr.\'. f 55,13957(1999).
rlr.'r. rhe reaction of glycosyl 2-pyridyl le :,' the preparation of di- and trisacchas:.:-.. The difference in reactivity from
R^H
.of
SC(OTO3
-;;*
OH
' nt-* |
/cHo I
Mannich reactions. B-Amino ketones and esters are readily obtained from a Sc(OTf)j-catalyzed condensation of silyl enolates, aldehydes, and amines in water containing a surfactant.5Under the influence of Sc(OTf):, O-trimethylsilylnitronates add to imines in MeCN to orovide B-aminonitroalkanes.6
ScandiumflIl) triflate
Mechanistically related to the Mannich reaction is the formation of hydroxyarylglycine derivativesin a three-component reaction.T OH
OH
.
\
*o
!r)
NHAr
Sc(OTf)3- N.4gSOa
+ ArNH2 +
'.,A.oo*.
cH2cl2 25
Ttshchenka reaction. Reduction of B-hydroxy ketones with isobutyraldehyde while catalyzed by Sc(OTf)3 is stereoselective,anti-7,3-diol monoisobutyrates are the major products.s Cyclacondensation. A Prins-type reaction between aldehydesand 3-butenol leads to 4-tetrahydropyranolsand ethers.eSc(OTf).r assistsepoxide opening by an intramolecular attack of an enolate,resulting in the formation of three-, four-, and five-memberedrings.r0
) , t
? |
o t
't
Sc(OT03
7-
94To
tipurpose catalyst. Besides proflx{x Diels-Alder reactionand Meergern-
PhMe 25'
)t
)' ('
en\A,^oH
Scandium(Ill) tris(perfl uorullu DebenzylationI Benzyl e0rrs. cleavedby catalysisof Sc(CTf, r. Friedel-Crafts acylatian.: St-an
(Me3Si)2NLi
tr\
Secondary alkyl mesylates are adequate alkyl donors in this reaction.rr Both Sc(OTf)3 and TfOH can be used as the catalyst. It has also been reported that Sc(OTf)3 immobilized in ionic liquid forms a recyclable system for arene alkylation with alkenes.12 Friedel-Crafts
alkylation.
1,l-Diarylalkenes are formed in the reaction of areneswith l-phenylalkynes. Triflates of Sc. In, andZr aresuitablecatalysts.rr Hydrolysis.ta Esters bearing a coordinative group at a proximal position are hydrolyzed selectively under mild conditions, in the presenceof Sc(OTf)3.
o Z\A I
\.ry
ll
rlshihara, K., Hiraiwa,Y.,Yamamoro. ll rNishikido, J.,Yamamoto, F.,Nakarrmrt
Selenium. 18, 318; 20, 337 Alke ny lselenium compounds. alkenylzirconocene derivatives.Ttr 1 acetylated.2
Selcnides and diselenides.' 81 prepareeither RSeR' or RSeSeR'
o
),,,oRc -+
sc(orr)3 Z>A
MeoH- H2o
|
MeOH - H2O
ll
),,,oH
A--{\ I ll \.ry
BuLi + 2Se -
FoH
Silyl ethers.ts Silylation of alcohols at room temperatureusing methallyl(t-butyl)dimethylsilane as TBS group donor is catalyzedby Sc(OTf )3.
|rt
rAkiyama,T., Iwai, J., Sugano. \t. f 55. 2Manabe,K., Kobayashi,S. SL 5{7 r 199 rTian, H.-Y., Chen, Y-J., Wang. D,. Zrq alautens,M., Ouellet,S.G., Raeppel.S sKobayashi,S., Busujima,T.. Nagar arru 6Anderson,J.C., Peace,S., Pih. S. St S! THuang,T., Li, C.-J. TL 41,6715 r)U,t',t EGillespie,K.M., Munslow, I.J.. Sccn. P "Zhang,W.-C.,Li, C.-J. 256, 2.lO-1' l(n roCrotti,P.,Di Bussolo,V., Favero.L . \l rrKotsuki, H., Ohishi, T., Inoue. \1.. KqF r2Song,C.8., Shim, W.H., Roh. E.J . Ctn rrTsuchimoto,T., Maeda,T., Shiraltarr I ''Kajiro, H., Mitamura, S., Mori. A . Hrl; r5Suzuki,T., Watahiki,T., Oriyama. T l.I
Huang,X., Wang,J.-H..SC30,301rlCrI rHuang,X., Wang,J.-H.St 560(2ffi' 'Krief, A., VanWemmel, T.. Redon.\l . D
Selenium
r :::. Ii)rmation of hydroxYaryl-
p-.. $rth isobutyraldehydewhile ::: n{rl\obutyratesare the major r "..:cnrdesand 3-butenolleadsto r;r 'ncning by an intramolecular f, -.:-.,rndfive-memberedrings.rt) 1 l
'Akiyama, T., Iwai, J., Sugano,M. 255,7499 (1999). 2Manabe,K., Kobayashi,S. SI 547 (1999). 3Tian,H.-Y., Chen,Y-J., Wang, D., Zeng,C.-C., Li, C.-J. TL41,2529 (2000). alautens,M., Ouellet,S.G.,Raeppel,S. ACIEE 39,4079 (2000). sKobayashi,S., Busujima,T., Nagayama,S. SL 545 (1999) 6Anderson,J.C.,Peace,S., Pih, S. SL 850 (2000). THuang,T., Li, C.-J. TL 41, 6715 (2000). nGillespie,K.M., Munslow, I.J., Scott,P. TL 40,9371 (1999). ezhang, W.-C., Li, C.-J. T 56,2403 (2ffi0). 10Crotti,P, Di Bussolo,V, Favero,L., Macchia, F., Pineschi,M., Napolitano,E. f 55, 5853 (1999). lrKotsuki, H., Ohishi, T., Inoue, M., Kojima, T. S 603 (1999). r2Song,C.8., Shim, W.H., Roh,8.J., Choi, J.H. CC 1695(2000). lrTsuchimoto, T., Maeda, T., Shirakawa, 8., Kawakami, Y. CC 1573 (2000). 'uKajiro, H., Mitamura, S., Mori, A., Hiyama, T. BCSJ 72,1553 (1999). r5Suzuki,T., Watahiki,T., Oriyama,T. TL 41,8903 (2000).
Scandium(Ill)
tris(perfl uoroalkanesulfonyl)methides.
Debenzylationr
Benzyl ethers, N-benzylamides,
and benzyl ester(s) are efficiently
cleaved by catalysis of Sc(CTfj)3.
r
Frtedel-Crafts
-
acylation.2
Scandium tris(perfluorobutanesulfonyl)methide
tipurpose catalyst. Besides promoting
,ao, E:r- .irc adequatealkYl donors tn i- :r. catalyst.It has also been lt- ., rccvclablesYstemfor arene p. .i rth l-phenylalkynes.Triflates p .:' .r proximal Position are hYrl"- :Sc(OTf)r.
Diels-Alder
Friedel-Crafts
reaction and Meerwein-Ponndorf-Verlev
is a mul-
reactions, it is also useful in the reduction.
rlshihara,K., Hiraiwa, Y., Yamamoto,H. St 80 (2000). 2Nishikido,J., Yamamoto,F., Nakaiima,H., Mikami, Y, Matsumoto,Y., Mikami, K. Sf 1990 (1999).
Selenium. 18, 318; 20, 337 Alkenylselenium compounds. Selenium is easily inserted into the C-Zr bond of alkenylzirconocenederivatives. The products can be oxidized to dialkenyl diselenidesror acetylated.2 Selenidesand diselenides.t By manipulation of reaction conditions it is possible to prepareeither RSeR' or RSeSeR'.
3 ) ,OH
RX BuLi
+ 2Se
-
BuSe-SeLi +
BuSe-SeR
I err-i
Y
R'X
2 BuSeLi
t'\---\t
:F af -l
I:
BuSeR'
I >-oH
:c using methallyl(l-butYl)di-
rHuang,X., Wang,J.-H.SC30,301(2000). rHuang,X., Wang,J.-H.SL560(2000). rKrief, A., VanWemmel,T., Redon,M., Dumont,W, Delmotte,C. ACIEE38,2245(1999\.
Silica gel
Selenium-carbon monoxide. Ureas,' Nitroarenes undergo reductive carbonylation and the in situ trapping with unhindered secondaryamines leads to unsymmetrical ureas. Indoles.z 2-Nitrostyrenes afford indoles in the Se-catalyzed cyclization. The substratesinclude 2-nitrostyrene itself and various ct- and p-substituted homologues.
R
Se/CO Et3N - DMF
Itoh.A., Kodama.T.. Masakl.\'. 5f .r rDas,B., Venkataiah, 8., Madhusudl 'ltoh, A., Kodama, T.,Inagaki.S..\tr 'Baptistella, L.H.B.,Sousa, I.N|.O..Cr 'lwasawa, N., Sakurada. F..Iwamorol
100.
R = H .A r . . . . R ' = H . M e .. . .
rYang,Y, Lu, S. ?L 40, 4845(1999). 2Nishiyama, (1999). Y.,Maema,R., Ohno,K., Hirose,M., Sonoda, N. Zt 40, 5'71'7
Silicon tetrafluoride. 3-Fluoroalkanols.t Oxerarcs propargylic are opened by SiF. rr
additives. For example, good resu reaction seems to be suppresscdI promotingepoxideopening.
Silica gel. 15, 282: 18, 3 I 9; 19, 303-304; 20, 338-339 Selective reactions. Desilylation of triethylsilyl ethers in the presence of t-butyldimethylsilyl ethersis accomplishedwith a mesoporoussilica in methanolat room temperature.r Selective esterification of nonaromatic carboxylic acids using NaHSOa-silica in methanolhasalsobeendescribed.2 Oxidations. Photochemicaldegradationofa-hydroxy acids and phenylaceticacid derivatives(oxidativedecarboxylation)rtakesplacein the presenceof a mesoporoussilica. With acidic potassiumdichromate adsorbedon silica-zirconia,regioselectiveallylic oxidation is achieved.oThis reagentis better than CrO:-3,5-dimethylpyrazolefor oxidation of 1-menthenederivatives becausethe 3-keto products are largely absent.
f , )
R
Glycosylfluorides.2 Gllcals I tion of SiFaand an oxidant suchas acetate(HzO). In suchcases.a hnr
Fluorination.t Fluorinarron r SiF.,.The reagentcombinationals varenes. K2Qr2O7l ZrO2-SiO2
Ph
Diels-Alder reaction. Adsorption on silica gel of certain alkyne-Co2(CO)6 complexes that possessdiene and dienophile units separatedby a suitable distance serves to shift the equilibrium toward their cycloadducts, as compared with that in solution.5
Shimizu,M., Kanemoto,S., Nakah.rn :Shimizu, M., Nakahara,Y, Yoshrotr 'Tamura, M., Takagi,T., Quan. H.-D . !
Silicon tetrafluoride
'l:r: 1 rnd the in situ traPPingwith Sr ,.itrlvzed cyclization. The subhomologues. I .: -.ri-,.tituted
R' z
'-v-\
|\ , : . - A N >-R
lItoh,A., Kodama, T.,Masaki,Y. SL35'7(1999). 2Das,B., Venkataiah, B., Madhusudhan, P SL 59 (2000). 3ltoh,A., Kodama, T., Inagaki,S.,Masaki,Y. OL2,33l (2000). aBaptistella, L.H.B.,Sousa, I.M.O.,Gushikem, Y, Aleixo,A.M. ?4 40,2695(1999). 5lwasawa, N., Sakurada, F.,Iwamoto,M. OL2,871 (2000).
H
Silicon tetrafluoride. 3-Fluoroalkanols,t Oxetanesin which one of the o-positions is benzylic, allylic, or propargylic are opened by SiFa regioselectively. Also, the ring opening is influenced by J o . 5 7 l 7( 1 9 9 9 ) .
additives. For example, good results are obtained in the presenceof BuaNF, whereas the reaction seems to be suppressedby diisopropylethylamine-water, which is effective in promotingepoxideopening.
l!
i J::r.r\ in the Presenceof t-butylr, ,. .rlrca in methanolat room temrr-'. '.r1ic acids using NaHSOa-silica d: , , .rcidsand phenylaceticacid deh. :':..cnce of a mesoporoussilica. allylic ..,.1-./rrconia,regioselective lrt , : r-dimethylpyrazolefor oxidarr ... r. rre largelYabsent.
9r
t )
F. SiFa- Me2S + Et2O 0"
z-OH
,Y )
R
R
Glycosylfluori.des.2 Glycals are transforrnedinto glycosyl fluorides with a combination of SiFoand an oxidant such as 1,3-dibromo-5,5-dimethylhydantoin, phenyliodine(IIf acetate(HrO). In suchcases,a bromine atom or a hydroxyl group is also introduced. Fluorination.3 Fluorination of arylalkenes with xenon difluoride is enhanced by SiFa. The reagent combination also transforms aromatic aldehydes into difluoromethoxyarenes.
Ph P{-
SiFa- XeF2
;*;
Phr,/-F
pAr 7lYo
e . : .crtain alkYne-Co2(CO)ucomu:::.i hr a suitabledistanceseryesto r.::r:'rrcdwith that in solution.5
rShimizu,M., Kanemoto,S., Nakahara,Y. H 52, 117 (2000). rshimizu, M., Nakahara,Y., Yoshioka, H. JFC 97 57 (1999') , 'Tamura, M., Takagi, T., Quan, H.-D., Sekiya, A. JFC 98, 163 (1999).
Silver carbonate
Silver. Claisen reanangement.\ Together with KI in acetic acid, silver effects Claisen rearrangementof allyloxyanthraquinones. rSharghi, H.,Aghapour, G. JOC 65,2813(2000).
Silver acetate. Cycloaifulitions.t 1,3-Dipolar cycloadditions of isocyanoacetic esters are catalyzed by AgOAc. In the absenceof dipolarophiles, the estersdimerize to give imidazole-4-carboxylic esters.
P a l e ,P , C h u c h e I, . E J O C l 0 l 9 r l 0 0 l , rGyollai, V., Somsak,L., Szilagyi. L. n. I 'Hauser, F M . , Y i n , H . O L 2 . 1 0 4 5t l m ) ,
MeOOC AsoAc
MeOOC
^
+
cN^cooMe
>
\: N.4eCN
/-] \*'^cooMe H
I t
:
Silver nitrate. 18,320; 19,305--106.i
Cyclizatinn.t 2-Alkynylbenzorc Substitutedisocoumarinsare the malc
Carbonyl compounds from a4llir the a-amino nitrile derivativesof enel drolysisof the products.2
rGrigg,R., Lansdell,M.L, Thornton-Pett, M. Z 55, 2025(1999).
Silver carbonate. 2-Methylenetetrahydrofurans.t 4-Alkynols cyclize on exposure to silver carbonate. An oxygen functionality at the propargylic position has a remarkable acceleratingeffect.
-
-N'
LDA
t{c.
+
. :
Nc'a
I
\
/-o'
ry
BuCHO .zu::-,2:-
q
Ag2CO3 PhH 80'
Barbier reactian,3
A catalvtic am
action of benzylic halides with ArCHO
l-Amino sugars.z Displacement of an anomeric bromine atom by an acetamino group is achieved when glycosyl bromides are treated with silver carbonate in MeCN in the dark.
AcO
aOAc
nco\9$-coNH2 ncd A.
AcO aOAc As2co3 > nco$-\,.o' MecN ncd ,l,ro. 76Yo
Oxidation.r
Oxidation of a naphthol can go beyond the quinone stage.
tbrmed.
rBellina,F., Ciucci, D., Vergamini.P.. Rml r P i e r r e ,F . ,E n d e r s D , . fL40.5301 11999, 'Bieber, L.W., Storch,8.C., Malvestrrr.I . ,l
Silver(I) oxide. 18, 321; 20, 341 Coupling of l-alkynes.t The ft alkenyl and aryl halidesin THF ar (fl, 1 tivator.The salts.BuoNX (X : OH. Fr
rMori, A., Kawashima, J.. Shimada. T. S (2000).
Silver(I) oxide
r:- .r.rJ. silver effectsClaisenre-
Ag2C03- Et3N cH2ct2 25.
*r ..rfltrscetic esters a.fe catalyzed , .:.::rcrize to give imidazole-4-car-
rPale,P, Chuche,J. EJOC 1019 (2000). rGyollai, V., Somsak,L., Szilagyi, L. TL 40,3969 (1999). ' H a u s e rF , . M . ,Y i n , H. OL2,1045 (2000).
t,':.]OC
L-
/ \ \N'^cooMe H
Silver nitrate. 18,320;19, 305-306; 20,340 Cyclization.t 2-Alkynylbenzoic acids afford lactonesby the action of AgNO1. 3Substitutedisocoumarinsare the major products. Carbonyl compoundsfrom a-amino nitriles. A synthesisofct-hydroxy enonesfrom the a-amino nitrile derivativesof enals startsfrom alkylation with aldehydesand the hydrolysis of the products.2
'r c\posure to silver carbonate' , rrrarkableacceleratingeffect.
.) -N'
*"-\Z-
=-,O\
LDA
AgNO3
BUCHO
THF - H2O
83% overall
'a7 o 99o/o
ri
-:,'rnine atom bY an acetamino .,.'h rilver carbonatein MeCN in
-,1 i
aOAc
{-o ^rl - *-7--5''v'' I n^X auv NHAc 760/o
rn.: :hc qulnone stage.
OH
Barbier reaction.r A catalytic amount of AgNO. is important in the Zn-mediated reaction of benzylic halideswith ArCHO in buffer solutions(pH - l2) as lessbibenzylsare formed. rBellina,F.,Ciucci,D., Vergamini, P.,Rossi,R. 7 56,2533(2000). rPierre,F.,Enders, D. TL 40,5301(1999). 'Bieber,L.W, Storch,8.C.,Malvestiti, I., daSilva,M.F.f4 39,9393(1998).
Silver(I) oxide. 18, 321; 20, 341 Coupling of l-alkynes.t The Pd(0)-catalyzed reaction of terminal alkynes with alkenyl and aryl halides in THF at 60" proceedsin good yields when Ag,O is added as activator. The salts. BU4NX (X : OH, F) have similar effects. lMori, A., Kawashima, J., Shimada, T., Suguro,M., Hirabayashi, K., Nishihara,Y. OL 2,2935 (2000).
Sodamide
Silver tetrafluoroborate. 13,273-27 4; 18, 322 Cleavage of S-(2arimetfulsilyl)ethyl group.t Facile Ag(I)-mediated S-C bond cleavageis the basis for the use of the TSE group in thiol protection. The TSE-substituted thioglycosides are stable toward most reagents for carbohydrate transformations except the very strongly hard and soft Lewis acids and desulfonylating conditions, therefore their many applications can be envisaged. rGrundberg, H., Andergran,M., Nilsson,U.J.TL 40,1811 ( 1999). Silver tosylate-urea, Allylntion.t Silver tosylate is used in combination with urea, a Lewis base catalyst, to promote allylation of aldehydeswith allyltrichlorosilane. rChataigner, L, Piarulli,U., Gennari, C.TL40,3633(1999).
Desilylatian.2 The C-Sr I an aryltrialkylsilane suffers ro ammonia.
rChoppin, S.,Gros,P, Fon.\'. 5('. :Sun,G.-R.,He,J.-8.,Jie.H.-J..h
Sodium 13, 277; 18, 323--31{. Aromatic acylation.t .,\n , aromatic hydrocarbon such as boxylic ester in THF at room t DMF are used. Desulfunylation.2 A gena naphthalenide(Na + naphthala
Silver trifluoromethanesulfonate. 13, 274-27 5; 14,282-283; 16,302; 17,314; 18, 322-323; 19, 306; 20, 342 N-Alkylation.t Silver triflate is essentialfor an intramolecular alkylation of oxazole that contains an aziridine moiety. A I,3-dipolar cycloaddition is triggered henceforth.
OAc
OTBS AgOTf / N.4eCN
o
rPeriasamy, M., Reddy,M.R..Bh.i rBergmeier, S.C.,Seth,P.P.fL {0. (
'( )**" ( I
'Vede.is, 8., Klapars, A., Naidu,B.N.,Piotrowski, D.W.,Tucci,F.C."/ACS122,5401(2000). Sodamide.20,342 Alkylation.t Allyl phenyl sulfide undergoes alkylation using DME-activated sodamide.The processis adaptableto a synthesisof phenyl 1-vinylcycloalkyl sulfidesby a twofold alkylation with 1,
PhS.
( . )
'^'p
\ Dt\4E 0"
Sodium alkanethiolates. Arenethiols,t Sodium r-hr sulfides.
Decomplexation.2 Dicotral decomposedat room temperatu
rPincharti, A., Dallaire,C.,r'anBrc :Davis,D.S.,Shadinger, S.C.fa a.
Sodium alkoxide-aryloxide ct Ester interchange.t Thci the preparation of t-butyl esrer removing methyl acetate contl
useful in dealingwith enolizabk 7SYo
rKissling, R.M.,Gagne, M.R.OL 2-
Sodium alkoxide-aryloxide clustcrs
t .reile Ag(I)-mediated S-C bond n 1 :.,'l protection.The TSE-substituted
r - ..ri.rrhydratetransformations except
Desilylation.? The C-Si bond between an aromatic nucleus and the silicon atom of an aryltrialkylsilane suffers reductive severance on treatment with sodamide in liouid ammonla.
.;rJlbnylatingconditions, therefore
I Choppin,S.,Gros,P.,Fort,Y. SC30, 795 (2000). 2Sun,G.-R.,He,J.-B.,Jie,H.-J.,Pittman,C.U.SL 619(2000).
a:
': * ith urea, a Lewis basecatalyst,
J
.-rnc'.
Sodium 13,277 ; 18, 323-324; 20, 342-343 Aromatic acylation.t An acyl group is introduced to the skeleton of a polycyclic aromatic hydrocarbon such as naphthalene when it is treated with sodium and a carboxylic ester in THF at room temperature.Aldehydes are formed when formic esters or DMF are used. Desulfunylation,2 A general method for cleaving N-tosylaziridines uses sodium naphthalenide(Na + naphthalene)in DME at -78".
i!'
4. :.1 183; 16,302; 17, 314; 18, r. .:::rlmolecularalkylation of oxazole l, .,.jJrtronis triggeredhenceforth.
rPeriasamy, M., Reddy,M.R.,Bharathi, P.SC 29,677(1999). r Bergmeier, S.C.,Seth,P.P.TL 40,6 18I ( I 999).
(2000). r_.. l (-.JACSl22,5401
:.r.r l.rtion using DME-activatedsoe:::rrl l-vinylcycloalkylsulfidesby a
- ="'(O 75To
Sodium alkanethiolates. Arenethiols.t Sodium r-butanethiolate is useful for demethylation of aryl methyl sulfides. Decomplexation.2 Dicobalt hexacarbonyl complexes of alkynes are efficiently decomposedat room temperaturewith NaSMe in DMF. IPincharti,A., Dallaire,C., van Bierbeek,A., Gingras,M. TL 40, 5479(lggg). '1749(1999). rDavis,D.S.,Shadinger, S.C.ZL 40,
Sodium alkoxide-aryloxide clusters. Ester interchange,t These clusters are mild but highly effective catalysts (e.g., in the preparation of t-butyl esters by reaction of methyl esters with ,-butyl acetate,while removing methyl acetate continuously). They are kinetically less basic and therefore useful in dealingwith enolizableesters. rKissling,R.M.,Gagne,M.R. OL2,4209(2000).
Sodium bisulfate
Sodium amalgam. 18, 324; 19, 306; 20, 343 Desulfunylation.t Cleavage of the C-S bond of alkyl aryl sulfones shows rate dependence on the aryl portion. p-Fluorophenylsulfonyl and 2-naphthalenesulfonyl groups are more readily removed than the correspondingphenylsulfonyl analogues. 'Clive.D.L.J..Yeh.V.S.C.SC30.3267(2000).
methanol, NaBHa reduces methr'l nr hols.3Stereoselectivitychangesare cl
Sodium azide. 18, 325-326; 19, 307; 20, 343 I,2-Azid.o alcohols.t The regioselectivity for unsymmetrical epoxide opening with aqueoussodium azideis influencedby pH.
I 3 /
d"+NaN3+d_.d:i oH 9.5 oH 4.2
7
7't
35 80
: :
65 20
rl
a.
rFringuelli,F.,Piermatti,O., Pizzo,F.,Vaccaro,L. JOC 64, 6094(1999). 2yu.c.. Liu. B.. Hu, L. OL2, 1959(2000).
n:' K . a-a )7,
rI
oH
Vrn
Red-Ar
-tt*
Transesterificationto the nascentr observed in the case of 2.5-bist{ rented by adding someaceticacid.' Of interest is the reaction of an ,Y,N -Bis(2,2,Z-trifluoroethyl)anilirrs r
amountsof NaBHa, oxazolidinorrs cr Reduction of conjugated irir. rr conjugatedimines (i.e., 1-azadierr,s Ph
) -rqco | \-N
Sodium bis(2-methoxyethoxy)aluminum hydride. 15, 290. 3,5-Alkadienols.t This reagent (commercially known as Red-Al@) reduces homopropargylic alcohols to the (E)-alkenols.3,5-Alkadienols,and hence conjugatedtrienes, are readily acquired from the correspondingenynols.
Cl-l-..---
noneswhen conductedin DMSO.'
Reduction of carboxylic acids a ride to facilitate their reduction rrrtl
Azid.es, A direct conversionof alcohols to azidesinvolves activation with bis(2,4dichlorophenyl ) chlorophosphate.z
r-
Sodium borohydride. 13, 278-219. 1 344-345 Reaction media. While alcohoh bonyl compounds with sodium boroh or silica gel2 is added (heterogencu
oH
ct'y'"'7"-2-'n
Ph
Primary amines are obtained b1 r steps.r0 The iminating agentis madc r ing agentis NaBHa.
Nonchelate control. Diastereon context. Accessibility to defined srcr tones is desirable. Different profilcs borohydride (with slight modifi caum countable in terms of chelate and nsr
79To
HO rCrousse, G. 755' 4353(1999). M., Ducept,P, Alami,M., Linstrumelle, B., Mladenova,
,*l /,----i\
r.,reo-( y w
Sodium bisulfate. Esterification.r Heating a mixture NaHSOa.H2Oresults in ester formation. rLi,Y.-Q.,SC29.3S0l( lg99).
lF
of
carboxylic
acids and alcohols with
)
|o*ueo-
CfiHzt NaBHy' tle(
Zn(BH4)2T
Sodium borohydride
,.r.rl ar-rl sulfones shows rate u . : .. and 2-naphthalenesulfonyl n : : : nr lsulfonyl analogues.
s.:: ::crncalepoxideopeningwith
s- ' iYo" _ q_Aru. t :
65 20
..
,l\r-sactivationwith bis(2.4-
397
Sodiumborohydride.13,27g-279;15,290;16,304;It,326_327;19,307_309;20, 344-345 Reaction media' while alcoholic solvents are used in conventional reductron of carbonyl compounds with sodium borohydride, they can be replaced with hexane ifaluminar or silica gel2 is added (heterogeneousconditions). In a refluxing mixture of DME and methanol, NaBHa reduces methyl methoxybenzoates to the corresponding benzyric alco_ hols.3Stereoselectivitychangesare observed in the reduction of 2-substituted cyclohexa_ noneswhen conductedin DMSO.a Transesterificationto the nascentalcohol (alkoxide ion) during reduction, such as that observed in the case of 2,5-bis(4,_methoxybenzoyloxy)benzaldehyde, is largely pre_ vented by adding some acetic acid.s of interest is the reaction of aryl isocyanates with NaBHo and trifluoroacetic acid. ,\, N -B is(2,2,2-trifluoroethyl)anilines are generated in good yields.b Reduction of carboxyric acids and lactones. Acids are activated by cyanuric chlo_ ride to facilitate their reduction with NaBI{o to primary alcohols.TBy controlling the amountsofNaBHa, oxazolidinonescan be converted to either the lactolsor alcohols.' Reduction of conjugated imines. on forming the tricarbonyliron comprexes, conjugatedimines (i.e., 1-azadienes)are susceptible to reduction to give saturatedamines.e Ph Ph
/ t -
Fe(CO)3
\-N
NaBH4
\
\NHph
Ph t I
.r. Red-Al@) reduceshomornd henceconjugatedtrienes.
OH
-vlpn Tgok
ecids and alcohols with
90o/o
Primary amines are obtained by reductive amination of carbonyr compounds in two steps'r0The iminating agent is made up from (r-pro)aTi, NH4cr, and Et.N, and the reduc_ rng agentis NaBHo. Nonchelnte contror. Diastereoselectivity for reduction is important in a synthetic context' Accessibility to defined stereoisomers by reduction of o-amino-B-hydroxy ke_ tones is desirable. Different profiles from reduction with zinc borohydride and sodium borohydride (with slight modification of the substrates) are observed.The results are accountable in terms of chelate and nonchelatetransition states.il
Hor, r . ti r55,4353(1999).
I
EtOH
H,Na)
^\ '"o<_)-'
Ho ) ./,--i\ HN-
!o* r"o{)i''}o"
^,)
\:/
C'rzHzt
\
Ho )
* r"o{V
\-,
C6Hi27 NaBHa/MeOH
71To
Zn(BHa)2/THF B4yo
1 o,
$
CfiHzt 1 . . 1 9 4 9 :
1
Sodium borohvdride-metal salt
This compound is obtained (597o yield) from the diacetate
S-Acetoxy-I-naphthol.t2
by reaction with NaBH4 in a mixture of ethanol and toluene at room temperature. rYakabe, S., Hirano, M., Morimoto, T. CJC 76, 1916 (1998). 2Yakabe,S., Hirano, M., Morimoto, T. SC 29,295 (1999). 3Zanka,A., Ohmori, H., Okamoto, T. Sr 1636 (1999). aBarros, M.T., Maycock, C.D., Ventura, M.R. Tl 40, 55'7(1999). sPugh,C. OL2,1329 (2000). 6Tumbull, K., Krein, D.M. S 391 (1999). ?Falomi, M., Porcheddu,A., Taddei, M. TL 40, 4395 (1999). 8Reddy,G.V, Rao, G.V., Iyengar,D.S. TL 40, 2653 (1999). eAkisanya, J., Danks, T.N., Garman, R.N. "/OMC 603,240 (2000). roBhattacharyya, S., Neidigh, K.A., Avery, M.A., Williamson, J.S.SI, l78l (1999). I r C h u n g ,S . - K . ,L e e ,J . - M . T A 1 0 , l 4 4 l ( 1 9 9 9 ) . r2Becher,J., Matthews,O.A., Nielsen,M.B., Raymo, F.M., Stoddart,J.F.S4 330 (1999).
v- 1 , "_:l - ,
Reduction of nitrogcn fi causes reduction of azrdcs NaBHa-NiCl2 in methanol IRCH)2NH from RCN drn amines)is advisable.aThe cc useful application to a svnthe
Sodium borohydride-iodine. 17, 3 16; 18, 328; 19, 309: 20, 346 Reduction of carboxyli.c acids.t After derivatizing into the pentachlorophenylesters, acids are reduced to alcohols by this reagent system. This method is applicable to N-protected amino acids and peptides. Imides to amines.2 The last step of a convenient route to C2-symmetric 3,4disubstitutedpyrrolidinesinvolvesreductionof the correspondingsuccinimides.
ph
I ox/-A
,o
//
N a B H-41 2
N-Bn
Ph ",
+
\ |
rHF ^
N-gn
Tin(IV) bis( 1,2-benzenedr amines.6
.{ramini, A., Brinchi, L.. Gernr. B a r l u e n g aJ.. , F a n a n a sF. . J . .S e n Fringuelli,F., Pizzo,F., Vaccaro 'Caddick, S., Haynes, A.K.d€ K . 'Boukhris, S., Souizi,A. IL {1. I Bosch,I., Costa,A.M., Martn. !
ph/-J
76Yo
Sodium borohydride
Under
pl
.'t-tective for the removal of
rNaqvi,T., Bhattacharya, M., Haq,W.JCR(S)424 (1999). 2Rao,VD., Periasamy, M. S 703(2000).
Sodium borohydride-metal salt. Reductbn of enones, Dependenceof reduction pathways on reaction parametersis very apparent. In a typical example, I,2-reduction changes to l,4-reduction on adding cobalt0l) chloride. Micellar conditions are conducive to further reduction in the latter alcohols.l case.giving riseto saturated Cross-conjugateddienonesare converted by NaBHa-CeClj(heptahydrate) in methanol to ethers with the conjugated diene system.2Transpositional methanolysis of the initial products accountsfor the result.
.rtlord allyl amines.r Probabl
, * ' i t h s u b s e q u e n tl o s s o f e l e m
N-
Ph/\
Another elimination procc ,ierivatives)to alkenesuses\ ,)rohexylpheny)diselenide.:T
Sodium borohydride-
fr:. d :
;: '59? \'ield) from the diacetate . l.' Jt room temDerature.
o '
.tI"'_I ._.
ph.-\-,\Z\rn
"btt3
F.
OMe
ph.\-.\-,-\ph
)
86To
7
fr. f!
: \ 1 .l 7 8 l ( 1 9 9 9 ) .
b-
Reduction of nitrogen fanctionalitie,s. Addition of CoCl2 to the reduction milieu causes reduction of azides to primary amines.3Nitriles are also satufated using \aBHa-Nicl2 in methanor at 0o. In order to avoid the predominant formation of 'RCH2)rNH from RCN direct conversion of the products to acetamides(or N-Boc_ rmines) is advisable.aThe completereductionof oximes with NaBHa-Ticll has found a usefulapplicationto a synthesisofc-amino esters.5
.:.:,n.J F.St 330(1999).
I
-)(\
NoH
l-.-z\AcooEt
NaBH4 - TiCl3 Llartaric
t : .. 10. -1-16 l J . a - .:rtrrthe pentachlorophenyl esters,
oEt
acid
)--"fcooEtf',
(aq. buffer)
oEt 82To
n l:.;' nrcthodis applicableto N-pron
:rint route to c2-symmetric3,4:::. ponilng succinimides.
:N-Bn 160k
Tin(IV) bis(1,2-benzenedithiolate) has been usedto mediatethe reductionofazides ro
amines.6
Aramini,A., Brinchi,L., Germani, R., Savelli,G. EJOC1793(2000). :Barluenga,J.,Fananas,F.J.,Sanz,R.,Garcia,F.,Garcia,N.fZ40,4735(1ggg). 'Fringuelli, F.,Pizzo,F., Vaccaro, L. S646(2000). 'Caddick, S.,Haynes, A.K.deK., Judd,D.B.,Wiltiams,M.R.V.ZZ 41,3513(2000). 'Boukhris, S.,Souizi,A. TL 40,t66g(l9gg). 'Bosch, I., Costa,A.M.,Martin,M., Urpi,F.,MIarrasa, J. OL2,3g7 (2000\. Sodium borohydride-chalcogenide. Elimination. under phase-transfer conditions, the NaBHo-Te combination is cffective for the removar of ail the oxygen function of 5-tosyloxyoxazoridin-2-ones to alrord allyl amines.rProbably the displacementby a telluride ion initiates the process twith subsequentloss of elementalTe in the elimination step).
Bn l. : .:lh\\ays on reactlonparametersis n -:..rnsesto l,4-reduction on adding r:.r! r,) further reduction in the latter in methanol BI'I CeClj(heptahydrate) rf' .rrr()nalmethanolysisof the initial
,9
1,,r1 rn-'Yo -OTs
NaBHa-Te adogen 464 H2O- PhMe
B n --N H
n/v 93Yo
Another eliminationprocessthat transformsr,2-dior dimesyrates (e.g.,ribonucreoside derivatives)to alkenesusesNaBHo in conjunctionwith catalyticquantity of bis(4-perfluorohexylpheny)diselenide.2 The diselenideis readily recovered.
Sodiumchlorite
'Xu, Q., Dittmer,D.C. TL 40,2255(1999). 2crich,D., Neelamkavil,S.,Sartillo-Piscil,F.OL 2, 4029(2000). Sodium borohydride-zirconium(IV) chloride. N---0 bond scission, Heterocyclic N-oxidestand nitro compounds (both aliphatic and aromatic)2are reduced to the amine stageby this reagentpair. C-O bond cleavage. Alcohols are recovered after treatment of allyl ethers NaBH4-ZrCl4.3 The Lewis acidity of zirconium chloride also facilitates the cleavage of the C--{ bond of acetalsto allow reduction to give ether products.a 'Chary,K.P.,Mohan,G.H.,Iyengar,D.S. CL 1339(1999). 2chary,K.P.,Ram,S.R.,Iyengar, D.S.SL 683(2000). 3Chary,K.P.,Mohan,G.H.,Iyengar,D.S. Cl, 1223(1999). aChary, K.P.,Laxmi,Y.R.S.,Iyengar, D.S.SC29, 1257(1999).
I
r7
7 Vr 7t
v'
Sodium cyanoborohydride. a-Hydroxy esters.t cr-Chlorogl;r Jondensationare effectively convened Tributyltin hydride.2 It is adran :() generate Bu.SnH for synthetrc us rption. Introduction of a carbon ru .ubjecting the 2-iodoindole derivatrr
rlkene addends. Homoallyic alcohols.3 Alkenrl c s ith zeoliteH-ZSM 5) in 1,2-dichlct
1_O Ph/*
Sodium bromate. 18, 330; 20,347 Oxidatians. Ethers are susceptibleto oxidation by NaBrOj. Thus, THF furnishes 1butyrolactone (807o yield)r and tetrahydropyranyl benzyl ether gives benzaldehyde(95Vo yield).2 Debenzylation r Benzyl ether and benzylidene derivatives of carbohydrates are cleaved with NaBrO.,-Na2S2Oain a biphasic reaction system. Esters are stable under such conditions.
Grison,C.,Coutrot,F.,Comoy,C.. t emlb Fiumana, A., Jones,K. CC 176l (19991 Gupta,A., Vankar, Y.D.IL 40, 1369r ISag
Sodium formate.
?
OAc Fq Aco,,,(_r),,'oMe eno-"gprs
OAc NaBo3-Na2s2oa f O nco,,,(___r)",ove Hp;;;* 25 ua7"oa" 96%
rMetsger,L., Bittner, S. I56, 1905(2000). 2Mohammadpoor-Baltork, I., Nourozi, A.R. S 487 (1999). rAdinolfi, M., Barone,G., Guariniello,L., Iadonisi,A.TL40,8439 0999).
Sodium chlorite. 20, 348 Oxidations. The oxidation of primary alcohols to acidsr with sodium chlorite is catalyzedby TEMPO and bleach. On the other hand, when the oxidation is carried out at 0' with a silica-supportedTEMPO in the presenceof KBr and in a biphasic solvent system(aqueousphasepH 9.1) primary alcoholsafford aldehydes.2 tZhao,M.,Li, J.,Manoa,E., Song,2., Tschaen, D.M., Grabowski, E.J.J.,Reider,P.J.JOC 64,2564 (l999). 2Bolm,C., Fey,T. CC 1795(1999).
bl
Reductions.' Aldehydes are red tr ater.The conditions can be controlkt Deiodination.2 Iodopyrroles und :\ usedas a hydrogensource.
Bryson,T.A.,Jennings, J.M.,Gibson.J \t Leung,S.H.,Edington, D.G.,Gnffrrh.T L.
Sodium hexamethyldisilazide. l& -14-Iminopyrimidines.t A dramarrc Jensationof amidinesto alkvnvl ci anr
H
H
t
l
-.N.-zN I
I
Pn:CN
I
+ (MqS}2| + 1no bcel
Sodium hexamethyldisilazide
!
I :::r,r compounds(both aliPhatic :3:jnt palr. J:::cr treatmentof allYl ethers lir .rl.o facilitatesthe cleavageof i-::.r(rducts.4
Sodium cyanoborohydride. a-Hydroxy esters.\ cr-Chloroglycidic esters that are accessible from Darzens-type condensationare effectively converted to the hydroxy estersby NaBHjCN. Tributyltin hydride.2 It is advantageousto use only a catalytic amount of BurSnCl to generate Bu.SnH for synthetic use. The combination with NaBH.CN is one such option. Introduction of a carbon substituent to C-2 of indoles is accomplished by subjecting the 2-iodoindole derivatives to these reagents in the presence of AIBN and alkene addends. Homoallyic alcohols.3 Alkenyl epoxides are reduced regioselectively by NaBHjCN (with zeoliteH-ZSM 5) in 1,2-dichloroerhane.
ao'
r-O V
NaBH.cN
Ph''\,"\
Ph'^\-\
H-ZSM 5 ctcH2cH2cl
rr \.rBror. Thus, THF furnishes1ur . rhcr gives benzaldehyde(95Vo I .:-::retives of carbohYdratesare s\ . --: Estersare stableunder such
OAc
L^' \ , ,
" --. , \1
/
or"
Flua--.. OAc 96%
I . - ., 1999).
l
.rcidsrwith sodium chlorite is :n the oxidation is carriedout at KBr and in a biPhasic solvent
(i
.Jchvdes.2
F.
..r H.J.J., Reider,P.J.JOC 64'2564
l. : '
'r:
rGrison,C.,Coutrot,F.,Comoy,C., Lemilbeau, C.,Coutrot,P.TL 41,6571(2000). rFiumana, A., Jones, K. CC 1761(199q. rGupta,A., Vankar,Y.D. TL40, 1369(1999).
Sodium formate. Reductions.t Aldehydes are reduced to alcohols with HCOONa in supercritical water. The conditions can be controlled such that ketones are not affected. Deiodination.z Iodopyrroles undergo Pd-catalyzed dehalogenation when HCOONa is usedas a hydrogensource. rBryson,T.A.,Jennings, J.M.,Gibson,I.M. TL 41,3523(2000). rLeung,S.H.,Edington, D.G.,Griffith,T.8.,James, J.1.TL40,7189(1999).
Sodium hexamethyldisilazide. 18, 332; 20, 349 4-Iminopyrimidines,t A dramatic change in chemoselectivity is observed in the condensationof amidinesto alkynyl cyanides.
T .tN\ZN
l
'nfY
I l
+ Ph:CN
-
NH
HNs.\r,, t
atY*
.*YN
+ (MqSi)2NNa
3
97
+ (no base)
97
t
l
t
l
e
Ph
l
Sodium hydride
Twofold alkylation.2 Alkylation of 3,3'-bis(oxindole) derivatives with 2,3-O,Opropylidene-threose-1,4-ditosylatein the presence of MHMDS gives different diastereomers in accordanceto the alkali metal ion M, whether M : Na or M : Li.
r(N,le3Si)2NNa
X
Carbanion formation as a result of : reneration of a proximal alkoxide ion rs
Double annulation is observed rrtrrr .rlkynonesreact.aThe size of the alkll g rhe nature of the secondrine.
-l
J-l orsl.=,*
i
TsO
) f
CN
I
,2
T H F- D M P U
a
V, BnN
aac N /--;-ct.r NC
r. ,
v F a
lMcCauley,J.A., Theberge,C.R., Liverton, N.J. OL2,3389 (2000). 2Overman,L.8., Larrow, J.F.,Stearns,B.A., Vance,J.M. ACIEE39,213 (2000).
Sodium hydride. 14, 288; 16, 307-308; 18, 333; 19, 312-313; 20, 349-350 Cyclizations. Alkynones in which the two functional groups are separatedby two and three methylene units are converted to furans and pyrans,r respectively,on treatment with sodium hydride. N-Sulfonylated allylamines that bear a leaving group at the distal allylic position give aziridinederivativesby an intramolecularS"2' displacement.2
Claisen rearrangement.s Ba^se-Fr rlternative method for the ester Clarrc :his protocol is clearly advantageous.
v
ll nogys ^/_.,/""
t ---.-'' /'\"
/ ll \_j , \-8,
ori-* Mes
Br
t : /Y1 - N O2S-tttes 88o/o(trans : crs 97 : 3)
\
(J
Dehydrohalngenation.'
\'(
A comtu
1.5,8,9-tetraazabicyclo[3.3.3]undeca b Jrohalogenation.
W. EJ(rc J' \icola, T., Vieser,R., Eberbach, :Ohno,H., Toda,A., Takemoto, Y. Fu.yrr. \ .1
Sodiumhydride
rrndole) derivatives wtth 2'3-O'Occ : \IHMDS gives different diasterenL::rr \l : Na or M : Li. i.
Carbanion formation as a result of an O + C silyl group migration initiated by the generationof a proximal alkoxide ion is exploitable in carbocyclization.r
Ho"'\J'\z Me2SO
HO---\'uJ 7lYo
"i.s )2NNa
' . ' e' S t ) 2 N L i + --t
- D|\.4PU
Double annulation is observed when propylenedimalononitrile (and analogues)and 2alkynones react.4The size of the alkyl groups in the alkynones has an enornous effect on the nature of the secondrine.
v
BnN
,::.. l(XX)). \t , ' /t.r. 39,213(2000).
a--("* -r"* l
c
NaH a-fq" + 'l_ -"!f^
NC
Y"
Claisen rearrangement.s Base-promotedreaction of allylic malonates representsan alternative method for the ester Claisen rearrangement.For acid sensitive compounds, this orotocol is clearlv advantaseous.
f te. rt )-313;20,349-350 c :..rltlonal groups are separatedby two n- -:rJ p)rans,1respectively,on treatment t . :rrt bear a leaving group at the distal
o
tu:::.::)\)lecularSx2' displacement.2
L-",,4.
o
^rvcooM" +
(_Jl
\zBt
:
. -\<- N O2S-Ues : : ' , ( l r a n s :c i s 9 7 : 3 )
N
-,^
-
/
^"",r"r, # l lvelsicl \-\-COOMe Nacr'H2oNN''P
%$Dehydrohalagenation.6 A combination of NaH and 2,8,9-trimethyl-l-phosphahydrochloridegeneratesa powerful basefor dehy2,5,8,9-tetraazabicyclo[3.3.3]undecane drohalogenation. Nicola,T., Meser,R., Eberbach, W. EJOC527 (20C0). rOhno,H., Toda,A., Takemoto,Y., Fuiii, N., Ibuka,T. JCS(P1)2949 (1999).
Sodium naphthalenide
3Fleming, I., Mandal, A.K. CC 923 (1999). aGrossman,R.B., Skaggs,A.J., Kray, A.E., Patrick, B.O. OL l, 1583 (1999). sFehr,c., Galindo,I. ACIEE39,569 (2000). oliu, X., Verkade, J.G. JOC 64, 4840 (1999).
Sodiurn nitrite. Nitrosation. Nitrosatron Jitions usesNaNO,--oxalicr The more conventional r ureasto oxazolidin-2-oner I
Sodium hypochlorite. 15,293; 16, 308; 17, 316; 18, 334-335; 19, 313; 20, 350 Oxidation of nitrogen compounds. The following reactions have been reported: hydroxylaminesto nitrones.rN-alkyl a-amino nitriles to N-alkylformimidoyl cyanides,2 arylamines to quinones.3
rng an organiccosolvent(e.e Nitration.a Nitration of
Benzylic oxidations.a With a nickel salt as catalyst, substitutedtoluenes are oxidized by NaCIO to carboxylic acids. Isoxazolines.s Applying the conventional method that converts aldoximes to nitrile oxides to 2,2-di-(3-butenyl)malonoaldoxime leads to spirocyclic products. Development of such compounds into chiral ligands is expected.
controlled with the NaliO--
Sodium percarbonate. 19. -r
Oxidations,t A chromru r\ accomplishedin benzotnfh ls solvent.
f-l
J
v
I
ll HON
a, .'rl
,
u.
cH2ct2
NOH
' Cicchi,S.,Corsi,M., Goti,A. JOC 64,7243(1999). 2Perosa, A., Selva,M., Tundo,P.TL 40,7573(1999'). 3Hashemi, M.M., Beni,Y.A.JCR(S)672(1999). aYamazaki, S. SC29, 22Il (1999). 5Arai,M.A.,Arai,T., Sasai,H. OL l, 1795(1999).
Delaval, N.,Bouquillon. S..llct
Sodium periodate. l5, l9t. I Carbodiimides.r Format rion with Naloa in Dl\lF I lenonoamides.
H
Sodium iodide. t-Iodoallcynes.' l-Alkynes are iodinated by anodic oxidation in MeOH with NaI as the supporting electrolyte. Note that replacing NaI with LiCl leads to 1,1-dichloro2,2- dimethoxyalkanes. I Nishiguchi, I., Kanbe,O.,Itoh,K., Maekawa, H. Sa 89 (2000).
Sodium naphthalenide. Reduction of pyridines.t Sodium naphthalenideor Na/ammonia can be used to reduce electron-deficient pyridines to the 1,2-dihydro derivatives. Desulfunylation.2 Aziridines are releasedfrom their Ntosyl derivatives with sodium naphthalenidein THF. 'Donohoe,T.J.,McRiner,A.J.,Sheldrake, P.Of 2, 3861(2000). 2Bergmeier, S.C.,Seth,P.P.TL 40,618I ( 1999).
ar-N\
I
a
Oxidations.2 Epoxidarro tones)of alkaneshave treenr plex on an ion-exchangererrn
rKoketsu, M., Suzuki, N.. lrhrhz rMirkhani,V, Tangestaninela S
Sodium tetracarbonylcobell phrctams,t The solren
acid in nonpolar solvent it.rr polar aprotic solvents.are krx
Sodium tetracarbonylcobaltate
(
.l
158-l(1999)
6 . l t . i . r f - 1 3 5 :1 9 , 3 1 3 ; 2 0 , 3 5 0 .i rn-greactionshave been reported: f, n:r: r. tr) .\'-alkylformimidoyl cyanides,: cei: r.[. substitutedtoluenesare oxidized rr.1:: ..l that converts aldoximes to nitrile r':. : .prrocyclic products.Development
Sodium nitrite. Nitrosation. Nitrosation of secondary aminesl and thiols2under heterogeneousconditions usesNaNO2-oxalic acid in dichloromethaneand t-butanol, respectively. The more conventional method (NaNor-HCl) suffices to convert B-hydroxyalkyl ureasto oxazolidin-2-ones.r N-Nitrosationof the productscan be preventedby introducing an organiccosolvent(e.g.,EtOAc). Nitration.a Nitration of phenols stopping at the mononitro or dinitro stage can be controlled with the NaNO2--oxalicacid reagent system. tZolfigol,M.A. SC29,905(1999). :Zolfigol,M.A.,Nematollahi, D., Mallakpour, S.E.SC29,227j (1999). 'Suzuki, M., Yamazaki, T.,Ohta,H., Shima,K., Ohi,K., Nishiyama, S.,Sugai,T. SL 199(2000). 'Zolfigol,M.A., Ghaemi,E.,Madrakian, E. SC30, 1639(2000).
Sodium percarbonate. 19,314 Oxidations.t A chromium-c atalyzedoxidation of alcohols with sodium percarbonate is accomplishedin benzotrifluoride.PhCFj is a useful replacementfor 1,2-dichloroethane assolvent.
r'_
Delaval,N., Bouquillon, S.,Henin,F.,Muzarr,J.ICR(S)286(1999). SPRIX Sodium periodate. 15, 294; 18, 338-339; 19, 315 Carbodiimides.r Formation of carbodiimides from selenoureasis observed on reaction with Naloo in DMF. The selenoureasare obtained from nitrile oxides and selenonoamides.
tl
.N
Ar-'Y r tr:.,ilrc oxidation in MeOH with NaI as 3 \:l *ith LiCl leads to 1,1-dichloroF I .rtr
a:.rir- ()r Na/ammoniacan be used to relr, Jrnvatives. rc:r rheir N-tosyl derivativeswith sodium
rl I r{)t.
H
.N
' Se
-R
N,-,^
R
rrdrv4
-+ Dt\,4F \
/..
_N=C:N Ar.
Oxidations.2 Epoxidationof alkenesand hydroxylation (and partial oxidation to ketones)of alkaneshave been carried out with Naloa and manganese(Ill)porphyrin complex on an ion-exchangeresln. lKoketsu, M., Suzuki, N., Ishihara, H. JOC&,6473 (1999\. rMirkhani,V, Tangestaninejad, ,lgg9). S.,Moghadam, M. "|CR(S) 722
Sodium tetracarbonylcobaltate. plactams.t The solvent-dependentactivities of NaCo(CO)., namely, as a Lewis acid in nonpolar solvent for acylation using anhydrides,and as nucleophilic catalyst in polar aprotic solvents,are known. It can be usedin cycloadditionsby activatingketenes.
Sulfur dioxide
'ta
o
Tc
l-cooEt r
'
l
Ts
tl l
NaCo(CO)a
./---I-Yn ETOOC Ph
Ph
Phl"-
-O
rWack, H., Drury III, W.J., Taggi, A.8., Ferraris, D., Lectka, T. OL l, 1985 (1999).
Sodiumtriacetoxyborohydride. 13,283;16,309-310; 18,340;19,315-316;20,352 Reductionof indoles.t The stereoselective reductionof tricarbonylchromrum complexesof indolederivativesby NaBH(OAc):-CF:COOHproceedsafterprotonation.The hydrideattackmay involvemediationof themetalatom
-
Tantalum(V) chloride. Allylation.l TaCl5 is useful for pn trimethylsilane as well as acetylation of I achievedwithout isolation of the homoallr I
Chandrasekhar, S.,Mohanty,P.K..Reza-A 5(-.
Tetrabutylammonium borohydride. l& _ Reduction of bromo compounds. H1
NaBH(OAc)3
in THF. Since under the same condirrons : and bromoalkynes are converted to saturatc
cF3cooH
){arasimhan, S.,Swarnalakshmi, S.. Balatunrr. lJones,G.B., Guzel, M., Mathews,J.E. TL 41, ll23 (2000\
Sulfur dioxide. 20,354 Thiophenel-oxides. Treatmentof zirconacyclopentadienes directlyaffordsthe thiophene1-oxides.l
Tetrabutylammonium bromide. 20. -156 6-Ketoesters. A catalytic :unounr ( betweentin enolateswith ct,B-unsaturaral c Yasuda, M., Ohigashi, N., Shibata, I.. Baba-.\ i
RO-\/-Ar n ROr \:-Ar
"cp2zr"*o-aa-1, -+ n | *Oi
lJiang,B., Tilley, T.D. JACS 121,9'744(1999)
Ar
,ZrCp2+ Ar
RO-1/-_f\ n | RO_-/\_-y
.SOz Ar
Tetrabutylammonium fluoride, TBAF. 13 324-326; 18, 344-345; 19, 319-321 : Z). 15 Desilylation. The powerful desrlrh generatingvarious carbanion equivalenls S
accessto homoallylamines from imines and estersfrom ct-silyl-cr-diazoacetic estersand, compounds by 1-fluoro-1-methyldiptrnl treatmentof phenyl 2-trimethylsilylphenl ho
ar-siPhzMe .
"j.
.O 'ry<
Ts
.
.+Ph
ETOOC
Ph
. . . . . r r. . o L t , 1 9 8 5( 1 9 9 9 ) .
F, : ,r. t8. 340;19,315-316;20,352 omr - : . . - t r r ronf t r i c a r b o n y l c h r o mci u p r r r()H proceedsafterprotonation.The
Tantalum(V) chloride. TaCls is useful for promoting allylation of aldehydes with allylAllylatinn.t trimethylsilane as well as acetylation of alcohols, therefore these two reactions can be achievedwithout isolation of the homoallylic alcohols. rChandrasekhar, S.,Mohanty,PK., Raza,A. SC 29,25'7(1999).
nl
Tetrabutylammonium borohydride. 18, 344; 20, 356 Reduction of bromo compounds. Hydrodebromination is achieved with BuaNBHa in THF. Since under the same conditions a double bond is hydroborated, bromoalkenes and bromoalkynes are converted to saturatedalcohols.l rNarasimhan. R.,Velmathi, S. SC29,685(1999). S.,Swarnalakshmi, S.,Balakumar,
'ntrdienesdirectly affords the thio-
Tetrabutylammonium bromide. 20, 356 6-Ketoesters. A catalytic amount of BuaNBr promotes the Michael reaction between tin enolateswith ct.B-unsaturatedesters. rYasuda, N., Shibata, I., Baba,A. JOC 64,2180(1999). M., Ohigashi,
RO -.r- n^
RO
:.
Tetrabutylammonium fluoride, TBAFI, 13, 286-287; 14,293-294; 15, 298, 304:'l7 , 324-326; 18, 344-345 ; 19, 3 19-321 ; 20, 357-359 Desilylation. The powerful desilylation ability of BuoNF makes it useful for generatingvarious carbanion equivalents.Synthetic exploitations of this reactivity include accessto homoallylamines from imines and an allylsilane,r to B-hydroxy-ct-diazoalkanoic and a-fluorovinylationofcarbonyl estersand aldehydes.2 estersfrom a-silyl-cr-diazoacetic Benzyne is formed by compounds by l-fluoro-1-methyldiphenylsilylsilylethylene.r treatmentof phenyl 2-trimethylsilylphenyliodonium triflate4 with BuoNF.
OH
a.SiPhzMe *
O ll nApn
Bu4NF _-* rHF
V\Ph t F 61Yo
'
Tetrabutylammonium fl uoride, TBAF
A bicyclo[6.2.2]dodecatrieneinstead of the condensed 8:6-fused ring system is formed by a fluoride ion-triggered intramolecular alkylation.s Complexation with fluoride ion to render bis(allylsilanes) dramatically reactive is indicated.6 Protection of amines as triisopropylsilyl carbamates has been proposed, with the unmaskingsimply by exposureto BuoNF.? A synthesis of unsymmetrical azines is based on the formation of trisiopropylsilylhydrazonesand their reaction with different carbonyl compounds in the presenceof BuaNF.E A combination of BuaNF and HOAc selectively cleaves t-butyldiphenylsilyl ethers without affectingt-butyldimethylsilylethers.e Formation of transient bicyclo[2.2.1]hept-2-en-5-yne from phenyl-(3-trimethylsilylbornadien-2-yl)iodonium triflate is a reality shown by trapping experiments.r0An unusual elimination reaction is involved in the generation of perfluoroalkylethylenes from 1-iodo-l-trimethylsilyl-2-perfluoroalkylethanes.rrThe substrates are available from radical addition of perfluoroalkyl iodides to vinyltrimethylsilanes. Intramolecular alkylation accompanying desilylation of a silyl enol ether is expected in the case that a cis-decalin is formed.12For acquiring the /rans-isomer the cyclization must rely on activation by the nitrile group alone.
CI \*t-..,/r.,
t
w
I I
n
OTBS
R
BuaNF
t
l
-;;*l
Ng tl /^Y\
Inr
R
R
I
I
Aldol reactions. ct-Isocyanoalkanoic esters condense with aldehydes in the presenceof BuaNF to afford oxazolines.13 The reaction of hydrosilyl enol ethers with aldehydesafford 1,3-diolsas a result of aldol reactionand subsequentreduction.ra
o +
-*
l l HAptr
reactions. and [ArX
Two
n'pes
* Ar'rSn]r
c
are
rWang,D.-K., Zhou, Y-G., Tang,Y. Hou. \ -l :Kanemasa, S., Araki, T., Kanai, T.. \['ada. F, I 'Hanamoto, T., Harada,S., Shindo. K.. Korrjo'Kitamura, T., Yamane, M., Inoue. K.. Todrfr 11674 (1999). iFujishima, H., Takeshita,H., Toyora.\1.. thrr 'Shibato,A., Itagaki, Y, Tayama.E.. Hollc.'t' -Lipshutz, B.H., Papa,P.,Keith, J.i\{. ./(X-51. 'de Pomar, J.C.J.,Soderquist,J.A. TL {1. r:iJ 'Higashibayashi, S., Shinko, K.. lshrzu. T
l 306(2000).
"Kitamura, T., Kotani,M., Yokoyama. T. FuF iSzlavik,Z.,Tarkanyi, G.,Gomory.A.. Raher rFleming,F.F.,Shook,8.C.,Jiang.T.. Srcsud 'lto, Y.,Higuchi,N., Murakami,M. H 52.I I , : 'Miura,K., Nakagawa, T., Suda.S..Hosomr,I 'Laronze, M., Laronze, J.-Y.,Nemes. C . S+. ^Yasuhara, A., Kanamori,K.. Kaneko.\l . 529(1999). Yasuhara, A., Kameda, M., Sakamoto. T ('P8 'tsurns,C.J.,Field,L.D.,Morgan, J..Rrdlcy-D ''Mowery, M.8.,DeShong, P.OLl.2l3i ,Wq :"Fugami,K., Ohnuma, S.,Kameyama. \l . Srr
R
t
OSiHMe2
Coupling Ar'Si(OMe)jlre
BU4NF
Ph
THF _78"
65To
Indole derivatives. A method for hydrolysis of indole-3-acetonitrilesr5 is by exposing them to air in the presence of BuaNF. 2-Substituted indoles are conveniently preparedfrom 2-alkynylanilines in refluxing THF with BuoNF.r6 Reactions of sulfur compounds. MN-Bis(sulfonyl) arylamines lose one of the sulfonyl groups on heating with BurNF in THF.r7 Cyclic disulfides are obtained from l, or-dithiocyanotoalkanes.I8
Tetrabutylammonium hydroxide. Z). -t5 Partial hydrolysis.t The panial h1d using dry BuoNOH in THF or DME. Hasegawa, T.,Yamamoto, H. SL 84 ( 1999,
Tetrabutylammonium nitrate-trifl uorc Nitration,t This reagent system ru .electivity dependson existing substituuc
Deghati, P.YF.,Bieraugel, H., Wanner. \lJ . K
Tetrabutylammonium peroxydisulfrtc- I C--O regeneration, Oximes arxJsc Oxi"dations. Benzyl ethers :ue rcr alcoholysis3. Primary aminesare oxidrzal
Oxidative cycloaddition.s Tte orr presenceof cyclic enol ethers leads to iurc
Tetrabutylammonlum perorydisulfate
- : Jcnsed 8:6-fusedring sYstemis a.r....rtron.sComplexationwith fluoride a . .:rJicated.6 t.::r..rtc'r has been proposed, with the .: rhc'iormation of trisiopropylsilylhyI . :llpoundsin the presenceof BuaNF.o r. . .'lr'avest-butyldiphenylsilyl ethers :r,: !nc tiom phenyl-(3-trimethylsilylAn unusual n - . :r.rppingexperiments.l0 ?:. :' ol perfluoroalkylethylenesfrom l:.. \ubstrates are available from lr ::.:thrlsilanes. lr..:r:,'nof a silyl enol etheris expected r.t-::r:tsthe /rcns-isomerthe cyclization
Coupling reactions. Two types of Pd-catalyzedaryl-aryl coupling: [ArX + areassistedby BuaNE Ar'Si(OMe):J1e and[ArX -f Ar'oSn]20 lWang, D.-K., Zhou, Y.-G.,Tang,Y., Hou, X.-L., Dai, L.-X. JOC 64,4233 (1999). rKanemasa, S., Araki, T., Kanai, T., Wada, E. TL 40,5059 (1999). rHanamoto,T., Harada,S., Shindo,K., Kondo, M. CC 2397 (1999). rKitamura, T., Yamane, M., Inoue, K., Todaka, M., Fukatsu, N., Meng, Z'., Fujiwara, Y. JACS l2l, 116'74(1999). sFujishima, H., Takeshita,H., Toyota, M., Ihara, M. CC 893 (1999). 6Shibato,A., Itagaki, Y., Tayama, E., Hokke, Y., Asao, N., Maruoka, K. f 56, 5373 (2000). Tlipshutz, B.H., Papa,P, Keilh, I.M. JOC 64,3"192(1999). Nde Pomar,J.C.J.,Soderquist,J.A. TL 4t, 3285 (2000). eHigashibayashi,S., Shinko, K., Ishizu, T., Hashimoto, K., Shirahama, H., Nakata, M. SL r 306 (2000). l0Kitamura,T., Kotani, M., Yokoyama,T., Fujiwara,Y. JOC 64,680 (1999). 1| Szlavik,2Z.,Tarkanyi,G., Gomory,A., Rabai,J. OL 2,2347 (2000). rrFleming,F.F.,Shook,B.C., Jiang,T., Steward,O.W. OLl,1547 (1999). lrIto, Y., Higuchi, N., Murakami, M. H 52,91 (2000). rrMiura, K., Nakagawa,T., Suda,S., Hosomi, A. CI 150 (2000). rsl-aronze,M., Laronze,J.-Y.,Nemes,C., Sapi,J. EJOC 2285 (1999). r6Yasuhara,A., Kanamori, K., Kaneko, M., Numata, A., Kondo, Y., Sakamoto, T. JCS(PI) 529 (1999\. lrYasuhara,A., Kameda,M., Sakamoto,T. CPB 47,809 (1999). rBBums,C.J., Field, L.D., Morgan, J., Ridley, D.D., Vignevich,V.TL40,6489 (1999). reMowery M.8., DeShong,P. OLl,2137 (1999). roFugami,K., Ohnuma,S., Kameyama,M., Saotome,T., Kosugi, M. Sa 63 (1999).
Tetrabutylammonium
c:. -,'ndense with aldehydes in the r:.:,:r{rnof hydrosilyl enol etherswith reduction.ra ri. .rndsubsequent
OH
OH
:- >rY-Ph 65%
is by s.r.1. of indole-3-acetonitrilesrs : : \ubstituted indoles are conveniently F .'.:hBurNF.'n r. ..- tirnyl) arylamines lose one of the r'relic disulfidesare obtainedfrom l,
Partial
hydrolysis,t
hydroxide.
20, 359
The partial hydrolysis
of dimethyl
esters can be achieved by
usingdry BuaNOHin THF or DME. rHasegawa, H. SL 84 (1999). T.,Yamamoto,
Tetrabutylammonium nitrate-trifl uoroacetic anhydride. Nitration.t This reagent system nitrates l-deazapurine nucleosides.The regioselectivitydependson existing substitutionpatterns. lDeghati,P.Y.F., M.J.,Koomen,G.-J.TL4l,569(2000). Bieraugel, H., Wanner,
Tetrabutylammonium peroxydisulfate, 19, 322 C:0 regeneration. Oximesl and semicarbazones2are cleaved. Oxidations, Benzyl ethers are removed by oxidation with (BurN)zS2Os and alcoholysis3.Primary amines are oxidized to nitriles with Ni-Cu formates as catalyst.a Oxidative cyclaadditian.5 The oxidation of l,3-dicarbonyl compounds in the Dresenceof cvclic enol ethersleadsto fused acetals.
410
Tetraethylammoniurn hydrogen carbonate
'Chen, F., Liu, A., Yan, Q., Liu, M., Zhang,D., Shao, L. SC 29, 1049 (1999). 2Chen, F., Liu, J.-D., Fu, H., Peng, Z.-2., Shao,L.-Y. SC 30, 2295 QUn). 3Chen, F., Peng,Z.-2., Fu, H., Meng, G., Cheng, Y., Lu, Y.-X. 5L627 (2000). aChen,F., Peng,Z.-2., Fu, H., Liu, J.-D., Shao,L.-Y. JCR(S)726 (1999). 5Chen,F., Fu, H., Meng, G., Cheng,Y., Hu, Y.-L. S 1091 (2000).
Tetraethylammonium peroxydicarbc Oxazolidin-2-ones.1 This reagc'n Et4NClOl, CO2, and 02. It carborrle cyclizationto oxazolidin-2-oneson iunl
rFeroci,M., Inesi,A., Muccianti.y.. ft1x.r [. Tetrabutylammonium tribromide. Ether cleavage.r BuaNBrj in methanol cleaves several kinds of ethers but TBS ethers are the most susceptible. Thus, desilylation can be achieved in the presence of acetonidesand THP ethers. rGopinath, R.,Patel,B.K. OL2,4177(2000).
i
?
Tetrabutylammonium triorganodifl uorostannates. Diarylmethanes.t With (PhjP)4Pd as catalyst, unsymmetrical ArCH2Ar' are obtained from a cross-coupling reaction between aryl triflates and BuqN[BnrSnFz] in DMF. Disulfides.z BuaN[RjSnF2] act as nucleophiles toward sulfur. Oxidative dimerization of the thiols initially formed, results in disulfides.
Tetrakis(acetonitrile)copper(I ) hexefr Cyclic imines.r Alkynylamine. cr Diaryl ethers.2 The phenol-anl (MeCN)aCuPF6.
Epoxidation.3 Conversionof alkcn ascatalystproceedsat low temperatureI c
rMuller,T.E.,Grosche, M., Herdtweck. F- P Kalinin,A.V.,Bower,J.F.,Riebel.P. Snros 'Andrus. M.B..Poehlein. B.W.Il 41. lri:: '
Tetrakis(triphenylphosphine )palledit 16,3 17-323: 17, 327-33 | : 18, 3{7--U9
rMartinez, A.G.,Barcina,J.O.,delR.C.Heras,M., deF.Cerezo, A. OL2, 1377(2000). 2Kerverdo, X., Poulain,S.,Gingras, M.TL41,5841(2000). S.,Femandez,
Allylic displacements. Neu trp substitutionare B-allyloxyacrylicc':rc'r carbonatesand sulfonatescontainherrc Regioselective displacement of allr lx
Tetrachlorophthalimide. Primary amines.t When used in the Mitsunobu reaction, the litle compound converts primary and secondaryalcohols into the conesponding protected amines.
allylsilanes.2Allenyonitriles are obtarncrlt
tlia,ZJ., Kelberlau, S.,Olsson,L., Anilkumar,G.,Fraser-Reid, B. SL 565(1999).
Tetracobalt dodecacarbonyl. Pauson-Khand reaction.t With cyclohexylamine as activator, catalytic amount of Coa(CO)12mediatesthe Pauson-Khand reaction in DME under CO. rKrafft,M.8., Bonaga,L.v.R.ACIEE 39,3676(2000).
Tetraethylammonium hydrogen carbonate. 20, 360 Carbonates.t Treatment of 1,2-diols with Et4NHCOT in MeCN at room temperatureresults in the formation of cyclic carbonates. Sulf.des.2 EI4NHCOj or (EtaN)2COjcan serve as basein the alkylation of thiols. rCasadei, M.A.,Cesa,S.,Feroci,M., Inesi,A. NIC 23,433(1999). 2Feroci, M., Inesi,A., Rossi,L. SC29,2611(1999).
t(
, t*
n_*R,, ocooR
Displacementthat is followed hr cr,
1-hydroxyalkyl-1-lactones.5 Thndem coupling and cvcli/ir c-arylvinylated cyclopropanes6 and trt andoxazolidinones." Furanderivatrrc.r
6\o tl C,rHru/
+ Ptrl
Tetrakis(triphenylphosphine)palladium(0)
4tl
Tetraethylammonium peroxydicarbonate. Oxazolidin-2-ones,t This reagent is available from electrochemical reaction of EqNClOl, CO2, and 02. It carboxylates 2-amino alcohols and the products undergo cyclization to oxazolidin-2-ones on further treatment with TsCl.
( :e r()19( 1999). P l:q: (1000). '-\ .i 627(2000). -th il9g9). f., - ' r t
rFeroci, V, Rossi,L.TL40,6059(1999). M., Inesi,A.,Muccianti,
r.. .c'\erll kinds of ethers but TBS n . i:l he achievedin the presence of
Tetrakis(acetonitrile)copper(I) hexafl uorophosphate. Cyclic imines.' Alkynylamines cyclize under the influence of (MeCN)aCuPF6. Diaryl ethers.2 The phenol-aryl halide coupling is promoted by Cs2COj and (MeCN)+CuPFc. Epoxidation.3 Conversionof alkenesto epoxideswith MCPBA, using (MeCN)aCuPF6 as catalystproceedsat low temperature(e.g., -20').
!5.
a.!.:. unsymmetricalArCH2Ar' are r:-. .:r\l triflates and BuaN[BnjSnF2] s ' .r,ird sulfur. Oxidative dimerization
\ OLz. 1377(2000)Cr-: < \ J t (2000). [ {r
lMuller,T.8.,Grosche, 8., Pleier,A.-K.,Walter,E.,Yan,Y-K. OM 19, 170(2000)M., Herdtweck, rKalinin,A.V, Bower,J.F.,Riebel,P, Snieckus, v. JOC 64,2986(1999). rAndrus. B.W.TL4l, l0l3 (2000). M.B..Poehlein. Tetrakis(triphenylphosphine)palladium(0). 13, 289-294; 14' 295-299; 15' 300-304; 16. 3 11 -323 : l7 . 327-33 | : 18, 347-3 49 ; 19, 324-33 | : 20, 362-3 68 Allylic displacements. New types of substrates for this (Ph1P)aPd-catalyzed substitutionare B-allyloxyacrylicestersand p-allyloxyvinyl sulfones.rThese vinylogous carbonatesand sulfonatescontainbetterleaving groups. Regioselectivedisplacementof allylic acetatesthat contain a homoallylic silyl group gives are obtainedby reactingpropargyl carbonateswith Me]SiCN.r allylsilanes.2Allenyonitriles
L(-: .u reaction, the litle compound ;, :::.ponding protectedamrnes. R-'
r i. .: u. Sr 565(1999).
R \
q,, ocooR
h:. :rl lrs activator, catalytic amount of I I ) \ 1 F -u n d e r C O .
' R (Ph.P)4Pd> R + Me3si_cN Fc{ rHF ^ Nc
at room
/'\n i l -
FL-:ti.r.
n: .i. basein the alkylation ofthiols. 3ri
..)99).
R-
Displacementthat is followed by cyclization enablesthe synthesisof chromenesaand l-^y-lactones.' 1-hydroxyalky Tandem coupling and cyclization. Functionalized allenes are converted to and heterocyclesincluding epoxides,Ttetrahydrofurans,E cr-arylvinylatedcyclopropanes6 Furanderivativesare formed from allenyl ketones.l0 and oxazolidinones.')
:h
rr:. F-I.NHCOr in MeCN
'
+Ph-l
(Ph3P)4Pd .------------------*
tn\-
/ \\ ^t;in,l'#.'c''H"404
CtzHzs 75%
4t2
Tetrakis(triphenylphosphine)palladium(0)
In the presenceof sodium alkoxide (for generating alkoxyimino nucleophiles for the cyclization), 2-alkynylbenzonitriles afford isoindole derivatives.| | Cyclizations and cycloadditions. Treatment of N,N'-diacylhydrazinesl2 and "y,6-unsaturated ketone O-pentafluorobenzoyloximesrr with (Ph.P)+Pdgenerates1,3,4oxadiazolesand substitutedpyrroles,respectively.
N
'ococ6Fs
(Ph3P)4Pd Et3N / DtVtF
pn)*
A [4 + 2]cycloadditionbetweenenynesand 1,3-diynes,with the latter serving as the two-carbon component,results in substitutedbenzenederivatives.The adductsderived from 1.4-di-l-butoxv-1.3-butadivne are readilv convertedto coumaranones.ra
I ) )
+
l
+ rPh ,^/*NHR
2 2 ,;i
z><,
rrY
(PhrP)4Pd ll II
+ THF O"
a
2 2' 2'
Acylatians. 2-Alkynoic ester\ arr the presenceof (Ph:P)+Pdand base t D\l Stille coupling. The usefulne.. preparation of arylcoumarin inhibitrn < readily obtained from RSnBu. and hmm The Stille coupling is acceleratedhr
congestedsubstrateshas been develoFrl usine shd coupling of alkenylstannanes ( .ynthesisof )-wodeshiol.:'
-Y-
i
l
orf
91%
)
I + BurSnJ
Ot{
I
3
Alkylidenemalononitrilesundergocycloadditionwith Me.,SiCNand then N-allylation to sive 3.5-disubstituted tetrazoles in one step.rs OH I
CN I (rnrHl4'o> tn_Z^\7:r.r
CN tn*"*
+ AcO-'//:-:.-
+ Me3SiN3
rHF6o'
P>zy\sna" (.o-*\.,/ | ll l" l
>:F .-':Dvs:
N1-'N'N-"\
93%
Addition to alkynes. Nucleophiles add to alkynes in different addition modes. are Thus, c-substituted vinylphosphonium saltsr6 and 1,2-diphosphonylalkanesrT prepared from 1-alkynes,but apparently an isomerization-hydroaluminationpathway prevails when 2-alkynes react with amines under similar conditions.The products are allylamines.r8(Note the formation of N-benzyl-2-styrylpiperidinein an intramolecular reaction,but the correspondingN{osyl derivativefails to cyclize.)
(-F*
Tetrakis(triphenylphosphine)palladium(0)
ai :ri .rlkoxyimino nucleophilesfor the II k' .:::rr atives. c:" , 't N.N'-diacylhydrazines12and *ith (Ph.P)rPd generates1'3'4r.-.
ph'V.\\$runr, / R=rs
+ (Ph3P)4Pd
\':,'o-Q
phZ-""""ttNHR
Bn
, i
-
HN\
r
;
l
l
81%
/
f,h--f,\'/
i ncs. with the latter serving as the - Jcrivatives.The adductsderived .J to coumaranones.la
/Y
rr=a
Acylations. 2-Alkynoic estersare made from l-alkynes and a chloroformic ester in the presenceof (PhiP)aPdand base(DMAP-1,2,2,6,6-pentamethylpiperidine)'re Stille coupting. The usefulness of tosylates in the Stille coupling facilitates preparation of arylcoumarin inhibitors of gyrase 8.20 Benzylic and allylic boronates are I readily obtained from RSnBuj and bromomethylboronates.2 The Stille coupling is acceleratedby CuCl. An effective system applicable to sterically congestedsubstrateshas been developed.22Preparationof functionalized dienesby homousing slightly different conditionsenablescompletion of a coupling of alkenylstannanes ( of )-wodeshiol.r' synthesis
o'/:-
?'
1
/..
91Yo
{Ph3P)4Pd> ..\3;\t"utt'
o''
I
ll
*
I
o"^"^J-..ttu'" bu3r,, I
ricr_cucrI
ll
I
I
95% (93% ee)
h \le,SiCN and then N-allYlation
o ) o
OH (Ph3P)4Pd>
CN
/- ' : .-rZ: ru. - N,f.f
O-4\Sne'.
(oJ=/
ll
P
:',"1"":::\o 82%
l1
93o/o
t,
f.\ncs in different addition modes. are .::rJ 1.2-diphosphonylalkanesrT pathway . :: zation-hydroalumination
.:rlrlar conditions.The products are . l - rr rr lpiperidine in an intramolecular .. to cyclize.) r( d,
(Yo., (-)-wodeshior
(o)""gd
Ho,"n,'oH
(ori)""to' 'o^'-/
Tetrakis(triphenylphosphine)palladium(0)
1-Alkynes are convertedto (E)-alkenesin a microwave-assisted hydrosilylation-Stille coupling process,2aand both reactions are catalyzed by (PhjP)aPd.Interestingly, arylation oftributylstannylacetylene is achievedvia a Stille coupling and then C-stannylation.25
Bu3Sn:
+ Ph-l
Ph:
##
+ Bu3Sn-l11-
T\e 2-azabicyclo[3.3.I ]nonane f accessiblefrom an intramolecular ccr Organobismuth dialkoxides cor.rp
pn-----sngu. 83%
_ R +
E( Stille coupling betweenRSeSnBuj and R'X is applicableto the synthesisof diorganyl selenidesRSeR'.26 Suzuki coupling, A practical transformation of ArX to ArMe is by the Suzuki coupling with [MeBO]..2? Diarylmethanes are obtained from ArCH2Br and arylboronic acids.28 The coupling of 3-pyrrolin-3-yl triflates with arylboronic acids leads to 3-arylpyrroles becauseof concurrentdehydrogenation.2e A caveatof the coupling involving haloanilines is that deamination30 also occursto someextent. A route to alkynylarenes and enynes from l-alkynes involves formation of alkynylboronic esters flithioalkynes * (r-PrO)rB] and Suzuki coupling in situ.:rrSuzuki cross-couplingusing thallium(I) ethoxide32 as promoteris superiorto TIOH becauseof its stability, commercial availability, and easeof use. A convenientmethod for assembling conjugatedpolyenesis assured.
A testimony to the efficiencl of , Pd-catalyzedreactions is delineatedr
,-Rr il It
+
(1) +
-a' r- l"n -
(1) = (Ph3P)aPd
COOMe - TtOEt (Ph3P)4Pd
t-BUOOC
THF - H2O (3 i 1)
tBuOOC
(Ho)28'V\y'2..v.oH
-J
I-BUOOC
97%
In a two-stagecoupling of N-allyl-N-2-bromoallylamine,the N-sulfonyl derivatives are most suitable as B-elimination of alkylpalladium intermediates after the initial (likely by coordinationl.t' intramolecularHeck reactionis suppressed The coupling of arylboronic acids with acid chlorides is the basis of a ketone synthesis.ra It is found that the Suzuki coupling in an ionic liquid has severaladvantages: reducedcatalystconcentration,no homocoupling,and reactionin the air.ts Other coupling reactions. A model study has demonstrated the utility of intramolecular Heck reaction in the construction of the morphine skeleton.l6 It is surprising that only the desirableregioisomer is formed.
F--
Tetrakis(triphenylphosphine)palladi,,m(0)
r . . - .\ .t\ e-assistedhydrosilylation-Stille Z . :
^
., Ph,P)1Pd.Interestingly,arylation :.lrns and then C-stannylation.2s
415
The 2-azabicyclo[3.3.1]nonaneframework, a portion of the strychnos alkaloids, is accessiblefrom an intramolecular coupling of 4-N-(2-haloallyl)aminocyclohexanones.3T Organobismuth dialkoxides couple with electron-deficient aryl and alkenyl triflates.38
LDA
Sn-l +
Ph:SnBu3
Tfo
R.-..-f
(Ph3P)4Pd
83%
NMP 80'
Etooc
| | ) EtOOC""--'J
:- :.eble to the synthesisofdiorganyl I'
: .{rX to ArMe is by the Suzuki
i ' : . : :J liom ArCH2Br and arylboronic
3'
A testimony to the efficiency of constructing highly unsaturatedcarbon skeletons by Pd-catalyzedreactions is delineated in a synthesisof xerulin.3e
^, 'r()nicacids leadsto 3-arylpyrroles : thc coupling involving haloanilines
^ ----J
)t' a
i-llkynes involves formation of .: Suzukicouplingin situ.rrSuzuki ,: r\ superiorto TIOH becauseof its \ ,r)nvenientmethod for assembling
ll
f
i
)
-
+lJfLn:+ ----J
BrZn.-:-
ll
I
II a u u : (1)= (Ph3P)aPd
| ,r, V "
TBS lrt
l(1) V
'-f\
_
tt_]\ -TBS
__/-:\,, I
'\r,
//--:--:l
___J
97To
r ., . ..rnrine,the N-sulfonyl derivatives lr.:.r .-:n intermediatesafter the initial ^. -,',,rdination).rr u -:ll,rridesis the basis of a ketone I .::.:,'nicliquid has severaladvantages: : i'.rctionin the air.rs r:.r. |(: demonctrated the utility of ,r the morphine skeleton.36It is
|r]
t"t'
:---1\
V
:-3uOOC
l,
l o n ;z n e 2 ;
Itl
: BuOOC
LBt
':1E'5
\:_Br
cp,z(H)cl
r-\:-',. V' +
Tetrakis(triphenylphosphine)palladium(0)
Rearrangements.
Allyl
esters are directly
converted
to isocyanatesaO when the
modified Curtius rearrangementis carried out in the presenceof (Ph.P)oPd.A versatile construction of the core structure of antibiotic CP-263114 is highlighted in a reaction sequenceconsisting ofcarbonylation, lactonization, and siloxy-Cope rearrangement.al
co
-
(Ph3P)4Pd
i-P12NEt / PhCN
bothZlEisomers useful
R
JEt3sio
46-56%
rEvans,P.A., Brandt,T.A., Robinson,J.8.TL40,3105 (1999). 2Macsari,I., Hupe,8., Szabo,K.J. JOC 64,9547 (1999). iTsuji, Y., Taniguchi,M., Yasuda,T., Kawamura,T., Obora,Y. OL2,2635 (2000). aNay, B., Peyrat, J.-F., Vercauteren,J. EJOC 2231 (1999). sRudler, H., Parlier, A., Cantagrel, F., Harris, P, Bellassoued, M. CC'17 | (2000). 6Ma, S., Zhao, S. OL2,2495 (2000). ?Ma, S., Zhao, S. JACS 121, 7943 (1999). 8Kang,S.-K., Baik, T.-G., Kulak, A.N. 5L324 (1999). 'Kang, S.-K., Baik, T.-G., Hur, Y. 255,6863 (1999). roMa, S., Zhang, J. CC 117 (2000). "Wei, L.-M., Lin, C.-F.,Wu, M.-J. TL 4l,1215 (2000'). I2lutun, S., Hasiak,B., Couturier,D. SC 29,111 (1999). rrTsutsui,T., Narasaka,K. CL 45 (1999). 'oGevorgyan,V, Quan, L.G., Yamamoto,Y.JOC 65,568 (2000). r5Gyoung,Y.S.,Shim, J.-G.,Yamamoto TL 41,4193 (2000). ,Y r6Arisawa, M., Yamaguchi, M. JACS 122,238'7 (2O0O). r T A l l e nJ, r . ,A . , M a n k e ,D . R . ,L i n , W . T L 4 l , l 5 1 ( 2 0 0 0 ) . rsKadota,L, Shibuya, A., Lutete, L.M., Yamamoto, Y. JOC 64,4570 (1999). reBottcher, A., Becker, H., Brunner, M., Preiss, T., Henkelmann, J., DeBakker, C., Gleiter, R.JCS(Pr)355s(1999). 2{)Schio, L., Chatreaux,F., Klich, M. TL 41,1543 (2000). 2rFalck,J.R.,Bondlela,M., Ye, J., Cho, S.-D. TL 40, 5647(1999). 22Han,X., Corey, E.J. JACS l2l,7600 (1999). 2rHan, X., Corey, E.J. OL l, 187| (1999). 2aMaleczka, Jr., R.E., Lavis, J.M., Clark, D.H., Gallagher,W.P.OL2,3655 (2000). 25Antonelli,E., Rosi, P.,Sterzo,C.L., Viola, E. JOMC 578,210 (1999). 26Nishiyama,Y., Tokunaga, K., Sonoda, N. OI 1, 1725 (1999). 27Gray,M., Andrews, I.P., Hook, D.F., Kitteringham, J., Voyle, M. TL 41, 6237 (2000). 28Chowdhury S., Georghiou, P.E. TL 40,'1599 (1999). 2el-ee,C.-W., Chung, Y.J. TL 41,3423 (2000).
r0Hird,M., Seed,A.J., Toyne,K.J. Sl {-rt 'r Castanet,A.-S., Colobert, F., Schlmarn ' 'rFrank, S.A., Chen, H., Kunz, R.K.. i-in
rrLee, C.-W, Oh, K.S., Kim, K.S...{hn- X IHaddach, M., McCarthy,J.R. IL $. -rl( '5Mathews, C.J., Smith, P.J.,Welton. T Cr '6Frey, D.A., Duan, C., Hudlicky. T. OL l. rTSole,D., Peidro,E., Bonjoch, J. OL 2. : rNRao,M.L.N., Shimada,S., Tanaka.\l ( reNegishi,E., Alimardanov,A., Xu. C Ot '"Okumoto, H., Nishihara, S., Yamanxro. 'rBio, M.M., Leighton,J.L. OL 2. 2905, 2
Tetrakis(triphenylphosphine)pelli Coupling reactions. c-Fluorrn virtue of their capacity of partakrng r based on the Pd(0)-catalyzed erct followed by the Negishi coupling :
1,2-Alkadien-4-ynesare fornrcd b with 1-alkynes.3
""" *",r(
*
\
'Chen, C., Wilcoxen, K., Zhu. Y.-F..KrmrDabdoub,M.J., Dabdoub,V.B., Manm.. 'Condon-Gueugnot, S., Linstrumelle. G I
Tetrakis(triphenylphosphine )pbttr Hydrosilylation. This reacuoo complexes such as (PhrP)1Ptor radrc
Dib oratio n of methy le necyc Iq opening of the substratesoccurs oo can be transformed in various * ar s tr
Tetrakis(triphenylphosphine)platinum(0)
when the . :.rc'ft€d to isocyanatesa0 (:: nrcsenceof (Ph3P)4Pd. A versatile :P-:hrll-l is highlightedin a reaction n .::1.:.lloxy-cope reiurangement.4l
\
-
l
I
:
= *^l
l
Et3SiO
417
3oHird,M., Seed,A.J., Toyne, K.J. SZ 438 (1999). 3rCastanet. A.-S., Colobert,F., Schlmam,T. OL2,3559 (2000)3zFrank.S.A., Chen,H., Kunz, R.K., Schnaderbeck, M.J., Roush,W.R. OL2'2691 (2000)' 3 r l e e . C . - W . .O h , K . S . ,K i m , K . S . ,A h n , K . H . O L 2 , 1 2 1 3 ( 2 0 0 0 ) 34Haddach, M., McCarthy,J.R. Zt 40, 3109 (1999). rsMathews, C.J., Smith, P.J.,Welton, T. CC 1249 (2000). r6Frey,D.A., Duan, C., Hudlicky, T. OLl,2085 (1999). rTSole,D., Peidro,E., Bonjoch, J. OL2,2225 (2000). r8Rao,M.L.N., Shimada,S., Tanaka,M. OL l, l2'l I (1999). ieNegishi,E., Alimardanov,A., Xu, C. OL2,65 (2000)' loOkumoto, H., Nishihara, S., Yamamoto, S., Hino, H., Nozawa, A.' Suzuki, A' Sf 991 (2000)' arBio, M.M., Leighton,J.L. OL2,2905 (2000).
l 46-56Yo
iodide. 18' 349-350; 20, 369 Tetrakis(triphenylphosphine)palladium(0)-
I
t : a
". ()L2.2635(2000).
with 1-alkynes.3
\t cc77l (2000).
,. /// / Me3Si
C "c H r r /
+
(Ph3P)aPd'cul
\ \ t\-c'
-
i-Pr2NH
CsHrr \-r.-
r"-
//r Me3Si
84Yo
.-., I
( , , f ' { 1 5 7 0( 1 9 9 9 ) . : i : : r \ c l m a n n , J . , D e B a k k e r , C . , Gleiter,
':
rChen,C., Wilcoxen, K., Zhu, Y-F., Kim, K., McCarthy,J.R. JOC 64'3476 (1999). rDabdoub.M.J.. Dabdoub.V.B., Marino, I.P.TL4l'433,437 (2000). rCondon-Gueugnot,S., Linstrumelle,G. I56, 1851 (2000).
/\]irt.
r''\ t' ()L2,3655(2000). it -. tr1999). t . . ; . ,
\ . . \t. TL41,6231\20oo).
Tetrakis(triphenylphosphine)platinum(0) . 20' 369-37 0 Hydrosilylation. This reaction has been studied using either transition metal or radicalinitiators.l complexessuchas (PhrP)4Pt Diboration of methylenecyclopropanes. Regioselective functionalization with ring opening of the substratesoccurs on reaction with bis(pinacolato)diboron.z The adducts can be transformed in various ways to useful substances.
418
Tetrapropylammonium perruthenate, TPAP
+
'CF
(Ph3P)4Pt PhMe 80"
+
#n f('l- |
tl
-\:-\oH n=5-8
Allylic
displacement.r
Marko, I.8., Gautier, A., J5ukere\r,
(1999). ACrEE 38,1960
The Pt(0) complex is effective in mediating the reaction.
rltoh, M., Iwata, K., Kobayashi,M. JOMC 574,241 (1999) 2lshiyama,T., Momota, S., Miyaura, N. SI, 1790 (1999). 3Blacker,A.J., Clarke, M.L., Loft, M.S., Mahon, M.F., Humphries, M.E., Williams, I.M.I. CEJ
Thallium(tlD acetate. Oxidation of B,yunsatarr, acetates areformed.
1-f-coon | [ \,,-
-
-t :
6, 353(2000). a-Tetralol. Carboxyl protection. Tetralyl esters can be selectively cleaved by MejSiCl-NaI in MeCN at room temperahre without affecting benzhydryl estersandp-methoxybenzyl esters.
o5""
T,K,..:
'Slade,C.J.,Pringle,C.A.,Summer, I.G. TL 40,5601(19991. N,N,N',N' -Tetramethyl-S-( 1-oxidopyridin-2-yl)isothiouronium
salts. Peptide couphng.t The tetrafluoroborate and hexafluorophosphate salts are developed as peptidecoupling reagents,illustratedby the preparationof dipeptidesand tripeptides.
rFenaz, M.V.A..Srl H.M.C.,Grazini,
rBailen,M.A., Chinchilla, R.,Dodsworth, D.J.,Najera,C. JOC 64,3936(1999). 2,2,6,6-Tetramethylpiperidinoxyl,TEMPO. N-Alkoxy-2,2,6,6-tetramethylpiperidines.t TEMPO replaces the carecholboryl group from its B-alkyl derivatives. Thus, alcohols in a protected form are obtained from hydroboration if so desired, using this oxidant in the workup. Oxidation.2 The presence of TEMPO is essential to the smooth autoxidation of primary alcohols to aldehydes catalyzed by (PhjP)qRuCl2. Without TEMPO, further conversion of the aldehydesto carboxylic acids is observed. rOllivier,C.,Chuard,R.,Renaud, P.SL 807(1999). 2Dijksman, A., Arends,I.WC.E.,Sheldon, R.A. CC 1591(1999). Tetrapropylammonium perruthenate, TPAP. 20, 370 Isomerization r TPAP is a catalyst that converts allylic alcohols to ketones (8 examples,41-92Vo).
Thallium(IlD nitrate, TTN. 16. Cyclopentyl 2-hydroxyalhl contraction on treatment *'ith TT
-r ..'\..\/oH (/
-c
Ring expansion.' The nn showsdi fferentreeioselectivitre
Thallium(Ill)nitrate,TTN
^" -1-l \ = ,+_ ,-a t
+
r+^f f(l^ |
tl
-.ho',
/
, - \
n=5-8
IMarko,LE., Gautier,A., Tsukazaki, E, Urch,CJ', Brown,S'M' M., Llobet,A.' Plantalech-Mir, AC(EE38,1960(1999).
Thallium(Ill) acetate. Oxid.ation of B,y-unsaturated acids.t acetatesare formed.
COOH
rl: !. ::\ !- in mediating the reaction.
rl(Nos):
9
Either butenolides or degraded allylic
/-"a',
l l F o
cH2ct2
\.,,.-o
85To
. li..::r:hries. M.8., Williams, I.M.J. CEJ
(cooH
aoo" t(No3)r15H2o
,\r\
cic.::rclv cleavedby MejSiCl-NaI in d:-. . .:.tersandp-methoxybenzylesters.
l l | \r'\2
|
cl2ct?
a\-\
' l l | \/\,2
+ l l | \V\//
|
( 2 :1 ) 77o/o
rcrhiouronium salts. saltsare developed r \ .,:..:,,r()phosphate .l dipeptidesand triPePtides. a:, f>1.n9,r6( 1999).
t \l l'( ) replaces the catecholboryl r: .: :.r()tectedform are obtainedfrom r .. :kup. tO the smooth autoxidation of .a!:.1:.1;
rFenaz,H.M.C., Grazini, M.V.A., Silva, Jr., L.F., Longo, Jr., L.S. SC 29, 1953 (1999)'
Thallium(IlD nitrate,TTN. 16,326;18,351;19,334;20,371 cyclopentyl 2-hyd.roxyalkylketones.t 2-(l-cyclohexenyl)ethanolsundergo nng with TTN in aqHOAc. on treatment contraction
r l' RuCll. Without TEMPO, further !i".::r
rl /\'\oAc
|
r|.
'
419
r(No3)3./\)-\/oH
c'd.
(-)--
c . : .. i n \
allylic alcohols to ketones
*ffi
|
v
H
,P oH y
R=H
71%
R=Me68%
Ring expansion.2 The ring expansion of unsymmetrical l-vinylcyclobutanols shows different regioselectivities as effected by Tl(NOj)j and by (PhCN)2PdC12'
Thionyl chloride-trifl ic acid
:Olah. G.A., Marinez, E.R., Prakash.G.K-S
Thiourea. 19, 336; 20, 37 l-372 Episulfi.des.t In a convenion ol dn(IV)-porphyrin complex, thiourea fu 1,3-Dioxolane cleavage.: Hl& thiourea in aqueous ethanol at rcflr substrates such as 1,2;5,6-di-O-rs acetonideis cleaved.
:Tangestaninejad, S.,Mirkhani,V. SCt. f, : Majumdar,S.,Bhattacharjya , A. JOC g. 5
Thulium(Il) iodide. Tml2(dme)1 is rnct Alkylation.' the reaction of RX with ketones. Il 13
o Tt(N03)3 (PhcN)2Pdcr2
6.3: 1 1 i 7.1
rFerraz, H.M.C.,Santos, A.P.,Silva,Jr.,L.F.,deO.Viera,T. SC30,751(2000). 2Kocovsky, P.,Dunn,V.,Gogoll,A., Langer,V. JOC 64,101( l 999).
1-Thionoacyl 6-nitrobenzotriazoles. Thiono esters.t At room temperature and in the presence of imidazole, the benzotriazolederivatives transfer the RC:S group to alcohols.
must be avoided.
rEvans, W.J.,Allen,N.T."IACS122.I I I t , i
Tin. 13, 298; 17' 333-334;18' 352. 2l Alkylation. The allylating agcl consistsof two species,the initialll- fc Tin in combination with Me.SrO : bromomethylketoneswith aldehldcs rChan,T.H.,Yang,Y.,Li, C.l. JOC6. sj rSun,P.,Shi,B. "/CR(S) 318(1999).
iShalaby, M.A., Rapoport, H. JOC 64, 1065(1999).
Thionyl chloride-benzotriazole. Chlori.des and nitriles. The reagent combinant transforms alcohols to alkyl chloridesand acidsto acid chlorides,rwhile aldoximesare dehydrated.2
Tin(II) bromide. 14' 303-304: l& -15 With SnBrl as prc Allylation.t regioselectivity and diastereoselectrrr
rChaudhari, S.S.,Akamanchi,K.c. SL 17630999). 2Chaudhari, S.S.,Akamanchi, K.c. SC29, 1741(1999\.
I
\4.,Bt Thionyl chloride-triflic acid. Dinryl sulfuxides.t A Friedel-Crafts-type reaction between arenes and thionyl chloride is catalvzed bv TfOH.
+ PhcHo
;
Tin[D bromide
rOlah, G.A., Marinez, 8.R., Prakash' G'K'S' St 1397 (1999)'
Thiourea. 19,336; 20,37 l-3'12 that is catalyzed by a Episulfides.t In a conversion of epoxides to episulfides atom' tin(Iv)-porphyrin complex, thiourea furnishes the sulfur I,3-Dioxolanecleavage.2Hydrolysisofcyclicacetalsisaccomplishedwith Some selectivity is shown in thiourea in aqueous ethanol at reflux temperature' in which the terminal substrates such as 1,2;5,6-di-O-isopropylidenefuranoses acetonide is cleaved' rTangestaninejad, S.,Mirkhani,V. SC 29,2079(1999)' 2Majumdar, A. JOC 9,5682 (1999)' S.,Bhattacharjya,
:l
Thulium(Il) iodide. in mediating Alkylation.t Tml2(dme)2 is more powerful than SmIz(thflx-HMPA HMPA where situation a in valuable particularly rhe reaction of RX with ketones. It is
v
must be avoided. IEvans,W.J.,Allen, N.T.JACS 122,2l I 8 (2000)'
-
nrc\cncc of imidazole, the ,t.
u
:.rnstirrms alcohols to alkYl :ehr drated.r
Tin. 13, 298; l7 , 333-334; 18,352; 20,3'72-373 Alkylation.Theallylatingagentderivedfromtinandallylbromideinwater is more reactive'r consistsof two species,tfrl initiaty formed allyltin(Il) bromide of bromoacetonitrile and reaction the mediates MerSicl with Tin in combination bromomethylketoneswith aldehydes'2 rChan,T.H.,Yang,Y., Li, C.J.JOC 64, 4452(1999)' 2Sun.P..Shi,B. ,rCR(S) 318(1999).
Tinfl D bromide. 14, 303-304; 18, 352; 19, 336-337 interesting with SnBr2 as promoter, the carbonyl allylation shows Allylation.l absenceof BuaNBr' regioselectivity and diastereoselectivityin the presenceor
OH
\Z:,8, \'
. bctween arenes and thionYl
+ phcHo#
...,4.-,Irn * groNB,
I . y'Y-pn I 9 4 : 6 5 : 9 5
fin(IV)
chloride
rIto, A., Kishida, M., Kurusu, Y., Masuyama, y. JOC 65,494 (ZOOO).
Tin(II) chloride.13,298-299;15,309-310;16,329;18,353-354;19,337-338;20,373 Addition to enones.t The addition of tributylstannylaceticesters to enones proceedsin differentmannersaccordingto the catalyst:1,2-addition is promotedby Sncl2 andl,4-additionby MejSiCl.
a-.y''-.,2R' ll
o
SnBu3 +
vreoocj
+
RJ'^Y*. MeooC/
-"-;;
v
cooMe
SnCl2iMeCN
<1
Me3SiC / Ml e N O 2
>99:<1
:>99
Hydrostannylation,2 Allenes undergohydrostannylationon exposureto (Phjp)2pdCl2, SnCl2and HCI in DMF. Allylation of aldehydesby the ensuingatlyltin trichloride reagentsis completed at room temperature.
I
o
R
:C<
R'
.
ll HAR-
- (Ph3P)2PdC12 SnC12 HCt - DN.4F
OSiMe3
\ a + ""x$
OH
2Y'"R R '
'Yasuda, M., Matsukawa, Y., Okamoto, K., Sako, T., Kitahara, N., Baba, A. CC Zl49 (2OOO). 2chang,H.-M., Cheng,C.-H. OL2,3439 (2000).
Tin(IV) chloride. 13,300-301;14,304-306;15,311-313;17,335-340;18,354-356; 19, 338-339; 20, 373-37 5 Cyckzations, Activation of an allenyl group with SnCla and linkage to a C-nucleophile constitute a ring formation process.rThe reaction of N-arylaldimines with allylsilanes (or allylgermanes) in the presence of SnCla leads to 2,4-disubstituted 1,2,3,4-tetrahydroquinolines2due to rapid interceptionof the carbocationicintermediates. 1,3-Butadien-2-ylation.t Treatmenr of 2-tributylstannyl-1,3-butadiene with SnClo rendersit reactive as a nucleophile toward carbonyl compounds. Mukaiyama aldol reaction a Chemoselective ionization of a mixed-O,S-acetal by Lewis acid is noted. Thus, it is possible to synthesize B-alkoxyketones or B-organothioketonesat will.
Cleavage of p-methoxybenryl crb' cleavage.functional groups sensittrcto allyloxy, siloxy, acyloxy groups. and rr
rKitagawa,O., Suzuki,T., Fujiwara-H.. Trg rAkiyama,T., Suzuki,M., KagoshrmaH ll rLuo,M., Iwabuchi, S 5L I Y.,Hatakeyama. lBraga,A.L.,Dornelles, L., Silveira.C C . \l 5Yu,W.,Su,M., Gao,X., Yang.2.. ln.7- f,
Tin[D iodide. Allylation and proparylationlalet allylic alcohols to act as nucleophrles when SnI2 is replaced with SnBr, \
systemcontainingSnCl2. The analogouspropargylation or all mesylatesand 2-alkyn-l-yl mesllater 1
9t
R---:--l
OMs
R
5
OMs
rMasuyama,Y., Ito, T., Tachi, K., lto. A . Kr rMasuyama, Y., Watanabe,A., Ito. A.. Kuru
Tin0I) iodide
j
l .rrr.
. I tt. r5-l-354;19,337-338;20,373 estersto enones u:...l.rnnylacetic bY SnCl, .: . l-additionis promoted
f--
OSiMe3
v\
|
* I
\.,.' M"o^srn
-Aio,"
I
urr"
l
I ricro
423
o ll
\,/
\r'\r--spn
I A-/-,-rR'
,-,,,..R' ll
A -
'
+
\
t\
<1
9r.:
> 9 9 : < 1
'
86%
./'\
O
H
COOMe
:>99
on exposureto (PhjP)2PdCl2, ur. .1::,)n is : r:.-..rr! allyltintrichloridereagents
OH
r
y'\'/t",, ,/\
I
R R '
rl-, \
Baba.A. CC 2149 (2OO0).
to perform this ether cleavage of p-methoxybenzsilethers.s By using Sncla-PhSH cleavage,functionalgroupssensitivetoDDQorCANcanberetained.Thus'organothio, allyloxy,siloxy,acyloxygroups,andacetonidessurvivethereactionconditions' I Kitagawa,O., Suzuki,T., Fujiwara,H., Taguchi,T' TL 40'2549(1999)' rAkiyama,T., Suzuki,M., Kagoshima' H' H 52,529(2000)' rl-uo,M., lwabuchi,Y.,Hatakeyama, S.SI 1109(1999)' rBraga,A.L.,Dornelles, L'A S 562(1999)' L., Silveira,C.C.,Wessjohann, sYu.w., Su,M., Gao,X., Yang,2., Jin,Z. TL 4l' 4015(2o0o)'
Tin(II) iodide. Allylationandproparylntionlallcnylation.TheSnl2_BuaNI_Nalsystemactlvates reactions are observed allylic alcohols to act as nucleophiles toward aldehydes.r slow whenSnl2isreplacedwithSnBr2.Noreactionoccurswithaconespondingreagent systemcontainingSnCl2. l-Alkyn-3-yl The analogouspropargylation or allenylation uses propargyl mesylates.2 mesylatesand 2-alkyn-1-yl mesylatesgive different products' OH
l: : i. 17,335-340;18,354-356; ft r':(.1, and linkageto a C-nucleophile f \ ..rlaldimines with allylsilanes(or r I : Jr'ubstituted 1,2,3,4-tetrahydron:, ;:lnnediates. with SnClo u:, .:.rnnvl-1,3-butadiene )Unds. a ::::', i : 'r../.rtlonof a mixed-O,S-acetalby r,
.r nthesize B-alkoxYketones or
S n l ? - N a-l B u 4 N /l D M | i
R:_l
OMs
*\ *'
R'cHo fi R
R
Snl2- Nal - BuaNl/ DMI ;
OMs
rMasuyama, Y, Ito, T., Tachi, K.' Ito, A., Kurusu, Y' CC 126l (1999)' rMasuyama, Y., Watanabe,A., Ito, A., Kurusu, Y' CC 2009 (2000)'
R'
roH
i
Titanium(Il)
chloride-N,N,N',N'-tetramethylethylenediamine
TinflV) oxide. Meerwein-Ponndorf-verley reduction,l Hydrous sno2 catalyzesthe vapor-phase reduction of carbonyl compounds with isopropanol. Transacylationl Passing a mixture of an ester and an alcohol or amine throueh hydrous SnO2completes the acyl exchange.
Titanium(IlD chloride. 4- Ox o-2-alkc ny lp hosp ho n compounds involves nitrile orrd the resulting isoxazolines to tlx step is readily achieved bl the ur
rWaghoo, G.,Jayaram, R.V.,Joshi,M.V SC29,5130999).
_oH
Tin(II) triflate. 13,301-302; 14,306-307;lS,313-314;17,341-344;18,357_358; 19, 340:20.376 Ethers from ethyleneacetals.' C,O-Dialkylation of ethyleneacetalsis effected with silanesand silyl ethers using Sn(OTf)2 as catalyst.
91
| ph,^O
/
..
sn(orr)2
Mersi-v \ -
+ BnO-SiMe3
oBn
+ MecN 20
| .
ph,-93To
P
rLee,S.Y,Lee,8.S.,t ee.C.-\\'.(I Titanium0lD chloridelithiun Depropargylation.t f'-Prc{ in THF at room temperature. rRele,S.,Talukdar, S.,Baneqr..{ f
Aziridine opening.2 Hydroxylated compounds (alcohols, water) open N-tosylaziridines in the presenceof a Lewis acid [Sn(OTfy, or BF.,.OEtr]. rSuzuki,T., Oriyama,T. SC 29, 1263(tggg). 2Prasad, B.A.B.,Sekar,G., Singh,V.K.TL 41,4677(2000).
Titanium(III) chloride-zinc- lt McMurry reaction.: Sul 2,2'-diformylbiaryls by the \lcl
1 o
chloride-N,N,N', N' -tetramethylethylenediamine. AllElidenatian Methylenationof esterswith cH2(ZnI)2 is promotedby (tmeda)Ticlr.l Borylalkenes2and germanyalkenes3 are similarly preparedfrom [M]CH(ZnX)2. Titanium(Il)
q .e{
O
znBr ZNBT
o
ricr4 -f
+ H
\-Ph
o 1 o
".
;i -f;'\_* 42% (Elz
62:38)
Reductive couplings.a Benzaldehyde is converted to syr-hydrobenzoin with a TiCl2-amine system. Moderate asymmetric induction is observed when the reaction is carriedout in the presenceof a chiral trans-N,N,N',N'-tetramethyl-1,2-diaminocyclohexane. rMatsubara, S.,Ukai,K., Mizuno,T.,Urimoto,K. CLg25(lgg9). 2Matsubara, S.,Otake,Y., Hashimoto,y., Utimoto,K. CL741 .lggg). 3Matsubara, S.,Yoshino, H., Utimoto,K., Oshima,K. SL495(2000). aMatsubara, y., Okano,T.,Utimoto,K. St l4ll (1999). S.,Hashimoto,
lGies,A.-8.,Pfeffer,M. JOC6. 4
Titanium(I0 chloride. 13. -10r18,359-361;19,341-3M:4. 11 F unctional group exchatl
ethers,r silyl ethers,?and prop direct synthesis of c-(benzotnr with I -chlorobenzotriazole and Aldol and Mannich reuti by a twofold Mukaiyama aldol 1,2-diketones.s
=damrt
fitanium{IV) chloride
\nO. catalyzesthe vapor-phase
lL.
l
J an alcohol or amine through
Titanium(Ill) chloride. 4-Oxo-2-alkenylphosphonates.l
A synthesis of this class of apparently useful compounds involves nitrile oxide cycloaddition with allylic phosphonates,conversion of the resulting isoxazolines to the conjugated oximes, and hence to the enones. The last step is readily achievedby the use of TiClr.
N'oH
: 17.311-344;18, 357-358;19,
425
o
rich/DMF
,,\.,\-'.$:' *t
o
o
,,\z^-=,
: r.thvleneacetals is effectedwith lLee, S.Y.,Lee, B.S., Lee, C.-W., Oh, D.Y. JOC 65,256 (2000).
:- tr.,,k
'.'tC\
OBn
I ph--*.
!l
93%
Titanium(Ill) chloride-lithium. 19, 340;20, 377 Depropargylation,t N-Propargylamines undergocleavageon treatmentwith TiClr-Li in TFIFat roomtemperature. I Rele, S., Talukdar, S., Banerji, A . fL 40, 767 (1999).
rr 'ir. *arer) openN{osylaziridines
| tr-.
:
Titanium(Ilf chloride-zinc . 19,341;20,377 McMurry reaction.r Substitutedphenanthrenes have been synthesizedfrom 2,2'-diformylbiaryls by theMcMurryreaction.
,
I
gknediamine. H 1:.1'. rs promoredby (tmeda)TiCl2.l !L-r.r:r()lnlMlCH(ZnX)r.
(
CHO
o
cHo
- Z) n l c u TiCl3(DIVE
42o/o(ElZ
r.::'.l
62:38)
to .rrn-hydrobenzoin with a )r. :. rrfrssrvsd when the reaction is {. ::.,r]r!'rhvl1,2-diaminocyclohexane.
.r\)qt. - , r ) r .
.\r99).
o LJ
1 o
r")^)
ry 45%
Lrn
:
o
-l;'\
I
9 <
(
o
:" --+'O.
ta-
o
lCies, A.-E.. Pfeffer.M. JOC 64.3650 (1999).
Titanium(IV) chloride. 13, 3M-309; 14,309-jll; 15, 317-320; 16, 332-j37 : 17,344 *347; 18, 359-36 I ; 19, 341-344; 20, 377-37 9 Functional group exchanges. TiCL serves as a catalyst in the conversion of THP ethers,r silyl ethers,2 and propargyl esters3to the corresponding esters and ethers. A direct synthesisof cr-(benzotriazol-l-yl)alkylethersinvolves treatmentof dialkyl ethers with l-chlorobenzotriazoleand TiClo.a AMol and Mannich reactions. Formation of cyclopentenonesis readily achieved by a twofold Mukaiyama aldol reactionbetween 1,3-bis(trimethylsiloxy)-1,3-dienes and 1,2-diketones.5
Titanium(IV) chloride
Me3SiO
o ,\,"oor,
o
oEt
tl
Mo'Me3
tl
cH2ct2 -78.
\/l
;J-\ 63Yo
R=H,Et
Activated imines and aminal derivatives react with malonic esters to give precursors of B-amino acids,6while conjugated aldimines undergo 1,4- and 1,2-additions, both inducedby TiClo.i
.,X.,r".
.
*go*
-t'''"'o'-'
Schmidt reaction.tl l-actam in the presenceof TiCla. Interestr more rapid formation of the [R\H
6o"
*-=[ T-"Xf^
(l=o . *
7lYo
Baylis-Hillman reaction. When TiCla is used to promote the condensation, a chlorine atom is introducedinto the adducts.8rl
? \
*
o nArn
o o H i l l
-^l^rn cH2ct2 25
\", 61Yo
Biaryls. On treatment with TiCla in nitromethane,2-naphthol and derivatives afford binaphthol derivatives.r2 The oxidative coupling proceeds particularly well with substratescontaining electron-donatinggroups. N,N-Dialkylarylamines also afford substituted biaryls, via nuclear titanation,r3 but N-dealkylation is observedwith hindered amines and those containing a p-substituent. cyclimtions. Tetrahydrofurans and pyrrolidines bearing a 2-silylmethyl group are formed when alkenylsilanes and 5-substituted l-pentenylsilanes are exposed to Ticlo at 14'15 room temperature. A tetracyclic framework containing six contiguous srereocenters emerges from treatment of an aryltrienone with Ticl4.'6 The Nazarov cyclization triggers additional C-C bond formation.
rChandrasekhar,S., Ramachandar.T . 2lranpoor, N., Zeynizadeh, B. SC t. 3Bartels,A., Mahrwald, R., Qurnr-S 4Katritzky,A.R., Voronkov,M.\.. h 5l-anger,P.,Kohler, Y. OL2, 1591rJ 6Milenkovic, A., Fache, F., Faure. R. . iShimizu, M., Morita, A., Kaga.T II nWei,H.-X., Kim, S.H., Caputo.T D. 'Kataoka, T., Kinoshita, H., Krnorhru r0shi,M., Jiang,J.-K., Feng,Y-S. oL rrLi, G., Gao, J., Wei, H.-X., Enrighr-I r2Doussot,J., Guy, A., Fenoud. C. Il l3Periasamy, M., Jayakumar,K.\.. Bt 'oMiura, K., Hondo., T., Takahashr.T rsMiura,K., Hondo.,T., Nakagasa.T 'oBender,J.A., Arii A.M., West.F.G. . rTDesai,P.,Schildknegt,K., Agrros. K-r
Titanium(IV) Reductive
chloride-amincs. cyanation.t
presence of TiCl,5Et.N.
l
.Arot
c-Subsuo
resulting imines with K2CO, in rcl
fi tanium(IV) chloride-amines tJ
{"oo=, 78
z\
\ / l
n
I
Il
\.\--l 63Yo
\
\)
/.R
ll
,,1r^-.-
ll
cH2ctz-78
A R=H,Et
I r::h malonic estersto give precursors rn!:.:!() 1.4- and 1,2-additions,both in-
schmidt reaction.tl Lactams are formed when cycloalkanonesreact with RCH2Nj in the presenceof ricla. Interestingly, TfoH induces a Mannich reaction, indicatine the more rapid formation of the [RNH:CH2] + species.
Tict4
(-(o" -
- SnBur
Vr*v ,nAA,'s. TOTo
I \--l
| ( Fo \__J
+ p6,^11.
-
88ro
|
l
- v I
N-en
rfoH
(
n
FO
\-ruHpn L.,.t rrr promote the condensation,a 79Yo
o o H i l l
: - -Yrn ' \",
61To
h::r:. :-naphthol and derivativesafford i.c: rrr)ceeds particularly well with I .i.'nls. via nucleartitanation,l3but fl .i ih,rr8 containinga p-substituent. hr:. fl.aring a 2-silylmethyl group are x:.::rr lsilanesare exposedto TiCla at Dr::-\)u\ stereocentersemerges from isz*:,,r cyclization triggers additional
rChandrasekhar, S., Ramachandar,T., Reddy, M.V., Takhi, M. JOC 65, 4729 (Z0OO\. 2lranpoor, N., Zeynizadeh, B. 5C 29, 2123 (1999). rBartels,A., Mahrwald, R., Quinr, S. Zl, 40, 5989 (1999). lKatritzky, A.R., Voronkov, M.V., Pastor,A., Tatham, D. H Sl, lg77 (lggg\. 5langer, P., Kohler, V. OL2, t5g7 (2000',. 6Milentovic, A., Fache, F., Faure,R., Lemaire,M. SC 29,1535 (1999). TShimizu, M., Morita, A., Kaga, T. TL 40,8401 (1ggg). EWei,H.-X., Kim, S.H., Caputo,T.D., purkiss,D.W., Li, G. 256, 2397(2000). 'Kataoka, T., Kinoshita, H., Kinoshita, S., lwamura, T., Watanabe,S. ACIEE 39.235g (2000). r0shi,M., Jiang, J.-K., Feng,Y.-S. OL2,Z3gj (2OOO). "Li, G., Gao, J., Wei, H.-X., Enright, M. OL2,617 (ZO0O). r2Doussot,J., Guy, A., Ferroud,C. TL 41,2545 (2000:). lrPeriasamy, M., Jayakumar, K.N., Bharathi, p. JOC 65,354g (2000). raMiura, K., Hondo., T., Takahashi, T., Hosorni, A. TL 41,2l2g (ZOOO). rsMiura, K., Hondo., T., Nakagawa, T., Takahashi,T., Hosomi, A. OL 2, 385 (2000). r6Bender,J.A., Arif, A.M., West,F.G. JACS l2l,7M3 (Iggg). ITDesai,P., Schildlnegt, K., Agrios, K.A., Mossman,C., Milligan, G.L., Aube, J. JACS 122,7226 (2UJ0).
Titanium(IV) chloride-amines.20, 380 Reductivecyanation.t Aromatic ketonescondensewith aminoacetonitrile in the presence of TiClo-Et.N.ct-Substituted arylacetonitriles areobtainedupontreatmentof the resultingimineswith K2CO.in refluxingDMF.
Titanium(W) chloride-lithium-trimethylsilyl
chloride-nitrogen
o'^)-*
otY* * H2N cN J*= Et3N / DMF
{Ti oxr
NV,.CN
o
cN
Reductive couplings.z The low-valent titanium species formed by interaction of Ticlo with EhN is capable of transforming ArCHo and AICH:NAr' to hydrobenzoins and 1,2-diarylethylenediamines,respectively. Aldol and Dieclcmann reactians.3 These condensation reactions are readily achieved using Ticl-BujN and a catalytic amount of MejSicl. The effectiveness of the reagent system can be gauged by the reaction conditions (e.g., cyclization of dimethyl adipate in dichloromethaneat -78o affords methyl 2-oxocyclpentanecarboxylate in95vo yield). Michael reaction.a The conjugate addition of N-acyloxazolidin-2-ones to nitroalkenes is best promoted by a combination of Ticla and !pr2NEt. Excellent stereoselectivity is observed from reactions of substrates in which the heterocycle is
X = COOMe.CC
rAkashi,M., Nishida, M.. Mon. \l
Titanium0V) chloride+arne Ketones,t Reductive aTiCl,-Sm in THF.
substitutedat C-4 with an isopropyl group (stereocontroller)and gez-dimethylated at c-5.
*Y* o
syn-2,3-Disubstituted 4-pentenamides.s The reaction of allylamines with acid chlorides proceedsvia N-acylation and enolate-Claisen rearrangement.
r^l l ( ^ . ' \ oJ (/r
^ y
O rrhfl"ricr.
oBn
#
c"rcl,
C
l U
f^l\ oJ
)_.2
I Zhou, L., Zhang, Y. ? 56. 295,1r ll
Titanium(IV) chloriderecel Prenyl ether cleavagc. proximalcoordinativesiteto d
oBn
(syn : anti 9:1) rSelva,M., Bomben,A., Tundo, P. SC 29, 1561 (1999). 2Periasamy, M., Srinivas,G., Karunakar,G.V., Bharathi,p.TL40,757i. (lggg). 3Yoshida,Y, Matsumoto, N., Hamasaki, R., Tanabe,y. TL 40, 4227 (lggg). aBrenner,M., Seebach,D. HCA 82,2365 (lggg). 5Yoon, T.P., Dong, V.M., MacMillan, D.WC. "IACS l2l, gj26 (lggg).
Titanium(IV) chloride-lithium-trimethylsilyl chloride-nitrogen.20, 38O-3gl Tetrahydroindoles.tThe [Ti-N] complexinducesthe formationof 2-substituted 4,5,6,7-tetahyfuoindoles from2-(2-alkynyl)cyclohexanones. To obtainreasonable yields of theproducts,thealkynylmoietymustcarryan electron-withdrawing group.
A c \o'\l
Reductivecouplings.: Tr in effecting reductive couphng reagentundergo aldol reactronr
rTsuritani,T., Shinokubo.H.. O{fu 2Tsuritani, T., Ito, S.,Shinol-ubo. H
batn4ag
Titanium(IV) chloridFtetrabutylammoniumiodide
:
v \
,
<.co, a
N
D
\
M
Ar F
c
R
_ I
N
H
u::.':cirr'r formed by interaction of ) : : . : \fH:NAr' to hydrobenzoins (t 13-
n F:--
:. n r!'actionsare readily achieved Ilc c-tTectiveness of the reagent ...luauon of dimethyl adipatein . ..dlr) latein 95Toyield). : \-acyloxazolidin_2_onesro l:CI. and i-prrNEt. Excellent ,:-. rn *hich the heterocycleis
r , . ::
rAkashi,
35-82o/o (X = Me 3%)
M., Nishida, M., Mori, M. CL 465 (1gg9\.
Titanium(IV) chloride-samarium.20, 3g1 Ketones.t Reductive acylation of ketones by nitriles is accomplished using TiClo-Smin THF.
rnd (enr-dimethylated at C_5. -
Ph* Ph + Ph-cN ll
K
-----\.-- I
- .. '
X = COOMe,CONH2,COMe
NO,
|
o
o
TiCl4- Sm
tn---t\^. THF ^
-\-R
l Ph
ll F
n
81%
rE:. r trf allylamines with acid n::.r::Jngement.
)'+/ o c l
- tt I
rZhou,L., Zhang,y.T56,2953 eO}U. Titanium(IV) chloride-tetrabutylammonium iodide. Prenyl ether cleavage.t The cleavage shows pret-erenceto ethers possessinga proximal coordinative site to allow chelation control.
OBn
s/n ; a n t i 9 : 1 )
A -r-r
,$ :--I
I 1999). laoo,
f\cHo (";V-Jt
,f>
A
\
"^A
Js --Ji._
r . l
le-nitrogen. 20, 380-391 ir. ::r. lbrmation of 2_substituted h,::. To obtain reasonableyields x . .rrlhdrawinggroup.
Reductive couprings'2 Ticlo-BuoNl appears to have similar reactivity as Ticl4-EtjN in effecting reductive coupling of ArCHo. Enolates generatedfrom ct-haloketonesby this reagentundergo aldor reaction with aldehydes, providing predominantrythe syn_rsomer. rTsuritani, T., Shinokubo, H., Oshima,K.TL40,gl2l (19991. 2Tsurirani, T., Ito, S.,Shinokubo,H., Oshima,X..lOi iS', SOIOtZOOOt.
fitanium(IV) iodide
Titanium(IV) chloridezinc. 20, 381 Reductive couplings. Formation of 4,5-diarylimidazolidines from imines is readily effected.l The reagent system for coupling ArcHO to afford syn-hydrobenzoinscontains TMEDA.23 (The complex is prepared from TiCla, Zn, TMEDA, and PbCl2. Note that an alternative complex for the same purpose is derived from TiCla, Mn, MerSiCl, and a Schiff base,but diastereoselectivitydependson the Schiff base.4)
rShimizu,M., Shibuya,K., Ha!aliaslrHayakawa, R., Sahara,T., Shimizu. V 'Mukaiyama, T., Yoshimura, N.. lganC lHayakawa,R., Shimizu, M. Ct 7lJ ,: iHayakawa, R., Shimizu, M. OL 2. rfr-
Titanium
OH
TiClai Schiffbase II
Ph
,nlYtn
,n\'n.
Mn - Me3SiCl
H
OH
N,leCN 25'
OH
13. j
tetraisopropoxide.
18,363-364;19, 346-34'l'.20. -1SI pAmino acid derivatives. i condensation.l
OH (99 : 1) 75%
rLi, J.,Wang,S.,Hu, J.,Chen,W. TL 40,196l(1999). 'Li, T., Cui,W., Liu,J.,Zhao,J.,Wang,Z. CC 139(2000). 3oshiki,T., Kiriyama,T., Tsuchida,K., Takai,K. CL334 (2O0O). aBandini,M.,Cozzi, P.G.,Morganti,S.,Umani-Ronchi, A. fZ 40, 1997(1999).
Titanium(Il) halide-copper. Reductive couplings,t Aliphatic and aromatic aldehydes undergo reductive dimerization on exposureto TiBr2-Cu. pHydroxy carbonyl compounds.2 Aldol and Reformatsky reactions involving debrominative enolization of cr-bromoketones and cr-bromo thioesters with TiCl2-Cu-r-BuCN are readily achieved.Acceptors are limited to aliphatic aldehydes becausepinacol formation by aromatic aldehydespredominatesunder the conditions. rMukaiyama,T., Kagayama, A., Igarashi,K. Cf 336(2000). 2Mukaiyama, T., Kagayama, A., Igarashi,K., Shiina,I. CL ll57 (1999).
Titanium(IV) iodide. Reductions. Chemoselectivereduction of sulfoxides to sulfidesr and a-diketones to a-ketols2employs the title reagentin MeCN at 0'. Aldehydes are dimerized to give l,2-diols (dl- >> meso-)on exposureto TiIa, with or without addingCu.r'a Aldol reactions,5 Methoxyallene oxide forms a titanium enolate on treatment with TiIa. Addition of aldehydesor acetalscompletes the aldol reactions.
o /\
Tict4 +
OMe
RcHo
o o H ,\^. OVe
,//Y'oMe
+
\
NHCOOMe
AUylic displacements. In R pronucleophileson treatment\r'lth I Aldol reactians. A high &E
reaction mediatedby titaniumrl\-r chiral ct-hydroxy acids, :rsymmetrx In conjunctionwith PhrP.rr-P( roalkyl ketones with aldehydes...1 the ketone by (i-PrO)oTi in the \lct
Ph
Fo*
(
t
)
H
rKise, N., Ueda,N. JOC 64,751I r 199 :Poli, G.. Giambastiani.G.. Mordrnr..|" 'Mahrwald, R. OL2,4011 (2000r {Shen,Y., Zhang,Y., Zhou, Y JCS,P i '
fi r-nium tetrrisopropondc
tl::r-r./olldines from iminesis readily ) : .::: 'rti rlrr-hydrobenzoins contains Z: l \!EDA. and PbCll. Note rhat an r.J ::,,m TiCl.,.Mn, Me.SiCl, and a S . : . . : :h l s e . ' t
OH l ' P h - -P: ' ' h
= ( l
:
)-
Shimizu,M., Shibuya,K., Hayakawa,R. SZ 1437 (2000). Hayakawa, R., Sahara,T., Shimizu, M. TL 41,7939 (2C0,O). \lukaiyama, T., Yoshimura, N., Igarashi, K. CZ 838 (2000). 'Hayakawa,R., Shimizu,M. CL724 (2000). ' Hayakawa, R., Shimizu, M. OL 2, 4079 (2000).
Titaniumtetraisopropoxide. 13,3 I 1-3I 3; 14,311-312;15,322;16,339;17,347-348; lE, 363-364;19, 346-347; 20, 381-382 pAmino acid derivatives. (l-PrO)aTiplays a critical role in the Mannich-type condensation.l
oH 39
1)
r
*
\orrae
)
i-Pr2NLi/ THF
\"oo""
-70"
COOMe
NHCOOMe
{r
di:
DJ
431
.-
NHCOOMe
lqqT{1999).
.i)dc-hydesundergo reductive
.{r'r(\rmatskyreactionsinvolving
s ::..1 cr-bromo thioesters with r( ,::i lrmited to aliphatic aldehydes ' P : , : :nlnatesunderthe conditions. {- :e99).
t\-.:r'. t() sulfides'and a-diketonesto ler-. ir. are dimerized to give l,2-diols H::: (-u.'{
Allylic displacements. In Pd(0)-catalyzed reaction, titanates generated from the pronucleophileson treatment with (i-PrO)oTi serve adequately.2 Aldol reactions. A high degree of syn-diastereoselectivityis exhibited in the aldol reaction mediated by titanium(IV) alkoxides in the presence of ct-hydroxy acids. With chiral a-hydroxy acids, asymmetric induction is observed.r In conjunction with PhrP, (i-PrO)aTi promotes condensationof bromomethyl perfluoroalkyl ketones with aldehydes.Allylic alcohols are obtained owing to the reducibility of the ketone by (l-PrO)aTi in the Meerwein-Ponndorf fashion.a
Ph
Fo*
(
Br
Ph - Ph3P (i-PrO)aTi --;"-
FaC
r :::.!ntumenolateon treatmentwith l-.: . r.'actions.
OH
-J*
3Me
syn : anti 3 0 : 7 0 9 2 : 8
no additive + (i-PrO)4Ti
\/-oli'
FsC
90To
'Kise, N., Ueda,N. JOC 64,7511 (1999). zPoli, G., Giambastiani, G., Mordini, A. JOC 64,2962 (1999). rMahrwald, R. OL2,4011 (2000). aShen,Y., Zhang,Y., Zhou, Y. JCS(P1) [r59 0999).
Titanocenebis(triethyl phosphite)
Titanocenebis(triethyl phosphite).20, 383 Desulfurativealkylationand acylation. Titanocene bis(triethylphosphite)promotes desulfurative alkylationof allylic sulfides(dithioacetals) with r-alkylhalides.r
tn-Yt) sJ
?tn Ph#spn
.
The cycloelimination is also ap apparently involving the releasr ol
Z;),.
Cp2TiIP(OEt)3]2
?' -ZYPn
Phs-<._-./
* :l-"-'--tn l,
cp2TilP(OEt)312
'Takeda,T., Nozaki, N., Saeki.\.. Fut rTakeda, T., Taguchi, H., Fujiwara- T I rTakeda, T., Takagi, Y., Saeki. N.. Fupr rRahim, M.A., Fujiwara, T., TakedaT 5Rahim, M.A., Fujiwara, T.. Tateda T oFujiwara, T., Kato, Y, Takeda.T. t/ 5l
Ph 73Yo
Dithioacetals RCH(SPh)2 and vinylogues [i.e., RCH(SPh)CH:CHSPh] become carbanion equivalents [RCH2]- when they are treated with Cp2Ti[P(OEt)1]2and Mg. Thus, a subsequent reaction with nitriles furnishes ketones.2Conjugated dienes and
Titanocene
dicarbonyl.
Intramolecular
alkenylcyclopropanesare also obtained.3
19, -1{l-:
enc
rcoetiarl
ization in the presence of Cp,TrrCl
Sph
cp2rilP(oEt)3l2
--Y-^rn
l\.49, mol. sieves
o
MeOOC r:
X
ttcMpn
60Yo
" -\_
cp2TilP(oEt)3]2MeoSi.-'-1/,,,1rr1
t - *"l-) * SPh
Measi.-,,,\Z\spn
| |
|
\-,/ |
\,/
I cp?TilP(oEthl2
L_
w
u
53%
*
n
R
Meqsi .-\-.ry
-
v
R = H.... 80-85%
Cyclizations. Cyclization on elimination of a dithioacetal unit simultaneous with a thioestercarbonyl by Cp2Ti[P(OEt)1]2, leads to 2,3-dihydrothiophenes.a The analogous reaction of or-alkanoyloxyalkanal bis(phenylthioacetals)gives or-hydroxy ketones due to hydrolysis of the cyclic enol ether products.5
/-R
rSturla,S.J.,Kablaoui, N.M.,Buchu-r
Titanocene dichloridediisobotrl Reductive cyclization.t On m
certain alkadienal acetals undergo c formed in situ.
Titanocenedichloride-diisobutylaluminum hydride
a.'r'n.: bis(triethyl phosphite) promotes 6 . \ rrh t-alkyl halides.r
F
:
The cycloelimination is also applicable to dithioacetals with a remote C:CH2 group,o (a retro-Tebbereaction)' apparently involving the releaseof [Cp2Ti{Hz]
cp,rilP(oEt)312 >^ Y'\ // ,Sph N-Bn ll
-
rHF 25"-^
PhS-(,./
.N-An
\--l
72Yo
Ph 73o/o
c RCH(SPh)CH:CHSPhI become liiJ(l $ith Cp2Ti[P(OEt)1],and Mg. hc' kctones.2Conjugated dienes and
-.-
rTakeda, T., Nozaki,N., Saeki,N., Fujiwara,T' TL 40' 5353(1999). 2Takeda, T., Taguchi,H., Fujiwara,T. TL 41,65 (2O0O). 3Takeda, T., Takagi,Y., Saeki,N., Fujiwara,T. TL 41,837'7(2O0O). 4Rahim,M.A., Fujiwara,T., Takeda,T. 5L1029(1999). sRahim,M.A., Fujiwara,T., Takeda,T. T 56,'163(2000). 6Fujiwara,T., Kato,Y.,Takeda,T. H 52,147(2000).
Titanocene dicarbonyl. 19, 347-348; 20, 384 Intramolecular ene reaction.t Enynes and dienynes undergo this cycloisomerization in the presenceof Cp2Ti(CO),
'*T)<-*
pn
I
c
CpzTi(CO)z
x l
PhNIeA
.
Y' hcnn'
'.lelSi.r,,1,,1r1
R
(,
/-R G
53Yo
;
','te3Si\-21-,lJ
R
MeOOCf-?
t-\_/--'
_l cp2ri(co)2
;;;*-
f-/
GvJ---zc"cHR'
A R
R = H.... 80-85%
:::I()acetalunit simultaneouswith a The analogous ;:hr drothiophenes.o .. gives to-hydroxyketonesdue to
rsturla.S.J.,Kablaoui, S.L. "/ACSl2l' 19'76(1999). N.M.,Buchwald,
hydride. Titanocene dichloridediisobutylaluminum Reductive cyclizatian.t On treatment with the combination of Cp2TiCl2 and l-BurAlH, certain alkadienal acetals undergo cyclization as a result of attack by crotyltitanium species formed in situ.
Titanocenedichlorideaamarium
i
\
\
o-
i-Bu2AlH;
ro
o
n=1 n=2 n=3
Cp2fi0l2
\
Me3SiOTf
l
)tcH,)"
79To 64%o 71Yo
Titanocene dichloridezinc. 2O B icy clo t etr ahy dr ofu ra ns. sesaminis by a formal 1.3
?
"f
OH
Ar\o/ Cp2Tiol2
o'^-'--oH
rRana,K.K.,Guin,C.,Roy.S.C.Il I
i-Bu2AlH; Me35iOTf
Titanocene methylidenes. Deoxygenationt. The Tett selenoxides. rTheryN., Szymoniak, J.,Moise,C. EJOC1483(2000).
rNicolaou. K.C.,Koumbis. A.E..Snr
fi tanocene dichloride-manganese. 20, 384 Glycals.t This combination of reagents, which generatesCp2TiCl, is effective for eliminations such as formation of glycals from per-O-acetylglycosyl bromides. Reductive couplings.2 Aldehydes are converted to trimethylsilyl ethers of l,2-diols with CprTiClr-Mn and MejSiCl.
p -Toluenesulfonylacetylene. Thiol protectian.t As a Il thiols. Regenerationof the rhrols
rArjona,O., Iradier,F.,Medel.R . Ph
Reductive cyclizatian.s Epoxides bearing a 5-pentenyl chain undergo cyclization.
p-Toluenesulfonyl chloride. a-Chlorokctones,t TsCl ca
o a-.-/-\ | |
t Z |
\-^./
a ketone with LDA and then Tr polymer-bound TsCl is also uscfu Alkenyl tolyl sulfuncs.: A zirconocenechlorides (derired fn
o ) / Mn-co2ricr2 /'\-<, ---:"-| | ) collidineHcl \-'V
77o/o
O-Tosylation. The use of 1 faster and prevents formation of I catalytic amount (EtN as baser d
rHanien,T., Krintel, S.L., Daasbjerg, K., Skrydstrup,T.TL40,6087 (1999). 2Dunlap,M.S., Nicholas,K.M. SC 29, 1097(1999). iGansauer,A., Pierobon,M. SL 1357 (2000).
Titanocene Diaryl
IBrummond, K.M., Gesenberg. KD i 2Duan,D.-H.,Huang,X. St 317I lW 3Yoshida, Y., Shimonishi,K., Satatur aYoshida, Y, Sakakura, Y.,Aso.\.. 0
dichloride-samarium. disulfides.'
Arenesulfonyl
derivarives
(e.g., chlorides)
undergo reductive
coupling.
p-Toluenesulfonyl cyanide. pChloro sulfones.t TsC\
rHuang,Y, Guo, H., Zhang,Y.,Wang,Y. JCR(S)214 (1999).
B-chloro sulfones.
p-Toluenesulfonyl cyanide
n=1 n=2 n=3
79% 64Yo 7'lYo
o"-t--oH
Titanocene dichloride-zinc. 20, 384-385 Bicyclotetrahydrofurans.r A synthetic method for elaborating neolignans such as sesamin is by a formal l,3-dipolar cycloaddition between an epoxide and a styrenic double bond.
rRana,K.K.,Guin,C.,Roy,S.C.TL41,9337(2000).
Titanocene methylidenes. Deoxygenationt. The Tebbe reagent deoxygenates amine oxides, sulfoxides, and selenoxides. lNicolaou,K.C.,Koumbis, A.E.,Snyder, S.A.,Simonsen, K.B.ACIEE39,2529(2000).
:h -r'n.rates Cp2TiCl, is effective for ?' r-,':\ lslvcosylbromides. c! : :nmethylsilyl ethersof 1,2-diols
p -Toluenesulfonylacetylene. Thiol protection.t As a Michael reaction donor, this reagent forms adducts with thiols. Regenerationof the thiols is by treatment with pynolidine in MeCN. rArjona,O.,Iradier,F.,Medel,R.,Plumet,L JOC 64,6090(1999).
[!*:.:.n\ I chain undergocyclization.
^1,<
ro
-)'-/ 77%
{t '. r- r1999)
. . chlorides) undergo reductive
p-Toluenesulfonyl chloride. u-Chloroketones.t TsCl can serve as a chlorinating agent for ketones.Treatment of a ketone with LDA and then TsCl in THF at 0' sives rise to the cr-chloroketone. A polymer-bound TsCl is also useful. Alkenyl tolyl sulfones.2 A convenient synthesis involves reaction of alkenylzirconocenechlorides (derived from I -alkynes) with TsCl. O-Tosylation. The use of TMEDA as base makes tosylation of alcohols with TsCl faster and prevents formation of alkyl chlorides.r Alternatively, TMEDA or Me.NHCl a in catalytic amount (EhN as base) also shows an advantage. IBrummond, K.M.,Gesenberg, K.D. TL 40,2231 (1999). 2Duan,D.-H.,Huang,X. SL31'7(1999). rYoshida, Y.,Shimonishi, K., Sakakura, Y.,Okada,S.,Aso,N., Tanabe, Y. S 1633(1999). aYoshida, Y., Sakakura, Y, Aso, N., Okada,S.,Tanabe,Y T 55,2183(1999).
p-Toluenesulfonyl cyanide. pChloro sulfones.t TsCN adds to alkenes in the presence of TiCla to afford B-chloro sulfones.
Tliallylborane rMorgan, P.E.,McCague, R., Whiting, A. TL 40,4857 (19991.
(r\o phosphonates. B-(p-Toluenesulfonylhydrazono) Pyrazoles.t A synthesisof polysubstituted pyrazolesis completedin one stepby theEmmons-Wadsworth reactionof thesereasentswith aldehvdes. O
*,NHTS
Ero-p-YjJ Eto I
** A o ; - Y ,H
KH
HI,J-N
rAlrnirante,N., Benicchio,A., Ceni, A., Fedrizzi,G.,Manzzi, G., Santagostino,M.5L299 (1999).
2,8,9-Tlialkyl-1-phospha-2,5,8,9-tetraazabicyclo[3.3.3]undecanes. 19,3'10 trans-Stilbeneepoxdes.t Stereoselective deoxygenative dimerizationof aromatic aldehydes areobservedwith thetrimethylbase(1, R : Me) at roomtemperature. Rt
NiP- N'R
Rr
lz
H
iBubnov,Yu.N.,Pershin,D.G.,lgnacat rWatanabe, K., Kuroda,S.,Yokoi.A , tr rBubnov,Yu.N.,Pastukhov, F.V..\'anryr
Ttiarylbismuthine
dichlorides. Arylatian,t Enolates denrcd related systems are arylated ar deconjugatedproducts.
rAmauld,T., Barton,D.H.R..Normarr-l
1,5,7-Tiiazabicyclo[4.4.0]dec-5-ct Epoxidation.t This biclclrc deficient alkenes with l-BuOOH ar r
(1) Condensation reactians, The triisopropyl base is an efficient promoter for the nitroaldol (Henry) reaction,2 and condensation between alkanonitriles and carbonyl compounds.3 Alcohol-ester interchange. The trimethyl base can be used as a catalyst for acylation of alcohols (esters, and particularly enol esters, as acyl donors) as well as deacylation of esters.4(Desilylation of TBS ethers is also reported.s) rLiu, X., Verkade,J.G.JOC 65,4560(2000). 2Kisanga, P.B.,Verkade,J.G.JOC &,4298 (1999). 3Kisanga, P.,Mcleod, D., D'Sa,B., Verkade, J.G.JOC&,3090 (1999). allankumaran, P.,Verkade,l.G. JOC 64,3086(1999). sYu,2Z.,Verkade,J.G.JOC 65,2065(2000). TFiallylboran e. 20, 386-387 Reductive allylation.t N-Allylanilines are formed when nitroarenesare heated with triallylborane in toluene. The diallylated amines are minor products. Homoallylamines. A synthesis of homoallylamines from nitriles consists of consecutive treatment with diisobutylaluminum hydride and triallylamine.2 Lactams undergodeoxygenativediallylation.r
rGenski,T., Macdonald,G.. Wei. X.. l"-c
Tributoxysilyl hydrosulfide. Defunctinnalization.t Merho (t-BuO).SiSH.
tibutorysilyl
+"
hydrosulfide
437
, , no '
l/Y,'
H
v ,.r" is completedin one step by rr :iJchydes. HN-N
-l
/ \ \ n-\r/
I
r:
\rntagostino, M. St 299(1999).
]-l lundecanes.19r 370 I r.:rtr\ e dimerization of aromatic = \l: .rt room temperature.
90% rBubnov, Yu.N.,Pershin, D.G.,Ignatenko, A.V.,Gurskii,M.E.MC 108(2000). 2Watanabe, K., Kuroda,S.,Yokoi,A., Ito, K., Itsuno,S.JOMC581,103(1999). 3Bubnov, Yu.N.,Pastukhov, F.V.,Yampolsky,I.V, Ignatenko,A.V. EJOC 1503(2000).
Tiiarylbismuthine dichlorides. Arylation.t Enolates derived from a,p-unsaturated carbonyl compounds and related systems are arylated at room temperature with AriBiCl2 to provide the deconjugatedproducts. rAmauld,T., Barton,D.H.R.,Normant,J.-F.,Doris,E. JOCg, 6915(1999).
1,5,7-Triazabicyclo[4.4.0]dec-5-ene. Epoxidation.t This bicyclic guanidine (1) promotes epoxidation of electrondeficient alkenes with t-BuOOH at room temDerature.
r^rut\
(*.J.-",J
c .. .rn efficient promoter for the $:;:. elkanonitriles and carbonyl
(1)
tc -.rn fre used as a catalyst for ..:::.. rs acyl donors) as well as 1.. ::l,rned.5)
[p
. q99t.
tj ..::en nitroarenesare heatedwith tn ::rrrlucts. lxt::-.i. lrom nitriles consists of d..:.:; .ind triallylamine.2 Lactams
I Genski,T., Macdonald,G., Wei, X., Lewis, N., Taylor, R.J.K. SI, 795 ( 1999).
TFibutoxysilylhydrosulfide. Defunctionalization.t Methoxymethylethersare hydrogenolyzed on heatingwith (/-BuO)3SiSH.
^/-o'
z
\/
l
>{
^
r
+
\
o,_O-S|-SH
Y"
A
+ 87Yo
tibutyl[2-(trimethylsilyl)ethoxymethoxymethyl] stannane rDang, H.-S., Franchi,P.,Roberts,B.P. CC 498 (2000).
Bu3Sn Ttibutylphosphine. 20, 387-388 Transacylation.t 2,2,2-Tihaloethyl esters are converted to other esters via reductive fragmentation, formation of phosphonium carboxylates, and alcoholysis of the activated esters.For the analogousamidation, hexamethylphosphoramideis used. Reduction of disulfides. Optimum conditions are established for the reduction of disulfides to thiols2 using BurP-H2O in THF. The transformation of alcohols to S-xanthatesin one stepis accomplishedwith a mixture of BujP and (I-PTOCSS)2.3 Dimerization,a Activated alkenes are dimerized in the presence of BulP under pressure.
rFernandez-Megia, E.,Ley,S.!'.SL{55
Tiibutyltin hydride. 13, 3 I 6--119. 351-361; 18, 368-371; 19, 351--15 Reduction, Besides the redrr in hydroxylic solvents (e.g.. \le
dichloromethane2 in the prescnc high stereoselectivity.
CN /
cN
f
6u3P +
\ 50'
\
tl phz\,'-t---O+i ! R
CN
1,3-Dipoles.) 2-Alkynoic esters are presented as zwitterionic conjugated esters in which nucleophilic and electrophilic sites are located at the ct- and 1-carbon atoms, respectively, when they are treated with Bu.P and dipolarophiles. For example, trapping with aldiminesleadsto 2,5-disubstituted2,5-dihydropynole-3-carboxylic esters.
Aromatic
aldehydes bearing ut
M e , A l i s a d d e d . rT h i s s e l e c t i v i r r r s ; Reductive
amination.a
A nr
amines is by reaction with Bu,Sl secondary amines) in DMF at room
*\"oo.,
j:i * rsN...r.R' \,/ PhH''*r""(I)"'* 1ooa,
Nitriles,o A modified Mitsunobu reaction that transforms alcohols to nitriles employs BujP and N,N,N',N'-tetramethylazodicarboxamide as activator and acetone cyanohydrinas pronucleophile. rHans,J.J.,Driver,R.W.,Burke,S.D.JOC 65,2114(2OOO). 2Ayers, J.T.,Anderson, S.R.SC29,351(1999). rGueyrard, D.,Tatibouet, A., Gareau, Y, Rollin,P.OL 1,521(l9gg). alenner, G. TL4l,309l (2000). sxu, 2., Lu, x. TL 40,549(1999). 6Tsunoda, T.,Uemoto,K., Nagino,C., Kawamura, M., Kaku,H., Ito, S. TL 40,7355(19991.
Tributyl[2-(trimethylsilyl)ethoxymethoxymethyl]stannane. Hydroxymethyl anion equivalent.t After undergoing Sn-Li exchange (with BuLi), reagent I becomes reactive toward various electrophiles. The (trimethylsilyl)ethoxymethyl group of the products can be removed any time afterward.
Hydrostannylation,s
Resrosr
(to yield
o-stan
alkynes
mainly
complex. rKamimura, K., Wada, M. It 2(). 9O59r 2Ooi,T., Uraguchi,D., Morikawa. J.. Ilr rAsao, N., Shimada,T., Yamamoto. )' I| aSuwa,T., Sugiyama,E., Shibata.L. Brt 5Kazmaier,U., Schauss,D., PohlmannI
Tributyltin hydride-2,2'-ambis ir Defunctionalizttians. Hererq affecting a geminal C-F bond. A
corresponding thionocarbonatescall trimethoxysilane to recycle the spcn A method for synthesisof chrn hexyl halides involves derivarrz:rx (S)-2-bromophenylsulfinate, and rh
minum diphenoxidewith inadiauon
Tribogldn hvdrido-2J'-rzobis{isobotlmdtrih)
Bu3Sn"'\O"\g"\-SiMe3 (1) .::rc'd to other esters via . .rtcr. and alcoholysisof the h . : .rhoramideis used. r E - . .,.lr.hed for the reduction of r ' : :-.t()rmation of alcohols to r l 3 . P.rndI!PTOCSS)r.3 ':rr' preSeflc€of BujP under J
rFernandez-Megia, E.,Ley,S.V.S1,455(2000).
E-.
Tlibutyltin hydride. 13, 3 I 6-3 19; 14,312-318; 15, 325-333; 16, 343-350; 17, 35 l*361 ; 18, 368-371; 19, 352-353; 20, 389-391 Reduction, Besides the reduction of carbonyl compounds with Bu.SnH to alcohols in hydroxylic solvents (e.g., MeOH),r that of hydroxy ketones and diketones in dichloromethane2 in the presence of BF.,'OEt, is particularly interesting due to high stereoselectivity.
I
r) ll ph-\.,,\,.OH I R | . ...::.'rionic conjugatedestersin rl .: itc- 0- and ^y-carbonatoms, o .1- :'hrlcs.For example,trapping r: - i-earboxylic esters. Ts N ^
,/ >
-
.
\"'K
\
/
-' cooEt I ::.::r.lorms alcohols to nitriles t::r ..ic' rS activator and acetone
|.:.. l: .
S TL40,7355(1999).
nnane. r.:::: Sn-Li exchange(with BuLi), t::,philes. The (trimethylsilyl)r :::ric afterward.
OH - BF".OEI, BurSnH I - o^.1-r.r.^r.r-OH cH2ct2 I R
Aromatic aldehydes bearing an o-alkenyl substituent is reduced selectively when MejAl is added.3This selectivityis a manifestof chelativeactivation. Reductive amination,a A method for the conversion of carbonyl compounds to amines is by reaction with BujSnH and ammonium salts (derived from pnmary or secondaryamines) in DMF at room temperature. Hydrostannylation,s Regioselective hydrostannylation of several types of alkynes (to yield mainly ct-stannyl derivatives) is catalyzed by a molybdenum complex. rKamimura, K., Wada,M. TL 40,9059(1999). 2ooi,T.,Uraguchi, D., Morikawa,J.,Maruoka,K. OL2,2015(2000). rAsao,N., Shimada, T.,Yamamoto, Y. TL 41,9533(2000). aSuwa, T., Sugiyama, 8., Shibata, I., Baba,A. SL 556(2000). 5Kazmaier, U.,Schauss, D.,Pohlmann, M. OLl,l0l7 (1999).
Tributyltin hydrid*2,2' -azobis(isobutyronitrile). 19,353-357 ; 20, 391-394 D efunctionalizations. Heteroarenesulfonyl groups are reductively severed without affecting a geminal c-F bond.r A clean deoxygenation of alcohols via reduction of the corresponding thionocarbonatescalls for binding the tin hydride to a polymer and using trimethoxysilane to recycle the spent reagent.2 A method for synthesis of chiral cyclohexene derivatives from 4-substituted cyclohexyl halides involves derivatization to the Grignard reagent, reaction with menthyl (S)-2-bromophenylsulfinate, and then treatment with Bu:SnH, AIBN, and methylaluminum diphenoxide with irradiation by a sun lamp.3
n
Tributyltin hydride-2,2' -azobis(isobutyronitrile)
Amidoyl radicals uue generated from electron-richalkenesuch as enol deriraure.
""n\,\ \.',\*
fl? g^,*^."pn Group-transfer reactinns. A.Si- or P-linked aryl group separatedby five bonds to a carbon radical has the tendency to migrate to the carbon center.This reaction pattern can be exploited in a synthesisof 2-hydroxyalkylbiaryls from 2-bromobenzyl alcohols.a'5
R I
(Yo'\,
O ll- nr
Reductive cyclization, The Bu,Sn ensuingcarbonradicalsare liableto crch system.rr
[f\ao' %Ar
KF / H:O
A"lsi
BnOOC-N
\r This process is also applicable to arylation of secondaryaliphatic radicals,6and a carbon radical generated from O-S bond homolysis followed by radical transfer can be trapped.T
ar-l
OH
I I
w-'/
Cyclizations. Bromoarenes form radc cyclization routes to aporphines-indoldll
Ph
-\,.\ l
o-SAr
N-OBn
alkaloids.rl
Bu3SnH- AIBN/ PhH ;
,"\a"\
)-oe
R Bu3SnH- AIBN
%e,.
ph " P h- ^ r ' M"rsi'"''o I
oR
*
MeO
M&-y',
70o/o h eussnft-nlen
o
PhH
tl
'
o
----.t:-\ t / | l( |
fi-A.^on
L-J
MeO R
Bu3SnH- AIBN + PhMe r
I
MeO'\
*-./ R-\
R
R R 1,2-Migration of an acyl group to a nitrogen radical generatedfrom a-azido-B-keto estersto form amides(lactams)dis a pathway not observedin ionic reactions.
MeO MeO
t
I
r
A
r-"
MreoolNs
Bu3SnH- AIBN PhH
Bu3snH - AIBN PhMe
l
['/l€O\
rrc'
A
MeOOC 70To
MeO
R
Tritnvltiriydride-f2'-rtoDHisotrqmilrl"t
Ll
A m i d o y l r a d i c a | S a r e g e n e r a t e d f r o m a m i d o y l s e lqe n i d e s . I n t h e p r e s e n c e o f a n
electron-rich alkene such as enol derivative, addition occurs 3':S.H - AIBN + r,teAJl0Ph )2 \-
fl8
nv PhH
r. -' jl .eparatedbY five bondsto a e:-. - jnt!'r. This reaction pattern can 5 alcohols.a .'.hromobenzyl I :'
q^,*ot"pn
*
oR Aoa
o o o R ll il l
Bu3SnH- AIBN PhH A
ruVon
o
Reductivecyclization.TheBulSnradicaladdstoo.alkylaldoximesandthe groupr0 or conjugated ensuing carbon radicals are liable to cyclization with a carbonyl system.ll
K
I \'/-oH ...^Ar
t.
Bu3SnH-AIBN
BnOOC-N
\r
a#
PhH
\2,,
u 'NHBn
N-OBn 56lo
.1n aliphaticradicals,6and a car* cd by radical transfer can be
a. 1.
in synthesis,including cyclizations. Bromoarenesform radicals that can be exploited protoberberine-pavine and cyclization routes to aporphines-indolo[2,1-a]isoquinolines'r2 alkaloids.rl Ph
lr
\,\ -
MeO
MeO
0o/o Bu3SnH- AIBN
MeO :
I
- - .
PhMe A
R
MeO MeO R
i
MeO
R
K
T , il' l=3"" -.,1 eeneratedfrom ct-azido-p-keto rt'. ..'.1in ionic reactions. f:
*"oY)a\ ".o'YY
,a-\_ /-NH
ooc
70o/o
ftr Meo,\< OMe
""o6('l.fo Bu3snH.A,BN ^ PhN''!e veo'V\--l%orrre R=Me,cooR-620/o
Tributyltin hydride-2,2'-azobis(isobutyronitrile)
Ring closure is expected for a radical precursor set with an unsaturation four bonds away when such a compound is treated with BujSnH-AIBN. The versatility of such cyclizations is derived from allowance of many varieties of substitution patterns and heteroatomsbetween the reactive centers. Furthermore, as shown in a synthesisof 2,4-disubstitutedpyrrolidines,radiastereoselectivitymay be controlled in
Bu3SnH AIBN / PhH I
(
certain cases.
Phse) Ph._,\N,
Bu3snH-ArBN ai' rnr/*) ;;;*
a
R
. rnr/*)J
R
R
R=H 38 R = P(O)Phz 1
a,-.'\--
1
24
Bu:*
SiMe2Ph _\_ -SiMes
AlBri + r
"y-sultams,16 Basedon this method,expedientaccessto conjugatedexocyclic dienes,15 indoles.lTand ct-oximino-ry-lactonesr8 has beendevised. Also notable is the formation of a h 7,7-diyne.22 OH
/--\
pcPh3
fB,
( X . N -o_(
- AIBN Bu3SnH PhMe A
efi"
n
A
80%
The regioselectivity of cyclization through bond formation at either the ct- or r' B-position of a pyrrole dependson the electronic nature of the N-substituent.
ueo'y'-yt' l l V*Ao
R ,,N'.
A process involving cyclization-fra3l clopropanes23is a radical alternative to d 2-aminocyclooctenenitrile is formed in 56(
RN-1
Meolz\rA2 Bu3snH-ArBN \--l l + l l l l + Phi/e a \,A1rAo
Meo
NC
{^
SEM
SEM R=Me R = COOMe
43% 15Yo
-' LY^
Br
n=1.2.4 32o/o
Tandem cyclization is valued for synthetic efficiency. As illustrated, approachesto the BCD-ring segment of steroids2{)and a precursor of (*)-paniculatine2r are worth mentioning.
rWnuk, S.F.,Rios, J.M., Khan, J., Hsu. \'.-L ,l( 2Boussagnet,P., Delmond, B., Dumartin. G . R sImboden,C., Villar, F., Renaud,P. Ol l. 871 r aClive,D.L.J., Kang, S. ZZ 41, 1315 (2ffir sStuder,A., Bossart,M., Vasella,T. OL 2.9t5 t
Tfibutyltin hydride-2,2,-azobis(isobutyronitrile)
r .: r\tth an unsaturationfour r 11.- \nH AIBN. The versatility : - : " . \ a r i e t i e so f s u b s t i t u t i o n
Bu35nH
: : . i . . : t h r ' r m o r ea.s S h O w ni n a ) - : , , i r i l t \ m a y b e c o n t r o l l e idn
p
J
h
/
A I B N/ P h H A
74To \
SiMe2Ph
$*, K
SiMe2Ph
'.,.-\,,,".
1 24
Bu3SnH
SiMeq +
AIBN/ PhH A
d - ' . r e l r c d i e n e s , r1s- s u l t a m s , l 6
82o
(+)_paniculatine
Also notable is the formation of a bicyclo[3.1.1]heptaneskeleton from an acyclic 1.7-divne.22 OH
,^'vN \ l o\
Bu3SnH AIBN/ PhH
80%
Pi..,
A
Br > 85a/o
lltr)n at either the cr- or . ' . \ ' - s u b s t i t u e n t .I e
A process involving cyclization-fragmentationof 2-(o-bromoalkyl)-l,l-dicyanocycfopropanes23is a radical alternative to the Thorpe-Ziegler reaction of dinitriles. Thus, 2-aminocyclooctenenitrile is formed in 56Vo yield.
s
MeO
. I
\
-
il
Br
PhH ^
lH, I
NC_Yz\
L+4"
n=1.2.4
I
t
Bu"SnH- AIBN
32Yo
\. rllustrated,approachesto - -paniculatine2l are worth
rWnuk,S.F.,Rios,J.M., Khan,J.,Hsu,y-L. JOC 65,4t6g(2OOO). 2Boussagnet, P, Delmond,B., Dumartin,G.,pereyre, M.TL41,3377(ZOOO). 3lmboden, p. OL l,873 (1999). C.,Mllar,F.,Renaud, 4clive,D.L.J.,Kang,S. TL4t, l3t5 exn). sStuder, A., Bossart, M., Vasella, T. OL2,gg5 eOO}).
Tticarbonyl(pentamethylcyclopentadienyl)rhenium
oAmrein,S., Bossan,M., Vasella,T., Studer,A. JOC 65,4281 (2000). TPetrovic,G., Cekovic, Z. OL2,3'/69 '2OOU. sBenati,L., Nanni, D., Sangiorgi,C., Spagnolo,P.JOC 9,7836 (1999). 'Keck, G.8., Grier, M.C. SL 165'1(1999'). roNaito, T., Nakagawa, K., Nakamura, T., Kasei, A., Ninomiya, I., Kiguchi, T. JOC 64,2003 (Iggg). lrNaito, T., Fukumoto,D., Takebayashi,K., Kiguchi, T. H 51,489 (1999). r2Orito,K., Uchiito, S., Satoh,Y, Tatsuzawa,T., Harada,R., Tokuda,M. OL2,307 (2000). r3Orito,K., Satoh,Y, Nishizawa,H., Harada,R., Tokuda, M. OL2,2535 eO}U. raBesev,M., Engman,L. OL 2, 1589 (2000). r5Sha,C.-K., Zhan,Z.-P.,Wang, F.-S. OL2,20ll (2000). r6leit, S.M., Paquette,L.A. IOC 64,9225 (1999). rTTokuyama,H., Yamashita,T., Reding, M.T., Kaburagi, Y., Fukuyama, T. JACS l2l,37gl (Iggg). r8Clive,D.L.J., Subedi,R. CC 231 Q000\. leEscolano,C., Jones,K. TL 41,8951 (2000). 2oTomida,S., Doi, T., Takahashi,T. TL 40,2363 (1999). 2rSha,C.-K., Lee, F.-K., Chang,C.-J.JACS 121,9875 (1999). 2zBogen,S., Fensterbank,L., Malacria,M. JOC 64,819 (1999). 2rCurran,D.P..Liu. W. SL I l7 (1999).
Ttibutyltin hydride-triethylborane.15,333;16,350;17, 363-364;18,372; 20, 394 Cyclization,t Addition of BujSnH to B-allenyl-O-benzoyl oximes also causes cyclization.
)c"1
.
Bu3SnH- Et3B
\-N
SnBu"
\/Y
,n ,l\
|
!n P(
be'
t't">1, BulsnH-ArBN
'-;;;;*
+A Ph'
82Yo Radical additian.
rChen,H., Hartwig,J.F.ACIEE3t. -r,r9 Trichloroacetonitrile.
Hydroxyl protection.t Alcol reaction. Three sets of conditions I using DBU in MeOH, TsOH.H;( Zn-NHaCl in refluxing ethanol. Acid chlorides.: Sensitire rr treatment with Ph3P-CI.CCN ar roc
rYu,B., Yu,H., Hui,Y.,Han.X. Sl 75-r, rJang,D.O.,Park,D.J.,Kim, J. Il $. 5 TFichloronitromethane.
Dissulfides,t Treatment of r disulfides. ,l-Nitrosothiols are rhe rrr
bst 7 1o/o
\ /:c<
I
rDemir,A.S.,Igdir,A.C.,Mahasneh. .\ S
HN
OBz
\,4,/
\ ( Il ---\-o 'B-B' * --T-ct i
Conjugateaddition of primary radical to acrylic acid is realizable.2
rDeparture, M., Diwok, J., Grimaldi,J., Hatem,I. EJOC2'75(2OO0). 2Wu,B., Avery,B.A., Avery,M.A. TL 41,379'7(2000). Tiicarbonyl(pentamethylcyclopentadienyl)rhenium. Borylation.' Under photochemical conditions, alkanes are borylated at the terminal carbon on reaction with bis(pinacolato)diboron, with Cp*Re(CO)j as a catalyst and under a CO atmosphere.
Ttichlorosilane. 18,373; 19, -r@
Reduction. Carbonyl compor N-formylpynolidine.' Previousll. D! Radical reduction (photochemrc direction2 when the proper furrtrc trans-l,2-diols, with a trcnVcis rario u rlwasaki,F.,Onomura, O.,Mishima-K . 2Enholm, E.J.,Schutte, J.p.JoC 61.26t TFiethylboran e. 20, 395
Imine adducts.r Stable addrrr by treatment with triethylborane. N-Ethylation,2 Primary aru! N-Benzoyloxylation with dibenzol I 1 Alkylative amination.l Aldim addition. Thus, a mixture of RCHO. and EtrB to afford RR'CHNHOBn
Tliethylborane :(l)0). ':n r1999).
\, .,/. -7-d *or-i+ 'o1-
CO / cp.Re(Co)3
-|o.
-ldI
\
r: .: I . Kiguchi, T. JOC @,2003 (1999). | 5l r\9 ( 1999). R . .iiuda.M. OL2,307 (2000). \,.,tr 2.2535(2000).
65% (isolated) 95% (NMR) IChen,H., Hartwig,J.F.ACIEE
I
i . \ r\ ama,T. JACS l2l,3791 (1999).
B-r
38, 3391(199q.
Ttichloroacetonitrile. Hydroxyl protection.t Alcohols combine with clrcCN in a DBU-catalyzed, reaction. Three sets of conditions are available for the cleavage of trichloroacetimidates, using DBU in MeoH, TsoH'H2o in a mixture of dichoromethane and MeoH, or Zn-NHaCl in refluxing ethanol. Acid chlorides.2 Sensitive acid chlorides can be prepared from carboxylic acids by
I .'.".
treatment with Ph.,P-CICCN at room temperature.
17.363-364; 18,372;20,394 i' k-. r-()-benzoyl oximesalso causes
'.
v
SnBua ll
lYu,8., Yu,H., Hui,y., Han,X. ,1ggg\. SL 753 rJang. D.O..Park.D.J..Kim,J. IL 40, 5323(lgggt. TFichloronitromethane. Dissulfides.t Treatment of thiols with clrcNor-NaoEt disulfides. S-Nitrosothiols are the intermediates.
in MecN
leads to
rDemir,A.S.,Igdir,A.C., Mahasneh, A.S.f SS,l23gg(lggg). )Bz 7l Y o Sn
/:\/ FN
Dh
82% r;ial to acrylicacid is realizable.2
UTl.
,. .:.r.rocSare borylated at the terminal h t':' ' Re(CO).as a catalvstand under
Thichlorosilane.18,373; 19, 360 Reduction. carbonyl compounds are reduced by clSiH N-formylpynolidine.r Previously,DMF had beenused.
that is activated by
Radical reduction (photochemical conditions) with this reagent is subject to alkoxydirection2 when the proper functionality is present. Thus, cr-ketols give predominantly trans-l,2-diols, wirh a ftans/cisratio up to 134: 1 in one casehas beenobserved. I Iwasaki,F.,Onomura,O., y. TL 40,i507 Oggg\. Mishima,K., Maki, T., Matsumura, 2Enholm, 8.J.,Schulte, J.p.Joc 64,2610(1ggg). Tiiethylboran e. 20, 395 Imine adducts.' stable adducts RCH:N(BEI3)H by treatment with triethylborane.
are formed from RCH:NSiMer
N'Ethylation,2 Primary amines are converted to RNHET in two sreDs: N-Benzoyloxylation with dibenzoyl peroxide and reaction with triethylborane. Alkylative amination.3 Aldimines RCH:NoBn are susceptible to free radical addition. Thus, a mixture of RCHO, BnoNH2, and R'I react in the presenceof BF1.oEt2 and Et.1Bto afford RR'CHNHOBn.
T[ifluoroacetic acid TFA
Radical reactions,3 In the presence of air (or oxygen), EtsB promotes radical formation. A tin-free cyclization of
Et3B
O + Ph-CHO +
l
.
lHX
o
*l - X.
o
H ),,,oH
FoH
p(
Pr-i
(85 : 15) 44o/o
Simmons-Snith reaction.a A drarnet CFTCOOH is probably due to formation of e
lBouzide, A., Sauve, G.TL40,2883(1999r zKim,H.S.,Kim, T.Y.,Lee,K.Y, Chung.\'\l . k 3Kim,J.N.,Kim, T.Y.,Lee,K.Y.,Kim. H.S. krrarYang,2.,Lorenz,J.C.,Shi,Y Za 39,861I , I 99t
Substitution of the nitro group of nitroarenes with an alkyl residue on reaction with a trialkylborane/r-BuOK
combination
can proceed in good yields.T
'Chen, G.-M., Brown, H.C. JACS 122, 4217 (2000). 2Phanstiel,O., Wang, Q.X., Powell, D.H., Ospina,M.P, Leeson,B.A. IOC @, S03 (1999). 3Miyabe,H., Yamakawa,K., Yoshioka,N., Naito, T. f 55, 11209(1999). aDevin,P.,Fensterbank,L., Malacria,M.TL40,5511 (1999). 5Wakabayashi, K., Yorimitsu,H., Shinokubo,H., Oshima,K. OL2,1899 (2000). 6Yoshimitsu, T., Tsunoda,M., Nagaoka, H. CC l'/45 (1999). TShifman,A., Palani,N., Hoz, S. ACIEE 39,944 (20OU.
Ttifluoroacetic anhydride, TFAA. l& -tr6Dehydratian.
Endocyclic enecartarD
lactamsvia reductionand subsequentdchl& Regiochemically divergent lactonrzatro derivativeinducedby TFAA and Me,SiOTf r
J
TFifluoroaceticacid, TFA. 14,322-323; 15,338-339; 18,375 -376; 20,395 -396 Cleavageof p-methoxybenzylethers.t Simpleexposureto CFjCOOH effectsthe cleavageof the ethergroup at C-5 of furanosederivativeswhile retainingthe primary etherat C-6.
I
OPMB
OPMB PMBOY/
Ho',,) Y
BnO I
cF3cooH
CP /
\
>("
cH2ct2
H O I
\.'^-o \J/ \
o'---o 75%
Isomerization. The Baylis-Hillman adducts from aromatic aldehydes and acrylic esters undergo stereoselective isomerization to (E)-2-hydoxymethylcinnamicesters.2 Adducts derived from o-nitroaraldehydes behave differently due to intervention of an intramolecular redox reaction, leading eventually to N-oxides of 4-hydroxyquinoline-3carboxylicesters.3
Trifluoromethyl a-aminoalkyl L.rc TFAA-pyridine on N-substituteda-amino r Rearrangemenf. 2-Pynolidinemetherr expansion to give piperidin-3-ols.a Carbory less carbon by TFA-TFAA-NaNO:.
Ttifl uoroaceticanhydride,TFAA
r,: ,,\\'gen), Et,rB promotes radical o:r3'unds is effected.aRegioselective r. :::r t() a carbon radical center.s r:r .licomplishedwith RCHO.b ^'
ll
rt
F
l-1
'
"
\
+>( H
),,,OH
/
Ph 35 : 15) 44%
tf. .::. .rlkvl residueon reactionwith a g , ' . - :r r c l d s . T Ir .\ JOCU,803 (1999). x. : : ., 1999). F k,'.1 1899(2000).
Simmons-Smith reactian,4 A dramatic acceleration of the cyclopropanation by CF.TCOOHis probably due to formation of a more reactive speciesCFTCOOZnCH2I. rBouzide, A., Sauve, G.TL40,2883(1999). 2Kim,H.S.,Kim, T.Y.,Lee,K.Y.,Chung,Y.M.,Lee,H.J.,Kim, J.N.TL41,2613(2000). rKim, J.N.,Kim, T.Y, Lee,K.Y, Kim, H.S.,Kim, T.Y OL2,343 (2000). aYang,Z., Lorenz,J.C.,Shi,Y. 74 39,8621(1998).
Tiifl uoroacetic anhydride, TFAA. 18, 376-37 7 ; 19, 361; 20, 396-397 Dehydration. Endocyclic enecarbamates are prepared from the coresponding lactams via reduction and subsequentdehydration with TFAA-2,6-lutidine.l Regiochemically divergent lactonization processes of a hydroxynaphthoquinone derivativeinducedby TFAA and MerSiOTf are observed.2
)
cF3cooH
tL
I lt. .r75-376;20' 395-396 rr,,\ure to CF.TCOOH effectsthe ' .c. whileretaining the Primary
k'
OPMB
^ :
'v
l
,
/^o
--1 7 5o/o
:: rromatic aldehYdesand acrylic . i -hrdoxymethylcinnamic esters'2 i of an intervention to due :jrcntly -,,rides \ 4-hydroxyquinoline-3of t,'
a-aminoalkyl ketones,l The Dakin-West reaction using Trifluoromethyl TFAA-pyridine on N-substitutedd-amino acids affords the fluorinated ketones. Rearrangemenf. 2-Pyrrolidinemethanol derivatives undergo stereoselective ring expansionto give piperidin-3-ols.aCarboxylic acids are convertedto nitriless with one less carbon by TFA-TFAA-NaNO2.
Tiifluoromethanesulfonic acid (triflic acid)
Tr-rrr
Nitrodeboration.. lpso-substitution of arylboronic acids to give nitroarenes is accomplishedwith TFAA and NHaNOj. Reductive functionalization of (arylseleninyl)acetates.T when the pummerertype rearrangementof PhSe(o)CH2cooR is carried out in the presenceof a reactive silane (e.g.,
Dealkylation,5 Protodemethylation r! r ethyl group in the following reaction seqrrd
allylsilanes,MeqSiNs)carbon chain homologationor functionalizationof the estersresults. rOliveira,D.F.,Miranda,P.C.M.L., Correia,C.R.D.JOC 64,6646Oggg). 2Qabaja, G.,Perchellet, 8.M.,Perchellet, I.-P.TL4l, 3007(2000). 3Kawase, M., Hirabayashi, M., Kumakura, H., Saito,S.,Yamamoto, K. CpB 48,I l4 (2000). aCossy, J.,Dumas,C.,Pardo,D.G.EJOC 1693(l9gg). sSmushkevich, Y.I., Smushkevich, V.Y, Usorov,M.I. "/CR(S/tj2'l (lggg). 6Salzbrunn, S.,Simon,J.,Prakash, G.K.S.,Petasis, N.A.,Olah,G.A.Sa 14g5(2000). TShimada, y.ZZ 41,4637(2OOO). K., Kikuta,Y.,Koganebuchi, H., Yonezawa, F.,Aoyagi,S.,Takikawa, N-(T[ifl uoroacetyl)succinimide. Trifluoroacetylation.t Alcohols, phenols, and amines are acylated by the title reagent(14 examples,83-997a). rKatritzky, A.R.,Jang,B., Qiu,G., Zhang,Z.S 55 (1999). 21212-Triflioroethyl
carbamates. ureas,t The carbamates RNHCooCH2cFs are obtained by an electrochemical reaction of primary amides (RCoNHr) in cFjcH2oH. They undergo aminolysis to afford unsymmetrical ureas. rMatsumura, Y, Satoh,Y.,Onomura, O.,Maki.T. JOC 65.1549(2000). Tlifluoromethanesulfonic acid (triflic acid). 14, 323-324;15,339; 18,377;19, 362-363:20,398-399 Allylation.t Triflic acid is capableof catalyzingthe reactionof allyltributylstannane with aldehydes(not ketones) in water. Michael reaction.2 For conducting a Michael reaction of g-ketoesters with conjugated esters and ketones at room temperature under solvent-free conditions, triflic acid is useful. cyclizations. A stereocontrolled synthesis of trisubstituted tetrahydropyrans by condensationof homoallylic alcohols with aldehydesis developed.3Treatmentof rHp ethers derived from unsaturatedalcohols with triflic acid leads to oxygen heterocycles.a
CI".L,-O
cF:So:H'r"tb 65To
rhazinilam
I Loh, T.-p., Xu, J. TL 40, 2431 (1999). 2Kotsuki, H., Arimura, K., Ohishi, T., Maruzasr RrCloninger,M.J., Oveman,L.E. JACS l2l. l09l , I aDixon, D.J., Ley, S.V.,Tate,E.W ./CS(P/r 183 , I 5Johnson,J.A., Sames,D. JACS 122,6321 (?Vnl
T[ifl uoromethanesulfonic
anhydride
t triffc
15, 339-340; 16, 357-358; 18, 377 -37 8 : l).'. Nitrile oxide generation.t O-Silllaod precursors of nitrile oxides, by virnr of Tf2o-EtjN.
1,3,4-Oxadiazoles.2 Tf2O-pyridine rs : diacylhydrazines.
'Muri, D., Bode,J.W.,Carreira, E.M.OL 2. 5-t9r! 2Liras,S.,Allen,M.P.,Segelstein, B.E..tCgl. r_r: ,
Tfifluoromethanesulfonic anhydride (triflic anhydride)
.rcids to give nitroarenes rs
).:. tue\.
Dealkylation.s Protodemethylation is the key to functionalization of an unactivated ethyl group in the following reactionsequence.
When the Pummerer-type
r. :r-c.\enceof a reactive silane (e.g., c:..,r.rlizationof the estersresults. !-:'
COOMe
1999).
l l
r:
K. CPB48.I 14(2000). cFlso3H
-_- re99). : h (. \.t1.1485(2000). S .
cH2ct2
Irliikawa,Y.TL41,4637QUn).
cFlcH'oH
a:r'.::',d\are acylated by the title
70"
I
I
I V
COOMe N
I ^r.irned by an electrochemical 1'. . undergoaminolysisto afford
.t.
_ rx)t.
. : : r 1 5 ,- 3 3 91;8 , 3 7 7 ; 1 9 , hr :J.icrionof allyltributylstannane :, --'.retion of B-ketoesterswith t"r-: ., )lvent-freeconditions,triflic
by u:...^.riruredtetrahydropyrans :. .:-'\!'loped.r Treatment of THP tr . .,.i.t()oxygenheterocycles.a
I Loh, T.-P., Xu, J. TL 40, 2431 (1999\. 2Kotsuki, H., Arimura, K., Ohishi, T., Maruzasa, R. JOC 64,37'10 (1999). 3Cloninger,M.J., Oveman,L.E. JACS l2l,lO92 (1999). aDixon, D.J., Ley, S.V.,Tate,E.W. JCS(PI) 1829 (2000). 5Johnson,J.A., Sames,D. JACS 122,6321 (2OOO).
Tiifluoromethanesulfonic
anhydride
(triflic
anhydride).
13, 324-325;14,324-326;
15, 339-3 40; 16,357-3 58; 18,371-37 8; 19, 363-365; 20, 399 Nitrile oxide generation.t O-Silylatedhydroxamicacids are identifiedas stable precursorsof nitrile oxides, by virtue of their susceptibilityto transformationby Tf2O-EtrN. 7,3,4-Oxadiazoles.2 Tf2O-pyridineis a mild reagentfor the cyclodehydration of diacylhydrazines. tMwi, D.,Bode,1.W.,Canetra, E.M.OLZ,i3g (2N0. 2Liras, 5., Allen,M.P.,Segelstein, B.E.SC30,437(2N|D.
(Tiifl uommethyl)trimet}ylsilane
Tlifluoromethanesulfonyl azide. Diazocarbonyl compounds.l The title reagent is particularly useful for the introduction of an ct-diazo group to cr-nitro carbonyl compounds.
IBlazejewski,J.-C.,Anselmi,8.. \'\'ilmshun rlshizaki,M., Hoshino,O. Z56. g8l-rrl[fJrr
rCharette, A.B., Wurz,R.P, Ollevier,T. JOC 65,9252(2O0O).
Tii-2-furanylgermanFtriethl'lborer Organotrul Defunctianalimtion.t with this reagentvia radical intermedrrc
3-(Tiifluoromethanesulfonyloxy)-3-trifluoromethylpropeniminium triflate. 2-Trifluoromethylquinolines.r Reagent 1 transforms arylamines into 2-trifluoromethylquinolines in one step.
G"',.
Me2N
rfo83% (1)
I Baraznenok, I.L., Nenajdenko, V.G.,Balenkov a, E.S.EJOC937(1999).
; )
I Ia
t 7
a"
if NaBH4is usedin conjunction. rNakamura. H., Shino\utr..ll T..Yorimitsu,
Tiiisobutylaluminum. 19, 367--16.q Reductive rearrangement Errcr enol ethers establishes a horrxrk ATCHTOC(=:CH2)Meto ArCH:CH :CH Carbocyclesare formed on subjecuq
Claisen realrangementfollowed br rod one step.3
2-(TFifluoromethanesulfonyloxy)vinyl aryliodonium trifl ates. Aryliodonium salts.t Unsymmetrical diaryliodonium triflates and aryl(a1kyny1)iodonium triflates are readily synthesizedfrom the title compounds by reaction with ArLi and alkynyllithium reagents,respectively.Ethylene is one ofthe byproducts. +
Ar-l-A/ Ar-l Tfo
i_
Tfo-
OTs
-a Ar-l:R Tfo-
rPirguliyev, N.Sh.,Brel,VK., Akhmedov, N.G.,Zefirov,N.S.S 81 (2000). S-TFifluoromethyldiarylsulfonium trifl ates. Trifluoromethylation. These reagents are prepared from ArS(O)CF.,. They donate the trifluoromethyl group to suitable nucleophiles (e.g., arenes).
rdu Roizel, B., Sollogoub,M., Pearce..{J - i rSollogoub,M., Mallet, J.-M., Sina1.P .{Clt 'Wang, W, Sollogoub,M., Sinay.P. ACIEE
rYang,J.-J.,Kirchmeier, R.L.,Shreeve, J.M.JOC 63,2656(1998).
(Tiifl uoromethyl)trimethylsilane. I 5, 34 | ; 18, 378-37 9 ; 19, 366-367 ; 20, 400 Trifluoromethylation. Imines show similar reactivity as carbonyl compounds in accepting the MejSi and CF3 groups from MesSiCFj.r In the presenceof CsF of KF, the title reagentconverts l-alkynes to alkynyltrimethylsilanes.2
I -Ttiisopropylsiloxy- 1,2-propadicc Acrylic acid a-anian equivalcat the title compound with t-Buli rn Tl alkylated.Quenchingwith aldeh!desg
--15-, rStergiades, I.A.,Tius,M.A. JOC61.
1-T[iisopropylsiloxy-1,2-propadiene 451
:. particularly useful for the lr':la()Unds. ni
) lpnrpeniminium triflate. s: ::r\ arylamines into 2-trifluoro-
lBlazejewski, J.-C., Anselmi, E., Wilmshurst, M.P. TL 40, 5475 (1999). 2 l s h i z a k iM , . , H o s h i n o ,O . 2 5 6 , 8 8 1 3 ( 2 0 0 0 ) .
Tii-2-furanylgermanFtriethylborane. Defunctionalizatian.t Organobromides,iodides, and xanthatesare defunctionalized with this reagentvia radical intermediates.Only catalytic amount of the germaneis required if NaBH4is usedin conjunction. rNakamura, T.,Yorimitsu, H., Shinokubo, H., Oshima,K. SZ 1415(1999). Ttiisobutylaluminum. 19, 361-3 68 Reductive reanangemenf. Extension of the previously discovered reaction to enol ethers establishes a homologation route for alcohols, for examples., ATCH2OC(:CH2)Me to ATCH2CH2CH(OH )Me.I Carbocyclesare formed on subjectingunsaturatedS-, Se-, and C-glycosidesto r-Bu.1Al.2 Claisen rearrangementfollowed by reduction of the resulting ketones is accomplishedin
'_:-
.999).
one step.3
n triflates, triflatesand ary1(alkynyl)I::-:r le . npounds by reaction with ArLi r':: ,l the byproducts.
r
o-OH 57% + p_OH38%
:'-l:-A/ Tfoi-Bu3Al
Ar-l----E-R
BnO
).
OBn
96%
:000).
- i:i:lL'\
l
eno"')-ion
Tfo-
r.J rr()m ArS(O)CFj. They donate
._^\ t
rduRoizel,8., Sollogoub, M., Pearce, A.J.,Sinay,P CC 1507(2000). 2Sollogoub, M., Mallet,J.-M.,Sinay,P.ACIEE39,362(2000). rWang,W, Sollogoub,M., Sinay,P.ACIEE39,2466(2N0).
lw.
l-" 19.366-367;20,400 r1:.:l\ as carbonylcompounds in : I: rh!'presence of CsFof KF, the aa-
1-TFiisopropylsiloxy- 1,2-propadiene. Acrylic acid a-anion equivalent.t O + C Silyl migration occurs on treatment of the title compound with t-Bul-i in THF at -78'. The ensuing lithium enolate can be alkylated. Quenching with aldehydesgeneratesBaylis-Hillman adducts. rStergiades, I.A.,Tius,M.A. JOC 64,7457(1999).
Thimethylaluminun
T[iisopropylsilyl triflate. 20, 4Ol This reagent is a valuable component of [4 + 3] 2-(Triisopropylsi.lory)acroleinl by prepared from 2-methoxy-2-methyl-1,3-dioxan-5-one It is conveniently cycloadditions.
Diels-Alder reaction.u The Drelr-A stereoselectiveon using Me,Al to tether h each of which contains an allylic hydrorr 5
reaction with i-Pr:SiOTf-Et3N.
rKurosu.M. TL 41,591(2000). rAbe.N., Hanawa, \t \ H., Maruoka,K.. Sasalit. rSchneider. J.TL 4l' j04-1(lffrl C..Brauner, aBertozzi, F.,Olsson,R.,Frejd,T. OL 2. I lti '-lI
o
A
i-Pr3Si-/.\ i-Pr3SiOTf- Et3N
x;"
i
r'Yo
*;-
H
Silyl carbamates.2 Primary and secondary amines are protected as triisopropoxycarbonyl derivatives on consecutivetreatrnentwith carbon dioxide (EtrN--CH2Cl2,-78') and i-PqSiOTf. The silyl carbamatesare decomposedby BuaNF at ice temperature.
Ttimethyl orthoformate. Methyl 7,7-dimethoxyalkanmtcsHC(OMe)3-MeOH in the presenceof T
Trimethylsiloxytrioxorhenium. Pn Isomerization of allylic alcohok. silyl ethersare equilibratedin the pre\ttl-c (
rHarmata, M., Sharma, U. OL2,2703(20OO). 2lipshutz,B.H.,Papa,P.,Keith,l.M. JOC9,3792 (1999).
15, 34 | -342; 17, 372-37 5 ; 18, 365-367 ; 19, 369-37 0 Peptide synthesis.t Mediated by MejAl, thiol esterscondensewith amines to form amides. Note the reactivity differentiation of two thiol esters in the amino acid
rBellemin-Laponnaz, S.,Le Ny,J.P.Ostnm l \
T[imethylaluminum.
Trimethylsilyl azide. 13,24-25'. l{. ::. lS,
20,403 pAzido alcohols.t Opening of egr'rr is catalyzedby BuaNF under solvent-iret cc
componentsin the following equation.
''*\'D .,,- €'.ry,,^.X.*-ri,Cil*,
rschneider, C SL 1840(2000).
Epoxide opening. Regioselective opening of epoxides substituted with different activating groups at the two carbon atoms on reaction with Me.Al-H2O is observed.2 [A report is on epoxide opening with Et.Al using Lewis base,e.g., (MezN)rP,as catalyst.s]
BnO-v/
cooEt
Trimethylsilyl chloride. 15, 89: 16. 85-t'6. Functional group manipulations. .l catalytic amount of MerSiCl and I !-{lurr treatment.MerSiCl also catalyzes thc rcl
trimethyl orthoacetate.2 Temporary protection of a-amino ar'rd facilitates certain transformations.includr isocyanate.rThus, Fmoc-derivativesof c esterson reacuonr o-isocyanatocarboxylic
t tr .-r When de-N-(r-butoxycarbonylation priman amrn of the Selective reaction been dernr has trimethylsilylationof both
BnO H2O - CH2CI2 -20"
94Yo
still derivatizable.
Ttimethylsilylchloride
.i \ iluable component of [4 + 3] by lh,,rr -2-methyl-1,3-dioxan-5-one
Diels-Alder reaction.4 The Diels-Alder reaction is facilitated and rendered stereoselectiveon using MejAl to tether both diene and dienophile components when each of which contains an allylic hydroxy group. rKurosu,M. TL 41,591(2000). rAbe.N.. Hanawa,H., Maruoka,K., Sasaki, M. TL 40' 5369(1999)' M', Miyashita, 3Schneider, I.TL 41,3043(2000). C.,Brauner, aBertozzi, F.,Olsson,R.,Frejd,T. OL2' 1283(2000).
? , s- o
zYo
Trimethyl orthoformate. Methyt 7,7-dimethoxya.lkanoates.t Admixture of 2-acylcyclohexanones with HC(OMe)r-MeOH in the presenceof TsOH at foom temperaturecausesring cleavageto afford the ketoesteracetalsin good yields (3 examples,8V937o)'
H
tflrr. rrl' protected as triisopropoxyr*' I dioxide (Et3N-cH2Cl2,-78') ti I-i:,\F at ice temperature.
rMartins.M.A.P.,Bastos, HG'' Zanatta'N SL A.P, Flores'A'FC', Bonacorso, G.P, Sinhorin, (1999). 789
Trimethylsiloxytrioxorhenium. Isomerization of altylic alcohols.l Primary and secondaryallylic alcohols and their silyl ethersare equilibratedin the presenceof (MerSiO)ReOr'
,.t r .t67;19,369-370 with aminesto form :1r.:. condense c rr:rrl estersin the amino acid
.Y-n_ri,,0 o
-Ph
cr rrJes substituted with different g.,:. rrrth MerAl-HzO is observed.2 l\ 1r.c. e.g.,(MezN):P,as catalYst.3l
3H
'---/''-a-cooEt I 94To
rBellemin-Laponnaz, S.,Le Ny,J.P.,Osborn,J.A'.TL 41, 1549(2000)' -37 2 ; Trimethylsilyl azide. 13, 24-25 ; 14, 25 ; 15, 3 42-343 ; 16, l7 ; 18, 379-3 80; 19, 37 1 20,403 pAzido alcohols.t Opening of epoxides with the title reagentat room temperature is catalyzedby BuaNF undersolvent-freeconditions. rschneider, C. SL I 840(2000). Trimethylsilyl chloride. 15' 89; 16,85-86; 18, 381; 19, 374-315;20,404405 Functional group manipulations. Aliphatic TBS ethers are hydrolyzed with a catalytic amount of MejSicl and I equiv of H2o in MecN.r ATOTBS survives such treatment.MejSiCl also catalyzes the selective acetylation of aliphatic alcohols with trimethyl orthoacetate.2 Temporary protection of a-amino acids (and N-derivatives)as trimethylsilyl esters facilitates certain transformations,including conversionof the free amino group to an give isocyanate.sThus, Fmoc-derivativesof a-amino esters undergo elimination to esterson reactionwith Me.SiCl-Et,N'a cl-isocyanatocarboxylic When de-N-(t-butoxycarbonylation)is carried out in MeOH, esterificationalso occurs.s Selective reaction of the primary amine in the presence of a secondary amine after The monosilylatedprimary amine is trimethylsilylationof both has been demonstrated.6 still derivatizable.
Tbimethylsilyl chlorosulfate
Reductive acyl.ation.l Azides are converted to amides with a mixture of an anhydride and MeqSiCl. Hydrohalogenatinn of alkynyl ethers.s cr-Haloalkenyl ethers are formed. Such ethers are useful as acyl anion equivalents. Bis(indol)-3-ylalkanes.e Nitrones condense with indoles under acidic conditions. When Me]SiCl is used as promoter, the adducts serve as alkylating agents.
a
Vn ' N / * an-i,-) 'r' H
O
I
Trimethylsilyl cyanide. 13, 87-88: l{. lt} 20,405 a-Cyanohyd.rin derivatives. .{ccul groups in catalyzed reactions with \lc,Sr well with acylals derived from aliphauc d this alternativemethod is an improrenrnt
Regioselective1,2- or \,4-additron to modificationof the reasent.r
N4e3SiCl I t
rBassindale,A.R., Katampe,I., Maesano.\t G .
cH?cl, -
I
EtO\72',*.CHF2
85To
ll
+ LrqS_
o
I ncrr w"or0"
EtO-4t -u.CzFs + ite39 _ ]l
o
94Yo
I Grieco, PA., Markworth, C.I. TL 40, 665 ( I 999). :Sabitha,G., Reddy,B.V.S.,Reddy,G.S.K., yadav, J.S.NJC 24,63 (2000). 3weiberth, F.J. TL 40, 2895 (1999). r C h o n g ,P Y . , P e t i l l o ,P . A . T L 4 0 , 4 5 0 1 ( 1 9 9 9 ) . 5Chen,B.-C., Skoumbourdis,A.P, Guo, P., Bednarz,M.S., Kocy, O.R., Sundeen,J.8., Vite, G.D. JOC 64,9294 (1999't. 6Wang,T., Zhang,Z., Meanwell, N.A. ZL 40, 6745(1999). T B a r u aA, . , B e z ,G . , B a r u a ,N . C . S L5 5 3 ( 1 9 9 9 ) . f Yu, W., Jin,Z. IACS 122,9840 (2000). "Chalaye-Mauger,H., Denis, J.-N.,Averbuch-Pouchot,M.-T., Vallee,Y f 56, 791 (2000).
Trimethylsilyl Sultones.t
chlorosulfate. Upon
admixture
with
iodosylbenzene,
trimethylsilyl
provides nascent sulfur trioxide, which can be trapped by alkenes.
chlorosulfate
In the presenceof a lrl alkenesto furnish isonitriles. Isonitriles.a
Nitriles by substintion. Gllcosrl (Pd-catalyzed reaction),5 whereas S.l ra ' activateMerSiCN (hypervalentsilicater Glycosylation,? A glycoside r*rth o
sugar (except the OH at the anomenc s-a acid anhydrideand MerSiClO., uhich rr p Me3sir ll+ l l
Me3siPhr=o - /r M e- 3 S- i -cO SHO 22- C lc r 2 L S l Y O , 57Yo
rTanaka,N., Masaki,Y.SL12'17(19991 :Sandberg, M., Sydnes, L.K. OL 2, 6870rIOS rKruchok,I.S.,Gerus,I.I., Kukhar,V.P f 5a.( aKitano,Y.. Chiba,K., Tada,M.Sl 288( 1999 5Hayashi, M., Kawabata,H., Arikrta.O. IL a.
TrimethYlsilYl cYanide
o .1::rdes with a mixture of an
lBassindale'A.R.,Katampe,I.,Maesano,M.G.,Patel,P.,Taylor,P.G.TL40,.I41.7(|999).
)..,.:nrl ethers are formed' Such
102-104; 17' 89; 18' 381-382; Ttimethylsilyl cyanide.13,87-88; 14,107;15,
h '..l.,les under acidic conditions. r. .: :.\latlngagents.
20,405 oxy and acylals2 exchange one -of-their u-Cyanohydrin derivatives' Acetalsl works The exchange using KCN-DMSO groups in catalyzed reactions with MerSiCN' therefore aldehydesbut not for ArCH(oCoR,)2, well with acylals derived from aliphatic
t9'375;
this alternative method is an improvement' Regioselectivel,2-orl,4--additiontop-alkoxyvinylketonesisrealizedbyproper modificationof the reagent'r
85%
eto-g2'rzcHF2 tl
+ M%si-cN
n
Et3N
ErO,,/^'
0'
NC'
'OSiMe3
80%
EtO,,r'r--.*,'"t'' il
_
M e"? S i - C N +
r, 50"- 60'
EtO-.*r1,r,'CzFs I I CN OSiMe3 89%
94Yo
Isonitriles'alnthepresenceofasilver(I)salt'MelSiCNdeliverstheCNgroupto alkenesto furnish isonitriles'
t(n0). O . R . . S u n d e e nJ, . E . ,V i t e , G . D .
Me3SiCN AgCIOa
c c . Y . ? " 5 6 , 7 9 1( 2 0 0 0 )
!:.-J:rj. trimethYlsilYlchlorosulfate u - . .rlkcnes.
91To
esters cyanides are formed from glycal Nitriles by substitution' Glycosyl to ion fluoride requires halides of alkyl (Pa ""t"ivr"a reaction;,5 whereas Sp2 reaction activate Me',SiCN (hypervalent silicate)'o protected free hydroxyl group and another Glycosylation./ A glycoside with one aid of an the with treatment center) condenseon sugar (except the OH at the anomeric acidanhydrideandMerSiClOa,whichispreparedinsitufromMerSiClandAgClOa'
.c
Me3Si t l
^
v l
LSOz
57Yo
(1999)' rTanaka, N., Masaki,Y.SL12'7'1 2Sandberg, L'K' OL2' 6870(2000)' M., Sydnes, tx-"toi t.S.,Gerus,I.l.' Kukhar,V'P'I56' 6533(2000)' aKitano, Y.,Chiba,K., Tada,M SL 288(1999)' 'H"V"rfti, M., Kawabata,H', Arikita, O'TL40' 1'129(1999)'
Trimethylsilyldiazom€thane
6Soli, 8.D., Manoso, A.S., Patterson,M.C., DeShong,p., Favor, D.A., Hirschmann,R., Smith III, A.B. JOC 64,3r71 (1999). Twakao, M., Nakai, Y., Fukase, K., Kusumoto, S. CLZi ,lggg\.
Trimethylsilyldiazomethan e. 20, 405406 HomologationI one-carbon extension of alkenes via hydroboration (with catecholborane) is by furthertreatmentwith Me.,SicHN2beforeoxidativeworkup.
Tiimethylsilyldi(ethyl)aminc. : Alkylation. Cyclopropar:
dimethyl 2,3-dihalopropanoarc modification of the Michael rc leadsto 6-ketoaldehydes.:
Ar '
R _ C H O+
ea_/ * \1.t, h* *,Yt-d
SiMe3
SiMe3
R
n---1^oH R
Aldol
reactions.3
Reacrro
conditions. It is perhaps usetul f Ether
cleavage.a
A comt
same reactivity as MerSiX in efl
[2'3]-Sigmattopic rearrangement.2 Transpositional rearrangement with one-carbon insertion of allylic sulfides occurs in the reaction with MqSicHN, that is catalyzed by FeCl2(dppe). cycloadditions. Direct cycloaddition of Me.SicHN2 to N-sulfonylimines afford aziridines with high a.t-selectivity.sDue to stereoselectivering opening and replacementof the silyl group by a carbon chain offered by the products,syntheticpotentialsare indicated.
R-rt
SiMe3 \
\
N-SO2R' -
-
l
\rrr_ t\2
SiMer oroxane
-;-
I
'so2R'
lHagiwara,H., Komatsubara.\ . Hr rHagiwara,H., Kato, M. 7L 37. 5l l rHagiwara,H., Ono, H., Komarsuh aOshita,J., Iwata,A., Kanetanr.F . I
TFimethylsilyl N,N-d ialk.r-lcerl
Enamines,l Reactionoi d enamines. More than 2 equrr dehydrating agent besides doo valuablefor the preparationoi.t methodsare not suitabledue lo I
Alkylidenecyclopropanes are formed by reaction of the lithiated trimethvlsilvldiazomethanewith carbonylcompoundsin the presenceof alkenes.a R
tnlo Ph-.J
.
SiMe3 LiANz
.- f-) \-/
-------_ +
tn-\-,,f-)
,*{
R
O OS*
*_/---\, 69% I Kardon,F..Mitrtl. M.. Knausz.D
'Goddard, J.-P.,Le Gall,T.,Mioskowski, C. OL2, 1455e000). 2carter,D.S.,vanVranken, D.L. OL2,1303(2000). 3Aggarwal, V.K.,Ferrara,M. OL 2, 4107emCf|t. aSakai, A., Aoyama,T., Shioiri,T. f 55,3687(1999).
4-(Ttimethylsilylethorym€tho! Subsftluted benryl ethcttethersis accomplishedby alkl la
4- (Trimethylsilylethoxymethoxy)benzyl
' :
'r. D.A.. Hirschmann,R., Smith III,
l*"
bromide
Trimethylsilyldi(ethyl)amine. 18, 382; 19, 376; 20, 407 Alkylation, Cyclopropane formation is observedl in the reaction of aldehydes with dimethyl 2,3-dihalopropanoate in the presence of EtzNSiMer. This process rs a modification of the Michael reaction between aldehydes and methyl vinyl ketone that leads to E-ketoaldehydes.2
:.rcDCS via hydroboration (with hc'foreoxidative workup.
Br
lll\
Y
R...,,'CHO +
R",/c'o
Br
Et2N-SiMe3
COOMe
/\-rcooMe
MeCN 25'
a-
H
SiMe3
- -
-
I
nt^\r^oH l t(
Aldol reactians,3 Reaction between two aldehydes proceeds under solvent-free conditions. It is perhapsuseful for the preparation ofa-substituted cinnamaldehydes. : Ether cleavage.a A combination of Et2NSiMe. and MeX (X Br, I) shows the samereactivity as MejSiX in effectingethercleavage.
n -.:. r!'arrangementwith one-carbon s::: \lc,SiCHN2 that is catalyzedby ,\ ( l{\: to N-sulfonylimines afford n:. , - nng openingand replacementof lr:- .\ ntheticpotentialsareindicated.
SiMe3 ?
--
>
-
a\<
)
| -N 's02R'
h E
Ttimethylsilyl N,N-dialkylcarbamates. Enamines.t Reactionof the title compoundswith ketoneswithout solvent leadsto enamines. More than 2 equiv of the reagents are employed because they serve as dehydrating agent besides donating the amino group. This procedure is particularly valuable for the preparation of N,N-dimethyl enamines and the like becauseconventional methods are not suitable due to the volatile nature of the anhydrousamines.
"O
: the lithiated trimethylsilyldia.,lkcnes.r R
,
,*{
R
Ph
O OSiMe3
_f--
l-Y'-Ta o l o
Ph
R N R
YY
RzN
O
69Yo I Kardon.F..Mijrtl, M., Knausz,D. TL 41,8937(2000). i"
4-(Ttimethylsilylethoxymethoxy)benzyl bromide. Subsfrtuted benzyl ethers.t Protection of alcohols in the form of substituted benzyl ethersis accomplishedby alkylation of RONa in DMF. Theseethersare cleavedwith BuaNF.
Ttimethylsllylnethylltthium
rJobron, L., Hindsgaul, O. JACS121,5835(1999).
t Trimethylsilyl)methylenetriphenl'l p@ 4H-Chromen-4-ones.) This rA'itttgr
Tlimethylsilyl fl uorosulfonyldifl uoroacetate. gem-Difluorocyclopropanation.t Formation of gem-difluorocyclopropanes from electron-deficient alkenes such as acrylic estersis surprisingly efficient using this reagent and catalytic amount of NaF. 'Tian, F., Kruger,V., Bautista,O., Duan,J.-X.,Li, A.-R.,Dolbier,Jr.,W.R.,Chen, Q.-Y. OZ 2, 563(2000).
rhe a-acylphosphoraneby elimination thn tntramolecularWittig reactionpresent\rtY r. r* the formation of a 411-chrom"n-4-6n!'
o
\ 4>1,r--OtBS R .yo-1 i ll ,o R'
Tiimethylsilyl iodide. 16, 188-1 89; 18, 383; 19, 37 6-37 7 ; 20, 407 Ketones from alkenyl sulfoxides.r The functional group transformation does not occur with the correspondingsulfides or sulfones.
:
M.S.OL2,3821t)(tt' Kumar,P.,Bodas,
2-T[imethylsilyl nitrate. a-Nitro ketones,t Functionalrratr \lerSiONOu-CrO3 in MeCN is chara.ra oxidation state.Under the samecondttt.'n
Me3si-l
.,..oMe H
+ J
Prl .-"
+
o
NPh 50To
fAversa,M.C., Barattucci,A., Bonaccorsi,P., Bruno, G., Giannetto,P., Policicchio,M. TL 41, 444t (2000)..
Tiimethylsilylmethyllithium. pKeto silanes.r 1-Bora-l-bromoalkenes are homologated and refunctionalized on reaction with MqSiCH2Li followed by oxidative workup. l-Trimethylsilyl-2-alkanones are obtainedin good yields (6 examples,63-75Vo).
O
. Me3Sr-
Shahi,S.P, Gupta,A., Pitre.S.V..RedJr 1509( l 999).
Trimethylsilyl phenyl selenide.20. {t\ pNitroalkenyl selenides.r p-\rtrr reactionwith Me3SiSePh.
Br
Li
\./ siMe.
H2O2- NaOAc
B-O
o
A.. Kinornc.\. Abe,H., Fujii,H., Yamasaki,
)
'Bhat, N.G., Martinez, C., De Los Santos,J. TL 41, 6541 (2OO0)
Ttimethylsilyl phenyl telluride. Reductive silylation.t Quinonc. er quinoneswith Me.,SiSePhin THF at rrr-r initiatedby a singleelectrontranslerin'nt
rYamago, S.,Miyazoe,H., Iida.K.. )bshr& J
Tf imethylsilyl phenyl telluride
o: i.,rn-difluorocyclopropanesfrom u::r.rngly efficientusing this reagent
l i),.lhrer.Jr.,W.R.,Chen,Q.-Y.OI 2,
(Trimethylsilyl)methylenetriphenylphosphorane. 4H-Chromen-4-ones.1 This wittig reagent reacts with a silyl carboxylate to give the a-acylphosphorane by elimination through siloxane elimination. Opportunity for an intramolecular Wittig reaction presentsitself in the case of a silyl 2-acyloxybenzoateand the formation of a 4H-chromen-4-oneis observed.
o z\)-orBs ^
BPh, -* \siM".
+rl
R' 9; o { l l
7 Rr-
\
R'
L :--: 20,407 x':.ri group transformationdoes not
l K u m a r ,P . ,B o d a s ,M . S . O L 2 , 3 8 2 1 ( 2 0 0 0 ) .
H
o
NPh
2-Tiimethylsilyl nitrate. a-Nitro ketones.t Functionalization of alkenes by MejSiONO2-DMSO or MeTSiONO:-CrO.rin MeCN is characterizedby the generationof products in a high oxidation state.Under the sameconditions,cyclic ethersare oxidizedto lactones.
o 50%
/-\ (_-jJ .
Me2So aYo -"*;* Me3Si-ONO2 UNO,
(;:rnnetto,P., Policicchio,M. TL 41, 70o/o
b. :.,,logated and refunctionalizedon r , ': r.:rp I -Trimethylsilyl-2-alkanones
lshahi, S.P, Gupta,A., Pitre,S.V.,Reddy,M.VR., Kumareswaran, R., Vankar,YD' JOC 64' 4509( r 999).
Trimethylsilyl phenyl selenide. 20, 408 pNitroalkenyl selenides.t B-Nitroalkenyl sulfoxides undergo group exchange reactionwith Me.SiSePh. LAbe,H., Fujii,H., Yamasaki, T. SC30' 543(2000)' Y.,Harayama, A., Kinome,Y.,Takeuchi,
\4
,o LSiMe3
70%
I,.
Trimethylsilyl phenyl telluride. Reductive silylation.t Quinones are converted to trimethylsilyl ethers of hydroquinoneswith Me.rSiSePhin THF at room temperaturein excellentyield. The reactionis initiatedby a singleelectrontransferfrom the reagentto the quinones. rYamago, J. OL38,3671(2000). H.,lida,K., Yoshida, S.,Miyazoe,
Ttimethylsilyl triff uoromethanesulfonate
Trimethylsilyl(tributylstannane). Acylsilanes.t The reaction of acyl chlorides with Me.,SiSnBusis Pd-catalyzed. B-Aryl allylsilanes.2 The Pd(0)-catalyzed reaction of allenes with MejSiSnBus in the presenceofArl proceedsby addition and Stille coupling.
Y
il
+ Ph_l + Bu3Sn_SiMe3 +
(dba)2Pd
Ald.ol reactions. The \lu\r peroxyacetals4and trimethll onh rntroducethe lactonic carbonll gru
Y rn,J\-,r,r". MeOOC
85%
MeOOCTO
Ring expansion,r A Barbier-type reaction occurs when 2-(2-iodoallyl)cyclohexanonesare treatedwith a mixture of MerSiSnBur and CsF.Fragmentationfollows the intramolecular addition if a leaving group is installed at C-3 of the substrate
l,o-Bisacylsilanesundergoc1c
cyclohexanonesand, as a result,4-cyclooctenones are formed.
Srl/b
MsO
.-|
M"
A
./-<^ t -
A
\_
S{U
X1\+\A-sna" o 70% (in THF)
o 86% (in DMF)
Ring expansion. Acttr atod C-{ bond attendantthe anac\ h 8 largerring.7
I Geng, F., Maleczka,R.E. fL 40, 3 I 13 ( 1999). 2Wu, M.-Y, Yang, F.-Y, Cheng,C.-H. JOC 64,2471 (1999). rlmai, A.8., Sato,Y., Nishida, M., Mori, M. "/ACSl2l,l2l1 (1999).
Tlimethylsilyl triffuoromethanesulfonate.13,329-331;14,333-335:15,346-35O;16, 363-3 64: 17, 3'l 9-3 86; I 8, 3 83-3 84; 19, 379 -38 1; 20, 4084 10 Desilylation.t On treatmentwith Me3SiOTf and then MeOH t-butyldimethylsilyl ethersare hydrolyzedchemoselectively. t-Butyldiphenylsilylethersare not affected. Elimination.2 B-Siloxyalkyltri-2-furanylgermanesthat are adducts of silyl enol etherswith (Fu)1GeHdefunctionalizeon reactionwith Me.SiOTf. Thus, hydrodesilyloxylation is achievedby combining the two reactions. Iminium salts.3 The condensationof acetals with Me.SiNR, is catalvzed bv Me.SiOTf.
Cyclopropanation. P-Sunn ring. Methods three-membered containinga cYcloPr compounds
Tbimethylsilyl
h \lr SiSnBuris Pd-catalYzed. tr : ,'t alleneswith MerSiSnBur in
trifluoromethanesulfonate
461
Aldol reactions. The Mukaiyama-aldol reaction has been extended to using to peroxyacetals4and trimethyl orthoformates as acceptors. The latter process serves (+)-cP263114. of core bicyclic the group across carbonyl introduce the lactonic
Me3Si-OTf HC(ON4e)3
85To
J :
,li .-
t :
..:. *hen 2-(2-iodoallyl)cyclo: t'.F. Fragmentationfollows the , i..J at C-3 of the substrate
MeOOC
QH2Cl2
-78'- 0'
MeOOC
undergocyclization (live-, six-memberedrings)6with Me'rSiOTf. l,r,r-Bisacylsilanes
: rr c d . ,SiMes
(\o
Me3Si-OTf
\_<"
CH2CI2
-50"
Me3si
SiMeg
78%
86% (in DMF)
.: :
15, 346-350;16, lJ. -l-33-335; D .: . - 1 1 0 r.: :i.n \teOH t-butyldimethylsilyl r . . .r I cthersare not affected. r.. :r.it are adductsof silYl enol
internal Ring expansion. Activated fused cyclopropanes undergo cleavage of an a products containing C-{ bond attendant the attack by silyl enol ethers which leads to largerring.78
rY">.Y
Me3Si-OTf MeCN -40'
oSiMe3
\,-r
OAc 81Yo
ri \1- \rOTl. Thus, hydrodesilYloxY.
...::: \le,SiNRr is catalyzedby
of a Cyclopropanation, B-Stannyl carbocations collapse by formation and hence intermediates, active such generating for Methods three-membered ring. available'e'10 are unit, a cyclopropane compounds containing
Tbiphenylphosphine OMe l + Ph oMe
y'vsnBu"
'
!
N.4e"Si-OTf CH2C\2 40"
OMe
Ph]X
1
87%
(\'v'\cloHzt -oH
+
oEt Bu3Sn'^OEt
t
Ph3P
co
Me3Si-OTf cH2ct2 25.
rWatanabe, Y.,Mase,N.,Tateyaru! rKumar, A., Ishar.M.PS, K., Kapur,
rHunter,R., Hinz, W., Richards,P. TL 40,3643 (1999). 2Tanaka,S., Nakamura,T., Yorimitsu,H., Shinokubo,H., Oshima,K. OL2,l91l rGrotjahn,D.B., Albers, R.A., Beckman, J. SZ 633 (2000). aDussault,P.H.,Lee, R.J., Schultz,J.A., Suh, Y.S. ZL 41, 5457 (2000). 5Chen,C., Layton, M.8., Sheehan,S.M., Shair,M.D. "/ACS122,1424 (2000). 6Bouillon,J.-P.,Portella,C. EJOC 1571(1999). TSugita,Y, Kawai, K., Hosoya, H., Yokoe, l. H 51,2029 (1999). 8Sugita,Y, Hosoya,H., Yokoe, I. I/ 53, 125I (2000). eSugawara,M., Yoshida,J. CC 505 (1999). I0Sugawara, M., Yoshida,I.TL40, l7l1 (1999).
(2000)
Ttiphenylphosphinedieth$ u 387; 19,384-385;20,413 Dehydration. The Mitsur carbonylcompounds.l
a o
Ttimethylsulfonium methylsulfatedimethyl sulfi de. Methylide precursor.r Carbonyl compounds are transformed into epoxides in the presenceof KOH when they react with the mixture of these two reagentspretreatedwith sulfuric acid at 40'. IForrester, J.,Jones, R.V.H.,Preston, P.N.,Simpson, E.S.C.,/CS(P1) 3333(1999).
Ttiphenylbismuth-copper(Il) acetate. N-PhenylatinnI A method for the preparationof l-aryl-l-phenythydrazinesis via phenylationof N-arylaminophthalimides. rAoki,Y, Saito,Y, Sakamoto, T., Kikugawa, Y SC30,131(2000).
tiphenylphosphine. 18, 385-386; 19, 382-383; 20, 411412 Alkyl sulfinates.t Reductive esterification of ArSO2Cl with Ph.,P, and in situ sulfinylation,is accomplishedin one flask. By using a chiral alcohol in this process,two diastereomers are obtained [8 + 2]Cycload.dition.2 Zwitterionic adducrs from PhjP and allenyl kerones or 2,3-butadienoic estersare dipolarophiles toward tropone.
The homobenzopyran s\st butenols2at room temPerarureI are not fonned.
/>/^ 9o"
Inverted sugars.s A syul ring openingandreclosurerra ( by a Misunobu n accomplished
Thiphenylphosphine-diethyl azodicarborylate
?
:
-,
OMe |
..t
Ph"^'v\
Ph3? :c-- - t c o R - Ph3P .'{--con+-\
(}"
G"
87o/o
coR H
a-\
I
I l)"'CrcHzt \^,i H 85%
) . . - , K 0 L 2 . 1 9 1 1( 2 0 0 0 ) . 'l'-
70-95yo
: r)()).
; l : : - r l 4 {2 0 0 0 ) .
' Watanabe, Y.,Mase,N.,Tateyama, M.,Toru,T. TA10,737(1999). rKumar, K., Kapur, A.,Ishar,M.P.S. OL2,787(2000). Triphenylphosphine{iethyl azodicarboxylate.13, 332;14, 336-337; 17,389-390;18, 387; 19,384-385;20, 413 Dehydration. The Mitsunobureactionconditionsinduceconversionof l,2-diols to carbonylcompounds.l
'c-."' OH
cHo
Ph3P- DEAD PhH O'
? fr )!
V, 75To
.lormgcl into epoxidesin the r\\o reagentspretreatedwith
r.r.1.t (1999).
The homobenzopyran system is readily elaborated from 4-(2-hydroxyaryl)-2butenols2at room temperature as shown in the following equation. Dihydrobenzofurans are not formed.
.,n I- I-phenylhydrazinesis via .2\r,-\--
I ll Vo, J:
..:I]
| \o"
Ph"P ' - DEAD
Z
.^"'/---\
-l ll rHF2s' Vo/
\}-
87To
\':o Cl with Ph.,P,and in situ r .: .:.tl alcoholin this process,two rr':. Ph,P and allenyl ketones or
|}(
Inverteil sugors.s A synthesis of L-hexoses from o-glucono-1,5-lactones involves ring opening and reclosure via O-benzylhydroxamic acid intermediates.The latter step is accomplishedby a Mitsunobu reaction.
TFiphosgene
D., Bhawal.B,\l . Krishnaswamy,
._OBn a-OBn Ph3P-DEAD -;;-;i ]_o "B?oV:o, r{Hr ano,$-oH nHoBn egf;$f\-*orn
71Yo N-Allcylations. ,S-methylisothioureas,
The Mitsunobu and
hence
guanidines.a l, l-Dialkylhydrazines
protocol is applicable to N-alkylation the
preparation
of
unsymmetrically
of protected
TFiruthenium dodecacarbooYl Atninatians. Allylic amu madeup of Ru:(CO)r: and a tns Aromatic ketimines are fon Interestingly, styrenesafford ad
substituted
are similarly accessible.5
'Barrero,A.F., Alvarez-Manzaneda, E.J.,Chahboun,R. ZL 41, 1959 (2000). 2Yamaguchi,S., Furihara, K., Miyazawa, M., Yokoyama, H., Hirai, Y. TL 41, 4757 (2000). rTakahashi, H., Hitomi, Y., Iwai, Y., Ikegami, S. JACS 122,2995 (2000). aKim, H.-O., Mathew,F., Ogbu, C. SL 193 (1999). sBrosse,N., Pinto, M.-F., Jamart-Gregoire,B. JOC 65,43'10 (2000).
Tliphenylphosphinediisopropylazodicarboxylate.15, 352-353;17, 390;18, 387-388;19,385;20, 413414 Isocyanates.t N-Carboxylationof amines with carbon dioxide followed by treatmentwith Ph.1P-DIAD deliversRN-{:O. pl-actams.2 Hydroxamic acids obtained from aminolysis of B-lactoneswith O-benzylhydroxylamine undergocyclizationagainwith Ph3P-DIAD. Ph BnONH2 Ph3P- D|AD Et2o 25
/t
l-l 5f*-orn
Ph_NH
Ph_NH
Fo Cyclocarbonylations. ard via carbonylation alcohols 1-Lactones with a different sub from ketones (including o{tlc
74Yo rHorvath, M.J.,Saylik,D., Jackson, WR., Elmes,PS.,Lovel,C.G.,Moody,K. TL 40,363(1999). 2Yang,H.W.,Romo,D. JOCU,'7657(1999).
Ph-Ycm o
Tliphenylphosphonium bromide. Bromohydrins.r As a source of hydrogen bromide, [Ph:PH]Br is useful in opening of epoxides. rAfonso,C.A.M.,Vieira,N.M.L.,Motherwell, WB. 54 382(2000).
Tiiphosgene. 18, 388; 19, 386; 20, 415416 plactams. Carboxylic acids are converted to ketenes by a mixture of triphosgene and triethylamine. The nascentketenescan be trapped with imines.l
Under a CO atmosphere i converted to unsaturated t-h 5-alkynaldimines.T When ethylene is also pt products are deconjugatedand
Ttiruthenium dodecacarbonyl rKrishnaswamy, D., Bhawal, B.M., Deshmukh, A.R.A:S. TL 41, 4I7 (2000).
-OBn --s-\--O .^.r '3io$-*orn
71% pr'.:..rblc to N-alkylation of protected o:,,t unsymmetricallysubstituted
Tliruthenium dodecacarbonyl. 18, 308; 19, 386-387 ; 20, 416417 Aminations. Allylic amination with nitroarenesr is catalyzed by the Ru complexes made up of Ruj(CO)12and a bis(arylimino)acenaphtheneunder CO. r Aromatic ketimines are formed by hydroamination of l-alkynes with arylamines.2 Interestingly, styrenesafford adductsfrom o-aminoarylation.r
:'..: ^ Ii.
: Jl .e59(2000). H ii:r:r. Y.TL4l,478l (2000). t.:..<,1000).
Ph Ph_NH +
Rug(co)rz, fu-]f Pn ,n-
ill
70'
ll 85%
- rtr).
H tr. 15.-152-353;17,390; 1.8,
ph-N/H * rr::h carbon dioxide followed by
Ru3(CO)r2
('n
Wtn
n ::. .rminolysis of B-lactones with *:::. ['h.P DIAD.
-Nl
-OBn
/Y*I
83%
Cyclocarbonylations, Formation of 1- and E-lactones from the proper allenyl alcoholsvia carbonylationand cyclization by heating with Ru.(CO),2-CO is observed.a 1-Lactones with a different substitution pattern are formed by a[2 + 2 + l]cycloaddition from ketones (including ct-diketones),ethylene, and carbon monoxide.5
74%
':.'oo"" r: , (l . Moody,K. TL40,363(1999).
Ph
_
COOMe
Ru3(CO)12
tl F^f -J
cr..::. IPhrPH]Bris usefulin opening -
l-\ \
I
\--.1-P , / l
CO - ethylene PhMe 160"
"Y 94%
- , r t )
) \r:jncs by a mixture of triphosgene ) c . \ : l hi m i n e s . r
Under a CO atmosphereand in the presenceof Rui(CO)12, 1-aza-1,3-dienesare converted to unsaturated ry-lactams.6Bicyclic lactams are formed in the reaction of 5-alkynaldimines.T When ethylene is also present in the reaction involving conjugated azadienes the products are deconjugatedand ethylated at the ct-position.8
Ttiruthenium dodecacarbonyl
Tris(xcrrR
R=Z=_zN.o, ''
Ketone synthesis,tt A merhc
\--\_
R"(CO)" CO- ethylene
-i-methyl-2-aminopyridine and e\Pl to stabilize cyclic rhodia-ketinunc r In situ hvdrolvsis of the demetalata
/ \ \ 04tt'
150"
R' R = R'= Ph 49Yo
rrY \*AttH
3-Alkoxy-2-cyclopetenones.e In a cycloaddition processwith alkenes,cyclobutenediones participate after losing [CO]. This method is complementary to the Pauson-Khand reaction
+
\\Z\
PhMe
' -J:'
Ph
n'\
7x.C
- Et3P RU3(CO)12 CO / THF '160"
1+c
\-o
o R=Bu 75%
Deacylation.to Removal of an entire acyl side chain from an aromatic ketone occurs when the acyl group is ortho to a potential ligand for ruthenium. Accordingly, this processexhibits excellent regioselectivity in the casesof certain diacylarenes.The importance of the coordination is shown by the fate of a B-(2-pyridyl)-ct,B-unsaturated ketone.
rRagaini,F., Cenini, S., Tollan. S . Tur rTokunaga, M., Eckert, M., tA'aliat-
rYoneda,E., Kaneko,T.. Zhang. S -\r tChatani.N., Tobisu,M., Asaumr.T f "Morimoto, T., Chatani,N.. Muru. S : -Chatani, N., Morimoto, T., Kamtum. sBerger,D., lmhof, W CC l-{57 ,1999 ''Kondo, T., Nakamura,A., Okada.T : ')Chatani.N., Ie, Y, Kakiuchi. F.. \lurt : r J u n .C . - H . .L e e , H . , P a r k ,J . - 8 . . L . t . I
Tf is(acetonitrile)cyclopentadhoy
3 ? r y c"",]\11-/$f^-
Addition
**,-fi-7-JJ( ;# (/ 160"
o
to alkynes
and
.l
alkenes proceeds regioselectl\ r'l\ presence of bromide
salt(s I an ;
proceeds.2
Bs%
,2 CoHrs
o ' \tA
Ru3(CO)12 CO i PhN4e 160"
90Yo
Couplings involving allenrl al accompaniedby the formation of I amines are tolerated in thesereact
Tf is(acetonitrile)cyclopentadienylruthenium(I)
R
\2\ "
Ketone synthesis.lt A method for ketone synthesis is based on N-allylation of 3-methyl-2-aminopyridine and exploiting the coordination ability of the pyridine moiety to stabilize cyclic rhodia-ketimine intermediatesthat are active in insertion to l-alkenes. In situ hydrolysis of the demetalatedketimine products affords ketones.
N ,/ x
a =Ph
hexafl uorophosphate
49%
rrY \N.ANH
f :, \ !"\ with alkenes,cyclobutener:-.:.i nlentary to the Pauson-Khand
Rus(CO)rz
. (2"-
\NtAN
\NtAN
tl
PhMe 130'
Ph
rY
'r'Y i l l Ph
R'"--t"t-\,,,,\
n'\
n^\Ln
I
I
t-
t"
o
o
tH.o
lH.o
Ph
R,-..-,,]t*
R=Bu 75%
B .:.rln tiom an aromatic ketone il.rr.i lrrr ruthenium. Accordingly, s :. r'. rri certain diacylarenes.The or .. .i l-pyridyl)-a,B-unsaturated
nt\.V*
rRagaini,F., Cenini, S., Tollari, S., Tumrnolillo, G., Beltrami, R. OM 18' 928 (1999)' 2Tokunaga,M., Eckert, M., Wakatsuki, Y. ACIEE 38,3222 (1999). r u c h i m a r u ,Y C C l l 3 3 ( 1 9 9 9 ) . aYoneda,E., Kaneko,T.,Zhang, S.-W.,Onitsuka,K., Takahashi'S OL2' 441 (2000). 5Chatani,N., Tobisu,M., Asaumi, T., Fukumoto,Y', Murai, S. ,/ACSl2l"7160 (1999)' 6Morimoto,T., Chatani,N., Murai, S. JACS 121, 1758 (1999). TChatani,N., Morimoto, T., Kamitani, A., Fukumoto,Y., Murai, S. JOMC 579' 177 (1999). sBerger,D., Imhof, W. CC 1457 (1999). eKondo,T., Nakamura,A., Okada,T., Suzuki,N., Wada,K., Mitsudo, T JACS 122' 6319 (2000)' r{}Chatani, N., Ie, Y, Kakiuchi, F., Murai, S. "/ACS121, 8645 (1999). l r J u n ,C . - H . ,L e e ,H . , P a r k ,J . - B . ,L e e ,D . - Y . O L l , 2 1 6 1 ( 1 9 9 9 t .
hexafl uorophosphate.
Tris(acetonitrile)cyclopentadienylruthenium(I) Addition
to alkynes
and
allenes.
An
ene-type
reactionr
between
alkynes
and
alkenes proceeds regioselectively at room temperature with [CpRu(MeCN)r]PF,,. tn the presence of bromide sa(s) an atom-economical coupling of l-alkynes and enones Droceeds.2
85%
i> 4N'u \.-'
-z
CoHts-
+ -
\.r\
ff
B r [cPRu(MecN)3]PF6 cuH,,.,A,,.-A
O
LiBr- snBr. l\4e3CO
8 8 %( E : Z 1 : 6 . 6 )
Couplings involving allenyl alcohols and amines (without halide incorporation)are accompaniedby the formation of heterocycles.r'aMany functional groups including basic aminesare toleratedin thesereactions.
This(acetonitrile)cyclopentadienylruthenium(I)
hexafl uorophosphate
Bn
Ttis(dibenzylideneacetone)dipalleditr 389-393; 19' 388-390; 20, 41742O
I
-NH _^_
lCpRu(MeCN)3lPF6
* a>/R tl o
( /-"\_J4 n=1,2
Substintion reactinns of allylic tw substitution by MeCOSK with (dbatJ benzodioxanes are readily formed rn i carbonates.2
l\4eAlCl2 + cocatalysl DI\4F
R=Me,Ph
Cyclnisomerizations. 1,6-Enynes and 1,7- analogues cyclize to furnish 2-vinyl-lmethylenecycloalkanessin the presence of [cpRu(MecN)3]PF6. The regioselectivity is contrary to that catalyzed by Pd-catalysts. Substitution pattern of the substrateshave profound effects on the products of the Ru-catalyzed reaction. For example, cycloheptenederivatives may be generated.6
z'>/oH l \,
l
l on
lll + l Aocoorr
'r<
Ph
-
lCpRu(N.4eCN)3lPF6 l\y'e2CO
COOMe
Ph
o'.-o
.<
ff-coon,r" 77o/o
Cycloadditions. When the double bond of 1,6- and l,7-enynes is connectedto a ketoneTor cyclopropaneunit,8'ethe cycloadditionreactionpathwaysprevail.
/.
--R
-
u
lCpRu(MeCN)3lPF6
Lr-;f\ .o \___.(/ \\
B-Siloxy-e-acetoxy-1,0-unsatuiucd sition on exposureto HCOOML. (dbarf products with (all) syn-isomers predm
(
aldol access to the substrates. thrs 1 polyketide synthesis. The scoPe and lll N-Arylation. N-arylation with ArBr has been defrrd'
any problem.s Sodium alkoxides cooter. basesin the N-arylationreaction.6
Besides BINAP, biphenylphosphtr particularty the N-arylation of indoles- r of the reaction enablesprotection of akr releasethe alcohol moiety on conversto! Usually, only one halogenated sitc t also exhibits chemoselectivity as gerrrrl
R'
cl
n=1,2
I
ur A7 rTrost,B.M., Machacek,M., Schnaderbeck,M.J.OL2,1761 (2000). 2Trost,B.M., Pinke(on, A.B. A CIEE 39,360 (2000). 3Trost, B.M., Pinkerton, A.B., Kremzow, D. JACS 122, 12007 (2000\ aTrost, 8.M., Pinkerton, A.B. "IACS l2l, 10842 ,]1999). sTrost, B.M., Toste, F.D. JACS 122,714 (2000',. 6Trost,B.M., Toste,F.D. JACS 121,9728 ,11999\. TTrost,B.M., Brown, R.8., Toste,F.D. JACS 122,5877 (2000). 6Trost, B.M., Toste, F.D., Shen, H. JACS 122,2379 (2000). 'Trost, B.M., Shen,H. OL2,2523 (200U.
I t
\z\",
I
( d b a ) 3 P d 2 ' D P P F(
RNH2
I
Aryl hydrazides such as ArN(BctI BocNHNH2). I I A phosphine-freecardyr 1,3-bis(2,6-diisopropylphenyl)imrdazolr this additive becomesligated to the Pd r
Trb{rtibcozylidencccctom)diFtrtd@
&9
tl.hph!tr
14'339;15'353-355; 16'372;17'394:18' Tris(dibenzytideneacetone)dipalladium' 389-393r19,388-390;20,417420 accessto allylic thiolsl is based on Subsfinfian reactions of allylic systems' An as catalyst. 2-Alkylidene-3-alkyl-1,4substitutionby MeCOSK with (dba)rPdt-dppb catechols and propargylic are readily formed in a reactionbetween benzodioxanes carbonates.2 ! L . . . \ i l r r c t o f u r n i s h2 - v i n y l - l is I'l: The regioselectivitY C\ f, . -.t. on the Productsof the a: . .' :nJ\ be generated.6
F.
( l \Ao,.,
ill lll
l+
- (R)-BINAP (dbahPdz
l Ao"oo""
rHF25"
4->ao-/ t i l l \,4g"\
99%
Ph
J . , o -f
COOMe / 77%
-'!'n)'nes is connectedto a 3: .: [ . :::]\\a!s pfeVail.
.y''g
>,- . ,./\^,
undergo reductive transpop-Siloxy-e-acetoxy-"y,6-unsaturatedcarbonyl compounds and BurP in DMF to afford the 8'e-unsaturated sition on exposure to HCoONlIa, (dba)rPdz' In conjunction with the enantioselective products with (all) "yr-oo-"*-pt"dominating'3 aldolaccesstothesubstrates,thisprocessexpandsthemethodologyofexisting polyketide sYnthesis. of the Pd-BINAP combination for N-Arytntion. The scope and limitations without 2,4-Disubstituted azetidinesare arylated N-arylation with ArBr has been defined.a suitable be to a p-hydrogen atom are shown any problem.5 Sodium alkoxides containing basesin the N-arylationreaction'6 have found use in these reactrons' Besides BINAP, biphenylphosphine ligands particularlytheN-arylatronorinaotes'andvinylogousamides.8Moreover,theefficiency as 4-halobenzyl ethers,9becausesuch esters of the reaction enablesprotection of alcohols ROC6IIaNHBn and treatment with SnCIa' releasethe alcohol moiety on conversion to
R
* ..
-4\-OH
Usually,onlyonehalogenatedsiteofapolyhaloareneissubstituted'lOThereaction expected'
K
also exhibits chemoselectivity as generally
c
cl
,iYt' V\",
- DPPF (dba)3Pd2
l H
H
Y****il-**, cl
ArylhydrazidessuchasArN(Boc)NH2areavailablebythismethod(fromArBrand for for N-arylation specifies addition of BocNHNH2).rr A phosphine-freecatalyst system from chloride'r2 Apparently' carbene derived 1.3-bis(2,6-diisopropylphenyl)imidazoiium this additive becomesligated to the Pd atoms'
Ttis(dibenzylideneacetone)dipalladium
Other aromatic substitutions. Aryl cyanides can be preparedfrom aryl chlorides in the Pd(0)-catalyzed reaction with Zn-Zn(CN)2,13 and from aryl bromides and iodides, with CuCN.Ia
Synthetically useful methods er.olrc I of cyclobutanols2sand capture of pall' intramolecularHeck reaction.:6
Benzannulatedoxacycles are formed by ring closure of o-bromoarylalkanols.ls Suzuki and Stille couplings. The coupling of sterically hindered ArBr with phenylboronic acid in the presence of (dba)jPd2, (MeO)rP, and KIPOa is not problematic.r6 By using a (dba).,Pd2-t-Bu:P-KF catalytic system, the Suzuki coupling operateson a wide range of aryl and alkenyl halides, typically at room temperature,with a reactivity profile showing ArCI > ArOTf.r7 Very similar reaction conditions are effective to achieve Stille cross-couplings.18
H O H
+ Ph
f-ff* \,,r
R
l,l-Dibromoalkenes afford (E)-bromostilbenes by the Suzukire or the Stille protocol.20Diarylacetylenes are obtained when the Stille coupling is conducted in the presenceof a tertiary amine.
MeooC{
MeOOC (dba)3Pd2.cHc
\__r
)_sr
(o-Tol)3P-KCk
Br
THFI
( \
n
Bu.sn{") \__{/ (4-An)3Pi DMF
MeOOC
i-Pr2NEt 80'
91%
Facile Suzuki coupling is also effected in the presenceof the 1,3-dimesitylimidazol-2ylidene ligand.2r Related to the original Suzuki coupling is the ketone synthesis from acid chloride and trialkyl boranes22and thiol esters with arylboronic acids.23The latter procedure is Pd-catalyzedand Cu-mediated. Heck reactian The possibility of applying the Heck reaction to achieve multibond formation is once again substantiatedin the elaboration of the xestoquinoneskeleton.2a
Other couPling reactions. Far effectivenessof a carbeneligand for Fd I imidazolium chloride has been notcd leading to diarylacetylenes,the ligard o(
Symmetrical and unsymmetrical l-l Alkynylpalladium intermedu alkenes.2e the reaction medium. On the other ha of other 1-alkynesfor their ultimate rn Zircona-arenes are readily fonncd I from such species and ArX afford funl (e.g.,iodination).30
\---"t
(] X = O halenaouinone X = H,H xestoquinone
BuLi/THF -50' cp22(Me)cl
)-, \_/
Ttis(rlibenzylideneacetone)dipalladium
s . in he preparedfrom aryl chlorides in ' ..:rJ tiom aryl bromides and iodides,
Syntheticallyusefulmethodsevolvefromcouplingafteraregioselectiveringopenrng that are generated from an of ciclobutanois25 and capture of p-allylpalladium species intramolecularHeck reaction.26
rs l. . -rc,rl o-bromoarylalkanols. rn- ,'t qterically hindered ArBr with r i'.: . (MeO)jP, and KjPOa is not ..::.:lrtic system, the Suzuki coupling dt.. :r pically at foom temperature,with
Hli (dba)rPdr'cHcl3
Ph
+ ph_Br-,;^^-
K2CO3/ dioxane
:imilar reaction conditions are
\::.
ft-'|""'\tn
9,.,,.rn R
1oo"
R= H 96% R=Me 95%
:r.:. hr the Suzukire or the Stille r': \trlle coupling is conductedin the
a\ '1,'
Q",
-*u+o
-N'oo/
a )
91Yo
pi-'r nrc of the 1,3-dimesitylimidazol-2hr r.r'loncsynthesisfrom acid chloride It : ,rre acids.z3The latter procedureis I :::: l{c'ck reactionto achievemultibond ri . It ()l'thexestoquinoneskeleton.2a
),,,,y'-.
(dba)3Pd2'CHCl3 (o-Tol)gP- KOAc THF A
N
N
N' I
SEM
SEM
SEM
(1
leadingtodiarylacetylenes,theligandofpreferenceistris(mesityl)phosphine'28 prepared from 1'l-dibromo-lSymmetrical and unsymmetrical l,3-diynes have been when cul is present in homocoupling undergo alkenes.2eAlkynylpalladium intermediates can await addition intermediates persistent the the reaction medium. on the other hand, of other l-alkynes for their ultimate transformation' The coupling products derived Zircona-arenesare readily formed from aryllithiums. regioselective functionalization for opportunity from such speciesand ArX afford further
\ - - l\ \ .
/ \.._^o l
/ +
+
o
o
X = O halenaquinone X = H,H xestoquinone
1)
(ArMgX + Ar'X)' the Other coupling reactions. For the Kumada coupling 1,3-bis(2,6-diisopropylphenyl)from situ in formed effectivenessof a carbeneligand for Pd sonogashira coupling imidazolium chloride has been noted.2?In a low-temperature
(e.g.,iodination).30
,\
471
\
-50"; )a-,zrxcp BuLi/rHF cp2z(Me)cr
\--l
- DPPP (dba)sPdz
u,$.' 12| CH2C|2
Tf is(dibenzylideneacetone)dipalladium
The Negishi coupling is applicable to the synrhesis of B- and ^y-aminoacid derivatives.31
(dha.P3-
-'" | Et3Si
r/-\i^cooMe NHBoc
lZnl/\)/ cooMe Nttgoc
--
(dba)3Pd2
ph-^\^COOMe
(o-Tol)3P
:
"
/\ f\ -1:/-T-\
-l
flggoc
Ph-l
lPd(c&: 73o/o
laat> FTT?
[2 + 2 + 2]Cycloadditions. Several versions of this reaction have been developed, leading to hexabenzotriphenylene (trimerization of benzyne)32and heavily substituted dihydroisobenzofurans.33
S i M e"a
CsF- (dba)3Pd2
.................."......................'.-'.'MecN 25
OTf
39Yo
Isomerization of cyclopropanols. Ring opening of cyclopropanols gives enoneson Pd-catalysis. Formation of ct-methylene ketones is favored by the use of (dba)qpd2, molecular sieve 44, and benzoquinone(reoxidant) in toluene.3a
Rj (dba)3Pd2
A
HO
p-benzoquinone MS 44 / PhMe
R' ^ l "Y\ tl
o
Reductive cyclization.3s 1,6-Enynes cyclize to give 2-methyl-l-methylenecyclopentanes on treatment with (dba)3Pdz,PhrP, and EtrSiH. Inrerestingly, a different isomer predominates when the same substrates are exposed to pd(OAc)2, phrp, and HCOOH.
!
lDivekar. S., Safi, M., Soufiaour.\l . S 2Labrosse,J.-R.,Lhoste,P.' Sincu- D l rHughes,G., Lautens,M.. lrtv'en. C ()l aWolfe,J. P.,Buchwald, S. L.. Tornwt5Marinetti. A., Hubert, P.. Genet- J -P /
6Prashad,M., Hu,8., Lu, Y.. DraPa. R 7old, D.W., Harris, M.C., Buchraid S 8Edmondson,S.D., Mastracchlo.A h ePlante,O.J.,Buchwald, S. L.. Sc.tEtl roBeletskaya,I.P., Bessmertn.vkh.A 6 . ttWang,Z., Skerlj, R.T., Bridger.GJ I r2Huang,J., Grasa,G., Nolan. S-P Ot l rrJin, F., Confalone,P.N. fL 41. -1::l ' raSakamoto,T., Ohsawa, l<. JCStP I ' 1 r5Torraea, K.8., Kuwabe, S.-1..Brr-lnr r6Grifflths,C., Leadbeater,N.E. fL ll. r?Littke.A.F., Dai, C., Fu, G.C. .r'{('J I rsLittke.A.F., Fu, G.C. ACIEE 3t. :Jl reShen,W. SL'137 (}UJO). 2 o S h e nW, . , W a n g ,L . J O C 6 . 8 8 - 3 ' l ( 2tZharlg,C., Huang, J., Trudell. \l L. I r2Kabalka,G.w., Malladi, R.R.. Tcr* 2rLiebeskind,L.S., Srogl,J. JACS l2l 2alau, S.Y.W.,KeaY,B.A. SL 6O5I l9{l 2sNishimura,T., Uemura,S../ACs l2l l6Overman,L.8., Rosen,M.D.,'f Crff 27Huang,J., Nolan, S.P.JACS l2l. St rsNakamura, K., Okubo, H.. Yamagri 2qShen, W., Thomas,S.A. OL 2' :85- ' 3oFrid.M.. Percz,D., Peat.A.J.. Bu-hr 3lDexter,C.S., Jackson,R.F.!*'..Llhfi 12Pena, D., Perez,D., Guitian. E . Cx 33Yamamoto,Y., Nagata,A.. ltoh. K I r a P a r kS . . - B . ,C h a ,J . K . O L 2 . l t ; t f i r5oh, C.H., Han, J.W., Kim. J S. t (2000).
Tris(dibenzylideneacetone)dipalladium
mlir'.rr of p- and ^y-aminoacid deriva-
:Da)3Pd2 pnrr-\-.ACOOMe e'ror)3P
NHBoc
Ph-l
(dba)3Pd2 - Ph3P
{'s
73Yo
{tr.-g'R47To
5o/o
,/t"'-'
HCOOH PhN4e 60'
l-\\ / 1 \ - 7--f-\ / l \ 69%
n\ I
thls reactionhave been developed, rcnzyne)32and heavily substituted
\"YY? =-Y
:7O
\ I \ 4
39o/o
,t cl'clopropanolsgives enoneson
iti
.rrored by the use of (dba)jPd2, l uene.l{
s t'
,-\
R' I
c
V. tr:, ;
::l
' give 2-methyl-l-methylenecyEt.SiH. Interestingly, a different r'\posed to Pd(OAc)r, PhrP, and
rDivekar, S., Safi, M., Soufiaoui, M., Sinou, D. Z 55' 4369 (1999). 2labrosse. J.-R., Lhoste, P., Sinou, D. TL 40,9025 (1999); OL2' 52'7(2000)' rHughes,G., Lautens,M., Wen, C. OL2' 107 (2000). aWolfe.J. P..Buchwald, S. L., Tomori, H., Sadighi' J.P, Yin' J' JOC 65' 1144' 1158(2000)' 5Marinetti, A., Hubert, P, Genet, J.-P.EJOC l8l5 (2000). 6Prashad,M., Hu, B., Lu, Y, Draper,R.' Har, D., Repic, O., Blacklock,T'J' JOC 65,2612 (2000)' 7Old, D.W., Harris, M.C., Buchwald, S.L. OL2,1403 (2000). sEdmondson,S.D., Mashacchio,A., Parmee,E.R. OL2' 1109(2000)' ePlante,O.J.,Buchwald, S. L., Seeberger'P.H.JACS 122'7148 (2000)' r{)Beletskaya, I.P.,Bessmertnykh,A.G', Guilard, R. SZ 1459 (1999)' rrWang,2Z.,Skerlj, R.T., Bridger, G.J.TL40,3543 (1999). r2Huang,J., Grasa,G., Nolan, S.P.OL 1, 1307 (1999). r3Jin.F.. Confalone, P.N. IL4l, 32'71(2000). raSakamoto, T., Ohsawa,K. JCS(PI) 2323 (1999). r5Torraea,K.8., Kuwabe, S.-I., Buchwald' S.L. JACS 122' 12907 (2000)' r6Grifflths, C., Leadbeater,N.E. ZL 41, 2487 (2000). r?Littke, A.F., Dai, C., Fu, G.C. JACS 122' 4O2O(2000)r8littke. A.F.. Fu. G.C. ACIEE 38,2411 (1999). reShen,W SL'73'7(2000). 2oShen, w., Wang,L. JOC 64,8873 (1999). 7tZhang,C.,Huang,J., Trudell, M.L., Nolan, S.P-JOC g' 3804 (1999)' 22Kabalka,G.W., Malladi, R.R., Tejedor,D., Kelley, S. TL 41,999 (2000)' 2rliebeskind, L.S., Srogl, J. JACS 122, 11260 (2000). 2alau, S.Y.W.,Keay,B.A. SL 605 (1999). 25Nishimura.T.. Uemura,S.,/ACSf21, 11010(1999). r6Overman.L.8., Rosen,M.D. ACIEE39' 4596 (2000). 2?Huang,J., Nolan, S.P..IACS121,9889 (1999). 2sNakamura,K., Okubo, H., Yamaguchi,M. SZ 549 (1999). 2eShen. W.. Thomas,S.A. OL2,285'1 (2000). 3{)Frid,M., Perez,D., Peat,A.J., Buchwald, S.L. JACS l2l'9469 (1999)' rrDexter. C.S.. Jackson,R.F.w., Elliott, J. JOC U"7579 (1999); r 56' 4539 (2000)' 32Pena, D., Perez,D., Guitian, E., Castedo,L. OL1,1555 (1999). 33Yamamoto, Y., Nagata,A., Itoh, K. zL 40, 5035 (1999). raPark,S.-B., Cha, J.K. OL2, 14'7(2000). 3 5 O h ,C . H . , H a n , J . W . , K i m , J . S . , U m , S . Y . , J u n g , H ' H ' , J a n g ' W H ' ' W o n , H ' S ' T L 4 l ' 8 3 6 5 (2000).
Tris(dibenzylideneacetone)dipalladium-chlomform
Tlis(dibenzylideneacetone)dipalladium
19, 39V392; 20, 420422 Fragmentative elimination. Cyclobutoxime benzoatesare converted to unsaturated nitriles (except for the 3,3-disubstitutedmembers whose products cannot accommodatea doublebond).r
(dba)3Pd2.CHCl3
tn{:*b"o*
*
,n/s-"*
(+)_BtNAP K2CO3/ THF A
,nJr.--""
84%o (dba)3Pd2.CHCl3
,**oaz \.,/--
(+)-BtNAp K2CO3/ THF A
An intermolecular couPling toll provides a key intermediate for the s1
\,,,,\N
\.--1 l N ur*. --:+=_/ Br
-
COOBn
4o/o
aN"* \\-\ 79%
(dba)rPdz'cHCrr f-k.*
a)^:,
\J v
be. ^,i1.'ilii o \J
-
67o/o Hydration of vinyl epoxides. l,2-Diols are formed from the pd(0)-caralyzed ring opening with bicarbonate ion,2 in contrast to conventional atlylic substitutions of such substrates. coupling reactinns. Scopes of many well-established reactions continue to be explored. The Heck reaction of alkenyl(2-pyridyl)dimethylsilanes is benefited by the direction of the heteroaromatic group during carbopalladation and the expediency in product purification and catalyst recovery.3
o-Diallylbenzenes are generatd ' involving benzyne intermediates Tl
oTl SrMq
N\ _
n,Zts,&
ll
./-\
|
(dba)3pd2.CHct3
+ Ar-t -^.:-::.*
T:::)
lr\ tt
Ar--Z'gi/2
I
f, ,''.
Useful structuresarise from regioselective coupling of alkenylstannaneswith benzylic bromides,a that of alkynylstannanes with allenyl bromides,s and hydrosilanes with alkenyl iodides.6
Cycloadditions. When onll t results in the formation of 9-sutrun synthesizedusing allyl tosllates el ligand allows 1-alkynesto panrcrFr
K
//r ,n-z-,
Ph'-z-si(oeo,
+ (Eto)3SiH ffi 25
g17.o
R
J R'J/
OTs
Ttis(dibenzylideneacetone)dipalladium--chloroform
rm. 19.390-392;20,420422 to unsaturated areconverted [!.:.1,r3tes a cannotaccommodate rh, .c products
Anintermolecularcouplingfollowedbyanintramolecularcyclizationintandem provides a key intermediate for the synthesisof ellipticine'7
I
\--.\
t r *
,z^\.cN
*
,nl-.--"*
Z\--\ I ll \,,,,-N
t'\)-BEt3
+
f
B --:=..-/
'ru-cooBn
r
ar
(dba)3Pd2'cHcll
l PhgP / THF 60'
booen
COOBn
4%
!-1',
64%
-CN
( !
l1
'.\
{"* a ' - c
elliPticine f :': rJ irom the Pd(0)-catalyzedring of such rrr:: .nrl allylic substitutions -<.:,,-.r.hedreactionscontinue to be rl .-:.::.rthylsilanesis benefited by the rt\ :,...rda(ionand the expediencyin
reactlon sequence o-Diallylbenzenes are generatedfrom a formal addition-alkylation halides' allyl and allylstannanes are involving benzyne mtermediates.sThe reagents orf
AYll Rr-
(dba)3Pd2'cHcrJ Z#
- . - K i t l DPPF CsF i MeCN
\,,,\
siMe3
\r,^\-r\
,i\,,/.snBu3
Z\,.c1
r.r\-rI
.-
ll
:"'
|
5:
,z-'r
R
Cycloadditions.Whenonlytheallylhalideispresent,theprecedingreaction benzenescan be results in the formation of 9-substituted phenanthrenes.ePolysubstituted synthesizedusingallyltosylatesandstablealkynes'Furthermore'using(PhO)rPasa ligand allows l-alkynes to participatein the reaction'ro
with benzylic ll::.-,t alkenylstannanes rl ^:,nrides.sand hydrosilaneswith
R
/ c-
Ph
v
,/;
.
R
\
-si(oEt)3
J
t,:
81Yo
R'J/
(dba)3Pd2'CHC|3 *
OTs
R
P h . P ,c t c H r c H r c l R'
R
Tiis(dibenrylideneacetone)dipalladiurn-chloroform
N-Protected2-amino-l-en-3-ynes undergo [4 + 2]cycloaddition with l,3-diynes regioselectively,thereby making many 3-substituted4-alkynylaniline derivativesavailable.rr 1,3-Oxazin-2-imines are prepared by trapping the zwitterionic species generated from vinyloxetanes and (dba)jPd2.CHCl3 with carbodiimides.r? The benzoannulated oxo-analoguesare derived from carbonylated 2-iodophenols.13
\ p n
llPh + C
(Y*Y*'n
(dba)3Pd2.cHcr3 . +
II
DPPE/THF
NPh
\v4"v'o H
A regioselective Diels-Alder reaction between 1,2,4-alkaltrienes and conjugated 14 dienes occurs in the presenceof (dba).,Pd2.CHCl.r.
R' R'\ + -_J
(dba)3Pd2. cHcr3 -
-.
CH2C|2
. \
_
Tris(dimethylarnino)phmPbonc As bases.t The ylides t\lc-l andthe Hc nitroaldolcondensation,
IPalacios,F., Aparicio, D., de los Saotcr
98%
tr<\-R .c
eYoshikawa.8., Yamamoto, Y. ACIEI I roTsukada,N., Sugawara,S., lnoue. \' 0 rrSaito,S., Uchiyama,N., Gevorgran-\ r2larksarp,C., Alper, H.,/OC 6f. {15: , r3larksarp,C., Alper, H. "/OC 61. 9lcl , laMurakami, M., Minamida, R.. ltan. K rsBraun.M., Laicher,F., Meier. T..4ClE)
J ./-\
'A R"<: \
R'
/"'R
Tris(dimethylamino)sulfonium dl Cleavageof N\2-trimcthyS on treatmentwith theur decompose I Dauben. P., Dodd, R.H. ./OC 6{. 5Ix
,
Tris(dimethylphosphinito)pletir Amidesfrom nilrilcs.t Nitnle at 160'to affordamidesin modcrar
Allylic displacements. l,l'-Bis(diphenylphosphino)ferrocene renders the Pd(0)catalyzedalkylation of enolatesusually highly diastereoselective.rs
R R-CN + R"
tl t \-/
i-PrMgCl
l
(dba)3Pd2. CHCI3 ferrocenyl(PPh2)2
Ffo. R-CN + H2fi
PhV\YP, OAc
'Nishimura, T., Uemura, S. ./ACS 122, l2M9 (2Om). 2Trost,B.M., McEachern,E.J.JACS l2l,86/19 (1999r. 3ltami, K., Mitsudo, K., Kamei, T., Koike, T., Nokami, T., Yoshida,J.IACS 122,12013 (2000). aKamlage, S., Sefkow, M., Petet M.G. JOC 9,2938 (1999). sKamlage, S., Sefkow, M., Peter, M.G. EJOC 2367 (1999). oMurata, M., Watanabe,S., Masuda, Y. TL 40,9255 (1999). Tlshikura, M., Hino, A., Katagiri, N. I/ 53, 1l (2000). nYoshikawa,E., Radhakrishnan,K.V., Yamamoto,Y. TL 41,'729 (2000\.
rCobley, C.J.,vandenHeuvel.It.. Att
Tris-(2,6-diphenylbenzyl)sill'l bn Carboxyl protectian.t Hrgh AgOTf-mediated esterification. Tt LiAlH4, but they are cleaved hr I reducedby iBu2AlH to alcohols rlwasaki,A., Kondo,Y., Maruoka.K I
Tf is-(2,6-diphenylbenzyl)silyl bromide
N '., . ,eddirionwith 1,3-diynesregiosDr..:.:irnederivativesavailable.ll :-:: ,/\\l(erionic species generated lr-'..1::mrdes.rl The benzoannulated p r . : : .i . '
eYoshikawa,8., Yamamoto, Y. ACIEE 39,173 (2000). r(rTsukada, N., Sugawara,S., Inoue, y. OL2,655 (2000). IrSaito, S., Uchiyama, N., Gevorgyan, V., Yamamoto, y. JOC 65,4338 (2000). r:Larksarp, C., Alper, H. JOC 64,4152 (1999). lrl-arksarp, C., Alper, H. IOC U,9194 (1999). IaMurakami, M., Minamida, R., Itami, K., Sawamura, M. CC 2293 (2000). rsBraun,M., Laicher, F., Meier, T. ACIEE 39, 3494 (2000).
\ P h
- -*NYNPh
Tlis(dimethylamino)phosphoranes. As bases.t The ylides (Me2N)3P:CR2 Sorve as bases in alkylation reactions,
-4""o
nitroaldol condensation,and the Horner reaction. IPalacios, G. f 56,663(2000). A., Bertrand, J.M.,Baceiredo, F.,Aparicio,D., delosSantos,
98Yo
r . l --alkaltrienes and conjugated
Tiis(dimethylamino)sulfonium difl uorotrimethylsilicate. Cleavage of N-(2arimethylsilyl)ethanesulfunyl group.t
SES-protected aziridines
decomposeon treatment with the title reagent.
;
-
_./ ,/-\
\
A
R"<-: \
h::.
R'
)'''R
rDauben. P..Dodd.R.H.JOC 64.5304(1999).
Tlis(dimethylphosphinito)platinum hydride. Amides from nilriks.t Nitriles and amines react in the presenceof [Mez(HO)P],.ftH at 160'to afford amidesin moderateyields.
t!.rTocene renders the Pd(O)-
h -r.lrtive.l5
Rl' N - H R*CN+ R'/
r l -'^---7\^, t,N
HO>
R-CN+ HzN
/
,P
H-PtlP(oH)Me2l3 R-{ ' N - R -+ Dl\'4E160 R" H-prlp(oH)Me2l3
,,O)
l----.-.-----------------------*R{r 'N / I Dl\'lE160'
lCobley, C.J.,van den Heuvel, M., Abbadi, A., de Vries, J.G. TL 41,2467 (2000).
Ft- .t.:
r JACS122,12013(2000).
Tris-(2,6-diphenylbenzyl)silyl bromide. Carboxyl protection.l Highly hindered silyl carboxylates are formed by the AgOTf-mediated esterification. The silyl esters are stable to aq HOAc, aq NaOH, and LiAlH4, but they are cleaved by I-BuOK-DMSO, or HF-pyridine in THF at 50', and reducedby i-Bu2AlH to alcohols.
: rn).
rlwasaki,A., Kondo,Y., Maruoka,K. "/ACS122,10238(2000).
Tris(trimethylsilyl)silane
Tlis(pentafl uorophenyl)borane. 20, 422 Irnine reduction.t In the presenceof (C6F5)jB,imines undergo hydrosilylation with PhMe2SiH. The reagentis probably [PhMe2Si]+ [(C6F5)jBH] . Silyl ethers.2 A general method for O-silylation at room temperature rn >85Vc yield employs Ph3SiH and (C6F5)1B.Under these conditions, epoxides are cleaved bur ethers,esters,lactones,nitro compounds, alkenes,and alkynes are preserved.
a*'
1)"-a I
(M€.S--g
"
M
>I
AIB\
\r^rtr'^---/
il
'
'Blackwell,J.M.,Sonmor,8.R., Scoccitti,T., Piers,W.E. OL2,392I (2OOO). 2Blackwell, J.M.,Foster, K.L.,Beck,V.H,Piers,W.E.JOC&,4887 (1999).
Tlis(trimethylsilyl)silane. 19, 393; 20, 423 Elimination. Radical formation from 2-(benzenesulfinyl)allyl bromides on treatmenr with (Me1Si).SiH-AIBN is immediately followed by elimination to afford allenes.l
o
(Me3si)3siH lO-liY-Y\C_-
Br
;;ffi
o
-
|
\o{2
rDelouvrie,B., Lacote,8.. Fensrrbr rBandini, E., Favi, G., Manelh. G . I ' B a t e y ,R . A . , S m i l , D . V f L { ) . 9 l S i lPatro, B., Murphy, J.A. OL 2. 159
TFis(trimethylsilyl)silyllithiun a- ( TrimethyIsiloxy )alhenyI productsfrom reaction of r! of the Si.- O r o Transsilylation
80% Hydrodehalogenation. A convenient access to pJactams2 consists of desilylative cyclization and removal of the bromine atom from the ct-positionwith (MejSi)1SiH-AIBN.
Ph
C=( Ph
tt\_..tn
Br\
/y-Ph
A
)-N MqSiO
(Mersi)3siH
Jrl, ;" '':
TI
..Ph
/-*
rNaka.A., Ohshita,J., Kunai. A . k 79Yo
a-Boryl radicals. Radicals are derived from halomethylboronates.Addition of the radicals to multiple bonds accomplishesa carbon chain homologation.3
Ttityl chloride. L'g Hydroxylprotection.: compounds containing differco Thus, o-hydroxybenzyl alcohol phenolicoxygen.
Ho---,\
* -.T.o-F-o
'
,-r,
(Me3Si)3SiH - AIBN ; NaOH - H2O2
to\ Ho--.\
rSefkowM., Kaatz,H.fL 40.6561 I
68%
Cyclization, Construction of a tetracyclic intermediate of aspidospermidine is based on an intramolecular radical addition to a double bond.4 The transposed radical interacts with an azide group to complete the process.
Trityl tetrakis(pentafl uoropbc
Glycosylatian.r \ranosll reaction with sugar derir atrr < cata\yzedby Tr[B(C6F5).]. An r
coupling component. Hower er. merely performing an oxidauoo
Ttityl tetrakis(pentafluorophenyl)borate
ur:. jnderso hydrosilylation*'irh tBll ! :i :,rrn1 temperaturein >8-S{ d::. :... epoxidesare cleaved bu lL: :.-.. rrc' preserved.
r*' ")-rY-
(Me3Si)3SiH A I B N/ P h H 80.
\ * v
H
i M .
aspidospermidine
40yo
.:-_ :r)o0). .r'.-.999).
rl:::r i ,allvl bromideson treatrnenl r.l:.i::,rnto afford allenes.l -\.rt^\.,r\a
C--
c'-..V
t t - \ 80To
-ir.t-1nts- consistsof desilylative r'..::,'n nith (Me3Si)qSiH-AIBN.
rDelouvrie,B., Lacote,8., Fensterbank, L., Malacria,M. TL 40,3565(1999). rBandini,E., Favi,G., Martelli,G., Panunzio,M., Piersanti,G. OL 2, 1077(2000). 'Batey,R.A.,Smil,D.v. TL 40,9t83(1999). rPatro,B., Murphy,J.A.OL2,3599(2000).
Tris(trimethylsilyl)silyllithium. a-(Trimethylsiloxy)alkenyl bis(dimethylsilyl)silanes.t These novel compounds are products from reaction of (MejSi)jSil-i with ketenes (after hydrolytic workup). Transsilylation of the Si+ O version occurs during the process.
Ph
(Me3Si)3SiLi
Ph r'::*
€..
PSiMe3
pfi
SiH(SiMe3)2 78%
sPh
r-l )_itn n'
Ph
C=O +
rNaka,A., Ohshita,J., Kunai, A., Lee, M.8., Ishikawa,M. JOMC 574,50 (1999).
79o/o
rnL.rhrlboronates. Addition of the l':::.'logation.3
| : -..
,-
-
tO)
Tiityl chloride. Hydroxyl protection.t
Useful variations in chemoselectivity for the etherification of compounds containing different types of hydroxyl groups use TrCl and l-BuMe2SiCl. Thus, o-hydroxybenzyl alcohol is silylated at the aliphatic moiety but tritylated at the phenolicoxygen. lSefkow, (1999). M., Kaatz,H.TL40,6561
rro=\ 68To
ncJr.rtc of aspidospermidineis r ^.,nd.r The transposedradical
Trityl tetrakis(pentafl uorophenyl)borate. Glycosylation.r Pyranosyl phenyl carbonates serve as glycosyl donors in their reaction with sugar derivatives containing a free hydroxyl group. The reaction is catalyzedby Tr[B(C6F5)a].An anomeric thioether is not affected and may be present in a coupling component. However, it can be transformed into a glycosyl donor afterward by merely performing an oxidation in situ (adding NaIOa).
Thngstencarbeneand carbynecomplexes
PhrcB(coFs)a_ t-BuNc/cH2clz
+
O
lrr"J-
BE?[$3-o-.
o
:fo
Cycloadditions. Tttc r with enamines. Interestrngl
aOBn
,-OBn nno--$--Q o oph "'d;or-7-\,,")r
Ho\ azo:Tv_3\ -set Bzo_J*
"'!i$$-s='
:r-o
skeletons.
PhthN
O
MeO
OR'
fwlcoyu *
PhthN
F
^K ) t
AcOl
(oc)sw\
,-OAc
nco.-$.-Q strr AcOL-7-v'--' PhthN
nco-$-o. -oAcO# ..........................._ \ Fntnruazo-$-Q IBUNC / Naloa Bzoif) Ph3cB(c6Fs)4
HO\
PhthN
ezo-$-Q
oMe +
|
)
R
r
OMe
BzO-*\
ezd 3""
Alkylmetallation.2 The title compound effectively promotes the reaction of alkynes with alkvlzirconium soeciesderived from hvdrozirconation of alkenes.
cp2z(R)Cl
Ar---:
+ Ph3cB(c6F5)4 NIeOH- CH2Cl2
Ar"-1
lBarluenga, J.,Rubio.E..LcP 2Barluenga, J., Tomas.\1. B Nicolas,A., Yazqtez.l.TJ.\C rBarluenga,J., Ballesteros.A t28'74Q00$.
Ttrngsten(Vl) chloridc- l! Reduction.' Sulforx by the combination of rACl
R
Acetalimtion.' 'Takeuchi,K., Tamura,T., Mukaiyama,T. CL 122,124(2000). :Yamanoi, (199q. S.,Ohrui,H., Seki,K., Matsumoto, T., Suzuki,K. TL 40,840'7
Tlrngsten carbene and carbyne complexes. 20r 424425 ' Conjugate allylatian.t The reaction ofFischer-type conjugatedcarbenecomplexesof tungstenwith allylic alcohols under basic conditions proceedsvia an oxygen attack on the tungstenatom to initiate a reanangement.At somestage,transesterificationalso occurs.
Adm
WCl6 accomplishesthe dcr Ring expansian' C1 to the chlorinated l.&rd temperature.
A r S
X
/ s Ph Ph \ -
FW(CO)s Meo
,.
*
// HO
MeOH - MeONa
+
,/
( ) //
\
Fo o // \---l 82To
rFirouzabadi. H., Karinu. B I 2Firouzabadi,H., lranpoor. \. 3Firouzabadi,H., kanpoor. \
T[ngsten(Yl) chloride
Cyclaailditians. The same type of Fischer-type complexes undergo cycloaddition with enamines. Interestingly, acyclic2 and cyclic enamines3afford products of different skeletons.
-OBn .ryO
r\
fo--zv-\ C
Bzo-$^u1 BzO:J-* PhthN
-o
:
-SEt
OR'
OR'
. *-d*t"o" ^"'[*' -OAc vO
(oc)5w\
n
nzo-$-Q --szs__\-Z-) PhthN
oMe l \
-'---\r/"\
)F:-\
R
I
r. {r \-l()7(1999).
;i
+
lzlNa'
/
Hzo
I
12874 (zC0,O).
Ttrngsten(Vl) chloride. 19,395; 20, 425 Reduction,t Sulfoxides are reduced to sulfides and sulfonyl chlorides to disulfides by the combination of WCl6 with Zn or NaI. AcetaliZation,2 Admixture of carbonyl compounds with a trialkyl orthoformate and WCl6 accomplishesthe derivatization, usually giving the diethylacetalsin >857o yield. Ring expansian.3 cyclic dithioacetals(five-, six-membered)undergo rearrangement to the chlorinated l,4-dithiacycloalkenes on treatrnent with wcl6 in DMSo at room
Ar \
S=, / ".{cnz)"
l
wcl6 + l l N , t e z s oc -H 2 c r 2 25
Ar-''.'S-t' I ",Aa.(cHz)"
88-95%
\-
!o
/oJ 82Yo
Y"'*"
rBarluenga,J., Rubio, E., Lopez-Pelegrin,J.A., Tomas,M. ACIEE 38' 1091 (1999). 2Barluenga, J., Tomas, M., Ballesteros, A., Santamaria' J., Brillet, C., Garcia-Granda, S', PineraNicolas, A., Yazqtez,I.T.JACS l21., 4516 (1999). 3Barluenga,J., Ballesteros,A., Santamaria,J., de la Rua, R.B'' Rubio, E., Tomas, M'JACS 122'
Ph
(
\
R
n =1 , 2
f\
-
/
rHF_20.; __/ // t\ + cF' cooH: \:^icH,)"
temperature. l:: r ,. :rlugatedcarbenecomplexesof NJ..:. \ia an oxygen attackon the r:r..r'.tcrifi cationalsooccurs.
-
o
{''^,,
{'Y 1 . / LrN\.(cxr)"
+
OMe
\ i-:,'nrotesthe reactionof alkynes n i , : . , , la l k e n e s .
v-r
481
rFirouzabadi.H.. Karimi, B. S 500 (1999). 2Firouzabadi,H., Iranpoor, N., Karimi, B. SC 29,2255 (1999). 3Firouzabadi,H., Iranpoor, N., Karimi, B. SL4l3 (1999).
T[ngstan p€ntacarbonyl tetrahydrofuran
482
Thngsten pentacarbonyl tetrahydrofuran. Cycloadditian,t Cyclic Fischer carbenecomplexes are generatedfrom o-ethynylaryl carbonyl compounds with the title reagent at room temperature. When enol ethers or enaminesare present,a Diels-Alder reaction-retro-Diels-Alder sequenceoccurs to fumish substitutednaphthalenes(7 examples,54-847o).
R'
R
aro" \
(thf)w(co)5 THF 25"
4--€to
OR
R'
R'
\-\-\w(co)5
Ultrasound. L5, 363; 16, 371Selcctive cleavage of t-fu at an ortho-position of an aryl cation in MeOHtCl..
R"
OTB 54-84o/o
Z--/ I t
rlwasawa,N., Shido,M., Maeyama,K., Kusama,H../ACS122,L0226(2000).
TBSO./V
rdeGroot.A.. Dommisse. R.A . l.r
Urea-hydrogen peroxidetrl Oxidations. This svsten this regard, it is more effectrre Saturatedhydrocarbons an clohexanegives cyclohexll tn
rCaron,S.,Do, N.M.,Sieser. J.E rBalicki,R. sc29, 2235(t999, rMoody,C.J.,O'Connell.J.L.CC
Urea nitrate. A specia.l4 Nitration,t 4-halo-1,2-dinitroarenedenr a precursorsof benzimidezoles.c
*>^, \) X=F.
rMundla,S.R.21 41, 42'77rJffi t
brr'. :ue generatedfrom o-ethynylaryl rr. :.'mperature. When enol ethers or )r.. -Alder sequenceoccursto furnish Ultrasound. 15, 363; 16, 377-37 9 ; 18, 395; 19, 396; 20, 426 Selcctive ckavage of t-butyldimethylsilyl ethers.' Siyl ethers such as those situated at an ortho-position of an aryl carbonyl group is subject to rapid removal by ultrasoni-
ZY\'.R'
cation in MeOH-CCla.
\)\zl* OTBS 54-84To
cHo OTBS
' rl16 r2000).
OTBS
cHo
MeOH- CCla
)))) 50"
TBSO
OH 97To
rdeGroot,A., Dommisse, R.A.,Lemiere,G.L. 256, 1541(2000).
Urea-hydrogen peroxide-trifl uoroacetic anhydride. Oxidations. This system oxidizes electron-deficient pyridines to the N-oxides.r In this regard, it is more effective than MTO-H2O2. Sulfides are converted to sulfones.2 Saturatedhydrocarbons are functionalized by this oxidation system. For example, cyclohexane gives cyclohexyl trifluoroacetatein 807oyield.r rCaron,S.,Do, N.M.,Sieser, J.E.TL 41,2299(2000). 2Balicki,R . SC29,2235(1999\. 3Moody, C.J.,O'Connell,J.L.CC 1311(2000).
Urea nitrate. Nitration,t A special application of this method is a regioselective synthesis of 4-halo-1,2-dinitroarenederivatives from m-nitrohaloarenes.The dinitroarenesare important precursorsof benzimidazoles,quinoxalines,and related compounds.
x'""1'Noz urean*rate l l l - - - - - - - - - - _ l l l H2soa %ro, \?
xy"\'No2
X=F,Cl,Br 'Mundla,S.R.2241, 4277(2000).
-ir-/
PF
-N-
I Vanadyl ethoxydichloride. 20, 428 Reductive elimination.t Cross-coupling of two ligands of organozincs is a reductive elimination process, it occurs when the latter species are brought into contact withVO(OEt)Clr.
S9Yo
Winal dialkylation,2 The oxovanadium-induced reaction of cyclic enones with dialkylzinc reagentsis followed by oxidation of the alkylzinc enolates and another C-{ bond formation process,resulting in the generationof vicinal dialkylation products.
,1
o\\
t
a
/-1 \t6*rl"
vo(oEocb
I R2zn -r-25
R
"R<
F\
.l
).(cHz)" R
Isomerimtion of epoxides.t This vandyl compound is effective for promoting the rearrangmentof epoxides to carbonyl compounds. a-Dikctones.a a-Ketols undergo aerial oxidation to c-diketones and cr-hydroxy esters to a-ketoesters in MeCN at room temperature.VO(OEI)CI2 as well as VOCI3 are equally effective as catalyst. lHirao,T.,Takada, T.,Ogawa,A. JOC 65,1511(2000). 2Hirao,T., Takada,T., Sakurai,H. OL2,3659 (2000). 3Martinez,F.,del Campo,C., Llama,E.F.JCS(PI) 1749(2000). aKirihara,M., Ochiai,Y., Takizawa,S.,Takahata, H., Nemoto,H. CC 1387(1999).
Vinamidinium hexafl uorophosphate. Pyridines,t Reaction with ketones leads to annulation that provides trisubstituted pyridines. 4U
rMarcoux, J.-F., Corlel. EG R.D., Reider,P.J.OL 2. :l-19
Vinamidiniumhexafluorophosphat€
-tin.*/ -N-
tl
pr^
aA, +
|
oA*,
t-BuoK/THF:
, .'.i??J;l"
R-.ra1r.Ar ll
I
\*A*,
I
lrsands of organozincs is a .1---.cies are brought into contact
u, lc:
OMe
::
25o
\__/-"" 59Yo
:c: rcaction of cyclic enones with ilir.zrnc enolatesand anotherC-{ i r:. rneldialkylationproducts.
: -
CH)n
rr.:; rr effective for promoting the x i(, u-diketones anda-hydtoxy \ ( ),OEr)CI2as well as VOCIrare
t: t t 1.187(1999).
la::,'nthatprovidestrisubstituted
rMarcoux, J.-F., Corley, E.G., Rossen,K., Pye, P., Wu, J', Robbins, M'A', Davies, I'W', Larsen, R.D.. Reider.PJ. OL2,2339 (2000).
Xenon(II) fluoride. 13, 345; 19, 399; 20, 430 a-Fluoroketones.t The reaction of trimethylsilyl enol ethers with XeF2 in MeCN involves radical cation intermediates.
Ytterbium. 14,348: Silanes. Pheny on mediationby Yb.'
rRamsden. C.A..Smith.R.G.OZ 1. 1591(1999).
rJin,W.-S.,Makioka-l'
Ytterbium(Ill) chh Acetylation.t ! the presenceof YbCl \i Allylation.:
MeCN. o-Anisaldeh
,, t
g
e
conditions. Diels-AWer ra involving unactivato u-HydroxyoryL they are treated $ith crucial.
lClarke,P.A.,Holton.I zFang, X., Watkin.J.G rFang,X., Warner. B,P aLikhar,P.R.,Band;-o
Ytterbium(Ill) trif, Alcohols and alcohols with 4-ma
by transesterificatio involvesreactionof Benzyl alcohols catalyst.aByproduct
Detritylation-: THF (containing orr Conjugate & methoxymethylpyr optically active P-*
c1
lhr'rs r+ith XeF, in MeCN
Ytterbium. 14,348;15, 366; 16,384;18, 401; 19, 400; 20,431 silanes. Phenylsilanes of the type Ph(R)siH2 are arylated to provide ph(R)ArsiH on mediationby Yb.t rJin,w.-S.,Makioka,Y, Kiramura,T., Fujiwara,y. CC 955(lggg).
Ytterbium(Ill)
chloride. Acetylation.l Monoacetylation of symmetrical l,2-diols with acetic anhydride in the presenceof YbCl or DyClj is possible. Allylation.2 Various aldehydes react with allylsilanes on catalysis by ybclj in MeCN. o-Anisaldehyde is converted to 2-(1,6-heptadien-4-yl)anisoleunder thesereaction conditions. Dicls-Alder reqction. YbCli is effective as a catalyst for the Diels-Alder reaction involving unactivateddienes.s o'Hydroxyarylacetic esters.a Arylglyoxals are transformed into the esters when they are treated with YbCl., in an alcoholic solvent. The presenceof a base (e.g., EtjN) is crucial. rClarke,PA., Holton,R.A.,Kayaleh, N.E.ZZ41, 2687(2000). 2Fang,X., Watkin,J.G.,Warner,B.P.TL 41,447(2000). rFang,X., Wamer,B.P.,Watkin,J.G.SC30, 2669(2000). ll-ikhar, P.R.,Bandyopadhyay, A.K. SL 53S(2000).
Ytterbium(Ill) triflate. 18, 402403; 19,401402; 20, 431433 Alcohols and derivatives, Yb(or01 serves as a catalyst for etherification of alcohols with 4-methoxybenzyl alcohols.r Deacetylation of esters (particularly AroAc) by transesterification2to isopropanol is observed. A preparation of alkyl glycosides3 involves reaction of glycosyl esterswith trialkyl boratesin the presenceof yb(orf)1. Benzyl alcohols are oxidized to aromatic aldehydes by nitric acids using yb(orf)j as catalyst.aByproducts from this reaction are water and nitrogen oxides only. Detritylation.s Yb(or01 catalyzes cleavage of trityl ethers and N-tritylamines in THF (containing one equiv of water) at room temperature. Conjugate additions. The Yb(OTf)3 -catalyzed addition of a chiral N-amino-2methoxymethylpynolidine to alkenyl sulfones is crucial to a process for the synthesis of optically active B-sulfonylamines.6
Ytterbium(Ill) trifl ate
Allylation.l A free radical addition of N-bromoacetyloxazolidinones to branched allylsilanes with subsequentelimination effects homologation of the N-acyl group. Both the addition and the elimination stepsare promoted by Yb(OTflr.
ene2siD.''{3#+-* 8 1 o h( Z : E
91 :1)
OH
,'^\-'\
Diels-Alder reactions. deficient dienophiles is pron Radical cyclization.' oxidative radical cyclizatro is also added.
Reactions of imines. Silyl alkynyl ethers and aldimines undergo catalyzed condensation, the strained heterocycles that ensue open to afford conjugated amides.s Yb(OTf)i is also a useful catalyst for the reaction of organocuprates with Nsulfonylimines.' Friedel-Crafts reactions.lo A synthesisof a-hydroxyarylacetic estersis by reaction of areneswith glyoxalic esters.Such estersare amenableto resolution with lipase. Alkylations, Under high pressure, cyclopropane-1,1-dicarboxylic esters react with nucleophiles such as B-ketoesters.rrA polyfunctional carbon chain can be built from an activateddienebv sulfonvlationat one end.12
o Z>a\-acooMe \4,
f; coov" cooMe yb(orn3 ,.._rcooMe A>/\L2.1 boovte * Acoov" ;""i; \-\,
oSiMe3
PhA
'
o1
\..1 I
"".
so2iYb(orf)3 >
'|ift,.,j."
Ph 79%
Yb(OTf )3 catalyzes an ene-type reaction of N-tosylimines and cr-methylstyrene,that is dramaticallyenhancedby small amountof Me.rSiCN.r3 Oxymercuratinn. Homoallylic alcohols apparently form hemiacetals with acetone and benzaldehyde in the presence of Yb(OTf).. Reaction of the hemiacetals with HgClOAc completes a diastereoselectiveoxymercuration,raa key process for generating (l,3,5, . . .)polyols.Successof the reactiondependson Yb(OTf)r.
I Sharma,G.VM., Mahahngea :Sharma,G.VM., Ilangoran.! ' Y a m a n o i .T . . l w a i , Y . . l n a z u -
l B a r r e t t ,A . G . M . . B r a d d a \ . D 'Lu. R . J . ,L i u , D . , G i e s e .R \ t ' 6Enders.D.. Muller. S.F..R..l 'Porter. N.A.. Zhang. G.. Rcct s S h i n d oM . . , O y a .S . .S a t o .\ ' . u L i . C . . W e i . H . - X . .H o o \ . J D t"Zhang.W.. Wang,P.C.J(X'I rrKotsuki, H., Arimura. K.. \ls r r N a r k e v i t c hV, . , S c h e n \ .K . \ n Y a m a n a k aM , ., Nishida.{ . !
lrDreher.S.D.. Hornberger.X I ' 5 K i n s m a nA, . C . , K e n . \ t . \ d r o Y a n gD . . . Y e . X . - Y . .C u . S . !
Ytterbium(Ill) tris[l pcrfi Meerwein-Ponndorf thatAlCl,.tr-P conditions at 50' in E5 in isopropanol
Y tterbium(tr| ) tris[ (perf uorobutln€sulfonyl )mctbidel
\.:./\)lidinonesto branched r rhe -V-acvlgroup. Borh
oH
*
./'\r'\
l.(,.!
R--R'
*J(*
Yb(oTf)3
o^o : :
Hg(OAc)cl
O
,..-.rur-,,,-.HgCl
Me2CO
54-86To
o \-t\-Aruf t
,-)-: o ' v :1'" (Z : E
)
9 1: 1 )
with electronDiels-Alder reactions. The cycloaddition of l,3-cyclohexadiene pressure.15 high under Yb(oTlh of deficient dienophiles is promoted by the dihydrate formed by an Radicat cyclization.t6 The dehydroabietane skeleton is readily dihydrate Yb(OTf;. of amount oxidative radical cyclization reaction to which a catalytic is also added.
t , .:i:t)lnes undergo n
r
catalyzed
.,it,rrd conjugatedamides.' : ,rr3aflocuPfateswith I-
,\ .. :...rcc-ticestersis by reaction :. lutionwith lipase. L : ,-rrhoxylic estersreact with u-. ' .hain can be built from an l . :
COOMe /4.
\
79o/o
:. .rndc-methylstyrene,that is
.,(}..OA
<)? ,)'")-) \,,\o
Mn(OAc)s- Yb(OTO3 cF3cH2oH
-5'
p?-
77%
rSharma,G.VM., Mahalingam,A.K. JOC 64,8943 (1999)' rSharma,G.V.M., Ilangovan,A. SL 1963 (1999)' rYamanoi.T.. lwai, Y, Inazu,T. Il 53, 1263 (2000)' rBarrett.A.G.M., Braddock,D.C., McKinnell, R'M', Waller' FJ' SL 1489 (1999)' 5Lu, R.J., Liu, D., Giese,R.w. ZL 41, 281'7(2000). "Enders,D., Muller, S.F.,Raabe,G.' Runsink,J' EJOC 879 (2000)' TPorter,N.A., Zhang, G., Reed, A.D. TL 4l' 57'73(2000)' sShindo,M., Oya, S., Sato,Y, Shishido,K. H 52,545 (2000)' e L i . G . . w e i , H . - X . , H o o k ,1 . D . T L 4 0 , 4 6 1 1 ( 1 9 9 9 ) . tt\Zhang,W., Wang, P.G.JOC 65' 4732 (2000). I I Kots;ki, H., Arimura, K., Muruzawa,R.' Ohshima'R' SL 650 ( 1999)' lrNarkevitch,V, Schenk,K., Vogel,P.ACIEE39,l806 (2000)' rrYamanaka,M., Nishida,A., Nakagawa,M. OL2,l59 (2000)' laDreher,S.D., Hornberger,K.R.' Sarraf,S.T', Leighton, I'L' OL2' 3197 (2000)' r s K i n s m a nA, . C . , K e n , M ' A . O L 2 ' 3 5 1 7( 2 0 0 0 ) ' r6Yang,D., Ye, X.-Y., Gu, S., Xu, M. JACS l2l' 55'79(1999)'
l ) : ,:nr hemiacetalswith acetone
Ytterbium(Ill)
, 'n of the hemiacetals with .r key process for generating t: t'L ( ) T f ) r .
Thus,PhcHo is reduced rharAlclr, (i-Pro)rAl,andYb(oTfh areineffective. condirions yield. in 85Va at 50" in isopropanol
tris[(perfl uorobutanesulfonyl)methide]' This catalyst shows high activity reduction.t Meerwein-Ponndorf-verley
under
Yttryl isopropoxide
Friedel-Crafts acllatian. With this catalyst acylation in fluorous biphasic system is achieved.zNote that the triflamide Yb(NTf2)3 is also useful for the same purpose (not specifiedin fluoroussolvent).r 'Nishikido, J., Yamamoto,F., Nakajima,H., Mikami, Y, Matsumoro,Y., Mikami, K. Sa 1990 ( 1999). 2Barrett, A.G.M.,Braddock, D.C.,Catterick, D., Chadwick, D., Henschke, J.P.,McKinnell,R.M.SL 847(2000). 3Nie,8., Xu, J.,Zhou,c. "/CR(S)4460999).
Yttryl isopropoxide TransacylationI
This compound, (l-PrO)1jY5O, cata\yzesacyl transfer from enol carboxylatesto alcohols, and in some cases(e.g., piperidine-2-methanol), the selective O-acylationof amino alcohols. rLin, M.-H.,RajanBabu, T.V.OL2,997 (2000).
Zeolites. 15, 36'l ; 18, 405-406: 19. { Reactions, Various types of I supports for common transformatrm 2,3-epoxyalcohols and alkenyl cpor
and thioacetalizationaof carbonyl co consistsof heating amines with rcts
rNarender. P. Kulkarnr.SJ N.. Srinivasu, rGupta,A., Vankar,Y.D. ZL 40, l -169r l99 'Talbakhsh, B.. Hcrau.I M., Mohajerani, lBallini,R.,Barboni,L., Maggi,R.. Sstc 'Bigi, F.,Frullanti,B., Maggi,R..Sancrr
Zinc. 13, 346-347 ; 14, 349-350: 15. 20,435436 Reduction. A selective redr.rrr near-criticalwater (at 250").r Clchzr 2-nitroaryl compoundscontaining a k to ArNR2 by a reductive alkylauon pn
-\ " A o
-n
orNV
A general method for accessrngr followed by reduction of the resulunl
1o o-\. N'o Bn-
__!
./t
\ MgBr
l O
a\ . .:: ,1 rn nuorousbiphasicsvstem a . ..::ul tor the samepurpose(no(
I
'.', .-:ri,'t,..\'.. \likami. K. St l99l_l
[
:i:r.chke.J.P.\{cKinnell.R.l\t.Sl
Zeofites. 15,367 ; 18, 405-406; 19, 403404; 20, 434 Reactians. Various types of zeolites continue to be exploited as catalysts or supports for common transformations: acetylation of alcohols with HOAc,l reduction of 2,3-epoxy alcohols and alkenyl epoxides with sodium cyanoborohydride,zacetalization3 and thioacetalizationaof carbonyl compounds. A synthesis of symmetrical dialkylureass consistsof heating amines with acetoacetanilidewith HSZ-360 at 180'.
{) -.,:.,trzc'sacyl transferfrom enol -: :-.r-l-methanol). the selective e<..::
'Narender, N., Srinivasu, P.,Kulkami,S.J.,Raghavan, K.V.SC30, 1887(2000). rGupta,A., Vankar,YD. TL 40, 1369(1999). 'Tajbakhsh, M., Mohajerani, 8., Heravi,M. M. SC29, 135(1999). rBallini,R.,Barboni,L., Maggi,R., Sartori,G. SC29,767(1999). 'Bigi, F.,Frullanti,B., Maggi,R., Sartori,G.,Zambonin, E. JOC 64,1004(1999). Zinc. 13,346-347;14,349-350;16, 386-387; 17,406401;18, 406-408; 19,404405; 20,435436 Reduction. A selective reduction of nitroarenes to arylamines occurs with Zn in near-critical water (at 250').r Cyclization that follows reduction is expectedin the case of 2-nitroaryl compoundscontaining a leaving group at proper distance,2AINO2 is converted to AINR, by a reductive alkylation processin protic solvents (promoted by Zn or Sn).1
\NAcrl
-a)
Zn - HCI
orNV
'o
(Ir 650/o
A general method for accessingallylamines from nitronesais by a Grignard reaction followed by reduction of the resulting hydroxylamines with Zn.
1o o'-\.
1o '/^\MsBro..-l.r-o I
Bn-N'o
Bn-N'oH
1o fiffi
0.',\Bn-
N'H
SOYo
Zinc-coppercouple
Zn-A\C|, in MeCN is reported for reductive coupling of carbonyl compounds to form alkenes.5 Nonaqueousreduction conditions compatible with ArSO2Cl employs Zn-Me2SiCl2 in dimethylacetamide (or dimethylimidazolone). Thiols are obtained as products.o trans-I,2-Cycloalkanediols (five-, six-membered) are synthesized by reductive coupling of the dialdehydes using Zn, CpzTi(Ph)Cl, Me.SiCl in THF.7 CpzTi(Ph)Cl is formed in situ by treating Cp2TiCl2sequentially with i-PrMgCl and PhMgBr. Organozinc reactions. Barbier alkylation of aldehydes with 2-arenesulfinylallyl Practical conditions for the Reformatsky reaction of halides is highly diastereoselective.E aldehydesare further defined.e The selectivity of Rieke zinc in its reaction with organic halides is demonstrated in coupling of a benzylic bromide.ro
Br
ph CH'=C191;t*"'
Zinc bromide. 13, -1{9 Cleavage of t-butrl ethers and estersemplo
'Wu, Y.-q.,Limburg.D C-
Zinc chloride. 13, },19Amides from oxit free) accomplishesthc t 1,4-Dikctones.: \ of ZnCl2, Et2NH, and t-
Heterocycles. A transmetallation(*irh addition to enones.and
7n, trHF -;a111,a.*
phll--.,,-.-ar
tMecozzi,T., Petrini. \t I 2Adrian,Jr.,J.C.,Barkra I
64To
rBoix, C., Poliakoff, M. ICS(P1) 1487 (1999). 2Le Gall, 8., Malassene,R., Toupet,L., Hurvois, J.-P.,Moinet, C. SI 1383 (1999). rBieber, L.W., da Costa, R.C., da Silva, M.F. TL 41,4827 (2000). aMerino,R., Anoro, S., Franco,S., Gascon,J.M., Martin, V., Merchan,F.L., Revuelta,J., Tejero,T.,
pAmino Reformatsky
( R'
Tunon, V SC 30, 2989 (2000). 5Dutta,D.K., Konwar, D.TL41,622'1 (2000). 6Uchiro,H., Kobayashi,S. 7t 40, 3179 (1999). TYamamoto,Y, Hattori, R., Itoh, K. CC 825 (1999). 8Marquez,F., Llebaria,A., Delgado,A. OL2,547 (2000). eChattopadhyay, A., Salaskar,A. S 561 (2000). I0Guijarro,A., Rosenberg,D.M., Rieke, R.D. JACS 121,4155 (1999).
Zinc
R"
The addition of or1 species. When the zrrr adducts can be conveflr
NNMe2 tl
couple. esters.
Substitution
of
N-protected
benzenesulfonylamines
reagents that are generated by treating ct-bromoesters with a Zn-Cu
by couple
in dichloromethane represents a new entry to the B-amino esters.r A second route involves addition of the Reformatsky reagents to aldimines derived from o-anisidine.2 No B-lactams are formed due to steric hindrance.
lrYo"" \Z\N
+
\*
Br \,/
.cooMe
zn-cu cH2ct2
r'\7oMe
"
^.2\
l R'
r&1
\ irt
rLoupy,A., Regnier.S. il 2Nevar,N.M., Kel'in. A \ rMendez-Andino,J.. Paq aNakamura,M., Hara- K-.
\rL*" MeOOC._z\* 51-92%
Zinc iodide.
2,3-Dihydroisora treatmentwith catallrr
Zinc iodide
n: , 'l carbonyl compounds to form .-\::O.Cl employs Zn-Me2SiCl2in r.- ,htainedas products.o a... .\nthesized by reductrvecouC :n THF.7Cp2Ti(Ph)Cl is formed I r:J PhMgBr. kjcrr rles with 2-arenesulfinylallyl n. :,,r the Reformatskyreactionof )ri,1nrc halides is demonstratedin
rWu, Y.-q.,Limburg,
64%
Zincchloride.13,349-350;15,368-371;16,391-392; 18,4lG-411;19,409410;20,43g Amides from oximes.r Microwave irradiation of aldoximes with ZnCl. (solvent free) accomplishesthe transformation into primary amides.
R--42o \ * oHc (
'1 1.183 (1999).
fr \!:-.
D.C., Wilkinson, D.E., Vaal, M.J., Hamilton, G.S.TL4l,2g4:. (2OUJ).
Heterocycles. A route to 2,3-disubstituted furans takes advantage of the Cu-zntransmetallation (with znclr) from enolates derived from conjugate organocuprate addition to enones,and aldol reaction of zinc enolatesto an alkoxyacetaldehyde.3
-'--..-\,.Br
r.
Zinc bromide. 13, 349; 15,368; 16, 389-391; 18, 409; 19, 409: 20, 439439 cleavageof t-butylethersand esters.t A mild procedurefor thecleavageof these ethersandestersemploysZnBr2in dichloromethane.
1,4-Diketones.2 Methyl ketones are alkylated with a-bromoketones in the presence of ZnCl2, Et2NH, and r-BuOH.
-^cl l.
tMecozz| T., Petrini, M. TL 41,2709 (2NO). 2Adrian, Jr., J.C., Barkin, J.L., Hassib, L. TL 40, U57 (1ggg).
lrn. F.L., Revuelta, J., Tejero, T.,
OTHP
-,\)
R2CuLi;
R'-{-
ZnCl2 TSOH/ THF
R
R'
The addition of organozinc reagents to vinylstannanes afford gez-diorganometallic species.when the zinc reagents are derived from a-lithio-N,N-dimethylhydrazones, the adducts can be converted to N-dimethylaminopynoles by oxygen.a
NNMe2 c.: h!-nzenesulfonylamines by h: ::1,'csters with a Zn-Cu couple B-i:rin() esters.rA secondroute rnc. icnved from o-anisidine.2No
OMe
R'-) R'
t-BuLi ; Buznr ; ,* \ 6nsur
NNMe2
*rtrznau R'
I
I
t""-*\
02 +
SnBu3 J
l
)
/:(
R
\ R'
'Loupy,A., Regnier, S. ZL 40,6221(1999). 2Nevar, N.M.,Kel'in,A.V.,Kulinkovich, O.G.S 1259(2000). 3Mendez-Andino, J.,Paquette, L.A. OL 2,4095(2000). aNakamura, M., Hara,K., Sakata, G.,Nakamura, E. OLl,1505 (1999).
NH ',1eOOC._z\*
51-92%
Zinc iodide. 2'3'Dihydroisoxazoles.t Propargylic N-hydroxylamines undergo cyclization treatment with catalytic amounts of Znl2and DMAP at room temperature.
Zinc triflate--tertiary amine
Cyclopropanation.z 2-Triethylsilylvinyl phenyl selenide behaves as ^ (2phenylseleno-2{riethylsilyl)ethylidenating agent for conjugated double bonds in the presence of ZnI2. Chiral adducts are obtained from reaction of di-(-)-menthyl methyl-
Zirconacycles. Cyclopentenes. Zirconz in the presenceof BuLi to gt
enemalonate.
reaction of zirconacYcloPen : provides cYcloPentadienes spirocycles. X.
phSe
\\r,4,.
+
SEPh
pOO(-)-Men
* coo(-)-Men
cH2ct2 -30'
et.si/""Xcoo(-)-Men Xs
COO(-)-Men
X = H. COOMe. COR'
o \(
\\F-r .
rAschwanden,P.,Frantz,D.E., Carreira,E.M. OL2,2331 (2000). 2Yamazaki,S., Kataoka, H., Yamabe, S. JOC 64,2367 (1999).
Zinc nitrate. canbe selectivelyhydroHydrolysisof acetoni.des.tIn MeCN,terminalacetonides lyzedby Zn(NOj)r'6H2Oto affordthediols. tVijayasaradhi,S., Singh,J., Aidhen, I.S. Sa 110 (2000)'
I,S-Dienesand 1,5'csY alkynylmetalsleads.afterhr.
R
R
/-\ Cp2ZrJ Zinc tetrafl uoroborate. Cleavage of TBS ethers,t
Trimethylsilyl ethers are cleaved on exposure to
Zn(BF)2 in water.l rRanu,B. C.,Jana,U., Majee,A. TL 40,1985(1999).
Zinc trifl ate-tertiary amine. Alkynylzinc rcagents. The direct alkynylation of aldehydes is subject to asymmetric induction in the presence of a chiral base such as (+)-N-methylephedrine.l Addition to the C:N bond of N-tosylimines and nitrones by this procedure is also successful.2
+
Zirconia, sulfated. Koch carhonYlationsulfatedzirconia (a solid st4 H Cyclodehydration.:
readily furnishes cYclic e0r Glycosylation.r Tttc s deoxyglucopyranosYlfl r.ron
Zn(OT02
R---:
rTakahashi, T., Huo,S..Hara-R rXi, C., Kotora,M., Naka.lrnrI lDumond,Y.,Negishi.E ./.'r(5
R---:-ZnX
i-P12NEt cq2cl2 23
rFrantz, D.E., Fassler,R., Carreira, E.M. "/ACS122,1806 (2000). 2Frantz,D.8., Fassler,R., Carreira, E.M. "/ACSl2l,11245 (1999)
BnO{ Brto-
Zirconia,sulfated
fl.clenide behaves as a (2' , .n.lugateddouble bonds in the r(-r.tr()n of di-(-)-menthyl methyl-
Zirconacycles. Cyclopentenes, Zirconacyclopentadienesprepared from two alkynes react with CO in the presenceof BuLi to give substituted cyclopentenones.'With CuCl as catalyst, the reaction of zirconacyclopentadieneswith p-iodo-ct,B-unsaturatedcarbonyl compounds provides cyclopentadienes.2In the cases of 3-iodo-2-cycloalkenones, the products are soirocvcles.
,. --
SEPh
),,,,. coo(-)-Men Etrsi' X COO(-)-Men X.'
o
P
o
h
h\\ _ r * "o,r'Vtn
:rd!'s can be selectivelvhvdro-
l,S-Dienes and l,S-enynes.r Regioselective insertion of zirconacyclopentenesby alkynylmetals leads, after hydrolysis, to acyclic products.
R /-\ Cp2Zr..,r2 x:.
Ph
48%
[r'
r.-
h
alA-
THF 25"
l..
P
R
23: + Li___-_R
+ Hro*
.lrc cleaved on exposure to lTakahashi, T., Huo,S.,Hara,R.,Noguchi,Y.,Nakajima, K., Sun,W.-H../ACSl2l, 1094(1999). 2Xi,C., Kotora,M., Nakajima, K., Takahashi, T. JOC 65,945(2000). rDumond,Y.,Negishi,E.JACSl2l,11223 (1999).
,t aldehydes is subject to c . .. r r\ (+ )-N-methylephedrine.l n::: :rd\ by this procedure is also (:
^
R
/
R'
'N-oH
Zirconia, sulfated. Koch carbonylation.t Tertiary alcohols give carboxylic acids on treatment with the sulfatedzirconia (a solid superacid)under carbonmonoxideat 150'. Cyclod.ehydration,2Heating l,n-diols such as l,4-butanediols with the zirconia readily furnishescyclic ethers. Glycosylation.s The stereoselectivity of the zirconia-catalyzed glycosylation of 2deoxyglucopyranosyl fluoride is found to be highly solvent dependent.
Bn
Ir 9..
,-oBn HO. eno-AVQ + - Bno-r-) F
zto2tsoal 1
/
-
Zirconocene, Zr-alkylated
Colzft:
a-OBn
(oT BB?FFI 9-
'i?i\Y\.'o_
lvle3Si:
O
MeCN 25'
88
tz
Et2o / MS-sA 0"
19
81
Pyrid.inesA . 2[ 2 + ] - : tadiene formation from an all' alkyne moleculein a nickeltII x
'Mori, H., Wada,A., Xu, Y. CL 136(2000). Q., Souma, zwali,A., piltai, S.M.tcR(s) 326(t999). rToshima, K., Kasumi,K., Matsumura, S.SZ813(1999). Zirconocene. 20, 4y'.1442 a-Silylamides.t "Cprzr" induces a retro-Brook rearrangement of 3-siloxy-2-aza1,3-dienes.The products can be alkylated. U
OSiMe3 N\
Ph
Cp2Zr-O
Cp2ZtCl2 B u L i/ T H F
BuLi/ THF
,n/*\
Mel 78"
tl pn^N/-y' H
siMe3
6iu".
61yo
Alkcnylcyclopropanes.2 T\e Cp2Zr-
3M H2so4
tl
n'A\Z\n'
.0,'1)tz-*,
EtMgBr
*z+ rTakahashi, T., Xi, C., Ura.\'.. \eb rTakahashi, T., Tsai,F.-Y..Kotora-I
Zirconocene dichloride. 14. ll Aldol reaction r Zirconrr. amides derived from ( .. Fp6 correspondinglithium enolatesr Cyclopentanones.: Clclo valuable method for the preg application is found in a svntlrr
CglZrc.:
fZ
nl'-Z-n' CpzztCl2
ccca€.
I
HcrI gNa 1x2.-*,
rGandon,V., Bertus,V., Szymoniak,l. T 56,446'7(2000). 2Bertus,V., Gandon,V, Szymoniak,J. CC I7l (2000). Zirconocene, Zr-alkylated. 15, 8 I ; 18, 414: 19, 412414; 20, 442443 u,pUnsaturated esters.t Zirconacyclopropenes derived from alkynes undergo alkoxycarbonylation. The resulting alkenylzirconocene derivatives can be functionalized with various electrophiles.
at Y
o
BuLr CC HOAc
rVicario,J.L.,Badia,D., Domrngr rTaber,D.F.,Zhang,W.,Campbtll.
Zirconocene hydrcchloride. l, Aldehydes from amidct. temperaturewith Cp2Zr(HtCl rt
rWhite,J.M.,Tunoori,A.R..GcccA
Zirconocene hydrochloride
-OBn
r-Q
/\
cp2zrEt2: .....-------..*
Me3Si-:R
*z rr | --.lrransementof 3_siloxy_2_aza_
78
o tl pn^ru\rH
l SiMe3
61/o
f
l .
Me3Si
cooEt
x
\-./ /-\
R
cooEt
Pyridines.2 A [2 + 2 + 2]cycloaddition is accomplished via azaziconacyclopentadiene formation from an alkyne and a nitrile and subsequentreaction with another alkyne molecule in a nickel(Il)-catalyzedprocess.
81
THF
x. +
/\l
12
.
/R
crcooEt cptzr .- \
\.,/
:
Me3Si
497
:'lcr behavesas a 1,3-dipole . .c on exposureto sulfuric acid
Cp2ZrEt2,
R
HI
R / ZrCo.
R
K : K
*...,&*" i l l
(Ph3P)2NiCt2
R'A-N,
R,
NAR-
rTakahashi, T., Xi, C., Ura,y, Nakajima,K. JACS122,3228eO00\. rTakahashi, T., Tsai,F.-y.,Kotora,M. JACS122,4gg4(2C/|lO).
Zirconocene dichloride. 14, 122; lS, 120-l2I ; lg, 4 15; 19, 414; 20, 443444 AAol reactionr Zirconium enolatesare employed in conductingaldol reactionsof amides derived from (+)-pseudoephedrine. These species are prepared from the correspondinglithium enolateson additionofCp2ZrCl2. cyclopentanones.2 cyclozirconation of dienes followed by carbonylation is a valuable method for the preparation of 3,4-cyclocondensed cyclopentanones. A new applicationis found in a synthesisof (-)-androst_4_en_3.16_dione.
:r'rng liom treatmentwith HCl. ,,, H2SO4
>-"{K (-fo'
*L*,
Cp2ZtCl2 |
BuLiC ; O; HOAc
1x%
R'
Y
H - t -
z
o
H I H
rVicario, J.L., Badia, D., Dominguez,8., Rodriguez,M., Carrillo, L. JOC 65,3754 (ZIO\. 2Taber,D.F., Zhang,W., Campbell,C.L., Rheingold,A.L., Incarvito,C.D. ,/ACSlZ2,4gl3 eZOIU.
-: i 20.142443 c. :crrred lrom alkynesundergo D('.:fn\atrvescanbe functionalized
Zirconocene hydrochloride.14,8l; 15,g0_gl; lg,416417; 19,415416; 20, 445446 Aaehydes from amides.r Tertiary amides are reducedto ardehydesat room temperature with CprZr(H)Clin THF (16examples, 75_99Vo). rWhite, J.M.,Tunoori, A.R.,Georg, G.I.JACS122,11995 (2000).
AUTHOR INDEX Abada,P.,232 Abaee,M.S.,202 Abarbri,M.,201,327 Abbadi,4.,477 Abbas,S., 160,165,179 Abbas,S.A., 165 Abbassi,M., 21 Abdel-Fattah,A.A.A., l8 Abe, H., 70,459 A b e ,N . , 4 5 3 Abernethy,C.D.,230 Abiko,A., 169 About-Jaudet,E., 358 Abraham,S., 359 Abu-Omar,M.M., 270 Aburel, P.S.,369 Ackermann,L.,52,375 Adachi, N., 89 Adam,W., 235,270,344 Adamo,M.F.A.,362 Adams,C.J., 15 Adams,D.J., 149,359 Adams,N.D., 298 Adams,R.D.,239,274 Adinolfi,M.,400 Adiyaman,M.293 Adrian, Jr.,J.C., 493 Adrio, J., 124,327 Afonso,C.A.M.,464 Agami,C.,82,205 Aggarwal,V.K., 160,362,456 Aghapoor,K.,242 Aghapour,G.,392 Agrios,K.4.,427 Ahmar, M.269 A h m e d ,G . , 3 6 2 A h m e d ,M . , 2 7 3 , 3 5 4 , 3 7 5 A h n ,K . H . , 4 1 7 Ahrendt,K.4., 123 Aidhen,I.S.,494 Ainge,S.W.,328 AirHaddou, H., 120 Ajami,D.,242 Akai. S., 246
Akamanchi,K.G., 155,420 Akashi,M.,429 Akermark, B., 308 Akhmedov,N.G.,450 Akimoto, K.,251 Akiyama, T., 14, 70, 189, 196, 389, 423 Aktah, D., 332 Akutsu,Y.,314 Aladro, F.J.,303 Alami, M., 334,396 Alayrac, C., l3l,293 Albanese,D., 37, 340, 341 Albaneze-Walker,J., 138 Albericio, F., 65 Albers, R.4,.,462 Alcaide,8.,20,227 Alcazar-Roman,L.M., 48 Alcudia, A., 122 Alcudia, F., 120 Alderfer, J.L., 165 Aldrich, C.C., 138 Aleixo,A.M., 391 Aleman,P.,246 Alessandrini,S., 65 Alexanian,8.J.,2'73 A\ezza,Y.,358 Alfonso, C., 385 A]i, B.E.,319
Ali,r.s.,143 Ali,T.,231 Alila, J.R.,249 Alimardanov,A., 233,417 Allan,J.F.,259 Allen,D.A., 82 Allen,J.V.,123 Allen,Jr.,A.,416 A l l e nM , .J.,314 Allen,M.P.,449 Allen,N.T.,184,421 Alter,E.,244 Allison,B.D.,155 M.,32'7 Al-Masum, Almeida, W.P.,314 Almendros, P.,20,22'l
Author Index
Almirante,N.,436 Aloise,A.D.,182 Alonso,D.4., 124,312 Alonso,8.,254 Alonso,J., 138 Alonso,R.,246 Alper,H., 152,328,477 Alper,P.B.,261 Alper,H., 167 Altundas,R., 363 Alvarez-Manzaneda, E.J.,277,4U Amano,4., 131,222 Amano,T., 73 Amarasinghe, K.K.D.,45 Amatore,C., 335 Amaya,A.S.,358 A m i i ,H . , 2 5 9 Amombo,M.O.,79 Amone,4., 192 Amouroux,R., 210 Amrein,5,75.,444 A n ,D . K . , 2 1 0 Anaclerio, 8.M.,223 Anand,R.C.,237 Anand,R.V.,341 Andemichael, Y., 122 Andergran, M.,394 Andersh,B., 72 Anderson, E.A.,181 Anderson, J.C.,389 Anderson, O.P.,123 Anderson, S.R.,438 Andersson, C.-M.,214 Andersson, P.G.,123 Ando,J, 146.,319 Ando,J.-I.,146 A n d oK , . , 7 . ,1 8 7 Ando,M., 61,268,385,457 Ando,T., l5 Andreu,C., 178 Andrews, 4.T., 124 Andrews, I.P.,416 Andrus, M.8., l2l, 124,l3l,4ll Angermund, K., 121 Angiolelli,M.E.,299 Anilkumar,G.,410 Anifkumar. R., 57,'lO,276 Anjaneyulu, S.,201 Anoro,5.,492 Anselme.G.. 13.63
Anselmi, E.,451 Ansorge, M.,332 Antilla,J.C.,123 Antonelli,8.,416 Antras,F.,269 Antus,S.,344 Anwar,U.,227,323 Anzai,5.,327 A o k i ,K . , 2 5 1 A o k i ,M . , 2 1 6 A o k i ,N . , 2 1 3 Aokt,Y.,462 Aoyagi,S.,448 Aoyama,T.,456 Aoyama,Y.,20 Aparicio, D.,477 Apella,D.H.,56,124 Apostolopoulos, C.D..2 I4 Aragoncillo, C., 20,227 Arai,H., 385 Arai,M.,88,314,4M Arai,M.A,4M Arai,N.,92,308 Arai,S., 120,340,341 Arai,T.,4O4 Araki,M., 323 tuaki,S.,230,231,290 tuaki, T., 131,409 Aramini,4.,399 Aranyos, 4., 175 Arasaki, H.,341 Arase,A., 180 Araujo,M.A.,294 Arbore,A.P.A.,159 Arbuzova, S.N.,351 Arcadi,A., 319 Archibald,S.J.,82 Ardeshir,K., 160 Arend,M., 175 Arends. I.W.C.E., 216,418 Aril A.M., 241,427 Arifuddin,M., 151 Arikan,N., 341 Arikita,o., 319,455 Arimura.K.. l3l, 449,489 Arioka,D., 58 Arisawa,M., 196,416 Ariza,X.,85,120,351 Arjona,O.,435 Armour,D.R.,328
Armstrong,A.,362 Arnauld,T.,375,437 Arnold,8.P.,354 Arnold, L.A., 31 Arpin, S., 59 Anate, M., 385 Artamkina,G.A., 338 Arterbum,J.B., 180 Asada,D., 55 Asakawa,K., 55, 57 Asami,M., 121 Asano,S., 23 Asano,T., 79,196 Asao,N., 7 , 17, 196,2I 2. J{fr. {1' Asaoka,M., 8l A s a u m iT , .,41,467 Aschwanden,P.,494 Asensio,G., 124,178.2'16 Asgari,D., 124 Asghari,J., l7 Ashtiani,A.M., 165 Askin,D., 23 A s o ,N . , 4 3 5 Asokan,C.V.,2l8 A s p i n a l lH , . C . ,l 2 l Ates,A., 92 Atherton,M.J., 188 Atkinson,R.N., 155 Attolini,M., 308 Aube,J., 70,427 Aubert,C., 163 A u d r a i nH , ., l2l Aufauvre,L., 164 A u g e ,J . , 1 4 1 , 2 2 7 , 2 5 7 Augostyns,B., 92 J.M.. 385 Aurrecoechea, Aurrekoetxea,N., 385 M.-T.. {5J Averbuch-Pouchot, Averell,K.M., 143 A v e r e t tD , .,24,232 Aversa,M.C.,458 Avery,B.A.,444 Avery, M.A., 398,444 Avolio, S., 201, 233, 298 Axenrod,T., 70 Ayers,J.T.,438 Ayers,T.A., 256 Azerad,R., 120 Azim, A.,24'7 Azuma. T., 21. 348
Author Index
i\
56 Ir 1S^
+
( I).214 : : 1 7 t Ir L:
IJI
t90
I
<.1
, .
. . : < . I
,.1 I F, :16.-ll8 l : .
t.j:a t. -l-19..189 ),/. -il6 _1
'
.\ I
Armstrong,A.,362 .\rnauld,T.,375,437 .\rnold, E.P.,354 A r n o l d ,L . A . , 3 1 Arpin, S., 59 .A,nate, M., 385 .\rtamkina,C.A., 338 .\rterbum,J.B., 180 Asada,D., 55 Asakawa,K.,55, 57 A s a m i ,M . , 1 2 1 Asano,S., 23 Asano,T., 79,196 .\sao,N., 7, 17, 196,212,409,439 .\saoka,M., 81 Asaumi,T.,41,467 Aschwanden,P.,494 A s e n s i oG. . , 1 2 4 ,1 1 8 , 2 4 6 Asgari,D., 124 Asghari,J., l7 Ashtiani,A.M., 165 Askin, D., 23 A s o ,N . , 4 3 5 A s o k a nC , .V.,218 A s p i n a l lH , . C . ,l 2 l Ates,A., 92 Atherton,M.J., 188 Atkinson,R.N., 155 Artolini,M., 308 Aube,J., 70,427 Aubert.C., 163 A u d r a i nH , ., l2l Aufauvre,L., 164 A u g e ,J . , 1 4 1 , 2 2 1 , 2 5 7 Augostyns,B., 92 Aurrecoechea, J.M., 385 Aurrekoetxea,N., 385 Averbuch-Pouchot, M.-T., 454 Averell,K.M., 143 A v e r e t tD , .,24,232 Aversa,M.C., 458 Avery,8.4.,444 Avery, M.A., 398,444 Avolio, S., 201, 233, 298 Axenrod,T., 70 Ayers,J.T.,438 Ayers,T.A., 256 Aterad,R., 120 Azim,4.,241 A z u m a ,T . , 2 1 . 3 4 8
Azzena,U.,247,254 Baati, R., 23, 140 Baba,A., 16l, 162, 213, 230, 277, 407, 422,439 Baba,A.R., 277 Baba,K., 239 Baba,S.,232 Babu,B.S.,230,255 Babudri, F., 66 Baceiredo,4.47'7 Bach,J., 3 Bach,T.,240 Back,T.G., 122 Backvall, 1.E.,290, 320 Biickvall,J.-E.,131,205, 303 Badia,D.,497 Badrian,4.,241 Bae,J.W.,269,314 Baek,H.S.,227,385 Bagnoli, L., 122 B a i k ,T . - G . ,3 7 , 1 4 6 ,1 5 7 , 2 2 7 , 4 1 6 8a1k,W.,227 BailenM , .A.,304,418 Bailey,W.F., 122 Bajwa,J.S.,59 Baker,R.T., 88 Balakumar,R.,407 Bafasubramanian,K.K., | 48, 230, 255 Balavoine,G.G.A., 120 Baldwin,S.W 70 Balenkova,E.S.,450 Balicki,R., 483 Ballesteros,A., 48 | Ballini,R., 159,202, 361, 491 Balme,G., 148,252 B a l s e l l s J, . , 1 2 3 Bandaru,R.,232 B a n d i n iE , .,479 B a n d i n iM , .,430 Bandyopadhyay, A.K., 487 Bandyopadhyay,T., 39 Banerji,A.425 Banik,B.K., 314,379 Banik,I., 379 Bao,W., 1l, 378 Baptistella, L.H.B., 391 Baragana,B, 130 Barakat,K.J.,314 Baran,P.S.,155, 156,236
Author Index
Baratta,W., 128 Barattucci, A., 458 Baraznenok,I.L., 450 Barba,G.R., 192 BarbasIII, C.F., 121 Barberan,O.,232 Barbero,A.,290 Barbero,M., l9 Barber-Peoc'h,I., 150 Barboni,L.,491 B a r c i n aJ, . O . , 4 1 0 Barfacker,L., 5l Barkin,J.L.,493 Barluenga,J., 70, 138,213,399,481 Barma,D.K., 140 Barnard,T.S.,239 Barnes,D.M., 123 Barnes,J.C.,347 Barnhurst,L.A., 89 Barone,C.,92,400 Barontini, F., 290 Barrero,4,.F.,277, 464 Barrett,A.G.M., l2l, 273, 375, 489, 490 Barrett,D.G., 85 Barrientos-Astigarraga,R.8., 294 Barros,D., 122 Barros,M.T., 398 Barta, N.S., 303 Bartels,A.,427 Bartok,M., 352 BartoliG , '65,93,248 B a r t o nD , .H.R.,437 Bartsch,M., 303 Barua,A., 454 Barua,N.C., 15,454 Basavaiah, D., 164 Basset,J.-M, 123 Bassindale, A.R., 129,455 Basros,G.P.,453 Bates,E.D., 192 Batey,R.A., 4,'70,72, I 68, 184,362,479 Batra,D., 360 Batrice,N.N., 155 Bats,J.W., 120, 196 Baucherel, X., 142,308 Baucke,D., 2 BaumgartneqM.T., 358 Bautista,O.,458 Bazureau, J.-P.,186 Beak.P.. 125
Beal\, 1.C.,213 Beauchamp,T.J.,2O2 Beaudry,C.M., 375 Beaulieu,C.,287 Becher,J., 398 Bechir,B.H., 178 Beck,V.H.,478 Becker,F.F.,379 Becker,H.,416 Beckman,J.,462 Beckmann,A.,252 Bednarz,M.S.,454 Beghetto,V., 55 Begtrup, M., 201 Begue,J.-P.,214,371 Behbahani,F.K.,243 B e i ,X . , 4 8 Bekaert,A.,232 Belderrain,T.R., 89 Beletskaya,LP.,48, 222, 338,413 Bell, A., 86 B e l l ,D . , 1 2 3 Bella,M., 124 B e l l a s s o u eM d ,. , 4 1 6 Bellegarde, J.W.,363 Beflemin-Laponnaz, S., l2O, 453 B e l fe r ,M . , 4 l , 3 0 3 ,3 1 4 , 3 2 3 , 3 2 7 . 3 3 5 Bellesia,F, 352 Bellina,F., 393 Bellucci,M.C., 65, 93, 248 Belluti,F., 53 B e l o k o nY , . N . ,l 2 l , 2 4 3 Beltrami,R.,467 B e l y a k o vS, . A . ,1 8 , 2 0 1 Benati, L. 444 B e n - D a v i dI,. , 7 l Bender,J.4.,427 Beni, Y.A., 146,308, 404 B e n i c c h i oA, . , 4 3 6 Benneche, T., 151,320 Benson,S., 222 Berens,U., 124 Berente,2.,319 Bergbreiter,D.8., 192, 3l2 Berger,D.,467 Bergmeier,S.C.,70, 395,404 Bergstad, K., l3l, 303 Beris,D.C., 341 Berkowitz,D.8.,294 Berlin,S., 348
Bernad,P.L.,386 Bernard,N., 290 Bernardinelli,G., 123 Bernini,R., 178 Berree,F., 186 Berrisford, D.J.,l3 Berry,C.R.,79 Berthiaume, D.,267 Bertilsson, S.K.,123 Bertrand,F., 5 Bertrand, G.,477 Bertrand, M.P.,299 Bertrand, S., 122 Bertus,P.,124,2ll Bertus,V.,496 BesetM.,444 Bessmertnykh, A.G..48. ::l Betzemeier, 8., 192,216 Betzer,J.-F.,290 Betzmeier, 8., 308 Beyer,J.,57 Bez,G., 15,454 Bezbarua, M.S.,l5 B h a n a gB e ., M . , 8 8 , 3 l . t Bhanumathi, N., 151 Bharathi,P.,395,427.118 Bhat,B., 150 Bhat,N.G.,458 Bhattacharjya, A., 42l Bhattacharya, M., 398 Bhattacharyya, S.,398 Bhawal,B.M.,465 Bhosale, D.G.,259 Bieber,L.W.,393,492 Bielawski, C.W.,375 Bienz,S.,76 Biermann, U., 185 B i g i ,F . , 4 9 1 Bigot,A., 286 Bilibin,A.Y.,205 Billard,T., 274, 348,3.19 B1lnov,K.A.,222 Binkul,J.R.,4 B i o ,M . M . , 4 1 7 Biran,C.,259 Bisi,A., 53 Bittner,S.,400 Bjerregaard, T., 201 Bjorsvik, H.-R.,241 Blackburn, L., 263
tuthor Index
ri , .173 LL. .: r[]. T.J.,202 r L. : . ( - .\ { . . 3 7 5 Lt-- ...('.. 287 r l98 t. t :i tl . I78 t . r i l 7 8 \-. rl:..179 l-' :1.l16 \:, . 1. 1 6 2 \ : ' . , ; t .. \ . . 2 5 2 lt.:- \1.S..;154 \ . -s5 h\t.tol r t'.)11.377 u, t.. I, K..243
\ - . h" \.132 lc--, r. I'.R..89 r . . , , . r . I P . 4 8 ,2 2 2 ,3 3 8 ,4 7 3 . r
li
l. \:
111
r . . - . 1M . ..416 ri . :.' J.W..363 : : ' I u p o n n a zS, . , 1 2 0 , 4 5 3 :r ''l -ll.-103,314,323,327,335 f. , r. r5l ll:
:
It
l9-l
\l C.6-5,93,248
rr
i
\ \. t21,243
a'
i{ . 167
u
\ \.. ltt,201
l;
j-l]
r.7l D, r' \ -117 ) . 116.308,404 i(
\
-l-16
e.'.1.157.320
r\
irl
rt. i' .ll9 r . . : I ) . E . .1 9 2 , 3 1 2 r i, -167
n . . S C . .1 0 , 3 9 5 , 4 0 4 r-,. tr l-il, 303 r-ll i) M l) 8 .294 t. \ .+x
Bernad,P.L.,386 Bernard, N., 290 Bernardinelli,G., 123 Bernini,R., 178 Berree,F., 186 Berrisford, D.J.,13 Berry,C.R.,79 Berthiaume, D.,267 Bertilsson, S.K.,123 Bertrand,F.,5 Bertrand, G.,477 Bertrand, M.P.,299 Bertrand, S., 122 Bertus,P.,124,211 Bertus, V.,496 Besev, M.,444 Bessmertnykh, A.G.,48,222,473 Betzemeier, 8., 192,216 Betzer,J.-F.,290 Betzmeier, B., 308 Beyer,J.,57 Bez,G., 15,454 Bezbarua, M.S.,l5 Bhanage, 8.M.,88,314 Bhanumathi, N., 151 Bharathi, P.,395,427,428 Bhat,B., 150 Bhat,N.G.,458 Bhattacharjya, A., 421 Bhattacharya, M., 398 Bhattacharyya, S.,398 Bhawal,B.M.,465 Bhosafe, D.G.,259 Bieber,L.W.,393,492 Bielawski,C.W.,375 Bienz,S.,76 Biermann, U., 185 B i g i ,F . , 4 9 1 Bigot,A., 286 Bilibin,A.Y.,205 Billard,T., 274, 348,349 B1lnov,K.A.,222 B i n k u lJ, . R . , 4 B i o ,M . M . , 4 1 7 Biran,C.,259 Bisi,A., 53 Bittner,S.,400 Bjenegaard,T., 201 Bjorsvik,H.-R.,241 Blackbtrn,L.,263
503
Blacker, A.1.,37,418 Blacklock, T.,59,358,377,473 Blacklock,T.J.,358,377,473 Blackwell,H.E.,375 Blackwell, J.M.,478 Blades,K., 303 Blake,A.J.,242 Blakemore, P.R.,86 Blanc,D., 124 Blanco,O.M.,375 Blanco-Urgoiti, J., 167 Bland,D.C.,95 Blaser,H.-U.,124 Blass,B.E.,359 Blazejewski, J.-C.,451 Blechert,S.,5, 375 Blettner,C.G.,319 Block,M.H.,298 Blomgren,P.A.,277,281 Bluhm,H., 121 Bo, Y.,96 Bobb,R.A.,l5 Bodas, M.S.,459 Bode,J.W.,449 Boeckman, Jr.,R.K.,64 Boelens, M., 65 Boeykens, M.,264 Bogdal,D.,218 Bogen,S.,444 Bohm,V.P.W.,48,205,224 Boiteau,L., 285 Boivin,J., 173 Boix,C.,492 Boix-Bernardini, C., 178 Bolm,C., 54,120,121,123,362,369,400 Bolourtchian, M.,247 B o l sM , . ,4 3 , 2 3 4 Bomben, A.,428 Bonaccorsi, P.,458 Bonacorso, H.G.,453 Bonaga, L.V.R.,167,410 Bondlela, M.,416 Bonin,M., 293,358,385 Bonini,8.F.,218,227 Bonitatebus, P.I.,273 Bonjoch, J.,417 Bonnet,V., 201 Bonnet-Delpon, D., 214,377 Booker-Milburn, K.I.,242 Bootle-Wilbraham, A., 4
Aut}or Index
Bora,U.,218 Borah,R., 1,280 Bordeau, M.,259 Bordoloi,M.,259 Borg,G.124 Borths,C.J.,123 Boruah,A., 59 Bosch,L, 399 Bosch,M.P.,241 Boschetti, C.8.,2'l6, 314 Bosco,D., 241 Bosco,M., 65,93,248 Bose,A., 312,314 Bose,A.K.,314 Bose,D.S.,155,342,362 B o s eG , . ,2 1 8 Bosica, G., 159,361 Bosnich,8.,222 Bossart, M.,443,444 Boto,A., 235,346 Bottcher,4.,416 Bottke,N., 344 Bouchet,C., 358 Boudier, 4.,298 Boudjouk,P.,142,320 Bouillon, I.-P.,462 Boukhris,S.,399 Bouquillon, S.,405 Bourgeois, D.,375 P.,443 Boussagnet, Boutros, A., 314 B o u y s sD i ,. , 1 4 8 , 2 5 2 BouzBouz, S., 121 Bouzide, A.,263,44'l Bovicelli, C.,252 Bovicefli,P.,l'78, 237 Bowden, R., 188,189 R.D.,189 Bowden, Bower,J.F.,411 Boyer,B., 59 L.,201 Boymond, Braddock, D.C, l2l, 2'73, 3'75, 489,490 Braga,A.L., 186,423 Braier,A.,252 Brain,C.T.,266 Brandsma, L.,247,351 Brandt,T.A. 120,416 Braun,M.,477 Braun,N.A.,344 Braun,R., 332
Brauner, J.,453 Braverman, S., 160 Bray,1.D.,344 Breit,B, 151 Breitling,F.M.,120 Brel,V.K.,342 Bremberg, U.,37, 120,l2l Brenek,S.J.,362 Brenner, 8., 280 Brenner, M., 428 Brestensky, D.M.,351 Breton, G.,201 Breuer,E.,349 Bricout,H.,320 Bridger, G.J.,54,473 Brigas,A.F.,299 Brillet,C.,481 Brilman,M.H.G,3l Brimble,M.A, 346 Brinchi,L, 399 Brindisi,D, 336 Brion,J.-D,232 Briot,A, 375 Brogan,J.8.,369 Brook,M.A.,222 Brookhart, M., 54 Brooks,P.R.,66 Brosius, K.,239 Brosse, N., 464 Brown,C.D.,70 Brown,H.C.,9, 20,64, 125,128,160,446 Brown,R.E.,468 B r o w nS , . M .3 , 41,419 Brown,S.P.,172 Brummond, K.M.,435 Brun,E.M.,251 Bruneau, C.,52,375 Brunel,1.M.,120,123 Bruneton, J.,309 Brunner, H., 314,319 Brunner, M.,416 Bruno,G.,458 Bruns,S, 121,274 T.A.,401 Bryson, Bubnov,Yu.N.,437 Bucher,8., 192 Buchwald,S.L.,38, 54,56,122,124,149, 175, 212,320,323,32'1,354,433,473 Buck,R.T.,369 Budnikova, Y., 281
Buezo,N.D.,124 Buhr,W., 181 Bui,G.,243 D., 120 Buisson, Bujard,M.,375 Bulger,P.G.,159 B u l l ,S . D .3, , 9 2 , 1 2 0 Bumagin,N.A., 320 M.W.,354 Bundesmann, T., 358 Bunlaksananusorn, Bunz,U.H.F.274 Buono,F.,323 Buono,G., 120,123 Burd,A.P.,188 K., l2O Burgess, Burk,M.J.,124 Burkart,M.D., 130 B u r k eS, . D .3, 5 1 ,3 7 5 , 4 3 8 S., 124 Burkhardt, Burns,C.J.,409 Burt,T.M.,359 E.,2 Buschmann, N., 375 Buschmann, J.,96, I 2 l. l{t Busch-Petersen, Buske,D.C.,169 D.A.,375 Bussmann, J.M.,303 Bustamante, T., 122,149.389 Busujima, Buzard,D.J.,65 Byrne,L.A.,246 I., 181 Bytschkov, Byun,I.S.,385 I., 54 Cabanal-Duvillard, I2l Cabezza,l., S.,88,335 Cacchi, C a d d i c kS,. ,1 5 , 3 9 9 A.B.,341 Cadwaller, Cahiez,G., 201,204,261 CaLC., 123 Cai,W, 362 A., 366 Caiazzo, S.,293 Campagna, A.D.,210 Campbell, C.L.,49'7 Campbell, K.R.,120 Campos, P.J.,149 Campos, Camps,P.,345 B., 248 Camuzat-Dedenis, D.J.,159 Cane-Honeysett,
AuthorIndex
J -:a-l u . .> . 1 6 0 .+
|
t : .
,F\1.120
B.L. . 17.120,121 ' J
. .ol
E :\0 \t rt8
r )\ t . . 3 5 1 ,,l l :l -l.l H :lt )
51..173 t- : e 9
u - l
\t HG.3l \t \. .116 L, :rq f) :16 D lrl
169
t8 I
1
- - -
r. \l . 5-l tR.6(r K :re i..lh-l
-tt llr I ( . r .1 0 .6 4 , 1 2 5 , 1 2 8 , 1 6 0 , 4 4 6 i I J6,\ \1 r1l.4l9 P .-l u r ' \ 1 . .4 3 5 't l< I (' r :. -175 \t r:0. 123 . : rtt9 H r Il. -ll9 It :t6 . i:' l7l :: " { - i r) l
f- \
-137
- .r]
: L .r8,54,56,122,124,149, : ;r t. -323, 327,354,433,473 :^\) a \ ltsl
jM
ilil li ltr
il
Buezo,N.D.,124 Buhr,W., 181 Bui,G.,243 Buisson, D., 120 Bujard,M.,375 Bulger,P.G.,159 B u l l ,S . D .3, , 9 2 , 1 2 0 Bumagin,N.A., 320 M.W.,354 Bundesmann, Bunlaksananusorn, T., 358 Bunz,U.H.F.274 Buono,F.,323 Buono,G., 120,123 Burd,A.P.,188 Burgess, K., 120 Burk,M.J.,124 Burkart,M.D., 130 Burke,S.D.,351,375, 438 Burkhardt, S., 124 Bums,C.J.,409 Burt,T.M.,359 Buschmann, E.,2 Buschmann, N., 375 Busch-Petersen, J.,96, 121,248,370 Buske,D.C.,169 Bussmann, D.A.,375 Bustamante, J.M.,303 Busujima, T., 122,149,389 Buzard,D.J.,65 Byme,L.A.,246 I., 181 Bytschkov, Byun,I.S.,385 Cabanal-Duvillard, I., 54 121 Cabezza,l., Cacchi, S.,88,335 C a d d i c kS,. ,1 5 , 3 9 9 Cadwaller, A.B.,341 Cahiez,G., 201,204,261 Cai,C.,123 Cai,W.,362 A., 366 Caiazzo, Campagna, S.,293 A.D.,210 Campbell, C.L.,497 Campbell, K.R.,120 Campos, P.J.,149 Campos, Camps,P.,345 Camuzat-Dedenis, B., 248 Cane-Honeysett, D.J.,159
Cannes,C.,280 F.,416 Cantagrel, Cao, G., 335,340 Cao,G.-Q.,335 Cao, P., 41,124 Cao, Y.-Q., 340 Caporusso,A.M., 290 Caposcialli,N., 86 Capozzr,M.A.M., 29, 2O2 Cappa,A., 93 Capriati,V., 81, 161 Caprio,V.8.,346 Caputo,T.D.,427 Caracoti,A., 385 Carboni,8.,232 Carda,M., 375 Carde,L., 123 Cardellicchio,C., 29, 202 Cardillo, G., 120 Carelli, I., 335 Carnell,4,.J.,178, 362 Caron,S.,360,483 Carpino,L.4.,86,270 Carreira,E.M., 121, 261, M9, 494 Carretero,J.C., 124, 327 Carreyero, C., 124 Cuillo,L.,49'l Carro, C., 146 Canoll, M.A., 344 Carter,C.A.G., 88 Carter,D.S., 240, 369, 456 Casadei,M.A., 88,410 4.L.,299 Casalnuovo, Casamrbios,L., 167 Casati,S., 247 Case,B.L., 192 Cassayre,J., 143,16-7 A.-S.,417 Castanet, Castedo,L' 152, 375, 473 Castillo, E., 375 Catellani,M., 319 catt, J.D.,251 Catteau,J.P.,248 Catterick,D.,490 Caturla,F., 159 Cava,M.P., 150 Cavazzini,M., 192, 308 Cavicchioli,M.,252 CazeavP.,259 Cazes,B.,269
Author Index
T 2
v
*
Ceccarelli,S., 123 Cekovic, 2.,444 Cenini,5.,467 Cere,Y.,227 Cermola,F., 2l Cemy,M., 172 Ceni, A.,436 Certal,V., 138 Cesa,S, 410 Cha,J.K., 210,473 Cha,K.S., 170 Chada,R.K., 214 Chadwick,D.,490 Chahboun,R.,277,464 Cha|B.,267 Chaikovski,V.K., 233 Chakrabarty,M, 193 Chakraborti,A.K., 23 Chakraborty, V., 259 Chalaye-Mauger,H., 454 Chamberlin,R.M., 329 Chambers,R.D., 188, 189 Chan,A.S.C.,122,124 Chan,J.,45 Chan,K.S.,324 Chan,T.H., 15, 19, 153, 156, 157,227, 421 Chand,P.K.,232 Chandra,K.L.,149 Chandraiah,L., 163, 354 Chandrasekaran, S., 25, 80,377 Chandrasekhar, S., 57, 70, 76,163,165, 177,20r, 276,354, 407, 427 Chang,C.-1.,444 Chang,G.X., 387 Chang,H.-M., 48,422 Chang,H.-Y., 385 Chang,J.-W., 120 Chang,S.,52,248 Chang,S.-J.,248 Chapleur,Y., 150 Charette,4.8., 29, 234, 450 Charonnet,E., 159 Chary,K.P.,400 Chataigner,I., 13, 123,394 chatani,N., 41, 89, 90, 167,467 Chatgilialoglu,C., 329 Chatreaux,F., 416 Chatterjee,A.K., 375 chatterton,c.,85,324
Chattopadhyay, 4.,492 R.V.,312 Chaudhari, S.S,155,420 Chaudhari, K.,l2l Chaudhary, M.K.,218 Chaudhuri, B.P.S.,142,320 Chauhan, K.K.,231 Chauhan, Chauhan, M., 142,320 Che,C.-M.,344 Chemla,F., 290,298,299 Chen,B.-C.,454 Chen,C., 124,201,308,344,385,417, 462 124 Chen,C.-C., Chen,C.-D.,201 Chen,C.-H.,344 Chen,C.-P.,308 Chen,C.-T.,385 Chen,D.-J.,347 Chen,F.,254,410 Chen,G.-M.,9,64,446 Chen,H., 122,335,417,445 Chen,J.,202,351,355 Chen,J.S.,202 Chen,J.-X.,351 Chen,K.,122 Chen,M.-F.,15 Chen,P.,70 Chen,Q.-Y.,458 Chen,R., ll, 196,378 C h e nS, . , 7 9 , 2 1 4 Chen,S.-F.,214 Chen,W 85.,192,324,430 Chen,Y., l2O,124,265,363,375, 389 Chen,Y.J.,265 Chen,Y.-J.,363,389 Chen,2., 39,319,320,329,344,347 Chen,Z.-C.,329,344,347 Cheng,C.-H.,35,48,281,282,422,460 Cheng, D., 80,175 Cheng, H,58 Cheng, K.,237 Cheng, Y.,410 Cheong, J.H.,201 Cherkinsky, M, 160 Chervin,5.M.,232 Cheung, M.,285 chi, D.Y.,178 chlz.,194 Chiarini,M., 319
Chiarotto,I., 335 Chiba,K., 88,4-5-i Chibiryaev,A.M.. :l Chieffi,A.327 Chinchilla,R.. 3O1. Chisowa,E., 29.1 Chiusoli, G.P..3-16 Cho, C.-G.,358 C h o ,C . S . , 3 1 9 l.- 1 5 Cho, G.Y., 163 C h o ,J . H . , 6 1 .l 8 - 1 Cho, S.-D.,224. 1t6 C h o ,S . W . , 3 2 3 C h o ,S . Y . ,2 1 0 Cho, Y.J.,269. -1lJ Choi, C.-K., 331 Choi, B.Y.,341 Choi, J.-C,88 Choi, J.H.,389 C h o i ,J . - H . ,1 9 6 Choi, J.-K.,24 Choi, J.Y.,48. I I I C h o i ,M . C . K . . l l { Choi, S., 122. l5 t' C h o i ,S . - C . ,1 5 7 Choi,Y.J.,261 C h o i ,Y . K . ,5 l Choji, K., 298 C h o n g J, . M . ,3 1 . r t ) Chong, P.Y.,4-5.1 Chopa,A.B., 29-l Choppin,t., 36. -19 Chorev,M, 221 C h o u ,W . - C . .2 l J Choucair,B, 217 Choudhury,P.K..:: Choudhury,S.K..{: Chowdhury,C.. l{t Chowdhury,S..-ll6 Chrisman,W.. 166. Christe,K.O.. l9 Christensen.T.8.. .1 C h r i s t i eS, . D . R . .l 8 Christoft'ers,J.. l{l Christos,T.E.. -ld) Chu, F., 88, 9-5.96 Chuang,C.-P. 16.1 Chuang,L.-W.. :r.6 Chuang,S.-C..l:: Chuard,R., .118
thor lnder
rr rr. .\.. J9l R \ - 1l :
\ s . l - i 5 .- 1 2 0 K. lll \t K. :lg aPS.l-ll.-120 \ N . l - 1I \1 1J].320 :qo. 198.299 r < I
t : t 0 l . - 1 0 83.4 4 3 , 85,417. ('.r llJ ( - : r . l r l l C i: rJ-.t (- i' :r)\ C I : r 5 [) . rJ; F :<j. {10
(: \1 e.61.446 li :r. .r35..117,445 J - :.r51.-355 Jr ltl J \. r:l h : l \l : 15 P ' (, -t . -:58 rq6.378 R - . I l s s i :tl \\ .< 192.324,430 I ,. 124.265,363,375,389 \ I j :f,5 \ . 16,1.389 7 :.' 319.320,329,344,347 7 t 119.344,347 : ( l l . 1 5 . 4 8 ,2 8 1 ,2 8 2 , 4 2 2 , 4 6 0 ' l r r r t .I J J '
li
<\
t .R : r 7 t -) : l { ) g j tl .201 r u : . . . :\.1 . 1 6 0 tr: \ \t.. 232 L g\ 1 . 1 8 5 r\ .-3 ,.
- !-i
n : .\ l . l l 9
Chiarotto.I.. 335 C h i b a .K . , 8 8 , 4 5 5 4.M.,241 Chibiryaev, C h i e f f iA , .,327 Chinchilla,R., 304,418 Chisowa,8.,294 Chiusoli,C.P.,336 Cho,C.-G.,358 Cho,C.S.,319,335, 3'76 Cho,G.Y., 163 C h o ,J . H . , 6 1 1 , 83 Cho, S.-D.,224,416 Cho. S.W.,323 C h o ,S . Y . ,2 1 0 Cho,Y.J.,269,314 Choi, C.-K., 332 Choi, B.Y.,341 Choi,J.-C,88 Choi,J.H.,389 Choi, J.-H., 196 Choi, J.-K.,24 Choi, J.Y.,48,121 C h o i ,M . C . K . ,1 2 4 C h o i ,S . , 1 2 2 , 1 5 1 C h o i ,S . - C . ,1 5 7 Choi, Y.J.,261 C h o i ,Y . K . ,5 l Choji, K., 298 C h o n gJ, . M . , 3 1 , 7 0 Chong,P.Y.,454 Chopa,A.B., 294 Choppin,S., 80, 395 Chorev,M,222 C h o u ,W . - C . ,2 1 4 Choucair,8,227 Choudhury,P.K.,227 Choudhury,S.K., 45 Chowdhury,C., 148 C h o w d h u r yS, . , 4 1 6 Chrisman,W.,266,363 Christe,K.O., l9 T.8., 385 Christensen, C h r i s t i eS, . D . R . ,1 8 0 J., 241, 308 Christottbrs, Christos,T.E.,360 Chu, F., 88, 95, 96 Chuang,C.-P.,263 Chuang,L.-W., 286 Chuang,S.-C.,122 Chuard,R., 418
Chuche,J., 393 Chui, H.M.P.,45 Chung,8.Y.,l'70,221 Chung,D.M., 162 Chung,I.H., 170 Chung,K.-Y., 135 Chung,S.-K.,398 Chung,Y.H.,24 Chung,Y.J.,4'\6 C h u n g , Y . K . 1, 4 1 ,1 5 2 Chung,Y.M.,447 Churchill, M.R., 124 Cicchi,S.,404 Ciucci,D., 393 Cififreda,P,247 Ciufolini,M. A., 314, 344 Clark,A.J., 143 Clark, C.G., 143 Cfark, D.H., 355,416 Clark,J.H., 149,359 C l a r k eM , .L.,37,418 Clarke,P.A.,369,487 Clausen,R.P.,43 Clayden,J., 84 Clifford, A.A., 88 Clinet,J.C.,329 Clive, D.L.J., 396, 443, 444 Cloninger,MJ.,449 Clyne,D.S.,32 Coates,D.,223 Cobley,CJ.,477 Cocquet,G., 309 Coe,D.M., 121,369 Coe,J.W.,66,327 C o e l h oF , .,314 Cogan,D.A., 124 Cohen,T., 80,254 C o l a sC , .,319 Colasson,B., 55 Colbry,N.L., 336 Coldham,I., 159 Cole,M.L., 230 Coleman,K.S., 308 Coleman,R.5., l'7,222 C o l l a r dD , .M,314 C o l l a r dS , .,312 Collet,H., 285 Collier,T.R., l7l Collin, J., 387 C o l l i n sC , .J.,64,249
Author Index
Collins,L, 181 Collman,1.P.,20 Colobert,F.,417 Colombo,L., l2l Comanita,B.M.,79 J.Y.,294 Comasseto, Combret,J.-C.,358 Comes-Franchini,M., 2L8, 22'7 Comesse,S., 82 Comina,P.J.,189 A., 285 Commeyras, C o m o y ,C . , 4 0 1 Concellon,J.M., 130,386 Conde,J.J.,243 Condon,S., 280 Condon-Gueugnot, S., 4 l'l Confalone,P.N.,293,473 Consiglio,G., 124 T., 120 Constantieux, C.,329 Constantino, Contreras,J., 65 Cook, P.D.,150 Coppe,M., 308 Coradin,T., 363 Corbel,B., 261 C o r b i n ,F . , l 3 l , 2 9 3 CoreyE , . J . ,1 , 9 5 , 9 6 , 1 2 0 ,1 2 1, 1 2 2 , 1 4 6 , 190,248,370, 4t6 C o r l e y8 , .G.,485 Correa,A.G., 5l Correia,C.R.D.,448 Corrette,C.P.,222 C o r s i ,M . , 4 0 4 Coskun,N., 341 Cosma,C., 285 Cossu,S., 37 Cossy,J., 1 1, 121,263, 448 Costa,A.M., 85, 399 C o s t aM , .,336 Costa,S.C.P.,347 Costelfo,D.P.,259 Cottrell,I.F., 159 F,.A., 214 Couladouros, Coutrot,F,401 Coutrot,P.,401 C o u t u r i e rD, . , 4 1 6 Couty, F., 205 Cowden,C.J., 159 C o w e n ,1 . 4 . , 2 3 Cox.8..242
Cox,C.,246 Cozzi,P.G.,430 Cramailere,D., 120 C r a w l e yM , .L., l2l,303 Crescenzi, B., 178 Crich,D., 192,400 Crimmins,M.T., 121 Crosby,J., 341 Crotti, P., 389 Crouch,R.D., 264, 341 Crousse,8.,214,396 C r u d d e nC, . M . , 2 1 2 Cruz,R., 23 Csaky,A.G., 308 Cuadrado,P.,23 Cucullu,M.8., 89 Cuenca,4., 124 C u g i n i ,F . , 3 1 9 C u i ,D . - M . , 2 8 0 C u i ,W . , 4 3 0 C u i ,X . , 1 3 , 2 4 Curini,M., 362 Curran,D.P.,29, 192, 444 Cutri, S., 293 Czira,G.,246 da Costa,R.C.,492 da Silva,M.F.,393,492 Daasbjerg,K., 385, 434 Dabard,O.A.C., 124 D a b d o u bM , .1.,299,417 D a b d o u bV, . 8 . , 2 9 9 , 4 1 7 Daeuble,J.F.,35I D a i ,C . , 4 7 3 D a i ,G . , 3 5 9 Dai,H.G.,264 D a i ,L . - X . , 4 0 9 D a i ,R . , 7 0 Dakamin,M.C., 11 Dakternieks,D., 124 Dalla, V., 248 Dallaire,C., 395 DalleyN , .K., l2l Dalpozzo,R., 65, 248 Dalvi, P.V.,65 D a n g ,H . - S . , 4 3 8 D a n g e lB , .D.,l2l Danheiser,R.L., 369 Danishefsky, 5.J.,246 Daran,J.-C.,120
Darkins,P., 178 D a r s e sS, . , 3 1 9 D a s ,B . , 3 9 1 Das,D., 293 Das,J., 27, 30,39 D a s ,K . K . , 7 0 Das,S.K., 375 D a s ,U . , 2 1 4 Dash,A.K., 267 Dash,J., 377 Daskapan,T., I Dau,M.E.T.H.,286 Dauben,P.,344,4'77 Dauge,D., 143 Daugulis,O., 120 Dave,P.R.,70 Davey,M.H., 76 David,E., 153 David,G.A., 299 D a v i d ,H . , 6 5 , 3 8 5 Davidson,J.E.P.,l8l Davies,A.J, 159,230 Davies,H., 123,369 Davies,H.M.L., 124.369 D a v i e sl,. W , 2 1 6 , 4 8 5 Davies,S.B.,369 D a v i e sS , . G . ,3 , 9 2 , 1 2 0 .l l I D a v i s , 8 . A . 1, 9 3 D a v i s ,D . S . ,3 9 5 Davis,F.A., 122, 156.201 Davis,Jr.,J.H, 192 Davoille,R.J.,180 Davoli,P., 167 D a y ,M . W . , 3 7 5 Dayan,S., 223 de Buyck, L., 352 de FCerezo,A., 4 l0 dc Farias,F.M.C, l6l de Groot, A., 483 De Kimpe, N., 65. 241. lf'r de Koning,P.D.,l2l d e l a H o z ,A . , 2 3 7 de la Rosa,V.G., 246 d e l a R u a ,R . B . , 4 8 1 De Los Santos,J.,4-58 de los Santos,J.M..'177 De Lucchi,O., 37 de Mallmann,A., 12-3 de Marigorta,M.E.. 290 de Meijers,A., 210
Author Index
;a :r{) L'-.:r 129 r \1i lll.303 y
i.
lTll
,t. -100 ) \ r.. l f .l2l :l I
_'
. '
)
l
,!., 16-1.341 :. i: I Il. .196 n, \l.ll2 l t ) S
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j'
, 1.1 . \ 1 ' . \ 9 .
i
I .\1
l
. ,l -rl)
.
-.1
\r ...1 I' : :e. 192,444 , - " l9l a i' r''l :.r93..192
r- .. r85.43,1 ' \( i . 1 2 . 4 \, t 1 r )99. 411 t.l,.)t)9.417 : : r5l I
:-t i
I ',, n "1(:.l7 r - , 1 ) .I 2 z l
. . . . -I \:, ', i
'.r5 lll h5. 248
l.:.rs Fi.) lll c- :i 1.. -169 r.. . \ J..246 , ll()
Darkins,P., 178 Darses,S., 319 D a s ,B . , 3 9 1 Das,D., 293 D a s ,J . ,2 7, 3 0 , 3 9 D a s ,K . K . , 7 0 Das,S.K.,375 D a s ,U . , 2 1 4 Dash,A.K., 267 Dash,J., 377 Daskapan,T., I Dau, M.E.T.H.,286 Dauben,P.,344,477 Dauge,D., 143 Daugulis,O., 120 Dave, P.R.,70 Davey,M.H., 76 David,E., 153 David,G.A., 299 D a v i d ,H . , 6 5 , 3 8 5 D a v i d s o nJ,. E . P ,l 8 l Davies,A.J, 159,230 D a v i e sH , .,123,369 Davies,H.M.L., 124,369 D a v i e sL, W . , 2 1 6 , 4 8 5 Davies,S.B.,369 Davies,S.G.,3, 92, 120, l3l D a v i s ,B . A . , 1 9 3 D a v i s ,D . S . ,3 9 5 Davis,F.A., 122. 156,201 Davis,Jr.,J.H, 192 Davoille,R.J.,180 Davoli,P., 167 Day,M.W.,375 Dayan,S., 223 de Buyck, L., 3-52 A.,410 de F.Cerczo, de Farias,F.M.C, 161 de Groot,A.,483 De Kimpe,N., 65, 241,264 d e K o n i n g ,P D . , l 2 l d c l a H o z ,A . , 2 3 7 de la Rosa,V.G.,246 d e l a R u a ,R . 8 . , 4 8 1 De Los Santos,J., 458 de fos Santos,1.M.,4'71 De Lucchi,O., 37 de Mallmann,A., 123 de Marigorta,M.E., 290 de Meijers,A.,210
De Nino, A.,248 de O.Vieira,T., 178 de O.Mera, T., 420 de Pascali,F., 336 de Pomar,J.C.J.,409 de Saint Laumier, 1.Y.,354 de Vries,A.H.M., 31 de Vries,J.G.,31,477 D e ,D . , 2 3 0 D e ,S . K . , 2 1 Deadman,J.J.,188 DeBakker,C.,416 DeBrosse,C., 124 Deganello,G., 314 Degani,l, 19., 166 Degirmenbasi,N., 23 DeHaai,S., 88 Dehmel,F.,201 Deiters,A., 125 del Campo,C.,484 def Prado,M., 122 del R.C. Heras,M.,410 Del Zotto,A., 128 Delacroix,T., 261 Delarue,S., 73 Delaval,N.,405 D e l g a d oA, . , 2 3 2 , 4 9 2 Defmond,8.,443 Delmotte,C., 363, 389 Delouvrie,8.,479 Demir,A.S.,445 Demko,2.P.,303 A.,376 Demonceau, D e n g ,J . - F .2, 1 8 Deng,L, 120 Deng,M.-2., 335 Deniau,E., 293 D e n i s ,J . - N . , 4 5 4 A., 175 Denisenko, Denmark,S.E.,37, 48, 121,27| Denton,S.M., 210 Departure,M.,444 Derien,S., 127 Desai,D.G., 244,259 DesalP.,427 Deshmukh,A.R.A.S.. 465 DeShong,P, 1l, 48, 143,4O9,456 Deslongchamps,P.,7 Desmurs,J.-R.,59, 123 Dessanti.F.. 247
510
Author Index
Dessolin,M., 65 Deudon,S., 143 Devasagayaraj, A., 280 D e v i n ,P , 4 4 6 Devine,P.N.,35 Dewkar,G.K., 143 Dexter,C.S.,473 Dhar,S.,218,268 Di Bussolo,V., 389 D i D e o ,M . , 9 3 Di Giacomo,M., l2l Diaba, F., 96 D i a z ,D . , 7 0 Dickinson,L.C.,362 Diederen,J.J.H.,48 Dieter,R.K.,82,290 Dietrich,H.-J.,369 Diez,8.,131,201 D i j k s m a nA, . , 4 1 8 Dinesh,C.U., 385 Ding,K'277 Ding, S., 375 Ding, Y., 123 Dinh, L.V., 192 D i n n e l l ,K . , 3 6 2 D i n o i u ,V . , 2 1 5 Dinsmore,C.J.,95 Dinter,C.L., 120 Dittrner,D.C.,400 Divekar,S., 473 Diver,S.T.,375 Diwok, J.,444 Dixneuf,P.H.,52, 127,375 Dixon, D.J.,449 Djakovitch,L.,334 Do,B., 70 Do,N.M.,483 Dcibler,C., 303 Dobrolsky,J.M., 215 Dodd, R.H., 344,477 Dodsworth,D.J.,304,418 Dogra,K., 121 Dohle, W, 299,360 D o i ,M . , 1 8 2 Doi,T.,444 Doisneau,G., 385 Dolbier, Jr.,W.R., 458 Dolbier, WR., 72 Dolenc,D.,234 Dolling,U.-H., 159,266, 364
Dominguez, E.,497 Dominguez, G.,167 Dommisse, R.A.,483 Donde,Y., 124 Dong,V.M.,428 Donohoe. T.. 254,303.404 Donskaya, N.4.,222 Doris,E.,437 Dorman, S.C.,192 Domelles, L.,423 Dorta,R.L., 153 Dossetter, 4.G.,123 Doty,M.J.,319 D6tz,K.-H.,138 Douat,C., 248 Doussot, J.,427 Doutheau,4.,369 D o y eS , . ,1 8 1 Doyle,M.P.,369 Drager,G., 303 Draper,R.,473 Drauz,K., 123,369 Drauz,K.-H.,123 Dreher,S.D.,489 Dress, K.R.,303 D r i v e rR, . W . , 3 5 1 , 4 3 8 Drowns,M., 359 DruryIII, W.J.,l23, 406 Drury,W.J.,56 Drysdale, M.J.,369 du Roizel,B., 45I D u a nC , . ,7 1 , 4 1 7 Duan,D.-H.,299,385,435 D u a nH , .D.,331 Duan,J.,72,458 D u a nJ, . - X . , 4 5 8 Duan,Z.,146 Dubac, J.,59 Dube,D.,222 Dubinina,T.N.,85 Ducept,P.,396 Duchene,4.,327 Dudding,T., 56 Duddu,R.,70 Dueno,E.8.,88,95,96 Dughera, S.,19,166 Dumartin,G.,443 Dumas, C.,448 Dumestre, P.,77 Dumond, Y.,2ll, 495
Dumont,W., 294,363.389 28J.-r]9 E.,164,281. Dunach, Duncalf,D.J.,143 Duncan,D., 181 M.S.,434 Dunlap, Dunn,K., 124 Dunn,V.,420 Dupont,J.,312,320 Dupuis,L, 65 M.,280 Durandetti, Durden,D.A., 193 Durst,T., 256 P.H.,13,309.461 Dussault, G.,280 Dussin, Dutta,D.K.,492 Dutta,P,22'1 ,231 Duval,E., 8 Duval,O, 309 I.A., 125 Dvornikova, Dyck,B.P.,122 A.J.,51,135 Dyckman, Dyson,P.J.,8 Dzierba,C.D., 122 J.,303 Eames, Earle,M.J.,15 W.,403 Eberbach, Eberling,G.312 Ebitani,K., 88,308 Ebner,G., 193 G.R.,73 Ebrahimian, A.M., 353 Echavarren, Echigo,T., 92 Eckert,M., 314,335,467 B.S.,96 Edelson, D.G.,401 Edington, S.D.,473 Edmondson, K.R.,320 Edvardsen, G.L.,79 Edwards, Efremov,I, 375 Egami,Y., 13 Eger,E.I.,71 Egi,M., 343 Eguchi,S.,344 A.,323 Ehrentraut, M.J.,153 Eichberg, Eikawa,M.,284 E i l b r a c hPt ,. , 4 1 , 5 1 Eisch,J.J.,249 Eisen,M.S.,267
