Chem,
,pd z,t/i/
Fieserand Fieser's
\J
Reagentsfor OrganicSynthesis VOLUME SIXTEEN t\ llr:-rr lFR(,
Mary Fieser HarvardUniversity
t ):: N
Ek, .
/-+\ (w) v_/ A WILEY-INTERSCIENCE PUBLICATION
John Wiley & Sons,Inc. NEW YORK / CHICHESTER / BRISBANE / TORONTO i SINGAPORE
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N-J.T A
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VOLL
ADVISORS Cnur,Rott Blacr MIre Cnlrr,R KRRlr,Ne A. CtuPntcH DeNrr,l ELseut\,l Dr,noRRHEvRRno Mnpcnnsr FaurJopt-le Geucunr TruorHv J. GntNsrstNPn MrcHnr,l H. KnEss Ducx HvuNc Lee
KuRls MacFEnRtN ANnRPwM. MncMIll-nN Jr,NNIeB. NeneNeEnc Hownno Nc Cnetc PRRISH CuRIsroPHenS. Poss Jerp RoHoE Ntcole S. SnuPsoN H. MenrlN Seloel
Mery I
Harvan
EoweRo M. SUHand PrRsr,psoxeDeuETERos, Chairmen
A wlu John I NEWY
what has beenwntt€n' In recognitionof the importanceof preserving booksof enduring have to inc'' Sons' & Wiley ii i. u p"ofi.yof John valuepublishedintheUnltedStatesprintedonacid.freepaper,and we exirt our best effortsto that end' Copyrighto 1992by John Wiley & Sons,Inc' in Canada' All rightsreserved.Publishedsimultaneously thisvork part of any of Reproductionor translation beyondthat permittedby Section107or 108of the tqZOUnited'statesCopyrightAct without the permission of the copyrightowner is unlawful' Requestsfor to permissionoifurther informationshouldbe addressed Department,John Wiley & Sons'Inc' ihe Permissions ISBN 0-471-52721-l ISSN0271-616X Printedin the United Statesof America 1 0 9 8 7 6 5 4 3 2 1 Printcd md boundby Corricr Ccnpanies. Inc'
PREFACE This volumeof Reagentsincludesreportson syntheticuseof reagentspublished :trr the most part in 1989and 1990.As in previousvolumes,the advisorshave rrovided invaluablehelp. Scott Virgil, Greg Reichard,and Mark Bilodeau have readand improvedlarge portionsof the manuscript. Mnnv FrEsEn L ambridge, MA !)ecember 10, 1991
CONTENTS
Reagents I Author index 395 Subjectindex 415
Acyl(carbonyl)cyclopentadienyl(triphenylphosphine)iron, 12, l-2; 14, l-2 cr)
r-...p(cuH,), Fe'
cp/
\coR
Rcview. Daviesr has reviewed use of the chiral iron auxiliary [CpFe(co)P(c6Il5)31for effectingasymmetricreactionsof an acyl group, including alkylation, aldol reactions.Michaeladditions. ' S. G. Davies, Aldrichim. Acta,23,3l (1990). Nkylaluminurn halides. Reactionof'ester enolates with epoxides.t Lithium enolatesof estersdo not openepoxides,but the aluminumenolatesdo. Li to Al exchangecan be effectedwith diethylaluminumchloride. The less substitutedo-c bond is cleavedand the syzdiastereomerpredominates.Reactionsof optically activeepoxidesproceedwith high OH It )l LLuDAA
o ,/\
.3lJ9a4l.> ""'"!ltn', CHrCooC(CHrl, 6%
I
C |
H 2cHcH3
t cHrcooc(cH3)3
?" -) CH3cH,cooC(cH3)j
.-, .^,..^z.lr^.. t"'"Hc(cttr3)3 jIj#g cH3cHcooc(cH3)3 (synlanti = 95l.5, 92Vo ee)
Alkylatuninum halides
2
Hydrolysisand cyclizationof the productsprovide a route to enantioselectivity. -2,4-disrbstituted t rans Y-lactones' Intramolecular clcliution o! a double bontl with ilienones.2 Treatmentof the trienoneI with a typical Lewis acid, c2HsAlcl2, resultsin a non-photochemical (2)' In contrast,useofthe strong [2*2] cycloadditionto form a cyclobutanering product 3' bicyclic in the results resin 15 Amberlyst acidic EilPcr& trld
rings,as shown Thesecyclizationsarealsousefulfor formationof six-membered for cyclizationof 4 to 5 and 6'
/...-}'.,-c(cH3)2
.*
l
l
-
-
-
-
-
-
-
")-?'2
)
l
l
cH(cH3)2
l
+
o
CH,
CH. 4 c2H5Alcl2 Amberlyst15
a-Th-cH(cH3)2
5
45Vo 85Vo
cycloalkenone.r.3 cycloalkenonescanbe preparedby a retro Diels-Alder reacof type l, conductedat25-70' in the presenceof CH3AlCl2(l tion of norbornenes equiv.) and a reactivedienophile,usually maleic anhydrideor fumaronitrile.The acid (4), which epi[4*2]cycloreversionwas usedto preparel2-oxophytodienoic The precursor noracid. to merizesat C13to the trans-isomeron brief exposure of3 at room Treatment as shown. bornene3 waspreparedfrom the known dienone2
T.' S : G Il{. ' P A G
.{fyn od lniro
I
Alkvllithium
riule to nI rrf the :hemical c itrong
\
.
/-Y\.=\ ll \ I
)
f!,:---l----",-1lBu
P I 'illi:5f";T' 11 _____-_-_)il I 86qr
\-,\
I
tcmperaturewith c2H5Alcl2and fumaronitrilein clcH2cH2cl provides4 in 60To yield.
-Severalsteps 40qa
(CHr),COOH i snown
4,0D+ l(X'
I T.-J.Sturm,A. E. Marolewski, D. S. Rezenka, S. K. Taylor,J. Org.,54,ZO39 (1989). t G. MajetichandV. KhetaniTetrahedron Letters,3l,2243,l990't. , rP. A. GriecoandN. Abood,J. Org.,54,6008(1989). Alkyllithiums. a-Lithiophosphonates,tReactionof triethyl phosphatewith a primary alkyllithium(RcH2Li,2 equiv.)in THF at -78 + 0o resultsin an a-lithioalkylphospho-
o ll
-fl' (c,H5o),iioc,H, cr reac\lcl: (l le The ich epior norel room
prl
l-
2BuLi.rHF I
t
I
tc,n,ol,e-cHr-i I I
L
o
l
*o,1""oo",", .l,
Pr
I
(crHso)rPcHCHO
o
{
Allylncrcrry
chlorldcs
nate, the intermediatein wittig-Horner type reactions. Both linear and branched (suchas i-Buli) primary alkyllithiums can be employed,but the reactionwith methyllithium is too slow and inefficientto be useful. This one-stepalkylation/metallation providesa generalroute to a-formylalkylphosphonates. I M.-P.Teulade andP. Savignac, Tetrahedron l*uers, 2t, 405(1987);p. Savignac andC. Patois,Org.Syn.,submitted (1990). Alkyllithium/Cerium(Ill) chloride. vic.-Diamines. Reetzet al.t reporteda stereoselectiveroute to vic.-diamines from N,N-dibenzylaminoaldehydes,readily availablefrom amino acids.The correspondingN-benzyl aldimines (2) undergo addition of alkyllithium compoundsin ether to provide the chelation-controlledadducts.yields are generallyimprovedby useofRli/cecl3 (equationI). The diastereoselectivity canbe reversedby changeof the aldiminegroupto an N-tosyl group by reactionof the aldehydewith N-sulfinyl-ptoluenesulfonamide. TheseN-tosylderivativesreactwith Grignardreagentsto give BzlrN
NBzl
Bul-i/cecl,, Bzl,N .
NHBzI
eilEr
u
%
\S
S,/
j Bzl-
H
\ -Bu
93:j
BzlrN
\_1
Bzl
o H
TsNs:o -
Bzl.N ' Bzl
NTs //
\s i
\
1
H
BuMscl t
tr It'+ I /rv + (Nlt G. A. R'lrd
Ah/
clbl Prcpilit
llC-CCH.o
Bzl.N. ' \ s R .NHBzI / 'Bu Bzl'
3
(ID
(
%
nil*J mbpin ol btr(cthylcr c 2. Rcpai to cyclopcc
I
-Yn=
--4.". mainly the nonchelation-controlled adducts(equationII). Sincemany aminoacids areaccessible in boththe (s)- and(R)-form,it is possibleto preparetheenantiomeric vic.-diamines. ' M. T. Reetz,R. Jaeger, R. Drewlies, andM. Hiibel,Angew.Chem. Int. Ed.,30,103(1991). Alkylmercury chlorides. Rcductivealkylation ol arp-enones. This reactioncan be effectedby a photostimulatedfree-radicalreactionwith RHgcl anda base(KI/K2s2o8,NaI, DABCo).r
Allenyl chlorornethyl
o
branched nth meth-
r* aY\uu-' +r-BuHgc'
:rallation
\-^Y
u i a n dC . hv fiv + NaI lrv + (NHo)rSrO*
{ramrnes fhe correpunds in prored by changeof rulhnyl-pts to give
sulfone
*,o1lY"u'
\-Y
o
o
347o 9Vo
l4Vo 527o 95Vo
'G. A. Russell, (1989). B. H. Kim,andS. V. Kulkarni, J. Org.,54,3768 Nlenyl chloromethyl sulfone (l). Preparation: HC-CCH2OLi + CICHTSCI -f,!i+ CHz:C:CHSOCH Tg +-->
HBzl
";;:":""so,cH2cr l, m.p. 39o
U
Homologation of lr34ienes.r The reagentis particularly useful for cyclohomologationof 1,3-dienes. Thusthe adductI of a Diels-Alderreactionof I with 1,2bis(methylene)cyclohexane undergoesRamberg-Bdcklund rearrangement to the triprovidesthetetraene3. The sequence ene2. Repetitionofthe sequence is applicable to cyclopentadiene, furan, and 2,3-dimethyl-l, 3-butadiene.
(-'Y"t' \-,'\cH, Bu t rino acids 0ltomeric
Koc{cH,, s7%>
-..*. lafrso'cH'cl \-\A.",
J -'YcH' /Y, t i l l \.'\AcH, t R{% "|
g_r,t99l).
Irl
/'Y, I a photorABCO).'
l) l, 60'
Koc(cH,),
-Y, -YcH'
(-\-$.", 3
6
B-Allytbis(2-isocerenyl)borene
I E. Block and D. Putman,Am. Soc., ll2, 4012 (1990)'
Allenylsilanes. at C1 react iuran annelation.t Allenylsilanes substituted with an alkyl group -20o to form furans in at in cH2cl2 (1 each) equiv. Alcl3 and with acyl chlorides 50-80% yield.
c2Hs\
C,H,CH:C:C.
/
si_r_Bu(cH3)2
Arcr
+ Bzrcocl#
/siRl
ll \\ nrr46)-cH,
cH" lR.L.Danheiser,E.J.Stoner,H.Koyama,D.S.Yamashita,andC.A.Klade,Am.Soc,' llr, 4407(1989).
B-Allylbis(2-isocaranyl)borane'
A ( )....),BCH,GH:GH, \ . /
(1).
Atryltribr$h Atybbt rcd by TiCL. b dlylrtal bydroq
+ o
cH"
of (+)-2-carenefollowed Theboraneis obtainedbyhydroboration[BH3.S(CH3)2] bromide' with allylmagnesium reaction and by - methanolysis Asymmitric allylation o! RCHO.T The reagentconvertsaldehydesto homoallylic alcoholsin 94-99Voee, which is significantlyhigherthanthe enantioselectiviThe enantiomerof ( + )-2-carties obtainedwith B-allyl(diisopinocampheyl)borane. of (2) behavesasan enantiomer B-allylbis(4-isocaranyl)borane but known, eneis not aldehYdes. of 1 in allylation
A
T. Trllb. T. h (r9S).
o
cH3vcHs
a
tri Allyhitrnirr Scleaivc & orum triisoPropo cerbonalom.
A funbcr rd copling of trib cquiv.)in THF lJJ.ctll eo c-eltor; ng
rCH,lJ
-cH' (2)
cH3{-/"")'BCH'GH:GH' I cH" Am.Soc.,l|2, l H. C. Brown,R. S' Randad, andU. S. Racherla, K. S. Bhat,M. Zaid|ewicz, 2389(1990).
HJ
Allyltributyltin
p at Cr react Drm iurans in
(l)' Allyltitanium triphenoxide, CHz:CHCH2Ti(OC6H5)3 Selectivecleavageof oxiranes.r This reagentis more effectivethan allyltitanium triisopropoxide for selective cleavagesof oxiranes at the more-substituted carbonatom.
cH"r '\.I
l)o
\/
SrR t_
7
I '-'6tt' '.cH,cH:cH, ;?"w |\+oH| (translcis- l0: l)
CH. lT. Tanaka,T. Inoue, K. Kamei, K. Murakami,and C. Iwata, l.C.S. Chem.Comm.,9O6
(r990). rd,c..1m.Soc.,
Allyltributyltin, Bu3SnCH2CH:CHz (1). Allylation of quinones.t This reactionhasbeeneffectedwith allylsilanesmedi atedby TiCl4, but allyltin reagentsactivatedby BF3etherateare now preferred. The allylatedhydroquinones can be oxidizedto quinonesdirectly by FeCl3.
o tl
CH,CH:CH,
BFr.O(CrH,),
llll \-
BuTSnCHTCH:CfI, jffi-.+ .
tl
o tne followed s to homoalDttoselectivi-
)f | + \-z-carnantiomerof
A further advantageis that the tin reagentis preparedin quantitativeyield by couplingof tributyltin chlorideand allyl chloridein the presenceof Mg turnings(l equiv.)in THF underultrasoundirradiation. 1,2,3-syn-Triols. , Allyltributyltin, activatedbyZnCl2, addsto acylsilanesbearofthe ing an c-alkoxy-p-silyloxygroupwith high syn-selectivity. Protiodesilylation OMOM |
-
(CHr)jSi\,,+-+,,CH,
i l I
O
OTBS OMOM
ln
S o c . ,l l 2 ,
znct,
+ BuTSnCHTCH:CH, G-
","=-{+ \"", OH OTBS (syn/anti= 91 :9)
"#
H,c*1\
OMOM
OH
cH,
OH
t
Allyltributyltin
a syn-l'2'3-lriol'2 The required product affords the monoprotectedderivative of dihydroxylation of CrOsOa-catalyzed acylsilanescan be p^r"puttOby Sharpless alkoxy crotYlsilanes.' OH (cH,),si-\arL,cH,
svr'svn-isomer
(cH3)3si\y,\t",
#
.] . 4'5:1
oAc oH
oAc
T.Alkoxyaltyhizs'aThereactionofl-alkoxyallyltinswitha.alkoxyaldehydes components'Highly stereoselec(14, 16)hasbeenextendedto reactionswith chiral obtained,dependingon the chiralityof tive additionsto provioesyn-I,2-diolscanbe catalyst.Thus additionof (R)-1 to the the tin reagentandthe choiceof the Lewis acid a l d e h y d e 2 c a t a l y z e d U f n f r e t h e r a t e p r o v i d e s t h e h o m o a l l y l i c a lin cohol3asa92:8 by BFr etherateresults a 67 :33 mixture.The reactionor rsi-r with 2 catalyzed
o
BF,.O(C'H'),
--#----
+ cH,
O,"l-y"H,
MoMd
Bu,Sn OMOM (R)-1
OBzl )
9"
cHr--Z^--',"\' t
cHl :
+ cHr6
OBzl
#
Bu.Sn
OMOM
(s)-r
2 OBzl
O
oD HA/--.orBS
ffyfrnrr NbLia ,l lt rerr r
o
il I, CH,CClt
= 92:8) 3 (sYnlanti
o ,t,,"\cHr :
Y lreruu rd K Mru;-rm. : P F. Cinllo I ' U.t, An. 91 'J A. Itersh.I
oBzl
o
OH
ll
retcrscd. lt is t dorblc bood. This diestet percd from l< etrords a singl
I
c:H;,2r.'.././--,f.cts'3 MOMO
lr, c.H.cct
OBzl
= 93:-7) 4 (sYnlanti Jcobb rd t ir@rdrr hlorn rrd
+tsl-rsffs
OBzl
t S-. X.
5
r'\
OTBS
rb-a-
W 6 (oo-38")
the pair); but use of MgBr2 as catalystprovides mixtureof 1,2_diols(mismatched signifiare promotedby MgBr2 homoallylicalcohor4 as a 93:7 mixture. Reactions cantlyslowerthanthosep,o'not"abyBF3'butthematched/mismatchedpairingis
h ldtoFt otrcr n qgr
Alumina
lquired of cr-
le hr des Dselecalrtl'of I ro the a 92:8 r6?:33
,CH. Bzl
)
reversed.It is alsonoteworthythatthe productsfrom either(R)- or (S)-1havean (E)doublebond. This diastereoselective reactioncan be extendedto an aldehydesuchas 5, preparedfrom l-diethyl tartrate.Reactionof 5 with (S)-l catalyzedby BF: etherate affordsa singleproduct6 in72Vo yield (equationIII). I Y. NarutaandK. Maruyama, (1989);y. Naruta,y. Nishigaichi, Org.Syz.,submitted and K. Maruyama, ibid.,(1989). : P. F. CirilloandJ. S. Panek, (1990). J. Or9.,55,6071 \ Idem,Am. Soc.,112,4873 (1990). ' J . A . M a r s h aal ln dG . P . L u k eJ, . O r g . , 5 6 , 4 8(31 9 9 1 ) .
Nlyltrifluorosilane, CH2: CHCH2SiF3. Allylation of o,-hydrory ketones.r An allyltrifluorosilane and triethylamine (l:l) react with c-hydroxy ketonesin refluxing THF to form tertiary homoallyl
o Ho. .cH. ll ",., , (r)cH.icH(oH)cH, + CHr--/,-..,.siF. -IS{5 Z'--)Vcn, H' c (E tZ =e j:3t 1", J" o ll
.cH,
9
tll) C.H.CCH(OH)C6H. + (CH.)'C:CHCH2SiF3
Nzl
Ho\ .c6H5
",", ,
.. ^Z\r)\.CuH, /'..^,, I H -, C H,,C tt,OH (l00%ode\
I
alcohols with predominant syn-selectivity of the hydroxyl group, probably via a pcntacoordinateallylsilicate.'In fact, only one diastereomer is formed on reaction of benzoin with (3-methyl-2-butenyl)trifluorosilane (equation II). I K. Sato,M. Kira, andH. Sakurai,Am. Soc.,lll,
6429(1989).
:l
..-oTBS
desthe srgnifii r i n gi s
Alumina. Hydrohalogenationof alkenesanil alkynes. In the presenceof Al2O3or SiO2, hydrogenhalidesor their precursorsadd to alkenesor alkynesat useful ratesand oftenin quantitativeyield.' CTH,,CHTCH:CH, %
CsHrTCH2CHCH3 CI
Aluminum
chloride
C
(cocl)?, Al'o.
C6H5c= CcH3 ----jE----t
I H \__-/ CH
CUH'
96Vo
Cl. .CHl
9H,
.&cH, \_/
H
CuHt
3Vo
|
cH.
cl
CH,
/-'.'r"', ------,1
|
=-
|
\z-
73Vo
22Vo
Under theseconditions alkynes and alkenesundergo syn-additioninitially, but rearrangeto the more stableadduct. I P. J. Kropp,K. A. Daus,S. D. Crawford,M. W. Tubergen' K. D. Kepler,S. L. Craig'and (1990). V. P. Wilson,Am.Soc.,112,7433
Aluminum chloride. 2-Methyl-1,3-cyclopcntanedione.This dione is commerciallyavailable,but it can be preparedin one stepby reactionof succinicacid with propionyl chloride and aluminumchloride(3 equiv. each)in refluxingnitromethane.l
o tl
o tl
occrH5
..COH * c.H.cocl I "
Arcr' cHrNo. a -Hcl
L
-coH
I
-/\ >
r
63-6e%
\,,-ococrH5 tl
il o
o
-CHCH, -c)HrcooH A ) | V
hitU't r.rl Alclr (l rbrygearx Ar proccdl Cnlb rati ? G tlcti :L lrCor.l !.. l79J I tt A Jur{b
r-(
l'tudl' red *ryo (rl clrf,N of I drin
tt
)-cH.
\\
o
o
Enol ethers via a Dicls-Alder reaction. Reactionof the diene I with the benzylideneaniline2catalyzedby AlCl3 resultsin the adducts3 and 4 as the primary products,evidentlyformedby a Diels-Alder reaction.2
ar
fuHoR
w'"'
I *N\
osi(cH3)3
I
cHc6H5 (R = H, CH3,
ocH3) t
D X,cru laul. r
r) Alcl,,cH,cl, 2) NaHCO, +
!.r*t d
Tb bqt (sFli{
3-Amino-2-hydroxybornanes
9uHoR
!uHnn
a**Y''"' $a os(cH3)3
w
20"
tialll , but
Craig,and
ble.but it orideand
CuH,
--{-*-.,
3 (exo) -780
ll
osi(cH3)3
4 (endo)
70:30 2:98
Fiedel-Crafts alkylation, Reactionof areneswith acid chlorides in CH2CI2 with AlCl3(l equiv.)and(C2H5)3SiH (2.5-3 equiv.)resultsin the alkylatedareneby dcoxygenation of the intermediate acylatedarene.Yieldsof 95% areobtainable,and this procedureavoidsthe problemof polyalkylationobservedin regular FriedelCraftsreactions.3 ' P. G. Meister,M. R. Sivik,andL. A. Paquette, (1989). Org. Syn.,submitted : L. l* Coz,L. Wartski,J. Seyden-Penne, P. Charpin, andM. Nierlich Letters, , Tetrahedron 30,2795(1989). rA. Jaxa-Chamiec, V. P. Shah,andL. I. Kruse,J.C.S.Perkin1, 1705(1989). Numinum(Ill) iodide. Reductivedehalogenationof p-halo ketones.r c-Bromo or c-chloro ketones undergoreductivedehalogenation on reactionwith freshlypreparedAlI3 in refluxing CH3CN(80-957oyield). The reactionprobablyinvolvesan aluminumenolatesince additionof benzaldehyderesults in an aldol condensation.
-CH,
-l o l- oAlr" t,\,t I l.. ll cH'cN cuH,tcH,Br l_c.H,c:cHJ*h
o tl a.",da",
I c6HrcHo,80.
r rheben: primary
0
o o H i l l
c6H5ccH2cHc6H5 I D. Konwar, R. C. Boruah,and J. S. Sandhu,Synthesis,337(1990);H. N. Borah,R. C. Boruah,andJ. S. Sandhu, J.C.S.Chem.Comm.,154(1991).
(1). 3-Amino-2-hydroxybornanes The bornanes la and lb are prepared from 3-endo-2-endo-la and 3-exo-2-exo-lb and (S)-N-(benzyloxycarbonyl)proline, respectively.
(SFl -Amino-2-methoxymethyl-l-pyrrolidine (SAMP)
y"q
cHr-rcHr
-F--/J. l\r../ \ I"ilil''|y/
CH,
fiFo?
trt
cc
iGdl DEr
CH, endo,endo-la
exo,exo-lb
Enantioselcctiveaddilion oI (CzH)zZn to RCHO. Theseare the first secondary aminoalcoholsknown to effect efficientenantioselectiveadditionof dialkylzincs to aromaticand aliphatic aldehydes. l&.
CtHta...oH
/r&t TL FF!
dtt t fror r +dn
C6H5CHO+ (CrHr)rZn# "\;,
CH;CTl
R , 9 2 V oe e
c6Hr3cHo+(crHr)rzn #
I
tt";xll,, S,74Voee
'K. Tanaka,H. Ushio,andH. Suzuki,J.C.S.Chem.Comm.,1700(1989).
(SFl-Amino-2-methoxymethyl-l-pyrrolidine (SAMP). Diastcreoselective synthcsis of lr2-diols.t Thekeystepin anasymmetric synthesisof 1,2-diolsis an enantioselective 2 with silylationof SAMPhydrazones
rl *-*-(-
I) LDA 2) FPro(cHr)lsicl OCH. ji_:l-
7e%
cH,-Ac,s,
n
cH.,.,y A _C,H, Sr1cu,;ro-i-n
,
(RF3 (>907oee)
c r c ,litD.
614 | LiBHICH(CH,)CrH.l.
* -Jc6H'cH" -78'
OH
OH
*0,*".o. I I t",Y^",", t",y^.,r, -# OH
(2S,3R)-s
rrcm3
S(CH3)rO-t-Pr 4 (94Vo de)
frdl
& r:E - g 5r.l
Arene(tricarbonyl)chromium complexes
13
isopropoxydimethylsilyl chlorideto furnish, after ozonolysis,a-silyl ketones(3) in 9{J%ee.Stereoselective reductionof the carbonylgroup followed by oxidativecleavageof the C-Si bond (12,243-245) furnishesvic-diols(5) in -90Vo de. D. Enders andS. Nakai,Ber., 124,219(1991).
s€condlv lzincs
.{nthracene. Diethyl methylidenemalonale. This reagent(3) polymerizeseasily and can be preparedby depolymerizationof oligomers, but is more readily available in sufficiently pure form from diethyl malonate(1) by conversionto the Diels-Alder adduct 2 from anthracene,paraformaldehyde,and 1. When heatedat 190-200" with maleic anhydride,the adduct2 decomposes to 3 in an overall yield of -50%.
Z\...\r-\ C H . 1C o o C ,H ,),+l ll \-'\Z\Z I
|
|
TlToJHcHo, cu(oAc),
66:
o4\o.,*-,,.
tlc syn2 with
CHr:g1ggOC2H5)2 + 3
4
'C. J. C. DeCock,J.-L. De Keyser,J. H. Poupaert,and P. Dumont, Org. Syn.,submitted
(r989).
Arene(tricarbonyl)chromium complexes. Stereoselectivelr3-dipolar cycloaddition of nitrones,r The cycloaddition of thenitroneI with an electron-richalkenesuchasethyl vinyl etheror vinyltrimethylsilaneprovidesa regioselectiveroute to 3,S-disubstituted isoxazolidines(2) (12, 566), but with low stereoselectivity.
t4
Arene(tricarbonyl)chromium complexes
-O\*,,,CH3
docrH,
+ l l CH,
CuH,
cH'\*,o1--ocrH, ---------+ 1A%
."^y
= 1:l) 2 (cisltrans
I
(u
I
ir TD
F.
benzIn contrast. the nitrone 3, derived from tricarbonylchromium-complexed only the cisto give essentially these1,3-dipolarcycloadditions aldehyde,undergoes disubstitutedisoxazolidine(2) after decomplexationwith CAN in methanol.How-
o"-ir,-cH'
d,
CH, -OC,H. - - 2r))^c A N > t \ * r o ; - - o c r H , ( *' 63% cH, \J F.-t
C"H:) ( c i s ,> 9 8 : 2 )
ever, cycloadditionof 3 with acrylonitrile,an electron-pooralkene,showsno improvementin diastereoselectivity. Silyl dienol ethers.2 The isomerizationof 1,3-dienesby (naphthalene)chroThus (lz)-l' mium(Co)r (p4,25) hasbeenextendedto (silyloxy)methylbutadienes. to (silyloxymethyl)-butadienes such as I are isomerizedexclusively silyl dienol
I
CI osiR3
osiR3
T
Ne.ctrcot, --/
f^"
\z-cn,
%
\-t,n, 2
(z)-r
ethers(2), whereas(E)-l is not isomerized.Silyl dienol etherssuchas 2 are useful oftheir high endo-selecDiels-Alder reactionsbecause for inter-andintramolecular tivity (equationI).
osiR3
o) / <.,\-r\Z--
coocHs
15
Arene(tricarbonyl)chromium complexes
The precursors(1) to the silyl dienol ethersare preparedas a mixture of (E)- and rZ)-isomersby Wittig reactionswith R3SiOCH2CHO. s-SubstitutedbenzXlalcohols.t Reactionof the complex I of o-triisopropylsiandhydrolysisprovides with L-valinolfollowedby chromatography lylbenzaldehyde rvo opticallyactivecomplexes[(-) and (+)-2)] in aboutequalamounts.The complex (*)-2 can be convertedinto either (+)- or (-)-3 (c-methylbenzylalcohol)by
cHo
I benzhe cisHow-
l) L-valinol,iMs 2) H,O' ------------1'
YAr o
si(t-h)l
(-ol,cr
,/1r'SiR' i l t
(co)rcr
.
i
'%'*, l
|
(co),cr (+)-2 (3r%o)
(-)-2 (29Eo)
I
/"\'cHo
l) cH,Li 2) BUaNF
-,-2
tt nu'o',
(+) 3 (1007oee) l) CH,Mel, MgBr,.O(C,Hj),
no lm-
- ,- 2
2) BU.NF 3) tv. o.
r)chro-
(-)-3 (1007o ee)
lzt-ldienol
reactionwith CHrLi or CH3\'IgI. The differencein selectivitybetweenCH3Li and CH:MgI is attributedto the greater Lewis acidity of the latter reagent. Aklol-type reactions.4 The lithium anion generatedwith LDA from 2-ethylpyto give a single aldehydes ridinechromiumtricarbonyl(l) reactswith nonenolizable ddol-type product (2) shown to be the syn-diastereomer.The samereaction, when
/'\
rCO),Cr-{f
lii'.,ft1[i-^-,.
|
\*z1,cH,
useful 'selec-
_
-----;A-(CO).Cr
CuH,
syn-2 esq. hv lo,.
CH, syn-3
16
Azidotributyltin
carried out on uncomplexed 2-ethylpyridine, results in syn- and anri-3, with some preference for anti-3 (48Vo de). I C. Mukai, W. J. Cho, I. J. Kim, and M. Hanaoka,Tetrahedron Letters,3f ' 6893(1990). 2 M. Sodeoka, Am. Soc.,l12,4906 (1990). H. Yamada,andM. Shibasaki, 3 S. G. Daviesand C. L. Goodfellow,Synlett,59 (1989). a S. G. Daviesand M. R. Shipton,Synlett,25,(1991).
Aryllead triacetates, ArPb(OAc)r. Amine arylation.t This reactioncan be effectedat25' with arylleadtriacetates by in the presenceof Cu(OAc)2.Yields are high in reactionsof anilinessubstituted albeit groups.Only primary linear aliphaticaminesare arylated, electron-releasing in poor yield. P-CH,OC^H.Pb(OAC),.
.FNH, ---z
cH.o-< ---5\
/
c(oA:l::cH'crr > cHro< , et%
lJ,At cjorrdcr d DllF eob Tfl
rt!d.
rtrordc.
c'lto
l---\ \
lNHcuH*ocH,-p " /
:
rD.H.R.Barton,D.M.X.Donnelly,J.-P.Finet,andP G.uJi.r y , T e t r a h e d r o n L e t t e r s , 3 0 ,
I t-. ar lra
1371(r98r. l|'..rt ,Cll{L
(S)-Asparticacid, H.. -CH"COOH
-Elt
rtcr
urNxcooH Asymmetricamino-acid synthesis.t The (S)-l-t-butyl 4-methylN-benzyloxy(1), preparedin 80% yield from the 4-methyl esterof aspartic carbonylaspartate alkylationat the p-carbon(LDA or lithium hexadiastereoselective acid, undergoes Bzl
H.. -cH.coocH. --liLiP' socHN4cooc(cH,). I
50"-
n...//
)-coocH.
gocHN^cooc(cHr)r 2 ( 5 :l )
with a numberof electrophiles.This reactionoffers a potential methyldisilazide) routeto opticallyactiveacids,sincethe methylestercanbe selectivelyhydrolyzedby LiOH in aqueousmethanol. rJ. E. Bafdwin, andM. North,J.C.S.Perkin/' 833(1989). M. C. Moloney, (f). The azideis preparedfrom Bu3SnCland NaN3in Azidotributyltin, Bu3SnN3 refluxingTHF (86% yield).
Far b. riI
c
Azidotrimethylsilane
l. qrth some
619.:r 1990).
|,2-Azido alcohols.r This azideis considerablymore reactivefor cleavageof whichrequiresa Lewis acidpromotor'Although epoxidesthanazidotrimethylsilane, DMF enhances the reactivityof the silyl azide,it lowersthe reactivityof the stannyl azide.The reactivity of the latter azide is also decreasedby neighboringester, acetonide,or ethergroups.
p. A
ld Inacetates rhrtituted by llated. albeit
CuHt
?n
f'
+ c6H5cHcH2oH
* | #cuH,CHcHrN,
l: 14
oH
o
f,
C.HTOCHT-Ja + I =;--tc.HrocHrcHCH2N3 95%
+
c6H5ocHrC"""ro"
17:l
l.OCH,-p
a Lcrters,30,
l7
I S. Saito,S. Yamashita, Tetrahe' M. Inaba,andT. Moriwake, T. Nishikawa, Y. Yokoyama, 4153(1989). dronLetters,30, Azidotrimethylsilane. (l).t Reactionof NrSi(CHr): with (R)-l in Reactionwith (R)-epoxystyrene (S)-2 as the productin 907oee. Use of provides CH2CI2catalyzedby Al(O-j-Pr)3 (S)-2, provides Useof Ti(O-i-Pr)a in lower enantioselectivity. but othersolventsalso deproduct, provides but the enantioselectivity major 2 as the as the catalystalso
l-benzyloxy'oi aspartic h h i u mh e x a -
">-\
t c u ' l , s i N ,C u "H r . "'>.?'-iii;il, >\
c.H.
CuHr.
H o (R)-r
N3
+ Al(O-i-Pr), 50Vo + Ti(O-i-Pr)4 56Vo
os(cH3)3 (s)-2 9OVoee 43Voee
(cH3)3sio 3
N3
93:'l
pendson the solvent.Use of THF provides(R)-2 in 63-99% ee; use of CH2CI2, hexane,or etherprovides(S)-2 in 3l-72Vo ee. a potential d r o l v z e db y
nd NaN3 in
I K. Sutowardoyo, Letters,30,4673(1989). M. Emziane, andD. Sinott,Tetrahedron
bcyl co ;rtryo d \
Barium manganate, BaMnOa. Selectiveoxidation of diols.r BaMnOais handicappedby insolubility in organic solventsand by instabilityto acids.It is a more usefuloxidantwhen supportedon This supportedreagentefficientlyoxidizesbenzylic,allylic, Al2O3andCuSOr.5HzO. but oxidationof saturatedprimary alcoholsis negligible.Its main andsec-alcohols, value as opposedto that of supportedKMnOais for the selectiveoxidationof primary-secondary diols suchas I and 2.
ltd
UJ.t r TL nq rord Sn ?rtir Drn
cHfl:. OH
I
BaMnQ/Al,O,/CuSO.
C.HTCH:CHCHCH2CH2OH
--+#r-
?
:cHccu,cu,ou cuH,cH CrK
I OH CHTCHCHTCHTOH Ef 2
CHTCOCH2CH,OH
>t
'K. S. Kim, S. Chung,I. H. Cho, andC. S. Hahn,TetrahedronLetters,30,2559 (1989)'
,.cH2oH 1,2-Benzenedimethanol,
Erl[ rl (}.i
(r).
cJ
cHroH \ This diol (1) reacts sluggishlywith carbonyl com,.C:O. poundsunderacidcatalysis,but the orthoformate2,3-methoxy-1,5-dihydro-3ll-2,4(3). The carbenzodioxepine, derivedfrom l, reactsto form2,4-benzodioxepines Protectionof
-s rr#L ' +HC(ocH'r' oe^:"", Qil, 2, n.p. 44"
3 I
I H.. Pd(0). q u m r .I r i o
J-
R'coRt
t t ' l L
E tl .-q cJl
Benzeneselenenylchloride
19
by Pd-catalyzedhydrogenation.Theseprotective bonyl compoundis regenerated carbonylcompounds. groupsshouldbe usefulin the caseof acid-sensitive ' N. Machinaga Letters,30,4165(1989)' Tetrahedron andC. Kibayashi,
Z-"to,, r rnorganic Pponedon l r c .a l l y l i c , lc Its main titrnof pri-
ll [,2-Benzenediolato-o,o'loxotitanium' t\.r.\O
(1).
1l:o
The reagentis preparedby reactionof catecholwith (i-PrO)zTi:O followed by removalof the 2-propanolby-product. Michael reactions.r This reagentservesas a nonacidiccatalystfor Michael ofketenesilyl acetalswith c,p-enones,andis moreeffectivethandialkoxyreactions titaniumoxides,(RO)zTi:O. The reactionproceedsat -78o in varioussolvents, CH2CI2,ether,and toluene.
lt.oH
o,,
ll C.HTCCH:CHCH,
O ll
R.SiO CH. I I I - cH,cr, r*'ocH, C.H,A_r\.AOCH, __ OSiR.
._ _/ + CHr:Ca
R,=(CHrIC(CH.\
1 9, 1 9 3 9 ; .
$-Hydrory esters.zThis Ti complex(1) is an efficientcatalystfor an aldol-type with ketenesilyl acetalsto form p-hydroxyestersas reactionofactivatedaldehydes the O-silyl ethers. OSiR,
OSi(CH.),+-Bu + CH,:C(^ C6H5CHO
oc"H. onrI comro-3H-2,4. The car-
U R '
,(
-Rt -ot
I T. Mukaiyama andR. Hara,Chem.Letters,l171 (1989). : R. HaraandT. Mukaiyama, ibid.,1909(1989).
chloride. Benzeneselenenyl (10, l8).r cyclizationof the homoallylicalcoholI Phenylselenoetherification tetrahydrofuran(2) proceedswith and KzCOrto a 2,5-disubstituted with CeHsSeCl
t'"')r \\.,'\
i R.
c"H,secl.
?"
ZnBr..DME. ----;*-
cHrosi(c6H5)rc(cHr)l
55'
C^Hr---rO\...CH2OSiRr \
I
\-J cuHrSe 2 (16:r)
20
BenzeneselenenYlchloride
in cH2cl2, but yields are poor much higher ,rdns-selectivityin THF or DME than more reagent' After someexperibecauseof low conversioneven after addition of was found to give the highest mentation,the combinationof c6H5Secl and ZnBr2 yields with high rrans-selectivity' C6H5SeCl(l) and silica gel with Cyclizttiin of allylic ureas' The reactionof allylicureasinCHCI3at25.provides2-oxazolinesin30-90%yield.TheCoHsSe "'n'H"HtSecuHt
t'"''f-i.-""'SecuH'
au*-r^aH, - -
|
r, cucr,,zs.-
, 1
*
2:t *Yo
t \
livo
NHCONH,
I NH,
NHt
SeC.H.
Pr-rC. PrCH:CHCBU
H
--)
|
NHCONH2
8r%
S H Xtrt 'C Eans ,l9tl9l I Frart. 'D Bit r
frd tr€d fril U.t tsr'rrn of r.& c rd &ld
..Bu
/
\
ovN I
NHt
(c6H5)3snH.Hydrolysisof the groupof theseproductsis removedin high yield by proOort,is known to provide 1,2-aminoalcohols'2 or 5'6providesimida^zolines The samecyclizationof allylic O-methylisoureas triflate)'3 (whencaialyzedby benzeneselenenyl dihvdro-1,3-oxazines CuHr\
Cunr-.;AC". | ' _ NHC-OCH,
.
r
> ot*
NH
*a
loty rdd
gn
...CHrSeCnH.
""Y* -\
ocH3
ooz" fc"H.s"orr
"u'l- ?".."' *\-o I
" t I fF"l
NHt
of carboxylic acids reactswith Acyl selenides.aThe triethylammoniumsalt in 62-85%yield' Theseproductson andBu3Pin THF to form selenoesters C6H5SeCl ,*"iion with Bu3SnH(AIBN) furnish acyl radicals'
I JS
Benzotriazole
Poor Perighest \1ith H.Se
2l
l) N(crH5)r, cHzcl!
RcooH l[4#{j5
RCoSeCuH,
I S.H. Kang,T. S. Hwang, W. J. Kim,andJ.K. Lim,TetrahedronLetters,3f ,5917(1990). : C. Betancor, E. I. Ledn,T. Prange, J. A. Salazar, andE. Surirez, l.C.S. Chem.Comm.,450 0989). r R. Freire,E. I. Ledn,J. A. Salazar, andE. Sudrez, ibid.,452(1989\. ' D. BattyandD. Crich,Synthesis,273 (1990).
H.
Benzeneselenenyl trifluoromethanesulfonate, C6H5SeOSO2CF3. The triflate is preparedfrom C6H5SeCl and AgOTf in CH2CI2. Selenolactonization.r Chlorinatedby-productscan be formed when selenolactonizationis effectedwith the usual reagent,C6H5SeCl(8, 26-28; 13, 26), Reaction of 1,6- and6,6-unsaturated proceedsevenat -78o to give 1acidswith C6H5SeOTf and 6-lactones,respectively,in high yield. cHr.
cH,
t
\
-Srliif,Jr
/'\. H,J
/
_
\
cuH'SecH'--\oAo
loo"
(translcis= l0:l)
the
i.6
Selenoethcrification.2 CoHsSeOTfalso convertsalkenessubstitutedby an hydroxygroupin the 5- or 6-positioninto tetrahydrofurans or -pyransin generallyhigh yield. C^H.ScOTf
/
\
n,cy' sg^cH,
-cir,bt,.o' 8;-
/
\
coH,SecH/\olctt, (cisltrans-- l'.l\
\\,,
CHrcHroH
/-1",
mu- (-,,|--/
(1987). S. MurataandT. Suzuki,Chem.Letters,849 : Idem,Tetrahedron Letters,25, 4297,44I 5 ( 1987). r rth i0n
Benzotriazole. Enamines.r Enaminesare generallypreparedby condensation of the carbonyl compoundwith a secondaryamine with removalof the water formed. In a new
22
O-Benzylhydroxylamine
method, an aldehydeand a secondaryamine are addedto benzotriazolein ether at room temperature(3-A molecularsievescan be used). On treatmentof the product with sodiumhydride, sodiumbenzotriazolateis formed with releaseof an enamine.
\\
N
"{l + cH3cH2cHo.
e5%
N
A.-.*
I-6^ctqt
iE-fY\*
N
o
::ao
\.,+-N'
sr'l6pa rctccd
b
A T-GI
6t%lNaH
fcyfn ,*
CH, H
N
\
\__/
i'ert.- r for dcol
cll
rA. R. Katritzky, 8153(1990)' Q.-H. Long, P. Lue, andA. Jozwiak,Tetrahedron,46'
cyanide. Benzylamine/Potassium synthesis.rA new variationof NHy'HCNfor the nitrile Streckera-amino KCN, andHOAcin CH3OH. BzlNH2, uses synthesis Strecker
Kgy R,coR,+BzlNHr+
ttt"l,Xl) rgA.sr:oH. 3 hfr ,ltltl
' M. P. Georgiadis 616(1989). Syzthesis, andS. A. Haroutounian,
frlr (l). O-Benzylhydroxylamine,C6H5CH2ONH2 1,2-cis-Amino slcohols.r o-Hydroxy ketones can be converted to 1,2-cisprovidesthe amino alcoholsin two steps.Reactionwith O-benzylhydroxylamine
4 l-
o ,-/'-"" ll |
<-[-",
N-ot" ,' rPv y ' z>*o" l ll
7\Ao)
I
Tr, ,",.,", /'1/1oa j -'*'
\Ao)
( c i s l t r a n s =9 : l )
th d rbrl
Benzyne
erherat product namine.
N oH
,,-OBzl
r) H,.pdrcA...o" 2)l.Pv
I
TH, BH,.THF _--.-.---.-)l
I
6s'
l 68% t\oAa"rorBDMs
cHrorBDMs
-'\."OH I
I
I
\oA"",orBDMS (cisltrans= 96:4)
(cis- andt/@nJ-mixtures). Theseoximesare corresponding o-hydroxybenzyloximes to cis-l,2-aminoalcohols. reducedby BH3.THFstereoselectivity rA. K. Ghosh, Tetrahedronl*tters,32,711(1991). S. P. McKee;andW.M. Sanders, Bcnzyltriethylammonium borohydride-C hlorotrimethylsilane. Reduction ol alkenes to alcohols. This combination(l) of CoHsCHz(CzHs)r4nti-MarkovniNnUn- and ClSi(CH:): (1: l) convertsalkenesto the corresponding in DME is lesseffective. kov alcoholsin goodyield. NaBHa-ClSi(CH3)3
l90r
CH3(CHr)6CH:C", .-!IE}:I--r
+ CH,(CH,)7CH: CH,(CHr)66HrCH2OH 727o
ior the
lSVo
f",
ffir \r.- *do",l,#'"" (r) ' S. Baskaran, l. C.S. Chem.Comm.,903 andS Chandrasekaran, V. Gupta,N. Chidambaram, ( 1989).
I .l-cisidesthe
OH
Benzyne. Phenanthridinones.rBenzyne,generatedin situby Pb(OAc)roxidationof l(l),2 undergoes[4 + 2]cycloadditionto cyclic vinyl isocyanates aminobenzotriazole to form phenanthridinones.
a).fY\* Y \'/-( NCO
Pb(OAc). cH:clr,25' -> 58%
NH,
l,l'-Bi-2,2'-nephthol(BlNOl)-Dichlorodiisopropoxytitanium
24
rhb rype rre ur 3lyoxdetes ri srcrcosclectivi
rJ. H. Rigby,D. D. Holsworth,andK. James,J' org',54,4d19 (1989)' 2 H. Hart and D. Ok, ibid., 51,979 (1986). (1)' 15' 26-27 ' (BlNOl)-Dichlorodiisopropoxytitanium l,l'-Ri-2,2'-naphthol The reacglyoralate. Asymmetrti ene ant! Diels-Alder rcactions with methyl complex tion of methyl glyoxalate with isoprene catalyzed by the BlNol-titanium (R)-1 provides not only the expected ene product (2), but also the Diels-Alder product(3),bothin97%ee(equationl).Thischiraltitaniumcomplexisalsoan
V. Tcrde. K.
(l) or (SFl,l' At..a1 hgendin thc P u (S)- or (R) rldrocerboryl
CH.t-CllCH.I
9"' (r)H'cxAcH,
tn)-t'* t'ts
?
H Alper rd
+ Hlcooc", g**%
oocH.tl' ."-G.oocHj 3 (9'l9o ee)
2 (97Vo ee)
ocH.
OD
2 I
ocH.
o ll
(R), I, CHrCl, - 55"
^;
72%
\.
+ HCCOOCH,--)
\CH,
l l . l coocH,
+ 2,6+rans-4 ee) 87:.13(>9OVo
Frrldlc-t t|ylnp urcot of l
bg1ndir. I CntWr \s efecr Li rG. rilbcl l b-vdrqg
l{o
2,6'cis'4 (96Voee)
ocH , OII)
/
I CH,
'
oll
-
it"' /to
+sdcoocu,*#l.[ I fcoocn, CH,
?", ./\n lr
+ l l
cH.(
Y
lvcrd
I
93:7 \z-"OOCH3
: CH,
5 (9OVoee)
Ert3.i (f,}'rbt h
effectivecatalystfor a Diels-Alder reaction of methyl glyoxalatewith 1-methoxyto providethe cis-adduct4 in 96%ee (equationII). Dihydropyransof 1,3-butadiene
tfEp6i
acr. lb rc Flcfr.In
Bis(acetonitrile)dichloropalladium
25
this type are useful precursorsto $lactones (10, 258). The cycloadditionof methyl catalyzedby R-l proceedswith high glyoxalateswith l-methoxy-I,3-pentadiene stereoselectivityat three stereogeniccenters(equationIII). tT
I M. Terada, (1991). Letters,32,935 K. Mikami,andT. Nakai,Tetahedron
reacnplex Alder so an
(R) or (S)-1,1'-Binsphthyl-2,2'-diyl hydrogenphosphate(l), 12, 49. Asymmetrichydrocarboxylationof styrenes.r Use of (S)- or (R)-1 as a chiral (2) results ofp-isobutylstyrene hydrocarboxylation ligandin thepalladium-catalyzed in obtains in (S)- or (R)-2 (ibuprofen)in 83-847oee. Similar enantioselectivity to form naproxen. of a 2-vinylnaphthalene hydrocarboxylation
cH.' (cH3)rcHcH,
ll ll
PdCl). CuCl, I Har
CH+CO+HrO;ff
CH,
I (cH.)"cHcH.
u
3(83-84Voee')
' H. AlperandN. Hamel,Am. Soc.,ll2,28Oi (1990).
Ls{
Bipyridine-Palladium(Il) acetate. Hydrogenation catalyst.t A supportedform (l) of this complex is preparedby treatmentof H-montmorillonite(Fluka) with SOCI2,followed by BuLi, and then bipyridine.The resultingmontmorillitebipyridineis then treatedwith Pd(OAc)2. Catalyzedhydrogenationof alkynes, alkenynes,and alktdienes,r This catalyst effectshighly cis-selectivehydrogenationof triple bondsof alkynesand alkenynes,with easyrecoveryof thecomplexby filtration.It alsoeffectsonly I ,2-addition 1,3-butadienes. of evenhindered1,4-substituted in hydrogenation
eel
islg HoH2cc-ccH,oH
HOH"C "
><
H CH,CH:CHCH:CHCOOCH:
CH"OH H
---------, CH3CH2CH2CH:CHCOOCHT 979a
Chem.Int. Ed.,28,465(1989)
lH.
roxyns of
Bis(acetonitrile)dichloropalladium. (E\-Vinylsilanes.r Thesesilanes(2) are obtainedin goodto high yield by ally(l) with this Pd(II) catalyst.2 Moreof C1-acyloxy(E)-crotylsilanes lic transposition over, the rearrangementof optically pure substratescan proceed with complete preservation of opticalpurity.
26
Bis(acetylscetonate)cobalt(Il)'
Co(acac)r
rcoad to b dltr iso 6r hYdrl roprovc d rfur rcri raombl
Pd{trr59H'cl' CH,1,z'\''SiRr t
CHt\rySi(cH3)3 :
o -ccH"
CHrg/ ll
I o
o
slmt
G)-2
(s)-1
Lewis acids such as BF3 effectedby a number of This rearrangementis also
"/"n:"',.: otin (":^! o! |) 3 rhe s organ ;TTtfi effectedby :! (2) :T "iit" tu"to"y"tit dit"tp"niutrophone
**::;H;;'ITffi
final step in a synthesis coupling';;;;tde carbonylative
with vinyltin cataiyzedby
CH,TCH
bis(acetonitrile)-
t -r.sxl t'-rCH,(
dichloroPalladium'
Cq :tqtng
CHr...
cH, E$lliTlf'lr, cH,
*rfrct
24%
rd
CJ
rrrrfil!
o
CH,
, can add to actiof activatctl-a/renes'aAlcohols Alkoxylationantl acetylation or Licl is reAddition PdflI) catalvst' vated doubrebonds in 'n::;:;;:;$; acid' q"it"a a effect addition of acetic O It---
c5'tcu:cH,
Pdcl,(cH,cN), ? H'cr,'25" - -) coHricH,cHrocH.
+ cH'oH --t*
o
crur[cu:cHcH,
3t"'
+ Bzlo1 -5;> c'H'icH'cHoBzl
5564(1990)' ILT S. PanekandM' A' Sparks'J' Org''55'
ttsslt' 2L. E.overma n, Angew''inii'tn''Ea" zl'.srsAm 8465(1990)' S' Hegedus' Soc"112'
I A. C. Gyorkos' J' K' Stille't"i l' 2001(1989)' s'-r' ru"*lJi-cr'em' Letters' a r. Hosokawa, T' shi"";i;'""' t5"u' t"[
co(acac)2 and Bis(acetvracet";T#:::ttl?l?l-,:?1'un u, .tr""t"dwithoxvgen is asspecies cyclopentanol)'The reactive and a seconduryur.orroi't2-p.opunot,
TT :cl
*f, c I I ,It sl Ii nl r 'l I
Bis(acetylacetonrto)nickel(Il)-Diiosbutylaluminum hydride
27
sumedto be HOO(acac)zCo(IID.A mixture of a secondaryalcohol, a ketone,and an alkaneis obtained,with the alcoholasthe major product.rOn further investigationof was shownto markedly this hydration, use of bis(trifluoroacetylacetonate)cobalt(Il) is oxidizedduring product. sec-alcohol The solvent improvetheyield of thealcoholic are oxidized to alcohols variety of secondary fact, a ketone. In this reaction to a +-A tr'tSin (20 containing mole at75'in toluene oxygen and Co(tfa)2 %) ketonesby yield.2 80-100% h as BF3 lr r The fectedby o nr t r i l e ) -
o} R,cHoH .-jIIlL---->
CH1(CHr)?CH:CH,
+ cH3(CHr)sCHr+ CH.(CHr)'coCH, cH3(cHr)?cHoHCH,
,CH, CH.
'lVo
22Vo l3va
45Vo 81Vo
Co(acac), Co(CH,COCHTCOCF.),
2Vo
Coupting of ar$-unsaturatednitiles, amides, or esterswith RCHO.3 This as the hydrogen as catalystand C6H5SiH3 couplingcan be effectedwith Co(acac)2 with acrylonitrilein 1,2-dichloroethane source.Thus the reactionof benzaldehyde (2 equiv.) anda catalyticamountof Co(acac)2 at 70" providesthe pwith C6H5SiH3 silyloxynitrile as the major product(equationI). C6H,SiHr. Co(acac),
d to actriCl is re-
(D C6H5CHO+ CHr:Ql1gN
c6H5siH2o H.o.
c6HscHcHcH3 ;o%+ CN
crcH'cHpl'70'
>
OH I C6H5CHCHCH3 I
CN
The same coupling of aldehydes and o,p-unsaturated amides and esters can also be effected. In these couplings the best catalyst is bis(dipivaloylmethanato)cobalt rll), Co(dpm)2.4
L, 1 9 8 9 ) .
Coracac)2 ies ts as-
T. Mukaiyama,S. Isayama,S. Inoki, K. Kato, T. Yamada,andT. Takai, Chem.Letters'515 ( 1989). :T. YamadaandT. Mukaiyama,ibid.,519 (1989). ' ibid.,2005 (1989). andT. Mukaiyama, S. Isayama ' F. A. CottonandR. H. Soderberg, Inorg. Chem.,3, 1 (1964).
hydride. Bis(acetylacetonato)nickel(Il)-Diiosbutylaluminurn Hydrosilylation of 1,7-diynes with Hydrosilylative qclizntion of |,7-diynes.r HSiX3 promoted by a Ni(O) catalyst, prepared from Ni(acac)z and DIBAH, results in
2t
1,4'Bis(bromomagnesio)pentane
1'7-diyne with a (Z)-vinylsilanegroup' An internal a 1,2-dialkylidenecyclohexane forms a diyne unsymmetrical An yield' iower undergoesa similar.y.ri'uiion, but in is introducedexclusively into the terminal single product in which,i" ,ilyr group acetylenegrouP.
C:
ftrrt-lt(E
L llter s ? Crn
Ectfi crcIo, taa. F t S' of [,]+
N(o) (Ytt*' + HSiX,Er*'(.A-Cn,
f.ir
n
//----cH' |
r(o) --r*-+ 115i1OCrH5)r
si(oc,HJ3
rl
3nq.
H
\-cH,
C:
N(o) lYti*, _-*_ +HSiX,
t""
Diels-Alder reactions'The silyl group The exocyclicsilyl dienesare usefulfor to a pO-.utufy"J toupling with aryl iodides as well as oxidation can also undergo hydroxyl grouP. (1989)' lK. Tamao, andY' Ito' Am' Soc''Ul' 647E K. Kobayashi,
ctd (l)' 13' I 38- 140' l,,l-Bis(bromomagnesio)pentane steCanonneet al't haveobservedhigh Reaction with lactones,anhydrides'
Itc
reoselectivityinreactionoflwitharomaticlactonesandanhydridesresultinginthe
z>A
o
l=Ar"*t";
z>A I ll
w
6
o-HOCHrCuHn..,OH
0*'
ar ar a.
o O+
o
|- -------+ 4n%
I
CH,
\
It ,-
Bis(cyclooctadiene)nickel
l 1.7-diyne rneforms a r terminal
29
trans-isomerin the caseof the former substratesbut in the cis-isomerin reactionwith the latter substrates. I P. Canonne, Tetahedron,45,2525(1989). andM. Bernatchez, R. Boulanger,
Bis(cyclooctadiene)nickel,Ni(COD)2. Cyclizttion of dienynes.r This Ni(0) catalystin combinationwith a triarylphosphite, particularly tri-o-biphenyl phosphite,permits intramolecularcycloadditionat 25" of14+21 dienynes,in which the dieneand the alkyne are separatedby 3- and 4atom units. This reactionis a useful route to productscontaininga cyclohexadiene group, which are oxidized to an areneby DDQ. OAc N(COD),, (ArO).P -------.------85%
CH, ( 1 . 8 l:)
""r^
(cH3)3si-1o
srlll group tdationto a
F,,H "","'\:.h
98%
(cH.),si/
\--g
( 9 9 :l )
d high sterltingin the
Cyctizttionof diynesto iminocyclopentadienes.1,6-1,8-Diynescyclize with isocyanidewhentreatedwith Ni(COD)2,I equiv., to form bicy2,6-dimethylphenyl
N(COD),,
(cH,)" \,\
+ CNC.HT(CHr), -IIF
jo"-
NC6H3(CHJ'
R
n=3,R=CcHs n=4,R=CzHr n=5,R=CrHs
87Vo 94Vo 47Vo
clic iminocyclopentadienes.R can be alkyl, aryl, or trimethylsilyl, but not H . 2 I P. A. WenderandT. E. Jenkins,Am. Soc.,fff, 6432(1989). 2 K. Tamao,K. Kobayashi, andY. Ito, J. Org.,54, 3517(1989).
30
Bis(1,3-diketonrto)nickel(Il)complexes
Bis(dialkylamino)magnesium' [R2N]2Mg' amidesby reaction Amides.r carboxylic acids can be converteddirectly into
!irJ rrcld
withabis(dialkylamino)magnesium,preparedinsitubyreactionof2R2NHwithn(Alfa). butyl-sec-butylmagnesium
Enl| E
rR. Sanchez, Syn'Comm''19' 2909(1989)' G. Vest,andL' Despres'
, ?d
Lrt T I
o{
(1)
(-)-1,1'-Bis(2,4-dicyanonaphthalene), CN
acid). The reagentwas obtainedin about 70% ee from (-)-1,1,-bis(2-naphthoic known is 1,3-cyclohexadiene Enantioselectivctiplex Diels-Alder reaction.r with irradiated when dienes to undergo Diels-Alder reactions with electron-rich sensithe involving triplex a involve arenesensitizers.The reactionis presumedto reactionhas tizer (15, 129). The first enantioselectiveexampleof this Diels-Alder beenachievedusing(-)-lassensitizer.Thusirradiationofl,3-cyclohexadienewith rrcns-p-methylstyreneinthepresenceof(-)-1at_65.providestheendo-adduct2 increaseof the in 15% ee (equationI). Til enantioselectivitydecreaseswith an temperature,being l% at 25' .
('u^'
z> l +
c)l \,,/
ll
fl
--\'-! (-)-r.rv'-65", lL\
cH(
9tt, I CuHt
2, l59oee
(1990)' fJ.-I. Kim andG. B. Schuster, Am' Soc',1f2,9635 Bis(l,3-diketonato)nickel(Il) complexes' can be effectedby oxygen Orygenation of RCHO to RCOOH'| This oxidation Ni(acac)z' bis(acetylacetonato)nickel' as such when catalyzedby nickel complexes However,thehighestconversionandyieldsareobtainedwiththecomplexprepared Ni(dmp)u' Ether or an alcohol from 1,3-di(p-methoxyphenyl)-1,3-piopanedionate'
o tl
Q?-CH3OC6H4C)rCH2 GdmP)
-
a .J
F DT
-
(
3l
Bis(l'3-diketonsto)nickel(Il)complexes
tactron I ith n-
is a poor solventfor this oxidation,but ketonesor estersare appropriate.Highest (83-87Vo),but secondaryandeven aldehydes yieldsareobtainedwith straight-chain is oxidizedto yield. Benzaldehyde tertiary aldehydesare oxidized in reasonable benzoicacid in 79% yield. Epoxidation of alkenesby O2. This epoxidationcan be effectedwith Oz and a can complex.Reductants whencatalyzedby a bis(1,3-diketonato)nickel(II) reductant (which to is converted preferably, an aldehyde be a primary or secondaryalcohol2or, as is almost Ni(acac)z although an acid.3The most efficientcatalystis Ni(dmp)2, CH.
CH,
,.,\,,"-rr-\-"^.-oo. :id). known d with : sensiion has oe with dduct2 of the
o?.Ni{dmp)r
w
QH,
9H,
+
cH-k3,,'\,,\.,^-oAc
ltT;,]'"
O.',_,**Of, .-[---- e.'-F--
lD_l_',"- V,!
satisfactory.This epoxidationproceedsin high yield with styrenederivatives,l,land varioustrisubstitutedalkenes,but terminalalkenes.norbornenes, disubstituted internal alkenes.Of various alders generallyless effectivefor 1,2-disubstituted or pivaldehydeis more satisfactorythanbutyraldehyde' hydes,isobutyraldehyde Oxygenationol silyl enol ethers.a Oxygenationof a silyl enol ether under the spontaneously conditionscitedaboveresultsin a silyloxy epoxide,which rearranges ro an a-silyloxy ketone.The preferredNi catalystfor this epoxidationis bis(3Ni(mac)2.The c-silyloxy ketoneis converted methyl-2,4-pentanedionato)nickel(II),
oSi(CHr)ro:,RcHo.lN(mrc)r
cH.:Z\cuH, oxygen (acac)2. nepared alcohol
o\
pSi(cH3L-l
[",JX..",
I
------.",yA".",
>
J
os(cH3)3 75%JKF,cH.oH
o
""'f..", tl
OH
2,2'-Bis(diphenylphosphino)-l,l'-binaphthyl
os(cHJ3 Brl',/-oCH,
-
r*--
BzlCHCooCH, OH
to a silyl to an o-hydroxy ketoneby KF in CH3OH.The samesequencewhenapplied keteneacetalgivesan o-hydroxyester. rT.Yamada,O.Rhode,T.Takai,andT'Mukaiyama,Chem'Letters'5(1991)' ibid',1657'166l(1990)' 2 T. Mukiyama, andO' Rhode, T. Takai,T. Yamada, ibid" l (1991)' 3 T. Yamada, T. Takai,O. Rhode,andT. Mukaiyama, a T. Takai,T. Yamada, ibid'' 281(1991)' O. Rhode,andT. Mukaiyama, Bis(dimethyla|uminum)selenide,[(CHl)zAl]zSe(1).Theselenideisobtainedinsiru with (CH3)2AlCl(2 equiv') in toluene' by reactionof [(CHr)rSi]zSe can be preparedby reactionof dialkyl ketones selenoketones.r Selenoketones hindered with I and trappedby a Diels-Alder reactionwith a diene. A sterically reaction. this from isolated has been selenoketene,selenofenchone,
N ;itrlbo .r.t)l
tac.,rl rrl I ,aar.vl
lM.Segi,T.Koyama,T.Nakajima,S'Suga'S'Murai,andN'sonoda'TetahedronLetters' 30,2095(1989). 2,2'-Bis(diphenylphosphino)-l,l'-binaphthyl(l' BINAP)' Isomcization of allylic amines(11, 53-54; 12, 56-57)'t The asymmetric (R)of allylaminesto enamineseffectedwith rutheniumcomplexesof isomerization dialkylamino evento oneswith an allylic and (S)-l is applicableto c5-isoprenoids, usedto groupat one end and an allylic O-functionat the other end' Thus it can be CH"' I Bzlo--,-\-,2.-N(c2H5)2 3
g caaf
|
Ft!
t r
o
9H,
)
Rh(R-lxcoD)clq)' l. Bzla...u.zpv-''N(c2H5)2 86%| H'o'
1", BzlO-.A-,,CHO
t fI I
(R)-4 (997o ee)
4, a usefulbuilding isomerize3 to the opticallypure 4-benzyloxy-3-methylbutanal block for isoprenoidtto.otols. In somecases2,2'-bis(diphenylphosphino)-6,6'-dimethylbiphenyl(BIPHEMP,2)issomewhatsuperiortoBINAPasthechiralcomponent. The(R)-and(S)-aldehydes4wereusedtopreparethefour(E)-stereoisomersof vitamin K, all of which haveessentiallyidenticalbiologicalactivity.
o t;
T I
2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl
CH, CH, I silyl
n sttu itones dered
Asymmetric hydroboration oI C6HyCH:CHz.2 The reaction of cateHydroboration cholboranewith styreneprovides,after oxidation,2-phenylethanol. catalyzedby a cationicrhodiumcatalyst,[Rh(COD)2]+BFa-and dppb, providesl(99: l) in 867oyield. A catalyticasymmetrichydroborationis possible phenylethanol of -78" provideslwith BINAP. Use of (-)-BINAP as ligandand a temperature phenylethanol in 96% ee (equationI).
(I) C.HTCH:CH,+
l) tRh(coD),1'BF4 , (-)-l 2) HrO} NaOH
,Q
HB
o
OH
allers,
netnc rf tR)tmlno sed to
(9670 R)
Stereoselectivehydrogenation.3 Hydrogenationof the cyclic p-keto ester 2 catalyzedby an (R)-BINAP-Rucomplex(l) proceedswith high dnti-diastereoselecof rivity to give a 99 : I mixtureof 3 and4. On theotherhand,catalytichydrogenation rhe acyclic keto ester 5a proceedswith no appreciableresolutionto give a l: I
o o H i l | ;\-coocH',*,-r,^1, ---;;- *u,,, /}"'coocH'
\-J
\J
3, (lR, 2R), 927o ee
lrldrng ; . 6- d i f,rmPon e r so f
c6H5..*r'cH3
I
91%
coocHs
si,
4 , ( l R , 2 S ) , 9 3 7 oe e
mixtur€of syn- andanti-6. However, the presenceof an amideor carbamategroup at to N-acetylr-C1 resultsin extensivekinetic resolution.Thus 5b is hydrogenated the configurationat rhreonine(6b) in 98% ee.In theseasymmetrichydrogenations, Cr is determinedby the chirality of the BINAP ligand and the C2 configuration Jependson the substrate. Ordinarily,theyield in kineticresolutionsdoesnot exceed50%. The highyield in :he presentcasedependson racemizationof the substratebeing more rapid than h;-drogenation. Asymmetric hydrogenation of allylic alcohols (14, 38-40).4 Full details are rr ailablefor thepreparationof Ru(OAc)z[(R)-or (S)-BINAP],thecatalystfor asym-
!4
2,2'-Bis(diph€nylphosphino)-l,l''binephthyl
o
o H o I ll -H,,ra",tfoc2H5
o
i l l l
cH,foc,H,
CH.
CH.
sYn-6a
5a
o
+ ani4a l-
o H O
o
t l l cH,"\r^oc,H,
i l l l cH,'A\'\oc,H,-
NHCOCH,
NHCOCH3
g;,r
NHCOCH3 ee 6b(2R,3R)' >9OVo
6b(2S' 3R)' 987o ee
5b
o H O t i l cH,AfAoc,H,
in the without effect on other doublebonds metric hydrogenationof allylic alcohols showshigh catalyticactivity' substrate.Ru(OCOCF:)r(SiNep)also preferred catalyst for this 9-o'o esteri's The Asymmetricnya*sr;tion'oi with HCI (2 Ru(oAc)zlBINAPl, reactionof reactionis RuclzlBINApl, preparedby catalystandusein asymmetrichydrogenaequiv.).Detailsfo, tn, p'effiion of ihe O ll
O I
cH,/$
H
? ' O I H Rucr,lRlBINAP] ,
o tl l) H). Ru-(S)-BlNAe C6H.CH'.4-
cu,81cu,;,cooc,u,
e6%
ctF|Ct
i
^A; Y
r
\* -r
Ur td. lt
in99'4vo ee and to methyl (R)-3-hydroxybutanoate tion of methyl 3-oxobutanoate esters hydtogtnutionis applicableto 3-oxo 96Voyieldareavailable'This asymmetiit with report the in at cz and c3 (23 examplesare listed with various substituents opticalYieldsof 88-100%)' A Ru catalystpreparedin situ by Asymmetricnya'oy'no'tion o! 4-oxo esters'6 of 4-oxo (2 equiv') effectshydrogenation reactionof Ru(OAc)z(BINAP)with HCI acetic with heated when to estersto 4-hydroxy.*.", *iitt' areconverted Y-lactones are lactones the with (R)- or (S)-BINAP' acid in toluene.tf ,nt nu is complexed obtainedin >98% ee'
2) HOAC. --------:=-
h
ocH,
(99'41a ee\
o
r:r d
ll O
cn,',\.
oc*r--=a--
N, dil rll tti
I
CH, ee (S),99'57o
preparationof optically active phthalides The sequencecan be extendedto (1-2).
q
iFr F I l-
l'-binaphthyl 2,2'-Bls(diphenylphosphino)-1,
o cooc"H. l l l cH,/*'..t1y'-n
l.
t
t
l
cH;" e1%
\-/
I
O H O
t t l /->-^ocrtt, : \HCOCH3 f l R . l R t . > 9 O V oe e
oublebondsin the it1 d catalystfor this \ . r P l . w i t hH C I ( 2 rnetrrchydrogena-
AsymmetricHeck-typearylation.l A catalystpreparedin situ from Pd(OAc)z and(R)-BINAPeffectsa highly enantioselective arylationof 2,3-dihydrofuranwith aryl triflates with diisopropylethylamineas baseand benzeneas solvent. Two products (2 and 3) are formed with oppositeconfigurations.The highly enantioselective formation of the major product (2) is ascribedto a kinetic resolution step which convertsthe enantiomerof 2 into 3.
Q.
'ol:*:"1'9.3'-3"'il"o" c6H5orf Q...",n, ,n1,,*",", 3 , S , 6 7 V oe e
2 , R , 9 3 V oe e
l)cH,
le n 99.4Voee and It lc to 3-oxoesters rn the rePortwith in situbY prepared o!enationof 4-oxo with acetic n heated ,P. the lactonesare
I
Use of phenyl iodide for this reactionresultsin racemic2 and3 in 23 and2% probablybecause theBINAP ligandin thecatalystis displacedby ;"ield,respectively, the iodide. Opticallyactivecis-decalins canbe obtainedfrom substrates suchas4 by a Hecktypereactionwith PdClz/(R)-l(l : l) as the catalyst.E Additionof varioussilversalts rmprovesthe yield and enantioselectivity. For cyclizationof 4 to 5, the highest wasobservedby useof Ag3POa cnantioselectivity andCaCO3(2 equiv.of each)with (NMP) as solvent(60'). l-methyl-2-pyrrolidinone
(,d' $Frei5 /\,cH2orBDMS
H 5 (807oee)
iq .e
11 rctive phthalides
Asymmetrtc intramolecular hydrosilylation.e The intramolecular hydrosilylwhen catalyzedby Rh(I) rrion of allylic alcohols(14, 137)can be enantioselective is depen;omplexedwith either (R)-BINAPor (R,R)-DIOP.The enantioselectivity &nt on the groupsattachedto silicon,beinghigherwith a phenylthanwith a methyl (93Voee) was obtainedwith the di(3,5-xylyl)silyl group.Highestenantioselectivity aher, ROSiHIC6H3(CH3)2-3,512.
36
Bis(l,3-bistrimethylsilylcyclopentadienyl)chloroytterbium(Ill)' Cp;rybcl
-1 j"' f"' f' Rh.,. f"' f"' t i"' ",.11),, H,c/+cH,'*'lilli'o',1""1A. liF os(c6H5)2H
Sitc.H'lJ
d-
L
,r,,l,l_nr,l' T l V oe e
particuReview.ro Noyori has reviewed homogeneousasymmetriccatalysis, larlybycomplexesof(R)-and(S)-BINAPwithruthenium.Hesuggestspossible .""ron, for the high efrciency of Ru-BINAP complexesin catalytic hydrogenation
aliphaticaldd reactto givc o rn the reac{io rith benzal&
V, F. trppca : L . G o n gu d , SbOi-isoprcl
(40 references). lR. Schmid Helv.,13,1258(1990)' andH.-J.Hansen' 2 T. Hayashi, andY. Ito,Am' Soc',llf ' 3426(1989)' Y. Matsumoto, N' H' Takaya'S' Akutagawa' 3 R. Noyori,T. Ikeda,T. Ohkuma, M. Widhalm,M' Kitamura' iDid',flf' 9134(1989)' andH' Kumobayashi, Sayo,f. Saito,T. Taketomi, (1990)' a H.'Takaya, T. Ohta,S. Inoue,andR. Noyori,Org' Syn',submitted (1990)' 5 M. Kitamura, N. Sayo,andR. Noyori,Org' Syn',submitted Letters'31' 5509(1990)' 6 T. Ohkuma, andR. Noyori,Tetrahedron M. Kitamura, ? F. Ozawa, , Am' Soc',f13' 1417(1991)' A. Kubo,andT. Hayashi 8 Y. Sato,M. Sodeoka, l' Org',54,4138(1989);idem'Chem'Letters' andM. Shibasaki' 1953(1990). Letters'3l' 7333 e K. Tamao,T. Tohma,N. Inui, O. Nakayama, andY' Ito' Tetrahedron 0990). r0R. Noyori,Chem.Soc.Rev.,18,187(1989)' CpiYbCl (l) ' Bis(1,3-bistrimethylsilylcyclopentadienyl)chloroytterbium(IID' Preparation.r effected Mukaiyamaaldol reaction(6, 590-591). This reactionis generally is complex lanthanide This promotor. with Ticla in stoichiometricamountsas the present'2 is also chloride alsoeffectiveandcanbe usedas a catalystiftrimethylsilyl in the caseof Yields are >80% in the caseof aromaticaldehydes,and are >50%
o H o cHr (I) C.HTCHO +
t
/osiR3
6)Va
(z)
r*-
oc2H5
CH, (E)
Blrluhcy
rbprm I
St-rl.
I
I
o H o ll I
osiR,
l, K1
, C6Hr,'^\yr,^\OC2H5
CH, = 78:22\ (sYnlanti
oc2H5
(II) C.HTCHO +
r l l
CcrfuSa
rtrrrred by Cngorrd rcq rh uscd n Horever. ;rrrlysr for t CH.Cu-BFr r noertrbl;
C6H5"^*OCrH5
CH, (antilsyn= 8l: 19)
l,}f*r larcra'r lld t> 'Inrb Ua.:. ul htlr F,!d
37 2,4-Bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2'4-disulfide
cH, cH"
-z\.r'\ r l
t -
OH
l OH
s ; e a n t i= 9 5 : - 5 lIc ee
ralysis,particurtgests possible c hrdrogenation
5
{kutagawa,N ItQ r 90,
E 1990). n. Chem.Letters, krrers, 31,7333
Cp,abCl (1). 3nerally effected rnrdecomPlexis I l\ alsopresent.2 )i rn the caseof ) I \ -()c.Hs
ls llr
) \*,",
aliphaticaldehydes,but highly hinderedaldehydesdo not react at all. a,p-Enals reactto give only the 1,2-adduct.Useof the complexalsoshowsdiastereoselectivity in the reactionsof the (E)- and (Z)-isomersof silyl enol ethersof propionateesters (equationsI and II). with benzaldehyde I M. F. Lappert, 1190(1981). Comm., J.C.S.Chem. A. Singh, J. L. Atwood, andW. Hunter, I L. GongandA. Streitwieser, (1990). J. Org.,55,6235 l. Bis(N-isopropylsalicylaldiminato)copper(Il),
-r:{,..fe .) eFi\:/Pr-i
Conjugateaddition of Grtgnard reagents.t CuI (or CuBr), particularly when activatedby ClSi(CH3)3and HMPA, is known to catalyzeconjugateadditionof to c,p-enones(14, 88). Surprisingly,CuBr2is aseffectiveasCuBr Grignardreagents whenusedin combinationwith thesetwo activators(3 equiv. each). andHMPA is usefulasa However,neitherCuI nor CuBr2activatedby ClSi(CH3)3 catalystfor conjugateaddition of CH3MgBr to c,p-unsaturatedesters.Even the complexis not usefulin this reaction.Surprisingly,theCu(II) complexI CH3Cu'BF3 is remarkablyefficient(equationI). r, crs(cH,), 9t' (l) PCH:CHCOOC,H5 + CHrMgBr *H-PTCHCH2COOC,H' with ClSi(CH)3can in cornbination Bis(salicylidene)ethylenediaminatocopper(II) esters,but is lesseffectivethanl. alsopromoteconjugateadditionto o,P-unsaturated ' H. Sakata, Letters,3l,l16l (1990). Y. Aoki, andI. Kuwajima, Tetrahedron de 2,4Bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfi ( Lawesson'sreagent,l), Thiomidizttion.r Reactionof the phthalirnide2 with Lawesson'sreagent(1) providesthe thioimide 3 as the only product, probably becauseof steric effects. Unlike2, whichdoesnot undergocyclizationundera varietyofbasic conditions,the (4) in 76% yieldwhenrefluxedin thioimide3 undergoes cyclizationto magallanesine is the first known isoinDMF dimethylacetal,(CH3O)2CHN(CH3)2. Magallanesine
Bis(oxazolines)
rcQ
ocH3
- l,(c^lL, ^ 71%
ocH3
rhatboth the diu R group, beinghi A (CH:)zCOHgn The estergroupo tion. The trotrs:c
o / \
o
l, C.HTCH:CH.
o
R = R =
rn cstalyzed rcE ilclopropanatim dlcnes, but mt ! Highly cfrcicr Percatalystscoq :r reactionof din -:!.ndsoftypc l. I Fopanationof srt
4 seerhodium(Il) alkaloid.For a relatedcyclizationto a benzazapin dolobenzazocine this volume. carboxylates, I F. G. Fang,G. B. Feigelson, (1989)' Letters,30,2743 Tetrahedron andS. J. Danishefsky, Bis(oxazolines). Asymmctric cyclopropanation, Three laboratorieshave reported that copper are effectivecatalystsfor asymmetriccycloprocomplexesof chiral bis(oxazolines) suchas I are readilyavailapanationof alkeneswith diazoacetates. Bis(oxazolines) followedby cyclizamalonate of c-aminoalcoholswith diethyl ble by condensation of Cyclopropanation tion, effectedwith dichlorodimethyltinor thionyl chloride. I indicates of type catalyzedby coppercomplexes styrenewith ethyl diazoacetate OCrH5
CrH50 -\rr,^\-y/'
il o
tl o f
o\.,,^--Zo
t*",
t
l
HN-._,.CH.OH
HOH,C-_,,,NH
'l
HOCH.CHNH.
l
:
R
5 resultsin e mir rro lll. Incrcesc rrrcr dcrived fru *,rnr-c;..cloprogy
R
R (cHJrsncl?
.,"-,,llL'
,o_ro*
|
I
(',H.CH:CH:
R = R =
.ro:r--ri-or ilJ
\'-i'r I
R
R I
r irdd by Lil p.drcrbyl por -lrrlo. rrc |ppo
Bis(oxazolines)
that both the diastereoselectivityand enantioselectivityincreaseswith the size ofthe R group,beinghighestwhenR:C(CH3)3 asin the productobtainedfrom r-leucinol. A (CH3)2COH groupis alsohighly effective,but this bis(oxazoline) is lessavailable. The estergroupof the diazoacetatealso effectsthe stereoselectivityof cyclopropanation. The trans:cis selectivityas well as the enantioselectivity are particularlyhigh
rl) C.HTCH:CH,+ NTCHCOTR'Ill"-
C'Ht;frrH
H
-CO,R' +
H
coH.7t
trans
R'= C:Hs R' = /-Men.*
rhodium(II) : - 1 3( 1 9 8 9 ) .
84Vo 7ZVo
'15:25 8 6 :1 4
H *\aor*'
cls '77Va ee 96Voee
in catalyzedreactionsof /-menthyldiazoacetate (equationI).t'2 This asymmetric cyclopropanation is generallyapplicableto monosubstituted andto I,l-disubstituted alkenes,but not to 1.2-disubstituted alkenes. Highly efficientcatalyticasymmetriccyclopropanation can be effectedwith coppercatalystscomplexedwith ligandsof type2.3 Thesebis(oxazolines) are prepared by reactionof dimethylmalonyl dichloridewith an c-aminoalcohol.As in the caseof ligandsoftype 1, particularlyhigh stereoselectivity obtainswhenR is r-butyl.Cyclopropanationof styrenewith ethyl diazoacetatecatalyzedby coppercomplexedwith
rhal coPper ic clclopro-
CH,
o
rdill'availaI br cyclizarpanationof : I indicates
)H
90Voee 98Voee
N
n \ N-J
2a, R=C(CHr).
2a resultsin a mixtureof trans-andcis-cyclopropylesters,both in >97% ee (equation II). Increasein the bulk of the estergroup increasesthe trdns-selectivity. The esterderivedfrom 2,6-di-t-butyl-4-methylphenol (BHT) forms essentiallyonly the rrans-cyclopropyl esterin997o ee. Estersofthe type cannotbe hydrolyzed,but can CuHt'.
IIr C.H,CH:CH,
cu.2a A ------------) ,ffi
+ NTCHCOTR'
H
R'= CzHs R'= BHT
77Vo 85Vo
,H 'COrR
99Vo ee 99Vo ee
+
H..n ,H H 'CO2R
CoHr73:27 94:6
9 ' l % oe e
bc reducedby LiAlHa to the corresponding primary alcohol(76Vo,)99Vo ee). The groups at the methylene eez-dimethyl bridge, which preventdeprotonation at that are apparently the optimal ligands for asymmetriccyclopropanation. oosition,
.10
Bis(oxazolines)
Diels-Alder EnantioselectiveDiels-Aliler reaction.4 Highly stereoselective prepared 2b, reactionscan be achievedby use of the 4,4'-diphenylbis(oxazoline) from(*)-phenylglycinol,asachiral,bidentateligandforironsalts.Thusreactionof be I-FeIs' which can FeI3with 2b anOlz in CH3CNforms a complexpresumedto at - 50o catilyzereactionof 3_acryioyl-1,3-oxazolidin-2-onewith cyclopentadiene (82% ee)' 2R-enantiomer to giue the endo-add'di;g;V" yield. The product is the
t"'\,rt"'
\fYo) N-J \-./N
'CuH,
",.=rLA.O t:,,+\,A{+
c. R' R'
' R. E. Lowenthal, A. Abitl : D. Miiller,G. Umbricbt.E I D. A. Evans,K. A. WocrF ' E . J . C o r e yN, . I m a i ,r d I
Bis(oxazolinyl)pyridince A typicalmember(lr) by reactionof pyridine-2
n",{!,';i.;}u";' Asymmetric transfer hydrogenatior.2 Bisloxazolines) lacking a methylene alcohols, bridgesuchas3 arepreparedby reactionof dimethyloxalatewith c-amino
o
"><"
o
\--1 , / \
ocHl
cHro
+ HOCH,CHNH" -l R
HOCHTCHNH
-------t
HN cHcHroH R
R
Enantioselectivc hy&r andla whenactivatedby r hydrosily enantioselective acidichydrolysis,(S)-scc mole %) improves the et
'l*uf'o.'
C]x-J J ' R 3a' R = CH(CH)t
of this type when complexed followedby cyclizationwith Socl2. Bis(oxazolines) transfer reduction of alkyl enantioselective catalytic effect with [Ir(coD)cl]2 can stereoselectivity' aryl kltoneswith i-prOH. Dialkyl ketonesare reducedwithoutany Preliminaryresultssuggestthatligandsoftype3areusefulforPd.catalyzed substitutionof allylic acetatesby the sodiumsalt of nucleophilicenantioselective dimethyl malonate.
t"ry o
obtainsin reductionof ldialkyl ketonesare reducc Replacement of the isq
coq
CH.
(957o*l
Bis(oxszolinyl)pyridines
Diels-Alder srereoselective lbrs,..razoline)2b, PrePared Drrrt n salts.Thusreactionof me.j to be I-FeI3,which can at -50" ith ;rcloPentadiene (82% ee)' he lR-enantiomet
\ H . ---;( /^-
o
Jl. -O \-J
4t
OH C6H5COR' + r-PrOH P' = CH: R'= CH(CHrL
"'*, 89Vo 70Vo
ArAR' 58Voee 91Voee
Bis(oxazolinyl)pyridines. A typicalmember(la) of this groupof chiral c2-symmetrical ligandsis prepared by reactionof pyridine-2,6-dicarboxylic acid chloridewith r-valinol (60% yield).
CON/
.'^: .'\o = 96:.4) R . S l . 2 9 oe e
r,lrne.t lacking a methylene lral.rtewith c-aminoalcohols, {) t.t\cHCH2OH : R
Enantioselectivehydrosilylation of ketones.r The complexformed from Rhcl3 rnd la whenactivatedby a silver salt, AgBFaor Agorf, is an effectivecatalystfor cnantioselective hydrosilylationof ketoneswith diphenylsilaneto provide, after rcidic hydrolysis,(S)-secondary alcohols.In all cases,additionof free ligand (4-6 mole vo) improvesthe enantioselectivity markedly.The highestenantioselectivity
I
I \-J
"?xi;l'
) .R
(93Vo ee)
; (-li CH,). | .ri this type when complexed ire :ransfer reduction of alkYl I u rthout any stereoselectivitY. 3 are useful for Pd-catalYzed lcerrles by the sodium salt of
obtainsin reduction of l-tetralone (99% ee) and of methyl aryl ketones,but even dialkyl ketonesare reducedwith significantenantioselectivity (>60% ee). Replacement ofthe isopropylgroupsof la by sec-butylgroupshaslittle effecton
t?x;-cooc'H5 (95?o ee)
"Titg;-"'t' (MVo ee\
"?xD-"'"' (66Vo ee)
42
Bis(2,2,6,6)-tetramethylpiperidino)magnesium
groupslowers the by r-butyl groupsor phenyl the enantioselectivity,but replacement catalytic activity' "nuniiot"f..rivity and also the 10' 500(1991)' andK' Itoh' Organometallics' I H. Nishiyama, M' Kondo'T' Nakamura' (f hydride dimer' (CpiLaH)z )' cvBis(pentamethylcyctopentadienyl)lanthanum effects lanthanide of amino alkenes't This lntramolecula' Wd;;;i;";ion nitrosix-membered and iyororurbon solventsto fiveclization of amino"k""""J genheterocYcles'
l.&Bis(trimethYlsilYl)-2'5atl This disilyloctadieneis obtaincdt rive dimerizationof a mixtureof rield). The main bY-Producris I Sub stitutcd cYcloPcntotct'l undergosubstitutionbY an cleo givc substitutedPentanes.In Po usefulrouteto l-alkYl-2'5divtq but it can bc end rneso-isomers,
H
cHlcOCl * 1-tr9-
! H2N(cH2)3cH:cH, dIt"'
t
-....-($.",
CH,CH:CH,
\.,^N'
NH,
cH2COCl
cHrcoocH 4108(1989)' I M. R. Gagn6 andT' J' Marks'z{m'Soc''111' (TMP)2Mg' This stable magneBis(2,2,6,6-tetramethylpiperidino)magnesium' TMPH' in Jr z'z'e 'e-i"'ramethylpiperidine' sium diamide i, out"in"a ily''"""i"" --'O refluxingTHF with dibutylmagnesium' t rulLut can be rt ho-^"tul l ation i s not li mited ::. :th n'.' i ati' gn sf e a n Dir ected thanlithium amides'Even diamides'which aremorestable effectedwith magnesium thesebases(equationsI' ID' esterscan be metallatedwith
Tctrolu \ TubulandM. Santelli,
tb(trimethYlsilyl)Peroxi&' (( Preparation.r Details ere rrth 2 equiv. of H2O2and for t rroxide I on a largescale.Tb dcquate for PreParationof thc uiety shields.
coocHj ,\
0)
V
l) (TMP)?Mg 2) COr l) cH,N!
coocH3 coocH3
A. Ricci,G. Socd P Dembech,
,
lis(triphenylarsine) Palledh
8l%
coocH3
'-io.l
coocH3 coocH3 coocH3 + ,\ 3:l
coN(c2H5)2
coN(CrH5),
I P. E. Eaton,C.-H' Lee, andY' Xiong' Am' Soc''lll'
i l l fcoocu,
coN(crH5)2
Cyclization ol allYl ProP
o
*y' leR = lb=
8016(1989)'
Bis(triphenylersine)pallsdium(Il) acetate
rl rrrrupslowersthe r r . 1 0 .5 0 0( 1 9 9 1 ) ' r C p : L a H )(z1 ) . rnthanideeffectscYnitrorir-membered
43
I,t-Bis(trimethylsilyl)-2,6-octadiene,[(CH3)3SiCH2CH:CHCH2]2 (l). This disilyloctadiene is obtainedas a mixtureof (Z,Z)- and (Z,E)-isomersby reductive dimerizationof a mixtureof butadieneand clsi(cH3): with lithium metal(55% yield). The main by-productis 1,4-bis(trimethylsilyl)-2-butene. Substitutedcyclopentanes.r The central methylenegroups of this diene can undergosubstitutionby an electrophile followed by intramolecularcyclization to give substituted pentanes.In particular,the reactionwith acyl chloridesprovidea usefulrouteto l-alkyl-2,5-divinylcyclopentanols. The reactionusuallyresultsin d/andmeso-isomers, but it can be stereoselective, as shownin the secondexample. O
CH3\...OH
CHTCOC| +
4Si(CH.),
,j#.",./fr^"", ."/L'fr^"", (537o\
(32Vo)
]H
cHrcocl CH2COOCH. + t
------------Ur{
CH,
= ll'5:l) (dllmeso This stable magneiprridine,TMPH' in ttr lrthiumbut canbe lrthrumamides.Even
( 1990). (1988);idem,Org.Syn.,submitted A. TubulandM. Santelli , Tetrahedron,44,3982 (l). Bis(trimethylsilyl)peroxide,(CH3)3SiOOSi(CH3)3 Preparation,t Detailsare availablefor the preparationof DABCO complexed rrth 2 equiv. of H2O2and for reactionof this complexwith ClSi(CH3)3to give the pcroxideI on a largescale.This preparationis relativelysafebecause35VoHzOzis rlequatefor preparationof the complex,but the productshouldbe handledbehind rafetyshields. (1990). P Dembech, A. Ricci,G. Seconi, andM. Taddei,Org. Syn.,submitted
fi-H,
lis(triphenylarsine)palladium(Il) acetate, [(CoHs):AshPd(OAc)z(l). Prepara::on.' Cyclizationof allyl propargyl ethers,2 This Pd complex is far superior in reC.H.
S
^coocH,
d-,Hs
)\,c:H5)2
*)-"-t"
9,
laR = H lb = CrHs
--l-----, "'f nFcn, 'l3%o 96Vo
2
U
Boron trifluoride etherate
2 I spectto yield andeaseof workupfor cyclizationof theethersla or lb to ,3-dienes and for the cyclizationof the more elaboratesubstrate3'
diastereoselectivity (equationII). Thir of 4, a precursorto statine.4 9CrH'
CuH,
tu"'t
crHsoocN-cHCHTCH(CH.; +
/\c:cH ot-1,^1,,""' cH,
Bzl
cH, BzINCOOCTH.
4
3
'T.A.Stephenson,S'M.Morehouse,A.R.Powell,J.P.Heffer,andG.Wilkinson,,I'C.S.' 3632(1965). J' Org'' 54' 4489(1989) 2 B. M. Trost,E. D. Edstrom, andM. B' Carter-Petillo' Boron trifluoride etherate. 4-amino|.2-Amino alcohols. Imines,particularlythosederivedfrom methyl (1-alkoxypropen-3with 1, couple as andan aryl or aliphaticaldehydesuch benzoate gcHoTHP (l) p-cH.ooCCuHnN:cHCuH, + Bu,SnCurcH +;15 1
2
(cH3)rcHcHrcH-GHCH :Cl OMOM = 100:0) (synlanti
C-Glycosidatior.3 Protected pyr tion whentreatedwith variousCr-ory Thus I -acetyl-2,3,4,6-tetrabenzylg penylsilanein CICH2CH2CIar l0' r glycoside3 in 74% yield as a miru resultsobtainwith other oxygenate
OTHP CH-:CH/
-l-
Y
-cuH, "
NHC6H4COOCH3 = 3:1) 3 (sYn/onti
BzlO
\cO
...OBzl + CHr:(|161
oA
yl)tributylstannanes(2) in the presenceof BF3 etherateto give derivativesof l,2aminoalcoholswith syn-selectivity(3-10: l), equation(I)'t andBF3etherateor TiCla(l equiv') with a 1The reactionof a-ethoxycarbamates alcoholswith moderateto high slnl,2-amino in results alkoxy allyltin reagent
(II) CH3OCHTOCH:CHCH'SnBu, +
c2Hsooc\ ?t'"' BF,. O(C,H5)' N-cHcH(cHr), w% Bzl
oMoM
oMoM GH;rHC,,a.)^,=4>CHz
I
cHcH(cH3)' I BZINCOOC.H.
+
(cH3)rHc-V)VCH'
' 28:72
l
CHCH(CH3)' BzINCOOCtH'
Polyols. Rychnovskyahasusedr itlllithium of Ganem(12, 68) to c 'lagent preparedfrom a p-hydroxy ek J BFr etherate(2.5 equiv.) to give d
Boron trifluoride etherate
2 lb ro I .3-dienes
(equationII). This procedureprovidesa stereoselective diastereoselectivity synthesis of 4, a precursorto statine.4
oc,H.
t - "
crH5oocN - cHcH2cH(cH3)2+ CH,oCHToCH:CHCH'SnBu, !li99ln\ I Bzl
CH. :H
. \ \ : l k i n s o nJ,. C . S . , Ite ,1989).
l) 9-BBN;HrOr(46%) 2) HCt, THF (43%) 3) Na/NH.(27%)
)THP
HN
o tl /\
-O
\J
/ , . (cH3)rcHcH, (cHr)roH
(synlanti= 100:0)
n methyl 4-aminoI -aIkoxyProPen-3-
4
C-Glycosidation.s Protectedpyranosidesundergostereoselective C-glycosidation whentreatedwith variousC1-oxygenated allylsilanespromotedby BF3etherate. (l) reacts with l-acetoxy-2-proThus l-acetyl-2,3,4,6-tetrabenzylglucopyranose penylsilanein CICH2CH2CIat l0' promotedby BF3 etherateto provide the C1glycoside3 in74Vo yield as a mixtureof a/p-isomersin the ratio l0:1. Similar resultsobtainwith other oxygenated allylic silanesand activatedglycals. OBzl
c^tt,
L
BzINCOOCTH, I (CH3)2CHCH2CH-CHCH:CHz I OMOM
...OBzl + CHr:Q11 cHSi(cH3)3
\HC6H4coocH3
BF,.O(C,H,)r c,H,ct, 14qo
OAc
r:rlr = 3:l)
OBzl d e r r r a t i v e so f 1 , 2 ,rlequiv.)withaYderate to high sYn-
BzlO AcO. \u12.\:
Bt
l'
'qc,H)1
---,xt.
+
OBzl OMOM I r-s "''2
n\ v
-//
cHCH(CH3)' Bzl\COOCTH'
3 (otl9= 10:l) Polyols. Rychnovskya hasusedthe BF3-catalyzed couplingof oxiraneswith an alkyllithiumof Ganem(f2, 68) to obtain polyol chains.Thus the tetraalkyltinI reagentpreparedfrom a p-hydroxyaldehydereactswith the oxirane2 in thepresence of BF3etherate(2.5 equiv.) to give the protecteddecanehexol 3.
Boron trifiuoride etherete
1i-n;,sio'-SftsnBu'
oxo
H,C
N.^n
+
\ :
o
I
l r l (l) ,-gu-\cH, * ,/Y' cH. r
I
o--o
,2\. cH, cH, ,,
CH,
t
M=Li M = TBS, BFr.O(C'H.):
I BuLi (l eq.) 62% I BF,.o(c,H')r(2.5eq.) rHF, -78' I
*
R3sio
YY oxo CH,
o>
OH
H,C
CH,
CH,
3 reaction). A-lthoughTicla Aldol reactionswith enol silyl etherss(Mukaiyama BF3etherateis more ethers, silyl enol is commonlyusedto effectaldol reactionswith as (Z)- and (E)-3such ethers enol effective for aldol reactionsof tetrasubstituted methyl-2(trimethylsilyloxy)-2-pentene(l)'Theseenolatesreactwithaldehydesin but with generallyhigher levels the samesenseas tne corresponiing metal enolates,
os(cH3)3
c6HJcHo BF.. o(c?H,)r-
CuH,
a9%
cH$(\cH,
r r r )r * s / *
o
osi(c2Hs).
ll
!
-cH.
: CH,
OH
OH
lithium enolate.An even more strih Evansand GageTin reactionsof thc , Surprisingly,the reactionofthe lithir aldol adduct3. The desiredsyn. r)r-i
syn-2 M=Li M = TBS, BF3.O(CrH:),
CH,
t
(z)-| osi(cH3)3
.^"€"3.,, ^,, BF"o(c':' -,
|
^,,,r\,rtnr
LHr
84%
(
syn-2
+
anti-2
, 20:80
CH, (E)-1 by a methyl andhigheryields' Since(Z)- and(E)-1differ only ofdiastereoselectivity, of (Z)- and stereoselectivity intrinsic substituent,their behavior sliouldreflect the (E)-enols. Diastereoselectivealdolreactions.HeathcockandFlippin6haveobservedthat of an enolate(l) of pinacoBF3etheratecan improve syn-selectivityin the reaction lonewith2-phenylpropunull"qoutiong.ttrus,thereactionofthe'-butyldimethylsis)"-selective than that of the lvl enolatein the presen., of BF, etherateis more
'.bc t-butyldimethylsilyl
ether and Bl eren reverse the aldehyde diastereol
V. A. Ciufolini and G. O. Spcncer.J. ' Y. Yamamotoand M. Schmid,.l.C.J.t J S. Panekand M. A. Sparks,J. Ory' S D. Rychnovsky, ibid.,54,49t2 (19 ' S Yamago,D. Machii, and E. Nrlrr ' C H. Heathcockand L. A. Flippio. A D A. Evansand J. R. Gase. Tctad
Boron trifluoride etherste
o M o l t l 0) ,-suAcH, * ,/Y
Y^
o- ,o
cH3
I
CH.
H
cuH'-l!*
M=Li M = TBS, BFj.O(CrHj),
t
o
OH
ll
:
/r!
,-su)*cuH' o
: CH,
syn
80:20 96:4
ct{
!a.lrr)n). Although TiCla lhe r.. BFr etherateis more rs .uch as (Z)- and (E)-3Gs react with aldehYdesin vrth generally higher levels
+ 'ttti-isomer
lithium enolate.An even more striking exampleof this effect has beenreportedby Evansand GageTin reactionsofthe enolatesof I with the aldehyde2 (equationII). Surprisingly,thereactionof thelithium enolatein this caseresultsmainlyinthe antialdoladduct3. The desiredsyn,syz-adduct3 is obtainedin 80% yield by reactionof
o i
l
osi(crHs)3 :
(u) r * n)*cH'-----: CH,
syn-2
CH,
M=Li M = TBS,BF3.O(CrH5)2
807o
ant12
osi(crH5)3
t.,zcH, t-Bu
anti-2
: syn,syn-3
+ anti, syn-3
I 8:82 98.'2
rb€ rbutyldimethylsilyl ether and BF3 etherate. In this example the Lewis acid can even reverse the aldehyde diastereofacial selectivity.
r E ,-l differonlYbYa methYl of (Z)- and nereoselectivity I Flrppin6haveobservedthat I raian enolate(1) of Pinacotrrrnoi the t-butYldimethYlsirn-:electivethan that of the
M. A. CiufoliniandG. O. Spencer, J. Org.,54,4739 (1989\. ' Y. Yamamoto andM. Schmid,J.C.S.Chem.Comm.,l3l0 (1989). l S. PanekandM. A. Sparks,J. Org.,54,2034 (1989). ' S D. Rychnovsky, ibid.,54,4982 (1989). ' S Yamago,D. Machii, and E. Nakamura,ibid., 56, 2098 (1991). 'C H. Heathcockand L. A. Flippin,Am. Soc.,f05, 1667(1983). D A. Evansand J. R. Gage,Tetrahedron ktters,3l, 6129 (1990).
N-(Bromomagnesio)-2,2,6,6-tetremethylpiperidide
48
9-Bromo-9-phenylfluorcr, Full details are availeH protectionof amino groupt
N-(Bromomagnesio)-2'2'6,6'tetramethylpiperidide' CH, (
r--tCHr 'NMgB,
rT. F. Jamison. W. D. Lub. (1990). submitted
(BTMgTMP)
\--4cH: tt, in tetramethylpiperidinewith C2H5MgBr This reagentis preparedby reactionof the ' refluxingTHF. -L.^:- r^.,,, possibleto obtain four stereotso(EbSilyl enol etherc.r In theory it shouldbe as I by controlling the geometryofthe meric aldolsfrom a singlechiral ketonesuch selectivity of the carbonyl group-by chelaenolate(E or Z)and the diastereofacial tion.Thetwopossiblesyn-diolshavebeenobtainedasexpectedfromthe(Z)-lithium andboronenolatesofl.Becauseofthepresenceoffourmethylgro ups0tothe 1 to the (E)-magnesiumenolate' which metal, this Grignard ."ug*t deprotonates
RC6H.C
Aliphaticprimarysilyl ci thesimpleestersformed fror mixtureof an aliphatical&
l) BTMgTMP
O
(cHr)3c---*,rJ1...-/-cHr
(l)
N-Bromosuccinimide. Radical oxidation otA NBScatalyzedby AIBN to i lower in a similar oxidatir spondingo-bromo ketorc ir
2)rsrg---t
(cH,),siA t-Bu
(I) 2CrHilC
?
(cH3).sio
t
CH.
,
t-Bu
(cHr)3sio
CH,
sameconditions,a mixedc{ oridationof a mixtureof er csreronly whencatalyzedb
95:5
(II) C.H,TCHO r
l) BTMgTMP 2) (t-PrO)JiCl' (G 3) RCHO
3
+ 2 95:5
(g2-g5:8:5) in ?5-85% yields reactswith various aldehydesto form ,ntlaldols it is necessaryto convertthe (E)(equationI). To obtaintnJon", po.rible anri-aldol magnesiumenolateintoanonchelatingmetalenolate.Transmetallationcanbeefresulting(E)chloridi, HMPA, and sonication.The fectedwith triisoproxytitanium product minor the is the anti-aldol which Ti enolateprovides as the major product with I reaction in with BTMgTMP from the Mg-enolate.fn' el-'"f"ttivity observed group' c-alkoxy presenceof an is not generaland dependsmarkedly on the J' Org" 56' M' T' Crimmins'andC' H' Heathcock' I N. A. VanDraanen, S' Arseniyadis' (1990)' 99 23' Acta' Aldrichin' i+s9i199r)tC. H. Heathcock-,
(III) C.HTCHO+
RCHO + RCOBr.2 R xovides acyl bromidesin; .ened into amides.
xDs
( )-cHo \_J
' r
I E. Markd, A. Mekhaltu. r i E. Markd and A. Mekhrll
N-Bromosuccinimide
49
9-Bromo-9-phenylfluorene, 13, 48-49. Full details are available for preparation of this reagent, which is useful for protectionof aminogroupsand which is not commerciallyavailable.r rT. F. Jamison, W. D. Lubell,J. M. Dener,M. J. Krischd, andH. Rapoport, Org. Syn., (1990). submitted
in 'sr,11ns with C2H5MgBr ! r(\ \rbtainfour stereoisoof the ollrngthegeometry chelabY grouP cart'r-nyl cctedfrom the (Z)-lithium r methyl grouPso to the ngnesiumenolate,which
N-Bromosuccinimide. Radical oxidation of silyl ethers.r primary benzylicsilyl ethersare oxidizedby NBScatalyzedby AIBN to thecorresponding aldehydesin70-87% yield. yields are lower in a similar oxidationof secondarybenzylicsilyl ethersbecausethe correspondingc-bromo ketoneis a by-product. .s-lII\ RC6H4CH2Osi(Cft,),
Aliphaticprimarysilyl ethersare oxidized,probablyvia an aldehydeor acetal,to thesimpleestersformedfrom two equivalents of the silyl ethers(equationI). when a mixtureof an aliphaticaldehydeand a primary silyl ether are oxidizedunderthe aH\ (I) 2C5HilCH,OSi(CH3)3
oi .
t-Bu
-
I
('t{,),SiO
u
RC6H4CHO
C5H,,COoc6H,r
OH l
l
t--
-
i
CH,
R
rameconditions,a mixedesteris obtainedin quantitativeyield (equationII). Similar 'rridationof a mixtureof an aromaticaldehydeand a silyl ether resultsin a mixed csteronly whencatalyzedby trimethylsilyltriflate (equationIII).
f i
(II) C6H,3CHO + C,rHrrOSi(CHr), +#\
c6Hr3COOcr2H25
NBS, AIBN.
(IID c6H5cHo+ c,rHrrosi(C"rl, i-*U#5
9 5 3 : 5 ) i n 7 5 - 8 5 %Y i e l d s Fce\saryto convertthe (E)can be eflransmetallation (E)resulting The orcation. rhrch is the minor Product )r\lgTMP in reactionwith I 'an o-alkoxYgrouP.
c N
J. Org.,56' H Heathcock,
c6Hscoocr2H2s
RCHO + RCOBr.2 Reactionof aldehydeswith NBS in the presenceof AIBN rovides acyl bromidesin goodyield. The products,without isolation,can be con,enedinto amides. ' NBS..CCt4
( \_J
FcHo -+_-( 83qa
//--\
3
)-ce' \J
'f""', soso
I
\-coNnsu
\J
E. Mark6, A. Mekhalfia,and W. D. Ollis, Synlett,345,347(t990\. E. Markd and A. Mekhalfia,TetahedronLetters,3l,7237 (1990).
50
BromotrimethYlsilane
N-Bromosuccinimide-Pyridinium poly(hydrofl uoride)' with diethylR2C:O + RzCFz. This reaction has been carried out directly reactionof by be effected aminosulfurtrifluoride (DAST, 6, 183-184).It can also
l-Bromovinyldimethylsilylchloridc, t( ( 1 , b . p . 8 0 " / 1 2 0m m ) .
hydrazonesofaldehydesorketoneswithbrominefluoride,BrF,generatedinsitu fromNBSandPy(HF)".Yieldsfromreactionsofhydrazonesofketoneareinthe range30-95%;theyieldfromreactionofthehydrazoneofanaldehydewas2Svo.
The reagentis preparedfrom [(CH3:C drobrominationto give [(CH2:CBr)Si(l cH3sicl3. rG.K.SuryaPrakash,v.PrakashReddy,X.-Y.Li,andG.A.Olah,synlett,594(1990\' Hydroacylation and hydrovinylotiot t is {2) silylatedby I to provide3. This prod BromotrimethYlsilane. trans-2,5-Djcryltetrahydrofurans|(|4,240-24|).Inasynthesisoftheplatelet t"ta haveusedCorey'sroute t activatingfactorknown as L-659,989(1), Merck chemists improvements'The some introduced have but to trans-2,S-diaryltetrahydrofurans, OH o-tt' lactol (2) to the c-bromoether mostsignificantis the conversionof the intermediate l-butyldimeththe on with BrSi(cH3)3.This stepis markedlyimprovedif conducted (CHg)zsioH' ylsilyl ether,in which casethe by-productis a disiloxaneratherthan subsequent the with which on dimerizationforms water, which can interfere
A
,
A
:l,u.Hr :ilu 2
so2cHr lll^l:Y:{Sr T zi'ctt,',sis' ---'*-, t l.
"o{oA1\
\Co" ocHl
I \^-[+
Ir,A"Aorl*
3
R,siosin n'siosin'
I| .",\/:\
ro* cH,o\ yluesr f| | cH,o/-' I I-i,cuctlrHr I
.p+QjJ"'
rs the major product.Hydroperoxidcori rll-cis)-S;basiccleavageprovidesthc vi
KOC(CH,),.
l, >98Vaee (translcis = 40: l)
useful for synthesisof cGrignardreactions.This anomericactivationshouldbe glycosides. of the Grignardcouplingcan be increasedby additionof The trans-selectivity coppersaltssuchas CuCN or dilithium tetrachlorocuprate' w. Russ'E' D' Little'T' R' D. McSwine, I A. S. Thompson, P. Simpson, D. M. Tschaen, (1990)' 6953 3f' Letters' andI. Shinkai,Tetrahedron Verhoeven,
o-#--
t""' cH.'
X. Tamao, K. Maeda,T. Yamaguchi, aodY
hrdiene-Iron carbonyl complexcs. R.eview. Grder has reviewedthe syt i:sr preparation(1930)until the pres€ntI
Butadiene-Iron cerbonyl complexes
drrecrlvwith diethylIct:ed by reactionof in situ [F. generated I oi ketoneare in the was28Vo. I aiJeh;-de 594(1990). l, -\.'rletr,
lnrhesisof thePlatelet re uied Corey'sroute The E rrxProvements. ether a-bromo the ro ) I trn the t-butyldimethbcr than(CH3)2SiOH' \rrth the subsequent
l-Bromovinyldimethylsilylchloride, (CH,)rSia (1, b. p. 80"/120mm). )C:Ctt, Br The reagentis preparedfrom [(CH2:CH)Si(CH3)2]2O by brominationanddehydrobrominationto give [(CH2:CBr)Si(CH3)2]2O,which is then silylated with cH3sicl3. Hydroacylationand hydrovinylation of allyl alcohols.t A typical allyl alcohol t2) is silylatedby I to provide3. This productundergoes radicalcyclizationto give4
t"'\ oH
/cH'
ort'-(tt'
.",J ll -5.",J li cH,\' cu, cH,/\. ,,\
b'
-\
Bu,snH
*H-.",
cH,
cH,
CH,
-l \.-l* '!
62Ea
R,SioSiR.
KF, KHcor
IHpl'
OH /"'\-\,"coCH3
CH.J
'-')""'
,
ctt. 5 (all-cis)
, ( 1 , .T H F
t \.'
I
cHr,\
SorcH,
\\ FOPr
rs the major product.Hydroperoxideoxidationof 4 providesthe acetylderivative ,all-cis)-S;basiccleavageprovidesthe vinyl derivative(all-cis)-6.
=<
OH Koc(qq)r,
ocH. {
*-
a\CH:CHz
cHrJ
i
cHr"\\^cHl 6 (all-crs)
ful ior synthesisof CL. Tamao,K. Maeda,T. Yamaguchi, and Y. Ito, Am. Soc.,lll, 4984(1989).
rre.rsedbY additionof , . R. R u . . .E . D . L i t t l eT
htrdiene-Iron carbonyl complexes. Review. Gr6el has reviewed the synthetic uses of these complexes since their :rst preparation (1930) until the present (109 references). The complexes undergo
52
(R,R)-(-)-2,3-Butanediol
as nonsubstitutedcarbon' They can function electrophilicsubstitutionat the terminal aprotectivegroupduringtrydrogenationofaremotedoubleortriplebond.Decomagents.Severalcomplexesare now availplexationis usually effeciedwittroxidizing groupshouldbe effectivefor diastereoseablein chiral forms, andthe bulky Fe(CO): lectivereactions.
o---""'
?
2-c,o
O{"\cH,+ ,
(1989)' rR. GrCe,SYnthesis,34l 80-81' (R,R)-(-)-2,3-Butanediol,11, 84-85; 12' Chiralacetalso!ArCHo.|Thechiralacetal(1)ofCr(Co)3-comple-xedbenza l d e h y d e u n d e r g o e s a n i g t r t y s t e r e o s e l e c t i v e r e a c t i o nAw subsequent i t h ( C H : ) d lRitter andTiCla(1 yield and 97'5To de' equiv.) to provide tn'n'njlZ in 72% CH,
/o)"'-
(CO).CrCuH'-1
|
blt", I
H-'--=O..I
:R.3R)-3+
si(cH'\
lCUrlrCCOrcfiH 4
cH3 6H(OH)CH3 l) A(cH,),, Ticl.
zrn'o'
't2qa
:
:
, (co)rcrc6H5-cHoc-cH3 I
H (RrR,R)-2(97.54ode) I t; cH.ct't'u'so. o""v |2) ...CH, c6H5C
reactswith (2R,3R)-3 !,laNlSi(CHr)r12, meric alcohol, separatedby flash chroo Sulfoxideeliminationof the arylthio I rKF), acetalhydrolysis(CSA in CHrCI group providesthe aldehyde6 in tOl and CeCl3(3 equiv.)ir LiNlSi(CH3)3]2
gH,oocc(cH3)l R,SiO I...b ^-i-z--\iH r)LiNrsrc |
,1,
l
cHo il reaction2anddecomplexationprovides(R)-N-acetyl.l-phenylethylamine(3)andthe by a methyl group thus proceedswith (R,R)-butanediol.The displacementof O retention,whereasthesamereactionwiththeuncomplexedacetalproceedswith inversion. for compounds'} The ove-rallstrategy Addition o! metal acetylidesto carbonyl (8) of core ofthe highly strainedepoxycyclononadiyne synthes-is an enantioselective consecutive involvesregio- andenantioselective the antitumoragentneocarzinostatin (4) with the carbonylgroupsof c-formylcyclopenJirn" reactionof a chiral "pof tenone'Enantioselectiveadditiontotheketonegroupwasachievedbyprotectionof and of the with (2R'3R)-2'3-butanediol' formyl group as the chiral acetal,formed 2-naphthalenethiol of by I ,4-addition doublebondby a 2_naptriiytthiogroup, formed which the two trons-diastereomers' of mixture i:1 a proviie' to 2. This reaction soThe yield' 50% about in by crystallizationto give (2R'3R)-3 can be separated with divne epoxy '"uiion of the monoprotected dium acetylideof 4, pt;;;;;;y
i
2 )N ( c l l ' , ' t r t
i
6
r;ngle diastereomerafter flash chroru ri{lr, the reactionis slow and incomp
andJ. M. l. R. F. Newton, S G. Davies, L I. KrimenandD. J. Cota,Org. Rcact andE. I t G. Meyers,P. M. Harrington,
r&tyl hydroperoxide. Stcreospecific epoxidation of hrt rrJroxy enonesI with H2O2in a basicu
,-Butyl hydroperoxide
bon Thevcanfunctionas lc or rriple bond. Decomconplexesarenow avail! efecttr.efor diastereose-
1.1
(
A
L
N(c,Hj)3 -i. /oa -#_.
f-\ F' /
-
.cH,'
..cH,
v
(
.H,+ 2-c,oFI,SH '
-
s
0
9
'
\
/
2
:R.3R)-3+
.SC,fi, 12R,3R)_3
si(cHJ3 NaNIS(CH.).1" .-..---------.--
H---=-
benzCrrCO)r-comPlexed rh CH,)rAl and TiCla (l Ritter .le .{ subsequent
XoAcH,
O::.1
40%
rcu,lrccorc(\
H
cHl cH(OH)cH3
5 ( 1 8t:)
c . H - c H' O Cl- c H 3 H R R R ''2 t97.59ode) | ', .n,.,u.n,,q
o'."v
lr) ...CH, c.lt C
NaN[Si(CHr)r]2,reactswith (2R,3R)-3to form an l8:l mixture of 5 and the epimeric alcohol, separatedby flash chromatographyto provide 5 in about40Voyield. Sulfoxideeliminationof thearylthiogroupof 5, deprotection of the silylacetylene tKF), acetalhydrolysis(CSA in CH3CN-H2O),and silylationof the free hydroxyl groupprovidesthe aldehyde6 in 80Vooverall yield from 5. On treatmentwith LiNlSi(CH3)3I2 and CeCl3(3 equiv.)in THF at 0o,6 cyclizesto 7, obtainedas a
cH,oocc(cHJ3
cH,oocc(cH3)3
l) LiNIS(CH,)]1,, CeCl,,THF,-78" 2) N(C?H.)r.3HF
r R -) ( + ) - 3
AU
En\.clhylamine(3) andthe with ct,\up thus Proceeds acetal lcr.'i Proceedswith ,.r The overallstrategYfor core(8) of 7l ; lononadiYne consecutive roselective nt !n.r 1t up. of a-formYlcYcloPenr a;hievedbY Protectionof )-: .l-butanediol,and of the ld rt r,.nof 2-naphthalenethiol which ,rdni -diastereomers, n rr'.rut 50/o y\eld' The soprotectedePoxYdiYnewith
6
7, R = SiRr 8,R=H
rrnglediastereomerafter flash chromatographyin 87Voyield. In the absence of CeCl3,the reactionis slow and incomplete. S. G. Davies,R. F. Newton,andJ. M. J. Williams,TetrahedronLetters,30,2967 (1989). L. I. Krimen and D. J. Cota,Org. React., 17,213 (1969). {. G. Meyers,P. M. Harrington,and E. Y. Kuo, Am. Soc.,f 13, 694 (1991).
rButyl hydroperoxide. Stereospecific epoxidationof hydroxyenones.r Epoxidationof the racemic rr droxyenones I withH2O2 in a basicmediumshowsonlya slightpreference for the
54
t-Butylhydroperoxide-Dislkyltrrtrate-Titanium(Iv)
o H o t t l R/-/\cH.
i l CH,
{CH,).cOoH. - c H , c r(o-t-Pr). l,.-ts',
isopropoxide
o H o I ll R,,Ay/\CH,
Do
-
2 0A0VosYn)
I
anti-epoxides.In contrast,epoxidationwith t-butyl hydroperoxideand Ti(O-i-Pr)r is resultsonly in the syn-epoxides(2). The presenceof a free allylic hydroxyl group essentialfor this oxidation. 31' 4509 TeffahedronLetters' rM. Bailey,I. E. Mark6,W. D. Ollis,andP. R. Rasmussen, (1990). l-Butyl hydroperoxide-Dialkyl tartrate-Titanium(IV) isopropoxide. all t-Hexoses,.,The groupsof Masamuneand of Sharplesslhavesynthesized possibleeightr-hexosesfrom the four-carbonallylic alcohol,4-benzhydryloxy-(E)(1). The first step is asymmetric 2-butene-1-ol,(C6H5)2CHOCHzCH:CHCH2OH The epoxideis openedregioselecee. in >95% L-( an +)-tartrate with epoxidation give thioetherdiol, which is cona to medium in a basic benzenethiol with tively reactionon 2 followedby yield. Pummerer A in 65% 2 acetonide into the verted hydrolysiswith epimerizabasic whereas 3, erythro-aldehyde provides the reduction tion at Cz results in the threo-aldehyde4.
(-o ll
lltri'in:'S'l'?fi;, Pocl.(loo%) ll (cH,),c(ocH.),,
A secondcycle involves convc (E)-allylicalcoholsby a Wittig ra reduction.Eachalcohol is then sul anda o-(-)-tartrate. Four epori& lectivitiesof > 20: l. Cleavageof t r-hexoses,all in high optical Ftri ' 'reagent-controlled'strategy. I S.Y. Ko, A. W. M. Lee,S. Masrn 46, 245(1990). Tetrahedron,
Butyllithium-Sodium f-butori&. Metalation of 2-substitud I efficientthan BuLi/TMEDA for ti BuNa. Moreover,the resultingu trophiles,evenepoxides,
rr a) s_
CuH'r---)HO
CH,
I B. H. LipshutzandE. Garcia,Icrn
::,.:{_
RO._-/' I
o"ov""*
cHo
il,xll". ,r* i1,"3{.2;r::",f.s"%r", I K,COI
JcHroH
Butyllithium-Tetramethylcllyl Oxiranyllithium reagcnts.t l at the activatedposition(7, 454
H. R .sn
"."f{"
Butyllithium-Tetramethylethylenediamine
) ilo?ropoxidc
o H o A -CHr R- Y
Do
I
100% s-rn)
and Ti(O-i-Pr)r I hrdroperoxide grouPis hydroxYl f a ireeallylic
55
A secondcycle involves conversionof 3 and 4 into the two-carbonhomologated (E)-allylicalcoholsby a Wittig reactionwith (CrHs)f:CHCHO followedby NaBHa reduction.Each alcohol is then subjectedto asymmetricepoxidationwith an r--(*)anda o-(-)-tartrate. Four epoxidesare obtainedin this way, eachwith diastereoselectivitiesof >20: l. Cleavageofthe epoxidesas in the first cycleprovidethe eight r-hexoses,all in high optical purity. The methodologydemonstratesthe value of a "reagent-controlled' strategy. I S.Y. Ko, A. W. M. Lee,S. Masamune, L. A. Reed,III, K. B. Sharpless, andF. J. Walker, Tetrahedron, 46, 245(1990).
Letters,3l,4509 t*r. Tetrahedron
tDtt\-) isopropoxide. all havesynthesized I Sh.rrplessr ic aicohol,4-benzhydryloxy-(E)lr The first step is asYmmetric bc epnxideis openedregioselecdiol, which is conI a throether trrcr reactionon 2 followed bY ba.rchydrolysiswith ePimeriza-
Butyllithium-Sodium l-butoxide. Metalation of 2-substituted1,3-dithianes.r This combination(l:1) is more efficientthanBuLi/TMEDA for this metalationat -78o. The activespeciesmay be BuNa. Moreover,the resultinganion undergoesfacile reactionwith variouselectrophiles,evenepoxides.
-,,\":::.'' a),
..",,*3 l'*'.,",,rkf.t-our, HO
CH,
HO
CH, ( 6 :l )
I B. H. LipshutzandE. Garcia,Tetrahedron Letters,Sl,7261 (1990).
::':{:
cHo
Butyllithium-Tetramethylethylenediamine. Oxiranyllithiumreagents.t Epoxidesstabilizedby a silyl groupcanbe lithiated at the activatedposition(7, 45-46), but lithiationof nonstabilized epoxidesresults
O C H'\1 , lr.. +
cH.
,/\ 3
O
OR
.J,A"u,'i?'JYn??o, [.;;A] ,u*J,.",,,.:o OH
H.R .1,.".,. c.n,z{H
56
t-Butyllithium
j C6H5(CHr)2I+2t-BuL
OH l) BuLi' TMEDA
-O
:t cu,cocs' ,
nu--zA{;-SnBu,
o l au-,.2/i.,-c(cH3), I OH
51ca
|
osiR3
yield by reaction of the alkyl iodidc -?80.r'2
of oxmainly in productsderived from alkoxycarbenes.However, transmetalation -90o the provides with butyllithiumandTMEDA (2 equiv') at iranytiincompounds the TMEDA' of corrcspondin!oxiranyllithium reagentsin high yield. In the absence major productsare c,c'-dialkoxy alkenes'
I W. F. BaileyandE. R. Punzalan'.1. Ory' ibid., 55,5406(199()). C. J. Rousset, r E. Negishi,D. R. Swanson'C. J' Rours Org. Syn.,submitted(1990).
lP.Lohse,H.Loner,P.Acklin,F.Sternfeld,andA.Pfaltz,TetrahedronLetters'32'6|5 t-Butyl methyl sulfone. (1991). sec-Butyllithium. synthesis(10,75) from Anthraquinonesynthesis.rThe originalanthraquinone can be improved ortho-lithiation a tandem involving benzamidesand benzaldehydes this version,the In component. second the as by useofan ortfto-bromobenzaldehyde yields'In in higher results which exchange, secondlithiationinvolveshalogen-metal theexamplecitedhere,theyieldwasonly|5vointheabsenceofthebromine on the aldehyde. substituent
N(CrH5),
Br +
not react with this reagent. Other elk this purpose.
' Y. Gai, M. Julia,andJ.-N' VerPceur.i
t-Butylthionitrate,t-BuSNOr. s.-Oximinoketones.t This ra3 othernitritesfor a-oximationof ket havingtwo owith ketones reactions
JecBuLi TMEDA
oHc
Cy clopropanation of l-alkctct -r situ from this sulfone with methy[id under catalysiswith Ni(acac)2. Termu are cyclopropanated in 70-95% yieK
CH,
oLi
uro" J,-""r, o tl
CH,
aiar,=-,W o
r X . W a n ga n dV . S n i e c k u sS,y n l e u . , 3 1 (31 9 9 0 ) '
r-Butyllithium. primaryalkyllithiums.rThesealkyllithiumsareusuallypreparedby reaction in 85-95% with lithiummetal,but canbe obtained or bromides of alkvlchlorides
o tl
c6H.ccH.cH
Y. H. Kim, Y. J. Park,and K. Kim. Ir
,-Butyl thionitrrt€, t-BuSNO2
OH
o l \,/t,c(cH3), ()t{
ether'penrane > C6H5(CHr)rLi + /-BuI 00-95Vo)
yield by reactionof the alkyl iodides with t-butyllithium (2 equiv.) in ether at -79o.t,2
of oxloo lr er. transmetalation (1 squir.) at -90o providesthe of TMEDA, the l- ln rheabsence
lz.'.:
c6H5(cH2)2I + 2 l-Buli
I W. F. BaileyandE. R. Punzalan, D. R. Swanson, and E. Negishi, J. Or9.,55,5404(1990); C. J. Rousset, ibid.,55,5406(1990). 'E. Negishi, D. R. Swanson, W. F. Bailey,E. R. Punzalan, andJ.L Patricia, C. J. Rousset, (1990). Org. Syn.,submitted
letrahedron Letters, 32, 615
(10,75) from :1,rnesynthesis )qi.j canbe improved o.:r ,-lrthiation t i ,:rponent.In thisversion,the r h : : h r e s u l t isn h i g h e yr i e l d sI.n of the bromine rn :rc absence
l-Butyl methyl sulfone. Cyclopropanationof l-alkenes.t t-Butylsulfonylmethyllithium, generatedin sjru from this sulfonewith methyllithium,servesas a methylenetransferreagent undercatalysiswith Ni(acac)2.Terminalalkenesandcyclic I ,2-disubstituted alkenes are cyclopropanated in 70-957oyield, but open-chain1,2-disubstituted alkenesdo not reactwith this reagent.Other alkyl methyl sulfonesare muchlesseffectivefor this purpose. I Y. Gai,M. Julia,andJ.-N.Verpeaux, Synlett,56(1991). t-Butyl thionitrate, l-BuSNO2. a-Oximino ketones.r This reagentis generallysuperiorto sodiumnitrite or other nitrites for a-oximationof ketones.It is also prone to afford dioximinesin reactionswith ketoneshavingtwo o-methylenegroups.
a )r
osz.r-r"r-r J
o ll
""it*o'
C6H.CCH2CH.'--i;----t
o ll-CCHr
C6H5C
NOH I Y. H. Kim, Y. J. Park,andK. Kim, Tetrahedron Letters,30,2833(1989).
a:.'
57
.ually prepared by reaction ran be obtainedin 85-95%
cl l) NHpH (9{, 2) H'(95*) ......+
Camphorsulfonicacid (CSA). Cyclization of hydroxy epoxides to tetrahydrofurans or tetrahydropyran\.r CSA is the most efficientand convenientcatalystfor this intramolecular epoxideopening.The cyclizationof /rans-epoxides is particularlyusefulbecauseit can leadto either5- or 6-memberedcyclic ethersas shownin equation(I) and (II).
sorcl
6. The practical advantageof this chrn obtainedin optically pure form by 0rl
(cHr)rcoocH3
H,CYG
t"'"",:"f, A-"",:1""T)
r\*
a-\s, l) Bu.B0fi 2) RCHO
(rrr)o(-\ \"'
------r HO
2
86%
o o H i l t
HC:CHCOOCH.
HC:CHCOOCH
Formationof S-memberedcyclic ethersis favored in cyclizationof cis-hydroxy epoxides(equationIII). The cyclizationcan be extendedto bicyclic or evenpolycyclic ethers. l K . C . N i c o l a oC u ,. V . C . P r a s a d P,. K . S o m e r a s ,n dC . - K .H w a n gA, m . S o c . , l l l , 5 3 3 0 (1989). l0-Camphorsultam(Oppolzer's auxiliary),l, 13, 62; 14,71-72. This reagentis now commerciallyavailable(Aldrich), but can be preparedwith muchlessexpenseby reductionof (-)-(I0-camphorsulfonyl)imine(2).' syn'Aldols.2 N-Acylsultamssuchas the N-propionylsultam2 on reactionof the lithium or boron enolatewith aldehydesfurnish syn-aldolsas the major product. The absoluteconfiguration dependson the enolatecounterion.Reactionof boronenolates resultsin (2R,3S)-aldols (3), whereasreactionoflithium or tin(IV) enolatesresults in (2S,3R)-aldols (4). Hydroperoxide-assisted hydrolysisof3 or 4 followedby esterificationresultsin recoveryofthe auxiliarysultamandmethoxycarbonyl aldols5 and 58
q
":'f*
CH, 3
",., '.-**1li!i,',1, o o H t -.A.l ./.\
cH3o
T
R
CH'
This sultamcan also be usedto obtrir (9). Thusreactionof 2 with r-butyldinrc providesthe (Z)-O-silyl-N,O-ketenc rr
l0-Camphorsultam
CH,
CH, l) NH.OH (90%) 2)H. (95%)
LiAlH4
--.-------------)
THF -------------)
92.3%
so2cl {urans or tetrahydrop!l).r ior this intramolecular it rnr;ularly usefulbecause (I) and(II). lcn ;n equation
2
l, m.p.183-184., [o]"-30.7.
6. The practicaladvantage of this chiral auxiliary is that the aldols3 and 4 can be obtainedin opticallypure form by flashchromatography and crystallization.
H-_l , \ _ / . 'o') ,('t{ r.COOCH, I
| "
l) BupOTf 2) RCHO
o2 ,
| ffi-\2qo J
o'
o o H i l t
:('ll('OOCHT
"i-J,^* I .\..rzalion of cis-hydroxy I r.. .rcrclic or even polycy-
H r rng. z{m.
S o c . .1 l l . 5 3 3 0
t-72. tl with br. rur canbe prepared l i , . n ri r i m i n e( 2 ) . ' t) l\ultam2 on reactionofthe rlr a. themajorproduct.The ofboronenolates t. Reaction results m or rrn(lV)enolates s of J or 4 followedby esterErho\) carbonylaldols5 and
o o H i l :
x,/-i
n
CH,
CH,
3
4
,.-*.Jli!tll;aq o o H i l t
cH,ofn
CH, S
,o_**Jllho,fi,",o, o o H i l : ,,\ -,\ cHso Y R CH, 6
This sultamcan alsobe usedto obtainenantiomerically pure (2R,2S)-anrd-aldols r9). Thusreacrionof 2 with r-butyldimethylsilyl triflate(TBDMSOTf) andN(C2H5)3 providesthe (Z)-o-silyl-N,o-keteneacetal7, which reactswith aldehvdesin the
l0-Camphorsultam
CH,
Asymmetric atom-transferand butynyl iodide with the acryloyl s followed by deiodinationprovidcs !
osiR" o i l :
*.tf*
TBDMSOTf N(C.H.),
2-----+ -tm%
CH, E
,z | \I
,,
I M. C. Weismiller,J. C. Towsoo,rr 2 W. Oppolzer,J. Blagg,I. Rodrige r D. P. Curran,W. Shen,J. Zhrag, I
9 (>99Vo ee)
presenceof a Lewis acid catalyst(TBDMSOTf, ZnClz, or TiCln) to give almost exclusivelycnti-aldols(E) with the (2R,3S)-configuration. Asymmetricradical reactions. Curran et al.3 report severalasymmetricreactions of radicalsderived from Oppolzer's camphorsultam.Thus the reactionof the iodosultamI with allyltributyltin initiated by triethylboraneprovides an epimeric
HrcJ
|
"
L
2 (14-25:l)
l (cH3cHrcoxl)
only one mixtureof productsin the ratio 14-25: I at 0-25'. At lower temperatures, diastereomeris formed. but the reaction is too slow to be useful. A combinationof allylation and additionto an acryloylsultam(3) furnishesan (equationI). adduct4 as an I l: I mixture of diasteromers AIBN .
|
Complete details for synthesis t sulfonic acid in 77 Vo yield te u active than other N-sulfonyloxezir ylation of lithium enolates of esre
o
o2
\-/
(10-Camphorylsulfonyl)oxezirl-
cH,\.4.,.-
+ CH2:CHCH,SnBu, #-
(D |
+ CHr:61-;6 J
o o H i l : .,,\ -,\ R cH3o T CH,
'"1.,<
-H
* cHr:gHcoXL + CH2:cHcHrSnBur-#f 3
4 (ll: l)
Enantio selective u-hy&o ry b lectivity (60-95% ee) obtainsio d compounds(ketones,esters,amid however.i or ( -)-1. This reagent, ing in tertiaryc-hydroxyl ketos. of ( +)-l is markedlysuperior.rs
(10-Camphorylsulfonyl)oxaziridines
? 'f*
t
I
6l
Asymmetricatom-transferannelationscan also be effected.Thus irradiationof at 80o butynyl iodide with the acryloyl sultam 3 in the presenceof Bu3SnSnBu3 provides product. followed by deiodination 5 as the major
osiR3
CH,
H
E
9H'
+ cH2:cHco{i!$i"":
J
a\coxl H \-_J
o o H i l :
.,\-
cH , o T
-r\
R
I M. C. Weismiller,J. C. Towson,and F. A. Davis, Org. Syn., submitted(1989). 2 W. Oppolzer,J. Blagg,I. Rodriguez,and W. Walther,Am. Soc.,112,2767 (1990). 3 D. P. Curran,W. Shen,J. Zhang,and T. A. Heffner,ibid., ll2,6738 (1990).
CH,
9 (>99Vo ee)
l:. or TiCL) to give almost pn Dn .ereral asymmetricreacrm Thusthe reactionof the toraneprovidesan ePimeric
(10-Camphorylsulfonyl)oxaziridines (1), 13, 64-65; 14,72. of ( + )- or ( - )-l from(lS)- or (1R)-10-camphorComplete detailsfor synthesis is less In general,this oxaziridine sulfonicacidin 77Voyieldare now available. reagent for hydroxactivethanotherN-sulfonyloxaziridines, butit is thepreferred ylationof lithiumenolates in 50-95%ee.' of esters,amides, andketones CH,
o
r, ..
ll
-v-
\z/
H'. C-s/. )
I
"
,),^f
L
2 ( 1 4 - 2 5l:) onlYone louer temperatures, useful. tte r Dl0\lsultam(3) furnishesan t lr
Enantioselectivea-hydrorylation of carbonyl compounils.2 Useful enantioselectivity (60-957oee) obtainsin the oxidation of enolatesof a numberof carbonyl (ketones,esters,amides)with the simplestmemberof this series,(+)compounds oxidationsresultor ( - )-1. This reagent,however,is not usefulfor enantioselective rngin tertiarya-hydroxylketones.For this purpose,the 8,8-dichloroderivative(2) of (+)-l is markedlysuperior,as shownin equation(I). This derivativecanalsobe
\IB\ il. r, --;-'
r(0'
CH.
CH,
4 (ll:1)
CH, -78' NaNtS(CH.),1,, +
(+)-r (+\-z
OH (16-30Voee) (>95Voee)
62
Carbomethoxymethanesulfonylchloride
more effectivethan (*)-l for enantioselective hydroxylationof acyclic ketones. Apparentlyelectronicas well as steric factorsplay a role in the enantioselectivityof hydroxylationwith theseoxaziridines. The antibiotic(*)-kjellmanianone(2) hasbeenpreparedby asymmetrichydroxylationof the sodiumenolateof the p-ketoesterI with several(camphoryl)oxaziridines. The highestenantioselectivity (68.5% ee) was obtainedby use of the p(trifluoromethyl)benzyl derivative3.3
o
o
ll
cHio
\
o
o
r)NaNlsi(cH,),r,
tl
-I
i.l
.",o
&,"-
|]
l +
Unlike plactams, unsubd at Caor dialkylation at N2 u the electrophile.
"o4 nv L__\ ll
ocH3
l) Ed.r
ocH3 2 (68.5Voee)
|
fu-
o-- T_| )S-NH ot/
rrc's v
(c2H5)rsi_
o- T-l )-s-x\
ot/ p-CFrCoHoCH, I O U"
I M. J. Szymonifta andJ. V. ll : J. V. HeckandB. G. Chrisrc
3 rJ. C. Towson,M. C. Weismiller,G. S. Lal, A. C. Sheppard, andF. A. Davis,Org. ,lyz., submitted(1989). 2 F. A. DavisandM. C. Weismiller,J. Org.,55, 3715(1990). 3 B.-C. Chen,M. C. Weismiller,F. A. Davis,D. Boschelli, J. R. Empfield,andA. B. Smith, lll, Tetrahedron,47, 173 (1991).
Carbomethoxymethanesulfonyl chloride, CH3O2CCH2SO2CI(l), b. p. 78-80"/
Carbon suboxide,O:C:( 4-Hydroxy-2H-Wrrru. lyl enol etherswith carbo s
cHrcH{HOSi(CHr)r -
0.5mm. Preparation frommethylthioglycolate:
osi cl,, cH,cl,, ol
HScH"CoocH,
30'
67%
, I
p-Sultams,t Reactionof I with iminesand a base(usuallypyridine) in THF resultsin 4-carbomethoxy-1 ,2-thiazetidinel,l-dioxides (2) in 20-93% yield. All p-sultamscan be obtained productshavethe tans-orientation.The N-unsubstituted by use of phenylselenenylethyl as the R group. This R group can be replacedby hydrogenin70-90Voyield by selenoxideeliminationto an enamide,which is then treatedwith L and Na"SO".2
,A \-J
I L. Bonsignore, S. Cabiddu. G
l, l'-Carbonylbis(3-methyt preparedby reactionof l,l'.
I,l'-Carbonylbis(3-methylimidazolium)triflate
drorr lationof acyclicketones. of I role rn the enantioselectivity preparedby asymmetrichydroxr r:h \e\ eral (camphoryl)oxaziriua. obtainedby use of the p-
o }Ir,
A\
T
ll
O.
n ' 4s-s3Ea
ll
Nt
-R
ot/
R
"#'\ :>l_I"
r) BuLi,-78"
ocHj I
| " > s1 4- N
rHF.
)
unlike p-lactams,unsubstitutedp-sultamscan undergoselectivemonoalkylation at c4 or dialkylation at N2 and Ca when the dianion is treatedwith a large excessof the electrophile.
o
ltr)
cH'ooc'.-.tA'
"Ar '\
r+
63
/rlt.57c ee)
(C2H5)3Si
:>l_I"
(c,H.)"si :\
t
:jr
t)Buli
-silcrHr),
(c,H,),sifH,
2)cH'r > tn%
\-
o>J-'l oz"-
-si(crHs)l
' M. J. Szymonifka andJ. V. Heck,Tetahedron (lggg\. Letters,30,2g69,2g7i : J. V. HeckandB. G. Chrisrensen, (l9gl). ibid.,22,5027 P('::J .rndF. A. Davis, Org. Syn., 'l* l l : . R E m p f i e l d ,a n d A . B . S m i t h ,
Carbonsuboxide,O:C:C:C:O (l). 4-Hydroxy-2H-pyranones-2. Theseheterocyclesare formed on reactionof silyl enol etherswith carbonsuboxidein etherat -20 - 25o.l
C C H - S O : C( lI) , b . p . 7 8 - 8 0 " /
+ l
LJ
ba..' usuallypyridine)in THF t r J : . , 2 ) i n 2 0 - 9 3 %y i e l d . A l l tu:.J D-sultams canbe obtained r! R lroup can be replacedby n : , rn enamide,which is then
d'
.K'r"'r___.__ 88q.
L. Bonsignore, S. Cabiddu, G. Loy, andD. Secci,Heterocycles,2g, 913(19g9). I'l'-carbonylbis(3-methytimidazolium)triflate (1, m.p. 7g-g0"). The reagentis preparedby reactionof I,l'-carbonyldiimidazolewith methyl triflatein cH3No2 at
Carbonyldiimidazole
Catecholborane. syn-1,3-Diols.t P-HYdroxYlct (CB) to l,3-diols with moderatcro equiv. ofthe boranesuggeststhu fon
o
ll pANANA*
cu,orr'cs,t'to,,
\J I
o H o in solid,but is usuallygenerated 10o.It canbe isolatedasa white,moisture-sensitive solutionjust beforeuse. Amino acylations.t This salt is far more reactive,particularly for O-acylation, Thus it effectsesterificationof N-Cbz protected than N,N'-carbonyldiimidazole. amino acidswith even hinderedalcoholssuch as /-mentholin 98Voyield without It alsocaneffectcoupling free from racemization. needofa baseand,consequently, of aminoacidsin high yields and without racemization.
Carbonyldiimidazole(1). Glycosithtion r The anomericC1-hydroxylgroup of glycosesreactswith carglycosides,which form glycosides bonyldiimidazoleto form 1-imidazolylcarbonyl RoH,znBrz
l
(cHr)rcHy'\/c"H,,-e + Rlrlt
o H o
(cH3)'cH+o
l;rffi-l
the keto grouP. In somecasesthc di clRhlP(c6H5)313. 2 lr4-Reduction This borane c enonesthat can adoptan S-cis-coof
CH,+[C
I
l
l
cH.
'A. K. Saha, Am.Soc.,lll' 4856(1989). P. Schultz, andH. Rapoport,
o-''"zo
r
l
8"rc^fYoR f
o"cr
"\1/ B,ro
'oBzl
OBzl ( o i F= 4 - 1 0 :l )
OBzl = (al9 3:97) on reactionwith an alcoholand zinc bromide.The intermediatealsocan reactwith acetyl chloride to give an anomericchloride, with almost completeinversionof configuration. 'M. J. FordandS. V. Ley,Synlett,255 (1990).
"'ta
a \
a single (Z) enolate(a) is fonncd t aldolization(equationI). amides.imidc c,P-Unsaturated if catalyzedby chlorotris(triphco can be effectedeven at -20" end
Catecholborane
-rCHt
\'\ir \J
20Tr
Catecholborane. syn-lr3-Diols.l p-Hydroxy ketones are reduced by excess catecholborane (CB)tol,3-diolswithmoderatetohighsyn-selectivity.Theneedforatleast2 reductionof equiv. of the boranesuggeststhat formation of a boronic esterpreceeds
I
in Dlrd.but is usuallYgenerated r. particularlYfor O-acYlation, nlication of N-Cbz Protected Denthol in 98% yield without tron lt alsocaneffectcouPling on . : i 5 6 r1 9 8 9 ) .
up of glycosesreactswith car;osrdes.which form glYcosides
OH I
t*
(cH.)rcHy'\+cuH,r-n
t
H l
O
cH'd (cH,),cHl)aA-=" CH,
OH l
(cHt)rCHy'\^cuH,r-n sYnlanti= 3: I synlanti= lO:l
e3%
+ Rh(I)
O r
OH t
2cB.-ro" -- rHF ---'
O ll
O
H
O
H
(cH,)rcHy')a^vcH' CH, synlanti = 35"I
theketogroup.Insomecasesthediastereoselectivityisenhancedbycatalysiswith clRhlP(c6Hs)313. of c,plA-neauition 2 This boranecan effect efficientconjugatereduction p-ionone of case the In at 25' in THF. enonesthat can adoptan s-cis-conformation
o H o
o,-../,,o Il "o"..",, ( a t.,
D B ,/ r ) l
I
CH,
so-ss* |
( t It BzlO
alsocan reactwith inrermediate b almostcompleteinversionof
CH, (synlanti= l0: 1)
r),r-selective a single(Z) enolate(a) is formedas an intermediate,which undergoes aldolization(equationI). c,p-unsaturatedamides,imides,andesterscan alsobe reducedby CB, but only (15, 90-91). This catalyzedreduction if catalyzedby chlorotris(triphenyl)rhodium -20o yields 55-82%. of and in canbe effectedevenat
66
Cerium ammonium nitrate
lr4-Hydroboration oJ 1,3-ilienes.3 This reaction, catalyzed by pd(0) or Rh4(co)12,provides(Z)-allylic boronatesin about85% yield. Hydroborationof a 1,3-enyne givesan allenicboronate(-55% yield). catalysis with LiBHa.a Hydroborationof alkeneswith catecholboraneis generally slow, but can be affectedat room temperaturein about an hour when catalyzed by a small amountof LiBHa. The catecholboranecan be generatedin situby reactionof BH3with catechol;after evolutionof H2 stops,the alkene(l equiv.)and LiBH4(0.1 equiv.)are added.Hydroborationis usuallycompleteafter stirring for 1 hour at 25'. Yields (after oxidation) are generallyalmost quantitative.
Cerium ammonium nitrate (CAN). lr$Diones.r cAN effectscross-coupling between1,2-disubstituted silyl enol ethersand a l-substitutedsilyl enol etherto give a 1,4-dione.The reactioninvolves oxidationof I to a p-oxo radical,RlcHCoR2,which addsto the l-substitutedsilvl enol ether (2) to form an adductthat is oxidized to the dione.
\-,
(CH3O)TCHCOOCH, + 2(CHr)rSiCHl
(CH3O)rCH(CH,)TCOOCH,+ 2(CI{3)rSiCll
o\a)
z)z
?ttt""
a\
Cerium(Il) chloride. Atklition of RMgBr to carbonyh.t r NdCl3)promotesaddition of Grignard rcr zation. aldol condensation,and reductic lessof whetherthe CeCl3(l equiv.) is 6r mixture with the ketone. THF or THF/c CH2CI2,or DME. Adducs cr C5,II5CH3, yields as high as 95% eventhough thc yi salt. CeCl3can also retard 1,4-additiooto of l,2-adducts. CeCl3 is also useful for agentswith esters,amides,and nitrilcs. Allylsilanestrom esters(f4, ?G7| highly dependenton strictly anhydrousc
*
.g,:ifl;9 ?t',.",), --^.r-"-.cocHl 8*-
Hrcy'-cH,
(,
I
Cyclizltion of unsaturated enol silyl ethers.2 Oxidation of certain 6,e- and t,p-unsaturated enol silyl etherswith eitherCAN or Cu(OTf)2can resultin radical cyclization.
\ / o-r
+ 2(cH,),sicH,M
drous CeCl3shouldbe preparedby rigot for 7 hours. They have extendedthe od Theseproductsare usefulfor [3+2] rings.3 six- and seven-membered
a,-5..OSi(CH3)3 fl + (CH,O),CHCH I I CAN ---------+ 75%
H (cisltrans= 20: l) t E. Baciocchi,A. Casu.and R. Ruzziconi, Tetahedron ktters, 30, 3707(1989). 2 B. B. Sniderand T. Kwon. "/. O r g . , 5 5 , 4 7 8 6( 1 9 9 0 ) .
rT. Imamoto.N. Takiyama,K. Neteun 43920989).
Cerium0lD chloride
ion. catalyzedby Pd(0) or l{ r reld. Hydroborationof a is gens 'r rth catecholborane rn eboutan hour when catain situ by rc can be generated (l lhe alkene equiv.) and Dp,i. p completeafter stirringfor 1 Do\r quantitative. !r fu ,:."n Lztters,30, 3789(1989). (1991). . omm.,205 S C a e mC
Cerium(IID chloride. Arldition of RMgBr to carbonyls.t cerium(Ill) chloride (also Lacl3, Prcl3, NdCl3)promotesaddition of Grignard reagentsto ketonesby suppressionof enolization, aldol condensation,and reduction. Enhancedreactivity is observed'regardlessof whetherthe CeCl3(l equiv.) is first addedto the Grignard reagentor to the mixture with the ketone. THF or THF/ether is the solvent of choice rather than coIIsCHr, CH2C!2,or DME. Adducts can be preparedby this simple expedientin yields as high as 95% eventhough the yield is zero in the absenceof a lanthanoid salt.CeClrcanalsoretard1,4-additionto c,p-enonesandtherebyimprovethe yield of l,2-adducts.CeCl3is also useful for enhancingthe reactivityof Grignard reagentswith esters,amides,and nitriles. Altylsilaneslrom esters(14,76-77). Lee et al.2 find that this conversionis on strictly anhydrousconditions.In particular,completelyanhyhighly dependent l) Ceclr
(CH,O)TCHCCH2Si(CHr)J
(CH,O)TCHCOOCHT+ 2(CHr)rSiCHrMgCl # silyl enol :n i.l-disubstituted -dr,rne.The reactioninvolves rdds ro the l-substitutedsilyl ? dr , . n e .
CH'
(cH3o)rcH(cH2)rcoocHr+ o\-
()
,-\.
'oJ
fi',
----'-+ (cHro)rcH(cH2)3ccH2si(cH3)3
2(cll3)3sicHrMgcl
+ 2(cH3)rSiCH zWgCl -----+ HO(CH,)3CCH2Si(CH3).
8",
cocg,
-l
)rrd.itron of certain 6,e- and lu,OTf t: can result in radical
salt at 150' drousCeCl3shouldbe preparedby rigorousdrying ofthe heptahydrate esters.3 for 7 hours.They haveextendedthe original methodto functionalized Theseproductsare usefulfor [3+2]annelationswith O-silyl enolatesto provide rings.3 six- and seven-membered
osi(cH3)3
fi"'
+ (cH,o)rcHCHrcCHrSi(CHr ), -ilS!:--
o I
\--.\
II
(-ftcH, a'''V-.-(,^, ---(-V
UK/
v.\/
: c.H. u = l|
OH
H
l)
nz., 10. 3707(1989).
}
ocH3
H
I
ocH3
rT. Imamoto,N. Takiyama,K. Nakamura,T Hatajima,and Y. Kamiya,Am. Soc.,lll' 4392(1989).
6E
Ceriurn(Ill)chloride-Tin(Il)chloride
2 T. V. Lee, J. A. Channon,C. Cregg,J. R. Porter,F. S. Roden,and H. Y'-L. Yeoh, Tetahedron,45, 5877 (1989). 3 T. V. Lee, R. J. Boucher,J. R. Porter,andC. J. M. Rockell,ibid.,45,5887 (1989).
Cerium(IID chloride-Chlorotrimethylsilane. In the presence of these two Addition of NaX or BuaItlX to l-alkyn-3-ones.t reagents, sodium or ammonium salts undergo conjugate addition to acetylenic carbonyl compounds. This reaction provides rrans-p-halovinyl ketones or N,N-diethyl
N
O +
dienesor enaminesat 25' . Thescra
cis-p-haloacrylamides.
which is then convertedto an oryellyl Nal, CeCl' ClSi(CHrL
?
,- --ff_----,,
HC
o
l
l
HC-ciN(crHr),
o
i .----+
l
rA, l
t
l'\rAr.r(CrH.),
-
+ \.
l
c,H,,-n o
l N(c2Hs)2
(67Vo)
(6Vo\
I T. Fujisawa,A. Tanaka,andY. Ukaji, Chem.Letters,1255(1989).
I S.Fukuzawa, T. Fujiu M. Fukushima, (1989).
Cerium(IV) trifluoromethancsuffc Oxidation.t This reagent is Pt equiv.)to form Ce(COr)2,which is O (4 equiv.).This oxidantis effectiveft (72-92%yield), and of alkylarenesto ' T. Imamoto, Y. Koide,andS. HiYrm.
chloride. chloride-Tin(Il) qcbadditions of u,a'-dibromo ketones.t This combinaand 13+21 l3t4l tion is a catalyst for cycloaddition of u,c'-dibromo ketones to furans and to 1,3-
Cerium(IID
o
,,,ot
\J*
ll 6H,*CH, l
l
Br
, \;-Tq'
c.ct,.sncr. rui.zs.', Br
e
o
o >--\"
%
I
62:.28: l0
Cesium fluoride. Rearrangement of arYl PrWl naphthylpropargyletherI at 215' rc product(40% yield'1.Addition of I cq major product, presumablyformcd vit irl KF, RbF, or BaF2are comPletelY providesa route to o-hydroxy ddchyt
"\
'x'*
H.C CH,
CH,
CH. CH,
I
I --------) 489o
CH,
:'r' fc'r.
Cesium ffuoride
o
andH. Y.-L. Yeoh, F S Roden, R.rrt.l. ibid., 45,5887(1989).
of thesetwo J.r In the presence iueateadditionto acetyleniccarbalorrnvl ketonesor N,N-diethyl
dienesor enaminesat 25" . Thesereactionsmav involve a cerium c-bromo enolate. OCeCl, which is thenconvertedto an oxyallyl cation, CH,CU:-E'-=CHCH3.
o I
. -^\-
U
crH,,-,
t H.
I S. Fukuzawa, M. Fukushima, T. Fujinami,andS.Sakai,Bull.Chen.Soc.Japan,62,2348 (1989).
o
- \.
N1crH.;, (67Vo)
. ll55 r1989).
Cerium(IV) trifluoromethanesulfonate, Ce(OSO2CF)a. Oxidation.t This reagentis preparedby reaction of CAN with K2CO3(2 equiv.)to form Ce(COr)2,which is then treatedwith trifluoromethanesulfonic acid (4 equiv.). This oxidant is effectivefor oxidation of benzylic alcoholsto aldehydes (72-927oyield), and of alkylarenesto aldehydesor ketones(65-70% yield). I T. Imamoto, Y. Koide,andS. Hiyama,Chem.Letters,1445 (1990).
lbromo ketones.t This combinan(, ierones to furans and to 1,3-
6 l : 2 8 :l 0
Cesiurnfluoride. Rearrangement of aryl propargyl ethers.r Claisen rearrangementof the naphthylpropargylether I at2l5o resultsin the benzopyran2 as the only isolable product(40% yield). Addition of I equiv. ofCsF resultsin the benzofuran3 as the majorproduct,presumablyformedvia an c-allenyl ketone(a). Relatedsaltssuchas KF, RbF, or BaF2are completelyineffective.This modifiedClaisenrearrangement providesa routeto o-hydroxyaldehydessuchas 4 from a phenol.
"\ (\
\,, ()
,.-^y4".
afro,,,", q% v\2 \-,\r' I
H
) 1cH,
'''' J"o'
p-Chlorobis(cyclopentadienyl)(dimethylaluminum)'F'methylenetitlnium
t
nr*
o.o'"1
Wl-@"+2 3 (577o)
I l) oso. | 2) HIO. 3) olf |
Two-carbon ring expansion. Paqucrr a cyclohexenonering by insertionof a -CH andthe doublebond. The initial stepinvoh n-chloroperbenzoicacid, which effecs cp to give an epoxy lactone(3), which reem lactone4. Both carbonyl groupsof4 undc Tebbereagent.The resultingallyl vinyl cil to a cyclooctenol,which is oxidized to 5' This ring enlargementwas applied src Claisenrearrangementwas markedly ral
' C. M. G. Philippo,N. H. Vo, andL. A- Prq
B-Chloro-9-borabicyclo[3.3.I]nour (l rne (2, ChxzBCl).PreParation.r (E)- or (Z)-EnoI borinates. Thesc a tion ofanti or syn-aldols,respectively.I tively by variation of the alkyl grouP rnr preparedin essentiallyquantitativeyicld I
^4'.r* \-\-2 4 ' H. Ishii, T. Ishikawa, Chem'Pharm. S. Takeda,S. Ueki,M. Suzuki,andT. Harayama' B u l l . , 3 8 , 1 7 7(51 9 9 0 ) . p-methylenetitanium F-chlorobis(cyclopentadienyl)(dimethylaluminum)(Tebbereagent,l). H
c,c6H.co,H>al-\o
\-/\Ao
\-\_J
O
l
?
./\
*Czt'-
tl
(I) RccHrcH3
H
al.)
l, i-.,rNcrl.'
H ,
,:'#,
l
0
@*l
Or'
(E).-
of t-amines,N(C:HI)r 0o in the presence formatioo of cr usefulfor stereoselective and2, which result in the (Z)- and (E)-i
cHo 4
CH:CHz 5
andS. U. Krl H. C. Brown.N. Ravindran, : H. C. Brown.R. K. Dhar,andR. K. Brtrli. l l r , 3 4 4 1( 1 9 8 9 ) .
Chloro(chloromethyl)dinethylsibnc, ( Corticosteroi.ds. Upjohn chemistsl (2), readilyaveil from l7p-cyanohydrins cyanohydrin2 with I provides the sily
-,-
u-meihtlcnctitrnium
Chloro(chloromethyl)dlmethylsil&ne
CH,
+ 2
3 (5't%) I l)OsO. | 2) HlO.
I
l) olr
CHO I
Z\-./\,-oH t l \-.t\Z
l
l
.l Suz..rrr.and T. Harayama,Chem.Pharm.
7l
Two'carbonring expansion. paquettelhasreporteda methodfor expansion of a cyclohexenonering by insertionof a -cH2cH2- group betweenthe carbonylgroup andthe doublebond. The initial stepinvolvesoxidationofthe enone with 3 equiv. of m-chloroperbenzoicacid, which effectsepoxidationand a Baeyer-villiger reaction to give an epoxy lactone(3), which rearrangesin an acid medium to the aldehydo 4. Both carbonylgroupsof4 undergomethylenationon reaction with excess lrctone Tebbereagent.The resultingallyl vinyl ether (5) undergoes a claisen rearrangement to a cyclooctenol,which is oxidizedto 6. This ring enlargementwas applied successfullyto testosterone. In this casethe Claisenrearrangementwas markedly retardedby the angular methyl group. ' C. M. c. Philippo, N. H. Vo, andL. A. paqueue, Am. Soc.,ll3, 2762(lggl.). B-chloro-9-borabicycro[3.3.r]nonane (r, B-cl-g-BBN); Dicycrohexyrchrorobor_ ane (2, Chx2BCl).preparation.l (E)- or (z)-Enol borinates. Theseenols are useful for stereoselective prepara_ tion of anti- or syn-aldols,respectively,and haveusuallybeenobtainedstereoselectively by variationof the arkyl groupattached to boron triflates.They can arsobe preparedin essentialyquantitativeyield by reactionwith dialkytboronchloridesat .-B-'-BBN
l, i-h,Nc,H,
H
rin u m )-p-methylenetitanium
t
'
o&t"r
sYn-Aldols
-
(z), - 96-9980
H z^
J,.t--\
\-
^ / ,t\.-O
\
u
'
tso8 ---:---+ %
OBChx,
8
frcm I
o."
R'-\ CH, (E),- 80-9950
-1
I I ) i-BurAl,25"
2) tol --.-------.-----
I
I
fr,I ]H:CH. :
cn.
86Eo
0o in thepresence of t-amines,N(C2H5)3 or i_przNCzHs. Of thesereagents,themost usefulfor stereoselective formationoir""r u"ri""es from alkyl ethyl ketonesare l and2, which resultin the (Z)_ ana (n)-isomers, respectively(equationI). 'H. vindran,anU dS . u l k a r nJi ,. O r g . , 4 4 , 2 4 1 7 .K 'l;f C . B r o w nN, . R aon"'andR' (lg.ig\.
,|il1?;*,1
\
r=o
---------+anri-Aldols
K'B'k'hi,;.'iill-oi,,..i,i,il;l;;;;.., soc., ,Am.
Chloro(chloromethyl)dimethytsilane, CICH2Si(CH3)rCl (l). corticosteroids. upjohn chemists' tuu" J"ulrra a new synthesisof corticoids . from l7p-cyanohydrins (2), readilyavailablerrom l7-keto steroids.Silylationofthe cyanohydrin2 with l providestire silyl ether J, which on treatment with LDA
Chlorodi(cyclopentadienyl)hydridozirconium
-T' khtcHr)z T.DMAP,N(.,H.), l
Lewis acid. ConsequentlYI ceo be evensensitivealkynesin Yicldso with isolatedreagent.A futtbcr rd more active when freshlYPrcFrl( Vinyl cupratcs.s'a An anrrti tion of vinylzirconates,availrHc ! reagentin THF at 25". Traosc
cHrcl
cN
roe
l
cHrcl
cHroAc
C:O
C:O c'',,*)cl'rHF)
#-$l\o"e-${oH o
v
e
r
a
l
l
RC-CH
l
l
l
l
[:
.4 4
5
Holc fzn, QH,
c:o
cJ,-l*.oH
Y ) 6 cyclizesto a, which is hydrolyzedin an acidic mediumto a 2l-chloro corticoid4. This productcanbe convertedto a corticoidacetate(5) or reducedto a l7c-hydroxypregnane(6). One advantageof this route is that it is compatiblewith a Aa-3-keto group in the starting material.
followedby CuCN.LiCl or with to c undergo1,4-addition cuprates particularly useful for Prepsnrir of fr Conjugate &ition of I by reaction prepared readily in thc to c,P-enones addition Pre
I D. A. Livingston, J. E. Petre,andC' L. Bergh,Am.Soc.,ll2' @49(1990). Chlorodi(cyclopentadienyl)hydridozirconium(Schwartz reagent), Cp2Zr(H)Cl (l). Preparation (14, 8l).t Full details are availablefor the preparationby reducdichloridewith LiAlHa followedby a methylenechloridewashto tion of zirconocene convertthe unwantedCp2ZrH2to 1. Overallyield is 77-92Vo. Generationin situ. Lipshutz2recommendslithium triethylborohydridefor reductionof CpzZrClzto l, becausethe co-productis (CzHshB,a relativelyweak cprzrCl,
LiAlH"rHF
> CprZrH, + CpTr( H)Cl
I | "",",,
cprzr
+ HC-C(CI
ct
Chlorodi(cyclopentsdlenyl)hydridozirconium
I
CH.CI
CHTOAc
C:0
c--o
1-^*o" s\)50"
Lewis acid. consequentlyI can be preparedand usedin situ for hydrozirconationof even sensitivealkynesin yields comparableto or even higher than those obtained with isolatedreagent.A further advantageof in situpreparationis that the reagentis more active when freshly prepared. vinyl cuprate,s.3'aAn attractive route to vinyl cupratesinvolves transmetallation of vinylzirconates,availableby hydrozirconationof I -alkyneswith the schwartz reagentin THF at 25o. Transmetallation can be effectedwith cH3Li (3 equiv.)
Rc-cH
cp,,,(H)cr. rHF >
c{ -co
[-rr-cl
L
) 4
""i1,?6'ni,., , [-.urcNlr-i,
L cHi
t,\ l\r
Zi. HOAG
o
CH.
C:O -'x'oH ) .---)
,\ \
cH
Ddru::rro a 2l-chloro corticoid4. ! | 5 ,,r reducedto a I7c-hydroxyit :. .ompatiblewith a Aa-3-keto 9.
/
xZ-.-
followedby cucN'Licl or with cH3Li (2 equiv.) and cHrcu(cN)Li. Thesevinyl cuprates undergo1,4-addition to cyclic andacyclicenonesin highyield. This routeis particularlyusefulfor preparationof prostaglandins. conjugate addition o! vinylzirconiums,s (E)-vinylzirconium reagents are -conjugate readily preparedby reactionof l with l-alkynes. The product undergoes additionto c,p-enonesin the presenceof a nickel catalvst.
tr2. &49 (1990).
Schuanz reagent), Cp2Zr(H)Cl Dle ior the preparationby reducd br a methylene chloridewashto -: rs -92%. rhrumtriethylborohydride for rer r. ,C:Hs)rB,a relativelyweak
H
cprzr
CI | fl + HC-c(cH2)5cH, -----+ , Cprzr\y'\(CH2)5cH3
CI l
o
u,n. *u**,, l$, r---/ I
- ('p,Z( H)Cr \
l
I
1
l o
5
6
73
i
(cH2)5cH3
Chlorodi(cyclopentsdienyl)titsnium(III)
74
I S. L. Buchwald,S. J. LaMaire, R. B. Nielsen,B' T' Watson'and S' M' King' Org' Syn'' submitted(1990). Letters,3l,725'1 (1990)' 2 B. H. Lipsirutz,R. Keil, and E. L. Ellsworth,Tetrahedron 3 B. Lipshutzand E. L. Ellsworth,Am. Soc',112,1440(1990\' a K. A. Bakiak,J. R. Behling,l. i. Oygos,K' T' McLaughlin'I' S' Ng' v' J' Kalish' S' W' Kramer,and R. L. Shone,ibid., ll2' 7441(1990)' 5 R. C. Sun, M. Okabe,D. L. Coffen,and J' Schwartz,Org' Syn'' submitted(1990)'
15, 8 I -82'
Chlorodi(cyclopentadienyl)titanium(IlD, Reductionunddeoxlgenationofepoxides.Theradicalformedonreactionof as cyclohexa-1'4epoxides with CpzTiCl (lican be trapped by a H-atom donor such of monoreduction for useful is not reduction This alcohol. provide an (2) to diene
o "*o
1,2
H
o,^--ao\
- l l .\o."--v/
C
* "*o..'
l
:
c.H.
CoH,
...OCH3
CuHt
OH
3
(129o)
(659o)
r "r.r I tz
. ot^Yo\ " or^\ao\..gCH, *.V i$"V
cuH,
-
CuH,
oH
(z)
doublebond as well as a hydroxymethylg completeretentionof the stereochemisry rT. V. RajanBabu, W. A. Nugent,andM' S' 2T. B. LowingerandL. Weiler,Can'l' A*r
Chlorodi(cyclopentedienyt)methylzirtr Preparation.r Altyhc amines.z Reactionof I si$ atesthe imine complex (a), a zirconaeziri metrical alkynesto form metallapyrrolir tlt bondsto provide (Z)-allylic aminesin elly version of this An enantioselective dimethylzirconiumderivative3, prepared indenyllzirconiumdichloride.3Displu followed by reactionwith a lithium anilil of methane.Reactionof a with a symrErti which is hydrolyzedto an (S)-allylemir variation in the lithium anilide. Terminl
(169o)
(189o)
s(cH3)3 to a l-alkeneis also obterminalepoxides.In this case,deoxygenation substituted This radicalreducis used' of cpzTicl equiv. if 2 reaction served,andis the major suchas 3' epoxides for carbohydrate useful particularly is tion anddeoxygenation radical of this version modified (15, A 82). alkenes2 Cyclization of a-epoxy an exocyclic with in a cyclopentane results vinylstannanes cyclizationusingro-epoxy
.",oo"\/"
coocH3 SnBu,
#
,),cu'oH (EIZ>98:2)
I + BzlNLi
4ry
Chlorodi(cyclopentsdienyl)methylzlrconium
Fn 3nd S. M. King, Org. SYn., t k : : e r s . 3 f, 7 2 5 7( 1 9 9 0 ) . EO lin J S Ng, V. I. Kalish,S. W.
{L
(1990). 3 5rn . submitted
ot-Yo> - '*o"'(-J
fcoocH,*,6-::" | SnBu,
(z)
radrcalformedon reactionof dtrn..rrsuchascyclohexa-1,4useiul for reductionof monofH
_
...ocH3 "oH
CoH, (t2qo)
doublebond as well as a hydroxymethylgroup. The cyclization involvespractically completeretentionof the stereochemistryof the double bond. I T. V. RajanBabu, W. A. Nugent,andM. S. Beattie, Am. Soc.,ll2, 6409(1990). r T. B. l,owinger andL. Weiler,Can..1.Chen.,68,16360990). Chlorodi(cyclopentadienyl)methylzirconium, Cp2Zr(CH3)Cl(l). Preparation.r A[ylic amines.2 Reactionof I with lithium trimethylsilylbenzylamidegeneratesthe imine complex(a), a zirconaaziridine, which coupleswith terminalor symmetricalalkynesto form metallapyrrolines (b). MethanolcleavesZr-C and Zr-N bondsto provide (Z)-allylic aminesin 48-75% yield. An enantioselective versionof this allylaminesynthesisemploysthe chiral (S,S)dimethylzirconium derivative3, preparedfrom (S,s)-[1,2-ethylenebis(tetrahydro-lindenyllzirconiumdichloride.3Displacementof one methyl group by triflic acid followed by reactionwith a lithium anilide resultsin a zirconaaziridine(a) with loss of methane.Reactionof a with a symmetricalalkyneprovidesa metallapyrroline(b), which is hydrolyzedto an (S)-allylamine(4) in 90-997oee. The methodtolerates variationin the lithium anilide. Terminal alkynesdo not react with a, but l-trimeths(cH3)3
Itrt\o to a l-alkeneis alsoobCl :. used.This radicalreducsuchas 3. x'hrJrateepoxides oJrtiedversionof this radical with an exocyclic lr cioPrentane :.
Q'lE>98:2\
I + BzlNLi
-[*?[::'']
Rc=cR[,d:] b I 4E-75%JcH,oH
tl
HrN._Y,,-cuu, /''..-.cH,oH
L1 2 ,, " ,
'l
I R
R ,
Chlorodi(cyclopcntrdienyl)methylzlrconium
NaphthalYnezircosra and use of benzYnezircom complexas a route to subo This naPhthalenesYntb ganometallicsneed not bc heterocYclicacYl grouPsce
-" ' (EBrHr)z(cH,r,3$#%le"t"oz,{ I T
r)r'H
-Nc6H5I
-""J
oo+l7o" (s,s)-3,
L
?
I P. C. Wailes,H. Weigold.r ' S.L. Buchwald, B. T' Wltto 0989). I R. B. Grossman, W. M' Dl a S. M. KingandS' L' Bwtr
lnc=cn J NC^H.
"'"'bR C
<--r9_rs-nqo EBrHt\z(Yt", ."-----,_>< H
,
R
R
(S) - 4 (>957o ee)
B-ChlorodiisoPinocrnPl Reductionol RCOSiI hols in 96-98% ee in isoL
R b
to give productsin which these ylsilyl- and l-phenylacetylenereact regioselectively (b) Hydrolysis of the metallapyrrolines terminal groups are adjacentto the mital. with the (S)-configuration' oio.Or oi i"uity active (Z)-allylamines
oMEM
"tr*LY5/"'' OMEM
l-
I J. A. Soderquist, C. L' Ar ktters, 31,4677(1990)
a#y'' li:;h.*",,1^A
w
fcu,rcu,rrr OMEM I
; u # ' € ^ l ' l *Q)- c/P' wa* \AzY 6"",
i-Pc(
I
(cH')'cHll
ocH3
ll o
ChlorodiPhenYlPhcPll Alkenestrom diols' primary and one secondr zole (4 equiv.), and iod involves a vic-iododiPb convertedto an alkenc r
C#''C
""I ocH3 o
Chlorodiphenylphosphine
IEBTHIIZ
-
Naphthalynezirconocenecomplex.a Buchwaldrhas extendedthe preparation and use of benzynezirconocenecomplexes(14, 133-134)to a similar naphthalyne complexas a route to substitutednaphthalenesand naphthoquinones. This naphthalenesynthesishas severalattractive features.The intermediateorganometallicsneed not be isolated; it is regiospecific;and aliphatic, aromatic, or heterocyclicacyl groupscan be introducedefficiently. rP. C. Wailes, H. Weigold, andA.p. Bell,J.Organomet. Chem.,33, lEl (1971). 2 s. L. Buchwald, B. T. watson,M. w. wannamaker, andJ. c. Dewan, Am. soc..lll. .14E6 (1e89). I R. B. Grossman, W. M. Davis,andS. L. Buchwald (Iggl). , ibid., 113,2321 a S. M. KingandS. L. Buchwald, ibid., ll3,25g fl991).
"/NC.H' I | | \ l
-""J
Il R c = c R
I
NC^H. tttr t,/
)--cH, I
R
R
B-Chlorodiisopinocampheylborane, Ipc2BCl(l), 13, 72; 14, g2. Reductionol RCosi\. Acylsilanesare reducedby ( -)-l to (R)-c-silyl alcohols in 96-98% eein isolatedyields of 6O-6SVI.
b rclr tr.rgive products in which these rolrsrs of the metallapyrrolines (b) I S r-configuration.
(-)-r t#-r-Prcos(cH3)'
H
oH
>\
i-pr l
Si(CH.). (98Voee\
I J' A. soderquist, c. L. Anderson, E. I. Miranda, I. Rivera,andG. w. Kabalka, Tetrahedron ktters, 31, 4677(1990).
TtCp
!
77
I
oMEM l*.,4
l#\A,\"-" 6"",
L,cH_l
I
Chlorodiphenylphosphine, (C6H5)2pCl (l). Alkenestrom diols. Reactionofvic-diols with two secondaryhydroxyls or one primaryandone secondary alcoholwith chlorodiphenylphosphinc(2 equiv.;, imidazole (4 equiv.), and iodine (2 equiv.) resultsin alkenes.The reaction presumably involvesa vic-iododiphenylphosphinate, which can be isolatedin somecasesand convertedto an alkenewith zinc in acetic acid. -5 caHreCH2CHcHrOH
C'H,'CHTCH:CH,
I
OH
cH,o ocH, ".t ocH, Y
,{o.", ll
7t
iodide 2-Chloro-l-methylpyridinium
rZ. Liu. B. Classon,andB. Samuelsson' J. Or8.,55' 4273(1990)'
C6H5OCH2COOH+ CuIIrCltsl
2-Chloro-1-methylpyridinium iodide (1), 8, 95-96. Mukaiyama's reagent has been used for macroRCH2COOH + frQll:Q:Q.r lactonization of ol-hydroxy carboxylic acids (14, I I 7- I 18). However, reaction of the substrate 2 with I and N(CzHs)r in refluxing CH3CN does not lead to the expected COOH
tf"'''
(\"t:":o-l
. oH 'i'i,!Tl'l-
cH,-,/\r-i I .",- ^-<\ ----------------) cH,)\-Jl---,/ I "",2\-J=/
,
L
a
| I "7
-
l
CH, CHt
COOH
R' ''T?l'' tl-ao ,o..o
.,/
N3CHTCOOH + p-CHTOC.H.C
|
Chloromethyl trimethYlsllYl ChloromethYlation.t CU electrophilicaromaticchloru carcinogen.ChloromethYleti a chlorohydrin PreParedas d presenceof stannicchloridc il tive for chloromethYlationof decomposedbY hYdrolYsis CIS(CH3)3by BrSi(CH)3.
I
60- 80%
*( 5
.O\
O O \-/ lactonebut to 3, presumablyvia a [2*2]ketene-alkene cyclization. Similarly the alkenoicacids4 are convertedto cycloadducts5 in reasonableyield. However, there is no evidencethat macrolactonizationwith I proceedsthrough a keteneintermediate. $-Lcctcnrs.2 Carboxylic acids and imines condenseto form $-lactamswhen treatedwith 2-chloro-N-methylpyridiniumiodide (1 equiv.) and tripropylamine (3 equiv.) in CH2CI2.The stereoselectivity dependsupon the temperature.Reactions conductedat 25o favor formationofcis-pJactones.Yields are increasedwhenthe reactionsare conductedfor 12 hours at reflux, but the cis-selectivitydecreases. Comparedwith triethylamine,tributylamineimprovesthe yield and the cls-selectivity. lR. L. Funk,M. M. Abelman, andK.M. Jellison, Synleu,36(19g9). 2 G. I. Georg,P. M. Mashava, andX. Guan,Tetrahedron Letters,32,Sgl(l9gl).
S{€1.
-
I S. Itsuno,K. Uchikoshi, tr
(R)-( - )-Ch\oromethyl p This reagent(pure) can h with NCS in the prescoc
gH
(R)-( - FChloromethyl ptotyl sulfoxide rrN
C6H'OCHTCOOH + C6H5CttNCuI{oOCHr.p
-r*i*
cuH'ot--.cuH,
scd for macroreacrion ofthe D rhe expected
l
l
--r-N \cuHnOCHr_p
o'
(cisltra6) = lJll
N,-raCuH.CH,-r I N3CH2COOH + p-CHTOCuHoCH:NCuHnCHr_p --------)
35%
/-*-"urr.ocH,-p (cis/ trans) = 10:1
Chloromethyl trimethylsilyt ether. chloromcthylation.r chloromethyl methyr ether has been generaly used for electrophilicaromaticchloromethylation, but ri is trrghtytoxic anJnow considered a carcinogen.chloromethylationcan be effectedby useofa trimethylsilylether(l) of a chlorohydrin preparedas shown from trioxane and chlorotrimethyisilanein the presenceof stannicchroridein chloroform. This reagent,generatedin situ, is effec_ tive for chloromethylation.of styrenein the presenceof sncla; any excessis easily decomposedby hydrolysis. Bromomethylation is possible by replacementof ClSi(CH3)3 by BrSi(CH3)3.
Sncln
-oJ Srmilarlythe )lrever,there DeintermediKtamswhen ryvlamine(3 r. Reactions rd whenthe I oecreases. cis-selectiv-
]=
Hrc:o'
' Snclo crs(cHi)r > Hrc'!si(cu')' ' -cl '
'S. ltsuno,K. Uchikoshi, andK.lto, Am. Soc.,ll2,glg? (1990). (R)-( - )-Chloromethyt p-totyt sulfoxide, l. This reagent(pure) can be obtained by reactionof (R)-( +)-methyl p+olyl surfoxide with Ncs in the presenceof K2co3 iotowed iy ,"u.r.r recrystalrizations.
crHr...3
Ncs. K,co,
72% ':'-ScHr--SL--r .a 9ll.
1
.,'13 I crHr/
t""r",
l, aD-239"
rn-Chloroperbenzoicacid
Chiral epoxides.r Alkylation of the anion (LDA) of | (97Voee) with l-iododecaneprovides2, which reactswith symmetricalketonesat -40o to give a single (S)-chlorohydrin(5) with complete1,2-asymmetric induction.However,use of an aldehydeor unsymmetricketonesresultsin formationof two chlorohydrins,which canusuallybe separated by chromatography. Thusthe reactionof 2 with 6-methyl-l-
_ I (97Vo ee)
o 'i..ll
I) LDA 2) CH,(CH,)J -_--71%
S
crnrT
r) LDA.rTrF cH3(cHr)e.
tiRi:o > '4-tnqa
\cncr
,C_c/
oH
snBut 8.. C6H5(CH2)2CHCH.---j-+
(cHr)3coK (cH.).coH 86-9%
.'"',/1,
tl
{t* !I
o
(cH2)ecH3 2 (9'l%oee)
3
SnBu,
cHi(cH,),.&R rnF::i'*., cH3(cH,),...&R t*
C,H,S7
6t-Bsq'
H(
ll o
t*
(SF5(977o ee)
4
protonolysisof an intermediateepoxidc. ll (2.5 equiv.) and KHCO: (excess),thc o formedby a Baeyer-Villigeroxidationof , major productis 3. The oxidationwrs I cortexolone(equationI).
heptanalprovides(*)-disparlure (6) and (7S,8S)-(-)+rans-disparlure (7) in a ratio of -40:50.
tntthat"' -
l ) ) l
cH3(cHr),...f\...(cH2)4cH(cH3)2 CHr(CHr)r...f\...H "fl" ( 7 R ,8 5 ) - ( + ) - 6
n^,"",)4cH(cH1)2 (7s,85)-(-)-7
I T. Satoh, T. Oohara, Y. Ueda,andK. Yamakawa, J. Org.,54,3130(1989). m-Chloroperbenzoicacid. RSnBq + ROH.t This reactioncan be effectedby treatmentof RSnBu3with bromine,which effectscleavageof one butyl group to form an alkylbromodibutylstannane.This productis oxidizedby basicn-chloroperbenzoic acid to an alcohol with retentionof configuration. Dihydroxyacetoneside chain of corticoi.ds(14,86-87). Details for the double hydroxylationof the enol silyl etherI arenow available.2 For highestyieldsof 2, an excessof oxidant(3 equiv.) is requiredas well as excesspowderedKHCO3.In the absenceof base,the main productis the 17-hydroxy-20-ketopregnane, formed by
.o r
I
(D
, l
ClqH.COJl , | | KllCO,rc -
9tt
aro.'-Dihydroxy ketoncs.t Reactioo enol silyl etherof a methyl ,lec-alkylkac intermediateallylic alcohol. This abmru pylsilyl group. Oxidation of ArCH:NN(CHJy to vertedto aryl nitriles by oxidationof thcu
m-Chlorop€rbenzoicacid
).{' ,ri I (97% ee)with l-iodoat -40o to give a single tcrones r rnduction.However,useof an bn ..f two chlorohydrins,which lc reactionof 2 with 6-methyl-l-
BrSnBu, I c6H5(cH2)2CHCH3
SnBu, c6H5(cHr)rtHcH.5
*"' oll3,, | "'"""'"o'"' ,, OH
H ( ' H .t " .
OH
I
(cH,)rcoK (CH.).COH
c -c / t ^ . . I t ni cr R ]I o
c6H5cH2c HTCHCH3
------* 51%
)
SnBu,
'
r
q
<
H
/ OH
R
(SFS(977oee)
protonolysisof an intermediate epoxide.If I is addedto a mixtureof CIC6HaCO3H (2.5 equiv.) and KHCO3 (excess),the major product is the l7-ketone,probably formedby a Baeyer-Villigeroxidationof 2. If only I equiv. of oxidantis used,the major product is 3. The oxidationwas also used for a synthesisof l6c-methylcortexolone(equationI).
- ,-rrrrns-disparlure (7) in a ratio
().
"''lb("'''",ti,:8,l.["Ti'"', g!R& 88%
H ,L)
/--\ '(cHr)4cH(cH.)2 H -s.8s)-(-)-7
hi
,Z\
\
',i"il',cHr(cH' )AR
t
1.
(
\__J
J
1* R
R", COOBzI ./
86 -999o
s { . 3 1 3 0( 1 9 8 9 ) .
led br treatmentof RSnBu3with p ro iorm an alkylbromodibutylacid to an alcohol rop'erbenzoic 86-87t. Detailsfor thedouble rble : For highestyieldsof2, an KHCO3.In the Itce:\ powdered formedby ny -lO-ketopregnane,
)) l
o)
. l
2
CIC.H.COTH (l equiv.) KHCO, (excess) ---------.---.-9t%
fr* 3
u,ro,'-Dihydroxyketones.t Reactionof this peracidin a basicmediumwith the enolsilyl etherofa methylsec-alkylketonecanresultin doublehydroxylationvia an intermediateallylic alcohol. This abnormaloxidation is favored by a bulky tripropylsilyl group. oxidation of ArcH:NN(cft)z to Arc=N.a Aromatic aldehydesare convertedto aryl nitriles by oxidationof theirdimethylhydrazones with m-chloroperbe n-
n -Chloroperbenzoic scid
*,0 |;;t6'otton I
't' *"* '
cHrOH
^" tso
ix.rl.", )___) can also be effectedwith HzOz zoic acid in 46-91% overall yield' The oxidation acid' The former methodis aPPlicable catalyzedby SeO2or 2-nitrobenzeneseleninic to aliphatic aldehYdes.
.'ii*€3i",".- gJ4''o''"' O{, $q Directedepoxidation.sEpoxidation(MCPBA)of1,6-unsaturatedamidesor or ester group' estersresultsmainly in a syn-epoxidewith respectto the amide
o tl /^NH-i-su
NH-i-Bu MCPBA
o..\J
Bz 1 o clc6H4corH 95-9'l% NBS; NaOH 62-11%
-
insoluble. The reaction can be exothermi (l-octene). Yields are generally about $
I J. W. Herndonand C. Wu, Tetrahedron Lct : Y. Horiguchi,E. Nakamura,and I. Kurrltr r Y. Horiguchi,E. Nakamura,and l. Kuwe.;u ' S. B. Said,J. Skarzewski,and J. MlochorC t F. Mohamadiand M. M. Spees,TclraAedm 6 M. R. Leanna.M. J. Martinelli, D. L. vrn ' F. Fringuelli,R. Germani,F. Pizzo' and G.
n-Chloroperbenzoic acid-Trifl uoroti Sincc I Baeyer-Villiger oxidation.t owing to hazards in its preparation. dtc tions are particularly desirable. n-Chlor always effective, but addition of TFA (l
/\'?O l
l
cr.H.cor c
H
(
l
-
\-,
o ll
c6H5ccH.-
syn(>20:l) cpoxidations.6 Epoxidationof the ergoline I with m-chloroDiastereoselective and yield' perbenzoicacid providesthe a-epoxide(z) wittr high diastereoselectivity high p-oxide (2) in equally In contrast,epoxidationvia the biomohydrin providesthe (7:1) selectively osmylationof 1 alsoprovidesthe 54,64-diol diastereoselectivity. for the c-face' preference with similar Dpoxidationinwater.lEpoxidationofalkenescanbeeffectedwithMCPBAin = 8'3) at 20o evenwhen both reactantsare un uqo.oo. solutionof NaHCO3(pH
S. S. CananKochandA. R. ChambcrlioI
ir.t
Chloro(phenylthio)acetonitrile, ClCl"lC with sulfuryl cblo tion of C6,H5SCH2CN Esters:macrolides. Trost and Gru basedon conversionof I into an alkorl
''.'H,,',
Chloro(phenylthio)acetonitrile
?\ .)..-A'' h-. '.....AA'"
a,a""."o," (2.9 equiv.) **" ' J K| H CO,(excess)
\_ Bz
Bz
I clc6H4corH g5_glVa NBS;NaOH 62-7tqo
cH20H
ff"" o OSiPr,
( -H.CO,H H ---il
u-2 (exo) p-2 (endo) 98-99:2-l | -2:98-99
' J. W. Herndonand C. Wn, Tetrahedron Letters,30, 6461 (19g9). : Y. Horiguchi,E. Nakamura,and L Kuwajima,Am. Soc.,Ul, 625? (19g9). r Y. Horiguchi,E. Nakamura,and I. Kuwajima,TetrahedronLetters,30,3i23 (19E9). 'S. B. Said, J. Skarzewski,and J. Mlochowski,Synrftesis,223(lggg). 5 F. Mohamadiand M. M. Spees,Tetrahedron Leiters,30, 1309(19g9). 6 M. R. Leanna,M. J. Martinelli,D. L. Varie,andT. J. Kress,iia.,'10,3935 (19g9). ? F. Fringuelli, R. Germani,F.pizzo, andG. Savelli,ibid.,30, l42i Qgggl. n-Chloroperbenzoic
XCPBA) of 1,6-unsaturated amidesor tcrrrct to the amideor estergroup.
acid-Trifluoroacetic acid. Baeyer-villiger oxidation.r Since 90% H2o2 is no ronger readily available owing to hazards in its preparation, alternative reagents for Baeyer-viilige. reactions are particularly desirable. z-chloroperbenzoic acid (g0-gi%) as such is not always effective, but addition of rFA (l: l) enhancesthe reactivity and the yield.
o
o il ,'^
.Bz
insoluble. The reaction can be exothermic, particularly with reactive liquid alkenes (l-octene). Yields are generally about 90-95To.
ilarrtrn can also be effectedwith H2O2 c acrd The formermethodis applicable
t,
-\
o CIC6HaCO,IUTFA (t : l),
cH,cr,,0.
NH-i-su
88%
o tl
C6H5CCH3 + CeHsoccH3 .tsqo
nn (>20:l)
rrlatr.rnof the ergoline1 with m-chlororrrh hrshdiastereoselectivity andyield. tprtrrrdesthe p-oxide(2) in equallyhigh (7: l) tt'r:desthe 5a,6c-diolselectively rlkenescanbe efiectedwith MCPBA in Jr ;t 30" evenwhen both reactantsare
o tl
I S. S. CananKochandA. R.
Chamberlin, Syz.Comm.,19,g29(19g9). $CuH'
chloro(phenylthio)acetonitrile,clcHCN(l). This reagentcanbe prepared by reaction of C6H5SCH2CN with sulfuryl chloride(75% yield). Esters;macrolides. Trost and Granjarhavedevelopeda new synthesis ofesters basedon conversionof I into an alkoxy(phenylthio)acetonitrile(2i, which can un_
N-Chlorosuccinimide-Dimethyl sulfide
ic.H, + cH,oH# 1j clSHcN
o
icu", cH,oCucn
L
I . r-) (CH3),S-\
cr
2
$CuH' Pd (o)
--;;2 + CH2:Q11CHCH, tzaa \,/
o
la o
l+H'C(COC.[\\
|
CHTOCCHTCH:CHCHzOH |
c
I S. Katayama,T. Watanabe,and M. Yameud
N
Chlorotrimethylsilane. |,2-Addition of RzCuLi to >C:O.l addition to ketones, but this reaction cl (1-2 equiv.) in THF (but mt il ClSi(CH3)3 axial attack in the caseof cvclohexanom
AgNO., CHrOH fl CH3dcHrcH:cH2oH r- --4-------t a6% 4 dergoPd(0)-catalyzedalkylation. The potentialcarbonylgroup in the productis then releasedby treatmentwith moist silver nitrate to form the ester (equationI).
( AgNO'
+ BurCuI; -
iCuHt
(II) I + CH,:gs1g",),oH+F
CHr:g111g"rlrOiHCN S sc^H. sc^H. ' ' l)cH?=cHMgBr | |
2) CH,OCOC|
o : CH(CH 2)eOCHCN ----1r%'----+
|
CH, : g11gg,CHr)eOCHCN
oco2cH3 t
-(
NC Pd(o) -------------)
es%
c6H5s
.rr#elo{^-1'o.^(cHr)?
Organocupratesundergo 1,2-additioor But additionof the silaneto reactionsin Tll the major product. Moreover, useof thc sil in a markedpreferencefor the syn-adduct., of a crown ether(equationII). cls(cHr),
+ BurCuLt tll) C.HTCHCHO #CH, This useof I asa carbonylsynthonhasbeenextendedto a synthesis ofmacrolides by use of a long-chainalcoholfor the acylationstep, followedby Pd(0)-catalyzed cyclizationand deblocking(equationII). I B. M. TrostandJ. R. Granja, Am.Soc.,ll3, 1044(1991).
N-Chlorosuccinimide-Dimethyl sulfide (Corey-Kim reagent,l). Sulfur ylidcs.r This reagent (l) reacts with active methylenecompoundsto form sulfur ylides in generallygood yield.
q
Protectionof -COOH.2 Trimethybi tion of carboxylicacid groupsduringhydn cstersneednot be isolatedand deprotcctio tion or iodination step. 'S. Matsuzawa, M. Isaka,E. Nakamura. ed ( 1989). : G. W. Kabalka andD. E. Bierer.Sya.Gn
Chlorotrimethylsilane
tr. r\
O
\\
* /\ (CH3)rS-N' "c;
-o -"2 f+H,C(COC.11.,.
Y
c.lr.
crr,cr,. rrc,i,r. (CH'),S:C(CoqHr), **-
o
CH CH:CHCHzoH
I S. Katayama, T. Watanabe,and M. yamau chi,Chem.Letters,973(19g9).
t\ -l
Chlorotrimethylsilane. |,2-Addition o! R2CuLito >C:O.t additionto ketones,but this reaction
H
Ordinarily cupratesdo not undergo1,2_ ..n-iJ''rr."ted in the presence of added
g:*:,'1".**,;;;ii.,"il1.L,,",00, il,lli*'IiiilH::,";ilfi
n1I eroupin theproductis then m rheester(equation I).
o
(cH')'Sior.'Bu
-(
?"un'
0f
lctr r-ocHCN $
) \_.^cH,
-$2vslr ^,, * Bu,culi S: n_.,s%
fcuH'
(\ (r1"", (78-96:22_4)
I =CHCH(CH,)TOCHCN
organocuprates undergor,2-additionto aldehydesin the absence But additionof the silane of the silane. to reactionsin THF t:t:1" resul in formationof the themajor prod""r. nn"."-"*;j^:::",1 sityl etheras :,i.:
()co,cHl
j;fru'ii:,',:lll;ffi ::[tff.Ti*;:';ti::***:ff ;:**l* ;htT
5
I . o<--z) g^{CH:),
(rI)cuo"""Ho tl'iill*, +Bu,cuL, -",...'_i11",,, * ",",_"iJ:",, cH'
d r,' a rvnthesis of macrolides [ol,,.u ed by pd(0)-catatyzed
I",
cH3 5.3:r
t c a g e n r l. ) . rc merhylene compounds
"!o' of - c o o H.2 Trimethyl .,^-':"o" silylesrer temporary acidsroups prorec_ ouring r,yoroi;;,,.',:::.^:::ttror :::::t_._*?"-yric e.sters ot anunsaturated neednotbeisolaiea acid.Thesilyl ana - oeprltec;;;;#t --r'vrw!rru'occurs tronor spontaneously iodinationstep.
'S.
ro
duringthe oxida_
Matsuzawa, M. Isaka, E. Nakamura, (19E9). and L Kuwajima, TetrahedronLetters, : G. 30,lg75 W. Kabalkaand D. E. Bierer,.9y2. Comm., lg,27E3 (lggg\.
t6
Chlorotris(trlphenylphosphine)rhodium(I)
Chlorotrimethylsilane-Sodium iodide' of water or an Generationo/IlI in situ.l Thesetwo reagentsin the presence Thus, reactionof allylic alcohols alcoholgenerateHI + NaCl + 1/2[(CH3)3Si]zo. (l) CH',,2;-'.....OH
+ HI
CH.CN 7l%
+ H'o
CH^,/2I
HI producesallylic iodidesin 55-90% yield. In contrast, with this in silu generated the samereactionbut with an allylic alcoholhaving a terminal doublebond is accompaniedby rearrangementto provide an allylic iodide (equationII)' (ll) CH,:QIiQHOH
68%+CH.' -f
- |
I
CH, This reactioncan also be usedto preparehomoallylicalcohols.Reactionof 3andNaI in acetonitrilefollowedby a reactionwith a butene-2-ol(l) with ClSi(CH3)3 ketoneand zinc provides a homoallylic tertiary alcohol (2) in 52Voy\eld. OH l) CIS(CHr)r. Nal, CH,CN
CHr:gg61t"", 2gfT#l:9 I OH I
I
CH,:CHCH-C-Pr l l
cH3 cH3 ,
'T. Kanai,S. Irifune,Y. lshii, andM. Ogawa,Synthesis,283 (1989)
Decarbonylntionof ahloses.z Aft since1968to effectdecarbonylationol rion of sugarsonly recently, probablyI reactionwhen carried out in N-rrtelht rremelyusefulin the caseof simpleeld with formation of carbonylchlorobis( 15-95%. This method of degradetb groups are not necessary.Deoxyrldr bonylatedin'l5-99% yield. A disadvr rhecomplexis required. Diels-Alder catalysis.s Severd I lystsfor intramolecularcyclizationof
'fu H
Chlorotrimethylsilane-Sodium nitrite or nitrate. Deoximation.r This reactioncan be effectedwith this combinationof reagents catalystat room temperaturein yields generally>90%. The and a phase-transfer actualreagentis believedto be nitrosyl chloride,NOCI.
cH,
'J. G. Lee,K. H. Kwak,andJ.P. Hwang,TetrahedronLetters,3f,6677 (1990) CH, Chlorotris(triphenylphosphine)rhodium (I). hydroborationproHydroborationof alkenest(f5, 91). The Rh(I)-catalyzed vides a highly diastereoselective reactionin a synthesisof a polyetherantibiotic. Thus the derivative(l) of an acyclic allylic alcohol is convertedto the primary (CB) catalyzedby ClRh[P(CoHsh]r alcohol2 by hydroborationwith catecholborane (12,484) wilh 94:6 selectivity.Note that hydroborationof I with disiamylborane proceedswith the oppositeselectivityat Cro(8:92).
* cH3ooc cH3ooc
in the presenceof water ::.n1. or an il:O Thus, reactionof allylic alcohols
o o{*
I
._ ('H,._-2.,_._I
o
+ HzO
\, in 55_90%yield. rn contrasr, :],::..: rerminaldoublebond is a.com_ :.'n: 1 c r , { r d e( e q u a t i oInI ) . + {'}i --Oa:,..-.I
h,,:.r3llyfls alcohols. Reactionof 3_ l.':.i:rle followed by a reactionwith a | : .rrf6f Q) in 52Voyield.
r\ l +
(-lj
OH I :CHCH-C_pr
cH, cH, , r83 il989)
I..
tsl*::h rhjscombination of reagents r.. . .,.,0, generally >90%. The r. \{ }cl roc i::ters,
.
Decarbonylation of ora^.^^ ,
ffi*w /---Z ^\Z
31, 6677 .lgg)\.
-cH ,aCH,
ll
\--\_/
''" br.CtRhtP1cus,l,;, -: :l'?1* r urrh 'l2. disiamylborane i;;;
13 cH3
,,,,3::;:::il,i{:l:::;, j;:,.:i.,,:,*:r:i,?:H:iil"ll,ll::ff :iTl: _r
[rl -caralyzed hydroboration pro_ of a polyether antibiotic. 3,1..,. ,: T :"n":ned to the primary
2 (94:6)
^/-'\Z
U
\-/
cHrooc cH3ooc
Rr,rrr,ss.
=;_* CH^ '.-CH,
i
l
'
=;----
tt
Chromium cerbene comPlexes
(TFE) as solventfor requiresuseoftrifluoroethanol simplestone, ClRh[P(CoHs)rlr' Rh0) complexesare efficient but more.elaborate ratesand tigh'ffi as reasonable diastereoselective' rhesecatalyzedreactionsare evenin THF at 25.. In fti*";
""t:;r##^:;'":;r^
f2.. wilkinson,scatalystcataryzes to benzenes.4 benzenes'
with monovnesto form substituted 2 +2lcycloaddition of t,O-i'ptuOiyn"s Intramolecular|2+2*Z|cycloadditionoftriynesisalsopossiblewiththiscatalyst.
e:=::*ps-cH#h*:ry. substitutedaromatic is useful for synthesisof highly This [2 + 2 * 2]cycloaddition c o m p o u n d s s i n c e s u b s t i t u t i o n r e a c t i o n s(2) w i tfrom h a r etriyne n e s a rl's eseldomregiospecific.An exampleis the synthestt"i""t"*"i"nolactone
ocH I c
(CO)'Ct
+ RC cH3C-c I
2 DihYdrobenzcncs' PYranYlidcc elco l. preparedas shown, react with - .Aaott a, which extrudesC(CO)' rerd Attempted chromatographyof 2
./
l)cx'crx 2)K6rcl!
OCH.-
(CO)rCr:C
\,", Sevenl
cH3 -j:e--t CH,
.T, /->/\r1.zcH.
PH
9H'ff
Ar* c,H,ouc.tl
E-H"' o , l' Org'' 55' 5192'(1990)' rD. A. EvansandG' S' Sheppard' ibid"54'5257(1989)'
2M. A. Andrews, o' "' oitlfi"ttiii' l"' icrn"ttn; 4e65(leeo)' ""i i' r--i"i"er';;"';'' soc''rr2' ;:H;il; 3R. s. rolly,G. Luedtke, (1988)' 1365 *o "'si."r"*,i, rc.s. Prr!:^!,1357, aR.Grigg, R. Scou, 45' 6239(1989)' 5 S. J. Neesonand P' J' "*t"t"i'
2
Imioo crr{ finole sYztftcsis'3 bY trcxaneat 70', Possibly a [2 + 2] d UsuallY,onlY a singlePYnole is incorPorr not is carbonmonoxide r alkyl imidate carbenecomPlcxcr major the Product' pyridinesas
Teirahedron'
/'o\
(CO)rCr
"t1#,T;:H;r::;nnt;Jj''
nes arkv withterminar 1reacts rh" Fir"h"r.carbene
a 2-vinylcyclopentene-l'3tzolJ to giu" asthe.majorf'odott monoxideas well asthe in benzene (excess) 'u'bon if molecule' two dione(2) with incorpor"ii"" "f alkyneis possible' bonds.Reactionof an internal C-C Jriformation alkyneand is lowet(27%'oneexample)' but theyield of 'ytfop"nt"o"Oiones
1N il
-4.
H
I
cJr
Chromium carbene complexes
uorethanol (TFE) as solventfor lc Rhrl) complexesare efficient as ecrronsarediastereoselective, instrn's catalyst catalyzes[2* DcsrLrform substitutedbenzenes. s airtr possiblewith this catalyst.
aromatic rsr: ,.i highlysubstituted ts! rre seldomregiosPecific.An f r o n :t r i y n el . s
?"",
CH3C:C--r
+RC-cH*F ffi
)
I
Dihydrobenzenas.2pyranylidenepentacarbonylchromium complexes such as prepared l, as shown, react with electron-richalkenes,suchas enol ethers,to form an adducta, which exrrudescr(co)o ro provide dihydrobenzenes (2) in high yield. Attemptedchromatographyof 2 results in aromatization.
(Co).Cr-Cl //(\
-ocH3' l)cH,cocH,coocHr 2)Koc(cH'),
f", fl
cY,
a)r\-
P
I
cH3 -i:!CH,
' - oH l
o-.",,llVrL--'
g-
ll (co)'cr{ / \\'}-CocH, s;;---------> \-_-/ .1c.H,
\ buH,
OH
*)-
(CO)rCr:C.
VCH, cH;
tl
l_
J""'=t"*'"'
o.",fl I
Ar"*"'#1"'*'ffi8*"'l l rirc,H, - j L
c,H,o,,gqH, ,
o
t
I99 J S{ 5157(1989). {m Soc.,112,4965 (1990). F!.
r . : r i - . 1 3 6 (51 9 8 8 ) . l,1e .989).
funole synthesis.t Imino carbenecomprexessuch as l react with alkynesin bexaneat 70o,possiblyby a[2+2lcycloaddition, to form pyrrolesin g0-9g%yield. Usually,only a singrepyrrole is obtained.This heteroannelation is unusualbecause carbonmonoxideis not incorporatedto give a six-memberedproduct. However, o_ dkyl imidate carbenecomplexessuch as 3 react with l-alkynes to form 3-hydroxypyridinesas the major product. ,CuHt
ene I reactswith terminalalkynes ro.Jucta 2-vinylcyclopentene-1,3I carbonmonoxideas well as the r of an internalalkyneis possible, l. rrneexample).
*'\-r^.
(co)5cr{ + RLC-CR';o_1;
il H
.."/;\".", C.H,
Chromium cerbene complexes
a."r.*r[",
,c#' (co),cr{
*1/@H,
(co)scr:c-
+
+ P,c:GH--------------, ll--/
CuH,
I CuHt
CuH,
ii
cuH'
-NHCH,CH:CH, - \ /ocH3 ,/ \_/
(4Vo)
*L [:
I
(517o)
3 Alkylation.a Alkylation of anionsof the usualalkoxy carbenecomplexesis not generallyattractivebecauseof low reactivity. However, the anion of dialkylamino chromiumcarbenessuchas I (R = H) canbe alkylatedreadilyandin a usefulyield.
3 l (F
O
,fl
(co),cr:c/ v
(1
,,BuLi,rHF.-78"
_1sftg:_-
(CO)ICr:C(SCH)C6HI 0). This co usualway from Cr(CO)6,C6H5Li,and CH presence of BF3etherate,Ac2O,andN(C2H
CHRC,H5
,
r R=H)
for alkylationof 1, R = CHr, andyields However,forcingconditionsare necessary are only modest. I undergoeshighly 2-Amino-y-butyrolactones.5 The (dimethylamino)carbene in of a Lewis acid with even the absence reactions aldehydes aldol diastereoselective to form syn-adducts2, from which the metal unit can be removedby photolysis.
./
N(CH.),
(CO)rCr:C__.
+ CH,
I
BuLi.rHF
-+-HcocH(c6H5)cH,
OCH, 4
(co)rcr:g/ LJ
cHrR
{
(cHr)2N
0)
I + C.H'C-CCOOCJ-|.;
OH
uH'
\co),cr2*c CH,
dihydrothionaphthoquinones, in which rhc (equationl).?Aversion ofthe reactionra gan (3) from the related methylthiofurylcr
2 (40:l) ,u* | ,",.t,"*
+ o
osi(cH! ll (CO),Cr:CA0/ + CH,CHC= scH3
Allylaminocarbenesl indanones.6 Thermal decarbonylationof the pentacarbonylchromiumcarbene1 provides 2, which reactswith a l-alkyne to form a complex (3) of an indanone(4).
Chromium carbene complexes
OH
\".r'2 I
[-cH,:.,,^-'l
*\-
.".-,-(',.*
I
+
lt \\
ArvA cuH, ii
CuH,
cuH,
llvo't
I
nrai alkoxycarbenecomplexesis not Hr1\re\ er, the anionof dialkylamino llr i.rtedreadilyandin a usefulyield.
L
)
V J
-16".,"",, .vQ#[ ocHj
+
I
-NHCH,CH:CH, | -NH I (CO)sCr:C /OCH3 eo" l(colncr:q aocHr I -----, /-\ 1 1 \ | \_/
t 5l7a)
N
9l
4
,
l_cH,:cncH,ft d.",
j
3
COr.Cr:C cHRC2H5
, [kr latronof I, R - CH:, andyields
(co)5cr:c(scr)ccHs G). This complex,a purple o', is preparedin the usualway from Cr(CO)5,C6H5Li,and CH3dH. It reactswith alkynesonly in the presence of BF3etherate,AczO,andN(C2H5)3 (5 equiv.each)to form acetates of 1.4_ OAc
rlamrno)carbene I undergoeshighly I * en in the absence of a Lewis acid lrr .rn be removedby photolysis.
L -...
(cH')rT
O
CuH,
l+C6H5C-CCOOCTH, 1;+
coocrH5
OH
+,cor,cr*t'n CH, 2 (40:l) 56%Jr'v,cHrcN
(cHr)2N
dihydrothionaphthoquinones, in which the alkylthio group can be read'y reduced (equationI)'7 A versionofthe reactiontnu, or"a ,o preparethe furochromene visna_ gan (3) from the relatedmethylthiofurytca.Uene i.
oAc osi(cHJ3 ' I ,"Orr"r:"/) + CH,CHC-coc2Hs /-/\acH:cH2 ,A < ll I scH3 b'\-oc,H5 scH3 s"l. J*"".a 9cH. o l - r l
CH,
rj ,lecarbonylation of the pentacarzcr. '*irh a l-alkyneto form a com-
/>/\ tt-\*Z\eAcH, 3
92
Chronium carbene comPlexes
Diels-Alder reactions.s Alkenylchromium carbenesundergo facile Diels-Alder reactionswith 1,3-dienesas shownby a typical example(equationI). Thus the vinylchromium complex I reactswith isopreneat 25o to give mainly one adduct, which is oxidizedby dissolutionin DMSO to the methylester3, the major adduct obtainedby a Diels-Alder reactionof methyl acrylatewith isoprene.However, use ofthe carbenerather than the esteranaloghas somedistinct advantages'The rate is significantlyfaster and the regioselectivityis significantlyhigher, being comparable to that observedwith Lewis acid catalysis. Alkenylchromium carbenesalso react with much higher endo-selectivitythanthe correspondinga,pwith cyclopentadiene esters. unsaturated
Chromium(Il) chloride. Nozaki reaction(12, 137;14, 96: 15. reactioncan effect cyclization eveo to I ! treatmentwith CrCl2 at a low tempcratur€( in which a cyclononadiynering is fuscd ro the secondaryhydroxyl group, the mixturc enediynering.
Cr€l-llf -.--{
5J - 69r
(DV*" *"'Y"''# Cr(CO)'
\
"r,
tn')a) ocH.
\)
6""""''' r^/J"'(
Cr(CO),
-ocH3 Cr(CO)'
, r* | o"ro, rr" J
a*,.._r-\
\) r*"' o
Alkylchromium(Ill) reagenrs,RC(Ill vitaminB12or cobaltphthalocyanine (CoPc larly l-iodoalkanes,to form an alkylchru out effecton ketoneor estergroups.2
( n-CrrHul + z-CrH,rCllO -
3
'Y.-C.Xu,C.A.Challener,V.Dragisich,T'A'Brandvold,G'A'Peterson'W'D'Wulff' andP. G. Williard,Am. Soc.,lf f ' 7269(1989)' ' S. L. B. Wangand W. D. Wulff, ibid., ll2' 4550 (1990)' 3V.Dragisich,C.K.Mur.uy,B.P.Warner,W'D'Wulff,andD'C'Yang'ibid"ll2'1251
(leeo).
Letters,30' 4061 (1989). . w. n. wulff, B. A. Anderson,and L. D. lsaacs,Tetrahedron 5 W. D. Wulff, B. A. Anderson,and A. J. Toole, '{rn' Soc" 111, 54E5(1989)' 6 K. H. Dtitz,H.-G. Erben,and K. Harms,J.C.S' Chem'Comm',692(1989)' 7 A. Yamashita,A. Toy, N. B. Ghazal,and C. R' Muchmore,J' Org'' 54' 4481 (1989)' t W. D. Wulff, W. E. Bauta,R. W. Kaesler,P. J' Lankford,R' A' Miller' C' K' Murray' and D. C. Yang, Am. 9oc., 112, 3642 (1990)'
o tl
CH3C(CH2),I+ C.HTCHO-
The reactionof a 3-alkyl-l,I-dichlorei resultsin an c-chloroallylchromium(Ill)r ddehyde in theory to form four differer rhc stereochemistryof the double bond a thisreactionprovidesessentiallyonly oc 1 -r-butene-l-ol.
Chromium(Il) chlorlde
rerb
93
Chromium(Il) chloride. Nozaki reoction (12, 137; 14, 96; lS, 95). , An intramolecularversion of this reactioncan effect cyclization even to a st.ained nine-membereo,ing. iio, t on treatmentwith crcl2 at a low temperature cyclizesmainly to 2, a mixtu-reof epimers in which a cyclononadiynering is fused to a cyclopentenering. After acetylation of the secondaryhydroxyl group, the mixture is dehydratedto 3, with a nine-membered enediynering.
s9 /--5=*-oH crcr,,rrF2t I =;--WCH:GH, 2 (l:l) (s2%) I t) Ac,O MsCt(25%) J2)
rr{
lz-)100" f-
u:,e ,rr/',.-./',(
-ocHl
<){/>CH:cHz 3
Cr(CO), t'
(K H.
Alkylchromium(Ill) reagents, Rcr(IID. In the presenceof catalytic amountsof vitaminB120r cobaltptrttratocyanrn" tc"p.i, cal ..u"u with alkythalides,particu_ larly l-iodoalkanes,to form an arkylchromiumreagentthat addsto atdehydes with_ out effect on ketoneor ester groups.2 crct:.DMF n-C.H,, " "\ coPc n-C,rH.,rl + n-CrH,rCHO ---8ra_/CHOH n-C,rHri
o
o W. D. Wulff. tacr,.ld.G. A. Peterson, l9}, fu.f andD. C. Yang,ibid.,ll2, l25l .164(d ron kners, 30, 4061 (19E9). . s'. lll,5485 (1989). .n Comm.,692 (1989). r h r . . r e . J O r 9 . , 5 4 , 4 4 8 1( 1 9 8 9 ) . lfc:: R A. Miller, C. K. Murray, and
tl
lt
cH3c(cHr)s\
CH3C(CHr)'I + C.HTCHO
;6_>
"u"'-""o" The reactionof a 3-alkyr-l,l-dichloro-2-propene, R2CH:cHCHCr2,with crcr2 resultsin an c-chloroallylchromium(IlD ;;g;, This speciescould reactwith an aldehydein theory to form four different +-iiio-r,o,noaltylic alcohorsdiffering in rhe stereochemistryof the do,ble uono una inly, /anti-configurations. In practice essentiaty
$ilil-',Tlrovides
-t;;;;;c"tl
az-suustit uted anti_(z)_4_chroro_
Cobaloxime(I)
94
OH
When refluxed in benzene,3 undcrgc t ketone4. When irradiated with a sunbq diol (5) as a 3 :2 mixtureof isomers.A $r possible.
= 97'.3) (ZlE= 97:3;antilsYn
I D. C. Harrowven andG. Pattenden. Tctr*
Crclr,
9H,
'cl
cunrtcnr)rlrrA'--
+ CHrCH:cHcHcl, # c6H5(cHr)rcHO
Reactionof RCHO with \,3-diene monoepoxides.aThe monoepoxidesof butadiene or of isoprene after treatment with CrCl2 and Lil (2:1) react with aldehydesto form cis-I,3-diols with a quaternarycenter at C2.
"'")
t"':"X'".",
al-a", \o
^En__cuH'CHC a ^,, e5%
.CH, i. -CuHt
* | oH
I oH
98:2
CobattGl) acetlte, (CH3CO)2Co. Tetrahydrofurans.r Co(OAc)2prr tate and terminal alkenesto form t.rrl synthesisof dihydrofuranseffectedwiri I oxygen is required with the cobatt carll tetrahydrofuranis formed and in reletivet dso formed, but only in minor amqttrr.
o
o
co(o^.\ tto*-
rP. A. Wender, (1990). andC. Mukai,,{n.Soc.,112,5369 J. A. McKinney, 2 K. Takai,K. Nitta,O. Fujimura,andK. Utimoto,J. Org.,54,4732(1989). 3 K. Takai,Y. Kataoka, Letters,30'4389(1989). andK. Utimoto,Tetrahedron a O. Fujimura, K. Takai,andK. Utimoto,J. Org.,55' 1705(1990).
ll ll curicurcocHr+ cHr:cHR
Cobaloxime(I),11, 135-136. Cyclizntion of unsaturated epoxides.t Reactionof the epoxy alcohol (2) de3. rived from linalool with cobaloxime(I),(1), forms the p-hydroxycobaloxime
I J. Iqbal, T. K. P. Kumar, and S. Urm;rr Tarakeshwar,J. Iqbal, and S. Manogeno, li
,H #""4'{.*+""4 Y; \'
cH"
--'-'acHr
cHr
3 |
'"' t"
Y
9H,
Copper(0). ArCHO -+ ArCrrV.r Aromatic ddc nitriles by reactionwith copperpowdcr (l pyridine under oxygen. Yields are gcud formationof CuCl2and NH3 (equatioot). NH3 with the aldehydeto form an eldil catalyzedby CuCl2. This methodis dso r CHO + (CHr):CC=N (90%).
(I) Cu(o) + 2NH.CI + * O, .
-rr2v n)./-'-t'oH I l...oH \.,AcH3
P. Capdevielle, A. Lavigne,andM. Muny.
5 (3:2)
t"'\
N
(/'o-=+
,
"'tF-a
"'"\ ,Icol
('Ao"
hv
d
("Ao"
Copper azlde. Se12-Rcactions.rReactionof NaNl r $ch as I proceedsas expectedwith invenir aainly with retention(syn-Sp2).
Copper azide
r ;
9H' c
l C-H.(CH:):
t
When refluxed in benzene,3 undergoesdehydrocobaltationto provide the methyl ketone4. When irradiatedwith a sunlampat 25o,3 cyclizesto a cyclohexane-l,2diol (5) as a 3:2 mixtureof isomers.A similarcyclizationto a cyclopentanol is also possible.
l
-
OH
= 97:3) Q./E= 9'7:3;antilsYn
I D. C. Harrowven andG. Pattenden, Tetrahedron lctters,32,243(1991\.
ofbutaidcs.r The monoePoxides to (2: l) reactwith aldehYdes d Lrl ).
at1,:uc{,c,n, H . c ' H ' ( : OH
e8:2
)'
OH
Cobalt(fl) acetate, (CHrCOz)zCo. Tetrahydrofurans,r Co(OAc)zpromotesa reaction betweenmethyl acetoacetate and terminal alkenesto form tetrahydrofurans.This reaction is similar to a synthesis ofdihydrofuranseffectedwith Mn(III) acetate(14, 198),but differsin that oxygen is required with the cobalt catalyst. Of further significance,only a single tetrahydrofuranis formed and in relatively good yield (68-71%). A dihydrofuranis also formed, but only in minor amounts.
o
o
, '.. co(oAc),, o, cH.ooc ll ll HoAc'6o' cHr..A ) curicurcocHr+ cHr:g11R
: r . . l l 2 , 5 3 6 9( 1 9 9 0 ) . I ( " e . 5 4 , 4 7 3 2( 1 9 8 9 ) . t k:iers.304 , 3 8 9( 1 9 8 9 ) . 5 . : - 0 5( 1 9 9 0 ) .
so"\o/"'n
+
xtrrrn of the ePoxYalcohol (2) de3' f66ni the P-hYdroxYcobaloxime QH,
o
Ql
85+
CH,
cq
,.oH
Copper(0). ArCHO + ArCrN.t Aromatic aldehydesare convertedto the corresponding oitrilesby reactionwith copperpowder(1.5 equiv.)and NHaCI(2 equiv.)at 60o in pyridine under oxygen. Yields are generally 80-99%. The reactioninvolves in .riru formationof CuCl2and NH3 (equationI). The conversioninvolves condensationof NH3 with the aldehydeto form an aldimine, which is then oxidized to a nitrile catalyzedby CuCl2.This methodis also applicableto tertiary aldehydes;(CH3)3CCHO - (CHrhCC=N (90%\. CuCl, + 2NH, + HrO
P. Capdevielle, (19E9). A. Lavigne,andM. Maumy,Synthesis,45l
tcH
OH
6-llqo)
' t. Iqbal, T. K. P. Kumar, and S. Manogaran,Tetrahedronktters,30, 4701 (1989); P. Tarakeshwar,I. Iqbal, and S. Manogal.an,Tetrahedron,47,297 (1991).
(I) Cu(0) + 2NHnCl+ * Or-+
zOH
Gc
.oH
ffi
cH,
(68-7t%\
ol'l
95
., ;q-
"'t\--a (,Aot
Copper azide. Sp2-Reactions.r Reactionof NaN3 with a 1-mesyloxy a,p-unsaturatedester $ch as I proceedsasexpectedwith inversion. The reactionwith NaN3-CuIproceeds aninly with retention(syn-Sr2).
96
Copper(I)bromide-Dimethylsulffde
TRe^^\.A/coocH3 rDov
.*
I
+ (R)-2(svn)
rsso^\rycoocH3 ---: N3
6tvts
an intramolecularUllmann reaction hrvc tions for Ullmann cyclizationshas led to r and the o-methyl deoxybouvardin3.1
(S)- 2 (ozti) NaN3, DMSO NaNr.CuI, HMPA
100:0 9:91
86Vo NVo
I Y. Yamamoto and N. Asao, J. Org.,55'
OR:
>'--
t
5303 (1990).
l
\./ R,J.
NH .",{,
Fo
L. A. Hulshof,and I H. L. Aalten,G. vanKoten,D. M. Grove,T. Kuilman,o. G. Piekstra, (1989). Tetrahedron,45,5565 R. A. Sheldon,
Copper(I) bromide-Dimethyl sulftde. Intramolecular l\llmann reaction.r A numberof antitumor antibioticsconsist of polypeptidescontaininga diphenyl ether group, arising by oxidative coupling of two tyrosinegroups.However, severallaboratorieshavereportedthat an intramolecular Ullmann reactionfails to effectthe desiredcyclizationto l4-memberedrings. A detailedstudyof the intramolecularUllmann reactionwith a model substratesuchas I revealsthat undermoderatelydilute conditionsat least2 equiv. of CuBr'S(CHl)z are required.Reactionsproceedwell in pyridine (130"), but DMSO, DMF, and C6H5CIare poor solvents.Racemizationcan be a problemin the caseof pyridine, but canbe minimizedby useof dioxane(110"). The presenceof an alkoxy or hydroxy substituentortho to the participatingphenolin the couplinghasan adverseeffect,but doesnot preventcyclization. Severalattemptsto usea 3-iodotyrosineas a partnerin
o\_
C>
I fr, NY(cH,), o 58va 2 467o 5lvo (S/R= 55:45) (S/R = 96 : ) 3l7o
(
rl o=1
Copper(I) bromide. ArBr + ArOCHgJ Bromobenzenecan be convertedto anisolein95Vo yield by reactionof NaOCHTin DMF/CHTOHat I l0o, catalyzedby CuBr. The activespecies -. is probablyNAlcu(OCHrrl
Py(130") l. R'. R2= H Rl= oCHr, R2= H ry Py R' = ocH' R2= coocHr R' = OCHr, R'= COOCHT Dioxane
t
HN \
R'-"-T Rt
3 4
R2
R3
R'
HCH3CH3H H H C H r H
R!
H H
I D. L. BogerandD. Yohannes, J. Org.,$. : idem,Am.Soc.,ll3, 1427(1991\.
Copper(I) chloride-Chlorotrimctlyh& Conjugue addition of nMg0l ad I generallybe effectedin good yield in Tlll (3%) and(CH3)3SiCl (1.2 equiv.).EveoI jugate addition, but yields are poor in ri noted with allylmagnesiumhalides. rfri replacedby CuCN with only a minor dccr be replacedby CHrSiClr (0.45 equiv.).
' G. CahiezandM. Alami, Tetrahcdroa l-cae
Copper(I) cyanide-Chlorotrimctlykfr Michael reactions.r Various ortrm or c-amino acid groupsundergoMichrl poundsin the presenceof CuCN, (CHr)j
Copper(I) cyanlde-Chlorotrimethylsllane
-
coocH,-
\--
+ (R)-2(syn)
yl
an intramolecularUllmann reaction have failed. Application of thesemodel conditionsforullmann cyclizationshasled to a successful synthesisofdeoxybouvardin4 and the o-methyl deoxybouvardin3.2
c4:.
100:0 9: 9 1
OR2
,)".-.o..(
/
\
R'J. cH,Y I...n' 4-N-\
ol
ned to anisolein95VoYieldbY d t'r CuBr. The activesPecies
NH "",{
tso HN\
L. A. Hulshof,and ) C Prekstra,
/NCH3 O=< )..."",
HN
cH. !o-
*._.FT-*-..Oo*, R'
of anritumorantibioticsconsist nsrneby oxidativecouPlingof tre reportedthatan intramolec[lrrrn to l4-memberedrings.A r u rth a modelsubstratesuchas lca.t 3 equiv.of CuBr'S(CHr)z 'r. t l q r b u t D M S O ,D M F , a n d Dlcmrn thecaseofPYridine,but lrnce of an alkoxYor hYdroxY rplrnghasan adverseeffect,but as a Partnerin r -r-rodotyrosine
+ \--o\:
.t'
-
/ \ \__/
gH, I l l
\-*-.N.\.,.(cHr), : l l R - O a t t [
2 S / R= 5 5 : 4 5 ) ,S,R= 96:4)
3 4
R2 R3 Ro R5
H CH3CH3 H H H C H 3 H
H H
O-methyl deoxybouvardin deoxvbouvardin
I D. L. BogerandD. Yohannes, J. Org.,56, 1263(1991). 2idem,Am.Soc.,ll3, 1427(1991\.
Copper(I) chloride-Chlorotrimethylsilane. conjugate addition of RMgcl and RMncl to e,,p-enoates,r This reactioncan generallybe effectedin goodyield in THF at room temperaturein the presencecucl (3%) and(cH3)3sicl (1.2 equiv.).Even p,p-disubstituted enoatesundergothis conjugateaddition,but yields are poor in the caseof cH3MgBr. Anotherexceptionis notedwith allylmagnesium halides,which give only the 1,2-adduct.cucl can be replacedby cucN with only a minor decrease in yields.(cH3)3sicl (l.2 equiv.)can be replacedby CH3SiCl3(0.45 equiv.). ' G. CahiezandM. Alami,Tetrahedron (1990\. Letters,3l,7423,7425
Copper(I) cyanide-Chlorotrimethylsilane. Michael reactions.r various organozincreagentsbearingremoteester, nitrile, or c-aminoacid groupsundergoMichaeladditionto c,p-unsaturated carbonylcompoundsin the presenceof CuCN, (CH3)3SiCl, and HMpA.t
98
Copper(I)iodlde-Tetrekis(triphenylphosphine)palledium(0)
Bromide2 undergoessimilar co enediynesin high Yield. This coq
CuCN, ClSi(CH])l
--*"_--)
zn(cHr)rcN + cHr:QllgoocHi
Nc(cHr)scoocH3
a 9uHt i l l ----+ HccHrcH(cH')3cooc'H5 IZn(cHr)rcoocrH,+ cuHrcH:CHCHO andz. Yoshida , Angew'chem' Int' Ed" 2t' 351 r y. Tamaru,H. Tanigawa, T. Yamamoto, (1989).
A. G. Myers,M. M. Alauddin'Mlznen, 7 Harrington,Tetrahedron
Copper(I) oxide' Cu2O. Benzoturans.r 2-Substitur reactionof o-iodoPhenolsand ldine. This synthesishas bccn co lides with o-halophenols,but , acetylidescan be exPlosive.
Copper(I) - A l l y l a iodide. tionof|.alkynes.lCu(I).promotedallylationofl-alkyneswasfirstreby useofa lportedin patents(195?-1959)and hassincebeenmarkedlyimproved uttynyt'ugnesiumhalideorbyuseofphase-transferconditions(BulNCl/NaCol)' the latter conditions' both of which allow use of sulstituted allylic halides. Under can be obtainedin76-95% yield' substituted1,4-enynes cul,Bu.Ncl
9H,
^'-L,
no8-c-cH
w
+ cHr: cHqHCl#'-t
1",
f"'
cHrcH:cHcHrc-ccou
I
ll
cHt)rclr'\/\oH
C. G. I. S. Doad,J. A. BarltroP. ( 1989).
+
E","'n 9H,
CH':CHCHC:CCOH r l CH,
Z' ,'.-('+ cH=c
CH,
(1988); idem,TetrahedronLetters,30' 2225(1989)' 'T. Jeffrey, J.C.S.Chem.comm.,909
Coppcr(I) trifl uoromethencld $-Lactams.t CuOTf (l q effectivefor cyclization of |r Mercury(I) trifluoroacetatcba O
H
r
Y"tI H ^2csi(c\' cH,'-Ht t l o:"a
*{-cr".oc sc6H5
iodide-Tetrakis(triphenylphosphine)palladium(0)' Copper(I) ^ g-bromide of ethyl (z)-2,3couptling of vinyl bromtulis nith olkyntt,r The in the presdibromopropenoate(l) couplesselectivelywith trimethylsilylacetylene enceofCuI,Pd(O),andabasetoprovidethebromoenyne2in86-90%yield' O ff
t
c,HplY)\B' gr
H O HC=cSitcH,\.
s#H\
|l
c,Hso'^Y\ Br
H I
si(cH j)3
' N. Miyachi, F. Kanda,and M. !
Crotyltributyltin, ll, 143; U CoCl2-Controlle d additbt l,ewis acid, TiClr or BF3 ctba rhe order of addition of rcg present,the addition Prodrrca alcohol(a-adduct).
Crotyltributyltin
ba,0t
Bromide2 undergoessimilar couplingwith a variety of l-alkynesto provide (Z)in highyield. This couplingcanprovidea varietyofenynesandenediynes. cnediynes
lc:
i
, NC(CH,),COOCHI
o
99
A. G. Myers,M. M. Alauddin, M. A. M. Fuhry,P. S. Dragovich, N. S. Finney,andP. M. Harrington,Tetrahedron Letters,30, 6997( 1989).
guH,
I I HCCH:CH(CH2)3COOC2H5
da. lnsew. Chem.Int. Ed.,28,351
Tlatronof l-alkYneswas first reDarkedlyimProvedbY useof a lfer conditions(BurNCl/NaCOr), dcs Underthe latter conditions, r reld
Copper(I) oxide, Cu2O. Benzoturans.r 2-Substitutedbenzofuranscan be obtainedin 65-837oyield by reactionofo-iodophenolsand l-alkynesin the presenceofCu2O suspended in pyridine. This synthesishasbeenconductedin the pastby reactionof copper(I)acetylides with o-halophenols, but yields are somewhatlower. In addition, copper(I) acetylidescan be explosive.
vr1't I
+ cH-c(cH2),cHr l*+
ll
CH,)3C'^YOH
|
ll
ll
(CH,),C'\.AOA(CHr)rCH.
' O. J. S. Doad,J. A. Barltrop,C. M. Petty,andT. C. Owen,Tetrahedron Letters,30,1597 ( 1989).
9H, I +
.CH:CHCHTC:CCOH I
cH,
9t'9
9H' I CHr:g11g"a-CCOH I
CH,
Copper(I) trifluoromethanesulfonate, CuOTf. $-Iactams.t CuOTf (l equiv.), particularlyin combinationwith CaCO3,is effectivefor cyclizationof p-aminothiolestersto cis-p-lactams(67-92Voyields). Mercury(Il)trifluoroacetate hasalso beenused,but it is highly toxic.
CH,
lc:, ; hedron ktters, 30, 2225(1989).
,ZCS\(CH)z
o:tt-\=-cuHnocHr-p
H
Y"ott" N;-CuHooCHr-p
sc6H5
plledium(0). The p-bromideof ethyl (Z)-2,3in the presnmerhllsilylacetylene 2 in 86'90% yiel,d. brrrmcrenyne
()
o-\y'\ Br
-si(cH,),
'N. Miyachi,F. Kanda,andM. Shibasaki,J.Or9.,54,35ll (1989).
Crotyltributyltin, 11, 143; 12, 146. CoCl2-Controlledaddition to aldehydes.r This reaction, when catalyzedby a lrwis acid, TiCla or BF3etherate,involvesan allylic rearrangement, regardlessof rhe order of addition of reactants(12, 146). In contrast,if CoClz (1 equiv.) is present,the additionproducesmainly or even exclusivelythe linear homoallylic alcohol(c-adduct).
Cyenotrimethylsilane-Di-p-chlorobis(cyclooctadiene)dirhodium
""r"t:CHCHzCHCoHT:-n
+ CHrCH:CHCH2SnBu,#n-CuH,rCHO
OH I J. IqbalandS. P. loseph,Tetrahedron ktters,30,242l (1989). Cyanoarenes. (DCN) and 2,6,9,10-teDiels-Alder reoctions.r Both 1,4-dicyanonaphthalene (TCA) have been used as sensitizersto effect photochemical tracyanoanthracene [4 + 2]cycloadditionsof electron-richdienesand electron-richdienophiles,which do not normally undergo thermal cycloadditions.These cycloadditionsare known as triplex Diels-Alder reactionsbecausethey are postulatedto involve as an intermedicomplexof sensitizer,dienophile,and diene.This reactionis atea three-membered from somesilyl enolethers,alkenes,or ofbicyclo[2.2.2]octenes usefulfor synthesis
Cyenuric fluoride. Amino acidflaorides.r Amino acidr ir the acid-stable9-fluorenylmethoxycarbooy ride andpyridine in CH2CI2to form FMOC r Butyl esterand ether groupsare also sublc r is compatiblewith most amino acids cocei group such as serine, threonine, and espl 0uoridesare more stableto water and mahl reactivethan the chlorides in reactionswid usedto preparea heptapeptideby solid-ptl L. A. Carpino,D. Sadat-Aalaee, H. G. Cht. ( 1990).
arylalkynes.
/> l
I T. Mukaiyama, T. Soga,andH. Takenoshirr : T. Soga,H. Takenoshita, M. Yamada, ad T. X (1990).
tJ". l
+
rcA. /rv
-
\-2
c^H^ --r*---'
tH,
/\
, /C6H5 I
0-
A'\
CH, endo - trans
/NHt
\osi1cH,),d
a v-J lD__l ./l
ocH. N
osi(cH3)3
Cyclic sulfatesof l,2-diols (15, 105-lO7) 1,2-Diamines.r The cyclic sulfarc 1t benzamidine(3) in refluxing DME to form d This product is convertedby known srcpe ;"ield.The overallprocessinvolvesinvcrsi ransformation was applied to severaldigl 1.2-diamines in high percentee.
o
r\oo
= l:l) (exolendo OH I N. Akbulut, (1989r. l. Or9.,54,2549 J.-I.Kim,andG. B. Schuster, D. Hartsough,
Cyanotrimethylsilane-Di- p-chlorobis(cyclooctadiene)dirhodium. Cyanation of acetals. This reactionhas beeneffectedwith CNSi(CH3)3and a Lewis acid catalyst(11, 150). It can also be effectedunderneutralconditionswith severaltransitionmetal catalysts,in particular, with [Rh(COD)CU2,CoCl2, and NiCl2, listed in the order of decreasingactivity. Basedupon this reaction,Mukaiand yamaet al.t haveexaminedthe useof the combinationof cyanotrimethylsilane the rhodiumcatalystfor generalactivationof silyl enolethersor ketenesilyl acetals. Aldol reactions.2 This combinationof catalystsis effectivefor promotingreaction of acetalswith silyl enol ethers and ketene silyl acetals.It can also promote reactionofaldehydesor imineswith ketenesilyl acetals.The reactionsoccurin high yield at 25"; eitherCH3CNor THF can be usedas the solvent.
I
)"''-zCuHt C.H, I OH (R,R)-r
O/-t
-
l
\
"^".4.'9 I I
C.l! 2
fH, cr'r/-{q NH.
(s,s>s
ldium
Cyclic sulfates ol l,2_diols
ll CH:CHCH"CHC.H,.-n I OH .
l
llliet
njene (DCN) and2,6,9,10-telrzers to effect photochemical ron-rrchdienophiles, whichdo r crcloadditions are knownas led ro involveas an intermedilc. .rnddiene.This reactionis : srlrI enolethers,alkenes, or
101
IT. Mukaiyama, T. Soea,and-H.Takenoshita, Chen.
'
Lctters,997 (19g9). H' rakenoshil, M. Yu.;;, ;;fi. ioill.,n a,Buu.chem. soc.lapan,63,3122
lrili:'
Cyanuricfluoride. Aminoacidflaoridcs.r Aminoacids in whichthenitrogengroupis protected by theacid-stable 9-fluorenylmethoxycarbonyirt"b"lgroup reactwithcyanuricfluo_ rideandpvridinein cH2cl2to form FMoa;;l;" acidfluoridesin 65-75voyield. r_ Butylesterandethergroups.are alsostableto cyanuricfluoride.Hence thisreaction is compatible with most
group such asserine,*ilH J:'*T:ffi T,':r"fi :iff T11'?#; :::mj**
fluoridesare more stableto water and methanolthan the acid chlorides, but are more reactivethan the chlorides in reactions *itr, unotrr". amine. In fact they have been usedto preparea heptapeptideby solid_phar.loupfing reactions. '1,'rfrr.tt*t""' D' sadat-Aalaee, H. G. chao,andR. H. Deselms, Am. soc., rt2,965l
L...--."", ('H, 3,
-:rdns
c)cHl osi(cH3)3
Cyclic_sulfates of l,2-diols (lS, 105_107). r'2'Diamines't The. cryl-ic sultate Q) of (R,R)-stilbenediol (l) reacts with benzamidine(3) in refluxing DME to ro.r ti, irioazolrne 4 as a single enantiomer. This product is converredby known tt"p, into'is,S)-stilbenediamine (5) in 44vo yield' The overallprocessinvorves inne.sionoi both ,ter"ogeniccenters of l. The transformationwas appriedto several aliphatic cyctic sulfatesand shown to afford 1,2-diamines in high percentee.
o \.--o
l1-; = l:I)
OH
J / t , q . 5 4 , 2 5 4 9( 1 9 8 9 ) .
^ -- )".,-""^,
LoHs
lldirhodium. rred *ith CNSi(CH3)3 anda mder neutralconditionswith I R h r C O D ) C I ] 2C,o C l 2 ,a n d d uponthis reaction,MukaiI of lanotrimethylsilaneand elhersor ketenesilyl acetals. cflecrivefor promotingreacrcerals.It can also promotc i. The reactionsoccurin high l s o l re n t .
-*".-\"9
9-\
I
OH (R,R)-r
I
CuH, 2
-4df*",/t:*o I "'* I \-"'"'l L
N
H
ao*Joue, a
f", "ur,/Y"u'' NH,
(s,s)-s
l) Acro _ 2) HBr, HOAc
"f1
-
/"u''
- \ N
44%
CuHrt
Y CrH, 4
J
lO2
[(Cyclopentodienyl)dlc.tl-
(-)-rl4ts-Cyclohexrne-(1R,2R)-dlsulfonamidcs
Aziridines;amino alcohols.2 The l,2-cyclic sulfates(1) of chiral diols react with RNHz to form p-amino sulfates(2), which are convertible into aziridines or amino alcohols.
NHSO2CF3 + Ti(Gt-h 'NHSO2CF3
oso2
gso;
l-
I
srxrr' ""^/l?c6H5 | .."&t'"'NHrBzlJI \o
I
L
,o*J.,n,". /r1.,.-.ZCuHt
CuH, n..' Bzl
(S, S, > 967o ee)
o9o' tl
r"- (Y \o
f
-Bu
(67Vo ee)
oso3Li I
[L , "N&, ' "J1
LiN',
binedwith Ti(O-i-Pr)r anddicthy enantiomericexcessesaPProrhir amounts. The processis an interestiot e substratereportedis benzaldehy is almostas effectiveas diethYlz ' M. Yoshioka,T. Kawakita,rnd [l
,ruft'o'". -rr-'.'-zBu
Bu N"' H
(S, S, 677oee)
I R. Oi andK. B. Sharpless, Letters,32'999(1991\' Tetahedron 2 B. B. Lohray,Y. Gao,andK. B. Sharpless, ibtd',30'2623(1989)' Cyclobutenediones. (13,97-98; 209-210). Liebeskind'hasreviewedthe useof Quinone synthesis of benzoquinonesfrom cyclobutenedioneand of the preparation for organolithiums with clco[P(coHs)r]r to form either benzoreaction of benzocyclobutenediones are particularly useful for regioselective routes These quinonesor naphthoquinones. quinones. substituted synthesisof highly ' L. S. Liebeskind, 45' 3053(1989). Tetrahedron, (-')-trans-Cyclohexane-(1R,2R)'disulfonamides(1). addition o! RzZn to RCHO.T A Ti-complex, formulatedas 2, Enantioselective particularlyl, when compreparedfrom a (-)-trans-cyclohexanedisulfonamide,
[ (Cyclopentadienyl)dicerboryl( :CHSC6ll5 phate, Cp(CO)2Fe+ phenylthioiron carbeneis obteir and then with (Ccl CICH2SC6H5 Cyclop entane annulatiot.' by insertioninto C-H bonds.Th
l) cfll, 2\t / -'I f i + l
lr
[(Cyclopentsdienyl)dicarbonyl(phenylthio)carbenium]lron hexafluorophosphate
yclrc sulfates(l) of chiral diols react lch are convertibleinto aziridinesor
Tf I
NHSO2CF3
+ Ti(O-i-Pr)o+ Zn(CrH,),-+
/YN'|
I
V"'^'/
[.,*j c^H.--i>,,-cuH' I
Bzl rS. S, > 967o ee)
ry""] r. '
ZnCrH,
^ i \o/ . l N
Tf
C6H5CHO + 2;5;+
Pr-i
l'i6\
tt
I
'o*Jr^,".
C"H.
pr_t
T
CuHrACrH, (98_99Vo ee)
binedwith ri(o-j-Pr)n anddiethylzinceffecrsadditions of diethylzincto aldehydesin enantiomeric excesses approachingr00% evenwhenthe comprexis usedin catalytic amounts. Theprocessis an interestingexampleofligand-accelerated catalysis,but theonly substrate reportedis benzaldehyde. It is noteiorthy thatthe less-reactive dibutylzinc is almostas effectiveas diethylzinc. ' M. Yoshioka, T. Kawakita, andM. Ohno,Te,ahedron Letters,30,1652(19g9).
Lr{lHr
,
-Bu . ./ :'\-/ t r
rS :
\ ' H 67Q.ee)
, r : e e 9( 1 9 9 t ) . J -ro :623( 1989).
[(cyclopentadienyr)dicarbonyt(phenyrthio)carbenium]iron hexafluorophosphate' cp(CO)2Fe+:cHSC6H5pF6- (1, m.p., 126"). This stable,crystalline phenylthioiron carbeneis obtainedin g0% yield by reactionor Nacpperco)2 with CICH2SC6H5 andthenwith (C6H5)3C*pFu-.' cyclopentaneannuration.2 This complex is useful for cyclopentaneannulation by insertioninto c-H bonds.Thusreaction of l with the enorateoik"ton" 2 provides
tl r. Lrebeskindr hasreviewedthe useof Docrfrom cyclobutenedione and of the Ktr[PtC6H5)3]3 to form either benzolC pdnlcularlyusefulfor regioselective
rides r l ). UO.t A Ti-complex,formulatedas2, lfonamrde.particularlyI, when com-
| | I | -\-f\.r'\^,, H
li fn,''
5
0 Lof,s
-
E
O il H
Fe(CO)"Cp '' (cH.)o'BF:
CH,CI,, o_zs;
sc.H. "
J
.
_
%
CuHt
104
l(Cyclopentadienyl)dicrrbonyt(phenylthio)carbeniumtiron
hexafluorophosphete
tetrafluoroborateprovidesa sulfothe adduct3. Reactionof 3 with trimethyloxonium niumsaltwhichliberatesacarbenethatinsertsintothebenzylicC-Hbondof3to formthecyclopentane-fusedproduct4.CyclopentaneannulationhasalsobeenobFe(CO)rCP
0)
(cH1)ro'BF.
SCuH,
(cH2)3CH3
cH2CH3
36%
3,4-Dialkoxyfurans. Diels-Atiler reactions.r Both 3,4{in dergo Diels-Alder reactionswith reactive cycloadditioncanbe markedlycatalyzedby i
I
BzlO:./r tainedbyaformalallylicC_Hinsertion'Insertionintoasimplealkylsidechainis possible,butinloweryield(36%,equationl)'InsertionintoatertiaryC-Hbondis particularlyfacile,asemployedforasynthesisofsterpurene(8)fromtheenolsilyl ether5.
I szloN
-,--,
.-zCWH,
o+ll CH'
Cn-cH'
l) cHrLi
ry t cH3 2)s99:L' CH, CH,
rty. This reactionhasbeenusedfor an e6ci (l).
' M. Koreeda, K.-Y. Jung,andJ. Ichita,.l'C'S
H 7
6' 988 ' Organometallics' andP' Helquist I C. Knors,G.-H.Kuo,J. W. Lauher,C' Eigenbrot' (1e87). Am. Soc.,|||,8527 (1989);S.-K'ZhaoandP. 2 S..K.Zhao,C, Knors,andP. Helquist, (1990)' J. Org',55,5820 Helquist,
l,t-Diazabicyclo[5.4.0]undecene'7 (DDU |,3-Dipolar cycloadditions.t On ucr paredby reactionof acid chlorideswitb tg
o l
CHINC + (CHr)rCCCl
l -----t
l
o
l
(CHr)rCCC:
cl I
["*rj=-i-r"]
hcniuoroPhosphate
tr
providesa sulforatlu!rroborate bond of 3 to C-H the oenzylic beenobalso has E annulation
o
H
3,GDialkoxyfurans. Diels-Aliler recctions.r Both 3,4-dimethoxy- and 3,4-dibenzyloxyfuranundergoDiels-Alder reactionswith reactivedienophilesin refluxingbenzene.This cycloadditioncanbe markedlycatalyzedby znl2, which alsoenhancesendo-selectiv-
---)-cH'cH3 H 3:o=2:l inro a simple alkyl side chain is nr\\n into a tertiary C-H bond is Frcurene (8) from the enol silYl
Bzroyz\,acooc:u, * \ ;t*l r . , "sztoL T#coocH3 8", ,,o/*o (endolexo= l5:l) (93%') I l) H,, ROr 2) LiN[S(CH,),1?(78%I ffi -"- | | l) BFv/c,H,sHI
Fc COt.Cp ^
sc^H,
Ja)
o"o...-,\.-
(cH,)ro'BF; >
CH,
(. .t ,l ,.
coocH,
a.o''Y
OAc
t
I
CH, cr. 9 l
I tw*t
t - l
487o from 5
--
nc:o
CH, CH,
rty. This reactionhasbeenusedfor an efrcientsynthesis of methyltriacetylshikimate (l). M. Koreeda, K.-Y. Jung,andJ. Ichita,J.C.S.Perkin1,2129(1989).
6, 988 P H.'l.1urst.Organometallics, : . - K ' Z h a oa n dP . rl . 5 l r ( 1 9 8 9 ) S
(DBU). I,t-Diazabicycto[5.4.Olundecene-7 |,3-Dipolar cycloadditions.r On treatmentwith DBU, imidoyl halides l, preparedby reactionofacid chlorideswith isocyanides, undergo1,3-dehydrochlorina-
o il
o
tl
CH3NC + (CH,)rCCCI ------+ (CHr)rC CC:NCH,
%
cl I
-coocH3
*-;p*\ ["",,,.8-.-fr-u;
o | --\N/ l \
(CHr)re
u f06
Dibromodifluorornethane/Zinc
tion to form a-ketonitrile ylides (a), which can be trapped by electron-deficient alkenesto form Ar-pyrrolinesin 45-65% yields'
"#LGh","',, , q;l'-y..",,,
Dibromomethane-Zinc/Copper(I) chloriib Cyclopropanation.r The cyclopropenr be facilitatedby sonicationor by Ti(IV) ctrlt dve. The effectivenessof this promotor mey and hydroxylic impurities. Yields using 6i t5%) than thoseobtainedby the originel Si methane.
E. C. FriedrichandE. J' Lewis,J' Org'' S5'2 (equationI)' The report includesone exampleof an intramolecularcycloaddition or in methanol in 20-80o at DBU by are cleaved Deacitylation.2 Acetyl groups In substrate' of the for solubility if required a mixed solvent, CH3OH/CH2CI2, tertiary or secondary than readily more general, primary acetatesare hydrolyzed ones.A bonusfor this methodologyis the selectivity: Esterslacking an u-hydrogen (benzoyl,pivaloyl) are stableto this cleavage.The reactionis probably not hydrolytic since it can proceedin benzenewithout a protic solvent'
Dibromomethyl(trimethyl)silane, (CHr)$ from CH2Br2and (CHr):SiCl.'
o ll
cocH3
OBz
65ea
I+*, o
2.cr{:cvr}f. qtt
o'Ybs""",'''''''''''''''iZVo\
AcO AcO
\',1/t
o il
o*"",
CH3(CHr)sCOCH,CH:CH,
CH,
CH,
(1989)' I W.-S.TianandT. Livinghouse, J.C.S.Chem.Comm',819 436 2 L. H. B. Baptistella, andA. J. Marsaioli,synthesis, J. F. dossantos,K. c. Ballabio, (l989). Dibromodifluoromethane/Zinc, CF 2Br2lZn. Difluorocarbene.r This carbenecanbe generatedfrom cFzBrz by reactionwith of zinc in THF catalyzedby 12.This reagentshouldprove useful for the generation
Alkenylsilanes.z A reagent(2)' prepo efficientfor conversionof estersor thiolcc ity.
andJ. F' Normer.I J. Villieras,C. Bacquet, : K. Takai,M. Tezuka,Y. Kataoka, andK' Ut
difluorocyclopropanes. F tt"';.X cFfrr'Zn,
tu"'Ya"" ' HrCt
7t%
HrC'
F
2,3-Dibromo-1-phenylsulfonyl-l-propcl
This reagentis obtainedby addition of Br Furan annelation.r The reagentrel (2) to form furan 3 in goodyield. A simit bY dt NaOCH: in CH3OH is accomPanied
l -propene 2,3-Dibromo-l-phenylsulfonyl-
n t'e trapped by electron-deficient
-^il-cc(cH3)3
,
..-rA^i
I
Dibromomethane-Zinc/Copper(I) chloride, 13, 93. Cyclopropanation.r The cyclopropanationof alkenesby this combinationcan be facilitatedby sonicationor by Ti(IV) chloride, but acetyl chloride is more effective. The effectivenessof this promotor may result from removal of tracesof water and hydroxylic impurities. Yields using this expedientare generally higher (4585%) thanthoseobtainedby the original Simmons-Smithconditionsusingdiiodomethane. rE. C. Friedrich (1990). andE. J. Lewis,J. Or9.,55,2491
nle;ular cycloaddition(equationI). br DBU at 20-80' in methanolor in frrr solubility of the substrate.In realily than secondaryor tertiary i\ rr\ Esterslackingan c-hYdrogen fhe reactionis probablynot hydro-
Dibromomethyl(trimethyl)silane,(CH3)3SiCHBrz(1). The reagentis prepared from CHzBrzand (CHr)rSiCl.t
o
tl
lc solvent. Pr\1t
'1,i,',11o\
=+.",
\?r' /[
CH,
.R b:i
\19 (19E9). , 36 . n d A . J . M a r s a i o l i , S y n t h e s i s4
xrated from CF2Br2by reactionwith [d nroveusefulfor the generationof
F
. nx
F
i{ (' t : . . . : e r . J . O r g . , 5 5 , 5 4 2 0( 1 9 9 0 ) .
O"*"'
cHs(cH3)3
r,"n,.-"., rr", f"-o"t, (ZlE= >95:<5)
o
tl
cHSi(cH.). "'
il
cH3(cHr)EcoCHrcH:cH, ------) ' 1 t % CH3(CHr)ECOCHTCH:CH, (ffi = 9l:9)
Alkenylsilanes.2A reagent(2), preparedfrom l, TiCl4, zinc, andTMEDA, is with (Z)-selectivefficientfor conversionof estersor thiolestersinto alkenylsilanes rty. I J. Villieras,C. Bacquet, Bull. Soc.Chem.,Fr., 1797(1975). andJ. F. Normant, I K. Takai,M. Tezuka, Y. Kataoka, andK. Utimoto,Synlett,l,27 (19E9).
Br 2,3-Dibromo-l-phenylsulfonyl-l-propene, >< 'cHrBr (1,m.p.65") c6H5so2' This reagentis obtainedby addition of Br2 to phenylsulfonylallene. Faran annelation.r The reagentreactswith the enolateof dimethyl malonate (2) to form furan 3 in good yield. A similar reactionof I with a p-diketone(4) and NaOCH3in CHgOHis accompanied by deacylationto providefuranssuchas 5.
2,3-Dibromo-1-phenylsulfonyl-l -propen€
2
L
-
"
L"^! l lt"'o"\,-----. I H
o
tl
-r-r. -
1"".",("\so'c''' I L
Dibutylboryl trifluoromethanesulfoerlc, Boron enolatesof a-benryloxycdett.' acetates(2) into the boron enolate,which rp syn-diastereoselectivity. Somewhathigbcr tylboryl triflate, whereasuseof LDA rcsuh 37 : 66-63). Diisopropylethylamineis csca
4",o"\_
c#scHpcHrcooR' + R'cHo 5
ll \\ "",o
J
o
t
cH2so2c6H5
R'= CH: R' = CcHsCH:C R'= C(CHr)r R' = CcH:CH:@ Rt= CHr R2=Pr
3
b
o ll
cH,Br
l- n
t"'t)
I
+1 *"*",, 1"",X"",{ro,",", I 8s% ti .",4o I I 4
L
/cH2so2c6H5
/l
' Y. Sugano andS. Naruto,Chem.Pharm.hl
cr)o/
J
I
Reactionsof I with a cyclic 1,3-diketoneresultsin a 2,3-fusedbicyclic furan (equationI). HY'SO'C6H5
o -\ (t)l
I
*r
ducedby lithium aluminum hydride follor glycerolderivatives,R2CHOHCHOHCH
Dibutyldicyclopentadienylzirconium, Cp equivalent)is preparedby reactionofBul i Bicyclization ol unsataratcd inba.l N,N-dimethylhydrazones, undergobicyclir cis-cycloalkylhydrazides.
N a o c H ' 'oAcH,B, /\
t
\--Ao
l
G;""')'"''uu', 8s%
|
cH2so2c6H5
zNN(CH][ \ccoH,
lA. Padwa,S. S. Murphree,andP. E. Yeske,J. Org.,55,4241 (1990).
ral
I E. Negishi,F. E. Cederbaum,and T. Trlrl 2 M. Jensenand T. Livinghouse,in. Soc.. ll
Dibutyldicyclopentadienylzirconium
109
Dibutylboryl trifluoromethanesulfonate, Bu2BOTf(l). Boron enolntesof a-benzJlory esters.r The triflate 1 convertsalkyl benzyloxyacetates(2) into the boronenolate,which readily undergoesaldol reactionswith high syn-diastereoselectivity. Somewhathigher syz-selectivityobtainswith dicyclopentylboryl triflate, whereasuseof LDA resultsin slight anrj-selectivity(synlanti:3437:66-63). Diisopropylethylamineis essentialfor the aldol reaction. syn-3 is re-
Br ->r BuOK
.H
F.H ()
oBzl
,oc ---n p
, \
-EtN(i-Pr)' -.f:-. ^2 *'c6HrcH2ocH2cooR' + R2cHo > 2 O
\\ o
cH2so2c6H5
syn-3
Rl = CH, R2= CoHsCHzCH, 82Vo R' = C(CHr): R'= CoHsCHzCH, 76vo Rr= CH, R2=Pr E4Vo
l
/.cH2so2c6H5
,--------------) tr\ -o,< I
cooRr + anrj-3 H
.4.
96:4 9 9 :I 97:3
ducedby lithium aluminum hydride followed by catalytic hydrogenation(pd/c) to glycerolderivatives,R2CHOHCHOHCH2OH.
./
cH.'
I Y. Sugano andS. Naruto,Chem.pharm.Bull.,17, E40(19g9).
!
ilrr rn a 2,3-fusedbicyclic furan
Dibutyldicyclopentadienyrzirconium, cp2zrBu2 (r). The reagent(a zirconocene equivalent)is preparedby reactionof BuLi (2 equiv.)with Cp2ZiCl2in THF (25").' Bicyclizntion ol unsaturated imines.2 Unsaturatedhydrazones,particurarly N'N-dimethylhydrazones, undergobicyclizationwhentreatedwith I (1.35equiv.)to cis-cycloalkylhydrazides.
so2c6H5 TFA I
/^---ZNN(cH3),
".,I cH2so2c6H5
(hcH, ^=
[^ -NlN(cH"):l cp,zBu,,lCt--ycp: l+O...NN(cHi), ,v. -..."", L\-_,v
J
TFA f'^ZNN(cH3), \-.\cc6H,
a1..'NN(cH3), ",ut r .__ \ CuH,
. 5-( {t4l 0990).
'E. Negishi,F. E' cederbaum,and r. Takahashi,Tetrahedron Letters,27,2g2g(19g6). 2 M. Jensen andT. Livinghouse, Am. Soc.,111,4495(19g9).
ll0
2,6-Di-r-butyl-+nethylpyridine
(BHA, butylatedhydroxyanisole), 2,6-Di-t-butyl-4-methoxyphenol 13, 94-95. 1,1,2- and 1,2,2-Trisubstituted dihydronaphthalenes.rBHA esters(l) of lnaphthalenecarboxylic acid react with alkyllithiums to form an adduct(a), which is not isolatedbut reducedwith lithium triethylborohydrideto the enolate(b) of an aldehyde.This intermediatecan be alkylated (c) and reducedto 2 in 75Vooverall yield. The samesequence whenappliedto 3 provides4 in93% yield. 1,2-Disubstitu-
corBHA
4\a\ \-V
l-nnno-aori BuLily't/-'<"" --------, ll ll
L\"^--Z
Dibutyl telluride, BuzTe. Preparationfm Tellurium-Wittig reactions.r The rer ketones,triphenyl phosphite,anda weal b Bu2Teresults in c,p-unsaturatedestcrs! phosphiteis the regenerationof Bu2Tefn + BurTe BTCHTCOOCH,
LiB(C,H.).H
I
' M. E. WrightandS. R. Pulley, J. Org..9.
-ffi:-+
-------.-.-:.-j.
g
(E)
cuH'cH:clloc
I
HPMA JcHrr. HOH2C\ ..CHr
t
OHC. ..CH3
a-././../..",'-Y'u.n."". lr)'\"" Tsso
\-/\2
L\-\2
2
Wittig-typereaction.Yieldsare > 70J[. I tion. I Y.-2. Huang, L.-L. Shi,S.-W.Li, lld X.{
c
Bu
air^rco'BHA^-fY\H,* e'%\-\r' \-\r' ted dihydronaphthalenes are obtained when the alkylation is omitted. The report suggests that the reductionof a to b involvesa keteneintermediate.
Dibutyltin bistriflate, BuzSn(OTfh. Carbonyl activation and dcutiYst aldol condensationwith silyl enol ahcr bistriflate. In contrast, the dimethyl 6 undergothis condensation(Mukaiyamr re almostcompletediscrimination,which i catalysts.Thus dibutyltin bistriflate actir
' K. Tomioka, (1990). M. Shindo,andK. Koga,J. Org.,55,22'16 2,6-Di-l-butyl-4-methylpyridine(1). Vinyl triflates (10, 123).t The most satisfactoryconditionsfor preparationof vinyl triflates from carbonyl compoundsusing triffic anhydrideand catalyzedby the pyridineI or thepolymer-bound reagent2 arediscussed by Wright andPulley.In the caseof aldehydes,the reactionis bestcarriedout in CHCI3or (CH2CI)2at 50-70o, and results in a gem-bistriflate,which decomposesthermally to the vinyl triflate. Theseconditions,whenappliedto a ketone,particularlyaldol-proneones,are usually not useful. The preferredsolventis nonpolar(CCla)with a reactiontemperature of about50o. In addition,the Tf2O shouldbe freshlydistilledfrom P2O5.
( r )...$osilcH,y, .)
o 1t
+ CHr:61169
Dibutyltinbistriflate
tr lled hydroxyanisole), 13, 94_95. oaophrholenes.r BHA esters(1) of l_ llrrhiums ro form an adduct(a), which is trr:\.rrq\ydlide to the enolate (b) of an lcc cr and reducedto 2 in ?5% overall 3 pr .r 16s54 in 93% yield. I ,2_Disubstitu-
)r. R 8' c:H. ),H
I
|----------'--'
Dibujyltetlwiile, Bu2Te.preparation from Te(O)an
b
r+r,ae Jor,r,
=t')"nN"sH. [4x]* 75% \ Lq/
lll
' M. E. Wright andS. R. pullel, J. Org.,54,2gg6(19g9).
(E)
C'HTCH:CHCOOCH3
+ Bu,TeO
J
nroc"H,r,
BurTe+ (CuHrO)rp:g Wittig-type reaction. , yil _-eldsare >70%, andthe products all havethe (E)_configura_ tion. I Y.-2.Huang, L._L.Shi,S._W.Li, and X._e.Wen,J. C.
S. perkint,2397(tg8gl.
Bi
t
CH. ('H.oH
r'" rn: ;llr.vlationis omitted. The report J d ^.'ieneintermediate. 5-r ii-6 rt990).
isir._r,'11 conditionsfor preparation of t rr::1r.anhydride andcatalyzed by the Wrightandpulley.In the ,dr.-ursed-by r n CHCI3or (CH2CI)2^i50_70.-, ry'.e. rhermallyto the vinyl triflate. !r .^ularlyaldol_prone ones,are usu_ h:' CCL) with a reaction temperature fre.rh distilledfrom p2O5.
Dibutyltin bistriflate, Bu2Sn(OTf)2. Carbonyl activation and dcacivation.t Aldehydes,.butnot ketones, aldol condensation undergo with silyl enol ettrers'at'-ir" ,n the presenceof oiuutyttin bistriflate'In contrast,the dimethyracetalsof ketoles, but not of aldehydes,can undergo thiscondensation (Mukaiyam. i...ir."i*rth silylenolethers ., _7g" *irh almostcompletediscrimination, wtrictrir';;;';;r"r"ed with the usuar Lewis_acid catalysts'Thus dibutyltin bistriflate ..riu"*r-uiJrhydes, but deactivates acetalsof
ur* | "4o*".
ovcrallJ CH:OH
aYl a,,\,4.
ll2
Dicerbonyl(cyclopentadienyl)cobalt
aldehydes.It is possibleto effect selectivereactionsof ketonesadmixedwith aldehydes by acetalizationand addition of other silyl nucleophiles,such as R3SiH or R3SiCN, in the presenceof this catalyst. Note that trimethylsilyl triffate can effect reactionsof acetalswith silyl enol ethersin competingreactionswith aldehydesor ketones(15, 349), but this Lewis acid does not discriminatebetweenacetalsof aldehydesand of ketones. Michael ddition.2 This triflate is an effectivecatalystfor Michael addition of enol silyl ethersto o,p-enonessuchas methyl vinyl ketoneto provide adductsin 6075% yield, equation(I). This variation is useful in Robinsonannelations.
OTBDMS l,Q :r Cl
CH, CH,
l
I T. Sato,J. Otera,andH. Nozaki,Am.Soc.,ll2, 901(1990). 2 T. Sato,Y. Wakahara, J. Otera,andH. Nozaki,TetahedronLetters,3l, l58l (1990). Dibutyltin oxide, Bu2SnO. Monoacylationof diols.r Monoacylationof unsymmetricalI ,2-, I ,3-, and I ,4diols can be effectedby acylationof the dibutylstannylenederivatives,followed by quenchingwith oxalic acid or CISi(CH3)2C6H5. This processeffectsmonoacylation of the more-substitutedhydroxyl group, even a tertiary one. This method also is
"",t::
CH,
\/
I E. P. Johnson andK. P. C. Vollherdt,,lr
Di-p-carbonylhexacarbonyldlcobdt, C Asymmetric Paason-Khand biry Khandbicyclizationsof enynesare pct (13,244; 14, 128-129) as the chird rr: ..'CuH,
""'jjb"
cH.
cH,;l-bcocuH,
C.lr(l
o.\-(cg2)3c=cH
(
Vo"CH,
Yo" CH,
tvl
I
cH3X/------cHl CH, \-6I{-61-q-O..(
usefulin distinguishing betweenprimaryandsecondary diols,but fails with 1,S-diols probably becauseof inability to form the dioxastannaneintermediate.
C.HrA
'G. Reginato, (1990). A. Ricci,S. Roelens, Org.,55,5132 andS. Scapecchi,J.
Dicarbonyl(cyclopentadienyl)cobalt. [2+2+2lCycloaddition to a hydrocyclobutaindane.r The framework of the sesquiterpenoid illudol (3) canbe obtainedin one stepandhigh yield by a12*2+21 cycloadditionof the acyclicenediyneI mediatedby CpCo(CO)2.Transformation of 2 to 3 involvesa numberof standardreactions.The cycloadditionof I to 2 is the first instanceof formationof threerings in a singlestepandwith stereospecificgeneration of three contiguouschiral centers.
CH, CH, (+)-6
Di-p-carbonylhexecerbonyldicobelt
Df keronesadmixedwith alderleophiles,suchas R3SiHor rimethylsilyltriflate can effect E reactionswith aldehydesor rcnminatebetweenacetalsof
l13
OTBDMS OTBDMS l) CpCo(CO)r,nv 2) CuCl, CH, ---------------.
CH,
92%
CH,
CH,
ral) st for Michaeladditionof lone to provideadductsin 60obrnsonannelations. CH,
)9C)r 1581(1990).
bon lztters,3l,
u r m e t r i c a1l , 2 - , 1 , 3 -a, n d1 , 4 Tlenederivatives,followedby prmesseffectsmonoacylation rn one. This methodalso is CH" .r'r
t
"
C.Hs-+-OCOC6H5
oF-
|
t
| \oH
coc.H.
CH,
3 ' E. P. Johnson 381(1991). Am. 9oc.,113, andK. P. C. Vollhardt, Di-p-carbonylhexacarbonyldicobalt, Coz(CO)a. Asymmetric Pauson-Khand bicyclization.t Efficient asymmetric PausonKhandbicyclizationsof enynesare possibleusing(lS,2R)-(+ )-phenylcyclohexanol (13,244;14, 128-129)as the chiral auxiliary. Thus the (E)-enolether(l) derived
''ff^ "A -"'"'"' o{)O \Ao&(cH,)ic=cH # "
H
cHr,7+cHr
x
Co,(COL
CH, \_ss:611_o...f/^) y drols. but fails with 1,5-diols oc rntermediate. )rr
cH. CH.
CuHrV
4
5 5 . 5 1 3 2( 1 9 9 0 ) .
| ,,.,,"",
| 2)smr, v
C..H, ue.t The frameworkof the r n d h r g hy i e l db y a 1 2 * 2 + 2 ) p(.rrCO)2.Transformation of loadditionof I to 2 is thefirst r rrh stereospecific generation
HcrHl CH,
CH, CH,
CH, H (+)-6
114
Di-p-carbonylhexecerbonyldicobslt
from this alcohol when treatedwith co2(co)s at 95o cyclizesmainly to the bicyclic 2 with high diastereoselectivity (7:l). This asymmetricsynthesis [3.3.0]octenone hasbeenusedto obtain an intermediate(5) to (+)-hirsutene (6). Note that the chiral auxiliary is reductively cleavedby SmI2with 9l % recovery(13,270; 14,2Zl). 12+2+llcycloaddition (14, ll8). The Coz(CO)6-complexed allyl propargyl ethers(1) undergol2+2+ llcycloadditionwhen heatedat 45-60' on an adsorbent
""'#o="
Oxymethylation(12, 166). Cyclic cd silanewhen catalyzedbyCoz(CO)g.'Thcr > > 6 or 7-memberedrings. Both elccrru tivity. The actual reagentis probably R$ CHr. CO, HSiCH](CrHr)r,CqfCOl, - CI{.
U-
Co'(Co)u CHTJCH' o,,sio,.45" ^Ac-cH \
--n
76%
CuHr.. \----7 co. Hs(cH,\.cotc
CH,
b
i
*
I HOCHrr.
cH.-fH' !olco). -,2-c*cn o \-l
\ / - +
ct e*
J--fl-o
#
cHcH3 (ElZ= 4:r)
CH, (exolendo = 4:l)
such as sio2, Al2o3, or Mgo.Sio2. The yield varies with the adsorbent,which shouldcontain 10-15% H2O, and decreaseson addition of a solvent.2 Diastereoselective aldol coupling of alkynyl aklehydes.t The co2(co)6 corlplexes (2) of alkynyl aldehydesreact with silyl enol ethers to form aldols with osi(cHr)3 1\
t\./ J
o
lorlco)u
s y n l a n t i= 1 . 7 : l
osi(cH3)3
g
OH -----' C,U,8r\co'(co)u c,Hrc:cHCH3 + C6H5CTCCHO Cor(CO)u
2r-',u.CHrOAc
I
ll
+ co + Hsi(cH
C.HTCH:CHCHTOAc
T \"".
\-/
Benzyl acetatesreact with trimethylril catalyst to give p-phenethylalcohols b1 catalystis assumedto be (CH)3SiCo(C atmosphericpressureat 25o. It fails wi6 benzyl formate and benzyl methyl ahcr.
cHro"\,,/
oH
BF"o(c,Hi), A/*"o'(co)u
+cH,c;cCno#LI 82%
H
,
cH. CH,J
-CuH, CH,
;{
I J. Castro,H. S
,ynlorri= 32,t moderateto high syn-diastereoselectivity, dependingon the structureofthe enol and on the temperature,but independentof the Lewis acid and the alkyne substituent.
Dichloroacetic acid. annelation.t I 3-Chlorobutenoliile chloroacetate (prepared with LDA) in Tl
Dichloroacetic
rt 95" cyclizesmainlyto the bicyclic h) ,' l). This asymmetricsynthesis (6). Notethat the chiral + r-hirsutene 9l { recovery(13, 270; 14, 221). Co,rCO)6-complexed allyl propargyl rn heatedat 45-60' on an adsorbent
cH't
c o . H s i c H ! (.H.)..cq(co). c , H t ) r . c o , ( c o )cH,, > g H r * -,^-
u
-osiR,J ?,
cH'-fosin,
(75Vo\
f7o
CO, HSi(CHr)r,Cor(CO),
-osi1cH.;,
HOCH,\
HOCHzrzl-.OSiRr
Y-;;-
osiR3
o
l{ r aries with the adsorbent.which I addrtionof a solvent,2 ryl aldehydcs.3The Co2(CO)5comil1l enol ethersto form aldols with
o
OH
11
I
L -^ I
.--
^
cH'
'
synlanti = 1.7: ,
9l l o H |
Benzylacetates reactwith trimethylsilaneandCO in the presence of Co2(CO)s as catalyst to give p-phenethylalcohols by a one-carbonhomologation.The active catalystis assumedto be (CH3)3SiCo(CO)r. The reactionproceedsunder CO at atmosphericpressureat 25o. It fails with benzyl alcohol itself, but is successfulwith benzyl formate and benzyl methyl ether.5
.",oOcH'oAc Co,(co)o
r.^,
_ c H.cy\co,(co)o -cuH' cH'
(25Vo)
".",)^osi(cH3)3
CuHr\
= 4:l)
|
\or,*.
5r,*,
CH.
U.' cd,t
l15
Oxymethylation(12,166). Cyclic ethersare cleavedby carbonmonoxideanda silanewhencatalyzedby Co2(CO)3.4 in theorder4 > 3 > 5 The reactivitydecreases > > 6 or 7-memberedrings. Both electronicand steric factorsaffectthe regioselectivity. The actualreagentis probablyR:SiCo(CO)r.
V
CH,
acid
+ co + HSi(cH3)3 +#-
C.HTCH:CHCHTOAc
-;+
"",o@cH2cH'osi(cH3)3
C6H'CH:CHCHTCHTOSi(CH3)3
I J. Castro,H. S
s,-nlanti= 32:.l
nirng on th€ structureofthe enol and rrs acid and the alkynesubstituent.
Dichloroacetic acid. 3-Chlorobutenolide annelation.r Reaction of a cycloalkanone with dilithiodichloroacetate (prepared with LDA) in THF/HMPA at - 84' results in a product that
lt6
Dichlorobir(ctcbtrl
Dichlorobis(cyclopentadienyl)titanium
120)and then with CO2providesoptitd (l) in74-92% yield. The prducts erc I as2-4.
CJCI \/
u |
o ,fiti*ii f$cooH -------------)
| oH
(
I T. Ito, S. Okamoto,andF. Sato,Tetralu{
\/
ep" MgBr, ether --------+ 7t% overall
cyclizesto a p-lactoneon treatmentwith benzenesulfonyl chloridein pyridine.Treatment of the p-lactonewith freshly preparedmagnesiumbromide results in loss of HCI and rearrangementto a fused 3-chlorobutenolide.The overall yield of this annelatedproduct increaseswith the ring size of the ketone, being 92Vo in the annelationof cyclopentadecanone.
Dichlorobis(cyclopentadienyl)tttuh c2H5AlCl2. Cyclizttion of alkenes.t This Zi4 intramolecular cyclization of unrrivt Grignardreagent(l) with Cp2TiCl2n
trtt--,\
.&r-tfl, Cp:
/2--/ HrC'
f T. H. BlackandT. S. McDermott, J.C.S.Chem.Comm.,l84(1991).
)--+ et*
H.
Dichlorobis(cyclopentadienyl)titanium, Cp2TiCl2. Hydromagnesiation;butenolides.t Reactionof optically pure 1-trimethylsilyl propargylicalcoholswith isobutylmagnesium bromidecatalyzedby Cp2TiCl2(14,
(cHr),si-fl
f -oH
-l '.i",T,'"T' l-rcH'l'si-ro-.'n L
BrMg
t
oMgBIl
(D\
I \--\--
,,_*l;l?,oi. (cHr)3s\
.n...,,
,-
(cH3)rsi\
jcH, (CH.).CuLi
*--'* o/.o\*
attto'tt
i
):
Bu.NF
o/.o,\*
84%
/ \ o4oA*
cHr
(rr) cH3 -+ t0*
) X = TiCtCpu (cHj)rcuLi I l)
- -" "J2)R'cHo
,n-*o
n
.(*' .'t".
o4oA* 4
treatmentwith CzHsAlCl2followed by une (3) in 88% yield. This cyclization is also uscful for and can be used to obtain bicyclic ry feature is the selectiveformatioo of t center is formed. In this respect,Ti-i radical initiation (equationIII).
Dich|orobis(cyc|opcntsdienyl)titanium-Ethylrluminumdichloride||7
120)and then with CO2providesoptically pure u-silyl-c,p-unsaturatedbutenolides such (l\ in74-92% yield. The productsare usefulprecursorsto variousbutenolides as2-4.
L 9 , F, +
I T. Ito, S. Okamoto, Letters'31' 6399(1990)' andF. Sato,Tetrahedron
tct
\,o
MgBr, erer
| "
1t% over..ll
I chloridein pyridine.Treatx.1lfon1 \rum bromideresultsin loss of lne lnrrlrde. The overall yield of this oi rhe ketone,being 927o in the
Dichlorobis(cyclopentadienyt)titanium-Ethylaluminurn dichloride, cp2Tic12c2HsAlcl2. Cyclizttion o! alkenes.r This Ziegler-Natta polymerizationcatalystcan effect intramolecular cyclization of unactivated alkenes. Thus transmetallationof a Grignardreagent(l) with cp2Ticl2 resultsin a titanium complex(2)' which on
'*>
HrC
HrC'
r r r . l E 4( 1 9 9 1 ) .
"'] +Ht^>''r*r'"' F"''jQ ,/
cl
-
L
r'*J",o'
y t i
o of opticallypure y-trimethylsilyl rornrdecatalyzedby Cp2TiCl2(14, -'l
2t=.-.R
l
I
l
OMgBI
;
( r )/-<"' ( .4=/' |
I
It '
,ricv,cl |
9H, c?H,Arcl, > fY
\
u % W H
a
""'"'1]rt)--*'bD (cis)
Bu.NF > .^ rtR
u%
() I
X = TiCtCpz
., , i,!"bt"t' 'R
;^-I
n
o4oA* ,
CH.
treatmentwith CzHsAlCl2followed by an acidic workup furnishedmethylcyclopentane(3) in 88% yield. This cyclizationis also useful for cyclizationof variousdisubstitutedalkenes, and can be usedto obtainbicyclic systems(equationsI and II). The most notable feature is the selectiveformation of cyclopentanerings, even when a quaternary centeris formed. In this respect,Ti-inducedcyclizationis more usefulthan freeradical initiation (equationIII).
nE
(
Dichlorobis(triphenylphosphine)palledium(II)
CH, -i)
.",J\
(rrr)cH3{',
a* --------)
| \-/
|
t
l/+
I, X = TiCtCpz 5,X=Br(BurSnH, AIBN)
93Vo 4OVo
l lVo 60Vo
' P. Rigollier,J. R. Young,L. A. Fowley,andJ. R. Stille,ln. $oc.,112,9441(1990).
intramolecularbiaryl coupling to i)ir naphthol1 with the c-iodobenzoicri cyclizes to 4 when heatedin N,Ndn sodiumacetateandClzPdlP(Colls)rhir undertheseconditionshas beenuscd f Reductivccoupling of ArCOA.t , drawing group coupleto biph€nylsrL the presenceof a Pd catalyst.
Dichlorobis(triphenylphosphine)nickel(Il). Coapling of dithioacenls with RMgX; butadienylsil.anes.rThis coupling is possiblewhencatalyzedby Ni(I!. Thus2-(2-phenylethenyl)-1,3-dithiolane (l) couples with (trimethylsilyl)methylmagnesium chloride in THF in the presenceof this nickel complexto form (E,E)-trimethyl(4-phenyl-1,3-butadienyl)silane (3) in9l% yield.
S-1. |
Nilr)
)
+ (CHr)rSiCHrMgCl
c.H,-*S'
#
c6H5^4./Si(cH3L
' Z.-J.Ni andT.-Y. Luh, Org.,lyr., submiued (1989). Dichlorobis(triphenylphosphine)palladium(II). Intramolecalar biaryl coupling.r A novel, conciseroute to the benzonaphthopyranonering system (4) of the aglyconesof the gilvocarcin antibiotics uses an
ts',
- L '\r-\
r f
COCI + C(CHr)2S
ll r
I
|
I P. P. Deshpandeand O. R. Martin, Ian : G. Bringmann,J. R. Jansen,and H.-P. I rT. E. Krafft. J. D. Rich. and P. I. McDc
( - )-c,c-Dichlorocamphorsulforyb Preparation from ( - )-camphorbc
*.t'i"?T*' i
--------i---:-9 %
' l) NaNlSi(C-ll,\l 2) NCS
HOrc,^....Z\CH2CH3 i",
\-NSo2c6H5
m.p. 93', ao-36' Pdcl, [P(c6Hr)]1, NaOAc,DMA, 130" ------------t 79%
cH2cH3
cH2cH3
( - )-o,a-Dichlorocamphorsulfonyloxaziridine T )
+
lVo 6040
,
Srrlie.,{m. Soc.,ll2,9441 (1990).
intramolecularbiaryl coupling to join ring B to ring D. Thus esterificationof the naphthol I with the c-iodobenzoicacid 2 provides the precursor 3. This product cyclizes to 4 when heatedin N,N-dimethylacetamideat l30o in the presenceof sodiumacetateandcl2Pd[P(coHs)r]z in79% yield. A relatedintramolecular coupling undertheseconditionshas beenusedfor the synthesisof naphthylisoquinolines.2 Reductivccoupling of Arcod.t Aroyl halidessubsritutedby an electron-withdrawing group coupleto biphenylswhen heatedwith a disilanesuchas I at 160oin the presenceof a Pd catalyst.
CoCl+ C(cH3)2Si-Si(CH3)2cl +fl#.+
dienylsilanes.r This coupling is t1 lethenyl)-I ,3-dithiolane (l) coupbc rn THF in the presence of this (3) in 9l% 7l-l .-1-butadienyl)silane
\ tt
-
-L ^ Hrr,,\-.,'\ \v s
l19
I
+ 2CO + 2(CH3),SiCl,
/Si(CHj)j
3
o
r)
I P. P. Deshpande and O. R. Martin, Tetrahedron lzuers,3l, 6313 (1990). r G. Bringmann,J. R. Jansen,gd H.-p. Rink, Angew.Chem.Int. Ed.,2i,913 (19E6). I T. E. Krafft, J. D. Rich, and p. J. McDermott,J-.Org.,5S, 5430(1990)-
conciserouteto the benzonaphthohc grlvocarcinantibioticsusesan
D., \? L(' ) J+
( - )-a,o-Dichlorocamphorsulfonyloxaziridine (l). Preparation from ( - )-camphorbenzenesulfonimine:
cHrvcH3 _F___-\ I
l)---L i", Bz.O
_
\-NSo2c6H5
m.p.93', ao-36"
OCHr
CH, t)NaNlsi(cH,),t, 80%
ctc^H,co,H ----------+isq..
Cl
NSO2C6H5 m.p. 142", ao-29"
CH, CI cH2cH3
t/
NS02C6H5
o
(-)-r, m.p.r22. a"- I 50'
120
Dichloro(dicyclopentadienyl)hafnlum-Sllver perchlorste
Chiral sulfuxidesor selenoxides.r This oxaziridine(1) is generallymore effective than the modified Sharplessreagent of Kagan (13, 52) for enantioselective oxidation of alkyl aryl sulfidesor selenidesto the correspondingsulfoxidesor selenoxides.The polar Cl groupsof L improve both rate and the enantioselectivity. I F. A. Davis,R. ThimmaReddy, Am.Soc.,1ll, 5964(1989). andM. C. Weismiller, Dichlorodicyano-o-benzoquinone(DDQ). Oxidation of allyl (or bcnql) methyl ethers.t These ethers are oxidized by DDQ in refluxing tolueneto carbonyl compounds.
c#scHpcH, g#g C.HTCH:CHCH2OCH3 lA+
c6H5cHo C6H5CH:CHCHO
c6H5ocH3 G*H,'ro. '8. Lee-Ruffand Can.J. Chem.,67, 699(1989). F. J. Ablenas, Dichloro(dicyclopentadienyl)hafnium-Silver perchlorate, Cp2HfCl2-AgClOa. Glycosidationof glycosylfluoriile.r This reaction can be effectedwith a l:1 ratio of thesetwo reagents,but a I :2 ratio is now favored. They shouldbe premixed at 25o to ensuregenerationof the effectivecomplexin situ, which is consideredto be Cp2Hf(ClOa). This glycosidesynthesisdoesnot require neighboring-groupassist(1.5-13:1). anceandis p-selective -OBzl
Bzro\<;=.-o\
CprHClr-AgCl.{l:2) cH,cl,, -50p 4-A Ms ._..:.-:.----.-.
sao\----\-\
88%
cH2oH
O-Glycosidation of pt,cr by reactionof glycosyl fruor activator system. This behi usefulfor glycosidationof d
F
( F / a= 1 3 : 1 ) C-Aryl glycosldes.2This combination(l:2) alsoactivatesglycosylfluoridefor p-C-olivosides The glycosidationwasusedto obtainthe anthracene C-glycosidation. 2 and3 of vineomycin82.
' K. Suzuki,H. Maeta,andT. I : T. Matsumoto, T. M. Krt$ti, 'T. Matsumoto, M. Katsuti,r
Dichlorodl (cyclopcntedlcrg "ZrCpr. " Treatmcnto equiv.) producesa new r€.!
l-La
Dlchlorodi(cyclopentadlenyl)zirconium-Butyllithlum
ilrne (l) is generallymoreefiecn r 13. 52) for enantioselective sulfoxidesor secorresponding nre and the enantioselectivity.
t2l
9CH,
nzro\--$.-..-o, \
szro\----\.-\
, .4m Soc.,lll, 5964(1989).
-
4.A.'
+t
\
t F
il
\.,\r'
|
r
_ -> 78&
t
O
H
I Theseethersare oxidizedby
, c.H.CHO ICH:CHCHO r, cH,cl" --------:+ 86%
H.OCH, oH
OCH3
oH
ocH3
I ,leEg). chlorate, Cp2HfCl2-AgClOa. rtron can be effectedwith a l: I lrc'rred.They shouldbe premixed to be in srrl. whichis considered assistneighboring-group aqurre
C; -nIl - A8cl.ll :2) C:. 5f+AMS -.------------.-
I l) Ac,o,r) (e6%) cAN(75%) l2)
3
taq
\-(]fo', ^ p*---ffi\o=\./ ( 0 / c= 1 3 :l ) lso activatesglycosylffuoridefor un rheanthracene P-C-olivosides
o'Glycosidation ol phenols.3 o-Aryl glycosidescan be obtainedin high yield by reactionof glycosylfluorideswith phenolsin the presenceof 4-A MS and this activator system. This hafnium complex is superior to Cp2zrcl2, which is more usefulfor glycosidationof alcohols. I K. Suzuki,H. Maeta,andT. Matsumoto, Tetrahedron Letters,30,4g53(19g9). IT. Matsumoto, T. M. Katsuki, H. Jona,andK. Suzuki,ibid.,30,6lg5(i9g9). ! T. Matsumoto, M. Katsuki,andK. Suzuki,Chem.Letters,43? (19g9). Dichlorodi(cyclopentadienyl)zirconium-Butyllithium, 14, 122-123. "ZrCpr. " Treatment of dichlorozirconocene with HgCl2(l equiv.)andMg (10 equiv.)producesa new reagentdesignatedfor convenience as "zrcp2."r This re-
122
Dichlorodi(cyclopentedicnyl)zirconium-Butyllithium
./si(cH3)r
Diclhraa
si(cH3)3
/s(cH3)3
l) BUlj 2) CHC-C€ilCpprCl, -----F
-r|-l
I
agent promotesbicyclization of enynesand diynes to zirconabicycles,which on carbonylationfurnish bicyclic enones. A more convenientway to generate"ZrCp2" involves reaction with an alkyllithium or Grignard reagent(2 equiv.). The reagentgeneratedfrom BuLi is formulatedas la or lb.
t'"'-6lr"o z €c'HsY'H 8-",,o0' HX;-" la
lb
be used:Oz, H* , and SeCl2.The "Cp2Z 1,8-nonadiene, and cyclizationof 1.7-oc
This reagentconvertsdiynes separatedby two- to five-carbonchainsinto (E,E)exocyclicdienescontainingfour- to seven-membered rings in 40-89Voisolated vields.
cH.
I
a-c-:cc*3
(c{{,)3
\-C:CBu
_!-(1 61%
-CH
\-^c
iu Phospholes.2Reductionofzirconocenedichloride(l) by BuLi in the presence of 2-butyneprovidesthezirconiummetallacycle 2, whichcanbe isolatedif desiredas air-sensitive,orange-redcrystalsin 85% yield. Reactionof 2 with dichlorophenylphosphineprovidesthe phosphole3 (1-phenyl-2,3,4,5-tetramethylphosphole). The intermediate2 can also be convertedinto arsoles,stiboles,bismoles,siloles,germoles,stannoles, thiophenes, andselenophenes by the useofappropriateorganometallics. Cyclizltion ol dienes.s "Cp2Zr" also promotescyclization of 1,6-dienesto trans-1,2-disubstituted cyclopentanes. Thus 1,6-heptadiene (1) on treatmentwith "Cp2Zr" followed by brominationaffordsthe rrars-dibromide2. In contrast,useof a relatedreagent, Cp*ZrCl (Cp* = pentamethylcyclopentadienyl), effects cyclization to the isomericcis-dibromide(equationI). Electrophilesother thanbrominecan
cyclizationof substituted1,6-hepradieu clopentanes.
q CH":CHCH(CH,)"CH:CH, I
oLi
l
Dlchlorodi(cyclopentadienyl)zirconium-Butyltithium
l,',
S(CH3)3
co
CH.
,-A
* l-t'\--L--o
123
CprZrCl,
l) BuLi 2) CHIC-CCHr, -78e25"
cH"
\ /\/ CprZr.
I
I
)o\"",
CH. Ines to zirconabicycles,which on
2 eto
I oilirJc"H'rct,'-za'-zs"
"
rnvolvesreactionwith an alkylpnt eenerated from BuLi is formu-
CH,
X"'""'
C^H.P " " ) o \ . "I ,
L:-H -ZrCp.
CH,
CH.
3
tb
F r0 hve-carbon chains into (E,E)ntrered rings in 40-89% isolated
be used:oz, H*, and Secl2. The"Cp2zr" cyclizationfails for 1,S-hexadiene and 1,8-nonadiene' and cyclizationof 1,7-octadiene resultsmainly in cis-products.But ,----CH,Br
"Cp,Zri'Br,
trans_2 (e7:3)
f",
--\c
I
.'CHrBr
\-J
cis-2(ee:t)
cyclizationofsubstituted1,6-heptadienes consistently affordsrrans-disubstituted cyclopentanes.
ilorrde(l) by BuLi in thepresence . u hrchcanbe isolatedif desiredas leacrronof 2 with dichlorophenyl,-1.J .5-rerramethylphosphole). The r. strboles,bismoles,siloles,ger; rheuseof appropriateorganomenorescyclizationof 1,6-dienesto bcpradiene(l) on treatmentwith u-drbromide2. In contrast,useof 4 clrrpentadienyl),effects cyclizaDcrrophiles otherthanbrominecan
CHrBr
.CH"Br
,1'" Bu
.
\;
)i';!p" Ho-.... .l f<"' \
-_-_____)
75%
CH,
\'2""'cHr
HoJ
(translcis = l0:l)
OH
OH
"O CHr:CHCH(CH')rCH:CH,""F" dV"'cH3 ol-i
88Vo
. Att"' 9cH, 9Vo
rll 124
Dichloroketene
D. R, Swanson,andT. l E' Negishi,S. J. Holmes,J. M. Tour, J. A. Miller, F' E. Cederbaum, (1989). 3336 lfl, Soc., Am. Takahashi. 2 P. J. Faganand W. A. Nugent,Org. Syn.,submitted(1989)' 3 W. A. NugentandD. F. Taber,Am. Soc.,llf ' 6435(19E9)'
NiCl2(dppe)' Dichloro[(1,2-diphenylphosphino)ethane]nickel(ID' of cH3MgI with allylic reaction The dithioacetals.r Eliminative alkylotion o! (3 mole %) efrects gem' catalyst Ni-phosphine this presence of dithioacetals in the 1,3-diene' of a formation favors C2 dimethylation. A substituent at . At\^\
2
Nicl,(dpD€)
-s
&v'r3r.6r Ytits"' l- ) *- 2cH,MgI 85-s5%
+ff*C
*--/?'\'cH3
sJ
1".
rP.-F. Yang,Z.-I. Ni, andT.-Y. Llh, J. Org.,54, 2261(1989). I J.-P. Depr6s,B. Navarro,and A. E. Grcr
Dichloroketene. a-Chloro-a,p-enones.r The c,a-dichlorocyclobutanones(1), availableby reaction of dichloroketenewith alkenes,are convertedinto c-chloroenol acetates(2) by reactionwith lithium dimethylcuprateor BuLi in aceticanhydride.Whenheatedat about90o for 24 hours, 2 rearrangesto an a-chloroenone(3). This transformation can be extendedto bicyclic dichlorobutanones,and in this case results in a two*\ cr,c:c:o
.("'#.-r{l'""",,
1.3-Dlchloro-1,1,3r3-tetralsopropylf 120'l15 mm. SupPlier:Aldrich. Protection of tliols. The reactio rcctedderivatives,which are cleavedb1 derivativesare exceedinglyuseful for p
(,-Pr)15i\ I o (
oHoH
l l -
r
d
J--{oH
o
CHt
2
so-oe* |
fiqn altcne I a
1o"Y-- ''t, N
Ho:
t /
v
R
6
6
%
l
O
H
carbonhomologationofthe original cycloalkene.This processprovidesan efficient synthesisof muscone(5) from l-methylcyclotridecene(4).
(
2
l
V
3 (2, lNVo)
\
(i-Pr),si-o
t c t /\I cH,- -o
l
H
I fu -1 'l
(j-Pr)'Si-
fo !7c.H'-c
,H'.P
"q
OH
;
r
O
t l (t-Pt)Si-(
1,3-Dichloro-1,1,3,3-tetraisopropyldlsiloxane
125
D R.Swanson,andT. H! Pdrc
l) Clrcl:C:O 2) (CH3)rCuLi 3) 9s', H'
cHroH,cHrcooNa -..-..----.--.-. 81%
lMo
F). lH.MgI with allylic ole %) effectsgemine.
-.,'CH, cH.
5 I J.-P. DeprCs,B. Navarro,and A. E. Greene,Tetrahedron,45,2989 (1989).
by reIt. available oroenolacetates(2) ride.Whenheatedat This transformation rc resultsin a two-
1,3-Dichloro-1,1,3,3-tetrelsopropyldisiloxsne, {[(CH3)rCH]rSi(Cl)]rO(1), b. p. l20"l15 mm. Supplier:Aldrich. Protection of diols. The reaction of diols with I and pyridine provides protectedderivatives,which are cleavedby aqueousHF or R3NHF.rThesedisiloxane derivativesare exceedinglyuseful for preparationofmlo-inositol phosphates.2 Thus
(iPr)1Si\ I o oH
,CI
tl tl
-ococHs
2 !
-
OH OH
l--l on 1oH \
l\l HO-T
/
t'PY> 66%
d
,J-{o-s(i-nL
/ ft")I
(r-Pr)rSi-O-
2
H,o,ra\,no,H,
-
*o,rlPlro,",
| O-S(t-Pr),
OH I
OH
4
3
l c l
Ao , lfi)'7r )
To ?7"u*t'o-" H,9
(?")
HO-I
OH
providesan emcient s
#eo%
"l
(t-Pr),Si-O
(t-Pr)rSi-O
OH OH
OTCuH,-c
l--lo ( ?| t\lq "/ ) -
+
l--{ oH
1os /)
t\t HrO3P-
OH
OH 7
126
Dlchtorotris(triphenylphosphlne)ruthenium(II)
Dr*
reactionof 1 with ,ryo-inositol (2) forms the bisdisiloxane3, which hasbeenusedfor the first synthesisof the rnyo-inositoltetrakisphosphate 4. The reactionof I with I ,2O-cyclohexylidene-zyo-inositol(5) providesthe disiloxane6, which was usedfor a (7) and zyo-inositol 1,3,4-trisphosphate. synthesisofzyo-inositol 4-phosphate I Aldrichim. Acta,15,ll (1982). 2 Y. Watanabe, (1989). M. Mitani,T. Morita,andS. Ozaki,.I.C.S.Chem.Comm.,482
nium(IV). This oxidationcan be usedto et by displacementof the t-butyldioxy glrop Reactionof p-lactamswith peracaic r on-carbonresultsin p-acetoxylation.Tbes toxy-2-azetidinones. This reactioncen be r
rat^'
Dichlorotris(triphenylphosphine)ruthenium(Il), RuClzlP(CoHs)rlr. g,$-Enones.r In the presenceof this Ru(II) catalyst, primary alcohols and allylic acetatesreact to form enones.The reaction is best effectedat 150' in the presenceof carbonmonoxideunder pressure.
+ CHr:QllgffOec -ffi C6H5CH2OH
).
tl
Oxidation s, to nitrogen 2 In the presenceof this Ru catalyst, r-BuOOH oxidizesamidesto the a-(r-butyldioxy)amidesin high yield, probably via an oxoruthe-
fl
+ r-BuooH #a'
\N/ I
coocH3
OSiR,
cH, f_l
C.H,CC:CHCH, I CH, (ZlE = 85:15)
CH,
o4N-s
o
Ru(Il), K,CO,
-
o4N-H
Reactionsof l,$epipcrofidcs ad H in thepresenceofthis complexcatruodcrlo tionation, reactionswhich difier from thor Fe(II) salts.Although severalproductsrre r singleproducts.
(}oo","",,,
Sl-
Joo"", 66% (CHr)rSiCHlCH:CH,, TiCr., -?8. J
3m-
[\.pAcHrcH:cH,
I
coocH3
I ll \-\-
A.@at I lo^< I
| +r-BuooH 9l% N-coocHl
Ru(lI)
N-COOCH"
Isomerizttion of 2-ynols.' This Ru r phosphine is aneffectivecatalystfor isoc ingtoluene.
ooc(cHJ3 7l%
n-CuH,rC=CCHTOH
ricl., -78o JC6H,CH,M8CI,
,-C8H,?CHC:CCHTOH
-=+
(}
RIIII DI
n{rH,{
N-COOCH3 o cH2c6H5
H
l
Dlchlorotris(triphenylphosphine)ruthenium(II)
lilorane 3, whichhasbeenusedfor phare4. The reactionof I with 1,26, whichwasusedfor a drsrloxane p rnositoll,3,4-trisphosphate.
nium(IV). This oxidationcan be usedto effectalkylation at the c-position of amides by displacementof the t-butyldioxy group by a nucleophileinducedwith TiCl4. Reactionof p-lactamswith peraceticacid catalyzedby CI2Ru[P(C6H5)3]3 or Ruon-carbonresultsin p-acetoxylation.Thus 2-azetidinonesare convertedinto 4-acetoxy-2-azetidinones.This reactioncan be effectedwith high diastereoselectivity.
(1989). l.C S Chen.Comm.,482
cH, rAt'' '
), RuClrlP(CeHs)rlr. llr catalyst,primarY alcoholsand bn rs best effectedat 150' in the
_N
o2
- t'
AcooH.AcoNa. *oo' HOAC,Ru-C
86%
osiR3
o
rlL'
c"i"F
ll tl
C.H'CC:CHCHT I CH,
;+
(ZlE = 85:15\ of rhrs Ru catalyst, r-BuOOH oxip r reld, probably via an oxoruthe-
|
)
_'_
o^N-tt osi&
a cH:"t'
oAN-H
oAc
o^N-n
Reactionsofl,4-epiperoxides and Ru(II).3 1,4-Epiperoxides(endoperoxides) in the presenceofthis complexcanundergofragmentation,reduction,anddisproportionation, reactionswhich differ from thoseinducedby thermolysisor reactionwith Fe(II) salts.Although severalproductsare usually formed, fragmentationcanleadto singleproducts.
*qA
lcH, I
lr-li = (-H.. TiCl., -78'
3re*CO
}|:CH.
Isomcrization of 2-ynols.a This Ru complex in combinationwith a trialkylphosphineis an effectivecatalystfor isomerizationof 2-ynols to c,p-enals in refluxing toluene.
y--(fi .i WN-coocH3
ooc(cH3)3 -,o ricl.,-78" J."","",tr"t,
z-C.H,rC=CCHTOH*FL
=CCHTOH + n-CrH,rCHC N-COOCH" cH2c6H5
OH
n-CoH,r..\.CHO
^\ n-CTH,TCHCH:CHCHO + n-CrH,,-{.O,2 OH (44Vo)
(14?o)
Diethylaminosullur triff uorlde
(1991)' rT. Kondo,T. Mukai, and Y' Watanabe'J' Org'' 56' 487 and S' Akutagawa"{m' Kumobayashi' H' saito' T' ilwab;' i' 2 S.-I. Murahashi,T. Naota,
l. org.,s4,s2s2(ts's)' Noyori, N.Hamanaka,-andR. , iiL,llft,tli3[li,l,t]r. Kameya, (1989)' X. Lu, J.c's. chem'comm"890
.;. ;;il
-l
: C : NCcHrr (DCC' 1)' 1r3-Dicyclohexylcarbodiimide,C6H11N out in esterificationsare generally carried solvent-free esteritrcation. ricc which can poor in the case of angelateesters' refluxing CH2CI2. Yields can be i s o m e r i z e t o t i g l a t e " ' t " " i n s l o w e s t e r i f i c a t i o n s ' I n t h e c a s e4-pyrrolidinopyriofthekhellactonel cH2cl2 with Dcc and esterificationwith angelica.io in r"no^ing
Ho-f= Ho-/4[i
DCC' 4-PPY
O
CH, CH;
HOoCcH:CHCHI I cH. '15%
CH,
o I
o:C-
z
lcu:cu.- CH,
pru Fluoromethylhomocystcinc'2 A DAS of obtainedin 67% yield by reaction possiblch tl). Deprotectionof 2 is not group.
CH;
ratio' esterandthe tiglate esterin a I : I I dine (4-PPy)givesa mixture of the angelate However,intheabsenceofasolvent,eithertheangelateandtiglateesterscanbe preparedin high Yield' 29' 1239(1989)' andR' H' Rupp'Heterocycles' I S.Bal-Tembe, D. N. Bhedi,N' J' deSouza'
(DAST)' Diethylaminosulfur trifluoride pASf with the optically active natu^ralinositol n"ut of + F.r n'"urtlon OH of the eachformed by replacementof one quebrachitol(1) resultsi" *" pt"A*ts' ( -)' provides each (BBr3) on deprotection two axialhydroxylgroupsof 1. However, fluoro-myo-inositol(4)'
o t x ll --z r . o cHrs(cHr),9HCOOCH! NHCOCH. I
a,,o'DifluoroalkYl ethcrc, RCF2OR docsconvert thioestersinto a,cdiffuon o
li
n-crH,rcoR
srl
ttcHrocJJsL t t'
J' M' I A. P. Kozikowski,A' H' Fauqaod ' M. E. Houston,Jr. and J' F' Honck' J'C'' 'w. H. Bunnelle,B. R' McKinnis' rnd B'
DiethYl azodicarboxYlate'
ic-ccnron + RcH-c-cEt
rronof a 2-alkyne-1-ol(l) into an alky
Diethyl azodicarboxylate
.t- 'l99l). andS. Akutagawa,Am. fum.-bayashi, IR \o1ori, l. Org.,54,5292(1989).
HO . H ( D C C ,l ) , Dn! are generallycarried out in lc oi angelateesters,which can In rhe caseof the khellactone1 r rrh DCC and4-pyrrolidinopyri-
88%JBBr,cHzClz,2s'
OH
CH
(-) -4
cti
-cu3cH .
CH,
/
\
CH,
d rhetiglateesterin a l: I I ratio. lneelareand tiglateesterscan be
Naoromethylhomoclsteine.2 A protectedderivative (2) of methionine can be obtainedin 67% yield by reactionof DAST with the protected methioninesulfoxide (l)' Deprotectionof 2 is not possiblebecause of the instabilityof a fluoroamino group.
o
DAsr
ll
atfft% cH3S(cH,),cHcoocH3
FcH2s(cH2)2cHcoocH. t ' NHCOCH3
NHCOCH3 luec Heterocycles, 29,1239(1989).
; oprrcallyactive naturalinositol ncd b1 replacement of one of the tcctron(BBr3)eachprovides( -)-
H . ..:r
t
,
aro,-Difluoroalkyl ethers, RcF2oR,. DAST does not react with esters,but it doesconvertthioestersinto c,c-difluoroalkyl ethers.3
o
il ,-^--.,i-. i
n-crH,rdoR [P-cHioc6H4Ps], > n-crH,r8oR
+F
n-crH,rcFroR
I A. P. Kozikowski, A. H. Fauq,and J. M. Rusnak, Tetrahedron Letters,30,3365(19g9). : M. E. Houston, Jr. andJ. F. ionek, J.C.S.i;;;. C"mn.,76l (1989). rW. H. Bunnelle, B. R. McKinnis, andB.e N".ufun"n, J. Org.,SS,76g (1990). Diethyl azodicarboxylate. RC-CCH2OH + RCH:C:CHz.t This reactioncan be effectedby conver_ sionof a 2-alkyne-l-ol(r) into an alkynylhydrazine (2), which on treatmentwith an
r30
IXly-t
Dlhydridotetrekis(triphenylphosphine)ruthenium
si(cH3)3
si(cH3)3
Y\
y'si(c\)3
V"z"r, cH2NHNH2
cHroH
OH
3
l(n=0, I, y=R, RO,CJIs)
2
presumablyvia a diazene,with lossofNz to an allene(3). SIow oxidantrearranges, to air in oxidationis observedin air, but azo compoundssuchas DEAD are superior terms of rapidity and Yield. This reactioncan be usedto obtain optically active allenes,as shownby conversion of 4 into 5, with completeretentionof optical activity'
..'oH C6H5C-C-9-H *,*l H CH,
cuH'\ C:C:C \
/
"
Lette|s,30, 5747(1989). l A. G. Myers, N. S. Finney,and E. Y. Ktlo, Tetrahedron
o lt
oxide'
substitutedby an alkyl, alkoxy, or pbcoyl dehydrogenationalso showshigh sclccrivir 1,S-diolsto 6-valerolactones(equationtr)- | are formed, but 2b with the more bulky d
...'cH'
(S)-5 (75% ee)
(R)-4 (76%ee)
Difluoromethyldiphenylphosphine
JoH
(D (c{,)"
(c6Hr)rPCHF, (f).
Rq rllr
PH
/
O...(
cH,'-f--o" I \_
R(n)
n
C.H.CH:C1|C@1, ---=+
\ot
CH,
( quanl.
2a, R=Bzl b, R=Si(CHr)it-Bu
Aldol and Michael rc.rctions of fit* reactwith aldehydesor kaos anoacetate
i
r) BuLi
?l l
.r.uart
(C6H5)fHT
1' m'P'93-e4'
l,l-DiflaoroalkenesrGf., ll, 180). The anion(LDA) of this reagenteffects or ketonesby a Wittig-Hornertypereaction. of aldehydes difluoromethylenation l) LDA
,
zln'con',
cF"' ll
PCHO+C2H'OOCCHTCN +
to form o,P-unsaturatednitriles by an ddol' nitriles react with c,p-enonesor c,0-Gorlt
*rl*:
l M, L. Edwards,D. M. Stemerick,E. T. Jarvi, D. P. Matthews,and J. R. McCarthy' lztters, 31, 5571 (1990). Tetrahedron
15' I 35' Dihydrldotetrakls(triphenylphosphine)ruthenium' -Dehydrogenofion transfer ol 1,4- or |,S-diolsto lactones.This Ru-catalyzed of I is 2-position the when high selectivity with be effected can dehydroienation
CH. l
c.H.oocAcN
-
* cH':?coc.t1 NC 9H'
c,H5oocvc0 iH,
r
-
!O (\
:
'>L"
t>--r .$"*q:#'*r"t\, cricH:cHcocH'> rig,l, )o
z.si(c\)3
\CO,C,HJ
Dihydridotetrakis(triphenylphosphine)ruthenium
(D
V.o"'
a
OH
3
'>4 +
tig,l,
)o \---J
>e:r
l(n=0, I, y=R, RO,C#,) loss of N2 to an allene (3). Slow lr as DEAD are suPerior to air in ire allenes,as shown bY converIactrvity.
substitutedby an alkyl, alkoxy, or phenyl group becauseof steric effects.r This dehydrogenationalso showshigh selectivity in the conversionof 2,4-disubstituted 1,S-diolsto 8-valerolactones (equationII). In the caseof2a, both possiblelactones are formed, but 2b with the more bulky substituentis convertedonly into 3.2
...CH, C:C:C'
*ot
\ 'H tll)
It-5
'5%ee)
Joa Lztters,30,5747(1989).
/oH
Ru(II) c'H'cH:cHCocH,,
O...(
"-l--c'\_ \o"
cH. I
RO,-O
V
to
+
cH.ro,fo,, V.{o tso
S a o..ro
CH,
i \ / CH, -1
OR
cH,/\cH.
o
2a, R=Bzl
quant.
3 84Vo
b, R=Si(CHr)z-r-Bu
63:37
4
r):rcHF: (l). Aldol and Michael reactions of nitriles.3 Activated nitriles such as ethyl cyanoacetate react with aldehydesor ketonesin the presenceof this rutheniumcatalyst t. q,r_94. nn rLDA) of this reagenteffects r \Arrrig-Hornertype reaction.
i:
P \lanhews, and J. R. McCarthy,
a+p PCHo+C,H,ooccH,cN
CN to form o,p-unsaturatednitriles by an aldol+ypereaction.under the sameconditions nitrilesreactwith c,p-enonesor c,p-enalsto affordonly Michaeladducts.
QH, c,Hrooc'\cN
r . 1 5 .1 3 5 . transfer n.t. ThisRu-catalyzed of I is when 2-position the ir rry
,cooc2H5
p'cH:c1
* cH':4coc6H5
#
Nc 9H,
c,u,ooclcoc6H5 CH,
Nc 9H,
osl:rc,H,oocf
coc.H, CH,
132
2,2'-Dihydroxy-3,3''bis(triplery||
2,2'-Dihydroxy-1,1r-binrphthyl
+ cH'cH:c(cooc2H')' # c2H5ooccH2cN
t'T:\-t::*,",
theenolate(BuLi) with CH3I (equationI). Tl of (S)-naproxen(4) by methylationof tbc ( drolysis(LiOH).
CH,
,r* 1"",:""""o OH
OH
cooc2Hs
/,,\,cooc,Hs cooc2H5 I l-Cooc2Hs+ ...CH, e5:5 \fcH, c2Hsooc cN c2Hsooc cN
Michael addition followed by an aldol cyclizationcan be usedfor stereoselective synthesisof cyclohexanes. Isomerizltion of enynonesto trienones.a Cyclic enonesconjugatedwith a triple bond such as I isomerize to trcns, frans-trienones2 in the presenceof this rutheniumcatalyst.
o
o Ru(ll), PBu, 80' 85%
oa""
ery"T^e 3
' K. Fuji, M. Node, and F. Tanaka, Tctrahelm
(R)- anit (S)-2,2'-Dihyilroxy-1'l'-Hn;l ori's reagent,BINAL-H), 9, 169-170:ll Enantioselectivc reduction ol Lctm sistent results obtain when BINAL-H it binaphthol,LiAlH4, and ethanolin THF I that the expensivebinaphtholcan be reco The samegroupused(R)-(+)-BINAL(3) in >95* a (c-alkoxyallyl)stannanes
CH,
cH2cH2cH3 l
R-4fSnBu, tl
2
g!
o
rY. Ishii, K. Osakada, T. Ikariya,M. Saburi,and S. Yoshikawa,J.Org.' 51' 2034(1986). 2 M. Saburi,Y. Ishii, N. Kaji, T. Aoi, I. Sasaki,S. Yoshikawa,andY. Uchida,Chem.Letters, 563 (1989). 3 T. Naota,H. Taki, M. Mizuno,and S.-I. Murahashi, Am. Soc.,ll1,5954 (1989). a X. Lu, C. Guo, and D. Ma, Synleu,357(1990\.
(BINOL). 2,2'-Dihydroxy-1,l'-binaphthyl Diastereosclcctive a,-alkylation ol arylacetic aci.ds.r The binaphthyl ester (l) phenylacetic acid undergoes highly diastereoselective methylation on treatment of of
,
obtainedin somewhatlower enantiosclct (2S,3R)-(+ )-4-dimethylamino1,2{iphcr t. 184)in combinationwith LiAllIr. 'J. A. Marshall, aodB. g. G. S. Welmaker,
2,2'-Dihydroxy-3,3'-bis(triphenylsllyl) I, 1 4 , 4 6 - 4 7 ; 1 5 ,1 3 6 - 1 3 7 .
c^H.
t"-
/ t
t
cH" l
\oAr("",),
2 (96:4\
+ (Rt-l I
2,2'-Dihydroxy-3,3'-bis(triphenylsilyl)1,1,-binaphthyl-Trimethylaluminum
)
coocF5 c H.ooc l l \c'l\*cooc,Hs
theenolate(BuLi)with cH3I (equation I). Thisalkylationcanbeusedfor preparation (4) by methylation of (S)-naproxen of the (S)-binaphthyl ester(3) followedby hydrolysis(LiOH).
I CH,
s I
'
CH-:CHCHO
o
H.
t /,.4\<,COOCrH5
H. s5.5
|
l-cooc,Hs
...\ c2H5ooc cN
'cH,
[on can be usedfor stereoselective !clrc enonesconjugatedwith a tri'icnr)nes2 in the presenceof this
o
'.-./\/\/\C]H,
q $2Vo ee\
3
' K. Fuji, M. Node, and F. Tanaka,Tetrahedron Lctters,3l, 6553 (1990). (R)- and (S)-2,2'-Dihydroxy-1,1'-binaphthyt-Lithium
o
l'orhrkawa,J. Org.,5f, 2034(19E6). Ar\a* a. andY. Uchida,Chem.ktters, i . { - r S o c . ,l l l , 5 9 5 4 ( 1 9 8 9 ) .
2
\_.r\z
(nl-l'-2a",R -r,l
O
-...SnBu, I
H
>952oee 1S)-3,
obtainedin somewhatlower enantioselectivityby use of the commerciallyavailable (2S,3R)-(+)-4-dimethylamino-1,2-diphenyl-3-methyl-2-butanol (Chiraldo,5,231: t, 184)in combinationwith LiAlHa. rJ. A. Marshall, C. S. Welmaker, andB.
i acids.t The binaphthylester(l) llecrrre methylationon treatmentof
aluminum hydride. (Noy_
ori's reagent,BINAL-H), 9,169-170;10, 148-149;12, 190-19l). Enantioselectivereduction of ketones. Marshall et al.t rcpoft that more consistentresultsobtain when BINAL-H is preparedby refluxing a mixture of the binaphthol,LiAlH4, and ethanolin THF for a short time beforeuse. They also note that the expensivebinaphtholcan be recoveredand reused. The samegroupused(R)-(+)-BINAL-H for reductionof acylstannanes (2) to (S)(c-alkoxyallyl)stannanes (3) in >95% ee. The epimeric(R)-stannanes (3) can be R-Z\fSnBu, i
t
Z \./
133
W. Gtng,Am.Soc.,ll3, 64:-(lggl).
2,2'-Dihydroxy-3,3'-bis(triphenylsilyl)1,1,-binaphthyl-Trimethylaluminum (l), 14, 46-47;15, 136-137.
\ C"H.
oH f",
o)i".", o 2 (96:4\
c.H.
t--
( fi",
\o4r,1"",y,
+ (R)-f cH' cl"-2oo> A 86% H,c !-rt,"",,, (809o ee)
Diisobutylaluminum hydride
Dllsopropyl Trrtrrrtc
cH'
9H'
si(cH')',*,.,, ^,r4-(t6si(cH3)3 'rsqa
",.f)H' c\ \_4..=.o
\A"",o (97:3)
(EF {Ctd
menthylp-toluenesulfinateprovides thc cbi with DIBAH providesthe equatorialp-hydro with DIBAH and ZnCl2 provides mainly t Hydrolysisof the ketal groupand sulfoxi& with silica gel and HzSOrto provide(RF er yield in the last stepcan be improved by pt
Claisen rearrangement.r Claisen rearrangementof simple allyl vinyl ethers efiectedwith (R)- and (S)-1 showslow enantioselectivity,but the rearrangementof allyl vinylsilyl ethersresultsin acylsilanesin high opticalyield (80-90%).
I M. CarmenCarrefro, M. J. L. Garcia-Ruano. Letters.31, 6653(1990). Tetrahedron
I K. Maruoka, (1990\. H. Banno,andH. Yamamoto, Am.Soc.,112,7191
Ipc2BH. Diisopinocampheylborane, syn-Aldols. I ,4-Hydroborationof an (l (Z)-vinyloxyborane (2), which reactswith r high enantiomericexcess.
Diiodosilane, SiH2I2. Acyl iodidcs.r This reagentconvertsacyl chloridesinto acyl iodidesat 25'. In combinationwith iodine (1: l) it also convertscarboxylicacids,esters,and anhydridesinto acyl iodidesin generallyhigh yield. This reactionin combinationwith an alcohol is a useful methodfor transesterificationof hinderedalcohols.
o ll CoHr'\'4611,
I E. KeinanandM. Sahai,J. Org.,55,3922(1990).
IpcrBH, THF.
20" ---------------cu1 !6r
I
Diisobutylaluminum hydride. Diastercoselectivereduction of chiral p-keto su$oxidest(13, I 15-l 16). This reaction, which can be controlled to provide either diastereomerof a chiral phydroxysulfoxide,hasbeenusedto obtain(R)- or (S)-4-hydroxy-2-cyclohexenones from the monoketal(2) of 1,4-cyclohexanedione. Sulfinylationof 2 with (S)-(-)-
1
G. P. Boldrini,F. Mancini,E. Tagliavini.C Chem.Comm.,1680(1990).
Diisopropyl Tartarate
o ,,\
t
X LJ
l
l) iPrilMSBr 2) (S)-Tol-SO,Mcnrhvt
--j_-_J,
'to%
&$c'H'o;";",X Hic'H'
"5
,,
(s,s)-4
3
,*Jil:i"
"X l l l
Yo
(R)-5 (957oee)
e-
siq, r|.so. 4t%
"K t
o
tl
i".., l C,H,
"X. LJ
(R,S)-4
r<
o*J'o,, ",.o
X"
V o
(S)-5(957oee)
(E)-7-[Cyclobcryh
(C6Hr rO)(CHj)rSiV^/,
I
I Preparation. Optically active anti-1,2-diols.2 srll.-l, rousy-alkoxyallylmetalreagentsto aldehy aldehydesto form anti-|,2-diol monoethcn contrast,the reactionof I with somechird r
."'J.:fi]:'-""(cH.){r
-#(l) CHTCHO
CH,\,A :
OH (69t e
r35
Dlisopropyl Trrtsr&te (EF1-[Cyclohexyloxy)dimethylsilyl]allylboronete
^v/--Y.si(cHr)3 tl r\ -.+--
-CH:
q-:-l)
menthylp-toluenesulfinateprovides the chiral p-keto sulfoxide 3. Reductionof 3 with DIBAH providesthe equatorialp-hydroxysulfoxide(S'S)-4'whereasreduction with DIBAH and ZnCl2providesmainly the axial p-hydroxy sulfoxide(R'S-4). Hydrolysisof the ketal group and sulfoxide elimination is affectedin one operation with silica gel and H2SO4to provide(R)- and (S)-5,both in high opticalyield. The yield in the last stepcan be improvedby prior acetylationor benzylation.
srmpleallyl vinYl ethers of , but the rearrangement ( 8 0 9 0 % ) . r r e l d I
I M. CarmenCarrefro, M. Garrido,M. PilarRuiz,andG. Solladid' J. L. Garcia-Ruano, Letters,31, 6653(1990). Tetrahedron
19:, :990).
Ipc2BH. Diisopinocampheylborane' of an (E)-u,p-enone(l) with Ipc2BHprovidesa syn-Aldols. 1,4-Hydroboration (2), which reactswith an aldehydeto providea syn-aldol(3) in (Z)-vinyloxyborane high enantiomericexcess.
nro acvliodidesat 25o.In c acrds.esters,and anhybn rn combinationwith an rcd alcohols.
?
rpc,BH..rHF. -*
CuHr"\-"\CH,
tBIPc,
c"H,cyo
C.HTSCH,-;*--
?"
C"Ur]
2
|
? CH, -cuH,
3 (X)Vaee)
t c s ' ( 1 3 ,l l 5 - 1 1 6 ) . T h i s tsrereomerof a chiral pb1drory-2-cYclohexenones l l a t r o no f 2 w i t h ( S ) - ( - ) -
rG. P. Boldrini,F. Mancini,E. Tagliavini,C. Trombini,and A. Umani-Ronchi, /.C.S. Chem.Comm.,1680(1990).
Diisopropyl Tartarate (E)-f-lCyclohexyloxy)dimethylsily[allylboronate,
o
xli"'"' ,
'x
s . s-)4 I
,'+ | sio,,urso.
T
o (C6HI rO) (CH3)rSi--72:--,
B.
Preparation.r Optically active anti-1,2-diols.2 syn-1,2-Diolsare availableby additionof variousy-alkoxyallylmetalreagentsto aldehydes.In contrast,this reagentreactswith aldehydes to form anti-|,2-diol monoethers,which can be oxidizedto the diol. In canshowhigh enantioselectivcontrast,the reactionof I with somechiral aldehydes .""'.[fil:t-rr.
-+#_+ (l) CHTCHO
(CH.)2siocoH, H,o,. KF
C".--,,I.-.C", --!#OH (69Vo ee)
S - 5 t 9 5 7 oe e )
(R,R)-r
o
oH
cH3-\,,&cH, OH
t.
1,2;5,6-Di-O-isopropylidene-c-o-glucofuranose
Enantioselectiveallylation.t Tb ether affordsa chiral orangeallyltitrri aldehydeat -78'to affordhomoally andwith releaseof I and a titanate6r Reactionof 3 with aryl ketonesrequire iry is only about50%. Enantioselective aklol reactiot; l butyl acetatereactswith an aldehy& it in90-96% ee. ity, owing to double or matchedasymmetricreactions.Thus reactionsof the aldehyde2 with (R,R)-l providesthe majorproductasan 84: l6 mixture,but the reaction with (S,S)-l resultsin an 89: ll mixture (matchedpair). 'W. R. Roush.P. T. Grover,andX. Lin, Tetahedron Letters,3f,7563(1990). 2W. R. Roush,K. Ando,D. B. Powers, Am.Soc., andA. D. Palkowitz, R. L. Halterman, 112,6339(1990).
oLi I
CHr:g-6"(CHr)r 4
+ CPfi
lr2;5,6-Di-O-isopropylidene-c-D-glucofuranose(Diacetone-o-glucose,1).
CH, .,,O-l
cn, ofol \on
>threo-P-Ily droxy -a-anino aE rynthesisof theseuncommonaminoc
/
\ b r ol l
6-t-cs'
9H,
CH,
(rr)
m.p.105-108' I (R*OH),a"-18.5",
(z-li-cH. |
cHr-ii-N\,-m Chiral Ti-carbohydratecomplex. Reactionof CpTiCl3 with 1 and N(C2H5)3 providesa yellow, crystallinesolid (2) that can be storedin the absenceof air and which is shownby X-ray analysisto consistof CpTiCl(OR*)2. (l) 2 + CHr:g11"trMgCl
CH,
------+ CpTi(OR*)'CHTCH:CH, 3 I Y
RcHo.-?8"
OH RA-zCHr:CHz 86-94Vo ee
+ R*OH + CPTi(OH'O)" I
M. Riediker and R. O. Duthalcr, ,lrg Hafner,U. Piantini,G. Rihs, and A. 1
1,2;5,6-Di-O-isopropylidene-c-o-glucofuranose
SICH,),OC^H,, t (84: 16) *r)'----:H, !
: OH rl
SrrCH,),OC.H,, ( 8 9 :l l )
- \ -"// - c H "
\/' I OH
of the alderea.tlons.Thusreactions tr a. an 84: 16mixture,but the reaction t c h e dp a i r ) . ?drtn lztters,3l,7563(1990). Am.Soc', iltc:man.andA. D. Palkowitz,
137
Enantioselectiveallylation.r The reactionof 2 with allylmagnesiumchloride in ether affords a chiral orangeallyltitanium complex 3. This complex reactswith an aldehydeat -78o to affordhomoallylalcoholsin 55-88% yield and in 86-94% ee andwith releaseof I and a titanatethat can be reconvertedto CpTiCl3 (equationI). Reactionof 3 with aryl ketonesrequiresa temperatureof 0o, andthe enantioselectivity is only about50%. Enantioselectivealdol reaction; p-hydroxy esters.2 The lithium enolate4 ofrbutyl acetatereactswith an aldehydein the presenceof2 to form p-hydroxy esters6 in90-96% ee. OTi(CP)(OR*),
OLi
I
cHr:g-o"(cHr), 4
CHz:c-oc(cH3)3 + cpTi(oR*)rcl ------+ 2 5 ,o-rr*J"""o,-rr" OH
1)' losr I Diacetone-D-glucose,
R,^\zCOOC(CH3)3 6 (9O-96Voee\ a-threo-p-Ilydroxy-a-amino esters.3 An example of use of the complex 2 for synthesisof these uncommon amino esters is shown in equation (II).
J o 6=--_CH,
cH" "
CH.
/- $r-cu,
|
(ID
13 .rti 108"
\
of CpTiCl(OR*)2.
I
CH,
OH
l
CH,-ii-N-*-COOC2H, Iron tri CpTiCl3 with I and N(C2Hs)3 en re stored in the absenceof air and
I)LDA
113".""o
cH,ncooc2Hj NH, I
53? ls*.o
overur
I
CrTrrOR*)rCHrCH:CHt
OH
3 | *."o. -rr' 0
CH,A.1cooc2H5 NHSoc (298Vode\
.CH.:CH, '9lji:e
+ R*OH + CPTi(OH,O)" I
I M. Riedikerand R. O. Duthaler,Angew.Chem.Int. Ed.,2t, 494(1989);M. Riediker'A' Hafner, tJ. Piantini, G. Rihs, andA. Togni, ibid. , 2E, 499 (1989).
f3t
IJ
3,3-Dimethoxy-2-trimethylsilylmethyl-l-propene
2 R. O. Duthaler,P. Herold, W. Lottenbach,K. Oertle, and M. Riediker, ibid.,28' 495 (1989). 3 G. Bold. R. O. Duthaler,and M. Riediker,ibid.,28, 497 (1989).
(cH3o)'cHco(
Annelation-ring clcavagc.t A tlif lanegroupcanbe usedfor annulatiooo carbocycles(equationI).2 The rerctic rhat undergoesintramolecularcyclizr
1-butene' 4,&Dimethoxy-2-trimethylsilyhnethylCH,
il-
(cH3o)rcHCH2CCH2Si(CH3 )3 Preparation.r Spirocycles.2In the presenceoftrimethylsilyl triffate,the silyl enol etherofan aldehydereactsselectivelywith the acetalfunction of I to form an intermediatewith a carbonyl group that can then react with the initially inert allylsilane Sroupof I to form a spirocyclic system.This methodologypermits synthesisof spirocyclic sys-
s ,1.-,OSi(CHr\
tt)l--ll
t
+
cH.o-
- |g* OAf*','"n"'''o"' lff"l HO
(CH,),C:CHOSi(CHr), + I
-flk
This annelationcan be used as r r members,which are difficult to obreiaI lane-acetalI with a silylated encdi<
CH, CH,
ocH3 temsof various sizesas well as six-memberedrings containinga quaternarycenter. is also availableand The homologof 1, 5,5-dimethoxy-2-trimethylsilyl-l-pentene, providesa route to seven-membered rings, generallyin yields lower than those observedwith |' 'T. V. Lee,J. A. Channon, andH. Yeoh,Tetrahedron, C. Cregg,J. R. Porter,F. S. Roden, 45,5877(1989). 2 T. V. LeeandC. Cregg,Synlett,3lT(1990).
l-propene, 3,3-Dimethoxy-2-trimethylsilylmethyl(ocH3)2(l). (15,72): Preparation
(CH3)35iCH2C(:CHdCH-
R,sio T \
or)
ll I
RrSiO/-;v
ll* r
3,3-Dimethoxy-2-trimethylsilylmethyl-l-propene
[c. and M. Riediker,ibid.,28, 495
f39
l) Cecll
(CH3O)TCHCOOCH, + (CHr)rSiCHrMgCt 3#+
t
{9- rl9E9).
Annel.ation-ing cleavage.r A bifunctionalreagentwith an acetalandan allylsilanegroupcanbe usedfor annulationof silyl enol ethersto six- andseven-membered carbocycles(equationI).2 The reactioninvolvesconjugateadditionto give an adduct that undergoesintramolecularcyclization.
)
iCH,t.
s(cH3)3 rl rrrflate,the silyl enoletherofan with toi I to form an intermediate rlly rnertallylsilanegroupof I to mrrs svnthesisof spirocyclicsys-
/,-V,OSi(CH3)j
o)l ll
.
\_24", I CH
cH3o/ -ocH,
*ldxl
I -5070 ricl. |
t '
..",i
HoY/-\YcH'
OH
-.*- a-\ ) It \ -I / tl Y I
!z
ocH3
This annelationcan be usedas a route to carbocyclescontainingsevento nine members,whicharedifficultto obtainby usualmethods.Thusreactionof the allylsilane-acetalI with a silylatedenediolprovides a bicyclic l,2-diol, known to be
ocH3 R3SiO
gs containinga quaternarycenter. is alsoavailableand 7l-l-pentene, crallr in yields lower than those
cH3o TMSOTf + | -;*---+
(D RrSiO
siR3
siR3 str"I oueratlJricl
andH. Yeoh,Tetrahedron, S Roden,
cHso\
F.
(CH3)3SiCH2C(:CHJCH-
<-
PXOAC). 98%
oH H
"".1ffi \,-t_!/ OHH
l4{l
Dirnethylamlnodlmethylchlorosilane
routeto a oxidizedto a ring-expandeddiketone.use of this annelation/ringcleavage alsoused was method The II. ring systemis formulatedin equation seven-membered rings.3 to prepareeight- and nine-membered I T. V. Lee, J. Channon,C. Cregg,J. R. Porter,F. S. Roden,andH. Yeoh, Tetrahedron,45, 5877(1989). 2 T. V. Lee. R. J. Boucher,J. R' Porter,and C' J' M' Rockell,ibid., 45, 5887(1989). 3 T. V. Lee. J. R. Porter,and F. S' Roden,ibid" 47' 1 3 90 9 9 1 ) .
|2, |96-|97). 1,3-Dimethoxy.l.(trimethy|si|yloxy)butadiene (Brassard'sdiene, stereoselecobtained (2) be can lactones These ur}-IJnsaturated lactones.r aldehyde' c-amino N-protected an with of I reaction tively by a Lewis-acidcatalyzed (3)' esters carboxylic 4-amino-3-hydroxy active Ozonolysisof 2 providesoptically groupas The steieochemistryofthe cyclizationcanbe controlledby the N-protecting
o
?"r, /torr1" l cHroAcH2
tl
,:li?ll,;]' ,1, cH3v,cHo t"'1;];?t) + ? 1""0,
I
ocH,nJzo
RC-CLi -5
nc:cs(Cl
' G. Stork and P. F. Keitz, Tetrahedra It
( - )-3-exo-(Dimethylamino)isoborr
Alkylation with RzZn.t After P this chiral, cyclic p-dimethylaminod( lectivealkylation of carbonyl compoo % of ( -) 1, diethYlzincand CclllCll
C.HTCHO+(CJl.
syn-2
-**Jo, OH "t,--,{-coocHj
I
NHCbz 3 l+
cH3 y cHo (ctHr)ilcl - )\ syn-2+ anti-Z u.,n' | (l:>9) NBzl,
Sincethe original report, abour 12 rhisreaction,but this reagentof Noyc mosteffective.In addition, both cen c tioselectivityover that of the catdysrrnvolvesa dinuclearZn complexsucl
*',
q cH.
a shown. These products are useful precursorsto natural products containing $amino alcohol grouP. I M. M. Midland Am' Soc.,f ll' 4368(1989)' andM. M. Afonso,
(1)' Dlmethylaminodimethylchlorosilane, (CH3)2NSi(CH3)2Cl reaction in Alk-enytor alkynyl silyl ethers. Thesecan be prepared high yield by with an product of the of an alkenyl- or alkynyllithium with l, followed by reaction alcohol.
\-ray analysis.At the presenttim. ( rlkyl groupscan be used for this dl mdergo alkeneelimination. S.Suga,K. Kawai,rndI M. Kitamura, S. Okada,S. Suga,andR. NoYori.ili Int.Ed.,30,49(l99l) Chem. .1ngew.
( - )-3-e.to-(Dlmethylemino)isoborneol
ng cleavagerouteto a methodwasalsoused
RC-CLi
'
9H, ' RC:CS(CH3)'N(CH't #h
RC:CSiOR'
overall
cH.
\ eoh.Tetrahedron,45, t . . s . 5 8 8 7( 1 9 8 9 ) .
liene. 12, 196-197). obtainedstereoselectcrl q-aminoaldehYde. carboxylicesters(3). r \-protectinggrouPas
o \ }
*",
on"-' *olro
I G. Storkand P. F. Keitz, Tetrahedron ktters,30' 6981 (1989).
./4.,4(cH3), (-)-3-ero-(Dimethylamino)isoborneot, (r[o"
(1).
C", Alkylation wilh R2Zn.r After pursuing severalclues, Noyori er a/. found that alcohol(1) is an effectivecatalystfor enantiosethis chiral, cyclic p-dimethylamino lective alkylation of carbonyl compoundswith R2Zn.Thus in the presenceof 2 mole % of (-) 1, diethylzincand CoHsCHOreactto form the (S)-alcohol(2) in98Vo ee'
"#X1.". +(c,H,)&n"* cuH,cHo
a
(S)-2 (987oee)
r-l
It '
t I
-_ coocH3 bz _l
ut-2
) roductscontaininga P-
havebeenreportedto catalyze Sincetheoriginalreport,about12 otherreagents of Noyori(1) andthatof Oguni(15,268)seemto bethe thisreaction,butthisreagent of enananincrease mosteffective.In addition,bothcaneffectchiralamplification, thatthealkyltransferreaction overthatof thecatalyst.Noyorisuggests tioselectivity by involvesa dinuclearZn complexsuchas3, whosestructurehasbeenestablished cH.-\
cH. ,/
rR
r,,M''.
\-l{'";.-{ :,, zn | +l cH,
*z-"t*{,// / \ CH, CH. 3
I
tlr. in hrgh yield by reaction n of the product with an
containingprimary X-ray analysis.At the presenttime, only dialkylzinccompounds and alkyl groupscan be usedfor this alkylationbecausesecondary tertiary groups undergoalkeneelimination. I M. Kitamura, S. Suga,K. Kawai,andR. Noyori,Am.9oc.,108,6071(1986XM. Kitamura, S. Okada,S. Suga,andR. Noyori,ibid.,lll, a028(1989);R. NoyoriandM. Kitamura, Int.Ed.,30,49(1991). Angew. Chem.
142
Dimethyldioxirene
(p-Dimethylaminophenyl)diphenylphosphine, (l). p-(CH)2NC6H4P(C6H5)2 This phosphinehasbeenrecommendedas an alternativeto triphenylphosphinein Wittigt and Mitsunobu2reactions, becausethe correspondingphosphineoxide is readily removedby an acid wash, facilitating work-up of thesereactions. I S. TrippetandD. M. Walker,J. Chem.Soc.,2130(1961). 2 M. vonItzsteinandM. Mocerino,Syn.Comm.,20,2049 (1990\. 4-Dimethylaminopyridine (DMAP). Dealkoxycarbonylation.r Enolizablep-keto estersundergothis reactionin 6070% yield when refluxedin slightly aqueoustoluene(90') containingI equiv. of DMAP andbufferedto pH 5-7. DABCO, N,N-dimethylaniline, andpyridinearenot effective.
more efficient than alkaline hydrogenpcror -enoates.a Epoxidationof glycals can be effectcdrr dioxiranein acetoneat 0o. In the caseof m epoxideis formed almost exclusively. Thcr hols with clean inversion to form p-glycoei
ao* * ?x""'
6")
o"cH,
Rf\--l
(cH'l F.
R=Bzl
coocHs DMAP, C6HrCHl' H,O.90' ---------------)
RO-
lOEo
Bzl
I
Acetoacetylationwith DMAP.z Alcohols (even ,ert-ones)undergoacetoacetylation whentreatedwith diketenein the presenceof DMAP (55-100%yield). The reactiongenerallyoccurs at room temperature.
ROH+
fl ? -4o'"j-Tl' --*ROCCH2CCH3 | I
Epoxidation of exocyclic cnol lulou. tions, are not useful for this epoxidationbc tion. Dimethyldioxiraneeffectsepoxidetir %-96% yield in 2-3.5 hours.It is dso ef,c lactonessuchas 3.
55_100%
>_o H^C'
I D. F. Taber,J. C. Amedio,Jr., andF. Gulino,J. Org.,54,3474 (1989). 2 A. Nudelman,R. Kelner, N. Broida, and H. E. Gottlieb, Synthesis,387 (1989).
_ A\o *.",x 'o cH,'
H,c{o
I,R = H,CHr Dimethyldioxirane. Oxidation. Benzylic secondary amines are oxidized in high yield by dimethyldioxirane to nitrones,r probably via hydroxylamines.2
3
-------+ e6s:iR AICH,NHR------+ l-ercH,Nn-'l
t
L
t
oHl
t
cH ah OAO\'-;;:X
o-
l
Epoxidesof enol silyl ethersor acetatescan be obtainedin high yield by reactions with dimethyldioxiraneat low temperatures.3Dimethyldioxiraneis generally
Reviews.T'tThe chemistry of diorin beenreviewedby two active investigaton
J. Org..35'2! R. W. MurrayandM. Singh, ' M. D. Wittman,R. L. Halcomb, andS. J. D
Dimethyldioxirane
(l). p-,CH,hNC6lI4P(C6Hs)2 in rnative to triphenylphosphine ilre phosphine oxide is c(rrresponding reactions. of these rr[-up l19^lr.
Itlus r 1990).
more efficient than alkaline hydrogenperoxide for epoxidationof c,p-enonesand -enoates,a Epoxidationof glycals can be effectedin almost quantitativeyield by dimethyldioxiranein acetoneat 0o. In the caseofnonparticipatingprotectinggroups,the oepoxideis formedalmostexclusively.Theseo-1,2-anhydrosugarsreactwith alcohols with cleaninversionto form p-glycosides.s
I
I elrersundergothis reactionin 60luene(90o)containingI equiv.of rmerhrlaniline,andpyridinearenot
143
-roR
-/oR I
(cHr)rc:o'o'> * ?Y""' eeqo 6"\ o"cH, _6\-{l
6") Rb\L/
O
R=Bzl
@19= 20:t)
'"'', **,.Jli ilbo"'
o " / \
*o5C1--or Bzl
r cn rert-ones)undergoacetoacetyyield).The I oi DMAP (55-l00%o
' l lo l o l *
ROCCHzCCHT
p9\------\-'--\,oCH, Epoxidation of exocyclicenol hctones.6 Peracids,evenunderbufferedconditions,are not usefulfor this epoxidationbecauseof rearrangement and decomposition. Dimethyldioxirane (l) in effectsepoxidationof y-methylene-y-butyrolactones 94-96Voyield in 2-3.5 hours.It is also effectivefor epoxidationof endocyclicenol lactonessuchas 3.
T s{. 3474(1989). ht 387 (1989). tl:c^ -SlntAesis,
H,c4o \o
+
CH,CI,, ' ' (CH,),C:O cH.. -2od' " Y.o l -.-.------------
cH,"o
-s6%
R I
/ d'o
\ Ao
o
l,R=H,CH:
orrJrzedin highyieldby dimethyline- : + ..---- \CH-NR
o tre ,rbrainedin high yield by reac' is generally : Drmethyldioxirane
"nO.I,xl-,*"r)O Reviews.T,tThe chemistryof dioxiranes,particularlyof dimethyloxirane, has beenreviewedby two activeinvestigatorsin this field. R. W. MurrayandM. Singh, J. Or9.,55,2954(1990). : M. D. Wittman,R. L. Halcomb, andS. J. Danishefsky, ibid., 55, l98l (1990).
lU
Dimethylgelliumchloride; dimethylgalliumtriflate
3 W. Adam, L. Hadjiarapoglou, X. Wang, Tetrahedron lptters,30, 6497(1989). a W. Adam, L. Hadjiarapoglou, and B. Nestler,ibid.,3l,331 (1990). s R. L. HalcombandS. J. Danishefsky, Am. Soc.,111,6661(1989). 6 W. Adam, L. Hadjiarapoglou,V. Jiiger, andB. Seidel, TetrahedronLetters,30,4223 (1989). 7W. Adam,R. Curci,andJ. O. Edwards,Acc. Chem.Res.22,205(1989). ER. W. Murray,Chem.Rev.t9, 1187(1989).
Dimethylformamide. Carboxamidation of RLi or RMgX.r This reaction can be effected by reaction of RLi (or RMgX) with DMF to give a hemiaminal a followed by an Oppenauer oxidation. The second step requires the presence of a magnesium alkoxide such as magnesium 2-ethoxyethoxide I, Mg(OCH2CH2OC2H5)2,either as a catalyst for the oxidation or for stabilization of a, possibly as a mixed cluster.
frF RLi+ (cH,),NCHo , l*Xott I LH' 'N(CHr),J
I, l-Dimethylhydrazine. 4-Alkyl-1,3-cycloalkuedioncs.t Tt bexane-or cyclopentane-1,3-diones by o
o
o
t7, 126-130),the dianionsof which ere d dkylation of the lithium enolatesof cycl A. S. DemirandD. Enders.TetrahedraIt
o
tl
a + (CuHr)rC:o
ff
;l;'
niNlcH,;, + (CuHr)rCHoH
Dinethyl methylphosphonate, CH!F(O Reanan gement of 2,2- dialLyr- I J-<, rrntes with the anion (LDA) of this phoq in 60-93% yield. Addi l
Formylation.z Dimethylformamide and trifluoromethanesulfonicanhydride form an iminium salt (l) that is more reactivethan that formed from dimethylformamide and POCI3,which is generallyused for formylation (Vilsmeier reagent).Alreacor phenanthrene, thoughthe Vilsmeierreagentdoesnot reactwith naphthalene in 507o yield and in tions with I results in l-naphthalenacarbaldehyde 3-phenanthrenecarbaldehyde in 25% yield. (CHr)ril:CHOTf OTf- (1) r C . G . S c r e t t a sn dB . R . S t e e l e J ., O r g . , 5 3 , 5 1 5(l1 9 8 8 ) . 2 A. G. Martinez, R. M. Alvarez,J. O. Barcina,S. de la MoyaCerero,E. T. Vilar, A. G. Fraile,M. Hanack, andL. R. Subramanian, J.C.S.Chem. Comm.,l57l(1990).
Dimethylgallium chloride; dimethylgallium triflate. Glycosi.dationr Thesegallium compoundsserveas efficientactivatorsfor glycosidationof glycopyranosylfluoridesin CH2CI2or toluenewith moderatep-selectivity. 'S. Kobayashi, (1990). K. Koide,andM. Ohno,Tetrahedron Letters,31,2435
:rarrangementis believed to involve e n Eorocr intramolecularreaction. l Yamamoto andT. Furuta,J. Org., 55.!
145
Dimethyl methylphosphonste
1.10. 6197(1989). I t990). (1919). ed,on k tters, 30, 4223(1989). l :05 (1989).
1,1-Dimethylhydrazine. 4-Alkyl-lr3-cycloalkanediones.r Theseproducts can be obtainedfrom cycloby conversionto the monodimethylhydrazones hexane-or cyclopentane-1,3-diones l) 2BuLi, THF,
""'*\. '8ffi''i'3:, 6t%
CH, can be effectedbY reaction followed by an OPPenauer ugnesiumalkoxidesuchas , errheras a catalYstfor the cluster. Ot-r N.C}{ I
melhanesulfonicanhYdride brmed from dimethYlformaion rVilsmeierreagent).Alreacrleneor phenanthrene, ? rn 50% Yield and in
I
I
crr,\Ao
CH,
(7,126-130),thedianionsofwhicharealkylatedatCain 56-65%yield.Incontrast, provide 6-alkyl derivatives. 1,3-diones alkylationof the lithium enolatesof cyclic I A. S. DemirandD. Enders,Tetrahedron Letters,30,1705(1989).
l
rC.H.),CHOH
CH.
O
o
tl
3,117; 11,203. Dimethyl methylphosphonate,CH3P(OCHJ2, Rearrangementof Zr2-dialkyl-lr3-cyclohexaneiliones.t Reactionof thesesubto 3-alkylstrateswith the anion (LDA) of this phosphonateresultsin rearrangement in 60-93% yield. Additionof ClSi(CH:)3improvesthe yield. The 2-cyclohexenones
9ll A<:"'+ I \
l r ( o
o cls(cH,)! ll 4 r-icH,ltoc",b -
CHt
s I
I
I I
I
o r i C e r e r oE, . T . V i l a r , A . G . C , . q n ' r .l .5 ? l ( 1 9 9 0 ) .
rs elficientactivatorsfor glYrluenewith moderateP-selecn 3 1 .2 4 3 5( 1 9 9 0 ) .
rearrangementis believed to involve a retro-aldol cleavagefollowed by a WittigHorner intramolecularreaction. andT. Furuta,J. Org.,55,3971(1990). Y. Yamamoto
N,N'-Dimethyl-N,N'-propyleneurea
o
tl (CH,)'S:CH,
(1). Dimethyloxosulfoniummethylide, Preparation.The original procedure(1, 315-318)for the preparationemployed reactionof trimethyloxosulfoniumiodide with NaH in DMSO. A newer, lesshazardous route involvesreactionof trimethylsulfoxoniumiodide (Aldrich) with potassium r-butoxidein DMSO at room temperature.r f J . S . N g , S y nC . o m m . , 2 0l l,9 3 ( 1 9 9 0 ) .
Dimethyl (phenyl)silyllithium. Cyclic silyl enol ethers.r This reagentundergoesl,2-additionto cyclic c,penonesusuallyin high yield. Brook rearrangement ofthe adductresultsin silyl enol ethers.
NaH.25.
MerPhSiLi
il- e4%-f I
a^a
,
I
\-/
72%
tl
c2H5co
I) LDA N 2) TlSt 3) lrol
t, cHr*
cH, il
> a,,\
CH,
(-,
\-,
o
ll t V"'c/
OSiPhMe,
Ho- -siPhMe,
?
cinogenicsubstitutefor HMPA. Tb that it can be used in higher core A number of factors other tht deprotonationof esters,such rs tl selectiveformationof (E)-silyl kar ularly sincethey are more rcrtitr The paper reports a highly c6c acetal(equationI) by use of DMPI lowersthe diastereoselectivityfror
'M. Koreedaand S. Koo, TetahedronLetters,3f, 831 (1990).
N,N'-Dimethyl-N,N'-propyleneurea(1,3-dimethyloxohydropyrimidine,DMPU, 11,207;13, 122). SiIyI kctene acetalsfrom esters.r Ireland has examinedvarious factors in the enolizationand silylation of ethyl propionate(1) as a model system. As expected from previouswork (6, 276-277),use of LDA (l equiv.) in THF at -78 - 25o resultsmainly in (E)-2, formed from the (Z)-enolate.The stereoselectivityis markedly affectedby the solvent.Additionof TMEDA resultsin a 60:40 ratio of (Z)- and (E)-2 andlowersthe yield significantly.Useof THFl23% HMPA provides(Z)- and (E)-2 in the ratio of 85: 15 with no decreasein yield. This systemhasbeenwidely used for (E)-selectivelithium enolateformation from estersand ketones.Highest stereoselectivityis observedby addition of DMPU, recentlyintroducedas a noncar-
CH.'\,
jli3i,
o ll
o-
C,H. " €
(z)-2
l THF THF|2SVo TMEDA THFZ3Va HMPA THF/457o DMPU
orBS
CH,''6o.')
90Vo 50Vo 9OVo 9OVa
orBs
-C,H. +
I
/-o.
!rH,
cH" (E)-2 6:94 60:z$0 8 5 l: 5 93:7
(S,S)-or (R,R)-2,5-trcns-I)'lnct
Preparation.l Asymmetri c radi cal re actio.t, cd reactionsobservedwith (S,SF 2 in the presenceof BufnH and I cyclicproducts3 in the ratio 14: I
(S,S)-or(R,R)-2,5-trdnr-Dimethylpyrrolidine
r lr . J) for the preparationemPloYed n D\{SO. A newer,lesshazardioJrdetAldrich)with Potassium
to cyclic c,Ppe s 1.2-addition rf rheadductresultsin silYl enol
OSiPhMe, t:'+
tl
crH,cg cHr:A (l) i il
l
I) LDA, THF, DMPU 2) TBSCI
l |
'v"'c/
1"Hr
""rfr
+ Cr-isomer
Hooc
il
cH,
98:2
i",
I R. E. Ireland,P. Wipf, andI. D. Armstrong,lll, J. Org.,56, 650 (1991).
lorohydropyrimidine, DMPU, craminedvariousfactorsin thc r a modelsystem.As exPected c q u r \ . ) i nT H F a t - 7 8 + 2 5 o is markc The stereoselectivitY and of(Z)ratio in a 60:40 sults (Z\and provides HMPA F :l'{ widelY been has This system ld om estersand ketones.Highest recentlyintroducedas a noncar-
o - '/
o
CH,
I l9qlt
NS
cinogenicsubstitutefor HMPA. The higher efficiencyof DMPU resultsfrom the fact that it can be used in higher concentrationsat -78o than HMPA. A number of factors other than the solvent can affect the stereoselectivityof deprotonationof esters,suchas the acid-baseratio and the natureof the base.But selectiveformationof (E)-silyl keteneacetalsfrom estersremainsa problem,particularly sincethey are more reactivethan the (Z)-isomers. The paper reports a highly efficient Claisen rearrangementof a (Z)-silyl ketene acetal(equationI) by use of DMPU to control the stereoselectivity.use of HMPA lowers the diastereoselectivityfrom 96 to 84% de.
tl
N : '
147
c.H, ' +
OTBS I -CrH, l/ - o t ' cH3 (E)-2
6:94 60:40 8 5 l: 5 93:7
(S,S)or (R,R)-2,5-trons-Dimethylpyrrolldine, (r) cH,-aJ...CH, H Preparation.l Asymmctric radical reactions. Severalgroupshavereportedasymmetricradical reactionsobservedwith (s,s)- or (R,R)-l asthe chiral auxiliary.Thusthe iodide 2 in the presenceof Bu3SnHand AIBN cyclizesmainly to two diastereomericendocyclicproducts3 in the ratio 14:1.2
"'."' - N l J CH,
3 (R/S= l4:l)
(S,S)-or(R,R)-2,5-lrazs-Dimethylpyrrolidine
l4t
Analogousresults obtain in intermolecularaddition of alkyl radicals to unsaturated amides.Thus addition of n-hexyl radical to the unsaturatedamide 4 derived from (S,S)-1 results in four products, two by addition o to the ketone and two by addition0 to the amideenol. The former productsare formed with slight selectivity, (60:40), but the latter products(5) are formed in ratio of 93l.7.3
cY,
? h */\o-y'u*2 o
cH.
? c.H,,-L -""/{(.,) cH,
5(S/R=93:7)
Stereoinductionis also possiblein addition of chiral radicalsto ethyl acrylate.4 Thus the radical formed from the bromo amide6 derived from (R,R)-2,5-dimethylpyrrolidine reactswith ethyl acrylateto give the mono- and di-adducts7 and t. The at C2. is formedwith 36:1 stereoselectivity monoadduct .CH,
\n,N:-
r
,\
T
CH,
"iiili
Br
-r>
+ cHr:cHCooc2Hi -C,H,
' R. P. Short,R. M. Kennedy, S. Masamur 2 N. A. Porter,B. Lacher,V. H.-T.Cheng.u r N. A. Porter.B. Giese,H. J. Lindner.arel 4 N. A. Porter,E. Swann, J. NallyandA. T. I Zehnder. M. Roth,andH.-G.Zeitz,ibid.. I r L. ChenandL. Ghosez.Tetrahedron ltncn Dimethyl sulfoxide. Deprotectionof acetals.r Dialkyl u when refluxed in aqueousDMSO. DcF! 1,3-dioxanes) requiresmoredrasticcood combinationwith a cosolventsuch as ct!
3 i",
4
[2 +2]cycloaddition with high facial scleo with ultrasonicactivation.
I T. Kametani. H. Kondoh,T. Honda.H. l*il 901(1989).
Dimethyl sulfoxide-Oxalyl chloridc. Oridation of alkyl trimcthtl- cta n (CzHs)r.r Silyl ethersof this type crn h by the Swern reagent.This oxidation pm hyde(2).
o
o
o-\ : ,/V""'
A
S,,",
\A-^-
cH,
. i'-.'1{-.*-..-cooc2* cooc2Hj\ucH,
o
I ' O lrl
\,\--osi(c2H5)l
cisilcrnr),
o
(-)- I
, o R / S= l : 1 ) I ( 1 5 - 2 5 V oC
S/R = 36:l) 7 (35-SOVo,
l
1-].'
c2H5cooc2Hs
.yt"'
ll
Asymmetric synthesisof cyclobutanones.s The o-unsaturatedketeniminium salts(a) formed from amides(2) derived from chiral R,R-l undergointramolecular
:n' N
r
CH,
t-
6rr l o (cF'so,):o> l lr--....-
l_^,
H
.ll3o:cc' r-1--ao -,"," >(
|
|
88%
:
H 3 (98Vo ee)
Dehydrogenation of dinziridinu.2 Ag2Oor NBS for oxidation of the dirzr becausethey are photolyzedto reactivec
l, ,,roi,ion of alkyl radicalsto unsatuItar ro rhe unsaturatedamide 4 derived br rddirion a to the ketoneand two bv Dduitrare formedwith slightselectivity, Dc.i:n rarioof 93:7.3
Dimethylsulfoxide_Oxalylchloride
l4g
[2*2]cycloaddition w facialselectivity,particularly whencarriedoutat 20o wirh ultrasoni.u.,luu,l*ligh IR. P. Short,R. M. Kennedy,S. Masamune,J.Org.,S4, 1755 (19g9).
j il t iixlr: i tti:r;t;r;.f,.:.}:"aJ::,#r:,,*ril1,T-'tr,' 830e (,e8e) BGiese M ',L. i;fe{t:5';d:.'it-i,:i:',y.;;il;ixfi;r;;';::,ii)L:,il'i,nno Chen andL. Ghosez, rr,r"i"i)"'r'"tirir^,"riri oou,Annor.
5 rS/R= 93:7)
m -: chiral radicalsto ethyl acrylate.a dc 6 Jerivedfrom (R,R)_2,5-dimethvl_ tht rono- anddi-adducts7 andg. Tie
Dimethyl sulfoxide. Deprotectionof acetars.t Dialkyr acetalsare cleaved to the carbonylcompound when refluxedin aqueous DySO. O"O-*U|" of cyclic acetals(l3,_lioxolanes, l'3-dioxanes)requires moredrastic*ioiri""r, ,"ch as refluxing combinarion witha cosolv"n, ,u"t,ur-.'rilnli or"z_uurunon". aqueousDMS' in rT. Kametani, H. 'rv' rsvr.'T' Honda,H. Ishizone, ' --' Kondoh. Y. suzuki,andw. Mori, chem. 901(19g9). letters.
Itr ::r at C: .
Dimethyl sulfoxide_Oxalyl chloride. oxidation or akvr tltnetbland triethyrsityr ethers, (CzHs)''rSirvrerhers Rosi(cH3)3 0r ROsior.tristipe
3- .-';
lir}ij:*"
;;;;';;'i:t;d reasent. rhis oxidation il;;;;;
directry to "u.uonyi'"ompounds effcienrrourerothecoreyarde_
CH
r) DMSO/(coct.),. _60"
g,H, - " cooc2Hs -
>/
f
2) N(CrHt)!
t
L t --.,+.--,A.-..'-.-Cooc2H, H
O
)
osi(crHJ3
62%
osi(qHJ3
, rVS = l:l) t r 1 5 - 2 5 V oC
(-)-l
The o-unsaturatedketeniminium chrralR,R-l undergointramolecular
q H, l ,
=i-l .---l
l
l
H
lii:;t* /'--+-4"
r - \
t
CHJ
8E%
'
\
-
I
I
H
3 (98Vo ee)
of diazirtdines.2rhe ?r!!o:.:t::ttion Swernreagentis more I or NBS for oxidationof rhe di.-:,: effective than ):__- , because theyarephotolyzed ,o ..."riu. .u.i"*^.
l::?,ll,i,'1,:ffi ffj'.T;:*,:::'":'*:T",J?'"':T,ff;;::',:';iJ
trdrs-Dloxo(tctrrr.-! 150
(S,S)-N,N'-Dineohexyl'2,2'-bipyrrolidine
HN_NH
><
cF,
RC"H;
I
Rcview.3Tidwellhasreviewedtheoxidationofalcoholsbyvariousversionsof on applicationsreportedin the recent tfre i*e.n procedure,with particular emphasis literature(198l-1989). and o. M. Kuznetsov, M. E. Adler,N. G. Komissarova, l G. A' Tolstikov, M. S. Miftakhov, 940(1989)' N. S. Vostrikov,Syntlresis, ' i.'i. ni"n"tOson andR. J. Ife, J'C'S' PerkinI' ll12 (1989)' (1990)' 3 T. T. Tidwell,Synthesis,857 97"' This reagentis preparedby reacDimethyltitanocene,Cp2Ti(CHr)2,(l) m'p' cH3Li (95% yield). It is stablefor tion of titanoceneoicnrorioe,iprricrr, with rapidly in or THF' but decomposes severalmonthswhen storedin the Oarkin toluene solid state.t the "'- -irinTrration.z effectsmethywhen heatedin THF at 60-65., this reagent of aldehydes and yield 60-90% in ones, lenationof ketones,evenreadilyenolizable (45-60voyield)'Italsoconvertsestersandlactonesintoenolethers,butthisreaction isgenerallyslower.ItisthusanattractivealternativetotheTebbeandGrubbs reagent.
,z--.-/oYo | - r80% | " \.\-/
l)m..r.-1f 2) N.fiSO,
R'
DMSO
N: N (cocr), > X- -cF, 1t-86qa Rc.Hi ,
V\'/
o-Y"'' |I J
I V. K. ClausandH. Bestian,Ann',654' 8 (1962\'-^ t ll. l. p.tntit and E. I. Bzowej, Am' Soc" ll2' 6392(1990)'
$-5t
R2
the complex (2) obtainedfrom osmyhir chelatedto Os.
':\) .":"1)-
{-
' M. Hirama,T. Oishi, and S. Ito, J'C'S' O :T. OishiandM. Hirama,J. Org',54. 5t]l
rrons-Dioxo(tetramesltylporpbyrldrl This porphyrincomplexis obtaincdb tCO)(tmP).'
*.,?r* Ru
{A'l (S,S)-N,N''Dineohexyl-2,2Lbipyrrolidine'
I
(cH3)3ccH2cH2 trp-137o.PreParation.r enantioselectiveosmylation of Enantioselective ilihydroxylation'2 Highly obtainswith osor oxidationsin the ,rons-disubstitutedand monosuistitutedalkenes p r " r " n r " o f l e q u i v . o f t h i s c h i r a l 2 , 2 ' - b i p y r r o l i d i n e l i g a n d a t - 7 8 oonly ' N o t e-65% 'however' cis-disubstitutedalkenesis that the enantioselecti"i; f- ;;,n;tutioi or eeandforosmylationoftrisubstitutedalkenesislessthan60voee,X-rayanalysisof
I
Epoxi.dttion.2 The comPlcxcld; Thusair epoxidationof cholestcrylel highly p-selectiveepoxidationofthc 5 >9% 0-selectivity.
drans-Dioxo(tetrrmesitylporphyrinato)ruthenium(VI) RuOdtmpl
R,
l) OsO., l, -78o
2) NsHSO,
\ \
cF,
tc.H.
R2
HO
151
OH
R''r-\'tr H R '
80_!r%
88- 1007oee
n t i alcoholsby variousversionsof reportedin the recent I applications
the complex (2) obtainedfrom osmylationof stilbeneshowsthat the diamine (l) is chelatedto Os.
and O. M. Kuznetsov, K.rmissarova, i e 8 9) .
' Thrsreagentis preparedby reaclH.Lr (95% yield). It is stablefor rapidlyin lor THF. butdecomposes 2
n-65'. this reagenteffectsmethy;. n 60-X)Voyield andofaldehydes E\ rntoenolethers,but this reaction lrnative to the Tebbe and Grubbs
M. Hirama,T. Oishi,andS. Ito, J.C.S.Chen.Comm.,665 09g9). :T. OishiandM. Hirama, J. Org.,54,5834(19g9).
"-t--oY.
nans-Dioxo(tetramesitylporphyrinato)ruthenium(Vl) RuOz(tmp), l. This porphyrin complex is obtained by chloroperbenzoicacid oxidation of RurCO)(tmp).t
'-"^\-r"
CH, \-
"'l"/
n .q9tlr
-r.It.''^-l |
t\N'
Ar
(s's)-l
N/ JltN
CHt
\.l
/ r,C('H.CH,
\
CHTCH2C(CHr),
*=4 V.", Y
Ar I
; enantioselectiveosmylation of ohrarnswith OsOroxidationsin the ine )rgandat -78o. Note,however, alkenesis only -65% drsubstituted lcr: than607oee.X-ray analysisof
Epoxidation,z The complexcatalyzesair epoxidationof variousalkenesat 25o. Ttus air epoxidationof cholesterylestersand variousA5-I7-ketosteroids resultsin frghfy p-selectiveepoxidationof the 5,6-doublebondin i2-gs% yield with usually >99% p-selectivity.
152
(rI
Diphenyldtselenide-Lithiumelumlnumhydride
I J. T. Grovesand R. Quinn,Am. 9oc.,107' 5790(1985). 2 J.-C. Marchonand R. Ramasseul,Synthesis,389 (1989).
n
?
a">/ocrHs ___+Ho(cH.) \J
(MoOPH)' Diperoxohexamethytphosphoramidomolybdenum(Vl)' 3-alkyl-3-hydroxyazetidine-2Some Vedcjs hydroxytation of 2-azetidinone.r ones are known to have interesting biochemical properties' but have not been readily available. They are now available by alkylation ofa 3-hydroxyazetidine-2-one deriv-
oretanesand oxolanesto y- and 6-ptcr contrastto the phenylselenideanioo prq
ative (3), which can be prepared by hydroxylation of (N-r-butyldimethylsilyl)azeti-
K. Haraguchi, H. Tanaka,andT. Miyrc{
OH
l]h%'"'-"-" l-----*(D L,|{ ^'\si_r_BulcHr;, )_* -siR, d' d/
1
2
n,*Ji[,1fi5]1,"",.,, I
)_N
d/
-
^'\H
n"rur' | - ffia" - - :CHr-l-l - l e{r% )_N
i
<
I)LDA
-
_2,cH,r - : -
--siR,
d/
5
-
'13
I l-l l
i
CoHl.NH:
)-N.
-siR,
d'
4
3
din-2-one(equationI). The anion of 3 reactswith a numberof electrophilesin 5085% yield. The protectivegroups can be removedselectivelyor simultaneously. r R . E . D o l l e , M . J . H u g h e s , C . - S . L i , aI n . KdrLu. s e , J . C 'C Sh' e m ' C o m m ' , 1 4 4 8 ( 1 9 8 9 ) '
Diphenyl diselenlde-Llthium aluminum hydride. Cleavageo! oxetancsand oxolanes.r The reaction of LiAlHa with diphenyl diselenidein dioxaneprovidesa particularly activeform of LiSeCcHs,which cleaves ^
D
(CoH'Se)r' LiAlH.
-#-
rt
HOCHz--*,,"\
\_f
Ho(cH,),SecuH, (C6H.Se)r' LiAlH.
'm"
u%
:::x"..-
os(cH3)3
os(cH3)3 --
oH CH,--l----t - l l <
(l,R)- end (S,S)-1,2-Diphenyl-ll.
, HOCH(CHz)rSeCoH,
l;,;'
coHr.../N
l cuHr"'\NH,
+
l c.Hr
(R,R)-(+)r 6+106o
Nr (S,S)-(-)l (b-16.
An alternaterouteto ( + )- and ( - Fl trcn of trcns-stilbeneusing dihydroquir as the chiral auxiliery fr shlorobenzoate
CuHrt\'-CuHt
t'44-----------+ 1
/
OH (ls.:
(R,R)-end(S,S)-1,2-Diphenyl-1,2-ethanediamine 153
, l,n,,
oc,H. /"\-OCrHs \ \-J
!!um(VI), (MoOPH). Some3-alkyl-3-hydroxyazetidine-2I properties,but havenot beenreadily derivr oi a 3-hydroxyazetidine-2-one (N-rbutyldimethylsilyl)azetirron of OH '. -. .r5' tri
l-r
l >-N
oc"H.
t " '
t - -
o
(1989t.
HO(CHr)3CHSeC.H, ______, _$, /
6
t
AcO(CHr)rCHSeCuH,
% ovemu
oxetanesand oxolanesto y- and 6-phenylselenylalcoholsin generallyhigh yield in contrastto the phenylselenideanion preparedfrom diphenyl diselenidewith NaBHa. ' K. Haraguchi, (1989). H. Tanaka, andT. Miyasaka, Synthesis,434 (R,R)- and (S,S)-1,2-Diphenyl-1,2-ethanediamine (l). Preparationl:
l
-siR,
o"
CuH*Vo
NH.oAc. HoAc. CuHs:y=\
l' *o{ \J )--=ry-es-e't%
2 o"o | ",ru.",r, '""1N(c,H.)t' cH,cl,
cuHrAo
- J| 2r))Li-NHr, Hro-
c)HroH
osi(cH3)l
tcH |
)
cn*AN/\J "n-** -' "
'!
/-1
f Y
-
'tr- -
l) LDA 2)cHil 13%
s,R,
I
NH2
C6Hrr.
)_N-
d'
\siR,
I I
I
CuHr"'\NH,
3 rrrh a numberof electrophilesin 50pred selectivelyor simultaneously' (1989)' Comm.,1448 lru.e../ C.S.Chem.
lride. Tte reaction of LiAlHa with diphenyl rrrr e form of LiSeCoHs,whichcleaves
lCH. r.SeCuHt
CoH5...--Mz r c T |
cuHr
i -
NH,
(R,R)-(+)1
(s,s)-(-)r
oo+ 106"
ao- 106'
r-Tansic d
coHr-aNH, I cuHr
NH,
(i)- l
An alternaterouteto ( + )- and ( - )-1 involvesasymmetricSharplessdihydroxylation oftrcns-stilbeneusingdihydroquininep-chlorobenzoate or dihydroquinidinep.'hlorobenzoate as the chiral auxiliary for preparationof ( - )- or ( 4 )- I ,2-diphenylCuHrcuHsA"cuH'-1n*-
C.H, ursct.rytzo*t C.H,. SuH, 2rNarii160?r> A -ts1 oH oH N3 N3 (rs,2s) (lR,2R) 91% | LiAlH,, ettrcr
"u"r...
t +
,CuHt
HoCH(CH2)3SeC6H5 l cH2OH
NH2
NH'
(lR,2R)-1
154
(r'rF d
G,R)-and(S,S)-1,2-Diphenyl-1,2'ethanediamine
ethane-I,2-diol.Remainingstepsinvolveconversionofthe l'2-diol viathe ditosylate to the l,2-diazide,which is reducedby LiAlHa to the diamine(1)'2 Thesechiral C2symmetric1,2-diamineshavebeenusedto preparechiral reagents containingaluminumor boron, which haveproved to be highly effectiveLewis acid catalystsfor severalsyntheticreactions. EnantioselectiveDiels-Alder catalyst.l The aluminum reagent2, preparedby reactionof (CH:)dl with the N,N-ditriflateof (S,S)-1,is an effectivecatalystfor asymmetricDiels-Alder reactionsof acrylateswith dienes.Particularly high enanwith cyclopentioselectivityobtainsin the reactionof 3-acrylyl-1,3-oxazolidinone-2 yield is 90Vo.The optical and the l, is )50: ratio tadiene.In this case,theendo-exo carbon the acrylyl to the catalyst of binding from results stereoselectivityprobably group.
c6Hs
(I) RCHO+(CrHr)rC:O
(Lr).{
wl 9tt
R = CcHs R = CzHs
This bromoboranecan eveneffectenerfitr esterand an aldehyde(equationII).
(II) C6H5CHO+ CHTCOSC.II,$
-c6Hs
Aldol reactionsof propionateestersuitl promotedby the more Lewis acidic broootl
/ \ (s's)-2 cF,so,t(-Allso2cF3 CH,
CF
o ? li A -U=vcHj +cH,ry.-\_)o *#a [\ f
i.\'{"
I'' to"'"' f''\
f^\ "
11
Frc-',_l A*-*-B'N-' o.' B I r a
L_/ (endolexo = 96:4), 94Vo ee
Enantioselectivealdol reactions.3'aA related borane reagent, (R,R)-4, preof (R,R)-l' can effect paredby reactionof BBr3with the N,N-bistosylsulfonamide highly enantioselectivealdol reactionsof ketoneswith aldehydes.Thus reactionof "u"r..
tCu"t (R,R)-4
TsN."rNTs Br leadsto a diethylketonewith (R,R)-4(l equiv.) anda base(diisopropylethylamine) in >95% * syn-aldols to afford chirai boron enolate,which reactswith an aldehyde (equationI).
\ conversionof (R,R)-l to the bis(3,3bwed by reactionwith BBr3. With this rcq rrn-aldols (equationIII), but r-butyl escrr
o tlIDcHr--AScuH,+ (n,nl-s-S
(R,R)-and(S,S)-1,2-Diphenyt-1,2-erhanedhmine f5s
lx
rersronof the 1,2-diolvia theditosylate H. to the diamine(l).2 tre beenusedto preparechiralreagents rcr ed to be highly effectiveLewis acid bY The aluminumreagent2, PrePared of rS.S)-1,is an effectivecatalystfor 6 * rth dienes.Particularlyhigh enanwith cyclopen111-l.3-oxazolidinone-2 i0 i. andthe opticalyield is 90Vo.The tg oi the catalystto the acrylyl carbon
(R'R)-4'r'IR'> ^--A
(I) RCHo+(CrHr)rC:o
H.oH
I
c,n,-)-n -tt H
R = CcHs R = CzHs
95% 9l%o
CH"
97Vo ee, synlanti = 94:6 98Voee, synlanti = 98:2
This bromoboranecan eveneffectenantioselectivealdol reactionswith an acerare esterand an aldehyde(equationII). O (tr) c6H5cHo + cH,coscoH, SLH%
H O H
c6H5sVc6H5 9 l % oe
:f
Aldol reactionsof propionateesterswith aldehydesproceedmore readily when promotedby the more Lewis acidic bromoborane(R,R)-s. This reagentis prepared
rS.S)-2
l : r Y 1
-;- lL4
cuHr.. rcuH, f., 'r<'
lt,
CH.
t\
f
3o*-{- - l O
nr
'\t
(R'R)'s
.,"^<*31.?,-_3)4"., l
.
t
-
N
B
.
N
t
l
r
t_/
(endolexo = 96:4), 94Voee
relaredboranereagent,(R,R)-4, prc' losr lsulfonamideof (R,R)-I, can effect iloneswith aldehydes.Thus reactionof
R .R ) - 4
by conversionof (R,R)-l to the bis(3,5-difluoromethyl)benzenesulfonamide folbwed by reactionwith BBr3. with this reagentphenylthiol estersare convertedto nn-aldols (equationIII), but r-butyl estersprovide anri-aldols (equationIV), both
o il
(lII) cHr\,AscuH,
* (R,R)-s
rr*J""n,""o o H o
l r l
leadsto r ba:e rdiisopropylethylamine) dchrde to affordsyn-aldolsin >95% e
c6H514sc6H5 CH, (>95Voee, synlonti = 99:l)
(llFr 156
(R,R)-and(S,SFI,2-Diphenyl-l'2-ethanediamin€
o
-l
qBRi
t-
9" l-.,",... ,'u', I *""o'fc'q I r{ I
N(c'H')r ' +G,R)-5 (,u)cH,..-,Ioc(cH3)3 f;fo.,"",.,,1
I TsN._rtlTs l
t I
,o*."",""o f
t
r
I l
t l c":c:cH:l
and2-chloroallyl groupsis possiblc' bur r rive synthesisof allenyl and propargtl o
o H o : l l c.H,/Y^oc(cH,)l
ble.6 Enantioselective dihyilrorybiot ta oyl-1,2-bis(2,4,6-trimethylbenzylami with mesitylaldehydefollowed by NeBll
CH, = 98:2) ee'antilsYn (93-91Vo Ethyldiisopropylamineis the preferred with high enantio-and diastereoselectivity. for the anti-reaction'a --^^.: basefor the syn-reaction,triethylamine 5' obtainedby reactionof the (R'R)-allylborane Allylationo! aklehytle|s't it'" to providehomoallylic 4 with allyltributyltin' addsto aldehydes (R,R)-bromoborane coH, "';( RCHO+
-coH, "
\ / TsN-rrNTs
CHt
"o\'" ^ cHrr?'-78''H,czV\R ee 95-97vo
rronsof OsOawith alkenes.Rapidrcrt,rr (E)-1,2-disubstitutedalkenesrcsuluq The diamine is used in stoichiomctricr recoveredeasily for recycling' Thc pq observedenantioselectivitybasedoo r C rnd OsOa.
I
CH,CH:CH' (R,R)-6
c.H.-cHo "
?"
+(R.R)-6-CuHr=,rr^\rACH, Y oMoM oMoM
+
A1' r C.Ht-.'/--,,ACH,
25:t
oMoM
,
R +O{) R'
with opticallyactive alcoholsin >govo yield and in95-97% ee. A similar reaction of 2-bromoaddition Similar (24-50:1)' aldehydesshowshigh diastereoselectivity
cF,...
,.ts,
f-\
+ CH2:C:CHSnBu,
TsN-"rNTs Br (R,R)-4
f
n"=""",.nuu,
----- ["o' I
jJL
NH }O
q': ] \
lT'il-rrNTt I inP-c4J L
RcHo "-""' -
Asymmetic ePoxidation of allcu complexessuchas 2 from (' manganese c6Ha
/\
/
t clq
/
VO,t R
(R,R)- and (S,S)-1,2-Diphenyl-1,2-ethrnedlamlne
oBR*
T
I
'' ' >1"/""(cH,),1 I
LcH,
-l
l-c'H'".-c'n' *."oIL ?" -CHrC-CH "(-)*. | 1..........-+
t L
80%Jc6H,cHo
o H o : t l c^H.'r'\"\oc(cH3)l I CH, e \ - 9 7 V o e e ,a n t i l s y n = 9 8 : 2 )
T
CH:C:CH3_I
l
and2-chloroallylgroupsis possible,but with lower enantioselectivity. Enantioselective synthesisof allenyl and propargylcarbinolsby a similar processis also possible.6 Enantiosclectivedihydroxylation with OsOa.1 The (S,S)-diamine6 [1,2-diphenyl-1,2-bis(2,4,6+rimethylbenzylamino)ethanel is preparedby reactionof (S,S)-l with mesitylaldehydefollowed by NaBHa reduction. It markedly acceleratesreac-
is the preferred fi\ rJnsopropylamine ri reaction.a u,: I h.:rne 6, obtainedby reactionofthe 3 : . ridehydesto providehomoallylic
CH,
( s,s) - 6 CH,
c
''
CH,
tionsof osoa with alkenes.Rapidreactionsevenat -90' arepossiblewith terminal or (E)-1,2-disubstituted alkenesresultingin 1,2-diolswith high enantioselectivity. The diamineis usedin stoichiometricamounts,but the ligand and osmiumcan be recoveredeasily for recycling. The paper includes a rational explanationfor the observedenantioselectivitybasedon a c2-symmetric l: I complexof the diamine6 rnd OsOa.
rH,C 95-977o ee
OH ?
cH,
*
( D / 25:t
OMOM
srmrlarreactionwith opticallyactive -51 I). Similaradditionof 2-bromq'
['n J'"' t i
*."o l l--.-------
lt't'?'*' I L
R,
ctH'-'"-(--''a'*
tH,c-cryl
(s,s)-6 HO ".-J + OsOn cH!cl,'-90', 80,95%
R'
/ Rt
OH \ R2
82-98Vo ee
Asymmetricepoxidationof alkenes. Two groupshavepreparedchiral (salen)svrnganese complexessuchas 2 from (+)- or (-)-l and salicylaldehyde derivatives CuHr. N1
..N
1_
<)
M;* o o PFu or AcO-
d-
fst
G,R)-I,2-Diphenylethene-1,2-dioldimethylether
and report that thesecomplexescan serveas catalystsfor enantioselectiveepoxida-mesityleneas the oxygen tion of unfunctionalizedalkeneswith iodosylbenzeneor atom source.The complexin which R is t-butylsis more effectivethan that in which R is l-phenylpropyl.ePreliminary resultssuggestthat sodiumhypochloritecan also be usedas the oxidant. The highestenantioselectivityobtainswith cis-disubstituted alkenesor with terminal alkenessubstitutedby a bulky group'
C.HTCH:CHCH,
C.HTCH:CHt
(cis,844oe) (trans,53Vo ee)
67Voee)
""'Y) a)\-/ \-A-r' (59Vo ee)
(78Vo ee)
I S. Pikul and E. J. Corey,Org. Syn., submitted(1990). (1990)' ' D. Pini, A. Iuliano, C. Rosini, and P. Salvadori,Synthesis,1023 3 E. J. Corey, R. Imwinkelried,S' Pikul, and Y. B' Xiang,Am' Soc', lll' 5493 (1989);S' Pikul and E. J. Corey, Org. Syn., submitted(1990). a E. J. Coreyands. S. Kim,-,{^. so".,112,4976(1990);idem.,Tetahedronl*tters,3l,37l5
(r990). (19E9)' 'i. J. Corey, C.-M.Yu,andS.S.Kim,,{n.Soc',111,5495
effective than the dimethyl etbcr of ( rlso high with acyclic o,p-unsaurra moderate. ' K. Tomioka,M. Shindo,andK. Kog
(S,S)-1,2-Diphenyl-1,2-ethuctu
Chiml aminals; l,HihydtqTi preparedfrom pyridine-3-carboryli reagentsin the presenceof mcthyl d of 1,4-addition,asexpectedfrom rcr eddition are formed, but l,Grddru dducts are formed in 82-95t & r groupsis best efiectedwith lithiun, groups is best effectedwith orgrr
6 E. J. Corey,C.-M. Yu, and D.-H. Lee, ibid., fl2' 878 (1990)' ?E.J.Corey,P'D.s'Jardine,S.Virgil,P.-W.Yuen,andR.D.Connell,ibid.'|||'9243
rI. cno
(19E9). Am' Soc" lf2' 2801 (1990)' t W. iftung, J. L. Loebach,S. R. Wilson, and E' N' Jacobsen, e R. Irie, i. ttodu, y. Ito, N. Matsumoto,and T. Katsuki, Tetrahedronl*tters, 31,7345
(1e90). cuHr.. lcuH, (l' oD- l4') ether, dimethyl (R,R)-1,2-Diphenylethane-1,2-diol fr, ocH3 cH3o aldimine.r This chiral diConjugateadditionoI RLi to an a,,$-unsaturuted It is more enantioselectivity. the also controls etheris a catalystfor thisreactionand
iii'ii.'iJ;'"' . *,. sdc#"-c R = Bu R = CcHs
9l7o ee 82Voee
80Vo 94Vo
2 (CHr)rCuMgBr (CrHr)rCuLi (CH':611;'gu"*
I I I
rddition of organocuprates can bc r tcyl chlorides can replace methyl c R. Gosmini,P. Mangeney,A. Alcut rl99l). : M. Commergon, P. Mangeney,T.Tci rl90). ' D. L. Cominsand A. H. AMullr!..1-
cH2oH CH,CH:CH-CH:NC.H'-
c + CuHrLi--+
t
1rC'Ht CH, (S)' >9Vo ee
(S)-1,l-Diphenylpropane-I,2il. The diol is preparedby reactiooof
(SFl,l-Dlphenylproprne-1,2-dlol
epoxidail1 sts for enantioselective trcneor -mesityleneas the oxYgen is more effectivethan that in which 1 that sodiumhypochloritecan also rir rrr obtainswith cis-disubstituted r bulky grouP.
)4) t
-\q
l
(59Vo ee)
ee)
effectivethan the dimethyl ether of (R,R)-butane-2,3-diol.The enantioselectivityis also high with acyclic c,p-unsaturatedaldimines,but chemicalyields are often only moderate. fK. Tomioka, M. Shindo, andK. Koga,Am. Soc.,ffl, 8266(1989).
c'H'>ic'H' (s,sFl,2-Diphenyt-1,2-ethenedimethytamine,
CH,
0r uAerrs.1023(1990). S. Soc.,111,5493(1989); [rrng.,,1m. I'etters,3l,3115 lt. dem., Tetrahedron
R I RM.THF
/,'tV,A* crco'cHr ' ll ll
Am.Soc.,1f2,2801(1990). tr'..bsen, l*tters, 31' 7345 btsukr.Ietrahedron
\N/
R
Hc, *" f*o ll ll >86%
I
coocH3 ,cuH,
llcr.
(l' co- 14")
ocH3 cH,o Eracd aldimine.r This chiral diIt is more olsrheenantioselectivity.
(l)
CH3NH HNCHs Chiral aminals; l,$dihydropyridine-3-carborqldehydes,r The chiral aminal 2 preparedfrom pyridine-3-carboxylaldehyde and (S,S)-12reactswith organocopper reagentsin the presenceof methyl chloroformateto give almostexclusivelyproducts of I,4-addition, asexpectedfrom reactionsof the free aldehyde.3No productsof I ,2addition are formed, but 1,6-adductsare minor products in some cases.The 1,4adductsare formed in 82-95% de (R-configuration).Addition of butyl and ethyl groupsis best effectedwith lithium cuprates,but addition of methyl, vinyl, or aryl groups is best effectedwith organomagnesiumcuprates. Under these conditions,
ll i{e5(1989). t-t ,1990). r. andR. D. Connell,ibid., lll'9243
c^Hr..
159
2 (CHr)rCuMgBr (CrHr)rCuLi (CHr:6Pr6u"t",
X)Vo
\*/
CoocH,
95Voee
9OVo
85Voee
%%
95Voee
rddition of organocupratescan be effectedwith high regio- and stereoselectivity. Acyl chloridescan replacemethyl chloroformateas activators.
rH
lll
,cr,+{
j+
9 l % oe e 82Vo ee
|cl
cH2oH ItL,
;;-
\rcuH' I CH, (S), >997o ee
O r g . , 4 7 , 4 3 1(51 9 8 2 ) .
cH" tri-"i?L, (S)-l,l-Diphenylpropane-l,2-diot.
(l). r.o.e3",co-1fi)"
HO OH Tle diol is preparedby reactionof ethyl (S)-lactatewith C6H5MgBr(75% yield).
160
DlphenylPhosPhorYlezide
t-Butyl alkyl sulfuxides.r The cyclic sulfite 2, preparedfrom l, reactswith RMgBr or RLi to form chiral alkylsulfinates,3 or 4, both convertible into chiral sulfixides by reactionwith a secondorganometallic.Particularlycleanreactionsof2 (with inverare obtainedwith t-butylmagnesiumchloride resulting from cleavage sion) at the more-hinderedsite.
c.H.
cH,
H;.;, o-"'o
u..!H, ,CuH' c6H'Li> qoTcu"r# CuHr-azo
./'",o
--\
l
l T TsN l T t--..2
,#t!
rff,"'#' o'
ls-Bu-t ':'
s
t
N
\-_z
o
\_61
'/t"'o (R, 857o ee)
o/-"., ,rurt
-g
o
l-Bu.^rCuH,
a
,, CH\
-\
N
{
Bu-"rBu-l
./-"'.o
TsN
U
(R. 10070 ee)
n T {
4 (90:10) t F. Rebiere Letters,30'3659(1989)' andH. B. Kagan,Tetahedron Diphenylsilane-Triethylborane. Deoxygenationof primary and secondary alcohols'r This deoxygenationhas been effectedby reduction of the thiocarbonyl esterswith tributyltin hydride and in AIBN astheradialinitiator(f f , 550).A newer,mildermethodusesdiphenylsilane thionosecondary Even air. and a radical chain reaction initiated by triethylborane at 25'. carbonates,particularly thosederivedfrom 4-fluorophenol,are deoxygenated
form macrocyclic lactams(cf., 4,211). 1 dilution andprovidesconsiderablyhigtcr 1 obtainedby reactionof the dicarborylic rr diphenylphosphoryl azide(2.5 equiv.)td a yield of 82%. L. Qian,Z. Sun,T. Deffo,andK. B. Mcrs
1,3-Dithiane, (l i
,c6H')'siH:'
a%g nodocuHoR-p
RH + (CuHr)rHSiOCoHoF-p 8O-96Vo
(1990). r D. H. R. Barton,D. O. Jang,andJ. cs. Jaszberenyi, Letters,3l,4681 Teftahedron Diphenylphosphorylazide, (C6H5O)2P(O)N3. Macrocyclic lactams.r Theselactamshavegenerallybeenpreparedby reaction of dicarboxylicacid chloridesanddiaminesunderhigh dilution' Yields are generally mediocrebecauselinear polyamidesare also formed. Actually, free dicarboxylic acids, when activatedby diphenylphosphorylazide, can condensewith diaminesto
Reviev.t A recentreview of 1.3{ifr literatureof 1977-1988(126 referenccr)
P. C. B. Page,M. B. vanNiel,andJ. C. Fn
1,3-Dithiane
preparedfrom l, reactswith f. both convertible into chiral Panrcularly cleanreactionsof2 og from cleavage(with inver-
[-,il-".._"oo"
U-r/
r-Bu-"rCuFt
L-n. r BuMrCl 'C.H. --------+ )
t.n:--"/-cooH. - r*l*)
:71
2
./'"..o
I , t(qH,O),RO)N} 82% | N(qH,L, THF.
I ""
(R, 857o ee)
o
_/.\ ,/---\ N I oA*l
Bu. rBu-l a
rs _.1_ TsN
, ./""'.o
t
(
r
s
t
//
a
I
T
t
N o - N l \,/- \__/-\_<.'\-/ b
' R . l 0 O 9 oe e )
'
3 5e 1989).
tls.t This deoxygenation hu 1 *rrh tributyltinhydrideand 'methodusesdiphenylsilane il d arr. Evensecondarythiono aredeoxygenated Gnr\1. at 25o.
form macrocycliclactams(cf.,4,211). This new approachdoesnot requirehigh dilutionandprovidesconsiderably higheryields.rhuslhe macrobicycliclactam3 is obtainedby reactionof the dicarboxylic acid l and the HCI salt of the diamine2 with diphenylphosphoryl azide(2.5 equiv.)andtriethylamine(5 equiv.)in DMF at 25o in a yield of 82%. L. Qian,Z. Sun,T. Defo, andK. B. Mertes,Tetahedron lztters, Sl, (y'169 (lgg0).
1,3-Dithiane, (l !., HSiOCoHoF-p
h.;tr,)nlttters, 3l, 4681(1990).
illr beenpreparedby reactioo drlution.Yieldsaregenerally . Actually, free dicarboxylic rn condensewith diaminesto
Review.t A recentreviewof 1,3-dithianes and2-lithio-1,3-dithianes coversthe literatureof 1977-1988(126 references). P. C. B. Page,M. B. vanNiel,andJ. C. prodger,Tetahedron,45,Tfy't3 (lgggl.
' E. J. CoreyandB. W. Erickson, J. Or3 r M. Hatanaka. Y. Himeda,andI. Uedr.,
Ethanolamine. Deprotectionofl-o-acylsugarc,Ethanolaminecanselectivelycleavetheglycosvl esterbond of evenperacylatedaldoses''
'n'xB CH.
Ethoxytrimethylsilylacetylene, (CHr Esters,lactones,and PcPtidet. condensationof RCOOH with alcob lactams,or peptides,usuallyin thc E
"t""r[-n,co<
R'cooH+I
I I
+ HTNCHTCHTOH
cHscooc'H. DMSO --*c"'
C6H5CH2NH(cH
+ AcNHCH'CHTOH
Chem.Res.(S), 152(1989)'
bromide (1). Preparedby 3-Ethoxycarbonyl-2-methylallyltriphenylphosphonium reactionofethyl4-bromo-3-methyl-2-butenoatewithP(c6H5)3.'
cooC,H, I CH
(1)
,rRt
I + HC-CHCH,
\cH,e*1coH.),Br-
,
reactswith a-bromo keCyclopentadienes.2This allylic triphenylphosphorane a [3 +2]annela' cyclopentadienes'by form to 25o of NaHCor at ,on"rin thepresence b' a and as such tion. The reactionmay involve intermediates
Rr = H, R' = Boc 73c 8091 R', R2 = Bzl R' = Bzl, R' = Boc 85%
Jrprotectedp-alaninals react with hi1 enhancedwith increasing steric hind
""'["",u, l9H' Ndco' L , fc,H,ooceul:cni(c.H r), r
c,H,oocr,-Ei c-cH, I
l -Ethoxy-3-(trimethylsilyloxy)-l'.}l 14* 2lCycloaddition to o,'anirr, cycloaddition of l t ZnBr2-catalyzed protecting grouPs. Thus the rerrr \HTos-protected2 reactsto give r
o N i o\ ll i l8l --------+ z^8.
il c
cHl
M. Tl Y. Kita,S. Akai,M. Yamamoto,
J. Jurczak,A. Colebiowski,and J. R.r
c,H5oocxl.--cH!
*- .",H "",4-r+,c.*),BJ
Ethyl diazoacetate, Nz:CHCOOCI RCHO + RCOCHzCOzCtCsj :oce of various Lewis catalysts. brn ocrmitting reactions at -25". Yicld
Ethyl diazoacetate
I E. J. Coreyand B. W. Erickson,J. Org.,39, g}l (1974). 2 M. Hatanaka,Y. Himeda,and I. Ueda,./.C.S. Chem.Comm.,526(lgg)\.
ine canselectivelycleavethe gly-
Ethoxytrimethylsilylacetylene, = COC2H,(l) , 12, 221. (CH3)3SiC Esters,lactones,and peptides. The reagentservesas a dehydration agentfor condensation of RCooH with alcoholsor aminesto provide esters,lacronesor lactams,or peptides,usuallyin the presenceof a mercurycatalyst(HgO). R'cooH * I
l ( . .
r'\..
-1 R'oH Hetut, l-n,cooc:cHsi(.--c H 3 ) r R'cooR' | | l;
oc2Hs
L
i i
+
J
c6H5CH2NH(cH2)3cooH +"
J",.un, + AcNHCHTCHTOH
Chc-.Res.(S),152(1989). pnium bromide (l). Preparedby irh PrCuHr)3.1
I t
' Y. Kita,S. Akai,M. Yamamoto, M. Taniguchi, andy. Tamura,Synthesis,334 (19g9). l-Ethoxy-3-(trimethylsilyloxy)-1,3-butadiene (1, Danishefsky,s diene). 14+2lcycloaddition to s,-amino aldehydes.t The diastereoselectivityof the znBr2-catalyzedcycloaddition of I to n-alaninals(2) canbe controlled by the Nprotectinggroups. Thus the reaction with NHBoc-2 is syn-selective, whereas NHTos-protected 2 reactsto give a l:l mixture of anti- and syn-3. In contrast,
T<1, i", o
,Rt
I
rph.ranereactswith q-bromokeglop€ntadienes by a [3 *2]annelal3:aandb.
o N'i\p' ( li r + Hi-cucH, ,
tn"',,
o
CH,
f
anti -3 R' = H, R' = Boc 75Vo gTVo R', R' = Bzl R' = Bzl, R2 = Boc 85Zo
T
25:75 9 0 :l 0 93:7
drprotected o-alaninalsreactwith high azrl-selectivityandthe diastereoselectivity is cnhanced with increasingsterichindrance.
a
J. Jurczak, A. Golebiowski, andJ. Raczko, J. Org., 54,2495(lgg!D.
-:'
c,Hsooc
Ethyl diazoacetate,N2:CHCOOC2H5(l). RcHo + RCoc*2co2czcs.' This reactioncanbe effectedwith l in theprescnceof variousLewis catalysts,but Sncl2, Gecl2, and BF3 are the most efficient, pcrmittingreactionsat -25o . yields are generally50_90To.
Ethyl isocy.norcetrte
o
tl
I, SnCl,
c#scH2cH2cno fr:tl-
C2H5CH2NO2+ CJL(
c6H5(cH2)2ccH2cooc2H5
'C. R. Holmquist J. Org.,54,3258(19E9). andE. J. Roskamp, Preparation(13, Ethyl a-(hydroxymethyl)acrylate,CH2:C(CH2OH)COOC2H5. 322\.1 a,-Methylcnc-'y-butyrolactozes.2Theselactoneshavebeenobtainedby reaction of the nickel carbonyl complex of 2-(bromomethyl)acrylatewith carbonyl compounds(6, 93). They are also formed by allylation of carbonylcompoundswith ethyl in 1,3-dimethylc-(hydroxymethyl)acrylateand SnCl2catalyzedby PdCb(CoH5CN)2 imidazolidinone(DMI)/HzO.
l-H I ouu,| )":.1 IC"H.
c
o CHr:Ca
t9ON,ttl'
PdOD,
+ C.HTCHOI
cHroH
n,c=Ao
q.
CuH,
This reactionshowshigh syn-selectivitywhen the hydroxymethylgroup bearsan alkyl substituent.
lcoocH3 + BuCHO;+ CHr:Ca CHOH
I
CH,
H,cfs
o tl
,H..Bu cH, (synlanti= 95:5)
' J. Villieras and M. Rambard,Org. Syn.,66,220 (1987). 2 Y. Masuyama,Y. Nimura, and Y. Kurusu, Tetahedronlztters,32,225 (1991).
CNCH2COOC2H5. Ethyl isocyanoacetate, furrole synthesis, A new route to pyrrolesr'2 is based on a base-catalyzed to a nitroalkeneto give an intermediate Michael additionof an alkyl isocyanoacetate that cyclizes to a pyrrole. The nitroalkeneis generally obtainedfrom a p-acetoxy nitroalkane(1), preparedby a nitro aldol reactionof an aldehydewith a nitroalkane. (2) is typical. The synthesisof ethyl 3,4-diethylpyrrole-2-carboxylate Barton observedthat this synthesisprovides particularly useful precursorsto porphyrins sincethe pyrroles are unsubstitutedat C5, and the 3- and 4-substituents
rre determinedby the structureof t The pyrrole-2-carboxylatescan bc reductionwith LiAlHr at - 20" ro p retramerizationdirectly to porphyri C,H. r,NaoH .'
C}L
)<
:r(CH:OH):, l9O' ,
(*)
H
Ethyl isocyanoacetate
o tl
r)N(c,H5), To, c2H5cH2No2+ crHrCHo l#; crHrCH-cHcrH,
+ C.H.(cHz)zccH2cooc2H5
so%
|
OAc
(19E9). . sa. -115E
I
'- ls,"a':'-","J--------------.,"#r,i :J ")":.a*o'l l o'u' [
(13, =C, CH:OH)COOC2Hs. Preparation havebeenobtainedby reaction !c lacrones with carbonyl comIodromethyl)acrylate with ethyl 11larronof carbonylcompounds in 1,3-dimethylllzcd b1 PdCI2(C6H5CN)2
cNcH'cooc'H' [*ootY*,
'lff;'J-""o' c,H. - - \
o
-)t
\
// \\ \*z-cooc,H, H
/
)
CuH, ; rhen the hydroxymethylgroupbearsan
o tl lfi r + r +
HrC\(
cH,
aredetermined by the structureof the nitroalkene,which is subjectto widevariation. The pyrrole-2-carboxylates can be useddirectly for porphyrinsynthesisby careful reductionwith LiAlH4 at -20" to provide2-hydroxymethylpyrroles. Theseundergo tetramerization directlyto porphyrinsin the presenceof acid (TsoH) andan oxidant C,H." ) - < ' C'H.-
O \
c,H. / ' -
,--n
ll
rc -> u'c=io
I
/
r)NaoH
,
Bu
(synlanti= 95:5)
2)(cH,oH),. reo. >
l) TSOH, C6H6, A
(
\ 'N'/
+ HCHO
2to'
'1 5q, orenll
>
H
l. ::., ,198?). f t :. : qedron l*tte rs, 32, 225 (1991).
t: I py:rolesr'2is basedon a base-catalyzed [lc (!r a nitroalkeneto give an intermediatc E r: generallyobtainedfrom a p-acetoxy rcac(ronof an aldehydewith a nitroalkanc. rl-carboxylate(2) is tYPical. por rdesparticularlyuseful precursorsto lrruredat C5, and the 3- and4-substituentr
N H
H N
Ethyl 3-oxo-+Pentenoote
(Ozor chloranil). Yields are improvedby additionof methylalas a sourceof formaldehyde.Under the best conditions,the pyrrole 2 was convertedto octaethylporphyof .in il) in 55% yield.zThis route to porphyrins is particularly useful for synthesis porphyrins containinghinderedaryl groups at C: of pyrrole' ap6ciaettrytporphyrin can also be obtained from 2 by a more conventional and proach.3fir" o-Lri"t group is removedby saponificationand decarboxylation, formaldehyde ihe resulting3,4-diethylpyirole is condensedin benzenewith aqueous air (yield with in the presJnceof TsOII with removal of water and then oxidized 75%1.3 fD.H.R.Barton,J.Kervagoret'andS.Z.Zard,Tetrahedron,46'7587(1990)' ibid'' 46' 7483(1990)' 2 N. Ono,H. Kawamura, andK' Maruyama, Mi Bougauchi, 70' 68 (1991)' Syn'' 3 J. L. Sessler, Org' Johnson, M. R. and A. Mozaffari, Ethyl 3-oxo-4-pentenoate(1, Nazarov reagent)' of the This annelationreagent can be prepared most simply by condensation lithium enolatdof ethyl acetatewith acrolein to provide ethyl 3-hydroxy-4-pentenketone(l) in63-67% overall oate(2). Jones'soxidationprovidesthe corresponding l) LDA, THF, -78" 2) CH':CHCHO
-# CH3COOC2H5
Ferric chloride. Nng expansion of l'silYloxYcl carbonring expansionof a-(silyln 120) can be extendedto ring crPr aldehydes(equationI), but shorr R"SiO
0)
z\.x,
CH
(A,,l
I -silyloxycyclohcxrrc substituted II, III). Lewisacid(equations
OH
I
llrC: cHCHCHTCOOCTHT
/l 0r)(
,
rcHo
\J
-#--
o tl
r."Osi(i-pr)r
R(rrl
tcH.
Hrc:cHCCH2cooc2H5 I
with only a yield. Methacroleinand crotonaldehydecanbe usedin placeof acrolein, vinylketoesters'r ,ligh, d"..""re in the yield ofthe corresponding r R . Z i b u c k a n d J . M . S t r e i boerrg, . S y n . , s u b m i t t e d ( 1 9 9O 1 )r;gJ"' 5 4 ' 4 7 1 7 ( 1 9 8 9 ) '
/--\
(lll) (
\Jl
,cHo
Y.. "OSi(t-Pr),
a
H,C'CH,
|,4-Atlitition to acrYlolcs.' F of primary or secood 1.4-addition
CHz:C11"OOC,H, + HNIC CHt:CHCOOC'H' +
Si-directed Nazprov c! chz4b dt€ stereoselectivityof this cycliz
I of methylalasa sourceof formalras convertedto octaethylporphyof panrcularlyusefulfor synthesis py-rrole. of ; m 2 by a more conventionalaPand ffication and decarboxYlation, cuene with aqueousformaldehYde ' and then oxidizedwith air (Yield 45, 7587(1990). ttahedron. 46,7483(1990). ibid., ryrma. 3 S r n. 7 0 ,6 8( 1 9 9 1 ) .
of the rsr .rmply by condensation prrtr rdeethyl 3-hydroxy-4-pentenrdrngketone(l)in63-67% overall
CCX)C.H.
Ferric chloride. Nng erpansion of l-silyloxycycloalkanecarbaldehydes.rThe methodfor one(14, I 19with CI2AIOC6H5 carbonring expansionof a-(silylmethyl)carbaldehydes 120) can be extendedto ring expansionof unsubstitutedsilyloxycycloalkanecarbaldehydes(equationI), but shows slight or no regioselectivityin expansionof 2-
substitutedl-silyloxycyclohexanecarbaldehydes. In this caseFeCl3is the preferred Lewis acid (equationsII, III).
i#rGDa):l' -osi1i-n;, 8e% ft q
4
\_/
'CH,
o tl
o,,*,+ 'cH,
t4: I
HrC:CHCCHTCOOCTII' I
prl rn place of acrolein, with onlY a r rnr Iketo esters'I t l+rl r: .I. Or9.,54,4717(1989\.
olr) ay::" q
'osi(i-pr)j
";.....-, ftor*, + 82%
\_,/ H,C'CH,
H,t-cH,
26:l
|,4-Addition to acrylates.2 FeCl3is the most efficient Lewis-acidcatalystfor 1,4-addition of primary or secondaryaminesto acrylates. FeCII
CHr:g11gOOCrH,
+ HN(C2H5)2t#
CHr:611gOOCrH,
+ BuNHr'
(C2H5)2NCH2CH2COOC2H,
l;-
BUUUCH2CH2COOC2H5
Si-directed Naurov cyclization (14, lM-165). Denmark et al.3 have examined fie stereoselectivity of this cyclization with optically active p'-silyldivinyl ketones
l6t
Ferric chloride
suchas(*)-and(-)-l.Ineachcasethecyclizationoccurswithessentiallycomplete control bY Si in the cnti-Sfi sense.
MOMO
NaBH., CeCl.
FeCly cH.cl". -50" _+-) 72%
The minor productof this dimerization.( provides(-)-3, which on treatmentwith K: (4\ in 40/o yield with retentionof the arid OH
85%
H
(s)-(-)-r
l) K,K: 2) N,O'
H
(4: l, both 86Vo ee)
(869o ee)
iDrt
(-)-3 H
(R)-(+)-1 (887oee)
(+)-2 (887o ee)
of the symmetrical Stcreoselectivcsynthesiso! perylenequinones'aSynthesis of two identical coupling by effected been perylenequinonephleichrom. iO ftut n.pntn.t.n"unitstoprovideabinaphthol,whichisthenoxidizedtoaperylene. quinone.Thusthebromonaphthalenelonhalo-lithiumexchange(r-Bul.i)followed byreactionofanhydrousFeCl3dimerizestotwoopticallyactivebinaphthyls'(+)and(-)-2, with 3:l diastereoselectivity' OBzl
of (S)-l bl' Inversionof the stereocenter is convertedby thc This bromonaphthalene calphostinD (5). In this casc6 lcnequinone rion stepis oppositeto that observedwith (
I ) rBdJ 2) Kl 3) f.Frc!
cH,o
l) rBuli 2) Fcclr -78 + 20'
(R)-r CH,
cH3o (S)-f, R = Si(CoHs)z-r-Bu
Of a number of metal salts tested, CoCll :,rupling of model naphthyl bromides, but t
CH
CH, a
CH,
(+)-2
3 :I
cH30
T. Matsuda,K. Tanino,and I. Kuwajime.Icn J Cabral,P. Laszlo,L. MahC,M.-T' Monurl ,1989). S E. Denmark,M. A. Wallace,and C. B. Wr 'C A. Broka, TetahedronLetters,32, t59 (l!
fcrrocenylphosphines, chiral, ll, 237 -2t Asymmetric cross-coupling.r lapam t mmetric ferrocenylphosphine, which coo
Ferrocenylphosphines,chiral
complete rron occurswith essentially
The minor productof this dimerization,(-)-2, on desilylationanddebenzylation provides(-)-3, which on treatmentwith K3Fe(cN)6is convertedinto phleichrome (4) in 40% yield with retentionof the axial chiralitv.
OH t H
HJI .\^i-
----------+ I
| | t5% \.4__a.-,,,
H
169
MOMO
OH
o
HO
|
H
(4 : 1, both 86Vo ee)
CH
)t?s.' Synthesisof the sYmmetrical fe;rcd by couPlingof two identical ilrr;r',rs then oxidizedto a perylene(t-Bul-i)followed D-i:lnrumexchange (*)1,. ..pticallyactivebinaphthyls,
M
,
MOMO
r+)-2 t887cee)
cu, i][]59t"$'cu,o ,
cH3o
CH3o
OH (-)-3
HO 4
Inversionof the stereocenter of (s)-r by the Mitsunobureactionprovides(R)-1. This bromonaphthalene is convertedby the samesequence as aboveinto the perylenequinone calphostinD (5). In this casethe axial stereoselectivity in the dimerization stepis oppositeto that observedwith (S)-1.
o H o MOMO
OBzl
ocH3
l) tsBuLi 2) Fecll 3) K.Fe(CN)^
---)
CH
CH, CH,
CH,
5 of a numberof metalsaltstested,cocl2, cucl2 , and (c6H5)2cucl2alsoeffected couplingof modelnaphthylbromides,but they are lesseffectivethan Feclr.
CH.O
Org.,55,5543(1990)
CH.O
MOMO
OBzl (-)-2
-240; 14, 165-l6j . fcrrocenylphosphines,chiral, ll, 231. Asymmetriccross-coupling.l Japanese chemistshaveprepareda new chiral c2rr mmetricferrocenylphosphine, which combineswith pdcl2 to form a highly active
l?0
N-Fluoropyridinium trlfluoromethenesulfonote
$.N1or,y, (f.H5)'
a \n
t>ru"r, (1) I
F
(CuHr)t
2
Hc'HN(cH3)' of alkylzinc chlorides with vinyl brocatalyst (1) for asymmetriccross-coupling mides.
""'t6".":.", t"'..^.,., ^,,"s!--[-t"'..o"J,,''lii1!l,i:u, '** /-----,pHMeCtc#,
l^,-/Lc.",
I J
CoH,
(R,93Voer')
lT.Hayashi,A.Yamamoto,M.Hojo,andY.Ito,,I.C.S.Chem.Comm.,495(1989).
N-Fluoropyridinium triffuoromethanesulfonate' are fluorinating reagentsare known' most Although a number of electrophilic toxic,unstable,anddifficulttohandle'Thesenew'stableN-fluoropyridiniumsalts in by reactionof a pyridine with FzlNz(l/9) are readily obtainedin-OO-SOfyield CH3CNin the presenceof sodium triflate'
A \N'
--[o-l Na.rf>o =o
ff;l
-oTf
Fluorination.,oneadvantageofthesefluorinatingreagentsiSthatthereactivThe 2,4,G substituentson the pyridine ring. ity can be controlled uy variatioi of the penwhereas reagent' active than the parent trimethylpyridinium triflate is less of range wide a Becauseoithis variation' tachloro triflate is the most reactive' nucleophilescanbefluorinated'andselectivefluorinationsarepossible.Benzeneand phenol and pentachloro salt in CHzClz' but naphthaleneu." noo'io"t"i Uy ttre contriflate trimethyl The unsubstitutedsalt. naphtholare fluorinateoiv-t#p"t.ni organolithium corresponding but not the verts alkyl or aryl Grignaio, inio fluorides, reagents.Thetrimethyltriflatecanalsofluorinateactivemethylenecompoundswhen ring, it is by variation of substituentson the activatedby znct2", ;iai;. Thus
possibleto fluorinatearomatics'carbrnkr or silyl ethers,vinyl acetate,and eveo d regioselectivefluorination. Thus fluorial silyl ethergroupswith I equiv. of thc pcn the 9c-fluorosteroid3. No reactionwrs t derivativeof1. The ortho/pararatioof tr ably by changein the counterion. In coc orrho-substitution. andK. Tomita,TetahcdroeIt T. Umemoto K' Kasrde' r K. Harasawa, G. Tomizawa,
FormaldehYde. Hy droty methy lation ol anthrtqrb' r iewedthis reaction,particularly for thc larly useful for preparation of opicell rldehydes(166 references)' 291(1990)' K. Krohn,Tetrahedron,46'
Formaldehvde
t7l
os(cH3)3
z\
It
(cH3)3sio
(oJ -orf
F
cH,cl, istk
o
I
It1 lzinc chlorideswith vinyl bro-
N = HBr
gHr.
nr'.' H.',,
.iHCtt:Ctt, ,/
CuH,
(R,93Voee) .C 5 Chen. Comm.,495(1989)'
t. areknown'mostare llng reagents salts cr . rtableN-fluoropyridinium on 0i a pyridinewith FzlNz(l/9)in
r'
' T. Umemoto andK. Tomita,Tetrahedron (1986);T. Umemoto, Letters,27,327l S. Fukami, G. Tomizawa, K. Harasawa, K. Kawada, andK. Tomita,Am. Soc.,ll2,8563(1990). Formaldehyde. Hydroxymethyhtion of anthraquinones(Marschalk reaction). Krohnr hasreviewedthis reaction,particularlyfor the synthesisof anthracyclinones. It is particularly useful for preparationof optically active rhodomycinonesby use of chiral ddehydes(166 references). K. Krohn,Tetrahedron, 6,291 (1990).
z\
tl \i F
possibleto fluorinatearomatics,carbanions,activemethylenecompounds,enol alkyl or silyl ethers,vinyl acetate,and evenalkenes.Thesetriflatescan also be usedfor regioselective fluorination.Thus fluorinationof the steroid2 possessing threeenol silyl ethergroupswith I equiv.of theparentN-fluoropyridiniumtriflategivesmainly the 9a-fluorosteroid3. No reactionwas observedbetween2 and the 2,4,6-trimethyl derivativeof |' The ortho/para ratio of fluorinationof phenolscanbe varied remarkably by changein the counterion. In contrastto triflates, tetrafluoroborates of I favor onho-substitution.
-orf
tnnaringreagentsis that the reactivls on the pYridinering. The 2,4,G hc parentreagent,whereasthe Pcnof this variation, a wide rangeof and pnnationsarepossible.Benzene but CHzClz, in ro salt Phenol and cor triflate trimethyl The salt. Nred organolithiun the corresponding rKlr whcl tc a.'tivemethylenecompounds it b ring, the on substituents !.f Dn
o i l
ft- c' s' cH3
reagents. Grignard -Benztnnelation
of ketones.r This reaction can be effectedby reaction of an chloride with the silyl ether of allylic Grignard reagentsuchas methallylmagnesium overall yield. u i-hyd.ory.ethylene ketoneas shownby conversionof I to 2 in86%
CH"
"oe", I
N{c:H.). r)(cH\),sicr, I ziiH,:crctt,rcit,Mgct,
t
osi(cH3)l
(-^J
"o"'t"""'"'o' ""lufff
Thususc yields requirea cation-stabilizinggroup at c2 of the Grignardreagent. High -onym"gn"sium benzmethyl-unsubstituted yields, but low from suffers chloride of Usc chloride. 2-trimethylsilyl-2-propenylmagnesium with annelationcan be effected Acyderivative' naphthalene a to in annelation results bromide of benzylmagnesium results in clic ketonesas well as phenonescan be precursors. Use of the latter + 4). biphenyls(3
172
,/
3
I M. A, TiusandG. S. K. Kannelgrn
Grignard reagents
o :t l o /t'{t"-t' t t l ../ cH, rn be effectedbY reaction of an m ;hloride with the silYl etherof i6n .ri I to 2 in 86VooverallYield.
f".
,,,,\
'CHt
Ho-
,2--l.. /
\
I
os(cH3)3 I
.,.^"t-Z
-L
tro". c6HrcHt,8oo
CH.
2
of rheGrignardreagent.Thusurc benzb. bur methyl-unsubstituted chloride.Usc propenylmagnesium derivative.AcY' ro a naphthalene rcrs Use of the latter results ir
3
H
-rsf cH, 4
'M. A, TiusandG. S. K. Kannangara, Org. Syn.,submitted (1990).
173
llYdrido{
T'
0) HTNNHR + O:C:NCHCOOR'
canbe of cvclization method r c'cl'-tion (14' r73-r74)' This 56-substituted of case in the iin'iyOriO"cyclization moreusetultfranreOuctile iodide'
"*#:tt*fl*fr;
in a vinyl ifr" furthlr advantageof resulting hexynyl iodidessuchas i "nOi", conductedby best is Th-ereaction which can be usedf", fu;;;;;..,i"nuri"u,ion.t catalytic amountsof hexabutylditin' photolysisin benzeneat 80o with 9H'
Bu,snsnBu'
I
l
J
1
\-J
,'l
l
'1t%n
IgH'
I
v
r
l
l
,,,St"o.,
^
\_J
t
\--il-o
+ N(CJ'\
2
111'6265(1989)' rD. P. Curran, M'-H' Chen'andD' Kim' Am' Soc'' (HMPA)' Hexamethylphosphorictriamide HMPA with disulfidesor diselenidesreactin oiattyt Vinyl sulfides("1;;i-;' sulfidesor selenides o. "Ur"n." of CuI to form vinyl vinyl bromidesin the ;;;"
jL cuH.cH:cHBr+ coH.SeS"cuH' HMPA {Cul)
CHr:6g11tuH,+ C.H,SSC.H, #I
'i. (1989)' Gante,SYnthesis,405 ' c.-J"p"y i"o J' L' Luche'Tetahcdroa'1
1 p , 1=7 5 : t ) ,tCH'
t#'"":t\^^,, sc"H'
andTHF and DMSO are lesseffectiveasthe solvent' asthe major product' DMF and dioxaneare ineffective' (1989)' rT. Ogawa,K. Hayami,andH' Suzuki'Chem'Letters'769
and propertiesof azapeptides, Ganterhas reviewedthe synthesis is replacedby r group of one or more amino acids substancesin which the a-CH 174
When thc Luche to improve the yield' t potassium addition of a strong base' Triethylrc yield' (KDA), improves the (equation[)' unstableepoxy hydrazone
c'H'c":tlTtJ'
Br
^tur#)Ii;*rr.
of intcn nitrogen atom. These peptides are reactions' activity or improved enzymic by ne naturai amino acids can be prepared follor ketonesto give the Boc-hydrazones' b1 formcd be can linkage of azaaminoacids r thc frequently' esterJlequationI). More flexibility' emolovedbecauseof greater Tl Wharton reactionz(f , 439-440)' sca has hydrazone alcoholsvia an epoxy Somc er field becauseyields can be low'
Ity ilrirtotris(triphenylphosphlne)coplt Reductiono! alkYnesto cisdlera intcrr reducesterminal alkynesat 25'; 2 require reductions These exclusively' sl for l0 equiv. of H2O is necessarY convctlG was acetate propargyl rcrtiary CHr(t)
-OAc
I
tr"r\"
l' M J. F. Daeuble,C. McGettigan'and
Ilydridotris(triphenylphosphine)copperhexamer
R' I (I) HTNNHR+ O:C:NCHCOOR,
Ihrs methodof cyclizationcan be 5bn rn the caseof 6-substituted ntaeeof resultingin a vinyl iodide, The reactionis bestconductedby Drsoi hexabutylditin. IH '.-,- I
'
----+ HTNNCO_NHCHCOOR,
nitrogenatom. Thesepeptidesare of interestbecauseof possiblemore potentdrug activity or improved enzymic reactions. Most of the azaaminoacids analogsof naturalaminoacidscan be preparedby reactionofBoc-hydrazinewith aldehydes or ketonesto give the Boc-hydrazones,followed by catalytichydrogenation.The amide linkageofazaaminoacidscanbe formed by reactionofhydrazineswith c-isocyanato esters(equationI). More frequently, the active estersusual to peptidesynthesisare employedbecauseof greater flexibility. wharton reaction2(1, 439-u0). This rearrangementof c,p-enonesto allylic alcoholsvia an epoxy hydrazonehas seenonly occasionaluse outsideof the sterol field becauseyields can be low. some expedientshave been shown by Dupuy and
\__:ro
i l 1 6 : 6 5( 1 9 8 9 ) .
reactin HMPA with ror irselenides vinyl or selenides torm sulfides rr. I
('-H.CH:CHSeCoH.
\
+ N(crHr), 73vo
lo"
Luche to improve the yield. when the intermediateepoxy hydrazoneis isolable, addition of a strong base, potassiumr-butoxideor potassiumdiisopropylamide (KDA), improvesthe yield. Triethylamineis the baseof choicein the caseof an unstableepoxyhydrazone(equationI). rJ. Gante,Synthesis,405 (1989). : C. DupuyandJ. L. Luche,Tetahedron, 45, 3,437ilgggl.
( U Z= 5 : l )
,^
/CHt
!-- 1 -11.611-g' l
\
sc6H. f,cctrreasthe solvent,andTHF and a.
R
/".".L cHo (D ( \ x + ; (,rilA \F "", cHy'
:
i
R
l7S
-r,9 tl9E9).
E!r\ andpropertiesof azapeptidcr, rnoreaminoacidsis replacedby r
Hydridotris(triphenylphosphine)copper hexamer (f ), f 4, I 75; 15, I 66. Rcductionotalkynes to cis-alkenes.t This relatively stablecopperhydride (l) reducesterminal alkynesat 25"; internal alkynesare reducedat g0o to cis-alkenes exclusively.Thesereductionsrequire2 hydrideequivalentsof the complex,and5l0 equiv. of H2o is necessaryfor satisfactoryyields. Under theseconditions,a tertiary propargyl acetatewas convertedto an allene (equationI).
rtAn
CH. (I)cJt,<"
l, 30. ----------t 8t%
CH" C:C:CH^ CuHr'
J. F. Daeuble,C. McGettigan,and J. M. Stryker, Tetrahedronl*tters, 31, 2397 (lgg1\.
176
Hydrogcn pcfod...Ie
Hydrogen azide-Dlisopropylethylemine
Hydrofluoric acid-Boron trifluoride. Cyclodehydration. The commercial preparationof an antihistamine(Loratadine, 3) requirescyclodehydrationof the ketone1. Use of the usual reagentfor this reaction, polyphosphoricacid at 190o, leadsto a mixture of two productsin about -30o, 45% yield. The most useful and reasonablypriced reagentis HF and BF3at which gives2 in >90% yield.
OTs
,
E <cu.t,cj?---*J
epoxyesterswith markedpreferencefor u obtainsin cleavagewith dialkylamincs(13. I high (10-73:1) for chiral trans-2,3'c'potya the Cr-substituent.However, the Crsclcctiv low (1.3-5.8:1). Even so, this reactiooPn amino acids. The reagentcan also convcn I ' S.Saito,N. Takahashi, andT' llol T. Ishikawa, :S. Saito,H. Yokoyama, N' Nin' T. Ishikawa,
N-
I
CH3 2
-'ool!]fiff'"' .,
Y
a\ t
l
\N/
Cooc,H,
Hydrogen peroxide-Areneseleninicdll Baeyer-Villiger ori.dation.r Aromerk t generallyhigh yield by oxidation with byd acid. Polymethoxyacetophc areneseleninic loweryields.
r
x8.?hT. |L ------------'--+ 2.5-(CH3O)rC6H,CHO
3 g* 2,4-(CH3O)rC6H3COCH3
rq
I D. P. Schumacher, B. L' Murphy,J' E. Clark, P. Tahbaz,andT' A' Mann,J' Org' ' 54'2242
(198e).
(1989)' L. SyPer,SYnthesis,167
Hydrogen azide-Diisopropylethylamine. selectivecleavageof 2,\-epoxy eslers.r The highly toxic reagenti-Prz(CzHs)NHN3(1)2,obtainedby combinationof hydrogenazideandthe amine,cleaves2,3OH
o
BzlOCH,. / \
"Y-
Bzlo:z'*:v'coocH3 I
-coocH.
N3
OH i
^., r^- -COOCH. ' CHr- )a : Br
OH r. -DMF,6op
aseo
>
cH-^/coocH3 ---5 I N3
Hydrogen peroxide-Dimethyl sulfori&' Hydration of nitriles. This conversir vieldby reactionof nitrileswith H2O2(30t caulyst. The reactionis completein l-3O oot affected.
A. R. Katritzky,B. Pilarski,andL. Urogdt.I
Eydrogen peroxide-Formic acid-PolyF t > S + > S: O. This oxidationcrn b or acetic acid in CHzClz.t If polyphotptt
Hydrogenperoxide-Formicacid-Polyphosphoricacid(PPA)
nrrronof an antihistamine(Loratar I Useof the usualreagentfor this r mrrture of two productsin about rd reagentis HF andBF3at -30o,
177
N, lcttrlrc--?-----'--/
Ot. ,, 84%
Gu,l,c_.?--J
epoxy esterswith markedpreferencefor attack at c2. Note that a similar tendency obtainsin cleavagewith dialkylamines(13, 312). The c2-selectivityis consistently high (10-73: l) for chiral tans-2,3-epoxyesters,and dependson the stericbulk of the c3-substituent. However,the c2-selectivityfor cis-2,3-epoxy esteris generally low (1.3-5.E:l). Even so, this reactionprovidesa useful route to p-hydroxy-oaminoacids.The reagentcan alsoconverthalidesand sulfonatesinto azides. ' S.saito,N. Takahashi, T. Ishikawa, andr. Moriwake, Tetrahedron Letters,32,667(lggl). I S. Saito,H. Yokoyama, T. Ishikawa, N. Niwa,andT.Moriwake,ibid.,32,663 0991).
I
CH, t
-* ^ ' 1.,.-.,", c6H.cH. I
Y
Y l\ N /
Hydrogen peroxide-Areneseleninicacids. Baeyer-villiger oxidation.r Aromatic aldehydescanbe convertedto phenolsin generallyhigh yield by oxidationwith hydrogenperoxide(30vo) activatedby an areneseleninic acid. Polymethoxyacetophenones are alsooxidizedto phenols,but in lower yields.
l
I
cooc2H5 3
H:O'C6H.SeO,H t ?l H:o'cHrctr' 2s'> 2,5-(cH3o)rc6HrcHo L^tatfl
%
,.r-rrrro)2c6HroH
H,O,
5ar. andT. A. Mann,J. Org.,54,2242
JgH% 2,4-(c\o) ;C 6H3cocH3
2,4-(cH3o)2c6H,oH
L. Syper, (19E9). Synthesis,167 I hrghlytoxic reagenti-Pr2(C2H5)a azrdeandthe amine,cleaves2,3OH Bzlo\-,1.-.coocH3
I
N3
Hydrogen peroxide-Dimethyl sulfoxide. Hydration of nitiles. This conversioncan be effectedconvenientlyin 65-99% r ield by reactionof nitrileswith H2o2e|To) in DMso in the presenceof K2co3 as .'atalyst.The reactionis completein l-30 minutesand esteror urethanebondsare oot affected. A. R. Katritzky,B. Pilarski,andL. Urogdi,Synthesis,949 (1999).
OH
| (^.. ,^ H -
-coocH. I Nl
Eydrogen peroxide-Formic acid-polyphosphoric acid (ppA). >s + >s:o.r This oxidationcanbe carriedout with H2o2andexcessformic or aceticacid in cH2cl2.t If polyphosphoricacid (l equiv.) is also present,this
178
(2S,5R)-(- )-2-Hydroxydiphenylmethyl-5-(dimethylamino)methytpyrrotidine
procedureis useful for oxidation of penicillin and cephalosporinesters,particularly diphenylmethylesters(generally > 90 % y ield).2 'R. G. Micetich, R. Singh,andS. N. Maiti,Heterocycles,22,53l (1984). 2 M. Tanaka, T. Konoike,andM. Yoshioka,Synthesis,lgT (1989).
1Q-6;';
(cH3)rN
I
Hydrogen peroxide-Tungstic acid, H2O2-H2WO4. Oxidative clcavageof alkenesto carboxylic oci.ds.t Alkenes are oxidized to carboxylicacidsby H2A2Q5%) catalyzedby H2WOain a weakly acidic medium(pH 4-5) maintainedby addition of KOH. The oxidation probably involves initial oxidation to a I,2-diol followed by dehydrogenationto an o-ketol, which is thencleavedto a mono- or dicarboxvlic acid.
^
(CH,)ily^
t t \z^oH
(62Vo)
(184o)
tI
oJ tl c.ttc}t
tioselectiveaddition of (C2H)2Zn to bcaz >95% yield and in94% ee. An intcrmcd
H.O,. H.WO.
' E. J. Corey,P.-W.Yuen,F. J. Hannon. ld
74%
+
r
H"'
i'Si'.fa:i.a^coon + a\o"
ll---------=_l I \-,2 !,cooH
CH3(CHr)5CH:CH,
H O H
CH3(CHr)5COOH + CH3(CH2)5CHOHCHTOH (33Eo)
(l6Vo\
lT. Oguchi,T. Ura,Y. Ishii,andM. Ogawa,Chem.Letters,E57(1989).
(R)-3-Hydroxybutanoic acid. Completedetails are availablet for depolymerizationof the biopolymer of this acid, which is produced on an industrial scale and is available from Fluka and Aldrich. ' D. Seebach, A. K. Beck,R. Breitschuh, (1990). andK. Job,Org. Syn.,submitted
[Hydroxy(tosyloxy)iodo]benzene'CH!C. Flavanones+ Isoflavoncs. Althoolf tosyloxylationof ketones,rthe reactioo r | ,2-aryl shift to provide isoflavones(3) ir effectedpreviously with thallium sdts. Z2-.,r'.O'.-/.CoHrR
R ' { lll#
\ry
o ,
(2S,5R)-(- )-2-Hydroxydiphenylmethyl-5-(dimethylamino)methylpyrrolidine, 1. The pyrrolidine is preparedfrom ethyl (S)-N-(ethoxycarbonyl)pyroglutamate. Enantioselectivcaddition of (C2H)2Zn to C5H1CHO.\ Guided by results of Noyori's groupwith a p-aminoalcohol(14,233-234)andof his own groupwith the oxazaborolidines,Corey et al.t have preparedthe pyrrolidine I as a controller for enantioselective additionof R2Znto aldehydes.Reactionof 1 with (C2H)2Znforms a crystallinecomplex (2). This complex can function as an efficientcatalystfor enan-
Review. Moriarty and Kosef heve r pound.It is particularly useful for vic, cit of ketones,and conversionof primary u
' G. F. Koser,A. G. Relenyi,A. N. Krlocr. 2487(1982). :O. Prakash, S. Goyal,S. N. $tl S. Pahuja, ! R. M. Moriarty,R. K. Vaid,andG. F. Kc
im rmcthylpyrrolidine
[Hydroxy(tosyloxy)iodo]benzene
phalosporinesters,particularly r . t 2 . 5 3 1( 1 9 E 4 ) . 9- ,1989).
rc).''t;;Xi
(CH3)rN
H
t79
CuH,
C#'
OH
I
I
C,H,
ddr.r Alkenesare oxidizedto yrn a weaklyacidicmedium(pH probablyinvolvesinitial oxidal-\etol. whichis thencleavedto
(cH3),N\^.\E:il: H""i I Zn-O I
i l
tun""
,-Yo" \-
"
os
l8q)
Ji \ 'Zn(CrHr), C,n. - "
tioselectiveadditionof (C2H5)2Zn to benzaldehyde to form (S)-l-phenylpropanol in >95% yield and in 94% ee. An intermediatecomplex such as a may be involved.
o.
rE. J. Corey,P.-W.Yuen,F. J. Hannon, andD. A. Wierda, (1990). J. Org.,55,7S4 ' CH,rCH')TCHOHCHTOH (l6Vo) r r s . 8 5 7( 1 9 8 9 ) .
[ron of the biopolymerof this d rr availablefrom Fluka and (1990). 3 5rn..submitted
lt lemino)methylpyrrolidine, n ry carbonyl)pyroglutamate. ItCHO.t Guidedby resultsof ') andof his own groupwith the trrrrlidine I as a controllerfor formsa ion of I with (CzHs)zZn rs an efficientcatalystfor enan-
(l), 14, I 79- I 80. CH3C6II4SO3I(OH)C6H5 [Hydroxy(tosyloxy)iodo]benzene, Flavanones+ Isoflavones. Although Koser's reagent(l) is known to effectatosyloxylationof ketones,rthe reactionwith flavanones(2) resultsin an oxidative | ,2-arylshift to provideisoflavones (3) in 74-80% yield.2This conversionhasbeen effectedpreviously with thallium salts.
.ery"'r**#^'e$",".* o
o
2
3
Review. Moriarty and Koser3have reviewedthis hypervalentiodine(Ill) compound.It is particularlyusefulfor vic, cis-ditosyloxylation of alkenes,o-tosylation of ketones,and conversionof primary amidesto amines. G. F. Koser,A. G. Relenyi, A. N. Kalosa, L. Rebrovic, andR. H. Wettach, t. Org.,47, 2487(1982). : O. Prakash, S. Pahuja, S. Goyal,S. N. Sawhney, andR. M. Moriarty,Synlett,337 (1990). ' R. M. Moriarty,R. K. Vaid,andG. F. Koser,Synleu, S65(1990).
lEO
(R)-(+F2-Hydroxy-l'2'2-triphenylethyl
acetate
(R)-( + )-2-Hy droxy-1,2,2-triphenylethyl acetate(1). Preparationfrom methyl (R)( - )-mandelatet: H
C^H.
"oX.oo"^,#
cH.cocr, "cs,cr, p".
H- C"H,
coH,MgBr,
"o\o"
G---
H- C6Hr 1i
A ll
cH,Ao)z-oH c6H5 c6H5
c6Hs c6H5
l, m.p.241', ao + 211",>997oee
m.p. 124-126", a" + 223"
$-Hydroxy carborylic acids(12,3).2 This acetateon doubledeprotonationwith aldol reactionswith aldehydes.The adductsare LDA undergoesdiastereoselective easily hydrolyzedto optically active p-hydroxycarboxylicacidswith releaseof (R)the precursorto 1. Opticallypure acidscan be (*)-1,1,2-triphenyl-1,2-ethanediol, with an optically activeaminesuchas (S)-(- )salt of the crystallization by obtained
r .l.
Indium, In. Cyclopropanation.r Electron{cf cicr bromidesand indium to form cycloproplu with dibromomalononitrile,lithium iodi&.
CH2:611"O"H,
+ BrrC(C!{}
l-phenylethylamine. ,,CN + BrrC( C2H5CHO -coocJt I + CH2:CHCHO
,,=[.,,
J.C'S.Chcn.Cq S. ArakiandY. Butsugan,
m*Jrou, H,o/cH,oH HO
H
cH,:gp1/"-'cooH
Iadium(IID chloride' InCl3. Catalyst tor reactions of Gtrid pliles.r Indium(Il! chloride in combinaio
H C^H.
+ "o1;o"
(83.5Vo ee)
I M. Braun,S. Schneider,and S. Houben, Org. Syn',submitted(1990)' 2 M. Braunand S. Schneider,ibid., submitted(1990).
C6H5 C6H5
c6H5. ,osi(cH3)3 + (Crtl),SiH X sc2H5 cH, for conversionof O-trimethylsilyl rtood ,C:Hs):SiH.
os(cHr
osi(cH3)3
*
c6H5c(
sc2H5
c.Hr^cHcl
u ** I:iliF,iT:lif i1""' J
sc"H.
t - -
C.H,CHCH,CH:CH'
from methyl(R)lr r I r. Preparation
Cti . , (-. h . i'i r-l -------.-J
O
H C.H.
.",Ao\fo' c6H5 c6H5
I, m.P.241", ee a" + 217",>99Vo with Eerareon doubledeprotonation E \r rth aldehydes.The adductsare rrtrc'r1licacidswith releaseof (R)tr ttr l. Opticallypure acidscan be icallr activeaminesuchas (S)-(- )-
r
I
Indium, In. cyclopropanation.r Electron-deficientalkenesreact with active methylenedibromidesand indium to form cyclopropane s in 35-95% yield. Reactionof aldehydes with dibromomalononitrile, lithium iodide, and indium alsoprovidesepoxides. In. Lil,
^LT
CHz:CHCOCH,+ BrrC(CN)r#
""rfiX;; o
c,HscHo * n,,c(cN -"-\cooc,H,
t'T:XXll^^., -- --) Hur%-
b/'cooc2Hj
' S. ArakiandY. Butsugan, "/.C.S.Chem.Comm.,12g6 (1999).
[oH. HlOrcHrOH
a4 ,
H )
H C^H. " ai"
.* cooH* "oir:o" ct
, iubmitted (1990).
C6H5
tndium(IlD chloride, InCl3. catalyst for reactions of o+rimethylsityl monothioacetats with nucleophiles.t Indium(III)chloridein combinationwith clsi(cH3)3 is an effectivecatalyst C"H..
C6H5
.OSi(CH,),
^,,"X^^sc2H5 -. cH,
c t s ( c H ! ) ,r.n c r ! C .H-."')-scr",
+ (crH,),siH--g'c!ll---' etw
cHr'
for conversionof o-trimethylsilyl monothioacetals to sulfidesby reductionwith rC2H5)35iH.
osi(cH3)3 /os(cH3)3 l!*r9t c6H5cH * - tr"r", cuH ,,{""cH,
fr i"'r'
c6H5ccHcHC6H5 CH,
*"-'- l"n,:a""",r,,"",,, lnct] JCtsi(cH,)j.
SC"H.
t - "
C6H,CHCHTCH:CH,
It2
lodine-Borene:N,N-diethylaniline
This system also promotes reaction of these acetals with silyl enol ethers or allyltrimethylsilanes.
lrC
BIr:amir
{
tT. Mukaiyama, Chem.ktters,22t9 J. S. Han,andS. Kobayashi, T. Ohno,T. Nishimura, (1990). HC-CR + Bl.:i Iodine. Iodolactamization(13,149). Full details are availablefor this conversionof y,6-unsaturatedamidesinto 1-lactams.tThe report includesnine examples.
This BI3 complex cleavesaryl mcrl good yield. Dialkyl ethers are coovcll into ddcbydcr, terminal gem-diacetates
$54*$'*"*'[."'H-"]
' C. K. ReddyandM. Periasamy, Tctr*/ ' ldem,ibid.,3l, 1919(1990). r C. Narayana, rd G. t S. Padmanabhan,
,* |l]k*,o,, xa,co, I
Iodine-Silver nitrite' I2-AgNO2. Iodination of arcnes.r Thcsc trt iodinate arenes,particularly mcthyhr numberof methyl substituents,bci4 t
I W.-W.SyandB. A. Lodge,Tetrofudta
.H ...I
Iodomalononitriles' RCI(CN)2. Tb RCH(CN)2with NaH in the prescc t Radicalreactions.t Unlikc kldc di- andtrisubstitutedalkenes.Thus thc
' S. KnappandF. S. Gibson, Org.9yn.,70,l0l (1991). Iodine-Borane : N,N-diethylaniline. providesa ROH + RLr Reactionof Iz (l equiv.) with BH3:C6II5N(C2H5)2 diiodoborane:aminecomplexin situthat convertsalcoholsinto alkyl iodidesin 6286% yield. It also effectsreductive iodination of carbonyl compounds.
./"
*.Yt CN I
G"'#--G, with 1.5 equiv. of ioB\:amine compler.2 Reactionof BH3:C5,H5N(C2H5)2 dine provides an amine complex of BI3. This complex when combinedwith acetic acid liberateshydroiodic acid, which undergoesMarkovnikov addition to alkenes and alkynesin goodyield.
*
./
CH,
-.CuH, ( t r t r l l *a
Iodomelononitriles
Dcralswith silyl enol ethersor
l) cHlcooH
Blr:amine"#
RcHcH3
I
I
Chem.lntters,2239 S Kobayashi, Hc-cR erailablefor this conversionof includesnine examPles.
",,r,oh*t,,"",,'l
o l I I l) I' t0* | 2) NarSOs, Na"CO' I
J
lt3
+ Blr:amine #5
Hrc:cR I
This BI: complex cleavesaryl methyl ethersto phenolsat room temperaturein good yield. Dialkyl ethers are convertedinto iodinated products. It also converts into aldehydes.3 terminal gem-diacetates ' C. K. ReddyandM. Periasamy, Tetrahedron lztters,30,5663(1989). 2ldem,ibid.,3l, l9l9 (1990). I C. Narayana, ibid.,31,6977(1990). andG. W. Kabalka, S. Padmanabhan, Iodine-Silver nitrite, I2-AgNO2. Iodination of arenes,r These two reagentsgeneratenitryl iodide, which can iodinatearenes,particularly methylarenes,at 28'. The yield increaseswith the numberof methyl substituents,beingg0-95Vowith tri- and tetramethylbenzenes.r ' W.-W.SyandB. A. Lodge,Tetahedron lctters,30,3769(1989). Iodonalononitriles, RCI(CN)2. These reagentsare prepared by reaction of (NIS). RCH(CN)2with NaH in the presenceof N-iodosuccinimide Radical reactions.r Unlike iodomalonicesters,iodomalononitrilescan add to I whenheatedat di- andtrisubstituted alkenes.Thusthe propargyliodomalononitrile H
r BH,: C6lI5N(CzHs)z Providesa ilcoholsinto alkyl iodidesin 62rrbonyl compounds.
./"
*YtCN
*
80. t"4, ( % NCj-
.rt"^'
CH,
I$rC:Hs)zwith 1.5 equiv.of iopler whencombinedwith acetic farkovnikov additionto alkenes
.r
cH" tl Bu,snH
--------+ K cuH' 82% {
CH,
CN
I
-/-t
\ j\)
A-C6H, \ / NC'_J.
3
4
,*""^[)+* tb s
CH,
CN
N.d1"
It4
Iodomethylzinc iodide
80' addsto an alkene(2) to form an iodine-containingadductthat cyclizesto 4 on treatmentwith Bu3SnH.The high trdtrr selectivity in a radical reactionis noteworthy. Similar reactionof I with a cyclic alkene(5) is besteffectedby a one-potgroup transferand cyclizationwith Bu3SnH. Reactionof crotyliodomalononitrile(equationI) with alkenesleads to adducts similar to those obtainedwith l, but cyclization with Bu3SnHresults in two products, the major one of which involves nitrile transfer.
cH"
(I)
1
"..r"'+
CN CHr-/
( l) 8oP 2) BurSnH -> g%
+
..Yt
H
1^Y \
CN
.*"p
CNH
20:l
ICH?ril + RSCI (R= r-C,
insertion products formulatcd rs e. trophile suchas an allylic halidc to fr ro the electrophileby a methyler g This procedureis apparentlyliu amides,heteroarylcoppercompoo!& zinc, (lCH)2Zn, resultsin prodrrr
' P. Knochel, N. Ieong,M. J. Rozcnr.r Macrocyclizationcan also be effectedwith an iodomalononitrilesuchas 7. To productwas reducedwith Bu3SnH.The facilitateisolation,the crudeatom-transfer resultingproduct,surprisingly,is the mononitrile8.
H C N NC
-X,
CN
l) 80' 2) BurSnH ----------, 54%
I
(CHr),nCH:CH, 7
-
a ) \ta",1,,/ E
I D. P. CurranandC. M. Seong, z{n. Soc.,112,9401(1990). iodide [(CoIIs)rFCgrI]t- (l). Preparation.t Iodomethyltriphenylphosphonium with the phos(Z)-l-Iotto-l-alkenes. Reactionof sodiumhexamethyldisilazane phonium salt I in THF generates iodomethylenetriphenylphosphorane, (C6H5)3P:CHI,which convertsaldehydesinto (Z)-vinyl iodides(15-62: l) in reactions conductedat -78' in THF/HMPT in 6l-91Vo yield.z ' D. Seyferth, Chem', J. Organometal G. Singh,S.O. Grim,andW. R' Hughes, J. K. Heeren, s,267 (1966). 2 G. StorkandK. Zhao,Tetrahedron Letters,30'2173(1989). Iodomethylzinc iodide' lCHzZril. organocopper-zinc reagents.r This Simmons-smithreagentis obtainedfrom CHzIzand zinc in THF. It can react with someorganocoppernucleophilesto give
N-Iodosuccinimide. NIS. $-Lactams.t A new synthcsisot ions of acyclic amidessuch as l. Pn The amide 1 is convertedinto thc di
(D+
r) &clrfo(rr 2)ncl|{q a-(
ocHl BuLi. On treatmentwith an oxida couplingto cis- and rrcns-p-lactrm regardlessof the R substituent,shc
I ) rBdJ
I ( R =C r H r ) #
I (R:Bztl
N-Iodosuccinimlde, NIS
inrngadductthat cyclizesto 4 on 'in a radicalreactionis noteworr besteffectedby a one-potgroup
lCHrZnl + RSCu{-
f$
IRSCUrCu.Znlr)
(R = n-C,oFIr,)
a o. I arcu,c:cH,. -l ls%l
Ir uith alkenesleadsto adducts rlrh BulSnHresultsin two prod,fer
"",
J
f",
RSCH,CH,C:CH,
r
a u
H
:"'H
-* ,r-n ----/ \A/ NC4 ,! u N"
CN'^
20:l iodomalononitrilesuchas 7. To t '*as reducedwith Bu3SnH.The I CN
insertion products formulated as a, which can then react with an activated elec_ trophile suchas an allylic halide to form a product in which the nucleophileis linked to the electrophileby a methylenegroup. This procedureis apparentlylimited to cyanomethylcopperderivatives, copper amides,heteroarylcopper compounds,andcopperthiolates.Useofbis(iodomethyl)zinc, (lCH2)22n,resultsin productsfrom double insertion. I P. Knochel, N. Jeong,M. J. Rozema, andM. C. p. yeh, Am. Soc.,lll, @74(lgEg\.
N-Iodosuccinimide, NIS. p'Lactams.r A new synthesisof p-lactamsinvolves oxidativecouplingof dianionsof acyclicamidessuchas l, preparedas shownfromp-anisidine(equation I). The amide I is convertedinto the dianion by BuLi (2 equiv.) and DABCb or by /-
NH, t) BcHrcooc(cH.)j.
,\
(I) ll '19{t'
I bkH:lll- (l). Preparation. with thephosnmerhyldisilazane methl lenetriphenylphosphorane, -r rnrI iodides(15-62: l) in reacI r reld.2 . R Hughes, J. OrganometalChem.,
|
N(c,H.)r
2)RcH'cocr' N(c'H')r 68 - e3%
>
J
//-
o
I ocH3
L tr, \coHoocH, I
BuLi' on treatmentwith an oxidant, NIS or cu(ocoR)2, the dianionundergoes couplingto cis- and trans-p-lactams(2). use of NIS favors formationof cis-lactams regardless of the R substituent,whereascu(II) is slightly trans-selective. r)lBuli
R.'.
I (R= C,H,) #-
1989t
tr
O'
/cooc(cHJ,
+ ffans-2 -A, cis-2
-Smith reagentis obtainedfrom to give lanocoppernucleophiles
I (R:BzlrN)
d
cis-2+ trans_2 7:1
l0:r
lodosylbenzene-Dicyclohexylcorbodiimide-Borontrifiuoride diethyl ether
lE6
Use of (R)-( + )-1-phenylethylamineasthe startingmaterialfurnishesan optically activeamide(4), which was usedfor an asymmetricsynthesisof a natural p-lactam. BzlrN--| I
.-COOC(CH3)r | -,
-I-'',
o
\."
C"H,
l) BuLi.TMEDA 2 )N l S
.CH.'
saqa
I
CuHt
OH
I
3 Bzl.Na
'F' ..COOC(CH3),
BzlrN..
l
,COOC(CH.)l
.
l
f*t*.
e5:5
/-*a**
a^) \-A
l,cHlclr> SnBu,
c6H5voH
a)
4
9r*
lT. Kawabata, Am.Soc.,f 11' 6843(1989). K. Sumi,andT. Hiyama,
CH. C6H5I: O. Iodosylbenzene, oxidation of 2-(rtnethylsilylory)furan.r oxidation of 2-(trimethylsilyloxy)2(5fl)-furanones. etheratecan afford5-substituted furan with iodosylbenzene-BF3 C6Hil:O,
Sorn.t,,,
2!""' t l \-
snBut
( 8 9 l:l )
BFr.O(CrHr)?
cHrcl,,cH.cooH,
OH
o"o-,f7o
I
C. A. Grob,Angew.Chem.Iu. Fl : M. Ochiai,T. Ukita,S. Iwati. Y. I
-<",' 4 l C " H . l : O | (cH,),siN,
+
t l Ni\oAo f R. M. Moriarty,R. K. Vaid,T. E. Hopkins,B. K. Vaid, Tetrahedron Letters,30'3019 (1989). Iodosylbenzene-Dicyclohexylcarbodiimide-Boron trifluoride diethyl ether, C6H5I:O, DCC, BF3.O(CzHs)2. Grob fragmentation.r The combinationof thesereagentscleavescyclic 1-tributylstannylalcoholsat 25" in CH2CI2to unsaturatedaldehydesand ketones.2The actual reagent is consideredto be 1, a modified Pfitzner-Moffatt reagent, which convertsthe substrateinto an iodine(Ill) intermediate.
Iodosylbenzenetetraflorobottc rgentsare preparedby additioool io Cl C6H5IOwith HBFT.O(CH3)2 a- Ketomethl t aryliodonfui r ;an be generatedby reactionof C Such saltsI oone,CoHsCOCH3. eliphaticketones,but the salt 2 cq
(Da) yosila
Iodosylbenzenetetrrff oroborates
diethyl ether
ftoride
ng materialfurnishesan oPtically ic sl nthesisof a naturalp-lactam.
c.H',N1",$iH 6-7Bn;
(1)
CuH,
t-
OH
Bzl,N..
y.
..COOC(CH3)3
- 'l-- 1 ': 5
,-N d,
A (-l
-l ]fcuH,,
| I, CH,Cr" _:t
SnBu,
?-I(C6H5)OCNHC6H|| I
lLYsns',
.",:cH(cH,),cHo
l-l
+ CuHrI+ (CuH,,NH)rC:O
\** CuHtt
'OH
o
.\ | | t..$SnBu,
1 .6 \ J , 1( 1 9 E 9 ) .
rl
T*-
CH,:CH(CH,)3iC6H5
CH."\./OH
rrdatronof 2-(trimethylsilyloxy)l 5-rubstituted2(5Il)-furanones.
r L
l:l ^.oAo\
3019 Letters,30, \ uJ. Tetrahedron
)o
-\...c,H, -I'
f
?ll
ter
cH3C(cH')3cH:CHCzH'
$snsu ( 8 9 I: l ) lC. A. Grob,Angew. Chem. Int.Ed.,t, 535(1969). : M. Ochiai,T. Ukita,S. Iwaki,Y. Nagao, (1989). andE. Fujita,J. Org.,54,4832
Iodosylbenzene tetrafloroborrtes,(C6H5I+)2O.2BFaor C6H5IO.HBF4. Thesereagentsare preparedby additionof HBFato C6H5I(OAc)2 in CHCI3or by reactionof C6H5IOwith HBF4O(CH3)2in CH2C[2. a.-Ketomethyl aryliodoniumsclts, C6H5I+CH2COC6H5BFT(2).' This salt(2) canbe generatedby reactionof CelIsIO.HBF4with the silyl enol ether of acetophenone,C6H5COCH3. Such saltsare not formed by reactionof C6H5IO.HBF4 with aliphaticketones,but the salt2 coupleswith enol silyl ethersofaliphaticor aromatic
trifluoride diethyl ether'
o Fle reagentscleavescyclic Y-triThc and ketones.2 Ired aldehydes which reagent, Pnrzner-Moffatt liate
tl
u'')-osi(cH3)3
2 -t*'l
,,ul.,CHrCCuHt
I
Itt
lodotrlnethylsilene
ketonesin about 50% yield to form l,4-butanediones(equationI) or with alkenes (equationII and III).
6H,\ (ID
+ 2 ,*+
,C:CH, CuHr'
fit'
OTs
C6H5CCH2CH2COC6H5
'._*[( ""rr.
(Itr)(CHr)'C:C(CH3), + 2 *+ ""r3
/"", CH,
r\a",
I CuH,
(C6H1I+)yO.2BF4-Q). This salt (yellow) is insolublein water or CHCI3but soluble in polar organic solvents(DMSO, CH3CN). The correspondinghexafluoroantimonateand hexafluorophosphate salts have similar properties.The reactivity of thesesaltscanbe enhancedby additionof HBFa.O(CHr)r.The principal difference betweenthesesaltsandC6II5IO.HBF4is their enhancedstability. Typical reactionsof I with alkenes,silyl enol ethers,and alkynesare formulated(equationsIV-VD.
' K.-Y. Jungand M. Koreeda, J. Oq
OAc
ceeD (cts) I
(V) cuHrc:cH, # osi(cH3)3
c6H5ccH2cHrfrcuH, o
o
Iron(0). Cyclization of triencs.t In o speciesprepared by reductioo of cquiv.) promotescyclizationof trir dlylic or homoallylic ether groop. rre formed, and the cisltrons il$ teometry of the allylic doublc bq rE.E)-l is cyclizedto cis-2.
I
(vD PrC-cH #
PrC-CI*C6H5BF;
' V. V. Zhdankin, M. Mulliken,R. Tykwinski, B. Berglund, R. Caple,N. S. Zefirov,andA. (1989). S. Koz'min, J. Org.,54,2605,2609
r--/'.ZCH, ig.r"-
V
F q o ) - b P t p/
\
\
I
\or't Iodotrlmethylsilane. Deorygcnationof lr$endooxides.r The transformationof a 1,4-endooxide(l) to the correspondingaromatic hydrocarbon(2) can be effectedin high yield with iodotrimethylsilane.The deoxygenationwas used for a novel synthesisof 1,4-di(3) as shown in equation(I). methylphenanthrene
:Z-E)-L, n = 1,2
The presenceof an oxygcn rto uon markedly, but cyclization ir rhis cyclization is a useful rour u
I (equationI) or with alkenes
a)fi
.hiJiil!i;',n1> e2%
\_-\=l-l
\-.A_2
l. :tt.cH:COC6H5 l'\
,CHt
r)-4."" 'q .2
Y
CoH,
rcluble in water or CHCI3but The correspondinghexafluorilar properties.The reactivitY lH, t: . TheprinciPaldifference I srability.Typicalreactionsof IV-VD. nulated(equations
uH,
CH" ;
' K.-Y. Jungand M. Koreeda,J. Org., 54, 5667 (19g9).
OAc
li
fonc
rcH.cc6H5
o
Iron(0). cyclizttion of trienes.t In combination with 2,2-bipyridyl (bpy), an iron(O) speciesprepared by reduction of iron(III) 2,4-pentanedionatewith AI(C2H5)3(3 equiv.)promotescyclizationof trienes(l) in which a 1,3-dieneunit is tetheredto an allylic or homoallylic ether group. vic-Disubstitutedcyclopentanesor cyclohexanes are formed, and the cisltans disposition of the substituentsis controlled by the teometryof the allylic doublebond. Thus (z,E-)l is cyclizedto trans-2,whereas (E,E)-l is cyclizedto cis-2. Hl
LBF.
/--2",2cH' d. R Caple,N. S. Zefirov,andA.
3WL'
ti.s,l"
'zt\
'OBzl
trans-2
H trans-3
n = 1,2 IZ,E\-L, (l) rmation of a 1,4-endooxide yield with be effectedin high rr a novel synthesisof 1,4-di-
The presenceof an oxygenatom in the linking chain lowers the yield of cyclizauon markedly, but cyclization is facilitated by a nitrogen atom in the chain. Thus thiscyclizationis a usefulroute to N-acylpiperidines (equationI).2
Iron(III) chloride
""ry ",",n,*.-^ o
""' jll8'''K, -_ -4" 85% "."'y*9'..cH,CH(oR), LoB"r
o
Lctters,2t, t J. M. Takacs,L. G. Anderson,M. W. Creswell,andB. E. Takacs,Tetrahedron 5627(1987');J.M. Takacsand L' G. Anderson,Am. 9oc.,109' 2200 (1987)' 2 B. E. Takacsand J. M. Takacs,Tetrahedron lttters,3f' 2865 (1990)'
Iron(IID chloride. Oxidative phenolic coupling.t This coupling with FeCl3'6HzO(l) is more efrby cient when conductedin the solid statethan in solution and can be accelerated effective' ultrasoundin the former case. A catalytic amountof FeCl3is sometimes Thus a mixture of p-naphtholand finely powderedFeCl3.6H2Owhen heatedto 50o in a test tube is converted to 2 in 95% yield. The same reaction in refluxing cH3oH-HrO provides 2 in 60% yield. The water moleculesof I are not involved in the solid becausecouplingto 2 can alsobe effectedwith [Fe(DMF)3C12]+FeClayield can also be state in 79% yield. The conversionof p-naphtholto 2 in 89% effectedwith 0.2 molar amount of FeCl3.6H2Owhen irradiated with ultrasoundat
1 1800, ZnBrr,25" FeClr/AlrOr,-78o
75* WL n*
F. Toda, K. Tanaka,and S- h : L. F. Tietze. U. Beifuss,td Beifirss,Org. Syn., submitlcdI
tron(IID sulfate. Dehydration of alcoholt. supportedon silica gel cfico I 25" . The order of reactivity gel is essentialfor dehydntil dchydrationis increasedby it
andC. Ikmio. J T. Nishiguchi
50'.
lsopropylidenetrlphenylpb Stereoscle ctive cycb2n1 paredfrom (lR,2S)-norcpto Tc
I
N-
cH3ooc^.,4Asymmetricintramolecular ene cyclizltion.2 l,7-Dienes, particularly thosc substitutedby two electron-withdrawinggroupson the enophile,undergoene cyclization to trans-disubstitutedcyclohexaneswhen heatedor in the presenceof Lewis acids (13, 349). This reaction can proceedwith high diastereoselectivitywhen ap plied to the chiral 1,7-diene1, obtainedby a Knoevenagelreactionof (R)-citronelld with dimethyl malonate.The highest induced diastereoselectivityobtains in reactions at -78o --+ 20'catalyzed by FeCl3adsorbedon alumina.Unlike the more commonLewis acids suchas znBr2, only 0. 1 equiv. of Feclr is required for cycli' zationat -78o.
Isopropylidenetriphenylphosphorene
9H,
CH,
H,C
_>
coocH3 ktters, 2t, Tetrahedron Takacs, . loe. 2200(1987). 1865I 1990).
H
I
l H coocH3
2a 75Vo 86Vo 777o
H
H,CAicH3ooc\....,f:AcH,
t l cH3ooc-AAcs, l H coocH3
cH3ooc
I 1800, ZnBrr,ZS" FeClr/AlrQ, -78'
9H,
/"'.r--\ I
19f
2b 89.7:10.3 96.6:3.4 98.8: 1.2
' F. Toda, K. Tanaka,and S. Iwata,J. Org.,54, 3007(1989). 2 L. F. Tietze,U. Beifuss,and M. Ruther,ibid., 54,3120 (1989);L. F. Tietzeand U' Beituss, Org. Syn., submilted(1990).
b FeClr.6HzO(1) is moreeffibn and can be acceleratedbY effective' FeCl, is sometimes to 50o heated when 6H2O f,l. refluxing in \ame reaction r oleculesof I are not involved +FeClr- in the solid )IlFt,Cl2l o 2 ro 89% Yield can also bc r rrradiatedwith ultrasoundat
Iron(IID sulfate. Dehydrationof alcohols.r This iron salt, as well as CuSOrandNaHSOa,when supportedon silica gel effectsdehydrationof alcohols in various solventsat 100125". The orderof reactivityof alcoholsis tertiary ) secondary> primary. Silica gel is essentialfor dehydration;other solid supportsare not effective,and the rate of dehydrationis increasedby increasingamountsof SiO2and then becomesconstant. ' T. Nishiguchi andC. Kamio,J.C.S.PerkinI, 70?(1989). (l). Preparation.l (C6H5)3P:C(CH3), Isopropylidenetriphenylphosphorane, Stereoselectivecyclopropanation.2 Reactionof the chiral oxazolidine2, pre' at reactswith I (3 equiv.) in benzene-hexane paredfrom (lR,2S)-norephedrine,
Ts cH,"V
tl
'/"-FcH' :
cHroocMo ,
I .--Dienes, ParticularlYthosc bc enophile,undergoenecYclitcd or in the Presenceof Lewir when aP tr drastereoselectivitY (R)-citronelld of reaction nagel obtainsin reacFreoselectivitY the more Unlike alumina. on d r. of FeCl: is requiredfor cYcli-
-L"u",
r'25"
*--
Ts cH"" J,
n
l
2,,__FCHr l
,l-\..."\o_J<6uu, cH3ooc 3 10% |
.t
cHvcHs
7\...cno
I cH3ooc
(1R,3R)-4
lg2
Isopropylidenetriphenylphosphorsne
25otoaffordthecyclopropane3inffi%yie|d.Thisproductisaprecursorto hemicaronicaldehYde(4)' Letters'3781(1912)' I P. A. GriecoandR. S. Finkelhor,Tetrahedron t0' 3733(1989)' ibid', 2 A. Bernardi, Villa, R' and Scolastico, C'
Lcad tetraacetate. | - Allcynylle ad triac etatcs (4. . pared more directly and in hi;l Pb(OAc)a.rThey are useful for 1 b€nzylesters(2). Thus the adduo genation(Lindlar) and reduclive kenylketone4.
o
tl
+ (AcO\ CH.CCHCOOBzI l CH, ,
Oridative ring exPansbn of rrcpine-2-onesinvolves oxidetiu :rs. which are easilYformcd b
x,o\l\,,,\
t(cHr),ctolp
I
ll
,.,.\r\z*
I
CH,
cH3o cH30
Thrs product is a precursor to
l . - t - 8 1( 1 9 7 2 ) . 13l 1989).
Lead tetraacetate. l'Alkynyllead triacetates(cl, 14, lgg). Theseorganometallics(l) can be prepared more directly and in higher yield by reaction of l-atkynyitithiumswith Pb(oAc)a.r They are useful for preparationof a-alkenyl ketones i4; rrom p-keto benzylesters(2). Thusthe adduct(3), from reactionof l with 2, on partial hydrogenation(Lindlar) and reductivedebenzyloxycarbonylation providesthe (z)-a-arkenyl ketone4.
o
o cooBzl cH?c' li ll I CH3CCHCOOBzI + (AcO).p66-ggu --3''"' CH3C-9-c-csu 2%'--+ | t cH, iu.
,oul - D u, Lindtecar. | 2) RueYNi
O
Y
ll
CH.C-CH _ l
^
.Bu
CH, 4,ZlE= 95:5 oxidative ring expansionof enamides.2 A generalroute to tetrahydro-3-benzrrepine-2-ones involvesoxidativering expansionof enamidesof dihyiroisoquino-roes,which are easily formed by reactionwith anhydridesor acid chlorides. The
'*'o1z)f).""*ff',o,"",oy)a) .x,o)wN
|
Jf,ti,i,,,
':;nf cH.o^.A'.Nco,c(ctt,), -"r" l'l
CH,
CH"
"",o-loY\,. I ll cH,o\.,\.{
cH,o..'ZY\ Nco,c1cH,). +O
| ll "",o\A_-('^' '
NH O 193
Lithium chloride-Dimethylformamlde
ring expansionis generalwith respectto substitutionon the aromatic system,but fails if the exocyclic methylenegroup is disubstituted. f S. Hashimoto, and S. Ikegami,J.C.S.Chem.Comm.,ll0{J Y. Miyazaki,T. Shinoda, (1990). 2 G. R. LenzandC. Costanza, J. Org.,53,1176(1988);G. R. LenzandR. A. Lessor,Org. (1989). Sln., submitted
Lithium di-f-butylbiphenylidc (LDB 2-Lithiotetrahydropylns.t LDI reduction of 2-thiophenyltetrahydrq pyrans,which isomerizeto the equdq of 1 and trapping providesmainly eri trapping at 20' provides mainly 2l(phenylthio)tetrahydropyrans.
Bzl Lithium N-benzyltrimethylsilytamide(LSA), LiN/
\s,(c",),
f",
(l).
Additionto methyl crotonate. LSA addsto methyl crotonateto give exclusively the (Z)-enolate(a), which reactswith aldehydesto form the anti, syn-aldol2 as the major product. The lithium enolate(Z)-a can be convertedinto the (E)-isomerby
l) LDBB, TXr. - t
. 2)- [(CH!):C:O
-
\o'^\
(
sc6H5 I r) LD88.na 2) (CHr!C=l r l -
BzlNSi(CH.).
cH3^.-coocH3 5
"1,;;'-'
""'\
Rcductive lithiation of oxenrct.t to 1-lithioalkoxides(a) which are trq
(z)-a BzINH OH
r
cH3-
:
BzINH
i
l
cH3 +
cHi^-cH,
cH,^<*"'
oLi (E)-a
-li'f"'
BzINH
?"
cH,fcH,
O r.ne
syn,sYn'2
BzINH ?"
+ cu,fcu,
COOCH3 90:10 syn,anti-2
l
COOCH3
COOCH3 82:18 anti, syn-2
BzlNSi(CHr), ^,, ]'OCH,
OH
rF
I
I
coocH3 anti,anti-2
reactionwith LDA and then ClSi(CH3)3.This (E)-enolatereactswith aldehydesto form mainly the syn, anti-aldol' (1989)' I T. Uyehara, J.C.S.Chem.Comm.,753 N. Asao,andY. Yamamoto,
Lithlum chloride-Dimethylformamide. Cleavageof ROAr.t LiCl (3 equiv.) in refluxing DMF can effect dealkylation of theseethersif the aryl group is substitutedby o- or p-electron-withdrawingsubstituents(NOz, X, COOR). f A. M. Bernard, (1989). M. R. Ghiani,P. P. Piras,A. Rivoldini,Synthesis,287
L(2q unl||lr
!i:'O'
Llthlum di-r-butylbiphenyltde
don on the aromatic system, but rcd 4emr. ./.C.S. Chem. Comm., ll00 : G R. tenz and R. A. Lessor,Org.
Lithium di-t-butylbiphenylide (LDBB), 7, 200; 10, 240. 2-Lithiotetrahydropyrans.r LDBB is superior to LDMAN (12,279-280) for reduction of 2-thiophenyltetrahydropyransat -78o to axial 2-lithiotetrahydropyrans,which isomerizeto the equatorialepimersat -20o or higher. Thus lithiation of I and trapping providesmainly axial 2a, whereaslithiation at -78o followed by trapping at 20' provides mainly 2b. This methodologyis widely applicableto 2(phenylthio)tetrahydropyrans.
Bzl
9H,
(1).
N
si(cHr)r to giveexclusively '{-h\I crotonate 2 asthe ) formtheanti, sYn-aldol bY con\ertedintothe (E)-isomer
.4. I I |
|
9H,
l:Xii#:-""A >r 2)(cH'
-o^scuH,
|
9H,
Il ^
/
oH
|
2a
a\ [ |
+
]
on
l e / / -o^cicurl,
96.8:3.2
l-2a )
*
- o/"'{rcur),
I) LDBB, THF, _78' 2) (CH,),C:O.20"
t{(1lr
195
2b
2b
4.8:95.2 Reductive lithiation of oxctanes.2 Oxetanes are cleaved by LDBB at 0. in THF to 1-lithioalkoxides (a) which are trapped by aldehydesor ketonesto give 1,4-diols.
-
-<-
,
r
i
al-t
OCH,
cH,^ '
l
cH.
l
coocH3
8 2 :l 8
syn,syn-2
t
BzINH CH H
OH
BzINH
9"
+ eo:l0
r
T-O l. nrr. o" EiCH"CHTCHTOLiI | | a
*,'JG.
OH
l
cH.YcH3 ' l COOCH3
ft)#O<[1,,,o"
anti,anti'2
lcnolate reactswith aldehYdesto )
C ( ) m m . , 7 (5139 8 9 ) .
!il:"O"'ol"'?o?"'li'l'"'' [t-*:'"f a tt cn,cs:cscno -^'- | zl | rrdn I
urng DMF can effectdealkYlatior ' o r p -electron-withdrawingsubsti287(1989)' funr.Sr'nrlresis,
(o)^-t"' cur_|CH,
196
Lithirr
Lithium dilsoproPylamide
Thesediols can be cyclized to tetrahydrofurans.Oxetanesare also cleavedin the sameway by lithium and a catalytic amountof LDBB' cycloalkenyllithiums.3 Alkenyllithiums are usually prepared by reductive lithiaiion of trisylhydrazonesof ketoneswith butyllithium, but this methodfails with the hydrazonesof cyclic ketones.However, the cycloalkenyl sulfides,preparedby reactionof cyclic ketoneswith thiophenol,can be reductivelylithiated with LDBB at -78". This lithiationfails in the caseof cyclopentenylsulfides,but is usefulin the caseof the vinyl sulfidesobtainedfrom 6-, 7-, and 8-memberedcycloalkanones.
cH. 9H, o
^
r| "*-N\**tA.oor,
H
d
il
[
"
tri.+l
cH(cH,r I
,
(Boc - Ala- Sar-CHrL:u)
G*,+G;:"o.-,,",iG"J D. Seebach, H. Bossler,H. Grundlcr,S. Sh
,,*1..",,, CuH,,
l,ithium tri-l-butoxyaluminumhydrl&-l tnti-lr3-Polyols.r Reduction of thc c thishydridecatalyzed by LiI providesttc
CH,
FH' 7-.t
r)
t.&
c|
OSiR. - --_+a |
!x,t
l. co-9"; R, = (CoHr)r-r-Bu r S. D. Rychnovskyand D. E. Mickus, Tetrahedron Letters,30' 30ll (1989)' 2 B. MudrykandT. Cohen,J. Org.,54' 5657(1989). 3 T. CohenandM. D. Doubleday, ibid.,55' 4784(1990).
Lithium diisopropylamide. C-Atkylationofpotypeptides. Seebachet al.t repottthat selectiveC-alkylation of a sarcosine(N-methylglycine)unit in a tri- or hexapeptidewith an N-protectcd terminal group is possibleif polylithiation is effectedwith excessLDA in THF witl mixture. In somecascl additionof LiCl (5-6 equiv.) to provide a homogeneous addition of an aprotic dipolar solvent (DMPU) or of BuLi can improve the yield. Under theseconditions, epimerizationand N-alkylation are slight. The new centar introducedby alkylation of Sartendsto havethe (R)-configurationwhen the configrration at the other centersis (S). In the methylationof the tripeptide formulatedb equation(I), th€ yield is particularly high becausethe Sar unit is flankedby an ilmethylaminoacid. In this case,aldehydescan also serveas electrophiles.Alkylatic and benzylationare also possiblein the presenceof addedDMPU' The resultsof this investigationsuggestthat C-alkylation may provide a uscfl route to novel PolYPePtides.
This stepwas usedfor a generalroutc to d ,lrri-triol unit as in 4.
O H O H q
"o--,I---I--;
a l
Mori and M. Suzuki, TetrahedronLencn.
Lithium tri-r-butoxyaluminurn hydride-Lithium iodide
, Orelanesare also cleavedin the .DBB. r usually PreParedbY reductive rllrthrum.but this methodfails with bY clcloalkenyl sulfides,PrePared reductivelylithiatedwith LDBB at nrenrI sulfides,but is usefulin the cYcloalkanones' od 8-membered
(D
u*._*&i:ri..-t:::: cH. 9H, o
ir
l) LDA, LiCl, BuLi, THF 2) CHrr,-78. 3) CH,N,
>
ao%
I
cH,
(Boc-Ala-Sar-CH,tru)
gH,
g
CH(CH3)2
?", t* --n{r**AorcoocHl H d C", J""
-FA.J Lz"'.Li
197
1
V S = 3 . 7 I: ' D. Seebach, H. Bossler, H. Grtindler, S. Shoda, andR. Wenger, Helv.,74,lg74(lggl).
7r%lc6H'rl
CuH,,
Lithium tri-t-butoxyaluminum hydride-Lithium iodide (l). rnti-1,3-Polyols.t Reductionof the chiral p-alkoxy p,-hydroxy ketone2 with this hydride catalyzedby LiI provides the anti-|,3-diol with high stereoselectivity.
CH,
, /--\/CH(OH)C'H"-c 't* , ll
' \ J
+ 2,ao-9"; R, = (CuHr)r+-Bu
anti -3
L z r : e ' r 3. 0 , 3 0 1I ( 1 9 8 9 ) . lql
4 reportthat selectiveC-alkylatiol or herapeptidewith an N-protectod rred with excessLDA in THF witl logeneousmixture. In somecascl' or ,.f BuLi can improvethe yield[1 lation are slight. The new centcr whenthe configr' { R r-configuration ltron of the tripeptide formulatedb lsc the Sar unit is flankedbY an l'ler serveas electrophiles.Alkylatic r of addedDMPU. t C-alkylationmaYProvidea uscfl
syn-3
95:5
This stepwas usedfor a generalrouteto anti-|,3-polyolscontaininga 1,3-syn-3,5a ti-triol unit as in 4. QH
OH
OH
OH
OH
OH
HO 4 l'. Mori and M. Suzuki,Tetrahedron Letters,30, 4383, 4387 (19g9).
P(C6HJ).. CB..
ncro-f,p.-
n
' H. XiongandR. D. Rieke, J. Org..51 : L. VanHijfte,M. Kolb,andP. Witz. n Magnesium' Mg. Complexeswith |,3-dienes. The reactionof activatedMg* (11, 307) in THF at resultsin the deep red complex (1,425' with (E,E)-I,4-diphenyl-1,3-butadiene This halide-freebismagnesiumreagent diphenyl-I,2-butene-I,4-diylmagnesium). (l) forms a 1,4-adductwith o,al-dibromoalkanes, which undergoesintramolecular
Magnesiumbromide, MgBr2. Thioacetals. Aldehydes,keros convertedinto thioacetalsby reacri<mr rn ether at 25o. The differencein rer sclectiveconversionof acetalsinto thi
Mg+, THF
C.HTCH:CHCH:CHCeHs
u"
,
cuur-(r)-Cuu,
C6H5CH(OCH.), + C"HJ
I alkylationto afford disubstitutedcycloalkanes.Productsfrom R2SiCl2are stable1,4adducts(equationsI and II). Stepwiseelectrophilic addition can be effectedin the (equationIII). caseof adduct2 of Mg* with 2,3-dimethyl-1,3-butadiene
(l) I + Br(CHr)rBr
TJ' C^H.GH:cH ***
c.H. "'X-Y
c^H. " "H
P K. Chowdhury, J. Chem.Rar.(S). t9
u" )si( CH, CH. CH, (il)
( ) Mg 2
CH'
cH"'\ l) a(cH,).Br. - ?8o
cH" /
ry"_--- ",.r)tt",r."' o1 CH.
RCHO + RC-CH. A new two-step method for conversion of RCHO to RC=CH involvesconversionfirst to a l,l-dibromoalkene,RCH:CBrz, followcd by debromination.The most convenientreagentfor this secondstepis magnesiumir refluxing THF.
r9t
J H. ParkandS. Kim, Chem.Lenen.6
lhgnesium iodide, MgI2. Deoxygenationof orirancs.t Mg rod 12in refluxing ether, effects dcor rlkenesvia an iodohydrin with rercri
,LJ CuH,
-ffi+ (ll) I + (cH,),SiCl,
C6H5CH(OCHr), +RCOCH,+
Yrgnesium monoperoxyphthellc (t Alkene epoxidation.r In thc pr ! 10,15,20-tetra-2,6-dichloropheny ooxidize alkenesin the presence of r I :i a base(pyridine)improvesthe nrc. Oxidation of furans to cnediota. .h)nescan be effectedwith MMPP rrd r-Chloroperbenzoic acid is lessefrcb Oridative cleavageof N,N4ialtyl r: rheparentketoneby treatmentwitb d :i 16-91%.No racemizationoccun ir
Magnesium monoperoxyphthalrte P(qHj)j,
RCHo-*H_'
CBr.
RCH:cBrz##
H. Xiong and R. D. Rieke,"/. Org., 54,3247 Qggg\. L. Van Hijfte, M. Kolb, and p. Witz, Tetrahedron Letters,30,
ir aredMg* (f f , 307)in THF at in rhe deep red complex(1,4dc-free bismagnesiumreagent rhrchundergoesintramolecular
n
:.H.'-\M,"-C6H'
199
RC:SH
3655(19g9).
Magnesiumbromide, MgBr2. Thioacetals. Aldehydes,ketones,or acetals,both cyclic and acyclic, can be convertedinto thioacetals by reactionwith a thiol or dithiol and MgBr2(2.l equiv.) in ether at 25". The differencein reactivity betweenacetalsand ketonespermits selectiveconversionof acetalsinto thioacetalswithout acetalization of a ketone. C6H'CH(OCH,), + C.HTSH
{P
c6H5CH(SC6H5),
I S-
arestable1,4rts from R2SiCl2 in the be effected rddrtion can (equation III). drene
c\t< ) \-J c.H.' C.H. .H
cuHscHl
I s-J
J. H. Park and S. Kim, Chem.Letters, 629 (lggg\.
Vagnesiumiodide, MgI2. Deoxygenationof oxiranes.r MgI2, prepared in situ from magnesiumturnings rnd 12in refluxing ether, effects deoxygenationof oxiranes to thlecorresponding rlkenesvia an iodohydrinwith retentionof configuration g5-90% in vield. P. K. Chowdhury, J. Chem.Res.(S), 1920990).
CH }I.
C6H5CH(OCH3)' +RCOCH.+ HSCHTCHTS" *#
,CH,
',--\rcH"l.Br t.c 'n1) CH,
I for conversionof RCHO to nlkene,RCH:CBr2, followcd ir brs secondstepis magnesium
llegnesium monoperoxyphthalste(MMpp, l), 14, lg7. Alkene epoxidation.t In trre presence of a Mn-porphinate, particularly i . I 0 ' I 5 ' 20+etra-2,6-dichtorophenylporphinatomangane se(III) acetate,2 MMpp can cpoxidizealkenesin the presenceofa phase-transfei catarystin highyield. Addition :f a base(pyridine)improvesthe rate. oxidation of furans to enediones.3 oxidation of 2,5-dialkylfuransto crr-enJronescanbe effectedwith MMpp rapidlyat 25" in c2H5oH/H2o in 90-99% yield. *Chloroperbenzoicacid is lessefficientfor this oxidation. oxidative cleavageof N,N-dialkylhydrazones.a These hydrazonesare cleaved r'the parentketoneby treatmentwith this oxidantin aqueous methanolat 0. in yields t( 1g-11%.No racemizationoccursin the caseof SAMp or RAMp hydrazones.
Manganese(lll)
acetate
o l l t l cHiTN(cH,CH:cH.l cH3co(cH, ),4\
!
CH,
"H2)2cocH3
o 'C. QuerciandM. Ricci,J.C.S.Chem.Comm.,889 (1989). 2 S. Banfi,F. Montanari, (1988). andS. Quici,J. Org.,53,2863 3 C. Dominguez, Letters,3f,7669(1990). A. G. Csriky,andJ. Plumet,Tetrahedron a D. Enders (1990). andA. Plant,Synlett,725 Magnesium oxide, MgO. o,rp-Enones+ alUlic alcohols.r This reduction can be effectedin 50-90% yield by hydrogentransfer from propanol-2 catalyzedby a finely powderedmagnesium oxide obtainedby thermolysisof Mg(OH)zat 350". No other metal oxide is satisfactory.Theseconditionsalso reducep,y-enonesto homoallylicalcohols. Alkorycarbonylation of malonates.2 This inexpensivebaseis particularly efficient for reactionof alkyl chloroformatewith dialkyl malonatesto give methanetricarboxylicesters.Yields are typically 55-70%, but this methodfails with methyl cyanoacetate.
, \J
?.,.\ ?
N(cH,cH:clL,
a'-Acyloxylation of cnoncs.t 'I\i enonewith Mn(IIf acetate(6 equiv.)r cquiv. of a Mn(II) carboxylatein bel
rJ. Kaspar,A. Trovarelli,M. Lenarda, Letters,30,2705 andM. Graziani,Tetahedron (1989). 2 J. Skarzewski, 4593(1989). Tetrahedron,45,
LI
r-(l CHt
Manganese(Ill) ecetate, MnrO(OAc)r (l). cyclizttion of allylic p-diesters.r The Mn(IID cyclization of allylic p-keto acids (12, 292-293)hasbeenextendedto lactonizationof allylic p-diesters.In general, yieldsare improvedby useof Mn(III) acetate(2 equiv.), Cu(OAc)z(l equiv.)' and NaOAc(l equiv.).
o
oAr1no""r.
Mn(lll), Cu(OAc), NaOAc
I
+
)r
CHt
o L.cH, o' Y-cooc,Hs \ |
CHt (53Vo)
a
CH,
CH,
7sq .-.- I Mn(l[]r
JcrcH,c0otr
o tl /,!octcHrc
Jl J..",
cH]-cH,
o
tl
CHTCHTCCH:CHCllr
(20Vo)
are oxidizedby Mn(OAc): to lactams Lactams.2 N,N-Dialkenyl-p-oxoamides and spirolactamsvia a radical cyclization. Ethanolis a better solventthan aceticacid or acetonitrile.
Addition of , CH2COOHto alLna -'{ dkenes to 1-lactonesis generdly r rnganese(Ill) acetate,but this rcege
Msngenese(III) scetste
o tl ,. 1".: f^(cH,),cocs, -_-------)|| 'r"
\.-..tcHr)rcocH,
o il cH;
o tl I--
Mn(OAc)r, -N(cH,cH:curl, SI#A
CH,
tl o
? ?
1 6 r, l 9 E 8 ) . d,i'q larers,3l, 7669(1990).
CH(-
o Dr'lroncan be effectedin 50-90% Ized by a finelYPowderedmagne1 ar -i50o.No other metal oxide is Fne: lo homoallYlicalcohols. rtpensive baseis particularlyeffito give methanetriil\r I malonates but this methodfails with methyl
NCH,GH:GH,
."frf
ll9E9t.
9H,
N(CHTCH:CHr).i? CHrCH:CH,
a'-Acylorylation of enones.3 This oxidation can be effectedby reactionof the enonewith Mn(IIf acetate(6 equiv.) and either 12 equiv. of a carboxylicacid or 6 equiv.of a Mn(II) carboxylatein benzeneat reflux temperaturefor 6-lg hours.
Letters,30' 2705 r.z:int.Tetrahedron
O
O
--,H##:a;, a\.ococ.n, A l! Ja""' 6'%- il L"'' cH, cHiv cnYcH,
III r l clizationof allylic p-ketoacion oi allylic p-diesters.In general, I cqurr.),Cu(OAc)z(1 equiv.),and
-.-u" |"^ I I
x t4
o Jt .CH. o- fcooc,H,
o + \
|
crL QoTo)
e orrdizedbY Mn(OAc)3to lactams pl rs a bettersolventthanaceticacid
?rq ' - - I Mn(lll) rcehre
lctcHrc@H
; il /,,4_\,/ococHrcl
ll
.,\ cH;
1.,-
l-cH.
-<--CHr
o _ i l CHTCHTCCH:CHCH3
o t
l
u,%-, CH3CHCCH:CHCH3
ococHcl, Addition of 'cH2cooVtoalkenes (2,263-265;6,3ss-356).4 Theconversion
of alkenesto y-lactonesis generallyeffectedwith aceticacid and l-2 equiv. of oanganese(Ill)acetate,but this reagentis expensiveand rather unstable.It can be
2O2
Manganesedioxide-Chlorotrimethylsilrne
c^H. Mn1f,4s1,-Cu1oAc,,
o ll
9uH,
H
riJ
C.H,CH:CHc.H,-jff#g-
*
c6H5ccH2cH,-
tl
o
F. Ghelfi,U. M. Pagnoair F. Bellesia, inexpensive generatedin the presenceof the alkene by anodic oxidation of the is usedin Mn(oAc)2 acetateby cu(oAc)2. In this indirectprocess,the iranganese(Il) yields the general, In catalttic amountswith Cu(OAc)2as the stoichiometricagent' the by obtained those obtainedby this anodicoxidation are significantlyhigher than conventionalProcedure. +
9H' (CH,),CCH,C:CH' + CH,CocH,cooc2Hs'#+
::,#t\:::.
Manganese(Il) tetramethylhepfu-l
a-Hydrory carboxylic cstcrt.t T genationof c,p-unsaturatedcarboryli vertsthe hydroperoxideto an c-hydrt Mn(acac)zshowsonly moderatcrtiv nined generallyin high yield from el or even from a-substitutedestcrs.
(cH1)rccH;
CH,CH:CHCO2CH:C.}L
tI
.CH(COOC,HJ,
IF + CHr(COOCrrfrl' eO
endT. I S. Inoki,K. Kato,S. Isayama, H
AnodicoxidationofMn(oAc)2(catalyticamounts)inthepresenceofnonacti. providesa routeto dihydrofurans(cf, 6' 356)' vatedalkenesandethyl acetoacetate of activated This electrooxidationof Mn(OAc)z has been extendedto coupling methylenecompoundswith alkenesand dienes' J. Org" 54' 56t' rH. oumar-Mahamat, J.-M. Surzur,andM. P. Bertrand, c. Moustrou, (198e). t i. CossyandC. Leblanc,Tetrahedron Letters,30,4531(1989)' 3 A. S. Demir,A. Jeganathan, andD' S' Watt,J' Org'' 54'4020(1989)' 831(1991). a R. Shundo, andT. Hirashima,Tetrahedron,4T, Y. Matsubara, I. Nishiguchi, Manganesedioxide-Chlorotrimethylsilane' to generateMnCL. J_qruro ketones.t This combination(l:4) is believed A methylenegrotp process. which convertsketonesin a-chloro ketonesby a radical is attackedin preferenceto a methyl group'
Menthol. Optically active a-hydroxy anl paredin siru from RMgX and ZoCl2 (l). Tl r -)-menthyl phenylglyoxalate (3).' acids hydroxycarboxylic
c6H5cocooM"n(-) SjSi I
R = CzH: R = n_CoHrr G. Boireau,A. DeberlY,and D. Abcl
Menthol
c.'H. 9uH, ' l \---l \ + o,{)
o
tl
MnO,, ClSi(CH,),
HOAc c6HsCCH2CH3.--------------90%
il
o ilc trridation of the inexPensive theMn(OAc)2is usedin I prr'rcess, ?rnc agent.In general,the yields hrgherthanthoseobtainedbY the
o tl
c6H5CCHCH3 I CI
'F. Bellesia, F. Ghelfi,U. M. pagnoni, andA. pinetti,J. Chem.Res. (S),l8g (1990). c{cH3)l Manganese(Il)tetramethytheptane-3,5-dionate,(=o.)"",r,
)-o'"
L I
coocrtt
-J CHr--/
\\
----Aol-cH,
c(cH3)3 a'Hydroxy carboxylic esters.r This complexis an efficientcatalystfor peroxygenationof c,p-unsaturated carboxylicesters.Reductionin sirz with c6H5siH3convertsthe hydroperoxideto an a-hydroxyester.2-propanolis the solventof choice. Mn(acac)2 showsonly moderateactivity in this reaction.a-Hydroxy estersare obtainedgenerallyin high yierd from esterswith only one substituent at the p-position or evenfrom c-substitutedesters.
rCH,).,CCHt
s
/,--;--1 \----.r-/
CH,CH :
!H(COOCTH5),
\)
oH or,c6HrsiH' CHCOTCHTC.H,--j-_-+ CH3CHTCHCO2CH2C6H5
S. Inoki, K. Kato, S. Isayama,and T. Mukaiyama,Chem.Ittters,lg69 (1990).
:
H Dunr\)in the presenceof nonacti' rureto dihydrofurans(cf,, 6, 356)rrended to couPlingof activatcl
Venthol. optically active a-hydroxy carboxyric acids. The organozinc reagents prepred in siru from RMgX and znCr2 0r znBr2 add serectivery to the keto group of ' -)-menthyl phenylglyoxalate (l). The adducts are hydrolyzed to optically active chydroxy carboxylic acids (3).'
J. Org.,54,56t| is \l P. Bertrand, 5 , : 1, t 9 8 9 ) . .. s.r.1020(1989). 47,831(l99lI Tetrahedron, lrshtma.
R
gcl-:-35 c6HscocooMen(-) t 6
R
iL cuH,J*coouen(-) n o
cuH,J*coou H
, l) rs believedto generate ndrcalprocess.A methYlene
R = CzHr R = z-CoHr:
88Vo 92Vo
75Vo de 88Vode
(R)-3 80Vo 83Vo
G. Boireau,A. Deberly,and D. Abenhaim,Tetrahedron, 45, 5g3Z(19g9).
204
(S)- or (R)-Menthyl p-toluenesulfinate
Menthone. DeracemizationoJfmeso-1,3-diolst(14,202-203). The spiroacetals(2) formed from meso-\,3-diols(1) and /-menthoneundergohighly selectivecleavageof the andTiCla. The resulting equatorialC-O bondon treatmentwith allyltrimethylsilane before removal of the be functionalized then frie hydroxyl group of the diol can yields. optical in high diol of the chiral auxiliaryto give chiral derivatives 2-alkyl-1,3-propaneto applicable products is also This transformationto chiral diols and meso-|.2-diols.
which is reducedby DIBAH r sis provide an optically purc (l Surprisingly,allylmagncs (R)-5, in 98% yield, whicb is
I + CHz:CHCHTMgBT;-
T,
9",
."...fn,?l t
CH:
CHI
a-ot"'cn.
-------+
-
-
OH
OH
/_.4--=-_/
I
2
1ft:31;;ou"n,,"
9", 9",
l) KNts(cH.),1,
o,,*oH
CHrr -,,\ ,.CH, ,,:FTi:ti' v
:
OH
-
e5eo
:
CH,CH:CH'
OBzl
Amine ( * )-6 can be coove tion, ozonolysisfollowedby ol acids(8) are obtainedby hydn (PCC;AgNO3-KOH),ard hyi
I
6 -;7"
cH3coNHC/ 'i c"H{
>95Vode
I T. Harada, T. ohnishi,andA. oku, chem.Letters,l44l(1990). H. Nakajima, Y. Ikemura, (S)- or (R)-Menthylp-toluenesulfinate(1), 14,203. ^|-amino acids.r Reac9- and chiral N-benlylidene-p-toluenesulfinamfutes; providessulfinamide2, (S)-l 0o at with tion of benzonitrilewith cH3Li and then
"\
t\ l) cHiLi
.rt ''lli' c6HscN ' rof
\ 'N:c' ,rCH, ottn" \
CoH,
"H l - \ u tt C-uH,
) 3 (96:4) ez*f cr,cooH
H"N ' \ . / cH"
c ,^r{
*I
tr Ho'
"'frx. coH, clt t
...'o
,zs:.'N-c- ./CHt , Tof
e2qo
I rrrn. | 2,rcE
'n
(s)-4
D. H. Hua, S. W. Miao. J. S. O
Hercury. Hydrodimeriution of olel ,15, 198),hydrodimerizatioo rron, and has the advantaged rubstrates: alcoholsandderivr :healkeneto give the moststrH :roncan be regioselective. Thc :le. In this casethe hydrodin i rcld.
Mercury
(2) formed The spiroacetals 0l' , hrehll selectivecleavageof the lr l.rlaneandTiCla.The resulting before removalof the ;1r,.nalized io. rn highoPticalYields' rgpircableto 2-alkyl-1,3-propane-
which is reducedby DIBAH at 0o to the (S)-amine3. chromatography andhydrolysis providean opticallypure (S)-amine(4). Surprisingly' allylmagnesiumbromide adds to 2 to give a single diastereomer, (R)-5, in 98% yield, which is hydrolyzedas aboveto the amine6.
"\ 2 + CHr:QllCHrMgBr
---------+Tol
9",
-A-
cH.g- )
1n... I
I
I
, I cs,:cscu,s(cs,),' lTicl., cHrcl,
N Ha.,rcH,
/cHl
c"u!"cn,cH:cH, (+)-6
Amine ( 4 )-6 canbe convertedinto opticallyactivep-aminoacids(7) by acetylation, ozonolysisfollowedby oxidation(AgNo3-KoH), and deacetylation. y-Amino acids (8) are obtainedby hydroboration(BH3) of the acetatefollowed bv oxidation (PCC;AgNO3-KOH),and hydrolysis.
6 -::"".ao*"a'""' e)a
CH,CH:CH,
H2N\
(R)-5
9H, 9H,
o//\^oH
cF,cooH -;;-
c.Hf'cu,cH:cH,
,------)-/--s/"'cH, ('lI
...'o
S
"cHrcH-6g,
crH{
l) o, 2) ASNOIAoH 50%
HiNvCH3
J'.. cuH, cHrcoo7
rliila,ill*df.*,
rj \ Oku. Chem.Letters,l44l (1990)'
| 3) Hro.
Y
't ti
n: 9- ant! 1-amino acids'r Reac2' lS,-l at 0' Providessulfinamide
"\ .."o .s. ,/\
'' - '" r Tol
N-C.
CuH,
3 (96:4) ez*Jcr,cooH
, / CH. C"'...
/ CoHt
/'-.
cuH,
CH2CHTCOO8
_CH, ,/
H! . . "' u ^
H.N , \
+ H,N.,CH,
n
(s)-4
D. H. Hua,S. W. Miao,J. S. Chen,andS. Iguchi,J. Org.,56,4(1991). lfercury. Hydrodimerizationof olefins.r In addition to dehydrodimerizationof alkanes 15. 198),hydrodimerization of alkenescan be effectedby mercury-photosensitiza'-rrn, and has the advantage that it is applicable to a wide range of unsaturated r.rbstrates: alcoholsandderivatives,ketones,andothers.sincethe hydrogenaddsto 5c alkeneto give themoststableintermediate (tert > sec > primary),this dimeriza3ro canbe regioselective. The last exampleshowsthat cross-dimerization is possirrc In this casethe hydrodimer of both componentsis also formed, but in lower .'cld.
N-fftnr
I -Methoxy-1,3-bis(trimethylsilyloxy)-l'3-butadiene
cH."
H, Hg*, lv
CH3(CHr)3CH:CHz -G+
\
CH_CH
-/ cH3(cHJr gHr\
CHTOTCCH:CH,
tzq"t
./ \
cH. (cH2)3cH3
CH.
/CH-CH
co2cH3
cH3o2c
(otlmeso - l:l)
(/
+ cH2:cHcH2si(CH3)i *
I G. A. Molander and S. W. Andrews, Tct* (Methoxymethoxy)allene,
CH3OCHpCII
201). Hydroxyquinone annclation Tbc lid silyl ether 3 to provide the adduct {. Cc resultsin 6, which undergoescyclizetbo ir as the methyl ether 7. This quinooc rr vinylogoussilyl ether.
"t,f'CH2si(CH3)3
cH,ocHr\ \-,-
osi(cH,)3 #
?
(1989). f c. A. Muedas,R. R. Ferguson, andR. H. Crabtree,Tetrahedronl*tters,30,3389
t-. a
l'3-butadiene' 1-Methoxy-1,3-bis(trimethylsilyloxy)(cH3)3sio 9cH' | | H,CMos(cHr)3
-' I r-H,ocH,o-^zcH' ffi'ct ',n"lxtSo:'"' "o\""o
(t).
l cy13+41 and 13+SlCycloadilitions.r In the presenceof TiCla, I undergoes ethers 2 to form bicyclic or with 2,5-heptanedione with 2,4-hexanedione cloadditions or 3, respectively.Comparableresultsobtainin reactionswith 1,4- or 1,5-oxoalde-
\-,
l
s
6
%
5
!
l 5
M. A. Tius,J. M. Cullingham, and S. Ali. ,.(
hydes.
ricr.,cHrcL,
o
I +cH,'l\t'"^Y.t''-H-
r--Methoxy-N-methyldlethytphcplonc -L-aoo"".
n = I n = 2
CH,
o
l+H
ll
\z.\a-\p , - , n Il
o
n=l,R=CH: n=2,R=CH:
-----.+ .K
(c2Hso)rP(o)cH.co
cn,'Q'tH,
H. 66Vo 7'l9o
This Wittig-Horner reagentis prcprcd ciloroacetyl chloride and N(C2H5)3in CH1 phosphite.The anion (BuLi) of I reacrsril &at€s, which are reducedto aldehydcsby l) BuLi
r #5
C
cuH,cH:cHcoN (ElZ = 95:5')
C
N-Methoxy-N-methyl diethylphosphonoacetemid€ 20?
\ /
.
CH_CH
;
/ \
CH"
I G. A. Molander and S. W. Andrews, Tetrahedron lztters,30, 2351 (19g9).
(cH2)3cH3
(Methoxymethoxy)allene, CH3OCH2OCH:C:CHz
(1, 12, 310; 13, 177; lS,
20r). ,.
CH.
H-CH\
corcH3 lre,
- l:l)
Hydroxyquinoneannelation The rithio anion (2) of I addsto the vinylogous silyl ether 3 to provide the adduct 4. conversion to the aldehydeand epoxidation resultsin 6, which undergoescyclization in baseto a hydroxyquinone,best isolated as the methyl ether 7. This quinone annelationfails when applied to an acyclic vinylogoussilyl ether.
cH,cH.cH,Si(cHJ3
cH3ocH2o I I
,
OSi(CH3)3
BurNF,
-65%-t
osi(cHJ3
'ct,ahedron l*tters,30,3389(1989). 3
4
me.
cH,ocHro{l).
ctqH.co,H n"HCor
/\'CHO l l
tsence of TiCla, I undergoescYhnedioneto form bicYclicethers2 with 1,4-or 1,s-oxoalde?actrons
+
nzc',
HO rl
{,
o [|_ _coocH, a - Y
/-,.or\ ...( )... cH, cH, k1n
CH,
o ll cHrc-octtrocH,
5
6
r) KoH.cHroH
O-l )
%
\-,
ocH, ";.A
rtcHo
2)cH,N, > | ,,\
"
s5%
(,
\-., 5
|
6
7
' M. A. Tius,J. M. Cullingham, andS. Ali, "/.C.S.Chem.Comm.,g67(1989). lY-Methoxy-N-methyldiethytphosphonoecetamide,
(crH5o),P(o)cH'coNlocH'(r). -a", This wittig-Horner reagentis prepared from o,N-dimethylhydroxylamine and chloroacetylchloride and N(C2H5)3in cH2cl2 followed by reaction with triethylphosphite.The anion (BuLi) of I reactswith aldehydesor ketonesto form hydroxrmates,which are reducedto aldehydesby LiAlHa ([l,2Ol_20D.1
t ll "r+?""coH,cH:cHcoN-ocH' cuH,cH:CHCHo -ocH. +5" t4% (Erz = 95-5\
zOt
2-(Methoxymethyl)pyrrolidine
Hcrftl
t J.-M.Nuzillard,A. Boumendjel, andG. Massiot,Tetrahedron Letters,30,3779(1989). 2-(Methoxymethyl)pyrrolidine (l). Enantioselectiveconjagate addition.r This asymmetric reaction can be effectedby useof(S)-1 asa chiral leavinggroup.Thusthe cyclohexenone 2, prepared by reactionof 2-(nitromethyl)-2-cylohexenI -onewith 1, undergoes conjugateaddition with cuprates,followed by hydrolytic elimination of the pyrrolidine, to give 3alkyl-2-exo-methylenecyclohexanones (3) in high enantiomericexcess.
o -\cH,rvo, I ll
(oc*3
o
.ocH.
;' ,,\,^.^/) + HN | -----------| ll 8e-e4% \__,
\-r,
\--'
a methylenegroup to the silicoo erm of 2, preparedfrom (S)-2-(merhoryl methylsilane,is alkylatedin >95t peroxideoxidation cleaves3 ro (SFf tion. rR. Tamura,K. Watabe, H. Kenyr-. (1990). ' T. H.Chan a n dp . p e l l o nA,n . f u . . l l
Methoxy(phenytdimethytsityt)rel|f a-Hydrory aldehydes,t A oer p anion reacts with a wide varicty of
\_/
tr cilro{
(s)-r
(I) C6H5(CH3)rSicHrBr -
t
o
tl
l) ZnBrl 2) (CHr)rculi
ztft_-..__t + a^'ft'' l ..*CH, I
(II)I+R'COR"C'4{C}l'
o
(S)-3(>907oee)
Diastereosclective alkylation of organosilancs.2 Use of chiral organosilanesin which Si is the chiral centerfor enantioselective reactionshas not beenpromising, but high diastereoselectivity hasbeenobtainedwhena chiral auxiliaryis attached by CH.OCH. f)sec-Buli
'll*:i9"")
l-A*---- tsi' cH2c6H5 58-86eo | V V , / \ CH.
t
D. J. Ager,J. E. Gano,andS. I. puctl.
CH.OCH. '
I
CH,
generallyin 75-95% yield and usuelly are convertedinto c-hydroxy aldctydc presence of Br2 (equationII).
B
\----.aa,'\-cuu, CH,
Vethylaluminum bis(4-bromo|51
, / \ CH,
( S ) - 3 , > 9 5 7 oe e
Br{ L
,o-r*
| Hp,/KF/KHcol
Fo_r / l t"(*,\a
,t
R I /-cuH' HO (s)-4 (98.5-99.54o ee)
Claisen rearrangement.r Allyl vil :rogementreluctantlyand in low yield, &-r-butylphenoxide), MAD; bur this dl rot readilyar -78o with high (Z)_sc iDotrol the stereoselectivity,for usc o{
Methylaluminumbis(4-brorno-2,6-di_r-butylphenoxide)
ktters,30,3779(1989). hranedron
is a\lmmetric reactioncan be ef2, prepared fhui thecyclohexenone conjugateaddic lr rrh l, undergoes oatronof the pyrrolidine,to give 3excess. h enantiomeric oCH, i N
I
2Og
a methylenegroup to the_siliconatom ofan organosilane. Thusthe anion (sec-Buli) of 2, preparedfrom (s)-2-(methoxymethyl)pyrrolidine and benzyl(chloromethyl)dimethylsilane,is alkylatedin >95% oe toli"e (s)-3 in 5g-g6%yield. Hydrogen peroxideoxidation creaves3 to (S)-phenylcarbinols (4) with retentionof configura_ uon. f R. Tamura,K. Watabe, H. Katayama, H. Suzuki,andy. yamamoto, J. Org.,55, 40g (1990). 2 T. H. Chanandp. pellon, Am. Soc.,lll, g73709g9). Methoxy(phenyldimethylsityl)methyltithium (l ). a'Hydrory aldehydes.r A new preparationof l is shownin equation(I). This anion reacts with a wide variety of aldehydesor ketonesto furnish adducts(2) l) CHTOH, ASNOr
(I) C6H5(CH3)rSiCHrBr
-i-*
----+
C6H5(CH3)2SiCHLiOCH. I
D
lL .cH.
(II) I + R'coR2-
-)
c6H5(cH3)2si\ cH3o
_.-CH,
XRI
lifi'"6?'o"o"oHC. ,Rl
,orr
V
-ffi% R2
Hol\R'
t I
3
>q )'i ee)
il vs.: Useof chiral organosilanes s reactionshasnot beenpromising, by rhena chiral auxiliaryis attached
generallyin75-957o yield and usuallyin a l:l diastereomeric ratio. The products areconvertedinto a-hydroxyaldehydesby oxidation of the acetatewith H202in the presence ofBr2 (equationII). D. J. Ager,J. E. Gano,andS. L parekh, J.C.S.Chen.Comm.,1256 09g9). Vethylaluminum bis(4-bromo-2,6_di_r_butylphenoxide),
CuH,
cH,
cH,
S r - 3, >957o ee ."
eo*. H?O,/KF/KHCOI I
s,4
o{"'':"'^.'':'r')-o
\:{
Fo_+,_o< |
\c{cHr;, cH'
\J
FBr
(l) \r,
cfc',l,
I
R I /-cuH' HO (s)-4 qE.5-99.54oee\
claisen rea,angement.r Allyl vinyl ethers such as 3 undergoclaisen rearnngementreluctantlyand in row yield whentreatedwith methylaliminumbis(2,6"tr-t-butylphenoxide), MAD; but this dibromoderivative,l, effectsthis rearrangercnt readilyat -79'with high (Z)-selectivity.Evidently the burkyr-butyl groups iDntrol the stereoselectivity, for use of methylaluminumbis(2,6-iiphenytptrnor-
Mctll^.ld-
2lO
Methylaluminum bis(4-bromo-2,6-di-t-butylphenoxide)
electroniceffectsmay ide\,2,resultsin (E)-4 almostexclusively.In the lattercase' are activesubstrates optically be involvedas well as the lower stericrequirements. 2' I and rearrangedwith conservationof chirality by both
<"Lr.
l l l ' -
) i-Bu-
i-Bu4o/
i l t
CHO
/"{cH' tt'"",4 to
4 EIZ = 7:93 EIZ = 97:3
3 + l, -78", 64Va + 2. -20". 85Vo
(3) with high cis-sclec enecyclohexanols reactionspromotedby the more tradiria contrast,useof thebulky organoaluminu This trcns-selectivityextendsto enc rcr (equationI) and to rigid cyclic substnt6
I, CHrcl: + 5t*
H.C4
CH,
of a bisallyl vinyl ether suchas 5 involvesthe more Moreover,rearrangement allylic systemto provide(E)- and (2)-6' substituted
CH, l. cH,cl--------+ 804
------",.=,(JH' "'t=i'l"o 5 | 2
6 EIZ = 24:'16 EIZ = 9O:10
97Vo 9lVo
Rearrangementofallylphenyletherswithlresultsmainlyinparc-substituted by thermal rearrangephenols rather than the oirfto-substitutedphenols formed ments.2
c.u,4?,,"-tosiR, f
oH
11/---rr2C(CHr),
l
r r . c H ? c r ,- ? 8 " > ( - \
/-\
c2%
\-)
V
+
o-isomer
ro:r ,,4.c(cH)'
CuH,
with an c-methyl Intramolecularene reactions.3Ene reactionsof 6,e-enals chlorideresult in cis-methyl' substituent(2) when promotedby dimethylaluminum
?li' rr--r.t", -",.A.1o" r--).t"'
-
.".A.r.to .,
(cH3)rAlcl |
aYt"'
,,r*"'o^ trans-3
cis-3 659o 85Vo
Epoxiilc reorrangemenl.' This reeg epoxysilyl ethersto p-silyloxy aldcby& groupto the epoxidewith no loss of thc nrded by relatedaluminumreagents($r groups.
9:l l:32
o:
QH,
This aluminumreagentis alsoan cfcrt or ketonesat -20o to - 7t' ro aldehydes croupsare replacedby diisopropylgrury
cuu,X3-c"H'-!
o:'
Methylaluminum bis(4-bromo-2,6-di-r-butylphenoxide)
!r .ase.electroniceffectsmaY are Oprrcallyactivesubstrates 2. rnd
enecyclohexanols (3) with high cis-selectivity.The samecis-selectivityobtainsin reactionspromotedby the more traditionalLewis acidssncla or BF3 etherate.In contrast,useofthe bulky organoaluminum reagentI resultsin high /rans-selectivity. This trcns-selectivityextendsto ene reactionswith a trisubstituteddouble bond (equationI) and to rigid cyclic substrates (equationII).
CHO (
{
2ll
l
)
r---rt"' l l -
t-o
cH,\
-
,.."..,. - .
1
s8s'
>
/t-\-cH' l l
H,c)\?..oH CH,
CH.
r :uch as 5 involvesthe more CH,
CH'
-) CHO
9 { ) :l 0
ulr. mainlYin Para-substituted ft rmed by thermal rearrange-
Epoxidcrearrangemen.4 This reagentpromotesrearrangement ofchiral a,pepoxysilyl ethersto p-silyloxy aldehydeswith anri-migrationof the -cH2osiR3 groupto the epoxidewith no loss of the optical purity.5The rearrangement is retardedby relatedaluminumreagents(suchas MAD, 13, 203) lackingthep-bromo sroups.
cuu,
I
r, cH,cl,,-78"
cH3\...OSiRl I
o-isomer
l0:I
CuH,
"osiRl -
/-osiR3
:
";-
cuH.^cHo
.<.('CH'1, ; of 6,e-enalswith an o-methy' rn chlorideresultin cis-methYF
aY'"'
a,c29"'ou ftans -3 e
l
This aluminumreagentis alsoan effectivecatalystfor rearrangement of epoxides :o aldehydes or ketonesat -20o to -7go.6 The relatedreagentin whichthe r-butyl froupsare replacedby diisopropylgroupsis generallyineffective.
c"H,XI.C,','' ;;?l',(c6H5 )2cHcHo
O:'.#O(":
212
bis(2,6-diphenylphenoxide) Methylaluminum
rK. Nonoshita, ibid',112' 316 (1990)' H. Banno,K. Maruoka,andH. Yamamoto, 2 K. Maruoka,J. Sato,H. Banno,and H. Yamamoto,TetahedronLctters,3l' 377 (1990). 3 M . I . J o h n s t o n , J . A . K w a s s , R . B . B e a l , a n d B . B . S n i d eOr r, g J '' , 5 2 , 5 4 1 9 ( 1 9 8 7 ) ' a K. Maruoka,T. Ooi, and H. Yamamoto,Am. Soc.,f12' 90ll (1990)' 5 K. Maruoka,T. Ooi, andH. Yamamoto, Am. Soc.,1l1' 6431(1989)' (1989). 6 K. Maruoka,s. Nagahara,T. ooi, andH. Yamamoto,TetrahedronLetters,S0,5607
+ CH.:O
a"r-a\ Methylaluminium bis(2,6-di-rbutyl-4-methylphenoxide) (MAD), 13, 203' silective conplexation of ethers.r This aluminum reagentshows remarkable selectivityin formation of complexeswith ethers.Thus it effectsvirtually complete complexationof alkyl methyl etherswithout effecton alkyl ethyl ethers.In general, etherswith less-hinderedalkyl substituentsform complexesmore easily with MAD than their more bulky counterpartsand the more basic etheral oxygenscoordinate morereadilyto MAD thanthe lessbasicoxygen.The two bulky phenoxygroupsare essentialfor this selectivecomplexation,sincemethylaluminiumbis(2,6-diisopro pylphenoxide)doesnot form complexeswith ethersundersimilar conditions.This selectivecomplexationcan be usedto separateethersby chromatographywith MAD as the stationarY Phase. |,4-Addition to quinone monoketalsand quinol ethers'2 Complexationof quinone monoketalsor quinol ethers with MAD permits l,4-addition of organo' tittriumandGrignardreagents.Highestyieldsobtainwith aryl, vinyl, andacetylenic organometallics. I K. Maruoka, Am' Soc',ll2,6l15(1990)' andH. Yamamoto, S. Nagahara, 2 A. J. Stern. Org',54'4413(1989)' J' S. Swenton, and J. J. J. Rohde,
MAPH (f )' Methylaluminum bis(2,6-diphenylphenoxide), ,
( \
/
,cuH,
/
cuHr, \
,)-o.\ . / .o<\ toH,
) (r)
\___/ A l / cuHr' I CH,
Formaldehyde-MAPl complexes.r Formaldehyde (gas) readily undergoo parrself-polymerizationand is usually generatedby thermal depolymerizatonof MAPH with formaldehyde,a linear trimer. Treatmentof trioxanein cH2cl2 at 0' generatesacomplex,CHr:g'yOtH,whichisstableat0ofor5hours'butwhich d".orpores slowly at 25'. The complexcan be usedfor aldol and ene reactionsof the aldehvdeitself.
I
+ cH':(
I CH,
K. Maruoka,A. B. Concepcion. ft( 1990).
o(Methylamino)benzenethiol ( I ). Protectionof carbonyls.t Tbc bcnzothiazolines in 80-90% vield.
2"\-\
U[,;
roder mild and neutral conditioosr acthylation(CH3OSO2F) followcd I rrful for selectiveprotection of r r Ttrerelativeorder is cyclic one > | (hindcrod i .f -dimethyl-3-pentanone H Chikashita, S. Komazawa, N. lshr a.2.l2l5 0989).
llcthyl azodicarboxylate, (E -Cl Mitsunobu reactions.t Thc pr rrnnges for Mitsunobureaction;it I :omparableyields.
L D. Arnold.H. I. Assil.andJ. C, I
Methyl azodicarboxylate
n . t b i d . ,l 1 2 ,3 1 6( 1 9 9 0 ) . vahedronlztters, 31, 377(1990). 6 c r .J O r 9 . , 5 2 , 5 4 1( 91 9 8 7 ) . t. eolr (1990). . f'l-lI (1989). ktters,30,5607(1989). nrahedron
CH, + CHr:Q.144P11
'nol
ethers.2 Complexationof Dermits1,4-additionof organol srrh aryl, vinyl, andacetylenic - . | 1 2 .6 l l 5 0 9 9 0 ) . a .rrt-1( 1989).
cH2oH
6t%
o
""'\,4 roxide)(MAD), 13,203. inum reagentshowsremarkable llus it effectsvirtually comPlete n alkyl ethyl ethers.In general, mplexesmoreeasilywith MAD tsrc etheraloxygenscoordinate r r*o bulky phenoxygroupsare ilryIaluminiumbis(2,6-diisoProl undersimilar conditions.This with MAD : b1 chromatography
213
|
cH, +CH,:Q.YAPH------)
|
?'"'
cHrcH2OH
CH,
CH,
f K. Maruoka,A. B. Concepcion, N. Hirayama, andH. yamamoto, Am. Soc.,112,7422 0990).
o-(Methylamino)benzenethiol (1). Protectionof carbonyls.r The reagentconvertscarbonyl groupsinto 3-methylbenzothiazolines in 80-90% yield. The productscan be hydrolyzedin good yields
4\I
V./
ll
u r
NHCH3
LiArH. ->
SH I
A P Hr l ) .
rl)
rhrde (gas) readilY undergoes of Pararrmal depolymerizaton MAPH with 0" roern CH2CI2at which but hours, ble at 0o for 5 of reactions ene cd itrr aldol and
undermild and neutralconditionswith AgNo3, Hgcl2, NBS, chloramine-T,or by methylation(cH3oso2F) followedby basichydrolysis.Benzothiazolinarion is also usefulfor selectiveprotectionof a carbonylgroup in the presenceof anotherone. The relativeorder is cyclic one ) linear one > cyclic enone> linear enone> > 2,4-dimethyl-3-pentanone (hinderedketone). I H. chikashita, s. Komazawa, N. Ishimoto, K. Inoue,andK. Itoh,Bull. chem.soc.Japan, 62, tzrs (1989).
Methyl azodicarboxylate,@ -CH2OCON:NCOOCHT (l). Mitsunobu reactions.r The polystyrene-supportedreagentoffers several advantages for Mitsunobureaction;it is easilyobtained,is nonexplosive, andprovides comparable yields. r L . D . A r n o l dH, . I . A s s i la, n d J . C . V e d e r aAs m , . S o c . , l l l , 3 9 7 3( 1 9 g 9 ) .
(2S,45)-N-Methylcarbamoyl-4'dicyclohexylploq-r 214
Methylbis(l-nephthyl)bismuthinrte
-Methyl benzenesulfenat€'C6H5SOCH3' and BF3with the diene I in ioly"n, cyclization.r The reactionof C6H5SOCH3 cH3No2initiatescyclizationtothetricyclicringsystem2viaasulfeniumion.This desulfuration prodo.r-n"u, converted to the diterpene nimbidiol (3) by reductive ltitt'io,onaphthalenide)andoxidativedecyanation(SnCl),anddemethylation (BBr3).
N-Methyl-N,O-bis(trimethylsilyl)hydroryt
40-41"/10 mm. The reagentcanbe prepuci hydrochlorideandN(CrHr)r hydroxylamine 25" with stirring for threedaYs. N-Methylnitrones. The reagentcoava N-methylnitronesin high yield via a bcoi isolatedin somecases.
t r"
c6Hrs@HI BF.. CH,NO, 85%
*'.. R/
H,C CHt
C:O+l----+l
ln'a ,x-t C .mr, [5,/
2 (l: l) I e2%| ,u
' J. R. Hwu,J. A. Robl,N. Wang,D' A. Andds ( l 989).
(2S,45)-N-Methylcarbamoyl-#dicyclolcq methyllpyrrolidine (MCCPM, l) 15. 52-5
"t't\-
(_,!
CH, CH,
I coNl
3 l*tters,30, 1499(1989). t S. R,.Harringand T. Livinghollse,Tetrahedron
?
The reagentis obtainedin 80% Methyl bis(1-naphthyl)bismuthinate, NpriiioCH} Np3Bi,with chloramine-Tin methaVtfA LV reactionof tris(l-naphthyl)bismuihine, nol.r N.Acetyla'ion.2Amides,thioamides'ureas'andthioureasareN-acetylatedat ofthis reagent.It canserveasa catalyst, 25. by aceticacidin CHzClzin thepresence yields' but sioichiometricamountsare required for high IT. ogawa,T. Murafuji,K. Iwata,andH. Suzuki,Chem.Letters,202l(1988). 'i. Oi.*", K. Miyazaki,andH' Suzuki'ibid" 165l(1990)'
Asymmetric hyilrogenation of a<-t tRh(COD)Cll, and (2S,4S)-1effectsbigli aminoketones.This reactionprovidcs r rer (2)' A numt aryloxy-2-oxo-l-propylamine cenatedundertheseconditionsto the corrct B-aminoketonesare reducedwith lower cr
r+ \aphrhvt- o/YNHcH(cH3): tl
o ',
=
(2S,4S)-N-Metnylcarbamoyl-4-dicyclohexylphosphino-2[diphenylphosphino)methyl]pyrrolidine215
rnd BFr with the diene I in 2 r ia a sulfeniumion. This b1 reductive desulfuration inCl:). and demethylation
a :
A CH t
/os(cH3)3 N-Methyl-N,O-bis(trimethylsilyl)hydroxylamine,CH3N (l), b, p. si(cH3)3 40-41"ll0 mm. The reagentcanbe preparedin 52% yield by reactionof N-methylhydroxylamine hydrochlorideandN(C2Hs)r(3 equiv.) with ClSi(CH)3 (2 equiv.)at 25" with stirring for threedays. N-Methylnitrones. The reagentconverts aldehydesand aliphatic ketonesinto N-methylnitrones in high yield via a hemiaminalintermediate(a), which can be isolatedin somecases.
*'\
?si(cH');-lR'.
i
lR'\ /N-CH3 C:O + 1 ------>
| -------)
[.,rt or,,"",,J
R,/
l:l)
\
l
9H'
C:N'-O-
R,/
62-98Va I J. R. Hwu,J. A. Robl,N. Wang,D. A. Anderson, J. Ku, andE. Chen,J.C.S.perkinI,lg23 ( I 989). (2S,45)-N-Methylcarbamoyl-4-dicyclohexylphosphino-2[diphenylphosphino)methyllpyrrolidine (MCCPM, 1) 15, 52-53. Cv.P. ..\ ( ) ^ . .N-
P(C6H5)'
-l
coNHcH3
t4e9 ( 1989)
I reagenris obtainedin 80% vlrh chloramine-Tin methaat foureasare N-acetylated !r Ir canserveasa catalyst,
Asymmetric hyilrogenation of a-arnino ketones.r A catalyst preparedfrom lRh(coD)cll2 and (2s,4S)-1effectshighly enantioselective hydrogenationof caminoketones.This reactionprovidesa ready route to (s)-propranotol(3) from a 3aryloxy-2-oxo-l-propylamine (2). A numberof relateds-aminoketonesare hydrogenatedundertheseconditionsto the corresponding (2s)-alcoholsin 85-96%ee,but $-aminoketonesare reducedwith lower enantioselectivitv. H,
- o-)f: -Naphthyt nz'r l02l (1988).
O 2
*rcH(cHr), H
*-#t.-! O
I - Naphthyl o/\)f -
NHcH(cH,), H
(S)-3, 9l7o ee
216
Methylcopper-Diisobutylaluminumhydride
I H. Takahashi.S. Sakuraba,H. Takeda,and K. Achiwa,Am' Soc',112, 5876(1990)'
c-Methylcinnamyl
b.p. 80-85"/0'5 mm'
alcohol, C.HTCH:CHCHOH,
3t, The alcohol is obtainedby reactionof CH3MgBrwith cinnamyl aldehydein THF at 0" (95%yield). Protectiono! carboxylicacids.r MEC esters(l) are stableto weakacid or base, (2) but are cleavedselectivelyby reaction with the thiostannane(CHr)zSn(SCHr)z (1 equiv.)at 0o. andBF:.O(CzHs)u
T. Tsuda,T. Hayashi, H. Satomr, T. : K. R. Dahmke andL. A. Paquenc(
Methyl diazoacetate,N2CHCOO M eth oxycarb onylme thylatiot.l or ketoneswith methyl diazoaceu propanecarboxylates, which arc q tones)to form c-methoxycarbooy
cH,),sio. l) 2,BF,.o(c,H5), 0" c6H'cH"
OAc I
2)HoAc ,-cp,rCu1cu2)r0cooMEc
cH,'
\_,/
OAc I
9H, I
+ cHrscHCH: > n-cuH',cH(cHr)r0cooH
/
H
\
7
N,cl|cuH Cu(lt). CH,Cffi.l 5
{
CH.
(94Vo)
1
----t c6HsCooH + cH3c6H4cooC2H5 c6H5cooMEc + CH,CuHoCooc2Hs (l0f.Zo)
(lffiVo)
An addedadvantageof theseestersis the readytransformationinto other estersby alkylation of the intermediateorganotincarboxylatesin the abovereaction. 2, BF.' o(c,H5),
9u'
c6HscoocHcH:cHCeHs
BztBr'csF
c6H'cHi > 3#L
CuH,CooBzl
I T. Sato,J. Otera,andH. Nozaki,Tetahedron Letters,30'2959(1989)'
Methylcopper-Diisobutylaluminum hydride. l-r4-Reiuctionof enones.r Reductionof CH3Cu,preparedin situ from CuI and cH3Li in THF, with DIBAH in the presenceof HMPA resultsin a form of coppcr nyariae that effectsefficient and selectivel,4-reduction of enals' enones,and enoates,and 1,6-reductionofdienonesand dienoates.The reagentdoesnot reduce isolated carbonyl groups or double bonds.2It can also be used for regiospecific preparationof enol silyl ethersfrom an enone'2
.9H,
l) CH,Li,Cul, DIBAH, HMPA
2)(cH')'sicr
> (cHr)isio
H -U. Reissig, I. Reichelt, andT. Kr
Ycthyl 2,2-dimethyl-1-cyclopro Preparation:
CH.OOCC-CH + Ct
217 Methyl2,2-dinethyl-l-cyclopropenecarboxylate
rn Soc.'ff2, 5876(1990)' b p 8 0 - 8 5 " i 0 . 5m m ' in THF at b crnnamYlaldehYde I arestableto weakacidor base' (2) (CHr)zSn(SCHr)z Dstannane
I T. Tsuda,T. Hayashi,H. Satomi,T. Kawamoto, J. Org',5f' 537 (1986). andT. Saegusa, 2 K. R. Dahmkeand L. A. Paquette,Org. Syn.,submitted(1990).
Methyl diazoacetate, N2CHCOOCH3. The reaction of silyl enol ethers of aldehydes Methoxycarbonylnethylation.r or ketones with methyl diazoacetate[Rhz(OAc)a or Cu(acac)2]forms silyloxycyclopropanecarboxylates,which are opened by N(CzHs):'HF (aldehydes) or HCI (ketones) to form c-methoxycarbonylmethylated aldehydes or ketones.
f"'
N(C,H,\'HF cH,cr, , 86ca
.cH.' cu(ra.cH,cooc,H.^ N?cHcoocH, (cH,),sio. loo:' ---j*A rCH, V{ .cH. CH,
(cH.).siq \-/ H
t{,COOH+CHTSCHCH:
? f",
Dtl - cHrc6H4coocrH5 (1007o) r bY ln:irrrmationinto otheresters reaction' ts rn the above
HC-C-CH2COOCHI CH,,
rCHr)rSiOr_ /-\ \--/-t"'
i : 3 ' ( \ F
-jj:=
62?
coH,cooBzl
. _101959(1989).
(1989). andT. Kunz,Org. Syn.,submitted L Reichelt, H.-U.Reissig,
in si,n from CuI ad Cu. prePared MPA resultsin a form of coPPr ad rrduction of enals, enones' reducc not Ire:. The reagentdoes rn rlso be used for regiosPecifc
(l). ltethyl 2,2-dimethyl-l-cyclopropenecarboxylate Preparation:
cH3oocc-cH
+ cH.ccH: "tl +
N
cHrooc
NzNr -CH, I''--,/ X-CHr
"
2
lr"
Y
9H, | ,sio
tn'vtn" /\ ,/_\ cHpoc/I
zlE
Methyl(R)-3-hydroxybutyrate
undergoesDielscycloadditions. This activated gem-dimethylcyclopropene showshigh 1,3-dienes with reaction The kbar. 6-10 pressures of at reactions Alder (2) of I precursor of the (I). reaction In contrast, in equation as shown exo-selectivity with the samediene followed by extrusion of N2 results in the sameproducts,but with oppositediastereoselectivity'
OAc CH.-
l0 kbsr ------------)
G ) r +(
18%
\cH,
+ 50:1
I F. Shirai,J.-H.Gu,andT. Nakai,Cl*:r
Methyllithium-Chlorotrimetbyldlrrr Methyl kctonesfrom cstcn (12. I esterwith CH3LiandClSi(CH3)3 to pro silyl protected(S)-3-hydroxy-2-burrn
o o il ___ tl * c,H,o\ c,H5o^\at"'t
endo -3
exo-3
silyl keteneacetal(2b), obtainedby re anli-diastereofacialselectivity in aldol
OAc
O 2\hY
(
\"r,
,exo-3+endo'3
93%
I :50
This reactionwasusedto generatea modelof the tricyclic ring system4 someterpenes.
presentin
is essential;useof NILCI , ClSi(CH3)3 dcohol.This routeto ketonesis appuu sith butyl- or phenyllithiumprormra rmountsof a tertiary alcohol and grni
9cu,
QCH,
6 kbar cH.cl, + I ----+
L. E. Overman andG. M. Rishton,Ory.
5a%
4 I J. H. RigbyandP. C. Kierkus,Am. Soc',11f' 4125(1989)' Methyl (R)-3-hydroxybutyrate (1). ester underanti-Selective ahlol reactions. The dilithium enolate (2a) of this thc contrast' In syn-selectivity. usual with the goes Ticla-promoted aldol reactions
OM
t
OM
t
cH./^\Z\6gI{, ,,
+ C.H.CHO
OH OH ricr. l^l 4 z ^., ?]"-r-CuH' unt
OH
+
coocH!
coocH3 86Vo 759o
llethyl (R)- and (S)-mandeletc, C.ll esefulchiral auxiliary becauseit is r :orms and is removableby hydrogemt Asymmetric Diels-Alder rcactiat cthyl (R)-mandelateundergocyclodr grrc l -hydroxy-1,2,3,4-tetrahydrone OH
OH
t l cH,4\f+cfl'
Z-:/ i t t \.AcH" t-
+
/'e' tl l l R*ooc'"
4 (syn,sYn)
3 (anti,anti) a)M=Li b) M = Si(C,H'\
G
I
l) l0 kbr
(II) 2 +
H
22:78 93:7
R*=
"y;
Methyl (R)- and (S)-mandelate
tloprop€neundergoesDielsshowshigh n * ith 1,3-dienes rcrronof theprecursor(2) of I ilts rn the sameProducts'but
219
silyl keteneacetal(2b), obtainedby reactionof 2a with (c2Hs)3sicl, showsdouble 4nti-diastereofacialselectivity in aldol reactionswith a variety of aldehydes. lF. Shirai,J.-H.Gu,andT. Nakai,Chem. Lctters,lg3l(1990). Methyllithium-Chlorotrimethylsilane. Metful ketonesfrom esters(12, 126).t The reaction of a carboxylic acid or esterwith cH3Li and clsi(cH3)3 to provide a methyl ketonehasbeenusedto obtaina silyl protected(S)-3-hydroxy-2-butanone (2) from ethyl lactare(l). The additionof
o
o
l l crHso'A\a""r
end.o-3
t
t l - crHro\,-cH,
OH
t) cHrl-i, THF, - l05o 2) ClSi(CH1)1,-100e0' --...-----.--.-.
9%
OSi(CuHr)r-r-Bu
t
o
tl cH.'\9.cH, 4 Presentitr ncrclic ring sYstem
OSilCuHr;r-r-Bu 2 (>96Vo ee)
rH, .coocH3 \ --r<"", .,4
clsi(cH3)3 is essential;useof NHacl quenchresultsin large amountsof a tertiary alcohol.This routeto ketonesis apparentlylimitedto methylketones,sincereactions with butyl- or phenyllithium promoted with chlorotrimethylsilanegive significant rmountsof a tertiary alcohol and starting material.
-cH.
( " H \.H
L. E. Overman andG. M. Rishton,Org. Syn.,submitted (1991).
.l
189r
nolate (2a) of this esterundctIn contrast,tb srn-selectivity. OH
OH
OH
f t A..n, * cH,4-f4cJ1 coocHs
rccH.
4 (syn,sYn)
a4:.
22:78 93:'l
llethyl (R)- and (S)-mandetate,C'H'6UIOH)COOCH3. This hydroxy acid is a esefulchiral auxiliary becauseit is availablecommerciallyin both enantiomeric :ormsand is removableby hydrogenolysis. Asymmetric Diels-Alder reactions.r Both the acrylate and the fumarate of acthyl (R)-mandelate undergocycloadditionwith c-hydroxy-o-quinonedimethane to grre I -hydroxy-1,2,3,4-tetrahydronaphthalenes in > 95% de. OH
OH
I
+ R*ooc'/
/,.cooR* Z,.-a\-...cooR* --------' ll ll I 52soI \&\cooR*
** = X"u"' H
COOCHT
(>957o de)
22O
(SF(-FMethyll-nrphthylsulfoxide
' J. L. Charlton and K. Koh, Synlett,333 (1990).
The anion (LDA) of (S)-l addsro , (2) in essentiallylN% de. Desulfo (S)-tertiary alcohols (3).t Reaaioo o almostno diastereoselectivity.
(S)-1-Methyl-2-[(N- l-naphthylamino)methyl]pyrrolidine,
tH. Sakuraba andS. Ushiki.Tetahedw
Q^*Q., CH,
l0-Methyl-9-oxa- I 0-borabicyclo[3J
()
Asymmctic aldol reactions.r This diamine (1) when coordinatedwith tin(ID triflate and dibutyltin diacetatepromoteshighly stereoselectivealdol+ype reactions betweensilyl enol ethersand aldehydes. sloJrL' PSi(CH.). ?H ? "" !' Bursn(oAclr ) cHr(cHr)u^y^scrH, cHr(cHr)ucHo + fJ--\ sc2Hs cH, cH. syn,>98Voee ' T. Mukaiyama,H. Uchiro, and S. Kobayashi,Chem.lztters, 1757(1989);T. Mukaiyama, S. Kobayashi,H. Uchiro, and I. Shiina,ibid.,129 (1990r.
(SF(-)-Methyl l-naphthyl sulfoxide (1). This sulfoxide is obtained in optically pure form by oxidation ofthe complex ofmethyl l-naphthyl sulfide and p-cyclodextrin with peracetic acid followed by crystallization; m.p. 58", ca-460'.
The borane is preparedby reactiooc methylamineoxide. Coupling with vinyl, alkenyl, o thesebromidesunder Suzuki condiri correspondingmethylatedproducrs. I becauseit is spontaneouslyflammebl
z-CuH,rC-CBr
n-CuH,,
+ | ,
Br +
' J. A. Soderquistand B. Santiago, Iarrd
(s)-r
2 (lNVo de\
r.rt ao-as*Jn-"r
guu''... f'' c
\on cHrl (s)-3
(S)-l-Methyl-2-[(piperidinyl)ncrtyl
Asymmetric aldol-type rcactiott -. tin(Il) triflateandtributyltin fluori& (i aldol+ypereactionbetweenketenesil; (2) has beensuggestedfor the prorlo3
(S)-1-Methyl-2-[(piperidinyl)methyl]pyrrotidine
221
The anion(LDA) of (S)-l addsto n-alkyl phenylketonesro give the (s,s)-adduct (2) in essentiallylN% de. Desulfurizationof the adductsprovidesopticallypure (s)-teniary alcohols(3).tReaction of the anion of I with aliphaticketonesshows almost no diastereoselectivity.
rolidine,
' H. Sakuraba andS. Ushiki,Tetrahedron Letters,3f,5349(1990).
\ ( , D 10-Methyl-9-oxa-10-borabicyclof3.3.2ldecane (l).
/ ilr when coordinatedwith tin(Il) aldol-typereactions rreoselective
o H o | ll cH.rcH,)utfsc,H,
| :
CH, syn,>98Voe kners. 1757(1989);T. MukaiYamr' 190t
sulfoxide is obtained in optically l-naphthyl sulfide and p-cycloder-
.rcH.,
ffi
t
The borane is preparedby reactionof B-CH3O-9-BBN with CHrLi and then trimethvlamineoxide. Coupling with vinyl, alkenyl, and aryl bronides.t This reagentcoupleswith thesebromidesunder Suzukiconditions(14, 124-125;cat. pd, base)to give the corresponding methylatedproducts.l0-cH3-9-BBN is not usefulfor this coupling becauseit is spontaneouslyflammablein air.
r-CuH,rC-CB, a 1 - !E!---*
D.m.p.58o,0D-460o.
^3,$:;
l
n-CuH,,
Br + I 5+
n-C.H,,C-CCH,
n-CuIJr,
'CH,
(2,994o\ rJ. A. Soderquistand B. Santiago,Tetrahedron Letters,3f, 5541 (1990).
2 rl$Mo de) .
I
.'*
| Rmey Ni
J
C . H ..... R - n
, c ,/\
CH.
OH
rS)-3
flA.-*"-'.'i
\p/ (S)-l-Methyl-2-[(piperidinyl)methyt]pyrrolidine, |
\-/
| (t)
CH, AsymmetrtcaWol-typereactions.r This chiral diamine (l) in combinationwith rin(Il) triflateandtributyltin fluoride(15, 314-315)effectsa highly enantioselective aldol-typereactionbetweenketenesilyl acetalsand aldehydes.A tentativestructure (2) hasbeensuggested for the promotor.
2-MethYl-P-ProPiolactone t
\
()^d J \_-J
N
)
2
cH( >:.s;-o\ -.o ,s4 Tfo F.' '\rn....o//
-cF,
I
Bu,
RcHo + tt':tto"r,
? o H /os(cHi)3-fu'ezro^+n
(s)' 89-987oee
6' 4653(1990)' andT' Sano'Tetrahedron' I T. Mukaiyama' S' Kobayashi'
-40 2-MethYl-P'ProPiolactone, ,[
O'
4-Methyl-l,2,4-triazoline-3,5dkrx,
Oxidation of hYdrazincsto dbiu' 'k idly and efficientlyin CHrOH at 0o by or diethyl azodicarboxylate(DEAD) rit spondingallenesin 50-?0% yicld' Tbc t and can be used to obtain optically rrivt
.OH r,cxr I I l|.rii
(l) C6H5C-CC\ t - H CHt (16% ee)
(r)'
CHt
ylides in tolueneat p-p'oploiactoJrer:acts with phosphorus a,!'Enones. rni' triphenyleliminate. when heatedtheseproducts 40o to form ketophosphori"", tll. interoxaphosphinine an possiblyvia oxidewith formationof c'p-enones' phosphine mediate(a).
o 9H, ""I'cLf- 1c.H'l'i'-4"!on I + (cuHr)rP:a11g 68Vo 55Vo
2a,R=H b, R=CHr
n
I
3 I
(c6H5)31
o
oH
Ofequal significance,the oxidetioor cen bc tures(-95o) that intermediates (3-pbcoyl of oxidation the that suggests of both the (E)- and (Z)-diazinc (2)' fi
C6H5CH-CCH2NHNH.
rso-r7o'
-
I
o ll ncu,icH:cHcH,+ (cuHr),P:o 4a,'l6Vo b,'1070
1464(1989) I J. Le Roux and M' Le Corre' J'C'S' Chem'Comm''
-70", Pocsib rangesmore slowlY at MTAD.2 with oxidations
4-Methyl-1,2,4-triazoline-3,5-dione
i-'
oA 4-Methyl-l 12rrl-triazoline-3,S-dione,
^zo
5 -
-cF,
,//
o o H
223
F\AO *
CH, Oxi.dationothydrazincs to diazincs. Propargylichydrazinesare oxidized rap(MTAD) idly andefficientlyin CH3OHat 0o by 4-methyl-1,2,4-triazoline-3,S-dione or diethyl azodicarboxylate(DEAD) with evolutionof nitrogento provide the correspondingallenesin 50-70% yield. The reactionoccurs with high stereospecificity, andcan be usedto obtainopticallyactiveallenes(equationI).t
;.- rroA-i* (S), 89-98% ee
a i 2i , t 4 . 4 6 , 4 6 5 3 ( 1 9 9 0 ) .
...oH
(t) C6H5C:CC\ t - H CH,
llfiii'.?f' 2NHNH'l ' )t lc6H5c-cc....H I L
C
H
,
J
(76Vo ee)
,,*Joroo, o',-*, I
...CH, C.HTCH:C:C-
ylides in tolueneu 3 * rth phosphorus Fd theseproductseliminatetriphenyl' inter. F.:sibly via an oxaphosphinine
o
cH"
H FrA-lo"
'H
(75Voee)
Of equalsignificance, theoxidationwith MTAD canproceedat suchlow temperaThis work tures( -95") that intermediates can be identifiedby NMR spectroscopy, (l) involvesformation thattheoxidationof(3-phenyl-2-propynyl)hydrazine suggests of both the (E)- and(Z)-diazine(2). (Z)-2 rearrangesrapidly to 3, but (E)-2 rear-
3
(E)-2
I
I rso-r'ro" J
(z)-2
)
lr
l('t.l:CHCH, + (CuHr),P:O la.767o b.70Vo
J-N, C.H,CH:C:CH, 3
vz
:16{ (1989).
formedon rangesmore slowly at -70o, possiblycatalyzedby the 4-methylurazole oxidationswith MTAD.2
224
Methyl(trifluoromethyl)dioxirane
tA. G. Myers,N. S. Finney,and E. Y. Klo,TetahedronLctters,30,5747(1989). 2 A. G. Myers and N. S. Finney,Am. Soc.,ll2,9il1 (1990\.
CHr____9 Methyl(trifluoromethyl)dioxirane, CF,, d Q), 15, 212. Oxidation of alkanes to alcohols and/or ketones.r This dioxirane oxidizes hydrocarbons in CH2Cl2/l,l,l-trifluoro-2-propanone (TFP) at -22to 0o to alcohols or further oxidation productsin high yield. Tertiary C-H bonds are attackedmore rapidly than secondaryones, and primary C-H bonds are scarcely affected. The oxidationapparentlyinvolvesinsertionof o-atom. oxidationscanbe stereospecific, as in the caseof cis- and tans-I,2-dimethylcyclohexane.
N-Methyl trlfluoromethanesutrord Methylation otalcoholst (6, 406). to the correspondingmethyl ethcr il t3 equiv.) and 2,6-di-t-butylpyridinc (3Or cleavageor epimerization.
o
o
"5S
o
cH, (
Bzl
CH.
.",\t',
CH.
#"",A/!",
CH,
CH, OH
-OH - -NTICH! Primeryorr secondary aminesby this triflamidcr phine,diethylazodicarboxylate) in 7(H sion,andis usefulfor preparation of q OH :
l
l
t'cJ
cHrAzcHt
X)Vo
OH
r--q /.----JcH3
f", -
f9o,
f",
L/_---Jat, 987o
Oxi.dationol alcohols.z This dioxirane oxidizes secondaryalcoholsto the ketonesvery rapidlyevenat low temperatures quantitative yield. Primary in essentially alcoholsare oxidizedmore slowly to mixturesof the aldehydeand the carboxylic acid. The oxidationpresumablyproceedsvia a hemiacetal. rR. Mello,M. Fiorentino, C. Fusco, andR. Curci,Am. Soc.,1ll,6749(1989). 2 R. Mello,L. Cassidei, M. Fiorentino, C. Fusco,W. Hrimmer, V. Jiiger,andR. Curci,/n. Soc.,ll3, 2205(1991).
I D. A. EvansandG. S. Sheppard, 1. OtS ' M. L. Edwards, D. M. Stemerick. ri l 0990).
Molybdenurn carbonyl. Chiral molybdenum comphrct cl2 plexes,(S)-and(R)-1, of2ll-pyrao ben 195) from p- and r--arabinose,respcc cleophilesat an allylic positionwith 961 sccondnucleophileat the other allylic 1 alsowith high enantioselectivity.Tbe r disubstitutedtetrahydropyranssuchrs 2 cat.
Molybdenum carbonyl
dron ktters,30, 5747(1989). I ,1s90).
r l t . 1 5 .2 1 2 . lctones.t This dioxiraneoxidizes rone(TFP)at -22 to 0o to alcohols tiary C-H bondsare attackedmore I bonds are scarcely affected. The n. Oxidationscanbe stereospecific, bherane.
N-Methyt trlfl uoromethanesulfonamide. Methylation of alcoholsr(6, 406). The sensitivealdol productI was converted to the correspondingmethyl ether in 83% yield by reactionwith methyl triflate (15 equiv.) and 2,6-di-r-butylpyridine (30 equiv.) in cHCl3 at 80" without retro-aldol cleavageor epimerization. H3C\_'CH3
o
H
-/-\ o o
CH,
CH. '
225
CH.
I
OH FCH. t
-OH + -NTfC&. Primary or secondaryalcoholsare convertedto protected secondaryaminesby this triflamide under Mitsunobuconditions(triphenylphosphine,diethyl azodicarboxylate)in70-86% yield. The reactionproceedswith inversion, and is useful for preparationof optically active secondaryamines.
-
CH,
OH
I --//\cH, ,
/
+
oH
rrNHcH.,
cHrA,-cH"ttt*;ouoo, OH I _-.'/\cH, -J-CH.
cH3NTf
cH..\/cH' l) Na, NHr, (cH!)rcoH
_ro* J| zrrna,l,b 3)H.o' I Y
't
CH"NBoc
cH'AzcH' CH.
I --ttou .-,__cH,
alcoholsto the kelize\ secondary quantitative yield. Primary :nrrall;aldehyde and the carboxylic f rhe lmracetal. r 5 , , r.' l l l , 6 7 4 9( 1 9 8 9 ) . V. Jiiger,andR. Curci,,{rn. flrirnmer.
I D. A. Evansand G. S. Sheppard,,/. O r g . , 5 5 , 5 1 9 ( 129 9 0 ) . : M. L. Edwards,D. M. Stemerick,and J. R. McCarthy,Tetrahedron Letters,Sl, 3417 (1990).
Molybdenumcarbonyl. Chiral molybdenumcomplexesof 2H-pyran.r Enantiomericallypure Mo-complexes,(S)-and(R)-1,of2ll-pyran havebeenpreparedby knownmethods(13,194195)from p- and r-arabinose,respectively.They react with a wide rangeof nucleophilesat an allylic positionwith96% ee. The resultingcomplexcanreactwith a secondnucleophileat the other allylic position to form cis-disubstitutedcomplexes, afsowith high enantioselectivity.The sequencecan be usedto obtain chiral cis-2,6disubstituted tetrahydropyrans suchas2, a componentofthe scentglandofthe civer cat.
Molybdenurn carbonYl
.f,
rco),Mo\K /{^"o" \o/
i\o/l l (s)-1
'T. Kamiyama, M. Inoue,andS. Enomo. C
(R)-1
Mo(CO)"Cp
Lcp
A
2) LicH,coocH,
CH,Li ---------+
R'-Z
I
l) Tr?F6-
(S)-l
Molybdenum(Vl) oxide-Bis(tribut5rhh) Epoxidation. The two reagents(prcr epoxidationof alkenesin HzO by Hp1 t pinene)addition of trimethylaminc is crr ingly, addition of a phase-transferotelyr
,/cp
92%
56%
CHr"
\o/"'.",coocH3 I ryrou, cu,on,Hp (s3%\
(84%) I 2) CF,COOH Hl. fto,(9o%) J3)
l l cH."'\o"'"'CHrcooH (R,R)-z,>9O7o ee
2-Morpholinobutadienes, in
Butadienesof this type are readily n dkene-l-ynes in the presenceof Hg(OAc Divinyl ketones.2 Thesebutadics I enceof MgBr2.O(C2H )2 or ZnCl2 to forr /cllzoc.H3
CH,
Thesecomplexescan also be usedto prepareoptically pure cis-2,5-disubstituted asan 5,6-dihydro-2ll-pyranssuchas3 by usinga molybdenumnitrosyl allyl complex intermediate. Mo(CO)'CP
\9/
r "'cHrcocH,
\' -"o (cH3ooc),cH...rd"-*o
t\o'l"'6HrcocH, l
2)NacH('oocHr), >
%$r)cAN 2) {oOcH,
i-r,
-1"-u |
A"",
^'
+ C"tLCl(
o - '
J. Barluenga,F. Aznar, R. Liz, and M.-P- | : J. Barluenga,F. Aznar, M.-P. Cabd, rd C,
r)No'BFl
t
LicH.cocH. f""""1 (R)-t-----.-----+[
\
o--'
cH3ooccH2...,rr\ |
|
t
l
\o/"'a",cocH, (-)-3, >9O7oee
r S . H a n s s o n ,J . F . M i l l e r , a n d L . S . L i e b e s k i n d , A m ' S o c ' , f 1 2 ' 9 6 6 0 ( 1 9 9 0 ) '
2-Morpholinobutadienes
227
Molybdenum(Vl) oxide-Bis(tributyltin) oxide, MoO:-(BurSn)zO. Eporidation. The two reagents(premixedin CHCI) can serveas a catalystfor epoxidationof alkenesin H2O by H2O2(60Voyield). In some cases(hexene, cpinene)additionof trimethylamineis essentialfor high yields, 57-87%. Surprisingly, addition of a phase-transfercatalystdepressesthe yield.
Cp it'COlu
I
I T. Kamiyama, M. Inoue,andS. Enomoto,Chem'ktters, ll29 (1989).
lvlo(CO)rCP
R'
(1).
2-Morpholinobutadienes, .,l:*4a""
o-..,'
g/"'cHrcoocH, I l) KoH,cH,oH,H'o (93%) | 2) cF,cooH (84%) H,,Pro,(mq,) l3)
t
l
,,,,CR,R,
Butadienesof this type are readily available by addition of morpholine to 3alkene-l-ynesin the presenceof Hg(OAc)2 G5-65% yield).' Divinyl ketones.z Thesebutadienesreact with aromaticaldehydesin the presenceof MgBrz.O(CzH)2 or ZnCl2 to furnish divinyl ketones(Nazarovreagents).
cH,"'\o/"'cH,cooH (R'R)-2' >9OVoee
trcally purecis-2,5-disubstituted enumnitrosYlallYlcomPlexasan
/cE2ocH3 CH.,-/C..,_, a^*\."."
oJ
"U,i3io:,X:'"r' cH^ZcHCH2ocH3 "Y"-+ cuH,cHo o),-o"r",^,
F. Aznar,R. Liz, andM.-P. Cabal,l.C.S. Chem.Comm.,1375(1985). J. Barluenga, J. Barluenga,F. Aznar, M.-P. Cabal,andC. Valdes,TetrahedronLctters,30'14l3 (1989). !r
fi ooccH2...r\ l l \o/"'""'"*tt, (-)-3,>90Voee .9..' . l12, 9660(1990).
Niobium(Ill) chloride-Dimctloryd Coupling of alhyncs ,irh 1.2. Cl3.DME (1) with alkynesrcacr rirh I up with aqueousKOH, 2,3{isub,rth Nickel boride, Ni2B. ArNO2 - ArNHz.r Aryl nitro compoundsare reducedto arylaminesby Ni2Bat 40" in 3N HCI or l5N NH4OH in 80-96Voyield without effect on alkene,keto, nitrile, amide, carboxyl, or ester functionalgroups.Nitroso-, azoxy-, azo-, and are reducedto aminesunder the sameconditions. hydrazobenzene
QH, Nm..DME
).
11l
*t
' (Tr{F)r.Ctiib{
I
si(cH3)3
I A. NoseandT. Kudo,Chem. Bull.,37,816(1989). Pharm. Nickel cyanide,Ni(CN)z.4HzO. Carbonylation of CHz:CHX and halodienes.r Ni(CN), is an active catalyst for carbonylationof unsaturatedhalidesunder phase-transferconditions.The effecofcetyltriThusin thepresence tive speciesis probablya cyanotricarbonylnickelate.
"\ C:C
cHl
/B'
t"",
*{9ll';9TB "t *co_-Iaolrl,o_1
seEo
'g:g'
/cooH
t.",
cHl
alkynes,two isomeric naphtholsrre r kynesresultsin high yield of a si.tk firrole synthesis.2 This rcegsr with an esteror DMF to form N-soh
COOH
I
+ CO ,*>
a\ \-,
CH'CH:(
HOOC.
R
Br. \ "u"r-"\--
)rc-cn:cH, .H
/fHc6Hs
)---1 ^^ | \-cHr + co, .-------' o4o.x;''
)._.":.",
// r c!6115 + ' H ' - c't" '
N\ CF,COOCH3+
|
frn,
CoH, 6oqd
(tleo)
I
?
Jsio, R /cH2c6Hs Y----1 / \ \ ol:62\cu, bromide(CTAB) and Ni(CN)2, carbonmonoxideconvertsvinyl methylammonium acids. halidesto c,P-unsaturated I H. Alper,I. Amer,andG. Vasapollo, Lettefs,30'2615'2617(1989). Tetrahedron 228
N. HCON(CH,),+
r
cJ
J. B. Hartung,Jr., and S. F. Pedcrser E. J. Roskamp,P. S. Dragovich,J. B. I ( 1989).
Niobium(Ill) chloride-Dimethoxyethrne
229
Niobium(Ill) chloride-Dimethoxyethan€,14, 213-214. Coupling of alkynes with |,2-aryl diatdehydes.l The complexes of Nbcl3.DME (1) with alkynesreact with phthalic dicarboxaldehydeto give, after workup with aqueousKoH, 2,3-disubstitutednaphthols.In the caseof unsymmetrical
re reducedto arylaminesbY Ni2Bat ld * ithout effect on alkene,keto, onp:. Nitroso-,azoxy-,azo-, and I sameconditions.
f',
i
E I si(cHJ3
Nbcr..DME
*t
-CH,
, (THF)r.CljM(
__--_-_______) _Si(CH3)l 70%
i i 1eR9).
OH
""'Y/)n ?r.r Ni(CN)2is an activecatalYst conditions.The effecbase-transfer ofcetyltriue Thusin thepresence
(>99:I )
H >
C:C
cH,
/cooH t"",
alkynes,two isomericnaphtholsare formed, but use of trialkylsilyl-substituted alkynesresultsin high yield of a singleregioisomer. fonole synthesis.2 This reagent effects coupling of c,p-unsaturatedimines with an esteror DMF to form N-substituted pyrrolesin 34-78Voyield.
C'OOH
't
CH,CH:CH,
HOOC\ ,CI{C"H5 7
r ('H K,,
(cHr)rsi-\,'j\2
OC-CH:CH. + CuHr-C,
t1
*
H
*) cF3coocH3.
"t'\*)
4,,,
iuH,
# '
fH,CH:CH'
A
cuH,
cH,
(15Vo)
Bzl
Bzl
I
ir
*) /cH.C6H5
I ( H ,
);. carbonmonoxideconvertsvinYl Lt ::c rs.30,2615,2617(1989).
HCON(CH3)' f
I
(\"r, CuH,
_-+ 8Wo
/ \ \ / / cuH,
CH
J. B. Hartung,Jr., andS. F. Pedersen, Am. Soc.,111,5468(1989). E. J. Roskamp,P. S. Dragovich,J. B. Hartung,Jr., and S. F. Pedersen, J. Org., 54,4736 ( 1989).
230
Norephedrine
Nitrosobenzene,C6II5N:O. Diels-Alder reactions.r Nitrosoarenesundergo Diels-Alder reactionsat 25o with cis- andlor trans-hexadienals 2 to give unstableadductsthat can be identifiedby IR and IH-NMR as 3 or the hemiacetals4. On standingor warming to 40o these primary products rearrangeto pyridinium betaines(5) or pyrroloindoles(6) as the
cHo (
c,HsocHoH
f"o
E+ o:NCoH,
\r"r.
fi \
c2HioH > fi -au", -"ur, ( Y
"t',
"t'o
o
tl
c6H5c(cH2)2cllo.
asymmetricconjugateaddition of dir Both Ni(acac)2and CH3CN rs rdl r Bipyridyl can be replacedby pipcrrzir loss of enantioselectivity.
o (E) ll
C6H5CH=CHCC.[\
+ 1C
' K. Soai, M. Watanabe,and M. Koyu. :K. Soai,T. Hayasaka,and S. Ugejir. ll
I
CuH, 5 (- l0Vo)
(- 4OVo)
major products. The latter products are particularly interesting becausethey are relatedto antibiotic and antitumor mitomycins. I A. Defoin,G. Geffroy,D. Le Nouen,D. Spileers, andJ. Streith,Helv., 72, I 199(1989). Norephedrine. y-Hydroxy ketones.r An asymmetricsynthesisof y-hydroxy ketonesemploys selectiveadditionofa dialkylzincto y-ketoaldehydes catalyzedby (lS,2R)-(-)- or (lR,2S)-(+)-N,N-dibutylnorephedrine (l). Conjugate addition of R2Zn to enones.2 A nickel catalyst (2) consistingof ( I S,2R)-(- )-N,N-dibutylnorephedrine (l), Ni(acac)2,and2,2' -bipyridylpromotes BurN
n"H"t CH,
OH
CUH'
(-)-r
BurN
OH
H..)---4H CH,
CUH' (+)-1
Norephedrine
p Diels-Alder reactionsat 25o r adductsthat can be identifiedbY uding or warmingto 40o these t5r or pyrroloindoles(6) as the c2H5ocHoH (tq - c. H.oH - > | | * \-2"'--
'"flt^'
C6H5C(CHr)2CHO fi
o ll
"
C6H5C(CH2)2CHC2H5 I OH (87Vo ee)
asymmetricconjugateaddition of dialkylzincsto c,p-enonesin CH3CN/toluene. Both Ni(acac)2and CH3CNas well as I are essentialfor enantioselectivity.2,2'Bipyridyl can be replacedby piperazineor l,lO-phenanthrolinewithout significant loss of enantioselectivitv.
I
CuH,
I CH,
rH.
o ll
4
o (E) ii
C6H5CH=CHCC.H, +
_-l
, cuH'-.. (C2H)27n+
o ii
/CHCH2CC6H5 C,H, (R,90Voee\
I K. Soai,M. Watanabe,and M. Koyano,J.C.S. Chem.Comm.,534(1989). ' K. Soai,T. Hayasaka,and S. Ugajin, ibid.,516 (1989).
CH, r - lOVc)
rl1 interestingbecausethey are Helv.,72,1199(1989). I J Streith,
;is oi y-hydroxyketonesemPloYs by (lS,2R)-(-)- or descatalyzed nrckel catalyst(2) consistingof 6 r,. and 2,2'-bipyridylPromotes Bu.\
OH
HFH cuH,
cH, t+)-l
231
0) (CH3)3SiSi(CHr),+ (
Organocerium reagents. Spiroketalsand oxaspirolactones.r An improvedroute to spiroketalsfrom lacsuchas l, preparedfrom 3,3tonesinvolvesuse of cerium 3- or 4-cerioalkoxides with lithium di-t-butylbiphenylide(LDBB) reductive cleavage dimethyloxetaneby lithium 3-lithioalkoxideas the of the intermediate Use followed bv transmetallation.
El:{"
LDBB' 0'' ['?G"I
(CH.).Sn-O
I Br t
-t*'- cr,ce^foCecr, I
lKt
dr'#O(1'J;, ofdouble attackofthe reagentresultsin low yieldsofthe desiredspiroketalbecause lactoneto give diols. A cerium reagentsuch as I also undergoesmonoadditionto anhydridesto provide an oxaspirolactonesuchas 2.
"n')-^ fl ^---, oAoAo ttE%.",1-X{ 2
(l) ir fi,N'-dibenzylasparaginc !-homoserineequivalent.Ra 6nal stepto a p-aminoacid isvu of nitrogen.
ato*'
BzlrNACcrcH l- I
I B. Mudryk,C. A. Shook, Am.Soc.,ff2, 6389(1990). andT. Cohen,
Organocopper reagents. Trimethylstannylcuprates; (CH)tSn(Bu)Cu(CN)Liz.t These cuprates are followedby mostconvenientlyobtainedby in situ generationof (CH3)3Sn-Si(CH3)3 reactionwith Bu2Cu(CN)Li2. Thesecupratesdeliver the (CH3)3Sngroup to organic substratesby conjugate is alsopossible. additionor substitutionof halo or triflategroups.Stannylcupration Chiral amino acids.2 The key step in a new synthesisof chiral p-amino acids involvesdisplacementof mesyloxygroupsby lithium dialkylcuprates.Thus (S)232
a* I H'N
7ctl a
The ring openingof t-butyl (S oratesprovides products (6 rnd rmino acids.3
organocopper
r€agents
TIIFA{MPA,
(D (cH3)3sis(cH3)3+ cH3Li
nproved route to spiroketalsfrom lacorrdessuchas l, PreParedfrom 3,3(LDBB) lirhrumdi-r-butylbiphenylide Dcdratelithium 3-lithioalkoxideasthe
-78to30P > (cHr)3sili + (cH3)4si
I tcn,),snct to-50' J-78 Bu'cu(cN)Li' (cHr)rsn-cu(cN)Li, . (cHr)rsn-Si(cHr), I
Bu I
?
l
l-
clce/)(^ocecl,
'.THF._?E"
CH,
CH, CH,
.\
cH3\
""-
CH,
CH,
-
CH,
kcHl
Sn(CHr),
I
\ \ ^-l I
HO(CH,),C-CH
CH' -CH,
I
HO(CH,).C:CH,
74%
Sn(CHr),
/ n )
ofdouble attackofthe roketalbecause as I also undergoesmonoadditionto hai2.
'"rox]o cH,
,
(1) is convertedby standardreactionsinto 2, an activated N,N'-dibenzylasparagine p-homoserine equivalent.Reactionof 2 with RzCuLigives3 in 50-70%yield. The final stepto a p-aminoacid involveshydrolysis ofthe nitrile group and deprotection of nitrogen.
,.coNH2lllilh?##l' 3) MsCl,N(C,H.),(97%)
I
--cN
I
-
|I
BzlrNAgggll
|I BzlrNAgllrgyg
,
l-l
o. . l12. 6389(1990)
)ttCu(CN)Liz,r These cuPratesarc lron rrf (CHr)rSn-Si(CH)3followedby
65% (CHr)rCuLi,ethq |
(cooH HrNAzcH' 4
by conjugatc up ro organicsubstrates possible. is also Stannylcupration lp. p-amino acids of chiral s]-nthesis ne\r r (S)Thus dialkylcuprates' lrthium br
l) Hro'(90%) 2) H,. Pd(OH),(99%)
_
-aCN | t
_.\-,cH,
BzlrN-
3
(5) with organocuThering openingoft-butyl (S)-N-tosylaziridine-2-carboxylate (6 pratesprovides products and 7) that are precursorsto optically active o- or prmino acids.3
234
Organocopperreagents
t
^cooc(cH,). rHF, HMPA + BuMgCl-CuBrS(CH'), ----------------t
f7
N
I
Ts 5
r" JT:oc(cH3)3 . r,*t Jol. cooc(cH3)l 7 (28Eo)
6 (47Eo)
Addition to allylic mesylotcs.t Coalr acyclic allylic mesylatessubstitutedI thr with higb Z involvesan SN2'-substitution induction. This reactionprovides a rootc
I
OMs ? 1
NHr.
t'^Y
il ..."
t -a,",
Bu._,,/...COO-
c^H./\H
(>95Vo ee)
( C H ) z C u ( C N ) L i 2 ' B r r ( 1 ) , a p r e p a r e db y a d d i t i o n o f B F I O ( C z H s ) zt o a highlydiastereose. (CHl)zCu(CN)Li2 at _78 - 0" (agingis important),undergoes (E)-o-methyl-p'T-enoates' provide to y-mesyloxy c,p-enoates with lectivereaction regardlessof the geometryof the startingmaterial,and with highly diastereostereoselective1,3-chiralitytransfer(>99:1). A 1-mesyloxyor a 1-tosyloxygroup and THF or THF/ether as solvent are essentialfor high chirality transfer. This reactionprovideschiral productsfrom r-threonine. OTBSH
OTBS |
^p r,,\.cH T
-----n2 :cHCook
-
'.THF-?8'
---:
-
+ cH,CucNLi ;il
*----+ -*,.
OMs
I
--,-/-.ycooR2
|
|
H
CH,
c
oMs I
r l l . . . ' . .. .( s'
""'
Y"-a,n, c^tt./\u
+ cH,cucNli;*
c
Reaction of RzCuLi with ser.-tosyll facilitatedby the presenceof S or O uq ethen methylethersor (methylthio)methyl O atomsarein a vicinalposition.This rer rnversionof configuration.As shownby d substitutionis low if a heteroatomis ebt oxygenfor coordinationto copPer.
(>99: I de at Ct)
OTs Chiral, unsymmetricaldivinylmethanolscan be preparedby reaction of (E,E)-dienoatc CHrCu(CN)Li.BF3,preparedfrom CH3Li, with a monoprotected with thc Sy2'reaction an involves reaction The L-tartrate. suchas 1, derivedfrom an (EI -78o and regiohigh with at readily proceeds mesyloxygroup. The reaction stereoselectivity.5
-
?t'
C zHTOOC -,2r'2,2--..42':COOC2H5 I TBSO I [TBS= t-Bu(CH,)rSi]
'"';i::flT;"' ---
x%-
+ (CH. 0) R'CHTCHCH2CH2R2 R' = -CH:SC.H. = -OCH$CH, = -OCH:OCH, = -{cHr):cH.
Allylic cyanocuprates.t Reagens ol :uantitativeyield by reactionof allyltribu L nlike allylic cuprates,thesenew dlylr -78". Thus they can displaceuoac'tiY rarrangement(equationII).
Organocopper reagents
L
.;i: HVPA ----------------
.,r,oo".-Z\,,,\-xiooc2H5 TBSO (99Vo de)
* ,r*"Jcooc(cHJ!
0C CH,r.
7 (28Va)
I
Addition to allylic mesyrates.6Conjugateaddition of organocyanocuprates to acyclicallylic mesylateszubstitutedat the p-positionwith a chiral sulfoxidegroup involvesan Sr2'-substitutionwith high z/E stereoselectivity and high asymmetric induction'This reactionprovidesa route to chiral trisubstituted vinyi sulfoxides.
g rvrr?
c^H o
i"'" 11..."' '"H'lt-.,",
+ cH,cuCNLi;;-\n-.,",
) coH,/\H I b r a d d i t i o no f B F 3 . O ( C 2 H 5t )o2 n3r: r. undergoes a highlydiastereosero pro\ide (E)-a-methyl-p,y-enoates, Ite::al. and with highly diastereoste.{ ,-mesyloxyor a y-tosyloxygroup f,ra. for high chirality transfer.This D nl n ( ' .
OTBSH
L n f/ycooR' H
CH,
t>99: I de at Cr)
r \. .BF, -!rF > _-,__________>
r....,
*
?"'[...''
c,H,.ys{:,",
94:6
cHr..'\cuH,
a"r^a.",
fl...,
f:",[.....
t . . " \ \ . . s i ^' 4. ., " , + C H , C u C N L i d \ - 3 { ^ . c-, ,H . A i : ' c , H , + ll I Y"-a,", cnH,-\H
a",^"u",
72:28
a";..(au".
Reqction ol R2caLi with sec-tosyrates.TDisplacement of tosyloxy groups is facilitatedby the presenceof s or o atomsin the vicinity. In the caseof methoxymethylethersor (methylthio)methyl ethers,optimumconditionsobtainwhentheS or o atomsarein a vicinalposition.This reactionis usefulbecause it involvescomplete inversionofconfiguration.As shownby the lastentry in equation(I), the yield ofthe substitutionis low if a heteroatomis absent.A sulfur atom is more effectivethan oxygenfor coordinationto copper. OTs
I .rn be prepared by reaction of rrrr r monoprotected (E,E)-dienoatc hon rnvolvesan Sp2'reactionwith thc 11 ,r -78" with high regio- and (E)-
o
t:"' X.....
| G) R'CHTCHCH2CH2R2 + (cHr)rCuli -_R' = {HzSCrHs = -OCHTSCH,
X)Vo
= -OCHTOCH:
64Vo
= {cHr)rcH,
40Vo
9H, :'" R'CHTdHCHTCH2R'
83Vo
Allylic cyanocuprates..t Reagentsof this type can be prepared in essentially quantitative yield by reactionof allyltributyltinswith (cHtziu(iN)Li2 (equation I). Unlikeallylic cuprates,thesenew allylic cyanocuprates are highly reactiveevenat -78". Thus they can displace unactivatedchloridesand cleaveepoxideswithout rearrangement (equationII).
Orgenocopper rergents
(I) 2 CHr:QHCHrSnBu, + (CHr)rCu(CN)Li,#
(CHr:g11"t)rCu(CN)Li, I 86% | CJrO(CHr)rBr, -78"
o
,Jl-.
(-,!. Hrc/
f", \cHrcu.cr
{
nr* |,"",,,":a"cHrcu.
+
C6H5O(CHr)4CH:CHz
o tl
.,O" .',"I"")"*"',r,, #(],..|rrn, by Cyclic allylic cyanocuprates can also be preparedfrom cyclic allylic stannanes reactionwith CH3Li followed by CuCN solubilizedwith LiCl. Thesecyanocuprates couple with enones,primary and vinylic halidesand epoxides(equationIII).e
arr]tn"u' ""..,, tQ.l
cucN.Lic,, j'$"t*" lt"."",o.", -" 'LJ I
't6% | | I
H
-t*
t
l
\:-A:-z\z.cHr I CH,
methyllithium,andCuI.LiCl in THF. d reactionis markedlyfacilitatedby thc pn and crotylcoppers,coupling occurs meil C-Glycosides. Transmetallationof cosyllithiumreagentsthat undergoI ,2-rd glycosides.r2 Reactionof the glycosyllit whenpromotedby a Lewis acid, procccd be markedlyimprovedby conversiooof t with 2-thienyl(cyano)copper lithium ( l.
H
|
*"'\o
c6H5cH2ocH'F,o H Dilithium diallylic cyanocuprates couple readily at -78'in triflatesto form 1,4-dienes(equationIV).r0
osrcH,.
H
R,sioAr"'snBu.h.",,,0
THF with vinyl
:CHCHT],Cu(CN)Li,--------> (IV) C6H5CHf H:CHOTf + [(CHr)rC (E[Z= 8:r\ : CHCHTCH : C(CHr), C.HTCHTCH (EZ = 8: l) Allylcoppers.rl In general,lithium diallylcupratesare not useful for conjugate addition to enones. Surprisingly, allylcoppers, prepared from allyltributyltins,
ciently with epoxidesin the presenceof yield.r3 Organobis(cupratcs),14, 225. A cnoneswith thesecupratesincludes I I e obtainable.
7
{CHr:Q11911r)rCu(CN)Lq I
a.
,u* | ".",o1"",),"r, -tt"
o
A
CH.
*
I /ac\
HrC-
THF 95%
CHrCu.ClSi(CHr),
+
C6H5O(CH)4CH:CHz
rzga tcu,),c:cHCH,cu. clSi(cH,), J
o
^Yo"
"""
t l l r--l"'curCCg,
CH,
CHt bY from cyclic allYlicstannanes rith LiCl. ThesecYanocuPrates I epoxides(equationIII).e
-r'':.-..)tCuCNLit
f
-'\)|
|
lc,H,cH,ocH,\
/l
-n+ |
I -t* |
H
methyllithium,andCuI.LiCl in THF, addto enonesevenat -78o, andthis Michael reactionis markedlyfacilitatedby the presenceof ClSi(CHr)r.In the caseof prenylandcrotylcoppers,couplingoccursmainly at the o-position. C-Glycosides. Transmetallationof glycosylstannanes with BuLi provides glycosyllithiumreagentsthat undergo1,2-additionto carbonylcompoundsto provideCglycosides.r2 Reactionofthe glycosyllithiumreagentswith epoxides,however,even whenpromotedby a Lewis acid, proceedsin poor yield. Couplingwith epoxidescan be markedlyimprovedby conversionof the glycosyllithium to a cuprateby reaction with 2-thienyl(cyano)copper lithium (1, 14,2261,15,228). This cupratereactseffi-
H
Y
l) BuLi, THF
c.H.CH,OCH .
|
1
^
|
|
^
^
|
'
-
9-'
^(cHr)roBzl
1i1...o.,".,, -rru-
nAtt 11 at -78" in THF with vinYl
-----+ ,CurCN)Li, LCH.CH:CHCH'CH:C(CH)t ( E l Z= 8 : l ) rares are not useful for conjugprepared from allYltributyltirt
(CHr)rOBzl
R3SiO
( 2 :l ) .-rcntlywith epoxidesin the presenceof BF3etherateto give C-glycosidesin good . rcld.l3 Organobis(cuprates), 14,225. A detailedreportraof the spiroannelation of cooneswith thesecupratesincludesI I examples.In all casesyieldsof 56-96Voare rbuinable.
Organocopper/zinc reegents
o
resulting dimetallic reagentsare coopu with electrophilesand in addition to ur This transmetallationhas bcen uscd reagentssuchas I from c-bromodkyl r mide to aldehydes.2
rB. H. Lipshutz,S. Sharma,and D. C. Reuter,Tetrahedron Letters,3f, 7253 (1990). 2 P. Gmeiner,TetahedronLctters,3l, 5717 (1990). 3 J. E. Baldwin, R. M. Adlington, I. A. O'Neil, C. Schofield,A. C. Spivey, and J. B. .l.C.S.Chem.Comm.,l852(1989). Sweeney, a T. Ibuka, M. Tanaka,S. Nishii, and Y. Yamamoto,Am. Soc., l1l,4864 (1989). 5 T. Ibuka, M. Tanaka,and Y. Yamamoto,,/.C.S.Chem.Comm.,967 (19E9). 5 J. P. Marino, A. Viso, R. Fernandezde la Pradilla,and P. Fernandez, J. Org.,56,1349
(leel).
7 S. Hanessian, B. Thavonekham, andB. DeHoff,J. Org.,54,5831(1989). t B. H. Lipschutz, R. Crow,S. H. Dimock,E. L. Ellsworth,R. A. J. Smith,andJ. R. Behling,Am. Soc.,ff2,4063 (1990). e B. H. Lipshutz, ktters,3l,4539 C. Ung,T. R. Elworthy,andD. C. Reuter,Tetruhedron (1990). I0B. H. Lipshutz andT. R. Elworthy,J. Org.,55, 1695(1990). rr B. H. Lipshutz, E. L. Ellsworth,S. H. Dimock,andR. A. J. Smith,Am. Soc.,ll2,UU (1990). '2P. Lesimple, andP. Sinai,Tetrahedron ktters,27,6201(19E6). J.-M.Beau,G. Jaurand, 13J. Prandi,C. Audin,andJ.-M.Beat,ibid.,32,769(1991). 11P. A. Wender, (19E9). Org. Syn.,submitted A. W. White,andF. E. McDonald, Organocoppcr/zinc resgents. RCu(CN)ZtI. Organozinciodides (or bromides)are readily formed by reaction of alkyl or aryl iodideswith zinc foil or dust. This insertionreactionis compatible with a wide variety of functional groups: ester, keto, nitrile, acetoxy, amino, thioether. However, thesereagentslack the high reactivity of organocoppercompounds. In contrast, it is difficult to prepare organocopPercompoundscontaining reactiveconstituentsbecausethey are usually obtainedby reaction of Grignard or lithium reagentswith a copper(I) species.
o RcHo + cHrcoBr#OAc -|H
R-\< / H
\ coocrtt
lr=cr <_ -
(>96Vo E\
R.
Allylcopper/zinc reagentscan bc pre reagentswith (iodomethyl)zinciodidc. d ptlzinc reagentsdo not couple witb rr readily with electrophilessuchas aldc! organodimetallicreagentsis apparcrly volume). CH,
il-
C
o t-
v\
CuH,
C"H.cH=cHCHo
Z>A
[
-#-')Ntcu,t,Cu(CN)ZnI o
N(CHr)3CHCH:CHCcE OH
Organozinchalides,RZnI, undergotransmetallationto RCU(CN)ZnIon reaction with CuCN'2LiCl, preparedby reactionof CuCN with anhydrousLiCl in THF. The
a,
Cu
rcHzi ---
Organocopper/zinc reagents
239
resulting dimetallic reagentsare comparableto organocopperreagentsin reactions with electrophilesand in addition to unsaturatedsubstrates.r This transmetallationhas been used to obtain novel a-acetoxyalkylcopper/zinc reagentssuchas I from a-bromoalkyl acetates,obtainedby addition of acetyl bromide to aldehydes.2
boa ktters, 31,7253 (1990). Sofield, A. C. Spivey,and J. B. r S<,c..lll, 4864(1989). (19E9). Comm.,967 J. Org., 56, 1349 d P Fernandez,
(I) RcHo + CH,CoBr +-
?A' RCncu(cN)zns. I (R = t-Pr)
OAc I
R,,\J /
. . s { . 5 8 3 1( 1 9 8 9 ) . rronh. R. A. J. Smith,and J. R..
9ot t\z^ nCne. ""#-
H
H
\
Hc=ccooc,H. c.H.cocr *# l#Rr'fc"H'
?ot
^,, tl
o
COOC2H5
'-J,d
(>96VoE)
l
l*tters,3l, 4539 ,cr. Tetrahedron
o
(l990). A J Smith, Am. Soc., ll2, 440t-
OAc rahedron ktters, 27, 6201(19861. 19lr 3 Sr'n. submitted(1989).
)tZ-*
t
\.r-
xr are readily formed bY reacds rnsertion reaction is compati, leto. nitrile, acetoxy, amino, rcli\ity of organocopper collF ocopper compounds containin3 rd by reaction of Grignard or
lrcHznr >I
cH.' ll
cuHr-c-cu
--( ,^{
Allylcopper/zinc reagentscan be prepareddirectly by reaction of vinyl copper reagentswith (iodomethyl)zinciodide, the Simmons-Smithreagent.Theseallylcopperlzinc reagentsdo not couple with an alkyl iodide or benzyl bromide, but react readilywith electrophilessuchas aldehydes,ketones,or imines.3This approachto organodimetallicreagentsis apparently limited (see Iodomethylzinc iodide, this volume).
cH,' ll
o
l
N(CHr)3CHCH:CHCJ! I I
o
OH
e3%Jc6H'cHo
cH" oH bn to RCU(CN)ZnIon reactic $ anhydrousLiCl in THF. TtG
"ut,U"ut,
I I
240
Organocopper/zinc reagents
A similar insertionof zinc with aryl iodidesrequiresN,N-dimethylformamideor -acetamideas solvent.Thesearylzinc iodidesreact with CuCN'2LiCl to form mixed zinc and copperorganometallics,ArCu(CN)ZnI, which react with a variety of electrophilesto give functionalizedaromatics.4
Organocopper/zir canbe prepared,and r
(II) l(cl
l) Zn, DMF,45" 2) CUCN.2LiCl +
Cu(CN)Znl
"'"I o.n,*", l''')"-''
Reaction with gd phenylsulfonyl groupr organocopper/zinc rc4
cooc2H5
ocH2ocH3
A
NC(CH2)rC
\,r^-y\cH,
NC(CH')rCu(CN)Z sulfur-stabilized derivatives.s a-chloroalkyl phenyl sulfidesundergo a very rapid reactionwith zinc to form the correspondingorganozincchloride, which reactr of reagentsuchas 1. Reagents with CuCN.2LiClto form an o-phenylthiocopper/zinc prepared rl 1, Thus this type show enhancedreactivity with various electrophiles. generally in shownin equation(I), undergoesthe usual reactionswith electrophiles high yield.
(D PTCHSC6H, # cl
CucN'2licl , PrcHSC6H5
prcHSC6H5
l ZnCl
l Cu(CN)ZnCl I
o
C.H.COCI + I A
Y . C . P . Y e h ,H . G . C T.-S.ChouandP. Km P. Knochel andS. A. I ' T. N. Majidandp. Kr S. A. Rao,C. E. Tuctc ' C. Rerherford p. and K
tl /r-'.SCut, .r_, I Pr
Organoiron resgents. AlkyltetracarbonyQ ztes with alkyl vinyl I r-etamide.Addition of
' C - H , , B r+ K r F e ( C O
o
o
A+,__+A 78cc
\-/ *t..",
Pr
V Yamashita,H. Tash
241
Organoiron r€agents
prres N,N-dimethylformamide c t 'r rrhCuCN.2LiClto form mird rhrch reactwith a varietyof elcc-
Organocopper/zincreagentssubstitutedby a phenylthio group at the y-position canbe prepared,and also show enhancedreactivity with electrophiles(equationII). l) Zn
(II) I(CHr)3SC.H,
j[flj!5
C6H,S(CH2)3Cu(CN)ZnI
X,H.
2 C6H5COCI * 2
ilI I
-CurCN)ZnI ocH:ocHr
't t
d
C6H5S(CH2)3COC6H5
Reaction with p-allqlthio nitro olefins.6 Nitro alkenes bearing an alkylthio or phenylsulfonyl group at the p-position undergo addition-elimination reactions with organocopper/zinc reagents to provide functionalized (E)-nitro alkenes.
tr r')t-'
fo'
,.;. r
I\
OCH.OCH. v
-.\
r_ C H ,
\-/
phenyl sulfidesundergoa very oreanozinc chloride,which reactr inc reagentsuchas l. Reagents of bcrrophiles.Thus 1, preparedar D\ \ rth electrophilesin generally
r':: (:>
r\-SC,Hs NC(CHr),Cu(CN)Znl+l |
fo, -=-l /,/V(CH,)3CN I 85qo \-/
NC(cH,),Cu(cN)ZnI + (cH,S),c:C"*o, J$**I!i [Nc(CH2)3],c:cHNo2 I M. C. P. Yeh, H. G. Chen,and P. Knochel,Org. Syn.,submitted(1990). ' T.-S. Chouand P. Knochel,J. Org.,55, 5791(1990). I P. Knocheland S. A. Rao,z{m.Soc.,112,6146(1990). a T. N. Majid and P. Knochel,Tetrahedron Lctters,3l, 4413 (1990). 5 S. A. Rao,C. E. Tucker,andP. Knochel,ibid.,31,7575 (1990). 6 C. Retherford andP. Knochel,ibid., 32,441 (1991).
PCHSC6H5
I Cu(CN)ZnCl I
o
Organoiron reagents. Alkyltetracarbonylfenates, K+ [RCOFe(CO)3]-.t The reaction of these ferrates with alkyl vinyl ketones provides 1,4-diketones when carried out in dimethylacetamide. Addition of 18-crown-6 improves yields.
^._-y.SC6H5 Pr
rr-CoH,.Br + KrFe(CO),--)
ff
9ff5 K*[n-C6H,rCOFe(CO),f
o il
o tl
n-CuH,.CCH,CH2CCHl 1/SCuHt h
I M. Yamashita,H. Tashika,and R. Suemitsu,Chem.Letters,69l (1989).
2A
Orgsnolithiumcompounds
Organolead reagents. o,-Alkoxy organolead compounds; lr2-diols.r a-Methoxy organoleadcompounds(1) canbe preparedby transmetallationof c-methoxyorganotinreagentswii BuLi followed by trapping with Bu3PbBr.They react with aldehydesin the presenot of Lewis acids to form 1,2 diols, with the stereochemistrycontrolled by the Lewb acid; useof TiCla resultsin syn-diols,whereas4nti-diols are favoredby BF3etheratc. OCH3 (r\ t^'
CrH,.-
-\ - S n B u ,
l) BuLi 9CH, 2) Bu'PbBr > -l-- - P b B - u, Tqa CrH'rI
I + crH,rcHo
+ TiCln + BFr.016rgr;,
-78JoP >
QCH'
9CH, crH,,
* \crH,, OH
"rr,,
\"r",, OH
Organomanganesehalides. iodides ere r RMnBr.r Organomanganese expeosir the from prepared sive sincethey are s i MnBr: because prepare havebeendifficult to soluHc is which LiBr, and by use of MnBr2 MnBr3Liis formed. This ate complexreactsrcr MgXBr, LiBr). By addition of commercid L ddition of MnBr2, RMnBr can be obtaincd rr rlkyl, alkenyl, alkynyl, or aryl' The RMnBr RMnI, but lessexpensiveand they do nu libc lr4-Adtlition to enones.2 In the prescre ndesaddto c,p-enonesin THF at 0o to givc I Tte nature of the alkyl group has slight cft reagentsare superior to R2CuLi reageDts'sr
o tl
99:l 39:61
84Vo 959o
a'\ I
The reaction has been carried out on an optically active c-methoxy organolead reagentand shownto proceedwith retention (equationII).
ocH,
OCH.
t"'
a",lrbBu,
+ cuH5cHo #
f CH'A-:"CuHt , l
l l +BuMnCl
E
+ CuCl(5ctr 9Y CH,. ""';6Hg9cH,
+ BuMncl i
CH,,
OH
(947o ee)
(94.5Voee)
I J. Yamada,H. Abe, and Y. Yamamoto,Am' Soc.,ll2,6l l8 (1990)'
Organolithium compounds. Rcaction with epory silanes.r A variety of organolithiumscontaining aryl' to alkenyl,alkynyl, amido, and cyanogroupsreactwith (E)- and (Z)-epoxysilanes form adductsthat on treatmentwith base(KH) are convertedstereoselectivityinto (E)- and (Z)-alkenes,respectively.Organocopperreagentscan be preferableto the correspondingorganolithiumwhen the carbanionis an alkenyl or aryl group'
+ CuCl (l9c)
6
+ CuCl (l7o) + MnCl'(104)
t
chlorotrimethylsilane.Use of both CuCl rnd I rheyield of 1,4-adductsof RMnCI to coocj
+ BuMnCl (I) CH'CH:C(COOC2H5)2
l) LiC=CBu
R /--)/
/
Bu
/Si(CH3)r
2)KH
, BUCH:CHC-CBU
eSeo
(>951o E\
I Y.Zhang, J. A. Miller, andE. Negishi,J. Org.,54' 2043(1989)'
Conjugateaddition of RMnCI to dkylitl goodyields (80-87%, equationI), which en useof RLi or RMgCI' A new synthesisof t
organornangrnesehalides
o-Methoxy organoleadcomEl€rhoxyorganotinreagentswith r 'r irh aldehydesin the Presenoe GmrstrycontrolledbY the Lewis bolsarefavoredbYBF3etherate.
9CH, ,.
I
*
crH,,
y'YcrHtt : OH
Organomanganesehalides. iodides are very useful for acylation, but expenRMnBr.r Organomanganese bromides sive sincethey are preparedfrom the expensiveMnI2' Organomanganese havebeendifficult to preparebecauseMnBr2is insolublein ether,but canbe obtained by use of MnBr2 and LiBr, which is soluble in ether at 20", probably because MnBr3Li is formed. This ate complexreactsreadily with RMgX to form RMnBr (* MgXBr, LiBr). By additionof commercialLiBr to RMgX in ether followed by additionof MnBrz, RMnBr can be obtainedin 80-98% yield. The R group can be alkyl, alkenyl, alkynyl, or aryl. The RMnBr reagentsare similar in reactivityto RMnI, but lessexpensiveand they do not liberate12,which can be a problem. chlo|,4-Atldition to enones.2In the presenceof CuCl (5%), alkylmanganese (88-98Vo). ridesaddto o,o-enonesin THF at 0o to give high yieldsof 1,4-adducts The natureof the alkyl group has slight effect on the yield. In general' RMnCI reagentsare superior to R2CuLi reagents,even when the latter afe activatedby
iq:61
.,\ l t \-/
11 activeo-methoxyorganolead t i o nI l ) . OCH. I t .a-y'CuHt ,., I OH ee) t94.5vo
o
o
a9:I
> l+ BuMnClrHF'o" Bu* + CuCl (57o) 95Vo
'!gH69gH, /
QH,
CH,.
+ BuMncl
organolithiumscontainingarYl, b rrrh (E)- and (Z)-ePoxYsilanes im stereoselectivity c c..rnverted reasentscan be preferableto tb is an alkenylor arYl grouP.
THF 0'> no rHF
CH,'
I
Bu-C-cHpocH,
1". + CuCl (l7o)
+ CuCl (17o) + MnClr(||/o)
l. 6ll8 (1990).
A
o'toqa
6'74o 88Vo
Useof both CuCl andMnCl2ascatalystscanfurtherincrease chlorotrimethylsilane. of RMnCI to enones. theyield of 1,4-adducts
(t) CH.CH:c(Cooc2H5)2 + BuMnCl #Bu /cHcH(coocrH,), CH,
Itl:CHC-CBu > e 5 7 cE )
l c l r - r( t 9 8 9 ) .
Conjugateaddition of RMnCI to alkylidenemalonicestersproceedsin generally goodyields (80-87Vo, equationI) , which are generallyhigher thanthoseobtainedby useof RLi or RMgCl. A new synthesisof citronellol(l) is basedon this reaction'3
OrgrnomolYbdenum reagents
9H, (tt
\
S-
c1ctt,;,
]
Ar"*n'
cH'cH:c(cc'oci'rr )
[f*"
l \ l -
\
L c(cH3)rj
cooc2n5
c1cH,)z
,rc * * ll i'fil?"so/,r?o, f
p-CH.OC.H.I + CHz:CHOCH'
CH" I
.l \
OrganoPalladium reagents' I |,z-Addition to CH2:CHY (Y + C)' rceg Heck-typecoupling of organopalladium bod carborylates,and related C-C doublc srdl Both palladium' lowedLy elimination of triphenylpboq rheregiochemistry.In general, ICU:CN) favor c-arylation' Also' the X 3rn
-oH
C(CHr)z
: O.NC.H.COCI+ CHr:6gOBu
+
P0: rF.
I
gercrd t \ryl triflates favor a-arylation' In 'iat of enol ethers.
3545 (1989)' IG. CahiezandB' Laboue'Tetahedron Letters'30'
(le8e)' ,;. ili;; ria rr'r.n..i, ibid',t0'3541
G. D. Daves,Jr. andA' Hallberg'Chcn Rtt'
t ltlem, Tetahedron, 45, 4163 (1989)'
"'-4"#ii;[?il#1iJii,
productbT asasingre isobtained 1 . 1]:::T{"I of LiCl' Tli "nn t'tO*gpnl.tollowedby addition
reactionof CpMo(COlrtiitttU ;;-i;;; complexreactswith .i;&i; I)' (equation diasiereoselectivity
(t) l+c.HscHo-+
regio-rd homoallylicalcoholswith high
f'"' ",aZ-Y^o" CH,
9uHt *
u.y''-'1/\ou r r ) -v
Organotitanium reagents' Ti-carbohydrate complexcs' ThGCiL :omplex (l) from the reactionof cyclopco rod 2 equiv. of commercially availeblc t :uranose(diacetoneglucose)and showoto t | *ith allylmagnesiumbromideprovidcs r. sive homoallylic alcohols3 with t5-91
lI
96:4
CH,
Cp(OR*)JiCl the samereactic analog(S-2) of (1) undergoes The neomenthylcyclopentadienyl (3) in >98% ee (equationtr)' to sive (+)-(R,R)-2-ttth;i;il;"vl-3-bitene-l-ol 9.Ht 0D (S)-2+2C6H5CHO'
urCy'{ou CH. R'R-3 (>987oee'924ode)
I
cH':cHcx'uect f
fn I R*o-Ti-oR*
I
CH,CH:CH. t
(1989)' TetrahedronLetters'30' 1?69 I J. W. Faller, J' A' John' and M' R' Mazzieri'
R*OH =
Orgenotitrnium reagents
f", ,'uY"ooc2H5 \
cooc2H5
il c(cH3)2 DMso/H,o, l8f -.*- - 1| 2,rLicr, )LiArH.
245
Organopalladium reagents. 1,2-Addition to CH2:CHY (Y * C). Davesand Hallberg have reviewedthe Heck-typecoupling of organopalladiumreagentsto vinylsilanes, enol ethers, enol carboxylates,and relatedC-C double bonds, which proceedby 1,2-additionfollowed by elimination of palladium. Both steric and electronicfactorscan determine the regiochemistry.In general,triphenylphosphineligandsand coordinatingsolvents (CH3CN)favor c-arylation.Also, the X group of ArPdX affectsthe regiocontrol. CH"
CH.
p-CH.OC.HTI+ CH2:CHOCH,
I
a'\
l
\
jll\
p-CU,OC.H.JOCH. (o-arylation)
l \OH
c(cH3)'
+ CHr:fHOBu n-OrNCuHnCOCl
I I rleE9).
fi",
------+p-OTNC.H.CH:CHOBu + p-OrNCuHoCOBu (p-arylation) (a-arylation) l0: l
Aryl triflates favor o-arylation. In generalvinylsilanesshow oppositeselectivity to that of enol ethers. lG. D. Daves, Jr. andA. Hallberg, Chem. Rev.,t9, 1433(1989).
obtainedas a singleproductby yred by additionof LiCl. Thir r alcoholswith high regio- and
.
9'"' ' cZ\a
)-
I
oH
Organotitanium reagents. Ti-carbohydratecomplexes. The Ciba-Geigygroup has prepareda crystalline complex(l) from the reactionof cyclopentadienyltitanium(IV) trichloride,CpTiCl3, and 2 equiv. of commerciallyavailable 1,2;5,6-di-O-isopropylidene-c-o-glucofuranose(diacetoneglucose)and shownto correspondto cp(oR*)2Ticl. Reactionof I with allylmagnesiumbromideprovidesthe complex2, which reactswith aldehydes to give homoallylicalcohols3 with 85-91% ee.'
cH.'
cH, I t undergoesthe samereactiol 3t n >98Voee (equationII).
!""' fo" CH. 3'i cc.92Vode)
Cp(OR*)rTiCl R*OH = I
lcH?-cHCH,Mscl Y
!n I
R*O-Ti-OR*
I
CH,CH:CH, oa ktters.30. 1769(1989).
t
.0---
X l - o . cH.'to-(
\
\?" /\ o o-fcH, CH.
246
Organozincreagents
providesa Reactionof the complex I with the lithium enolateof t-butyl acetate ee.2 p-hydroxy (5) in90-96% esters complex4, which reactswith aldehydesto form
o
l) Btznclttr=Ctr
ll
ll 2) BU.NF c6H5csi(cH3)t-
OH
+ ,+# RCHo
R/*cH, 3,85-94Vo ee
corresponding The main disadvantageof thesecarbohydratecomplexesis that the complexesfrom r-glucose are not readily available'
il-
oSi(cH,\ i
OH
CH"
CpT(OR*)'OCOC(CH3)3
2-CarboalkorY c! cloPcnl c ro.et.t (13, 349-350),can undergoa formel I ClSi(CHJ of CuBr.S(CH3)2, presence iavol probably tenones.The reaction cyclizulr followed by intramolecular
ocJt
RcHo
) .r,^V,COOC(CH3)I s1-8t% N 5. N-96Vo ee
4
cooc"H. '' CrE.s.Ct|.L | ,1,
Clicllrr
'l' Ro
r-crH,,
Organozinc -f_Keto reagents. the 0-iodo amiio acidsJ The organozincreagent(2), preparedfrom in the chlorides acid with couples Znlcu, with sonication by alaninederivative I presenceofPd(II)catalyststogiveenantiomericallypureprotectedr-.1-ketoo-amino acids(3).
, F^^-,t""* ,,n-..,NHB*ffii,3"fij cooBzl 1
L
I
cooBzlJ
li:b-!t''l;il"'t , ,s-wk
2 R-a,'---r,NHBoc i l : COOBzI O
Nuclcophilic disPbcescnt of t ethersundergonucleophilicsubair larly with thoseformed by rcacriooo alkyllithium.
3 of aldehydeswith Propargylation of acylsilanas'2 Attempted propargylation However' if propurgyti" brignard o, iin"reagents resultsin both o- and 1-adducts' be obtained can alcohols acylsilanesare usedas the electrophiles,homopropargylic inhighyieldafterdesilylation.HigherStereocontrolispossiblebyuseofthetriisopropylsilylgrouP.
**'o
"n,0*
(cisltrans= 57:'33)
Organozinc reegents
of r-butylacetateprovidesa Dr) esters(5)in90-96% ee.2
*a", J{
ee
cres is thatthe corresponding
o
o
247
H
tl "rZnCH,C=C(CH').CH, ll % C6H5CHCHTC-C(CH2)4CH3 C6H5iS(CH3), (u'/l = 93:7) 2-Carboalkorycyclopentenones.3The zinc homoenolate1, preparedas shown (13, 349-350),can undergoa formal [3 *2]cycloadditionto acetylenicestersin the presence of CuBr.S(CHr)2,ClSi(CHr)3,and HMPA to give 2-carboalkoxycyclopentenones.The reaction probably involves conjugateaddition to give an allenolate followed by intramolecularcyclization.
osi(cHr)3 4 oc2H5
I \,/cooc(cH3)3
(c,H.occH,cH,),zn I
q6(-; ee 0-
I
l. {9.1(1989);R. O. Duthaler,P. , 2t. 195 (1989). )t9 r. M. Riediker,A. Hafner,U.
(cH3)3siooc,H5 y I
-#4 *oI.,",, 1"""*^\-"'"'l cooc,H. ' " c u B r . s ( c H , ) , . H M PlA |
I
A
I
50-70%l
l). preparedfrom the P-iodo rs * ith acid chloridesin the r protectedL-I-ketoc-amino
o ).__r,cooc,u,
( t l
\-\zc,H,, l': nr
6*
o(.H.),L
!D ----------..--)
R-.ra"r:t
'NHBa
i l : O COOBzI
Nucleophilic displacementof anomeric sulfones.a 2-Benzenesulfonylcyclic ethersundergonucleophilicsubstitutionwith various organozincreagents,particularly with thoseformed by reactionof ZnBr2with Grignard reagents,ratherthan an alkyllithium.
3
\
|
\o,)-sorcuH, with ugllation of aldehydes - andy-adducts.However,if ylrc alcoholscan be obtained possibleby useof the triiso-
cuur^o^sorcuHr (cisltrans= 57:43\
lli,lt;Y'ii.
-itl
18%
"o
\
\o,y'-cuH,
c.ttr^oy'
"cuH,
Orgsnoytterbium reegents t"'t""t*", ,,
-\o'l-
+HC:ccoH,+--aI -o\a"*
Osmium tetroxide. (lt Catalytic asymmetric dihldrcrylab detailsare now availablefor this rcrtioo ri acetone/water(3 : l, v/v) with dihydroquhili
so2c6H5
zincate carbenoids.s Reaction of lithium trialkylzincates with a l,l-dibre' moalkaneresults in a double insertion into the C-Br bondsto provide a secondary zincatecarbenoid.2Theseproductsundergo Pd-catalyzedcoupling with acid chle ridesor vinyl bromides. Bu
Bu
_lJtot_. I c"1,|ff\, Bu/nlir r RiItcocuH, nCHzntRCHBT, ,rr^ | zncl' Pd(u) '''"J(cH,),c:cHBr
QH^V\G.&
I?
A new asymmetricsynthesisof enthrecy (5) is basedon dihydrory oxydaunomycinone thediamine(-)-2, which providesthc dit ! into (*)-5 by four known reactions.
-u'^'\
r-I{
|
Bu
."\\r/
r
\ 'N(ffi'$'
\/'
CoH,
I
CHCH:C(CHIL I R. F. W. Jackson,K. James,M' J. Wythes,andA' Wood,J 'C'S' Chem'Comm'' 644 (1989)' 2 A. Yanagisawa, S. Habaue,and H. Yamamoto,J' Org" 54' 5198(1989)' 3 M. T. Ciimmins and P. G. Nantermet,ibid., 55,4235 (1990)' (|989\. { D. S. Brown, M. Bruno, R. J. Davenport,and S. V. Ley, Tetrahedron,^4^5'4293 Lctters,32' 1573(1991). 5 T. Harada,Y. Kotani, T. Katsuhira,and A. Oku, Tetrahedron
Organoytterbiumreagents. Artditionto carbonyls.Reactionof an alkyllithiumor a Grignardreagentwith Yb(OTf)3,providesa speciesof organo tris(trifluoromethanesulfonate)ytterbium,
o ,\,"",
t
\.,/
l
THF,-?8"
+ CH"LilYb(OTf)' ----------+ et%
HO. .pH3 -\zcH, I |
\,./
I |
+ 98:2
ytterbium reagentsthat adds to aldehydesor ketoneswith high stereoselectivity' to provide almoa itrus the methylytterbiumreagentaddsto 2-methylcyclohexanone carbonyl group' on the entirely the axiai alcohol from preferentialequatorialattack rG. A. Molander, andP. Weinig,J' Org',55' 4990(1990)' E. R. Burkhardt,
(+)-5 Stereoselectiveosmylation. Ochiri a I rclectiveosmylationresultingfrom thc cnft
Osmium tetroxlde
Osmium tetroxide. Catalytic asymmetricdihydrorylation (14, 237-239; lS, 240-241)' Complete details are now availablefor this reaction with a solid substrate,trcns-stilbene,in as catalyst.r-a (3: l, v/v) with dihydroquinidine4-chlorobenzoate acetone/water
C#' llllzincates with a l,I-dibro' : bondsto Provide a secondarY couPlingwith acid chlc l;^.zed
Bu ) RCHCOC6H5
OH
c.H,1Ac.n,
c.H,'-/\ cu",#
OH (R,R = 907o ee)
A new asymmetricsynthesisof anthracyclineantibiotics such as (*)-4-demeth(5) is basedon dihydroxylationof I with OsOain the presenceof oxydaunomycinone the diamine(-)-2, which providesthe diol 3 in 82Voee.5The productis converted into (*)-5 by four known reactions.
"utr\--\
/--?"u''
...u*,"r,r*J... coH,
coHr'
);
c)-2
i. J C S. Chem.Conm.,644(19t9)' . s.. 5l9E (1989). I I 990). * . Terrahedron, 45, 4293(1989)' irc,lronlztters,32, l5?3 (1991)'
cocH3 '
OsO..2, THF . %
ocH3 3 (82Voee)
hium or a Grignard reagentwitl t. providesa sPeciesof orgaF
cH, \-,.cH,
//
r"o '"'" | ,a,",,,,t"'
JcFrcooH
cH3. ..oH
CHOHCH.
f\cHr
<-
"oH
3 stcps
V nf,',
Doeswith high stereoselectivity' to Providealmc lclclohexanone iel attackon the carbonyl groq' O , e. 5 5 , 4 9 9 0( 1 9 9 0 ) .
(+)-5
4
Stercosclectiveosmylttion. Ochiai er al.6 have reportedan exampleof highly sclectiveosmylationresultingfrom the conformationalpreferencesofcjs-1,3 substi-
osmium tetroxid€
o1 t
)
r-:-//-d
*o, es%
r/zl----___J Sn(CHr)3
,o.-:><
o-. -,O HO...-x.T
I
l
l
+
HO"'^$Sn(CH3)3
t
l
oH
l-
(t) c.H,\c6H5
o
ccl'> socL'
n
1."",#
L
Sn(cHr\
49;51 Ho/\\/
p-2
a-2 | , .".to. "., 8e%Jzr rin.cr
l)osq zlcH'M8Brr d-2 1t%
+
B-2
94:6
tuents.Thusthe cyclohexeneI undergoesosmylationto provide a mixture of two vicglycols (2) in approximatelyequal amounts'However, if one methyl group on Sn ir replacedby chlorine by oxidation with iodosylbenzeneand quenchingwith NHaCl, the product(3) on osmylationfollowed by methylationgives the a-vic-glycol almoa exclusively. The cyclohexeneI undoubtedly has the diequatorial conformation, complexwith oxygenresultwhereasin 3 the tin group can form a pentacoordinated ing in a |,3-diaxial conformation. The conformationaldifferenceresults in strong steric hindranceby the tin grouP. -SnX(CH3)2 into an The paper also reports a new method for conversionof hydroxyl group with the same configuration by oxidation with alkaline hydrogen peroxidein THF/CHrOH. OBzl
OBzl
I
^ \.,\
H,O,, KHCO. --::--------€
silanesbearing an oxygen frrnctionu Cr t droxyl is more effectivethan an qtter (r c silyl group also favors czti-sclectiviry. I effectsobtain with Cl-oxygenatcdcruybi isomers, CHt
(r) (cH3)3siY,,\"",.ry I OR R=H =Ac
65C 51*
75-80%
Sn(CH3)2
x Chiral amino alcoholsand diamines.T The chiral vic-diols availableby caOlytic asymmetricdihydroxylation of alkenes(14,237-239) can be convertedvia r derivedcyclic sulfite into chiral 1,2-aminoalcoholsand diaminesas shownin equrtion L The sametransformationsare useful in conversionof l-alkyl- or arylethane' 1,2-diols into the correspondingamino alcoholsand diamines. Dihydroxylation of allylic silancs.t Osmylation [OsOn,(CHr)rNO]of allylic
dihydroxylation of m OsO4-catalyzed reoselectivity,but dihydroxylation of r I essentiallyonly one product(2), end e rco isomer(3).e Selectiveosmylation of trieset.t' 1 preparedfrom the butadiene+ricarbooy give a single racemic, cis-diol 3 in 96t y imidazoleprovides the single carboolc {
Osmium tetroxide
*x f-]
OH
t
S
(I) CUH'}CE
OH
251
soc"' ccrl -#> [",t,.s"'t]
,,,,.,nl'Hogsn(cH')'
oH
p-2
Yi^
?"
# q",Ar-a"' ..",1/t''' : . NHt
N3
(>96Vo ee)
(>-96Voee)
I rl v'cr J2)
LiN,,DMF l2o'
H,, Y', # cuu('"1cuH'
N, a."-t'"'
NH,
N,
(2.96Voee)
a mixtureof twoYtcnto Drovide on Snis ;;. i; ;"" methYlgrouP withNHrcl' ;;; ;J quenching almo$ u-vic-glYcol ln oiuesihe 'ln.' conformation' ino*,orial result' with oxYgen ."t"On."0 stronS in ionrr Oiflt"nce results -SnX(CH3)2into rr rrersionof hYdrogcr ;.';;;;" with alkaline
A free hysilanesbearing an oxygen function at c1 show anti-diastereoselectivity' sizeofthe in.the increase An group' ether droxyl is more efiectivethanan esteror silylgroupalsofavorsanti.se|ectivity,buttoalessextent(equationl).Similar particularlyin the caseof the (E)effectsobtainwith Cl.oxygenatedcrotylsilanes, isomers.
f", 0) (cH,),sifcs,
OH I , C H ,oso..(cH,),No, (CH3)jSi\y/,'\ + syn-isomer
l
OR
OR
antt
OBzI I r
l
OH
R=H =Ac
65Vo 5'lVo
>97:3 6 . 5 :I
l
V\oH
a chiral vic-diols
availablebY c*
vir r canbeconverted i .ii-zlsl --^ ^L^t!'n in aan 'r
as shownin cqr' ,ofr-unOdiamines t l-alkYl- or arylethc l";**"
oror gN i8lfl1icH,) l ".1l"l'
osoa-catalyzeddihydroxylationofmonoallylicsilylethersshowsslightdiastesilyl ether such as I provides reoselectivity,but dihydroiylation of a bis-allylic (Z;, ana a seconddihydroxylationalsoprovidesa single csentially only oneProduct rsomer(3).e (tricarbonyl)iron-complexedtriene 2' Selectiveosmylationof tricncs'ro The (ll, 222), undergoesosmylationto grrpur.o from the butadiene+ricarbonyliron| g r v e a s i n g l e r a c e m i c , c i s - d i o l 3 i n 9 6 % y i e l d ' R e a c t i o n o f 3 w i t h N ' Nfrom ' - c a robonyldicarbonates,prepared midazole provides the single carbonate4.lrRelated
Osmium tetroxide
TBSO
osq
crH5ooc
#t
crHrooc*cooc2Hs
coocJt OTBSOH 2 (>99:
OTBS
lo'q' *o
J
c2H5OOC
3 (55'65)-5' respectively' riboseandxylose,havebeenusedto prepare(5S,6R)-5and 5'6-DiHETE' as known which are metabolitesof arachidonicacid
/-l
R,SiOH,CJ.....'{L-CHO Fe(CO).
l) OsO.,PY 2) NaS,O.
Jl--^
R,Sid
%
Fe(CO)3) (cHr)3coocH3
l, R = (CuHr);r_Bu
Similar stereoselectivityappliesto osmyhi be resolved,r2an asymmetricsynthcsisof 3
'8. H. McKee,D. G. Gilheany, aodK. B. L ' M. Minato,K. Yamamoto, ad J. Tsuji,/. q 3 H.-L. Kwong,C. Sorato,Y. Ogim, H. CLcr"r 2999(1990). ' B. M. Kim andK. B. Sharplcss, iDdd..31. il 5 K. Tomioka,M. Nakajima, andK. Kogr..l.C 6 M. Ochiai,S. Iwaki,T. Ukits, Y. Mlrre I (1988). ? B. B. lohrayandJ. R. Ahuja,J.C.S.Cf.r ( t J. S. PanekandP. F. Cirillo,,{n. Soc-.lU. t e S. Saito,Y. Morikawa, andT. Morir&,.f. ( '0A. Gigou,J.-P.Lellouche, J.-P.Bcest I E d . , 2 t , 7 5 5( 1 9 8 9 ) . rrJ. Adams,B. T. Fitzsimmons, Y. Ginrd. Y. I 107,464(1985). 12P. Mangeney, A. Alexakis,andJ. F. llqr
(hezaborolidlnes, 14, l l0-l l l, 156, 239Tl o,,a-Diaryl4-pynolincnclhaob.' erateyield by reactionof an arylmeguin of (R)- or (S)-proline.A newerandffii dcg proline into the N-carboxyanhydri&, rhitt obtain (R)-1. Conversionof I to tbc corrE? reactionof I with trimethvlbororir io rrl
n -il'"'"-" *l l-Q* ,
3 zs*Jrm,co.c"n"
(R)
L CGI
'10 o
(cHr)3cooH (cHr)4cH3 oH 5
4
o
.Theconfigurationof4hasbeenestablishedbyX-raycrystallography,andshort to the organometallicgroq" to correspondto cnri-additionto the free bond vicinal
0xozaborolidines
Similar stereoselectivity applies to osmylation of the trans-isomer of 2. Since 2 can be resolved,12 an asymmetric synthesis of 5 should be possible'
TBSO
OTBSOH 2Q9:
*"o fo"o, OH
QTBS
OH
c.H.OOC OH
OTBS OH 3
( 5S.6R)-5and(55,65)-5,respectively' pr^n as 5,6-DiHETE' l) OsO.,PY 2) Ns'S'Or -
L.
253
e6%
\__ \\ FerCO)3\
/ (cH,LCOOCH3
l
(cHr) 3
,r*f,.ro.".""
rB. H. McKee, D. G. Gilheany,andK. B. Sharpless,Org. Syn.,submitted(1990)' 2 M. Minato, K. Yamamoto,and J. Tsuji, J. Org.,55' 766 (1990). 3 H.-L. Kwong,C. Sorato,Y. Ogino,H. Chen,andK. B. Sharpless, lztters,tl, Tetrahedron 2999 (1990). a B. M. Kim and K. B. Sharpless'ibid', 31,3003 (1990). 5 K. Tomioka,M. Nakajima,and K. Koga,J.C.S. Chem.Comm',1921(1989)' 6 M. Ochiai,S. Iwaki, T. Ukita, Y. Matsuura,M. Shiro,andY. Nagao,Am. Soc.,ll0' 4606 (1988). ? B. B. lohray andJ. R. Ahuja, J.C.S. Chem.Comm.,95 (1991). s J. S. Panekand P. F. Cirillo, ,{nr. Soc.,112,4873 (1990). e S. Saito,Y. Morikawa,and T. Moriwake,J. Org.' 55' 5424(1990). lo A. Gigou, J.-P. Lellouche, J.-P' Beaucourt,L. Toupet, and R. Gree, Angew' Chem' Int' E d . , 2 8 , 7 5 5( 1 9 8 9 ) . rrJ. Adams.B. T. Fitzsimmons,Y. Girard, Y. lcblanc, J. F' Evans,J. Rokach,Am. Soc',
r07,464(1985).
'2 P. Mangeney,A. Alexakis, and J. F. Normant, Tetrahedronletters,29,2671 (1988).
Oxazaborolidines, 14, I l0-l I l, 156, 239-242. aro,-Ddaryl-2-pynolinemcthanors.rTheseproductsare obtainedin only moderateyield by reactionof an arylmagnesiumchlorideswith the methyl or ethyl ester of(R)- or (S)-proline.A newerandmore dependableroute involvesconversionofthe proline into the N-carboxyanhydride,which is then addedto the Grignardreagentto obtain (R)-1. Conversionof I to the correspondingoxazaborolidine2 is effectedby reactionof I with trimethylboroxinein refluxing toluene.
NH
'..cooH coct>R ""."-l-o-L cocl
(R)
l o N-v/ o
J
| ,, ""","r",
73% | 2) H,Sq 3) oH|
f"'
(cHr)3COOCq 4
a-,::q"' o-B-e t l
-*-"r\",
and lrd bY X-raY crystallograPhY' bonOvlcinal to the organometallic
(R)-2
cn;BtotB-a", c#rcH!, A +62-6%
f-\
9u"'
\N,/...c-cuH5 H 6 t (R)- l, 997oce
234
Oxezaborolidines
o! kctones Enantioselectivccolecholborancreduction
\
The oxaza-
C:o''
catalyst for catecholboranereduction of borolidine 1 can also function as a chiral ketones,whichisusefulforsubstratessensitivetoBH3andwhichcanproceedat t e m p e r a t u r e s a s l o w a s - T S " . I t i s p r e p a r e d b y r e a c t i o n o f ( s ) - ( - )ketones - ( d i p hwith enylhyacid. Reductionof aromatic droxymethyl)pyrrolidinewitrr uutytuoronic in90-94% -78' to provide (R)-alcohols catalyzedivi pto*"or at catecholborane reduction of c'p-enones to (R)-allylic for ee. This protocol i, pu'ti"ott'iy useful alcoholsin 8l-93% ee'
Oxrzolidlnones, chiral. Chiral primary amincs.t Alkylrti
o
s fuHr-, (r-i-{cuH' t o \-N-rz
3 T. K. Iones,J. J. Mohan,L. C. Xavicr, T. J. t Jones,R. A. Reamer,F. E. Robcrts, lod E- ,- ,
ll
-rs" rl sur-i.
cll.
C.H,^\ P-[+;lr* a"trlri \_J j
.gu
(cH3)rHC I
(s)-1
(cH,u{ 1(5t
Reductiono!ketones.Merckchemists3haveusedoxazaborolidine-catalyzcd (4)' e of chirality in a synthesisof MK-927 reductionof a ketone no' int'oOottion carbonicanhydraseinhibitor.Theyfoundthateventracesofwaterdecreasestb enantioselectivityinreductionsof2'Highestenantioselectivity(98:2)isobtainedbg n 9"H'
1-il;*"' \-*-",.
NHCHTCH(CH3L l) NaCrH;TsCl 2)t-BuNH, '13%
cH, BH,.s(cH,).'0"
S' o2
S' o2 ( R ) - 3( 9 8 : 2 )
/^\---\ i l
t
\
t i l \stS.
\
/
o2 4, (>951o e'e)
with 4-A molecularsievesand use of u careful drying of solutionsof 2 in THF boranecomplexedwithdimethylsulfideattemperaturesbelow_l0o.Underthcwith reproductbl: t",t1t],:::t:.t"::t:1":: conditionsa variety ot tetones are reduced
thandialtf withhigherenantioselectivity largescale.Alkyl arylrr,oi", ur" reduced mail while 82:18' theratio Thuscyclohe*Vittiftyf kebneis reducedin ketones. -n ^ffr
Substitutionon the phenyl group of phenyl ketoneis reducedinif'" tt'io 99:1' oxazaborolidineexertslittleeffectontheenantioselectivity'ChangeoftheB-ma the enantioselectivity' group to a phenyl group generally lowers I L. C. Xavier and J. J. Mohan, Org' Syn'' submitted^(1990)' (1990)' t i. i c-.v.nA n. r. Bakshi,TeirahedronLetters'3r' 611
cJq (t)-t
c-Alhyl s,-amino acids.z A ncw roc ovolves alkylation of tricyclic oxazolidir nlicylaldehyde, r-phenylalanine,and @ cccdsmainly with retentionof configurlir rr rqueousdioxaneto an c-alkyl g-rrnirror1 ,rydcalpurity. Similar alkylation of 6c orl bcine proceedswith lower enantiocchcir a-Azitlo acids.a Full details erc qrr arhcr (R)- or (S)-c-azidocarboxylic ridr r
chhd Oxezolldlnones,
.rnn2s
\c:o.t
The oxaza-
or catecholboranereductionof BH. and which can Proceedat rtion of (S)-(- )-(diPhenYlhYoction of aromaticketoneswith ror ide (R)-alcoholsin 90-94% n of c,p-enonesto (R)-allylic
3 T. K. Iones,J. J. Mohan,L. C. Xavier, T. J. Blacklock,D. J. Mathre,P. Sohar,E. T. T. Iones,R. A. Reamer,F. E. Roberts,and E. J. J. Grabowski,J. Or9.,56,763 (1991).
Oxazolidinones,chlral. Chiral prinary amines.t Alkylation of the lithium anionof the N-benzyloxazoto provide lidinone I (derivedfrom valinol) proceedswith high 1,3-stereoselectivity 2 in75-96% de, which can be improved by crystallizationor chromatography.The productscan be degradedto (R)-primary amines(5) by hydrolysis (3) and oxidation to an imine (4), which is then hydrolyzed to an amine. Slight racemizationis observedin theselast steps.
o tl c^H.
NAo j
LJ
(cH3)rHC I
l) BuLi,-78o 2) CHrI,- l0O. -----=+ 75%
CH. 9 I
ll
c^H.ANAo j
KoH
+'oh
\J
(cH3)rHC 2, (96%de)
cH" cH(cH"), -| | c.HrANAzoH H 3
used oxazaborolidine-catalYzed (4)' r rn a synthesisof MK-927 tbc decreases D tracesof water bY obtained is (98:2) nelectivitY
,r* | *
NHCHTcH(CH3)' (
H TsCl l\H
)
/^r-\
I
\stS'
i l )
o2 4, (>95Vo ee)
2SS
*
CH"
t coHr Nu,fr
cH" I c.u.AN-*cH,
I CH,
(R)-5 (92Voe)
4 molecularsievesand use of d -l0o' Underthcr raturesbelow oo :producibleenantioselectivity e dialkyl than rher enantioselectivity i ,n the ratio 82: 18, while methYl [rurion on the PhenylgrouPoftb rlecrivitY.Changeof the B-meth! mtioselectivitY. r 1990). ll. 6ll (1990).
a-Alkyl a-amino acids.2 A new route to optically active a-alkyl c-amino acids involvesalkylation of tricyclic oxazolidinonessuch as 1, preparedby reaction of salicylaldehyde,r-phenylalanine,and phosgene.3Alkylation of the anion of I proccedsmainly with retentionof configurationto give 2, which is hydrolyzedby LiOH in aqueousdioxaneto an o-alkyl c-amino acid (3) in high overall yield and with high opticalpurity. Similar alkylation of the oxazolidinonesformed from r-alanineand r-lcucineproceedswith lower enantioselectivity. g-Azido acids.4 Full details are now available for asymmetric synthesisof either(R)- or (S)-c-azidocarboxylic acidsas precursorsto c-amino acids.Oneroute
(ff' : Asymmetric aklol reactiont' frr (1) derived oropionyloxazolidinone dirstctt fair with but u*. onri-rel"ttivity, enolilc Transmetallation of the lithium alddl with reacts which nium enolate, of h diastereomer the from chelation, of reversel The "nofur" (11, 379-380)' not posibl is which iitoniut'reaction, il practical value, since it can result 1
Oxezolidinones,chiral
CHO
,,,\.o" ll V
I
("F
+
t H"N
+coclz--:r+
cooH I
samechiral auxiliarY' I l) LiNtsi(cH!\ll
I
rsr' PtvtPu
CH(CH3)'
I,O
oY*Y-r",
R O crH'-\i< o=ril-
O
I)LDA 2) cm(o-i-Pr)) 3)Rcllo,ff p
I (
O I
(45)'PhenYl'2-oxazo/fdlitose't' BF1 reductionof r--phenylglycineand maintrird complex at a temperature treated with trichloromethyl cilomft
\./ z
emprovsenoratel'j1T::,:',1'f11lj'11ilil",":'::::#lll:iilf H,u\_/o ;F,:,iS,i i::^"i|ul["ilff (l4, 242)',the comPtem I of theazidegroup' trisylazide(|4'32'|).*"*""iofthechiral"o*iriu.yiunbeeffectedbysaponifica. befor"o' "ft"' reduction either tion (LiOH)o"'un'"""ttiJo*n' "ua.
.ruu
{""'Q
o
t-
r)NBs
?
,', v,r-.s)-nrAp +' "':Afi q
n l] Bzl-rA*A.o
\J Bzi
?
*,-..F Bzl = R/S 94:6
TJ Bzl'
rrisyrN, {""'g ? ? I ll Bzl\9'^-N KHMps ^ #-tst% ,LJ o I , nzr_rA*A.o L
P Bzl"
N,-.j
Bzl g/ft= 97:3
coH, b"
ls
' R. E. Gawley,K' Rein'andS' Ctcl E' del$t' lld s' I 'i. rtl. zvao,rskY, , H. Sto.i andP- t. Faulkncr'J' Atr ' P. e. Sn"nt,T. C. Britton''' A' Ell r M. Nerz-Stormes andE' R' Tbrg" . i. tt. ptiog"n, org' Syn',subniacd(
singlet' OxYgen, hYdrorY/rrios't Tl Lro^utt i with singletoxygen(Roscbcngrl) Fl witb 2, which on deoxYgenation fotr initial reaction is presumcd to 2' to which rearranges
OxySen, singlet
, c"H')-{
o
o=ril-Zo I l-H o:A
+
tr
l r l \./
1 I tt LiN[s(cu,),],, I rnE'oueu l2)Rx Y R c.H'.J-(
257
Asynmetric aldol reactionss111, 379-380). The lithium enolate of the Npropionyloxazolidinone(l) derivedfrom r-valine reactswith aldehydeswith low syn vs. cnti-selectivity, but with fair diastereofacialselectivity attributableto chelation. Transmetallationof the lithium enolatewith ClTi(O-i-Pr)3 (excess)provides a titanium enolate, which reactswith aldehydesto form mainly the syn-aldol resulting from chelation.the diastereomerof the aldol obtainedfrom reactionsof the boron enolate(ll, 379-380).The reversalof stereocontrolis a resultof chelationin the titanium reaction, which is not possiblewith boron enolates.This differenceis of practical value, since it can result in products of different configurationfrom the samechiral auxiliary.
O
oorN-Zo I l-H '--Z\
ox
(45)-Phenyl-2-oxazolidinone.6A one-potroute to this chiral auxiliary involves reductionof r--phenylglycineand BF3etheratein DME with borane.dimethylsulfide complexat a temperaturemaintainedat -82" . The resulting phenylglycinolis then treatedwith trichloromethyl chloroformate(or the more expensivetriphosgene).
\,,/ 2 azi& I \l ith tetramethylguanidinium witt azidation enolate rlectrophilic saponifict by effected be rulrarycan or after reductionof the azidegroup'
"
H.N
.t{
cuH,
O
oH
' BF"o(c'H')' ' | F""'o" BH!.s(cHr), l-H.N
lguH,
I
J
.ct,oc*t
l-#*
o ll nNAo
TJ CuH,
r
\Bs
l
li
O ll
o .i'Bzl.-yANAo : \ I
l
N3 Bzl'
lR. E. Gawley, (1989). Or9.,54,3002 K. Rein,andS. Chemburkar,J. : T. M. Zydowsky, ibid.,55,5437(1990). E. de Lara,andS. G. Spanton, ! H. BlockandP. L Faulkner, J. Chem.Soc.C,329(1971\. ' D. A. Evans,T. C. Britton,J. A. Ellman,andR. L. Dorow,,{m. Soc.,ll2,40l I (1990). ! M. Nerz-Stormes andE. R. Thornton, J. Org.,56,2489(1991). ' L. N. Pridgen, (19E9). Org. Syn.,submitted
R'/S= 94:6
{6rvlN;
'o +i
?
?
nzr-1A*Ao
tt, u Bzl' S/R= 97:3
Orygen, singlet. Aromatic hydroxylation.t The reaction of f-isopropylidene-2-indanone(l) rith singletoxygen(Rosebengal)in CHrCN at -35' resultsin an unstableproduct affordsthe phenol 3 in 55% yield. The 2. which on deoxygenationwith P(OC2H5)3 rnitial reactionis presumedto form an endoperoxide(a) by a [4*2]cycloaddition, rhich rearrangesto 2.
oxygen, singlet
.dll Od;'^Le#; 2
,r*f.,o",*,,, OH
Pslladium(Il) acetate. Vinylation of cycloalkncs.t Tbit mole % Pd(OAc), in the Presenceof Pd(OAc)2,P(CoIIs):,and Ag2CO1ir ( Dienesare obtainedin 50-100* yicld.
(cH.).c.
L--\
, .
1625(1989)' r H. E. Ensley,P. Balakrishnan,and c' Hogan,TetahedronLetters'30'
B
u
l
\--
.e
O-,.
Arylannelation of l,34ietct.' Pd(OAc)2,BUNCI (l equiv.), and e b aryl iodidereactswith a 1,3{ier (c overallprocessis believedto involvet r -allylpalladiumintermediate. )2 rCH(CO2C2H5
Vr".u.CH
* BuCH
ll \r
I
(\"'''*n \.Ar
.(
\
{ lrf
t"'xt"l ?"
Z'vfo
I
o -()t'"]
ss* ntoc,tt,l, |
?"
/c(cH3
Pailadium(Il) acetate. Vinylation of cycloalkenes.r This reaction is possiblewhen catalyzedby 2.5 mole % Pd(oAc)z in the presenceof KoAc and BuaNCl in DMF. In some cases l'4Pd(OAc)2,P(ColIs)r,and Ag2CO3in CHrCN showsgreaterstereoselectivity. Dienesare obtainedin 50-100% yield.
(\aY"
(cH3)3c.i,, --l
\,/r-J
(cHr)rc-72-ff + \J
\J
r.t
3 (1989)' rt.tlron lztters,30, 1625
n
.zo:,
+\-J;;"'
Rzo:
\J
Oo,,.o#O.] Arylannelation o! lr3-dienes.2 ln the presence of catalytic amounts of or NaOAc (5 equiv')' an Pd(OAc)2,Bud'{Cl (l equiv.), and a basesuchas Na2CO3 aryl iodide reactswith a 1,3-diene(excess)to afford substitutedcarbocycles.The of a overallprocessis believedto involvean intramolecularcarbaniondisplacement r-allylpalladium intermediate. CHrCH(CO2C2H')2 + BucH:cHCH:cHz
P(c6H'L Pd(oAc),, 6o' Na'co"DMF' , 8't%
I
(Yc*'cooc2Hs __'rfr . r> !- 'ss* \A,
vPL) 259
Palladium(II) acetate
Bicyclic acctals.s Cyclic allylic el treatedwith Pd(OAc)2.OnIy a catdytic r presentas a reoxidant.The abscm ofd of this coupling.
a OH
Heteroannelationof 1,3-dieneswith a variety of oxygen-or nitrogen-containing aryl iodidesaffordsdihydrobenzofuransor nitrogen heterocycles'3
". ""3-eI$ "",!1)[, O'*ool*n"oo"' Ac
cugcunu + cH2:cHcHgcHsu --'z ="(YN 6r%
fY*"o \,,\
,
\--
|
coupling of Coupling o! ArI and unsaturateil epoxi.des.aPalladium-catalyzed by one or groups separated are the two in which CeIIsI with unsaturatedepoxides product. Highmajor as the alcohols provide allylic arylated more carbonatomscan as formate metal alkali of an equiv. l-3 catalyst, as estyieldsobtainwith Pd(OAc)z
+ CttlOCH:(
cH(ocH3)'
l,4-Additions to l,34ienc{ (12, 36 tion can be usedto effect intramolccuhr by a suitablenitrogen nucleophilc.Tbor acetatecatalyzedby Pd(OAch (with ba fusedheterocyclecis-2, in which tbc s by an overall tans-|,4-oxyamidatioo of t improvesthe yield andresultsin an oven midesand carbamatescan also bc usodit also be effectedby use of 2 equiv. of Li
-,/1.z-tr f' T
I
uol.. l.cL Prl(tr)
NFITs
AcO
65*
I
2\ (I) C6H5I+ CHr:91116Hr)"Ci-l-CH, n=l 4 l0
pd(oAc). -:==5 C6H5CH2(CH2)"CH:CHCHTOH (ElZ-3:r) 787o 62Vo 44Vo
as the reducingagent,variousbases,and alkali metalhalides.The yield decreases number of carbon atoms separatingthe double bond and the epoxide increases. Evidently the organopalladiumintermediatecan migrate along the carbon chain. Substitutionon the doublebond alsolowersyield, as shownin the arylationof 4,5(equationII). epoxycyclohexene
Di.dehydroamino acids, R|CH:( droamino acids (Rt = Ar) can be prq protected2-amidoacrylateswith lryl a transfer conditions, which resuls in t good yield (32-80%). This reactioa il benzyl, N-Boc-protectedaryl didchydm i
CH,:ggOO"zl
+ C"lqt J
NHBoc
(rr)c6Hsr.O"ryt't'Uo" (cisltrans= 67:33)
Cyclopentenonesfrom corfry&l sides(2) obtainedby reactionof Ghyd
Pallsdium(Il) acetate
261
Bicyctic acetals.s cyclic allylic alcohols couple with ethyl vinyl ether when treatedwith Pd(oAc)2. only a catalytic amountof Pd(II) is requiredif cu(oAc)z is presentas a reoxidant.The absenceofdouble-bond isomerizationis a useful feature of this coupling.
oc"H.
Df oxygen-or nitrogen-contalnlng m heterocycles.3
Ac I
tt' Z-,.fN-VCH=CHBu
=-]! I Palladium-catalyzed couplingof ro sroups are seParatedbY one or coholsasthe majorProduct.Highformatear 4urr . of an alkali metal
OH l .4', \ ll .
P{
/
earoe"!f;"[?A")' ---lr*+ CTH,OCH:CH, U cH(ocH3)'
\
\
cH(ocH3)'
(12,367-368; 14,249-250; 15,245)' This reacl,$Atlditions to 1,3-diencs6 tion can be usedto effect intramolecularcyclization of cyclic 1,3-dienessubstituted by a suitablenitrogen nucleophile.Thus reactionof the amido diene I with lithium cisu."trt" catalyzedby Pd(OAc)z(with benzoquinoneas reoxidant)provides the formed fusion, ring to the is cis group in which the acetoxy fusedheteroiy cle ci:is-2, of the dienesystem.Addition of a traceof Licl by an overall trans-1,4-oxyamidation (equationI)' Acetaimprovestheyield andresultsin an overallcis-1,4-oxyamidation can 1,4-Chloroamidation amides. place of canalsobe usedin midesandcarbamates of LiCl. also be effectedby use of 2 equiv.
LiOAc, LiCl,
AcO...
ACO
Pd(ID ----------..----
+
65%
N Ts
93:7
trans-2
> C.H.CH2(CH')"CH:CHCHTOH (ElZ-3:l)
as thc halrdes.The yield decreases increases' ePoxide the : txrnd and o migratealong the carbonchain' d. as shownin the arylationof 4,5-
cis-2
Dillehyilroamino acids, RtcH:c(NH2)CooR2.7 Review.E Aryl didehyof Ndroamino acids (Rr = Ar) can be preparedby a modified Heck coupling phaseprotected2-amidoacrylateswith aryl iodides catalyzedby Pd(OAc)' under to iransfer conditions, which results in the (Z)-didehydroaminoacid in moderate of opreparation good yield (32-80%). This reaction is particularly useful for benzyl, N-Boc-protectedaryl didehydroaminoacids' Pd(OAc),'BUJ'lCl
cHr:gg69uzl + cuH,Iiry#ryf NHBoc
cuH,\cooB"l NHBoc
glycocyclopentenonesfrom carbohydrates.e This transformation involves (1) an with sides(2) obtainedby reaction of 6-hydroxy-2,3-dihydro-6fil-pyranones
262
Palledium(Il)ecetrte
alcoholcatalyzedbyZnCl2.etherate(superiortoSnCl4).Theresultingcyclicacetals (3) whentreatedwith a catalyticamount (2) reanangeto substituteJcyclopentenones casethe alkoxy group in the of pafOl"l, and NaHCO3(iequiv') in DMF' In every group' product (3) is rrcrs to the free hydroxyl
7 A.-S. Carlstr
(CH,)rSiCHrCtlrOH
/:\
Ho{ \6J Fo -i#L
(cH3)3sicH,cH'oatso o---/
L
acetate-N'N'-Bb(b.rl
Palladium(Il)
r
2
Pd(OAc;- |
I
l-
'-,"JlllRii,;'^}H1ff,'
A
o
ll\\./ )"'ort \ bctlcttrslcu';, 3
Enyne cyclization.t Cyclizatioo o Pd(OAc)zin combinationwith Arf po cyclizationwith Pd(OAc)2and N.N'{i the desireddiene 3 in 8l% Yield. Th sterepolide(4) in ll stepsand 34* ovt
CH' 3.Arylcycloatkenes.|oTheseproductscanbeobtainedbyPd.catalyzedcoup containingtetrabutylammoling of aryliodides and cycloalkenis (5 equiv.) in DMF are less effective' A large bases acetate nium chloride and KoAc (2 equiv.) other monoarylation' effect to excessof the cycloalkeneis required
/'\ ?'5",11';,?i:)" 1> ----"-:t p-crHrorccu".a-J + p-crHrorccuHal \--rl
/---//
-cH'
-/\ CH," \-------:
i
oSi(cH.\-
RO
2, R = CHzCoH.OCH,T
CHt CHt
Pd(OAc)zpromotescoupling Coupting of vinyl haliiles with atlytic alcohols'rr presenceof silver carbonateand of vinyl ialides with primary allylic alcoholsin the tetrabutylammoniumhydrogensulfate' CuH,ra
\:,
A&co' Pd(oAc)r'
+ cH2:cHcH,onff'
CuH''t_
{,
o
' B. M. Trost,P.A. Hipskind' J. Y' L- Ct ( 1989).
Ha""",a"o
I R. C. LarockandW. H. Gong,J' Org',54,2047 (1989)' 'i. C. LarockandC. A. Fied, Am' Soc',112,5882{1990)' 3 R. C. Larock, N. Berrios-Pena, and K' Narayanan'J' Org'' 55' 3447(1990)' a R. C. Larock and W.-Y. Lewg, ibid',55, 6244 (1990)' ' i. C. Larock and D. E. Stinn, Tetahedron ktters' 30' 2767 (1989)' 6 J.-8. Biickvalland P. G. Andersson,Am' Soc',1f2' 3683(1990)'
Palladium(Il) acetate/Potrssiun lr Conjugate reduction of a,8-ut Pd(OAc)zsystemis convenientfor tn ketonesand esters and of 2-butco{ pounds.The reactionis carried ou ir
Pelladtum(Il).cetrte/Potrssiumformlte
r). The resultingcYclic acetals beatedwith a catalYticamount the ;r casethe alkoxYgrouPin
cH.o-( tso o_-J
7 A.-S. Carlstrdmand T. Frejd, Syntftesis,414(1989). 8 Review:U. Schmidt,A. Lieberknecht,and J. Wild, ibid.,l59 (1988). e B. Muchaand H. M. R. Hoffmann,Tetahedronl*uers,30,4489 (1989). r0R. C. Larock,H. Song,B. E. Baker,andW. H. Gong,ibid. ,30,2919 (1988);R. C. Larock and W. H. Gong, Org. Syn., submitted(1989). It T. Jeffery,Tetahedronl*tters,3l, 6641 (1990).
Palladium(Il)
acetate-N,N'-Bis(benzylidene)ethylenediamine,
,
;N:CHC.H,
Pd(oAc),-| t-N:CHCoHs
I
" -6?% 50 | :d,1S:)i'JH1ff J ' o
il
-a)"'oH
'@HrCHrS(CH3)3
263
(r)
Enyne cyclizntion.t Cyclization of an enyne such as 2 to the diene 3 with Pd(OAc)zin combinationwith Ar3Pprovidesmixturesand in low yield. In contrast, (1) provides cyclizationwith Pd(OAc)2and N,N'-bis(benzylidene)ethylenediamine the desireddiene3 in 8l7o yield. The product was used for a synthesisof (-)sterepolide(4) in I I stepsand 34Vooverall yield.
3 txained bY Pd-catalYzedcouP HF containingtetrabutylamme' rs€s are less effective. A largc ul lation.
.a""u- cH, 8t%
ROr'
cH,
OSi(CHr)t-t-Bu
2, R = CHzCoHTOCHT-p
osiR3
>p-C,HrOrCCr"re I Pd(oAc)zPromotescouPling tresenceof silver carbonateand
t
I B. M. Trost,P.A. Hipskind, Int.Ed.,28,1502 Angew. Chem. J. Y. L. Chung, andC. Chan, (1989).
CuH,,
cHTCHTCHO Bl ,990t. Ors .55,3447 (1990). I ). :?67 (1989). 6t,1(1990).
Palladium(Il) acetate/Potassiumformate. Conjugatereduction of arp-unsaturutedcarbonyl compounds.t The HCOOK/ Pd(OAc)zsystemis convenientfor transferconjugatereductionof c,p-unsaturated ketonesand estersand of 2-buten-4-olides to the correspondingsaturatedcompounds.The reactionis carriedout in DMF at 60' usingan excessof HCOOK.
2A
acctete-Trlphenylphorphlne
Prllrdlum(Il)
-(
CH" /
fuHooCHrn \
pd(r), --;a---)tnt
HcooK. DMF,6o'
/
,CrHoOCHt-P \
cH,Xe^o
;;:d.,\"
?
cuH'vc]H'lfr'
c6H5vcH3
3
(1991)' I A. Arcadi,E. Bernocchi, S. Cacchi,andF. Marinelli,Synlett,27,
can be as efficaciousas silver selts effect is attributedto an anion erch Aryl-v inyl couplin g; Fst 14< basedon the formal conjugateaddit dihydropyrimidinonesuchas I, prcl gine (cf , 14, 69-70). Thus 4-iodo Pd(OAc)2,Ar3P, triethylaminc.er
c(cH.). -| "*A*-"oocH3
Pelladium(Il) acetete-Triethoxysilane. is bestcarHydrogenation.r Hydrogenationofwater-solubleunsaturatedacids of the amount a catalytic with ried out on the sodium salt in an aqueoussolution oftriethoxyI equiv' Ifonly as the sourceofhydrogen. catalystandtriethoxysilane in 70-85% yield' silaneis added,triple bondsare selectivelyreducedto (z)-alkenes
|
f"-/
|
+ rCI.(
(R)-r
lJ. M. TourandS. L. Pendalwar, ktters,3f ,4719(1990)' Tetrahedron Paltadium(Il) acetate-Triphenytphosphine (1)' Heck intramolecular cyclizttion. silver carbonateor nitrate was addedorigibut they nally to tandemHeck arylation reactionsto depressalkene isomerization, of a number have used p-elimination et al.r step.Grigg alsoimp.oneselectivityin the (f5' 248)' formate sodium useful additivessuch as triethylammoniumchloride, phenylzincchloride,aswell assilver(I)andthallium(I)salts.In fact, thallium(I)salts
n
('.-('Y
with NaBHa/H3O+followed by ! methylether(3) in 85% yield aod PoIyene H eck-type cy clizttior,.r rrienyltriflatesto spirobicyclicsyrt Undcrtt and2 equiv.of N(C2H5)3. cyclizationis particularlyfacilc rl DIOP (4, 273) i\ a l: I ratio. ln d
Pd(t).P(c^H.).
co,cH,-
$1"-r,, o ..H co2cH!
+ AgNO, + TlrCO,
36Vo 784o
none none
265
Pslladlum(Il) scetlte-Triphenylphosphine
can be as efficaciousas silver saltsand can increasethe ratesof cyclization'The effect is attributedto an anion exchange:RPdI + TIX + RPdX + TlI. Aryl-vinyl coupling; F-aryl-9-amino acids.2 A novel route to p-aminoacidsis pure basedon the formal conjugateadditionof an aryl iodideto an enantiomerically (R)-asparaof suchas l, preparedby pivaldehydeacetalization dihydropyrimidinone gine (cf , 14, 69-70). Thus 4-iodoanisolecoupleswith I under Heck conditions, Pd(OAc)2,Ar3P, triethylamine,and DMF to give 2 in 78Voyield. Reductionof 2
/C6HPCH3-P
cH, f1 .".Xolo CH,
c(cH.). "*A*-""oocH3
! r n / e r r . 2 (71, 9 9 1 ) '
c(cH3)3 Pd0D, Ar,P
-9H + IC.H.OCHT-O carble unsaturatedacidsis best of the amount r eirh a catalYtic oftriethoxYequiv' I ao lf onlY to rZ)-alienesin 70-85%Yield'
,)_) (R)-1
"*A* r .A/'tf\
l i l l \
ocH3
t
".J;lu*'ts'
3t.1ll9 (1990).
NH' HOOC-..,,/....rr\
origionateor nitratewas added theY but N alkeneisomerization, of number a used l,rn ., ol.r have 248)' (15' formate noe. sodium salts nr I t salts.In fact,thallium(I)
i l l
\Z\ocH. (s)-3 with NaBHa/H3O+followed by hydrolysis (3N HCI) provides (S)-9+yrosine-Omethylether(3) in85/o yield and -9lVo ee. PolyeneHeck-typecyclization.s overman's grouphasreportedbicyclizationof (l :4) trienyltriflatesto spirobicyclicsystemsin the presenceof Pd(OAc)z/P(CoHs): yield. This in'72Vo to 2 I cyclizes these conditions and2 equiv.of N(CzHs):.Under (S,S)(R,R)or and Pd(OAc)z by particularly when catalyzed facile cyclizationis DIOP (4, 273\ in a l:l ratio. In this case,the tricyclic dienone(2) is obtainedin
fl,
H co2cH,
+ I 8:l
--cH,
Pd(OAc)r, P(C6Hr\ N(C,H.),, CH.CN
---------L:-:---
12%
none none
266
Palladium(Il)acetote-Triethoxysilane
>90Vo yield and in >45% de. The report includesseveralother bicyclizations involvingformationof spirocycliccenters. Spirocyclizntion.a Enamidesof 2-iodobenzoicacid suchas I undergospirocy(l equiv.), and cataclizationat 45-80' in CH3CNcontainingKzCOr, (C2H5)4NCI chloridepermits lytic amountsof Pd(OAc)zin a l;2 ratio. The tetraethylammonium milder conditionsand retardsisomerizationof the doublebond. The reactioncan be extendedto enamidesof type 2.
wasfirstreportedby Stille(14,469-4rc). for couplingof a vinyl triflatewith a viry tionof configuration of bothpartncn.Ho
R3SiO
CH,
fl
'z\atY f
CH, +
|
lf
o
iiiS-ii.".l
\y'1,-*-r,,
cri
orf
cofr
I
ffi
1
o
RST
I
"ir"Y
CH CH
-
Pdot), P(c6HJ)r KrCOr,(CrHr).NClsWo
n\N-n,r o t
Cyclizationof tetraenes.s This Pd catalysteffectscyclization of tetraenesconin taining two 1,3-dienegroups in an HX mediumto disubstitutedcyclopentanes HX trapping A number of which the X function is incorporatedat one terminus. HSOzAr.The trans/cisratio is reagentscan be usedincludingHOAc, HN(C2H5)2, sensitiveto the tetraenesubstrateandto the trappingreagent,andcanvary from l: I to >20:1.
CrHroocl/J'-"/cHz crHrooc\__1.1a",
* tu"'t"'o"
(2) underStille coodir the vinylstannane ( l:21 conditions with Pd(OAc)z/P(CoHs)r Cross-coupling of allcncs vitL l1 triarylphosphine(cat. A) can effecr crq l,1,3-trisubstituted allenesto provi& rs I tionsI, II). Theregioselectivity in thc ctr
R. (D " H . Fg-911,
+ R|C-CH =
PdOD 88%
*;":. 1r9 H'
crHrooc\,f-ffoBrl c,H5oocv.....
cH,
(translcis=7:l)
Coupling of vinyl triflates with vinylstannanes.6 Coupling of vinyl triflates using Pd(0) as catalystin combinationwith 2 equiv. of LiCl with organostannanes
lcooc.lt., + R'C t"",
to the fully conjugatedsystemis highl,r d be directedwith other catalyststo the u be usedto preparehighly unsaturatcdsyl Hydrovinylation of RCtCR.t Ret iodide(bromide)catalyzedby Pd(II) ed i
Palladium(II) acetate-Triethoxysilane
des severalother bicYclizations at-rdsuchas I undergosPirocY[C:H.)rNCl(l equiv.)'andcatanh1lammoniumchloridePermits loublebond.The reactioncanbe
wasfirst reportedby Stille (14,469-470).This couplinghasbeenusefulparticularly for couplingof a vinyl triflatewith a vinyltrialkyltinto give a 1,3-dienewith retention ofconfigurationofboth partners.However,couplingofthe vinyl triflate1 with
9H,
osiR3
R3SiO
Pd(OAc)r,P(CoHr), THF, ?0" .-..-_-.-----_.-
CH, CH,
6%
o
CH,
oTf
I
r
a
--1""./ -Y*-"t
CH,
3
o conbcts cyclizationof tetraenes in cyclopentanes n dr:ubstituted inur A numberof HX traPPing . HSO3Ar.The trans/cisratio is t reagent,andcanvarYfrom l: I
(2) underStille conditionsfails, but succeeds the vinylstannane readilyunderHeck (l : 2). conditionswith Pd(OAc)2/P(C6H5)3 Cross-couplingof allenes with l-alkynes.T Pd(OAc)2in combinationwith a triarylphosphine(cat. A) can effect cross-couplingof l-alkyneswith l,l-di- and 1,1,3-trisubstituted allenesto provideasthe majorproductconjugated enynes(equationsI, II). The regioselectivity in thecaseof couplingwith methyl2,3-alkadienoates
(l)
R
\ , )-C-CH,
A R . . C + R'C-CH .:- -::-+ 3o-ffi%
H'
tu tr
R!6:s 1ry H.
J{.ooc..J^fr\oBzl t\r.... rr.c,oc -/\. cH, (translcis=7:l)
rrs.6 CouPlingof vinYl triflates pmbinationwith 2 equiv.of LiCl
H
H/\
/
,coocH3
t"",
,
+ R,C-CH
A 30-80%
. tR'
RCH" '\_J
.,/
R'
COOCH.
"r.
to the fully conjugatedsystemis highly dependent on the choiceofcatalyst,andcan be directedwith othercatalyststo the nonconjugated enoates.This new reactioncan (equationIII). be usedto preparehighly unsaturated systemssuchas I ,5-dien-3-ynes Hydrovinylationof RC=CR.t Reactionof disubstitutedalkyneswith a vinyl iodide(bromide) catalyzedby Pd(II) and in combinationwith formic acid anda base
268
Pellodium(Il) chloride
(III) CH,:C:Ca
.coocH3 l) (cHr)lsic=cH ./ 2) BU.NF(56%) CH,
I
(83%),
7:T" 71% ^ Ir. CH,. "\--l
t'\,*/
selectivesynthesisof cis- or tans-2.| thechoiceof a substituent at C3.Thur at C3can determinethe cis- or tant-t groupat C4has slight effecton the sd reportedby anotherlaboratory.t
.COOCH3
--'G' (I)/ \
"r^
cHrooc,
\o"ooq
cH,
(formatereducingsystem)resultsin 1,2,4-trisubstituted 1,3-dienes. Configuration of the vinyl partner is retainedand syn-additionto the alkyne is observed.
I M. F. Semmelhack and N. Zhang..1.O : Review: T. L. B. Boivin, Tetahcdra. r M. McCormick,R. Monahan,Ul. r. Sq
(r989). C6H5C-CC6H, + BUCH:CHX
Pd(rD,HCOOH, N(C,4), 80P
BU
g
(E)
CuH,
CoH,
l R. Grigg, V. Loganathan,V. Santhakumar, V. Sridharan,and A. Teasdale,Tetahedron lztters, 32, 687 (1991). 2 J. P. Konopelski, K. S. Chu, andG. R. Negrete,J. Org.,56, 1355(1991). 3 N. E. Carpenter, D. J. Kucera,and L. E. Overman,ibid.,54,5846 (1989). a R. Grigg, V. Sridharan,P. Stevenson, (1989). andS. Sukirthalingam, Tetrahedron,45,3557 5 J. M. TakacsandJ. Zhu, J. Or9.,54, 5193(1989). 6 E. J. Coreyand L N. Houpis,Am. Soc., ll2,8997 (1990). 7 B. M. Trost and G. Kottirsch,ibid., ll2,2816 (1990). 8 A. Arcadi, E. Bernocchi,A. Burini, S. Cacchi,F. Marinelli, and B. Pietroni,Tetrahedron Letters,30, 3465(1989).
Palladium(Il)
chloride. 2,S-Disubstituted tetrahydrofarans. Semmelhackr has extended his synthesis of tetrahydrofurans by alkoxycarbonylation of 5-hydroxy-l-pentenes (12,372)2 to Pdcr,. cucr?
,tcHt
co'cHloH >
fl cH,
g11\cH,
,tcH,
fa cFt,AolcH2coocH3
Palladium hydroxide, Pd(OIIL. Hydrogenolysis of allylic accnua by hydrogenolysiscatalyzedby Prl(
AcO
hydrogendonor.The readiness ofhyt secondary) tertiary > acetatcs.brt
AcO
90ocH'
\{.o cH; " &n ^., I A. Bianco,P. Passacantilli, andG. R4
Gil cis,X)Vo)
(9OVocis) ,tCuHt
/ cnrAg11\ctt' (76Vo cis)
\
,tCuH.'
/ \ cu,AolcH2coocH3 (all crs, 1007o)
(R)-Pantolactone. Diastereoselectiveprobrain a describeda conversionof (R,S)-2-u forms. Thus I is convertedinto thc cl a chiral alcoholcan give opticdly r
(R)-Pantolrctone
r
H
selectivesynthesisof cis- or trcns-2,5-disubstituted tetrahydrofurans determinedby thechoiceof a substituent at Ca.Thustheconfigurationof a methylor a phenylgroup at C3can determinethe cis- or trans-relationshipat C2and C5. A methyl or a phenyl groupat Cahasslighteffecton the selectivity.Similarresults(equationI) havebeen reportedby anotherlaboratory.3
coocH. 'cH"
cH, /
,rnl t.n 0 cH,. .\J gH.ooc
-o'* l
\or\cH,
\
\o2".""r"oocH3
cH,
of Configuration nured1,3-dienes. lc alkyneis observed. ! \C H.r, BU
J"t' (I)/ \
.coocHs t"".
cHt',-/
269
lM. F. Semmelhack andN. Zhang,J. Org.,54,4483 (1989). 2 Review:T. L. B. Boivin, Tetrahedron,43,3309 (1987). 3 M. McCormick,R. Monahan, III, J. Soria,D. Goldsmith,andD. Liotta,J. Or9.,54,4485 fl989).
:g CuHt
CuH,
Palladium hydroxide, Pd(OH)2. Hydrogenolysis of allylic acetates.t This reaction can be effected in high yield by hydrogenolysis catalyzed by Pd(OH)2 on carbon and with cyclohexene as the
heran. and A. Teasdale,Tetrahedron O r e . 5 6 . 1 3 5 5( 1 9 9 1 ) . l a t . u. 5l 4 , 5 8 4 6( 1 9 8 9 ) . lrngam.Tetahedron,45, 3557( 1989). ll99O). Dr hrrnelli, and B. Pietroni,Tetrahedron
1
,cHt
t.AotcH2coocH3
-----65'k-(z\, )
o"o-\
hydrogendonor.The readiness ofhydrogenolysisdecreases in the order primary secondary> tertiary > acetates,but is increasedby sterichindrance.
AcO alhackrhas extendedhis synthesis .hr droxy-l-Pentenes(12, 372)2to
.""",'lg3tf,o"-j\-
-j\-
coocH3
)-r\ \--f-" cHr' "
G
6o,.(o.1.
OGlc(Ac)o
I A. Bianco,P. Passacantilli, Letters,30,1405(1989). andG. Righi,Tetrahedron
tall cds,907o)
.c.H. / " , \ \o"^cH,coocH3 rall cis. 100%)
(R)-Pantolactone. Diastereoselectiveprotonation ol arylmethylketenes. Merck chemistsrhave acids (l) into the optically active describeda conversionof (R,S)-2-arylpropionic (2). Additionof forms.ThusI is convertedinto the corresponding arylmethylketene a chiral alcoholcan give optically activec-hydroxy esters3 (andthe acids).Of a
(Z)-Pentenylboronates
270
By useof 1,2-dicyclohexyl-1 pentenylboronate I hasbeenprepu
9H, I
a, Acoou G,S)-r
!',
fr"'
R,AcooR*
,o-reCoH,, liry t'* cl,cH6 | to-"'^. -5,l1 I
e, Acoon* 3
numberofchiral alcohols,(S)-ethyllactateand (R)-isobutyllactateprovide(S)- and (4) is (R)-2-arylpropionate esters(3) respectivelyin -94% de, but (R)-pantolactone (R)-3 in about 99% de. The essentialresignificantly more effective and provides quirement for diastereoselectiveprotonation of the ketene is apparentlya chiral OH
I
cH3:xAfo
completetransferof chiraliry to fcr (3). sis of (S,S,S,S)-invictolide
cHi Lo 4
cllo
hydroxy group o to a carbonyl and p to a tert-alkyl group. The choiceof the amine or with trimethylamine,dimethylethylamine, canalsoaffectthe diastereoselectivity, N-methylpyrrolidinebeing most effective.
I
E
I R. D. Larsen, Am.Soc.,lll, andE. J. J. Grabowski, E. G. Corley,P. Davis,P. J. Reider, 76500989).
(Z)-Pentenylboronates, a\YB(oR\'
(1).
CH, CH, (Z)-pentenylboronates can be preparedby reactionof the (Z)-pentenyl Simple They are of interest becausethey add to reagent with different borates. Grignard (equationI).t alcohols to form syn-homoallyl aldehydes
^-o--t<:fi: (r\ (r) (\t'o-J4cu; t", i", R = CzHs R = CeHs
*'*o 'cHr------+ R 92Vo 95Vo
' M. W. Andersen, B. Hildebnnd.G" I R. W. Hoffmann, K. Dirrich,G. K6-
Periodinaneof Dess-Mrrti! (DMl vic-Tricarbonyl compoudt. I uctscontainthis group or a ftrnctir
Periodinane of Dess-Martin
271
as a chiral auxiliary, the chiral (Z)By use of 1,2-dicyclohexyl-1,2-ethanediol pentenylboronateI has beenprepared.This reagentreactswith benzaldehydewith r'H
. *
CH" f Ar A"-**
il#!u"':""","",,,,, cLCHiY"'"" /--{ {:I-''^" - 'cuH" 1", 3",
L6[rr
I
(R)
7l%JC6H'CHO
3
OH rrsobutyllactateprovide(S)- and (4) is l{ ,Je.but (R)-pantolactone reessential The de' 99% about chiral a aPParentlY is ketene bc
i
-cH,
C.HF CH, 2 (997o de)
completetransferof chiralityto form syn-2.lt hasalsobeenusedfor a shortsynthe(3). sisof (S,S,S,S)-invictolide
of the amine ; I group.The choice or dimethYlethYlamine, ir lamine,
cH,o\c"o#"",o CH,
CH,
CH,
CH,
CH,
,,.Jllla""
Am' Soc',lll' ! E J. J. Grabowski,
o CHr...
CH,
H,, Pd
u%
d t,1 reaction of the (Z)-PentenYl re of interestbecausetheYadd to i o nI ) . '
H,C
H : CH, 3
I M. W. Andersen,B. Hildebrandt,G. Ktister,andR. W. Hofmann, Ber.,l22'1771 (1989); R. W. Hofmann,K. Ditrich,G. Ktister,andR. Sttirmer,ibid.,122, 1783(19E9).
OH I
,*r'^Y'v CH, 96Vo de 944o de
CH"
of Dess-Martin(DMP, l), 12, 378-379; 15, 252-253. Periodinane hasnotedthatseveralnaturalprodcompounds.Wassermanr vic-Tricarbonyl fromit. A shortnewrouteto this derivable thisgroupor a functionality uctscontain
272
a) t
\N/
Periodic acid-Sodium bisulfite
o ll
l
ror.o"
rHF
+ udn
$cuH,
|
|
> \-N\^vn
Z)'\./.SC6H5
|
|
l+ ll O
I
1o-8wo H
O
q
|
ll
\-NV\7R
ll
O
ll O
o
system2involves an aldol-type condensationof an aldehydewith the anion of an cphenylthioamide.The mixture of productsis oxidizedto an a,p-diketo amideby the Dess-Martinperiodinane. 2'- or 3'-Oxonacleosides.s The periodinane(l) of Dess-Martin effectsoxida5'-silyl to the corresponding tion of 3',5'- or 2',5'-disilyl derivativesof nucleosides in yields as high as 96Vo.ln general,this derivativesof 2'- or 3'-oxonucleosides reagentis superiorto Swern-typereagentsor a chromium(Vl) oxidant.
r'cH'cr''Rrsiol Rrsio-1 . V-ro-.fd"nine roaAdenine
#
\ ) H t t oH
"
osiR3
( Ho
)
osiR3
Oxidation of allylic alchols. Dupuy and Luchearecommendthis oxidant (l) allylic alcoholsto c,p-enones(30over MnO2especiallyfor oxidationof secondary 92% yield,5 examples).
9H, /1onr,cH"cr",25. t t e2%
/'-("
,c:,
Peroxybenzimidic ecid (Paya'r rc Stereoselectivccpori&bt. E zoic acid, monoperphthalicrid. q gives a mixture of two epoxidcsir I In contrast,epoxidationwi$ Pry beenusedto preparemethyl 60-08 and removalof the acetonidcarq
coocH3
A l l
l
ocJlaox _ tt
o/'{
cH,+d CH, 2
9{.6Jc6H,c:NH(l)
l
4
\r/
: H,C.
'H. Ohta,Y. Sakata, T. Tateuchi,d
lr"
9H' t
drins canbe preparedby uscof NrE but terminal alkenesgive Martovrl terminal carbon.
: CH,
zzc:,
CH,.
CH,
Caution: Chemists at ICE5 report that the Dess-Martin periodinane can exhibit hazardous explosive properties. I H. H. Wasserman, Aldrichim.Acta,20,63 (1987). 2 R. G. Linde II, L. O. Jeroncic,and S. J. Danishefsky, J. Or9.,56,2534 (1991). 3 V. Samano andM. J. Robins,ibid.,55,5186 (1990). a C. Dupuy andJ. L. Ltche, Tetahedron,45,3437 (1989). 5 J. B. Plumband D. J. Harper,C and EN, July 16, 3 (1990).
Periodic acid-Sodium bisulfite, H5IO6-NaHSO3. Iodohydrtns.r This combination (l:2) presumably generateshypoiodous acid, IOH, since it converts alkenes into iodohydrins in moderate to high yield. Bromohy-
rS. Bowles,M. M. Campbcll, M. Sd 3 7 1 1( 1 9 8 9 ) .
Phenyldiazomethane,CollsCHNr. O- and N-Benrylotion.z T\bt at -40o in CH2C|2containiagr trr ted somewhatmore rapidly rhrn 11 possible.Yields are generally cid
' X. Creary,Org. 9yn.,64,2O7(lg8:t) : L. J. LiottaandB. Ganem.Tctmb*r
Phenyldiezornethane
o l - r - l l
t , \,-N\r,,\/R -d-80%
'R
t
ll
o
ll
o
ldehydewith the anionof an od ro an a,p-diketoamideby the ) of Dess-Martin effectsoxidaS'-silyl lcs to the corresponding high as 96/o.In general,this rnium(VI) oxidant.
drinscanbe preparedby useofNaBrO3.Internalalkenesgive a mixtureofproducts, but terminal alkenesgive Markovnikoff productsin which the iodine is boundto the terminal carbon. ' H. Ohta,Y. Sakata, (1990). T. Takeuchi, andY. Ishii,Chem.Letters,733 Peroxybenzimidic acid (Payne'sreagent),1. Stcreoselectivecpoxifution Epoxidationof the diene 2 with m-chloroperbenzoic acid, monoperphthalicacid, or r-butyl hydroperoxide-vanadylacetylacetonate givesa mixtureof two epoxidesin 89% yield.t In contrast,epoxidationwith Payne'sreagentresultsonly in 4. The epoxide3 has beenusedto preparemethyl 6c-fluoroshikimate(5) by treatmentwith HF in pyridine and removal of the acetonidegroup.
coocH3 )_-,ro-..fd"nin' ( ) \ /
n
o
osiR3
c' recommendthis oxidant(l) lrc alcoholsto c,P-enones(30-
CH,
273
COOH
COOCH3
I
z\
l l l o/'{
crc6H.corH>
-\-d
8ev'
lr"
90%Jc#rc:NH (l)
".Q"'"
" 1.}",:,
cnlo
"",\o
CH, )
/
<\^'-
CH,
CH,
3
4
I
4e% I
CH,
I{artin periodinanecan exhibit
I S. Bowles,M. M. Campbell, Letters,30, M. Sainsbury, andG. M. Davies,Tetahedron 3 7 1 1( 1 9 8 9 ) .
t. Ors., 56,2534(1991). r90r.
Phenyldlazomethane,CoHsCHNz.Preparation.I O- and N-BenzXl.ation.2This reactioncanbe effectedwith phenyldiazomethane at -40o in CH2CI2containinga trace of tetrafluoroboricacid. Alcohols are benzylated somewhatmore rapidly than amines;henceselectivebenzylationof alcoholsis possible.Yields are generally satisfactory.
acid, hYPoiodous rbll generates pderateto high Yield.BromohY-
' X. Creary,Org. !yn., 64, 207(1985). : L. J. LiottaandB. Ganem.Tetrahedron ktters,30, 4759(1989).
)t
274
Phenyllodine(Ill) bis(trlfluoroacetete)
Phenyliodine(Ill) bis(trifl uoroacetate). Dihydrobenzofuranes.r Oxidation of a mixture of a para-methoxyphenol(l) and an electron-rich styrene (2) with this oxidant results in a trazs-disubstituted
' S. Wang,B. D. Gates,andJ. S. Srtr 2 Y. Kita,T. Yakura,H. Terashi, J. lt (1989). Phenyliodine(Ill) diacetetc. Oxidative reanangcncil of s. convertedinto methyl c-methoryrr; orthoformate (7, 362). This ort CoIIsI(OAc)z(2 equiv.) in trinab:rl
cH30\i"\Y"\-'cH'
cH,o)\)
"",o-pcry::: QH,
RC6H.COCH' -
tl
cH"o IO. V. Singh,Tetrahedron Lcncn,ll.
3 dihydrobenzofuran(3), a structure common to some plant metabolitesknown as neolignans.This oxidation was usedto provide the dihydrobenzofuran4, a known precursorto kadsurenone(5), which is an antagonistto a platelet-activatingfactor.
"",opcry:"":"'' cH.
Phenyliodine(Ill) diecetetc-Io-., Angular methylation.r lrrdiri alcohol)with CoHsI(OAc)z rnd lr (l which is reducedto the alcohol 3.
cHrcH
cH3o
o
cH3o 4
CaHrl(OA.\, L +
5
/
Oxidation of ethynylcarbinols; dihydroxyacetonyl compounds.z This hypervalent iodine reagentoxidizes ethynyl carbinolsto dihydroxyacetones.
I\ I
,t"tr,
cHcrj, cH,cN..,,-.,!""ro"
oH _H-
(-,lo" o ll
"zrcsi(cH)t _*l
OH
Transannularcyclizttim of b containingC6llrlO in cyclohexane lll",4O%). Butthesamerrircti(t r zationto oxoindolizidincs or l-rer
Z>/''--
50%
ll
l-oH
}P o C6Hr3C=CH
lil-
CuH'
I
dircetate Phenyliodine(Ill)
(l) Dre of a para-methoxyPhenol trazs-disubstituted in a results !r
rS. Wang,B. D. Gates, J' Or9.,56,1979(1991). andJ.S. Swenton, 2 Y. Kita,T. Yakura,H. Terashi, I. Haruta,andY. Tamura,Chem.Pharm.Bull.,37, E9l 0989). Phenyliodine(Ill) diacetate. Oxidative rearrangementof aryl methyl ketones.r Theseketoneshave been on reactionwith Tl(NOr)z in trimethyl convertedinto methyl a-methoxyarylacetates orthoformate (7,362). This oxidative rearrangementcan also be effected with C6H5I(OAc)2(2 equiv.) in trimethyl orthoformatein equally good yield.
c,H3t(ococFr)r , 65%
r-H
CH"
')-{,, )--l
275
C6H'I(OAc)r,
>\-/'\'ocH3 ).(\o--\AocH, ll t
g#q Rc6H4cocH3
Rc6H4cHcoocH3 ocH3
}|,O ' O. V. Singh,Tetrahedron Lctters,3l,3055(1990).
3 rcme plant metabolitesknown as [rc dihydrobenzofuran4, a known nrst to a platelet-activatingfactor'
Phenyliodine(Ill) diacetete-Iodine, 13, 258-259; 14, 242-243. Angular methylation.r Irradiation of the hemiacetalI (formed from an allylic alcohol) with coHsl(oAc)2 and 12(l equiv. of both) results in an iodoformate(2)' which is reducedto the alcohol 3.
cH2cH OH \
o
1-g
|.O
qH,r,3"n"1,,,,,
i
lonyl comPounds.zThis hypervadrhl droxYacetones.
"13"Al#
$,
'A#
r,V \
)
cH.PH
rcH^PcHo
H
W
H
\
2
o ll
3 (cisltrans= 4:l)
a,,--*,CCHzOH
I \-/
l-oH
o il
rY-r:ff'o" o H ,CCHTOH
Transannular cycliZationof lactams.2 Photolysisof the 8-memberedlactam I in cyclohexanecontainingC6II5IOand iodine results in the genr-diiodide2 (m. p. lll",4O%). But the samereactionwith 9- or l0-memberedlactamsresultsin cyclirespectively,in high zationto oxoindolizidinesor l-azabicyclo[5.3.0]decanones, I
C6EIo, I,
'
cvclohcxmc
wa
,/
I
/-\l-1
, < V-NJ i l H
o
2
\
)
0
t-Phenylmenthol
Vilo
.....-.-m.ffi --*X V*i
c
o (l4Vo)
4 (82Vo)
showno reactionevenat higher yields.Lactams elevenor moremembers containing temperatures. ' G. StorkandR. Mah,Tetrahedron Letters,30,3609(1989). 2 R. L. Dorta,C. G. Francisco, 1168(1989). Chem. Comm., andE. Suarez,,l'C,S. Phenyliodine(Ill) difluoride, C6H5IF2(l). The simplestroute to this hypervalent reagentis the reactionof iodobenzenedichlorideswith aqueoushydrofluoric acid in the presenceof HgO (yellow). The p+-butyl derivativeof I is a stable,crystalline solid. Nuorination.r This reagenteffectsregio- and stereospecificfluorinationof the electron-richsteroiddienamine(2) to give the (axial) 6p-fluoro-4-cholestenone-3 (3). In the addedpresenceofcu(acac)2,reactionof2 with I resultsin 6o-fluoro-4(15%)astheonly products. (10%\ and6,6-difluoro-4-cholestenone-3 cholestenone-3
cH.l
a*
-y:r,
t^rw*'* \
)
Tq
+ HCOC@R'1
QHrl
f^]|l+cuH,r F
reagent A more significantchangeobtainsin the presenceof an electron-transfer with 6ayield together In this case3 is formedin2l% suchas N-methylviologen. (l3Vo)' of a Use (8Vo) and 6,6-difluoro-4-cholestenone-3 fluoro-4-cholestenone-3 radical two Apparently . the yield of 3 to 33% four-foldexcessof reagentI increases pathwaysare possible,both involving ArIF'.
(%% dc). Hi3|l (S)-diastereoselectivity tainedwith TiClr aspromoter; useof BCll tivity. A substituenton the Phcnol cx I stereoselectivity.Lower tempcre$rcsdG on the diastereoselection. ' F. Bigi,G. Casnati, G. Sartori,C. Delpra 861(1990).
(rS,2R)-( + )-[1-Phenyl-2-(t-pipcrtly'l
This chiral p-amino alcohol is obteirod 1,5-dibromopentane. Enantioselectiveadditiot (CtE tlhz. co;r I (l equiv.),diethylzincundergoes ketonesinSl-94/o ee. Use of catdyr. r to 60-80% ee. CuH'-.,/\(Bu+ tl
* 1cJ{.1
o
I K. Soai,M. Okudo,and M. Okermro. Ira
(1989)' tJ. J. Edmunds J.C.S'Chem.Comm-,881 andW. B. Motherwell, 8-Phenylmenthol. Diastereoselectivealkylation of phenols.t In the presenceof Ticla, phenols reactwith glyoxylatesat -30 to 20o exclusivelyat the ortho-positionto form 2hasno effecton the siteof substitution.Useof esters.A substituent hydroxymandelic a chiral glyoxylate,in particular(-)-8-phenylmenthylglyoxylate,resultsin high
(Phenylthiomethylene)trlphcrybrrr precursoris generatedfrom (Qttl){r. The ylide reactswith aldchydcsin Tll form phenylthioenolethers(3).r Tbc fm thio ketones, the latter to homologrrcd t
(Phenylthiotrimethylene)triphenylarsorrne
OH t
v^\
l , /
Ticl., cHrcl, 2V
\
+ HCOCOOR* ----::-, il-9J%
o
277
OH
,Ad"-** i l l R (97-98:3-2)
(l4Vo)
rs showno reactionevenat higher (l 9 E 9 ) . I168(1989). Comm., Chem.
are ob(94% de). Highestyields and diastereoselectivity (S)-diastereoselectivity tainedwith TiClaaspromoter;useof BCl3andTi(O-i-Pr)alowersthediastereoselectivity. A substituenton the phenolcan lower the yield' but has little effecton the stereoselectivity.Lower temperaturesdecreasethe yield, but havea negligibleeffect on the diastereoselection.
iimplest route to this hypervalent , sith aqueoushYdrofluoricacid in irarire of I is a stable,crystalline
Asymmetry,l' ' F. Bigi,G. casnati,G. sartori,c. Dalprato, andR. Bortolini,Tetrahedron: 861(1990). c.H. " "\-{,
fluorinationofthe d stereospecific (arral) 6p-fluoro-4-cholestenone-3 of 2 with I resultsin 6a-fluoro-4none-3(15%)astheonlyProducts.
+ CuHrI
(lS,2R)-(+)-[1-Phenyl-2-(l-piperidinyl)propanol-1,Hd
try1
(l)'
(, with This chiral p-aminoalcohol is obtainedby reactionof (lS,2R)-norephedrine 1,S-dibromopentane. addition (czH)zzn with enones.r In the presenceof (1s'2R)Enantioselective conjugateadditionto enonesto form (R)-o-ethyl I (l equiv.),diethylzincundergoes the enantioselectivity ketonesinSl-94Voee. Useofcatalyticamountsof 1 decreases to 60-80% ee.
C/Js..,/',{Bu-r reagent rnceof an electron-transfer 6cwith together rn 21Vo rd Yield a (13%). of Use J-cholestenone-3 radical two APParentlY 33 %. to rf 3
cH.
ll O
CoHrt.p,'1,Bu+ + lCrHr),zn 4}64w ll I CrH, o
(817o ee')
I K. Soai,M. Okudo,and M. Okamoto'Tetahedronlxtters' 32' 95 (1991)
. C ; , m m8. .8 1( 1 9 8 9 ) .
ln the presenceof TiCla, Phenols lr at the orrlro-positionto form 2rr r)nthe siteof substitution.Useof nenrhylglyoxylate,resultsin high
(Phenylthiomethylene)trlphenylarsorane, (C5,H5)3As:CHSCoIIs(l)' The ylide NaI, and CICH2SC6H5' from (C6H5)3As, precursoris generated THF to form epoxides(2) or in THF/HMPA to in with aldehydes The ylide reacts productsrearrangereadily to a-phenyl(3).t The former form phenylthioenolethers aldehydes. to homologated thio ketones,the latter
(l-Phenylthio-l-trlmethylsilyl)allyl-9-borabicyclo[3.3. l]nonene
R O H -sio'' *fC",SCu", RCHO-''rHF ,, X{ H SC6H5 g 2 I. TTIF. HMPA
RcHo--#
R
rf
\
=
2-(Phenylthio)-1,$lc reagentto a similar onc bucr (Z)-2-(phenylthio)l, 3-burrl (a) that undergoeither sylr- r
RCH"CHO
SCoHt 3
' B. Boubia,C. Mioskowski, Letters,30, 6023 S. Manna,andJ. R. Falck,Tetrahedron (1989). I (l). Preparation. Phenylthiotrimethylsilane,C6H5SSi(CH:)r are not readilyavailable.Thusthe reaction O,S-Acetals.2Acyclic O,S-acetals of methylthiotrimethylsilanewith carbonyl compoundscatalyzedby a Lewis acid but the only isolableproductis the formsthe expectedO,S-acetalas an intermediate, dithioketal(8, 352). is basedin part on the ability of trimethylsilyl A new, directrouteto O,S-acetals andsilyl ethers from carbonylcompounds triflateto mediatesynthesisof O,O-acetals (10, 439).Thus reactionof l: I mixturesof a silyl etherand phenylthiotrimethylsilane with an aldehydein the presenceof catalytic to stoichiometricamountsof in 37-93Voyield. Acetoneis amenableto trimethylsilyltriflatecan give O,S-acetals resultmainly in O,O-ketals. but reactionswith cyclohexanone this O,S-ketalization,
cH3cHo
+ (cHr)rsiocH2c6H4cHi
+ I
(cH,)ssioTf cH' cl"-78' t
ocH2c6H4cH' ?""2c6H4cH3 * cHr^ocH2c6H4ct! cHr^scuH, (8lvo\
(9vo)
'R. S. Glass, Chem.,6l,83(1973) J. Organomet. 2 A. Kusche, I. Miinster,P. Keiner,andR. Briickner,TetahedronLetters,32, R. Hoffmann, 467(r99t). l]nonane, (1-Phenylthio-1-trimethylsilyl)allyl-9-borabicyclo[3.3. s(cH3)3 C.HTSC:CHCHT-9-BBN(f). The reagent is prepared in situ from 9-BBN and
n-CrH,,CllO
t (
I W. H. Pearson,K.-C. Lir. r
3-Phenylthio-2-(trtmcrly paredfrom thatof Trod (tl
crt lt-
(cH3)3sicH2cct
ll ISl'3lAnnclatior.r hydes(or acetals)into maN the allylsilane group to ttc radical cyclization via thc r enhance6-endocyclizerir r ofbis(tributyltin) asthc inrti showsonly slight stereocdc
3b{-r.-r.l lnonsne
l:O.
3-Phenylthio-2-(trlmethylsllylmethyl)propene
C.H.S " . \ RCCH2SC6H5
/ (cH3)3si
o 5 c.H.
I
279
C:C:CH".
(2).t This boron compound(l) is an alternative 2-(Phenylthio)-1,3-butadienes reagentto a similaronebasedon titanium(11,377) for preparationof either(E)- or (2). Thus I reactswith aldehydes (Z)-2-(phenylthio)-1,3-butadienes to form adducts (a) that undergoeither syn- or cnti-elimination of trimethylsilaneoxide.
ncnrcHo
Falck. TetahedronLetters,30, 6023
OBBN
n-c'H"cHo+ I ---'-+ CrH,,5^cH, c6H5s s(cH3)3
l) Preparation.r x readilyavailable.Thusthe reaction catalyzedby a Lewis acid ompxrunds tc. but theonly isolableproductis the in pan on the ability of trimethylsilyl andsilyl ethers n carbonylcompounds srlr I etherand phenylthiotrimethylsilrllrrc to stoichiometricamountsof l:-q.l q yield. Acetoneis amenable to resultmainlyin O,O-ketals. bcranone
ocH.c6HlCH'
scuH,
9CH2C6H4CH3
*
cHr^ocH2c6Hlcq
\lq)
(9Vo)
I Letters,32, rnl R Brtickner,Tetrahedron
lcl clo[3.3.Unonane, is preparedin situ from 9-BBN and
a) I
xaoH
n%1
n-crH,,\fcH, sc6H5 2 (AE = 26:l)
sc6H5
n-CrU,,]
\ CHt 2 (E/Z = 50:l)
' W. H. Pearson, K.-C. Lin, andY.-F. Poon,J. Org.,54,5814 (1989).
3-Phenylthio-2-(trimethylsilylmethyl)propene(l). This conjunctivereagentis preannelation. paredfrom that of Trost (11, 258) for methylenecyclopentane
cH"' ll ll llX"l'1".".," "' ) (CH3)3SiCHrCCH2SC6H5 (1) (CH3)3SiCHTCCH2OH cH"'
13tSlAnnelation.t This reagentis used for conversionof 3-substitutedaldeThe conversioninvolves additionof hydes(or acetals)into methylenecyclohexanes. the allylsilane group to the aldehydeor acetalto provide an adductthat undergoes radical cyclization via the allylic sulfide group. The phenylthio group is used to enhance6-endocyclizationover the usual5-ero cyclization. In additionit allows use ofbis(tributyltin) asthe initiator (14,173-174). Unfortunatelythe radicalcyclization showsonly slight stereoselectivity.
B-3-Pinanyl-9-borabicyclo[3.3.llnonane
"H,?
qf.'
ff?"
cH.o
9H, c H . o g o B zl +l
#
Hc\Ar^.At/ i l t cH,foH
cH{Ii!"
fl,
cl
,r"J,"1,i",,
a
This sequence wasusedfor a syntbcsito CHrO-.,/.1r-CHl
t
l
V il CHt (l.l:l)
I Y. Shigemasa, M. Yasui,S.Ohrai,M. Suti, H (1991).
l-Piperidlnocyclopropenol (1, m. p. il-&l Preparation:
I D. E. Ward and B. F. Kaller, Tetahedronlztters,32' 843 (1991)'
Unonane(1), 10, 320-321' B-3-Pinanyl-9-borabicyclo[3.3. to dihydrofuransl(11,469-470)' Thereaction ol propargtl esters Conversion Thusreductionof 3of dihydrofurans. synthesis canbeusedfor anenantioselective hydroxy-l-alkynylketones(2)withMidland'sreagent'(*)-l,provides(4S)-2-buwith (4) followedby treatment tyne-t,i-Oiots-(j)in 84-gl% ee. Monoacylation o
H
o H "H R'c-c=c-1,""",, ;3-c=c-l(cn,), - -'.15 -"*
^,J' oI R R
ll 6
2
3,R=H (84-9l7oee) 4,R=COR I
80' 60-82%lAsB4,c6H6'
f\-J
o e t .-l,cH2)2cr+Y
Cyclopropanonecquivalcnt.r Unlitc c; late, I is stable, easily obtained froo 3d useful substitutefor the ketone. Thus rc providesadductsin which the OH group of I a useful precursorto pyrroles, pyrrolir, r
u),&C1'AO
H...>,ovCHl
*'z\-fcH, ocoR 5 (84-9lVo ee)
quantitativc AgBFr in benzeneat 80o provides the dihydrofurans 5' with almost transfer of stereogenicitY.
I H. H. Wasserman, R. P. Dion, and J. Futtyr
l-Plperidinocyclopropanol
lFI,O.o,'1a.CH,
I
r'-Br
'V,"", l4
cH{& 55%|
o
tl
HC CH,
(Bu,sn),
l n ' Y This sequencewas usedfor a synthesisof the antibiotic (S)-ascofuranone (6). CH,O-z^-'CHr
t \./
l
I Y. Shigemasa, M. Yasui,S.Ohrai,M. Sasaki, H. Sashiwa, andH. Saimoto, J. Org.,56,910 (1991).
tl CHt
(l.l:l)
l-Piperidlnocyclopropanol(1, m. p. 8l-82"). Preparation:
l. &r_r 0991).
o
) .3 r 0 - 3 2 1 .
{'*-l,cH2)2cr# \ -
resr (ll, 469-470). The reaction bl drofurans.Thusreductionof 3rgent.(*)-1, Provides(4S)-2-bur t4t followed bY treatment with OH
I
s
c(cH3)2
'L*"rCvt(cH,), n..m. \-JX -; CV"" J
z
r
/-\
Cyclopropanoneequivalent.r Unlike cyclopropanone,which is difficult to isolate, I is stable, easily obtained from 3-chloropropionic acid (Aldrich), and is a useful substitutefor the ketone. Thus reaction of the silyl ether 2 with RMgBr providesadductsin which the OH group of I is replacedby R. The carbinol I is also a usefulprecursorto pyrroles,pyrrolines,and pyrrolizidines(equationI).
I
OR 3.=H (U-glqoee) R=COR r:* | rgar., c.H",ao"
.
+
H . .s r o - - c H , R
a
\-/
F.rt
-ir% '-
| l) HBt, l4O"
|
2 )H , o -
ocoR 5 tM-917o ee)
lfirrans 5, with almost quantitative ' H. H. Wasserman, R. P. Dion, and J. Fukuyama,Tetahedron,45, 3203(1989).
2t2
Potassiumhexamethyldisilazide
Poly(4-vinylpyridine), 1. Azulenes.r In the presenceof this polymer as an acid scavenger,tropylium tetrafluoroborateundergoes13I2lcyclization with simpleallenylsilanesto form azulenes.Trimethoxymethylsilaneis the preferredscavengerin the caseof higher substitutedallenes.
gameteattractantdictyoptereneB, itr 70t removalof the diallylic proton follotod I SiR""
(\y
-
)BF'-
+ CH.CH:C:C. '
-/
\
' W. D. Abraham andT. Cohen,,{n.Soc..tl
cH,cN,1,25" --------------)
siR3
s6-se%
CH,
R:= t-Bu(CH:)z
I D. A. Beckerand R. L. Danheiser,Am. Soc.,lff,
389 (1989)'
Potassium9-sec-amyl-9-boratabicyclo[3.3. Unonane(1), 14, 2&' A'cN + ArCHO.r The reagentreducesaromaticnitriles to aldehydesat room (12 hours)in75-98% yield. Aliphaticnitrilesarereducedso slowlythat temperature selectivereductionof ArCN is possible. ' J. S. ChaandM. S. Yoon,Tetrahedron Letters,30,3677(1989).
Potassiumhydrogen fluoride, KHF2. a-Fluoro ketones.r Reactionof KHI c,p-epoxy sulfoxides in chloroform rcd the sulfinyl group in -35-E0% yicld. U provideso-chloro ketones.Olah's re4cr yields.
o l l ^ ceHsSAcH, wi cH,
Bzl
Potassiumfluoride. A-DiaZoketonesor esters.r KF supportedin AlzOr is an efficientbasefor diazo transfer reactionsof tosyl azide with active methylenegroups. KF/Alp' cHrcocHrcooCrH,
+ cHrC6H4so2N,#--
T' CH3coCCoocrH5
rT. Satoh,J. Shishikura, andK. lrmt'4
Potassium permanganete-CopPct(ll) r Heterogeneousoxifotion of bb r SO4.5H2Ois recommendedfor bacro;r lactones.This oxidationcanbe highly d
t A. B. AlloumandD. Villemin,Syn.Comm.,19,2567 (19E9\. Potassiumhexamethyldisilazide. Eliminative cyclizntion.r Treatmentof the allylic phosphateester I with this 2, the marine strongbaseresultsin eliminativecyclizationto the trans'cyclopropane
oPo(ocrHs), I
c,H,ff\./-=lcH'
,-l
i",
HOCH(CH2)rOH
KrrS. ( o
fl, A l l
Ho"'v
A CH,
HOHrC
I
Potassiumpermanganate-Copper(II) sulfate
",",O-V.._crL
E an acid scavenger'troPYlium to form azuimple allenylsilanes rcngerin the caseof highersub-
2 gameteattractantdictyoptereneB, in70% yield. The reaction apparentlyinvolves removal of the diaUylic proton followed by an intramolecularSn2 reaction' I W. D. Abraham Am.Soc.,f13' 2313(1991). andT. Cohen,
siR3 Potassiumhydrogen fluoride' KHF2. a-Flaoro ketones,r Reactionof KHF2 and BF3etherate(2 equiv. of each)with c,p-epoxy sulfoxidesin chloroform results in c-fluoroketoneswith elimination of the sulfinyl group in -35-80% yield. Use of MgCl2 in this ring-openingreaction oflow providesa-chloroketones.Olah'sreagent(HF.pyridine)is not usefulbecause
9 r1 9 8 9 ) . r D e( l ) , 1 4 , 2 & . at room nrlc nitrilesto aldehYdes that slowly so reduced are nrrnles
yields.
o
il *"t,i"'Ei."'! cuH,S. 7o1 rc", --',* 19
6-- '19E9).
r cg,
CHt
ll;O, is an efficientbasefor diazo lcne grouPs. N" ll'
r^
l-x+
cH.coccoocrH,
/cHt
fT. Satoh,J. Shishikura, Chem.Pharm.Bull',3t' 1798(1990)' andK. Yamakawa,
Potassiumpermanganate-Copper(Il) sulfate. Heterogeneousoxiilation of diolsto lactones.r A mixture of KMnoa and cuoxidationof 1,4- and l,5-diols to for heterogeneous SO4.5H2Ois recommended lactones.This oxidationcan be highly selectivesinceprimary alcoholsare oxidized
t ,1989). .Ir Y'-3
KMno. /cuSo.' 5Hro
otulcHrl,ou--
"iL
llrlrc phosphateester I with this r ra ns-cycloproPane2, the marine
!",
SOPO(OC'H,I
$/.7'"' l
t Ho"'\/
l
A CH,
HOHrC
cH,$o
2U
Potissiumperoxlde-Phenylphosphonlcdlchloride
more rapidly than secondaryones. Oxidation of isolatedprimary alcoholsto acids with this systemis not useful becausethe reactionis very slow unlessa baseis also added. Oxidation of alkcnes.2 A well-ground mixture of KMnOr/CuSOr'SHzO(2: l) suspendedin CH2CI2containinga trace of t-BuOH/HzOeffectsoxidation of alkenes at 25o to c-diketonesor c-hydroxy ketonesin modestto high yield. The t-BuOH/ H2Osolventis usually crucial for successfuloxidation. In somecases,epoxidesare the major products.
a)
'Y. H. Kim, S. C. Lim,and H. S. fr
Potessium peroxymonculfrtc (O! vic-Tricarbonyl systctr.r A r Oxoneoto cleaveylide double bcd oxygenis less selectivethan Orc' of acid chlorideswith t-butyl (tripE bis(trimethylsilyl)acetamidc(BSA). dized by Oxoneo in reactions cerrb
KMno./cusor.5H,o(4:2), ft' 50% \J
\_/
,H
- lm% / cusq. sH,o(4:2) JKldnq
C6H5C=CC6H t
"s)
a--Yt' * KcJ,\ 5
\-*u
? ?
;7
C6H5C-CC6H5
' C. W. IeffordandY. Wang,J.C.S.Chen.Comm.,634 (1988);C' W. Jefiord,Y. Li' andY. (1990). Wang,Org.Syn.,submitted 2 S. Baskaran, Or9.,54,5182(1989). J. Das,andS. Chandrasekaran,J.
t Oxidation of alicyclic taaa dizedto lactonesby Oxonco(f) En mixture. Efficient stirring is m about 80% for 5- and Gmcmbcra ketones.
cll
Potassiumperoxlde-Phenylphosphonicdlchloride' KO2-C6H5P(O)CI,(l). Oxifutive desulfuration of thiomidcs,t The reactionof thesetwo reagentsgeneratesa peroxyphosphonicintermediatethat converts thioamidesinto the corresponding amidesin9O-95% yield via a sulfine intermediate.
S O il JH'l',,ni' 1 1 . " RcNR'n'+ s, + c6H5P(oXoK)2 ndNn'n'* 1
G
t H. H. Wasserman and C. B. Vr. Tel 2 H. H. Wasserman,V. M. Rd.llo. Il (1989). 3 M. Hirano. M. Oose, and T. Mair
Potesslum Peroxymonosulfete 2t5
rlated primary alcoholsto acids 3 r'ery slow unlessa baseis also (2: l) a of KMnOr/CuSOr'SHzO H;O effectsoxidation of alkenes lest to high Yield. The t-BuOH/ ioo. In somecases'ePoxidesare
-vo
rY. H. Kim, S. C. Lim, and H. S' Chang,J.C.S. Chem.Comm.,36(1990)'
Potassiumperoxymonosulfete (Oxoneo)' vic-Tricarbonyl syslcns.r A new route to this systemdependson the ability of Oxoneoto cleaveylide double bondsmore readily than C-C doublebonds. Singlet oxygenis less selectivethan Oxoneo.The ylide precursorsare availableby reaction in the presenceof of acid chlorideswith t-butyl (triphenylphosphoranylidine)acetate bis(trimethylsilyl)acetamide(BSA).2 Even a trisubstituteddouble bond is not oxidized by Oxoneoin reactionscarried out in a two-phasesystemof benzene/water' p(C6H5)r
-,/-o, .uro.'t",o to,t,
-Y" [.*,r,.
a'-Yt'* [(cu o alJl,.',),# ,,"fY\oc(cH3)3 H.c) 8ffi
*
-Ao
o
) o l l l
:-cc6H5
H,c)
Y. Li' andY' I rl9t8);C. W. Jefford,
atAYoc(cH3)3 o o
oriddion o! aticyclicketoncsto lactones.s cycloalkanonesin cHzClz are oxidizedto lactonesby Oxoneo(1) mixed with slightly wet aluminaas a heterogeneous mixture. Efficient stirring is necessaryto obtain reproducibleresults' Yields are about 80% for 5- and 6-memberedketones, but are low with higher-membered ketones.
. 9r. 5lE2(1989). (f). ldc, KO2-C6H5P(O)CI, rcactionof thesetwo reagentsgentverts thioamidesinto the corres-
| 0xone | rnr, x,o
"t"' r.Ar,o, /-o, cH'c\ >|
FO
7g% \-/
rrmediate.
+ S, + C'H,P(OXOK),
I H. H. Wasserman Letters,3f , 5205 (1990). and C. B.Yv Tetrahedron 2 H. H. Wasserman, V. M. Rotelto,D. R. Williams, and J. W. Benbow,J' Org',54' (1989). 3 M. Hirano, M. Oose,and T, Morimoto, Chem'lztters,33l (1991).
Pyrldlnlun poly(hydrogen fluoride)
(q.-Pyridine)tricarbonytchromium, O
OH
(1).
0
C(col" Preparation:
/1,
Y
,N
-
I)T
s(cH3)3
,si(cH3)3 (
PXL. cl{.o-
-{lrF/h.
c(co).
si(cH3)3
"o.na
, I
s(cH3)3 Cr(CO), 2
Rcgioselcctivclithiation.r This complex undergoesselectivelithiation at the ortho-position,which can be trappedby methylationto give (2-methylpyridine)tricarbonylchromium.The disilyl complex 2 undergoesselectivelithiation at Cr becauseof steric effects.Reduction(DIBAH) of I provides(1,2-dihydro-pyridine)tricarbonylchromium(3) after quenching(MeOH). Reactionof I with RLi followed by alkylation with CHJ provides the complex 4.
d"" d*",, w \+/ Cr(CO), 3
I J. H. H. Meurs,D. W. Soptrcr,rd W" I ' G. A. Olah and X.-Y. Li, Synlcn.257(
Pyridinium p-toluenesulfonetc ( ryll a-Alkoxy carbonyl cospotdt.l methylhydrazonesof aldehydesor k presenceofthis reagentto form tbc co is more effectivethan alkyldumioun
C(CO)3 4
IS. G. Davies (1989). andM. R. Shipton, J.C.S.Chem.Comm.,995
(cHr)rN\^, o
i i l s\-S-cn
l
I
Pyridinium poly(hydrogen fluoride). Oridativc fluorination.r Reaction of phenol with PbO2 (2 equiv.) and HF/ pyridine (70130,w/w) in CH2CI2at 25o providesthe dienoneI in 30% yield. It can undergoMichael addition and aromatizationto give substitutedp-fluorophenols. Arenes are not oxidized by Pb(IV) reagents,but can undergo anodic oxidative fluorination. In this caseHF/N(C2H5)3is the preferred reagent. Olah and Li2 haveprepareda solid form ofthis reagentby reactionofanhydrous HF with crosslinked poly-4-vinylpyridine. It is comparableto pyridinium poly(hydrogen fluoride) for hydrofluorination of alkenesand alkynes and fluorination of alcohols,but is easierto handle.Work-up of reactionsrequiresonly a simple filtration, and the spentreagentcan be regeneratedwith HF for further use.
(CH,)TI N
"A-c 2
-M(
(l) KCN DMF -+ 9Ma
S|(CH.)r {
I e0%JH2' Pdrc
su.NF , ,
SirCH.), 0r.
OH
I dcrgoes selectivelithiation at the rion to give (2-methylpyridine)trirlo€s selectivelithiation at Cr beprovides( 1,2-dihydro-pyridine)trilcaction of I with RLi followed by
R
.1
,\CHt
' J. H. H. Meurs,D. W. Sopher, Chem.Int. Ed.,2t,927 (1989\. andW.Eilenberg,Angew. ' G. A. OlahandX.-Y. Li, Synlett,267 (1990). Pyridinium p-toluenesulfonate(PyH.Ts). a-Alkoxy carbonyl compounds.r The a-p-toluenesulfinylderivatives(l) of diof aldehydesor ketonesreact with a variety of alcoholsin the methylhydrazones (2). PyH'Ts c-alkoxy hydrazones presence ofthis reagentto form the corresponding is more efiectivethanalkvlaluminumhalidecatalvsts.
(COt. a r . e95 (1989).
(cH.LNy*
l-o",,,fr...-. I .",o" *L "A-3-"'n, "\"lr;g
'ry
bH.rs,|
I
ol *ith PbO2(2 equiv.) and HF/ rhe dienoneI in 30% yield. It can fve substitutedp-fluorophenols. bur can undergoanodic oxidativc ferred reagent. is reagentby reactionof anhydrous somparableto pyridinium poly(hyx and alkynes and fluorination of nions requiresonly a simple filtra'ith HF for further use.
(cH,LN\N CuCl",HO, THF _,'
"A--*"' \ T N
-fi".,"., o
li
uA't-ocH' 3
't
/N(CH3)2
ar
, / \ . /
cH,oH. ( PvH.Ts
'to%
\
FN
\--< ,/-ocH,
-N(CH3)'
288
Pyrylium perchlorote
The productcan be deprotected by CuCl2(7, 128).The alcoholcan be primary, secondary,or tertiary, as well as allylic or benzylic. I P. Pflieger, D. Weissbart, andF. Durst,Tetrahedron ktters, C. Mioskowski, J. P. Salaun, (1989). 30,2791
2-\
explosive. Pyryliumperchlorate,| . ll clo4- (l), potentially
\o /
QZ,4E)-Dienals.t This salt reactswith organometallicreagents,particularly Grignard reagentsand alkyllithiums by addition at C2to form an adductthat undergoesring openingto a (22,4E)-dienal(equationI).
Rhodium(Il) carboxyletcs. rl Cyclizationlcyclo&itbt ( (l)t of l-diazo-2,5-hexanedionc provides r 6r an adduo Rhz(OAc)r 2, which can be usedas a pnasurlF
O
l
il
^ (Dr+cuH,Li *,,-..",Aa"o F.:Ql
cH,c.clt.clq I
(-97:3\
K. Taylor,J.C.S.Perkin/,683 (1989).
o
r\
\!*,'o
\-\
'cJ{.
2,5-Disub stitated 3 (2 Hhfr,tt tion into an adjacentetherC-H bo furanones.This reactionwas uscd1 (2) from p-alaninevia (R)-2-brm
o \-^
R'<
b+,
canbeprimary, l18t. Thealcohol rylrc. tn. and F. Durst. Tetrahedronlztters,
antrallyexplosive. Eanometallicreagents,particularly rr C: to form an adductthat underrlr.
Rhodium(Il) carboxylstes. Cyclizttionlcycloaddition route to oxapolycycles (13, 266). The reaction of l-diazo-2,5-hexanedione(l)r (or of l-diazo-5-phenyl-2,5-pentanedione2) with Rhz(OAc)rprovidesan adducta that reactswith an aldehydeto form the ring system 2, which can be usedas a precursorto brevicomin(3).
o
=;t
CuH5
o
i l t l Rh'(oAc)'> cHricHrcHrccHN,
-,^,/\ |
cHo
I
(-97:3) a
7 S Perkin/,683 (1989).
r*J",".""o o \\ \
FH,
\./
,-\--\ /
\
\
o
-
\./ )-l
8
r)zn(orr),, HSCH,CHTSH 2t Rmev Nr 5
%
\ 'crH, 3
CrH,
= 2 (exolendo 2 :l )
2,S-Disubstituted3(2il)-furanones.3 c-Alkoxy diazoketonesundergo insertion into an adjacentetherC-H bond in the presenceof Rh2(OAc)a to form 3(2H)furanones.This reactionwasusedfor a synthesisof opticallyactive(*)-muscarine (2) from o-alaninevia (R)-2-bromopropionic acid (l). O \,o*, R'-{
tO^*,
O -\----'. Rh,(oAc). cH,cl,> I \ *-t* R'4olR' (cisltrans = 8-3:l)
Rhodium(II) crrboxylrtes
-]Uq
cH. "XcooH
[-cH,.acoou -------l
Br H
CH"
\o1cu,y,oBz!.1 64%
1nr'
COCHN,
(:
"X,"",,,or" lr*Jnr',rol"l.
1 o\-
-f
+
.ftrcn.l" .
/
^"Aox.t Lrrr
.-v.Er.,^ scvcnrstcPs
""f
f-\
o
.H'oBzl
( c i s l t r a n s= 8 : l )
2
Furans.a Highly substitutedfurans can be obtained by Rhz(OAc)r-catalyzed reactionof 2-diazo-I,3-dicarbonylswith arylacetylenes.A typical example5is formulated.
o
Rhr(OAc).,
ll
+ Cuttrc-cH #t-)u% cuHr-.,'o\-cH, cu,C-c-cooc2H5 ll \\ ll
catalytic amountof R}z(OAc)r ir provide 2, which is oxidized r additionof NaHCO3(3E%yicld) Rearrangement of Ntitnlr lation of primary aminesfollortt lar solventsat 80-1fi)' to forn presumeddiazoalkaneintcrmcdi which undergoesrearrangcrrcd mild, nonbasicversion of thc cL
N2 RI
cooc2H5
ur* r,o-1"n,oy,a.H,c=cH J 3,4-(CH30)rC6H: ---.zo1_- cH,
(D
\
,/ R2
!
CHCH,N(NO)Ac: _tor
\tl cooc2H5 azide, The report stressesthe advantagesof p-acetamidobenzenesulfonyl It for preparationof diazocompoundsby diazo-transfer. N3SO2C6H4NHCOCH3-p,6 by-productis removedby simpletrituration andthe sulfonamide is safe,inexpensive, with H2O. Carbenoid-monothiophthalimidecoupling.T The key stepin a synthesisof an and alkaloid3 involvescyclizationof an N-aziridinohydrazone isoindolobenzazepine group catalyzedby Rhz(OAc)r.Thus treatmentof I with a a monothiophthalimide
,o--lV ("-\z\
\,{
,ocH3
Rh,(oAc).,
"/--l-\-o"". H4
il"
N N
\J
A
/ \ . cuH, coH,
This reactionis appliceblco (secondexample).
Rhodium(Il) carboxylates
CH3\ /COCHN2 .\ 'O(CHr)rOBzl
, iffir --;lEzl
("
Br
ocH3
or*J*n,,oo",.
")a
ocH3 2
ccgr
laa
cH,
o^cHroBzl (cisltrans = 8: l)
n be obtained by Rhr(OAc)a-catalyzed ylacerllenes. A typicalexamples is for-
R: '){.)..
'-=
cuH'-zo1--CH,
\\ ll 4"oo",",
3
catalyticamountof Rh2(oAc)ain refluxingtolueneinducesa carbenoid coupringto provide 2, which is oxidized to chilenine (3) by dimethyldioxirane followed by addition of NaHCO3e8% yietd). Reanangementof N-nitrosoamides.t N-Nitrosamides(l), prepared by acety_ lation of primary aminesfollowed by nitrosation,are known to decompose in nonpolar solventsat 80-100o to form arkyl acetateswith elimination of nitrogen.eThe presumeddiazoalkaneintermediate(a) can be trapped as a rhodium carbene(b), which undergoesrearrangement to an alkene(equationI). The overall resurtis a mild, nonbasicversionof the classicalHofmanndegradation of amines.
(D
R''\
a
l-n' l"\^-----
-.
/cHcH,N(No)ec;fo+ | )cHcH:Nz
R'
R
Rh,(oAc).
#
'
\
l
l
,CHCH:RhLl
R
LBo I
,
J
b
I J
oi p-acetamidobenzenesulfonyl azide, I drazocompounds by diazo-transfer. It pr(\juct is removedby simpletrituration
RI
,rc:cHz R, )
L g.' The key stepin a synthesisof an hzationof an N-aziridinohydrazone and lh;rOAc)a.Thustreatmentof I with a
f
| l!
2gl
f,cHN(No)cocH3----->t /,,fcu, |
I
78%
\-/
i){ar..
\_/
Clr !.H.. I
-;--I \,4--{
N-NO
--+ fz^:zz\z,COOH I 87% *Cn"
This reactionis applicableto nitrosolactamsto provide ro-unsaturated fattv acids (secondexample).
Ruthenium(Vlll) oxide
30' 1491(19E9)' t A. Padwa,R. L' Chinn' and L' Zhi' Tetrahedron^Lett?rs' (1988)' Org"''53"2875 l' Ztti' 2 A. Padwa,G. E' Fryxell' ""0 f-' 3J.Adams,M.-A'Poupart'il:";#;;;'str''"irt''ll"o"it"'""0R'Frenette'Tetrahedron (1989)' Letters,30,1749,1753 44' 3343 (1988)' 4 H. M. L. DaviesonOf i ni*ines'Tetrahed^ro'r' (198e)' svn''submitted
cr#2,cH
o tl
cHroc-
org' w. R. ;;;i;;il"ii" -o l' s'-naum' s H. M. L. Davies. (1968)' 3610 33-' org" l' woff' e' wl and 6J. B. Hendrickson, 30' 2747 (1989)' ? F. C. Fangand S' J' D""#;ftky''it;rahe"dronl'etters' {1990)' s A. G. GodfreyandB' Aantt' im' Soc'' ll2^'^3717
l' org'' 54'5996(1989)' , fr. iir"i.io.t andB' Ganem'
chloride' with aSo6ium([D -"'"iiirin drosilylationof methacrylates nekne trimcthyhihl acetals.'t to di' .Hl'. resultsin rearrangement iili"ii.roul.m"ride cataryzeo trimethylsilane yield' trimethylsilyiacetalsin 65-85% ."iir*"*n" Rhclr'6HP
-f$;-+ (cH,),siH
,CH,
cH,:c(--'
.-^rOttttt"' (cH')'c:c\oR
* (1990)' I A. RevisandT. K' Hilty' J' Org'' 55' 2972 obtained as a bright Rh2(pfb)o'This reagentis acidand Rhodtum(Il) perfluorobutyrate' Jith perfluorobutvric
solidby'"il:il,fi;ti"iiiinrtonc)a yellow-green
'0"
Tltffi
thu enective I Rhodium(Il) n"lo:'::^Y:::: ''1.H:"-with trialkylis o/ Rssin' or "tondoty alcohols
primary asa catalystio' t"u"tion of Rhz(OAc)r areinertundertheseconditionr' iertiary-alcohols silanesat25oto form ,ilyt'r;;;;;. t-butyldimethyl"i.in"fr canbe realizedwith "nnt#;il;.w reactions Selective ,irun"uot not with dimethylphenylsilane' J' P' J' Lewis'andM' M' Pearson' I M. P. Doyle,K' G' High' V' Bagheri'R' J' Pieters' (1990)' Ors.,5S,6032
(rutheniumtetroxide)' Ruthenium(Vlll) oxide but sinceit ir Ruol useful for this reaction' Catatytico"aaotio'i oi oiiin"} is amountof Rucll generatedin-situ from a catalytic ir"uroullv lt toxic, and of r expensive (tt' iSZ-qs' ' In another-version with NalOr u, tr'" 'toi"t'io'n"t'ic-oxidant of acetaldehy& it'e primary oxidantfor autoxidation catalyticreaction,O, i' "'"J"'
"r' io Ruoa'ThisRuoz-CHrCHo-or o"io,*t'i"i ii"" "-loi'i' nuo' in of terminJ toperacetic cleavage usefulior oxidative "t ;dl;**ularly in acetone system carbonyl compounds' alkenesand o, p-unsaturated
CH, CH, I K. Kaneda,S. Haruna' T. h
Ruthenium(VIII) oxide O2, RuOr, CHTCHO
g). l19l (1989). l q S Et *r. .na R. Frenette,Tetrahedron F,t , 1988). (1989)' ir Srn.. submitted tXer a. :'17 (1989).
C,'H,CH:Ct' lO#4 o
c
ll il'
H
cH3oc-e-CH,
o
CH,
os(cH3)3
CH,r.C:C\
OR
bright reasent is obtained as a acid and ,i. oli,rt p€rfluorobutyric thao obutvrateis more effective trialkYl*.onAutY alcoholswith conditions' these under inert I are J realizedwith t-butYldimethylJ' P J trwis, andM' M' Pearson'
sinceit is rful for this reaction,but of RuClr amount , f.o* . catalYtic of a version roj-roll. In another acetaldehydc of n, fo, uuto*idation lo RuOo.This RuO2-CH3CHO-O2 of terminal lo, o*iaatine cleavage s.
o
o
lJ l,l_ cH3oc-CcH3
3 f"'
J;-
/
,
a5%-
0r
with ilrlation of methacrylates to diresulrsin rearrangement
Crfl2rCOOH
CH,CCH,C_CH,COOH CH,
I K. Kaneda,S. Haruna,T. Imanaka,and K. Kawamoto,J'C'S' Chem'Comm" 1467(1990)'
(ID AT,CH:
Samarium(Il) iodide. Pinacolcouplingofdialdehydes.|1,6-Dialdehydes,obtainedbyperiodate whentreatedwith SmI2undergocouplingto ciscleavageofcyclohexane-1,2-diols, with Ticlr diols in good yield. Similar cis-selectivityhasbeenobservedin coupling
jifr'
aYo"
+ 'rans-isomer
8r% a)"'ot V"'oH
9on
yield and diastereoselectivity(d intramoleculardelivery of hydril the hydroxy ketone and the ddctY less effectivethan SmI2, whic't d anti-a-methyl P-hydroxy kaos
e3:7
o H o
i-n\An' OR
OR
-,.,, - l A"'o" I "% \,/"'ott
/."o |
\.,,cuo l OR
,-*
o H o
l OR (99:1)
cll,
andZnlCu(15,317).Thepresenceofc-alkoxygroupscaneffecttheorientationof of the substituents' the cis-diol in favor of the diol with an orientationoppositeto that derivacarbohydrate of inversion a diol This pinacol coupling can be usedto effect tives as shown in equation(I).
firanose - cycloPcnota.' to a carbocycleinvolves ratitr t)(cJrvrr 2) PE r/*r
/'o"J'oH
t --:----:),
(D RO'
"'oH
l
o''\4osiR,
l) HIq 2) SmI.
cH,+ci
45%
RO"
CH, I
c-o-34.7"
cro- 50.4o
to the correReductivccouplingof imines.2 Aromatic ketiminesare reduced spondingsecondaryaminesbySml2,butaromaticaldiminescoupletol,2-diamines (equationII). between anti-lr3-Dio I monoesters.3SmI2caneffecta Tishchenko-typereaction in high anri-diol an of monoester a afford to aldehyde an a $-hydroxy ketone and 294
cHo ( t l
o_Y cH3to CH,
Samarium(Il)iodide
295
Ar'\_,NHAr2 2S'L
(II) Ar'cH:NAr'
,
I
82_93%
Ar'ANHArt (dl, meso\
ilch1des,obtainedby periodate ith SmI2undergocoupling to cisobservedin couplingwith TiCl3
+ t-1
yield and diastereoselectivity (anti/syn, )99:l). The reactionprobably involves intramoleculardelivery ofhydride from the aldehydeto the ketonevia a complexof the hydroxy ketoneandthe aldehydewith the samariumcatalyst.SmI3and Smcl3are less effective than sml2, which should be freshly prepared.Reductionof syn- and anti-a-methylp-hydroxy ketonesshowsequally high asymmetricreduction.
o
trdns-isomer
tl
-
*"..
o H o
t t l
t-PrlYRr+
RCHo
o o H t :
t't, 85-9%
, t-prv\Rl antilsyn>99: I
o
tl
RC..
o H o l i l
i-nYn'
: 1 ,
Nrpscan effectthe orientationof posite to thatof the substituents. derivalrersion of carbohydrate
o
"/-)
l
I
r'\r^on I OH
cr-,- 50.4o
iminesare reducedto the correildiminescoupleto 1,2-diamines 'ishchenko-type reactionbetween pno€sterof an cnridiol in high
s'!-r
85-95%
:
I
i-nA4n'
|
CH,
CH,
antilsyn>99 :,I + cyclopentanes.a One method for transformation of a carbohydrate \ranose to a carbocycleinvolves reaction of a lactol (1) with a wittig reagentfollowed by
aoy-o"
-o
o o H
RCHO,
t l oi\z^ostn, cn,-|o
| ) (C6Hr)3P:CHCOpH, 2' PDc (73%\
(74%,
CH, I
coocH3
gHo Ccoo",
o''\Ao''*, cH,Io CH,
l) SmIr 2) BU.NF ---t 69%
o''(.!oH "r,*ot CHt 3
295
Semarium(Il)iodide
of 2 inducedwith SmI2gives oxidationto an aldehyde(2). Intramolecularcyclization of cyclizationdependson the a singlecyclopentanl3 (99:1)' The stereochemistry "f doublebond. A cis-alkenefavors a syn-product' g*t*,w C o u p l i n g o f k e t o n e s w i t h a l k e n e s . s T h i s r e a c t i o n c a n b e e f f e c t e d wone ithSmlz be an activatedterminal "u,ufr.a uin-rrrpe (14,280-281)' The alkene.can diene' or a silyl dienol ether' tiffr:CffOec), a conjugated
o
:-l'V:.1-^^
i*^:l
il
+ cHr:cHoAc igiL c6H5(cHr)rccH, I
+ crq:f
!", gg :cH,
c6Hs(cH')'ccHpHpAc
d
2:l
cH,
Ho. ,(cHz)zcuHs CHrt( l +
s5%
'
smr.
*#
/(ct')lR
v
-oH
n = 1 , 2 'R = H ,C H r
tc:o
?
*r'--u
-
particularlyefficientwith o-sot hydroxy ester requiresa cerbox/ Dehydroxylationof (R,R)-on this caseethyleneglycol is 6c g OH I Pr-r-OOC-./,\CGi.i
Alkene synthcsis.) Thc tcy r involves reductive eliminetio c recentmodificationinvolveseliri (equationI).t Both synthescsrrc alkenesand conjugateddienesei tion of (E)-alkenes.In a direcro thanwith Na(Hg). CH
R|R2c-o-R|CH(CN)R2.?Thecyanophosphatesl,readilyobtained byre. and LiCN (f4' 187-188)' are action of ketoneswitt, iietfryf phosphorocyanidate in THF at 25o to nitriles in 8(F (l reducedby SmI2(r*r"rriuna '-SuOH equiv')
R'.
OH I
OH
coocrH5 ,/------COOC,H.'
I
cH3(cH2)lcHcoocll!
I
\-A--.,/\-Z
alkyne group.6 SmI2 can effect Reductivecyclizttion o! carbonyls with an couplingofaldehydesorketoneswithanalkynesubstitutedbyaphenylorethoxycar. bonylgroup.AdditionofHMPAandt-butanolisrequiredforsatisfactoryyields.
(cI,L--R \---so
OAc
crHrooccHrcHc0cJ,
""'\7"f"' ::'.tZi": c.Hr(cHr)i'cH'cHCH:cH'+ cuH'(cH2)'ccH'c
CH,
100%overall yield. The sam sGq enonesin75-97% yield. Deoxygenation of adbry(l fectedby smlz-HMPA in THF ri
R' (c,H,olf(o)cN NCVOiI(OCrH'), ,.6!tt"""to LicN >
8o-loo% R'AR' I
R'
N
HS-'/--\ ( l ) R C H. . X * "N" \ / J
*a",to,{)
nt+
f", !
Semarium(Il) iodide
o of 2 inducedwith SmI2gives oi clclization dePendson the prcxJuct. ion can be effectedwith SmI2 r br an activatedterminal one I ether.
lfi)% overall yield. The samesequenceprovidesc,p-unsaturatednitriles from c,penonesin75-97% yield. Deoxygcnation of a-alkoxy(hydroxy) esters.t This deoxygenationcan be effectedby SmI2-HMPAin THF with an alcohol as the proton source.The reactionis oAc
smt,,HMPA,THF
cH3(cH2)4cHcoocH3 --#"CH,, oH \ / ,H.rCH")rCCHrCHtOAc
lfl
cH.. ' \ / QH QH, | + C.H5(CH,)'CCHzC:C(CI{} l:l
297
OH
cH3icHr)rcoocH'
smt} HMPA, THF
I
c2HjooccH2cHcooc2H5 tt+*%
c2H5ooccH2cH2coocH3
particularlyefficientwith c-acetoxyand a-methoxyesters.Dehydroxylationof an chydroxy ester requiresa carboxylic acid (pivalic acid) as the proton source. Dehydroxylationof (R,R)-tartratesby this methodgives only (R)-malates,but in this caseethyleneglycol is the preferred proton source.
HO.
] { Y.(cH2)2c6Hs \.'^\r'^\
i
l
/'.-)\2
l
tr.tne grouP.6 SmI2 can effect ututedby a PhenYlor ethoxYcarqurredfor satisfactoryYields' cooc2H5 -_) {, '. ,-R 6oH
OH
t" ,
smlr R'. -.suoH -CHCN , \0- lm% "/ R'
(R)
OH
Alkene synthcsis.e The key stepin the Julia synthesisof alkenes(11,473-475) involves reductive elimination of a p-hydroxy sulfone with sodium amalgam. A recentmodificationinvolveseliminationof a p-hydroxyimidazolylsulfonewith SmI2 (equationI).' Both syntheses are particularlyusefulfor preparationof disubstituted alkenesandconjugated dienesandtrienes.Both methodsof eliminationfavor formation of (E)-alkenes.In a direct comparison,a higheryield was obtainedwith SmI2 thanwith Na(Hg).
cH" fiates l, readilYobtainedbY re: a n d L i C N ( 1 4 , 1 8 7 - 1 8 8 )a' r c LnTHF at 25o to nitriles in 80-
OH I Pr-t-OOCv,,\COO-r_h
sml,-THF
I
Pr-i-oocY^coo-t-Pr ry;I'olI
i",
t -
"s-/*)
RcHrs\'N) N(c2H,)3 '!r12n,,3, \J
(r) RcH,x. \J
cH" tI
o
"
RcH,so,Y*) liil{,H" -Yt\) iiJ/
-
n'Aon
crc#.cqH
l f",
i\J
-
*sF
R,cH:cHR
(Erz=3-8:t)
Samarium(II) iodide
Arylradicalcyclization.|oSmI2inHMPA/THFat25ocaneffectcyclizationof l-allyloxy-2-iodobenzenetoaSm(III)intermediate(a)thatcanbetrappedbyelecthat a similar mecha,ropfrit"r, including aldehydesor ketones'The report suggests nismoperatesintheBarbier.typecoupling:generationofanalkylradicalfollowed to form an adductthat is by formationof RSmIz,which addsto a carbonylcompound hydrolyzedto an alcohol. t
chloromethyl ether, 2,6.xylyl a,c,-Dihydroxy ketones.|| Reactionof benzyl -l5o in an intermediaE(a) that results at isocyanide,and sml2 in THF/HMPA of u,c'-dihydroxy imines such reactswith aldehydesor ketonesto form derivatives by hydrolysis' This method ketones as l. Thesecan be convertedto c,c'-dihydroxy p-ribulose (3), page299' (2) to was usedto convert a protectedo-glyceraldehyde
also reactswith aldehydesor ketom ro p intermediate(a) even reactswith e$cfJlto hydrolyzedto 1,2,3-tricarbonylcompord
smr,. i il' I
rHF/HMPA ) BnOCHTCI+ XYNC
["ocu,i-s.tJ I
*" lli:tT6:ff J
l-*r.. ,
CrHrBr
--srl,^. I **^, + 2XyNC I
n. i
l c' Ltn'
Xy N tl BnO.--A---,OAc
I CrHt I
*, X
o
W"#Oei'-""" vic.Diketones.l2Thereactionofethylbromidewith2,6-xylylisocyanidc resultsin an intermediatc' (XyNC, 2 equiv.) and SmI2(2'5 equiv') in THF/HMPA formulatedasa,thatistryOrotyzeabyH2Oat0otoadiimine(2)'Theintermediatc
N
N
i l I cI.c-c It
J
Review.rt Soderquisthas revicsed il cnces).
Samarium(II) iodide
of tlF at 25" caneffectcyclization elecbY trapped lc ra) that can be mechaDon \uggeststhat a similar followed radical nrtrtrflof an alkyl to form an adductthat is c(rmpound
Q" o.. I
cHo OH
Smr
,
at V " X -j--- "\-\ri..-_-
Y o H o oBn-------+no..'$,onn
: OAc
: OH
( 1 0 l: )
J",,.""
n,n'
./V. R'coR'-
----------> [| 65-s6% \.r\d
ll il
\
\,
/
R'
1o\1o" \
2
l--t
/'cH,oH
OH OH azr I chloromethYlether, 2,6-xYlYl (a) that results in an intermediate such imines dres of c,c'-dihYdroxY method This tetonesby hydrolysis' de r2) to o-ribulose(3), Page299'
X
v
3
also reactswith aldehydesor ketonesto providea hydroxy diimine suchas 3. The (s) evenreactswith estersto provideacylateddiimines,which can be intermediate hydrolyzedto 1,2,3-tricarbonylcompounds(probablyas the hydrate).
l
' ,.o.",1-r.r'l " _ l *.fllH,:ff Xy N
a"o-..,\onc
-l ,.,,ru* *F/HMPA ) ["t.r,t't' + 2XYNC c'H'Br
Xv Xv N
N
l l l l "o, crHsc-c-H )
Lrni[rt:--J*
,"iG"
CtHt
Xv Xv
Hro. I ? o' ii ii - c-Q -"i{__) c,",c .,",3
:*-
t isocyanide l t,romide with 2,6-xylyl 'HF HMPA resultsin an intermediate' ' I tr ro a diimine (2)' The intermediatc
n
Review.rsSoderquisthas reviewedthe usesof SmI2for synthesis(51 references).
Silver perchlorste
iltilto + CHTCOCOOCTH, d
ililil
CrH5C-C-COCH3
tT"
--+
o o o
ll ll ll
C2H5C-C-COCH3
c2H5s OH c2Hrs
.o
1
H
,,*l(-(""' J\,IruH,
N
N
)-
Samarium(Ill) chloride-Chlorotrimethylsilane and even a 1,3Cleavageof acetals.r A variety of acetals,1,3-dioxolanes, ( dioxane,canbe cleavedby reactionwith SmCl3andClSi(CH:)r I : l) in CH2C!2, to be (CH:):Si+SmCL-.DiTHF, or CH3CN.The effectivereagentis considered can be cleavedby useof only a catalyticamountof SmCl3combined methylacetals with 1.5-2 equiv.of the silane.Yieldsare generallyabove80%. I Y. Ukaji,N. Koumoto, Letters, 1623(1989). Chem. andT. Fujisawa,
Silver perchlorate,AgClOa. Cyclizationofhydroxy dithioketals. Nicolaouet al.t haveusedthis reactionfor constructionof oxocenes.The most satisfactorymethodinvolvesactivationof the sulfurof the startingmaterial(l) with AgClOr to producean oxocenederivative(2), (AIBN) followedby C-S cleavage.This secondstepcanbe effectedwith (CoHs):SnH with is cleaved which then or sulfone, sulfoxide or by oxidationto thecorresponding
(C2H5)3SiH/BF3.O(C2H5)2. Thc pn cyclization. Another limitatioo ir d nine-membered oxocene.
I K. C. Nicolaou,C. V. C. Pru.d. C.-
l r r , 5 3 2 r( 1 9 8 9 ) .
Silver trifluoroacetate, AgOCOC Regio cont roll ed alkt ldo..l tion of 2-(trimethylsilyloxy)furea 0 rr ts
ll \\ rsc' (CH,)"SiO-'\^,/ t
-1!r
Silver trlfluoroacetete
lH
1r9" t'o
o o o il il ll
, crurc-d-cocH,
c2H5s OH c2Hss
o
301
Agclq, NaHCOI ---_--#CH,NO, 93%
l4-'r7*',
7 t %l l
ll
J\,AIH,
l-\ \
/1 N
ff- - - lr)clc6H.cqH 2) (C?H,)iSiH/BF,O(C,H,)z J
/
H N
\ / / -2---1 coocH3 CrH, y'r,tafu11s7s, 1125(1991). t ,1990). i{r- r1990). 9t9t ,.,1.r)n lttters, 30, 2837(1989). Chang,iDid.,31, 4765(1990). 10. .1681(1989). !0.:e45 (1989). l9lil r. n , c r . 7 7 3( 1 9 9 0 ) . Irl.:437 (1990). lrrra.andY. Ito, J. Org.,56, I (1991).
(c2H5)3siH/BF3.o(c2H5)2. The presenceof a cis-doublebondis an essentialfor this cyclization.Anotherlimitationis thatyieldsare low whenextendedto synthesis of a nine-membered oxocene. I K. C. Nicolaou, C. V. C. Prasad, C.-K.Hwang,M. E. Duggan, andC. A. yeale,Am. Soc., lrr.532l(1989). Silver trifluoroacetate,AgOCOCF3(l). Regiocontrolledalkylation.t The usual Lewis acids are inefiectivefor alkylation of 2-(trimethylsilyloxy)furan (2), but useof severalsilversalts,of which I is the
s . 1 . , 1 - d i o x o l a n easn, d e v e n a 1 , 3 a n J C l S i ( C H 3 ) r( - I : l ) i n C H 2 C I 2 , iderc'dto be (CHr):Si+SmCla-. Diar.rlrtic amount of SmCl3 combined l r a l l r a b o v e8 0 % . ' r : i . , . 1 6 2 3( 1 9 8 9 ) .
Irruer4/.r haveusedthis reactionfor r methodinvolvesactivationof the derivative(2), Dproducean oxocene (AIBN) (CeHs)rSnH br effectedwith r :ulione,whichthenis cleavedwith
4,R=Bu,847o R = CsHs,85%
*-rr*1"",", + NrN) \
/
n
o4ol"'n 5
a
'
l
4cH, \
n_--rr"o4oA* 6
302
O-Silyl ketene N,O-acetals
3. alkylationof Cs to give the alkylbutenolides mostuseful,resultsin regioselective to 6 canbe obtainedby 1,3-dipolaradditionofdiazomethane The dialkylbutenolides 6. 3 to give 5, which on pyrolysisprovides4,5-dialkylfuran-2(5ll)-ones rC. W. Jeford,A. W. Sledeski, Helv.,72,1362(1989). andJ. Boukouvalas.
,zo-s(cH,). " { ) +RCHO
Silver trifl uoromethanesulfonate. of AgOTf or AgBFaallenicaminescyclize Amino clcliution.r In the presence to 2-substitutedpyrrolidines. A stereogeniccenter adjacentto N can induce asymmetric induction, which is dependenton the concentrationof Ag(I).
S'o.",
N\-cH,
\_-/ _!
!.--r
/--l .H ("r\ocu, c.Hr-CH,NHCH,
' A. G. MyersandK. L. Widdowsor, ,h i
'l
'
3 form essentiallyonly oneenantiomi:rll1 ity is attributedto interactionbct*a t in a high-energytransition stetc?irh ltt
Asorr -T
c.HfcHrNHCH,-
(
(80Vo de)
I D. N. A. Fox,D. Lathbury, J.C.S.Chem. M. F. Mahon,K. C. Molloy,andT' Gallagher, C o m m . , 1 0 (7139 8 9 ) .
O-Silyl ketene N,O-acetals. Aldol condensation.r Theseo-silyl enol derivativesof amidesare availableby amidescatalyzedby Wilkinson'scatalyst.A typihydrosilylationof c,g-unsaturated with aldehydesin the absenceof a catalystto form reacts 1, cal reagentof this type, This silyl aldol reactioncan be ex(2) unusual dnti-selectivity. with aldol adducts
Sodium-Ammonla. Reductivcdccyanation.r This rai acetonidesfrom p-trimethylsilylory rldd cyanide followed by acetonationgivcr e I This mixture is convertedinto e sia3lc b cyanohydrinacetonide.Reductivedocyr syn-diol acetonide(4). Thc rpFrcil ru results from preferential formetirx of r
*'f""o vrrv
osi(crHs)3 J.
*Hg Hrc:CHCoN(cHr),+ (c,H5)3siH
lcHr)rNl\cH' H
TMS6
lll8ilit-s" . R'-'r ,r-rr*---
J cllr
X
t( l:l
I
os(c2H5)3 cH.cr. -i'o;'
I + C.HTCHO ---
?
-/'\./\
(CHr)rN-
-CuH, Y CH,
+ syn-2 1 . 8I:
anti-2
tendedto a synthesisof an optically active anti-aldol. Thus the (S)-prolinol propionamide(10, 332) on metallation(LDA) and reactionwith (CHr)zSiCl2affordsthe bicyclic siloxane3 a singleproduct. This cyclic N,O-acetalreactswith aldehydesto
This reactioncan be extcndcdto rynt polyenemacrolideantibiotics.Tbur rr-ti cyanohydrinanionof 6 providcr, rftcr rd good yield.
303
Sodlum-Ammonla
r . . 7 1 .1 3 6 2( 1 9 8 9 ) .
,tt\
/o-si(cH")"
f-\
.H
t. * XoCu,
o o i l |
Hl (
n .\gBFaallenicaminescYclize d.;acentto N can induceasYmrationof Ag(I).
CH.
CH,
3' to give the alkYlbutenolides to nr additionof diazomethane 6' furan-2(5H)-ones
-N<-cHi
\-/
,'ff-
sa-n%
,l
+ (2S,3S)-syz-4 R
CH,
97-99.6-2.5:0.2
(2S,3R)-czti-4
3
form essentiallyonly oneenantiomericallypureczti-aldol 4. The high stereoselectivity is attributedto interactionbetweenthe Si and the amidecarbonylgroup resulting in a high-energytransition statewith hypervalentsilicon. I A. G. MyersandK. L. Widdowson, Am. Soc.,ll2, 9672(1990).
./-cHrNHcH, 30qrde) J.C'S' Chem' ry. andT. Gallagher,
Irrr esof amidesare availablebY b1 Wilkinson'scatalYst.A tYPiof a catalYstto form the absence s silyl aldol reactioncan be exosi(crH5)r
t - -
g-,cs,)rNAfcH' H I
osi(c,H5)3 t H,
-coH,
+ syn'2 1 . 8I:
Sodium-Ammonla. Reductivedecyanation.r This reaction is a key stePin a route to syn-I,3-diol acetonidesfrom p-trimethylsilyloxy aldehydes(1). Reactionof I with trimethylsilyl cyanidefollowed by acetonationgives a l: I mixture ofa protectedcyanohydrin(2). This mixture is convertedinto a single isomer (3) on alkylation of the anion of the cyanohydrinacetonide.Reductivedecyanationwith Na-NH3 at -78o producesa syn-diol acetonide(4). The apparent retention of configuration in the reduction resultsfrom preferentialformation of an intermediateaxial anion. r)LrN(c'HJ' R':2,\ R'-r-1.-cN li[!fi:]l]t 2)R'x I > I cHo J T M S o 8 5 - e s % d 6 6 5 - e r l %
r
---x-CH,
CH,
2 ( l :l )
*)-Y*'
cN" , R.:.^i.R' |
| O
|
X
CH,
3
| O
CH,
Nr, NH, ---:-> ls-ss%
o
X
CH,
o CH,
4
7 ddol. Thus the (S)-ProlinolProaffordsthe crion with (CH3)2SiCl2 to aldehydes with reacts ,O-acetal
This reactioncan be extendedto synthesisof alternatingpolyol chainsfound in polyenemacrolideantibiotics.Thus reactionof the dibromide5 with 2 equiv. of the cyanohydrinanion of6 provides,after reductivecyanation,the protectedpolyol 7 in goodyield.
Sodium borohydride-(L)-Tartaric acid
TIPSO (,-\r-cN tio
X
CH,
BrHrC..a.^.-.-,CHzBr l CH,
o +
Ol
-
:o
X 5
X
CH,
o
o
X
o
X
CH, CH,
CH, CH,
o CH,
7 r s. D. Rychnovsky, I. Org.,55,5550(1990). S. Zeller,D. J. skalitzky,andG. Griesgraber, Sodium borohydride. reduction. A new synthesisof (3s,4s)-statine (4) from N'Nstereoselective (1) dibenzyl-o-valine dependson reductionof a p-keto ester(2) with sodiumborohydride with nonchelationcontrol owing to the adjacentN,N-dibenzylaminogroup'
N z \?nn (/N-c-N\zl
R--/,cooH
capableof chelation.An c-mctho tioselectivereductionof c- eod ! rM. Yatagai andT. Ohnuki,r.C.S
CH,
CH,
6
l) LiN(C,H,)2(84%) 2) Li. NH,(69%) , >
Sodium cyanoborohydridc. Reductive amination. Cosvr accomplishedby reductionofrhc c in the presenceof an ami6 (f,q generallypoor in reactionsof hit or trifluoromethyl ketones.Yic*l ketoneand aminefirst with TiCLI imine or enamineand then wiri l\ primary aminescan be obtaiocdI ammonia(last example).
o
tl
C.HTCCH,+ Cfl
?
Ry\,cooc2Hs
i-PtugctrcH,tco,c,tt,lcoox I , BzlrN 67%
I NBzl,
2
I,R=(CH3)rCH,
** lfoJ.."".o" | + OH I Rvy'\,,COOH
I NHt 4 (99Vo ee)
OH r l pd/c. R---\-rCOOC2H5 Htoou , " s % l BzlrN
o
l
l
C6H5CCF3* *L
r
o tl
cuHrcc.ll, + H 3 ( 9 :l )
t M. T. Reetz,M. W. Drewes, andK. Lennick,'I'C'S'Chem'Comm',1474 B. R. Matthews, (1989). Sodium borohydride-(r)-Tartaric acid. Enantioselectivcreiluction of ketones.r Sodiumborohydrideagedwith r--tartaric acid can effect enantioselectivereduction of ketonesbearing an o-substituent
Piperidinc syndrcsil.t Tbc i mycin (3) can be preparedin rro ment with benzhydrylamincud I goesdouble reductiveaminrtirn t deprotectionprovides thc pipctn hydroxyl-directedhydridc dclivcr
Sodiurn cyanoborohydride
.CH.Br
l) LiN(crHs)l(84%) 2) Li, NHr(69%)
305
capableof chelation.An u-methoxy group is most effective(84% ee). Similar enantioselectivereductionof c- and p-ketoesters(81-85% ee) is possible. ' M. YatagaiandT. Ohnuki,J.C.S.PerkinI, 1826(1990).
t.
CH,
CH.
l. Org.,55'5550(1990)' i. Grresgraber,
(4) from N'Nris of (3S,4S)-statine borohy(2) sodium with $-ketoester grouP' N,N-dibenzYlamino d.;acent
Sodium cyanoborohydride. Redactiveomination. Conversionof ketonesor aldehydesto aminesis usually accomplishedby reductionofthe carbonylcompoundwith sodiumcyanoborohydride in the presenceof an amine (Borch reduction, 4, 448-449). However, yields are generallypoor in reactionsof hinderedor acid-sensitiveketones,aromatic amines, or trifluoromethyl ketones.Yields can be improved markedly by treatmentof the ketoneand aminefirst with TiClator Ti(O-i-Pr)+2 in CH2CI2or benzeneto form the imine or enamineand then with NaCNBH3in CH3OHto effect reduction. Note that primary aminescan be obtainedby use of hexamethyldisilazane as a substitutefor ammonia(last example).
o ''""'""'t"r + c6H5NH2 cuHrlcrt, f-
fn I
f_CuHrN:CCuHnj
o
r
-
tl R.--rA\.,COOC2Hs l
ea% NacNBHl J
Brl,fi
CH.
I
,
c6H5NHCHC6Hs
ro*| *if,.""""'o" I
Y
OH I g,,
R\/,-\.-COOC2H5
I
Bzl.N
cF,
o
rlricr' /--\ ll c6H5ccF3+ HN' . )lI#9\( ffi% \-J
\-J
o tl
c6H5cc6H5 + HN[Si(CH,)r],
d
I \-cHc.u,
(C6H5)2CHNH,
3 ( 9 :l ) I X Lennick,,l.C'5. Chen. Comm',1474
Sodiumborohydrideagedwith r-tarn of ketonesbearing an o-substituent
Piperi.dine synthcsis.3 The important glycohydrolaseinhibitor l-deoxynojiri(1). Thus I on treatmycin (3) can be preparedin two stepsfrom 5-keto-o-glucose ment with benzhydrylamineand sodium cyanoborohydridein CH3OHat 0o undergoesdoublereductiveaminationto form essentiallyonly one product(2), which on deprotectionprovides the piperidine 3. The high stereoselectivityis attributed to hydroxyl-directedhydride delivery.
SodiumcYanoborohYdride
306
Sodium hexamethyldisilui&' Ii Dcprotonation of kctorr,r.' lithium amideor LDA for prcFn
cHo
H HO H
I -ro"
-r" ="oN^
"o)
l-ot
r"
(cJt5)rcHNH, NaCNBH., " CH.OH u 14%
Ho\-->*
c6H5cH2cocHl
cuo
N.AdS.
-tffi 22"
cHroH I
o
tl
,cHr)zc:cHicH, I{!I%
o
7V
ztr 2 (96:a)
' M. Gaudemar andM. Belleslocd Pd(oH), eo%1H,,
HOCH2\
/H
/F N \ Ho...( ) \ /
bH
Hd 3
Sodium hydride. Coupling with hono2ff usedfor the first asymmetricsyi chiral AB unit (l) with 4-accrory to the CD-unit. The product (3) 93Voyield) and rearrangemcdo regioselectivityof the basc-indn ondary hydroxyl group of I ud
providesa routeto aminationof 5-keto-o-fructose A similardouble-reductive pyrrolidines(equationl).Thisreductiveaminationalsoshowssomestereoselectivity for theglucitolisomer. cH2oH
ro -r" --l-o"
HO (I)
H
r'
f"t".t,l, (c6Hr),cHNH, HoH,c--./N\.-cHroH NacNBHr I 68%
Hoj
toH
CrHt
"OH
+
(Y
\a
cH.o +
,
2isomers
86:14
cH2oH rC.L.Barney,E.W.Huber,andJ'R'McCarthy'TetrahedronLetters'31'5547(1990)' J. org.,55,2552(1990)' p. l. t-ro.t, and(. A.-Cowen, 2 R. J. Mattson, r. rrl.prram, 3A.B.ReitzandE.W.Baxtsr,TetrahedronLetters'31'6171(1990)'
Gl Y HO
Sodium hydride
Sodiumhexamethyldisilazide,NaNlSi(CHr)rlz. Deprotonationof ketones.r This amide is more useful than the corresponding lithium amideor LDA for preparationof (Z)-enolatesunderthermodynamiccontrol. ci\ H - a ; L l H
rt
NaNls(cH,)3t' 9*u 9rt, --jg{g--> cuHs:7AO*u CuHl.-?\ + C6H'CH2COCH, CH. -100" 22"
o
"o)
/cn(c$),
xo\--.-l-lN1
cH.
-70" 20"
(E)
l5Vo l00Vo
85Vo 0
cH" oNa
oNa
(cHr)rc:cHlcH,"^'t""t"'", "",,\A"
Ho\-1;f\
(z)
* (E)-iro.",
"r* "rpcg, (z)
0 5
35Vo 95Vo
65Vo 0
2 (96:4)
**f ",,.0,o",, HOCH2\ FN
"o(
/H
) OH
HO 3
providesa route to Leto-o-fructose stereoselectivity some r,n alsoshows
I M. Gaudemar andM. Bellassoued, Tetrahedron ktters,30,2779(1989). Sodium hydride. Coupling with homophthalic anhydrides (12, 448).t This reactio4 has been (4) by couplingof a usedfor the first asymmetricsynthesisof ( - )-y-rhodomycinone chiralAB unit (l) with 4-acetoxy-5-methoxyhomophthalic anhydride(2), a precursor (CF3COOH, to the CD-unit. The product(3) is convertedinto 4 by deacetylation 93% yield) and rearrangementof the quinonegroup (AlCl3, 66% yield). The high regioselectivity of the base-induced couplingis ascribedto chelationbetweensecondary hydroxyl group of I and the carbonyl group at Cr of 2.
o
o
OH
-/\ NaHo'> D l
:#'.
Wo
CHrCuHr)2 .\.'--CHTOH
\-/
Y*-ro"ss OAc
cH3o
cH30
o
8 6 :1 4
./ \ Letters,3l' 5547(1990)' , Terrahedron A C o w e nJ, . O r g . , 5 5 , 2 5 5 2( 1 9 9 0 ) ' n. 31. 6777(1990).
C,H,
\ C
B
-4
OAc 3, dD- 19'
2 isomers OH
OH
OH
OH C'H,
/ z \
D
HO
c l n 't -Z o
OH 4
A
OH
A
30t
Sodium nitrite
Dehydrohalogenationo! 6-halohexopyrunosides.2This reaction has been effectedwith DBU or AgF, but NaH in DMF at 0-50" is as efficient.Hydroxyl, azide, benzyl, and estergroupsare stableundertheseconditions.Yields of 5,6-hexenopyranosidesare 60-83%.
cH,
rBt
/
/-o\ * ' l r ? " t F-/ \ --
(ry, )
Bzlo\--locHl
o
I N. Nikolaides andB. Ganem,.l.Ory-
Sodium phenylselenotrietborybrr by reductionof diphenyldiseleni& Reduction.r a,p-Epoxykar evenwhenthe substrate(2) alsocc also resultsin the sameproducrt3t. including the fully saturaredkac
*"- -Bzlo\ .\ry, ,/A^.. ocH,
BuCH:CHCCH-CHB
OBzl
OBzl
o o ll 2.. 2
' H. Fujioka,H. Yamamoto,H. Kondo,H. Annoura,andY. Kita, J.c.s. chem. comm.,1509 fl989). 2 F. Chrdtien,Syn.Comm.,19, 1015(1989).
---lr*. s% | xx.ct crto,
3 + c,H,,cH,Ja".*, sodium hydride-sodium r-amyl oxide-Nickelacetate(NicRA, 10, 365; 14, 288). NiCRA-bpy.t A NiCRA complexcontaining2,2'-bipyridine(bpy) effectshomocouplingof aryl halides(Ullmanncoupling),often in high yield, which can be improvedin somecasesby additionof KI or NaI. Whenusedin a catalyticamount, reductionto an alkaneis the main side reduction. M' Lourak' I M. Lourak, J. Org.,54,4840(1989); Y. Fort,andP. Caublre, R. Vanderesse, ibid.' 54'4848(1989)' andP' Caublre, Y. Fort,R. Vanderessb,
Sodium hypochlorite,NaOCl. RCH(NH2)COOH+ RCHO.t Tryptophaneis oxidizedto indole-3-acetaldehyde by Chlorox@in C6H6at 50-55'. The crudealdehydethus obtained(33-60% yield) is purifiedvia a bisulfiteadduct.The overall yield of pure productis 60%. Carefulcontrolof the pH to >7 .7 is essentialsincethe substrateis unstableto base. I R. A. GrayandW. M. Welch,Or3.Syn.,submilted (1989).
Sodium nitrite' NaNO2. RCH2NH2+ RcH2oH. one methodfor this conversionis the thermalrearderivedfrom RCH2NH2.An improvedprocedureis rangementof N-nitrosoamides of derivedfrom a trihaloacetamide thatthe N-nitrosoamides basedon theobservation RCH2NH2can rearrangeat 0o in the presenceof HOAc.l
cclrcocr > RcHrNHCocl3 RCH2NH,
l) NaNOI HOAC, AcrO,0' 2) OH-
7O-90qo
RCHTOH
s8%
il
6 4 (t0%)
I M. Miyashita, T. Suzuki,andA. Yod
Sodium tetrachloropelhddc(Il), I Ethoxycarbonylation.t Allylethanolicsodiumethoxidewhen ct (diphenylphosphine)ethane, dppe. r yield. CH3"\"'\CI+CO+NrOCr I J. Kiji, T. Okano,H. Konishi.rnd U
Sodium triacetoxyborohydridc, Nr Reductive amination ol ccfi sodiumcyanoborohydridefor redrr
G*o*",*-$-
triacetoxyborohydride309 Sodium ks.2 This reactionhas beenef)" r. asefficient.HYdroxYl,azide, nndrrions.Yieldsof 5,6-hexeno-
'!ro
CH.
I N. Nikolaides andB. Ganem, J. Or9.,54,5996(1989). Sodium phenylselenotriethoxyborate, (l); prepared Na+[C6H5SeB(OCH2CH:)r]by reductionof diphenyldiselenidewith NaBHain ethanol. Reduction.r a,p-Epoxyketonesare selectivelyreducedto p-hydroxyketones, (2) alsocontainsan enonegroup.Reductionof2 with ZnlCu evenwhenthe substrate alsoresultsin the sameproduct(3), but in low yield as well as a numberof products including the fully saturatedketone4.
9 o
alO
il./\ BuCH:CHCCH-CHBu
OBzl
I'c,H5oHBuCH: > tmq,
2
d \ Kita,J.C.S.Chen'Comm.,1509
rttte (NiCRA,10, 365;14' 288). g 1.3-bipyridine(bPY)effectshooften in high Yield, which can be , rr\henusedin a catalyticamount' ); . Lourak, J ( ) r q . . 5 44, 8 4 0( 1 9 8 9 M lt{t t 1989).
I r. oxidizedto indole-3-acetalde: aldehydethus obtained(33-60% nll rreld of PureProductis 60Vo. is unstableto base. ce the substrate
ut*JtnHh.,",on 3 + CTH,,CHTCCHTCH(OH)Bu -tl 58Vo 6 4 (loEo) I M. Miyashita, Letters,30,l8l9 (1989). T. Suzuki,andA. Yoshikoshi, Tetrahedron Sodiumtetrachloropalladate(Il),Na2PdCla. Ethoxycarbonylation.rAllylic bromides(chlorides)undergocarbonylationin ethanolicsodiumethoxidewhen catalyzedby Na2PdClain combinationwith bis(diphenylphosphine)ethane, dppe, to provide p,1-unsaturated esters in 70-95% yield. cHj'\-/'\Cr
+ co + NaocrH,'Ht-
cH3A-/'\cooc2H5
+ NaCl
I J. Kiji, T. Okano, H. Konishi, Letters, 1873(1989). andW. Nishiumi, Chem.
rle89t.
hr. conversionis the thermalrearis H:\H:. An imProvedProcedure of I derrred from a trihaloacetamide I HOAc.l b\, I
,
Sodiumtriacetoxyborohydride,NaBH(OAc)3. Reductiveamination of carbonyls.r This borohydrideis generallysuperiorto sodiumcyanoborohydride for reductiveaminationswith weaklybasicamines. ( \_J
l-\
FcHo
+ H"N{
VcooH \:/
..^NaBH{oAc),. HoAc'crcr)cH)cr >
86%
HOAC, AcrO,0o ,
RCHTOH
G*,NHCuHocooH-p
310
N-Sulfonyl-l-oze'1,3'butrdienes
so,c^H.
C' A' fr' Synlztt' 53?(1990);A' F' Abdel-Magid' I A. F. Abdel-Magid andC' A' Maryano (1990)' 31' 5595 andK' G' cn"o"''iiiionedion'kuers' Maryanoff, SodiumPerborate' NaBOr'4HzO' with HzOz ff i' oxidationis generallyconducted Oxidationo1o'go'oio*n"'t milder this of yields canbe obtainedby use (30%) and3 N NaoH ., io; . c".parable of yield The HOz' more-stable'.andfar saferthan oxidant, which is less expensive' sodium of place (I) is 35% when HzOzis used in the reaction shown in equation borate.
", .,cHJXt,rp" ll*"$';,'.'f,?i3i",., I1^- -----6-
(I) CICHtC:CHz
trifluoroperborate in combination with Hydroxylationo! arenes'| Sodium methanesulfonicaciol,anartractive."ug"ntforelectrophilicoxidationofarenesto phenols. 30' 1483(1989); Letters' n' Tetrahedron ' G. W. Kabalka, T' M' Shoup'andN' M' Goudgao l. Ors.,54,5930(1989)' Svnlett'39 (1991)' , c. K. s. prakash, u. riass, Q. Wang,andG' A' olah'
I
a* l
/o
ll + cH.
coocfl.
provide usually a single produo (crdt Thus this reactioncan provide a diec dines. The addition of an electroo'ri positionof the dieneaccelerates$c rl the endo-selectivityof the pareor rzd 'D. L. Boger, T. T. Cun W. L. Corbcn,
Sulfuryl chloride. u-Keto-$-Iactams.t 3-(PbcoYhii type reactionwith SO2CI2to providc 3 of 78-95%. Theseare hYdrolYzrdto silica gel and ZnCl2 (catalYst).
cuHr$ t-l N-Sulfonyl-1'aza' 1,3-butadienes' imalkencs.r Simplec,g-unsaturated Dicls_Alderrcrriir-*iiitrrtron-rich dienophiles' with reactions undergoDiels-Alder ines (l-aza-l,l-Uotuoi"ne'j Jo not Incontrast,theN-phenylsulfonyliminesderivedfromanaldehydeorketoneundergo to conditions with electron-rich dienophiles Diels_Alder reactions'under iorcing $OrCuH,
. '\cH,
(""
d
eor
-
)-*
\c"H.R' I
|O'C.H'
(ntFo'
l*
H-*R'
"n*' [i'*Y*""'"' 54% Y*'
CuHt
I
CuHt
(>20: l)
io'"'"'
cp,ooc.\7N I \
io'cuu' crHioocy'Otot#'
/ocrlr,
. ll 'dH,
ll
Y CuH,
I CuHt
(>20: 1)
I J. M. van der Veen, S. S. Bari, L- Kttd 5758(1989).
Sulfuryl chloride
so"c^H.
C' A' A. F. Abdel-Magid' r. 5l: t1990); (1990)' 'r. -rl. 5595
with HuOz uron is generallyconducted milder this of b canbe obtainedby use of yield The , rnd far saferthan H2O2' sodium of tcn H1O2is usedin Place
!",
'l'::\rr
clcHrcHcHpH
borate in combination with trifluoroto for electrophilicoxidationof arenes Letters,30' 1483(1989); pa.ln. Tetrahedron 39 (1991)' 1 olah.SYn/err.
so2c6H5
t - - "
t - -
/,OC2H'
ll + cHt
l
7N-.rOCrH,
""' ll \./
provide usually a single product (endo) with preservationof the alkenegeometry. routeto 1,2,3,4-tetrahydropyriThusthis reactioncan providea diastereoselective group (COOC2H5) at the 2- or 4dines. The additionof an electron-withdrawing positionof the dieneacceleratesthe rate of [4 +2]cycloaddition without diminishing the endo-selectivityof the parent azadienes. ' D. L. Boger,W. L. Corbett,T. T. Curran,andA. M. Kasper, Am. Soc.,ff3, 1713(1991). Sulfuryl chloride. (1) undergo a Pummerera-Keto-P-lactams.r 3-(Phenylthio)-2-azetidinones (2) in yields to provide3-chloro-3-(phenylthio)-0-lactams type reactionwith SO2CI2 of 78-95%. Theseare hydrolyzedto the 2,3-diones(3) in 85-907oyield by moist silica gel andZnCl2(catalyst).
"i-i-*'
so?cl,, cHrcl,
c6H5s -10" -------.---..--'t8-95%
f*t""".*'
'cuHnRt
rJ
,
,,_*.
lorcuH'
,ri-.'ocutcP' l
I cooc2H5 (>20:l)
imI dLcncs.t Simplec,p-unsaturated dienophiles' with reactions Drcls-Alder undergo hed from an aldehydeor ketone to dienophiles electron-rich iions with
i
I
82%
cooc2H5
cuH.$ {-l
jj+ q+
3il
sio,(H,o) liffil,,
|
ll I \,/-cn. I CuHt ( > 2 0 l:)
o\-J*' l l 2-N, tcuHnR' o'
3 r J . M . v a n d e r V e e n , S . S . B a r i , L . K r i s h n a n , M . S . M a n h a s , a n d A . K .O Bo r 9s.e, ,5J4. , 57580989).
(>20: l)
(I) p-CHTOC.H.CHO {
Tantalum(V) chloride-Zinc. Trisubstitutedallylic alcohols. A low-valenttantalumpreparedby reductionof Tacl5 with Zn in DME/benzeneaddsto alkynesto form a complexthat reactswith aldehydesto form (E)-allylic alcohols. The regioselectivityis determinedby the bulkinessof the groups on the alkyne and of the R group of the aldehyde.
li-"r",,.
n-crH,,-c=C-CrH,,-n
racl!'zn >|
,crH,,-z-l
\:g'
\-/. TaL"
|L
aldehydewith diethylzincin rbc prerr of titanium(IV) isoproxide.Thu: rlc than diluted by addition of ao rhrn reactionseven ether or THF crn be r
I
I
I
(II) p-CHTOC.H.CHO +1
+ 0.12 + TrrOr{
q6q I t) c6Hr(cH,)rcHo -- -J2)
NaoH, H,o
(CH,),CHCHO + rCJ z-C.H,, ""\
H'
_ J C.H,,-z "" -(cHr)rc6Hs HO
In addition, the chiral tir-narc 2 cr CH3MgBrto aryl aldehydesto provrd
' K. Takai,Y. Kataoka, andK. Utimoto , J. Org.,55, 1707(1990). (R,R)-Tartaric acld. Addition of (CzH)zZn to RCHO.| The diol l, preparedby Barbier additionof C6H5MgBr(2 equiv.) to the acetonideof dimethyl (R,R)-tartrate,2converts Ti(OC2H5)4 into the optically active spirotitanate2. In the presenceof 0.05-2.0 equiv. of 2, diethylzincreactswith anisaldehyde in tolueneat 0o to form the (R)alcohol 3 (equationI). The enantioselectivityand the chemicalyield increaseswith an increasein 2. Surprisingly,the enantioselectivity is reversedin reactionsof the
H\/
"",\&-" H/\ c6H5 c6H5 l, m.p. 192',aD= 68.5' 3t2
+ ri(oc,H,)n
C6H5CHO + CH,MgJ;
so*lcs,:crrnJn r *
culf, 9uH,
cH,r7o-jfoH
(III) p-CHTOC.H.CHO + Cl
cH,. P "",\
OH ^. CuH, CH,CH:CHVS = 80'20 Seebachattributesthe high c6cE hydroxy(diphenyl)methylgroup. rh.
(R,R)-Tartaric acid c6Hr9Hr.
(I) p-CHTOC.H4CHO + (CrHr)rZn + 0.12 + 1.O2 +2.02 nt tantalumpreparedby reductionof s ro form a comPlexthat reactswith rgioselectivity is determinedby the : R group of the aldehYde.
t'n".. : ""c'H"-l [-"
\,f. J
L
^,- I l) coHr(cHr)rcHo *-| zl naon. u'o
u-
)-(cHr)rc6H5 HO
OH
>
X' Ar'R t,H, 33Vo 3. WS= 91:9 = 95:5 42Vo =99:l 89Vo
aldehydewith diethylzincin the presenceof 0. I equiv. of 2 by additionof I .2 equiv. of titanium(IV) isoproxide.Thus the selectivity inducedby 2 canbe reversedrather than diluted by addition of an achiral titanate (equationII). Furthermore, in these reactionseven ether or THF can be usedin place of toluene.
(II) p-CH,oC6H4CHo+ (CrHr)rzn + 0.12 + Ti(O-r-Pr)o
c"Y'c\ Ho- H -75+0" > X Ar s CrH, 86Vo 3, R/S= 3:97 OH
(CH3)rCHCHo+ (CrHr)rZn3:#\ tCu,l,cH^c,H, R / S= 3 : 9 7
r.c.H,,.1a,",,-, \-__J H/
H
In addition, the chiral titanate2 can effect enantioselectiveaddition of CH3Li or CH3MgBrto aryl aldehydesto provide(R)-alcohols(equationIII).
ts. r707(1990).
2, €ther
(III) p-CH,OC6H4CHO + CH,Li J#
liol l. preparedby Barbieradditionof converts t,lrmethyl (R,R)+artrate,2 mare2. In the Presenceof 0.05-2'0 gde in tolueneat 0o to form the (R)with rnd the chemicalyield increases of xrr\ ity is reversedin reactions the
o o t
, . p-CHrOCuHn* CH,
OH C6H5CHO + CHrMgl --------+ ,\ COH' CH' 8l:19 50%
|
CH,:CHCH2M8BT
?"
o o Ti
OH
96:4
QuHt
9.Ht
313
CuH,
CH'CH:CH, FJS= 80:20
Seebachattributesthe high efficiency of 2 for enantioselectivereactionsto the group, which is presentin severalchiral auxiliaries. hydroxy(diphenyl)methyl
3f4
(R,R)-Tartaric acid
A s y m m e t r i c D i e l s - A l d e r r c a c t i o n s . s T h e o b s e r v a t i o n t h aacrylic t s i m p lacid" eacyloxypreparedby reactionof BH3with boranessuchas HzBOCOCH:CH2' with reactionsof the o'P-unsaturatedacids can serve as Lewis acid catalystsfor acyloxychiral of to the preparation cyclopentadiene(15, 2) has been extended formulatedas 3' preparedby reaccomplex The acid. boranesderived from tartaric uiid2, "utulyres asymmetric.Diels-Alder tion of BH3with the In-ou.ytut"o tartaric The prowith high enantioselectivity. reactionsof a,p_enals*iri.yrrop"ntadiene generally aldehydeswith enantioselectivities cessis applicableto variousaienesuno of 80-97% ee.
?.",? 900H r$oy'-1-too"
,n,,
o"
Uo.",
(2R,3R)-2 3 /CHt -----4 + CHr:C. 85% .CHO
CHO
? cH.ooc+*4^
CHTOOC\ SCH]
l-
IfY'V o \ o scH,
(98% e.)
No reaction occurs with vinyl erhe-rr.I usuallyusedin thermal [2 +2lcycloddftitr exampleof the preparationof a chinl cyc Asymmetricintramole cular Dieb'Ay tem 4 is also effective for enantiosclec (equationI). In this particular casc, e di hancesthe endo-selectivity,and is coq
cH'
4 |
96Voee
canalsosene asthe Lewis aldol reactions'a The boranecomplex3 Asymmetric a c i d c a t a l y s t f o r t h e a l d o l r e a c t i o n o f e n o l s i l y l e t h e r s w i t h a l d eof hydes(Mukaiyama ee)in reactions enol ethers Asymmetricinaottion is modest(80-85% reactions).s 96% ee in reactionsof enol ethersof ethyl of methyl ketones,Uut tun i" as high as regardlessof the geometryof the ketones.Moreover, the reaction islyn-selective,
+ CH.:CI9
LJ"
CH, exolendo=9:l
?
(
ol
i
\l
) /'\'\N'\ l l l
l
v
s
X s
J
?l r
,^l a
enol.However,theasymmetricinductionissolvent-dependent,beinghigherin nitroethanethan in dichloromethane' t-he. chiral titanium reagent 4' prepared Asymmetrtctz+zlii'i"iiitior'6 to l, derived from L-tartaric acid and known from Ticl2(o-i-pr)2 and itre cniral diol asymmetpromote (14' 232-233)' can also effectasymmetricDiels-Alder reactions N-acyloxto o'p-unsaturated -Ui'tt"thylthio)ethylene Ji , f ric12+2'lcycloaddition azolidinones. ' B. Schmidtand D. Seebach,Angcw. Clut' 2 D. Seebach,A. K. Beck, R. lmwintclrbl
OH
I
c.g.-o--'XzOYC(C6H5)'
cH,
I
b-"'c(cuHr), OH
_cu(o-r-pr),(4)
0987). 3 K. Furuta,S. Shimizu,Y. Miwa, ald H' Y 'K. Furuta,T. Maruyama,and H. Yrmrnq r T. Mukaiyama,Org. React.,2t' 203 (l9fl 6 Y. Hayashiand K. Narasaka,Chcn' Lcwz' ? N. Iwasawa,J. Sugimori,Y. Ikwasc' ri l
(R,R)-Tartaric acid
observationthat simPle acyloxyt reactionof BH3with acrYlicacid, acidswith r oi the c,p-unsaturated the preparationof chiral acyloxyas 3, preparedby reacr frrrmulated asymmetricDiels-Alder l. catalyzes The proh hrghenantioselectivity. generally s * ith enantioselectivities
315
? ? cH3ooc^z\tfAp
+ CH2:C(SCH')r__
\J
cH3ooc\ scH3
-seveelsteps
f lhrrN-,,ro
tt
il
\ o
scH3
%%.____,
tl
o
R"SiOH,C
bcH2osiRj
1
(98Vo ee)
cooH ocH, o i l l
*o^Y
o.
--v\ocu. {-
o
BH
3
o::: 96Vo ee =9:l e.rolendo
nmplex3 canalsoserveastheLewis etherswith aldehydes(MukaiYama )-t5 % ee)in reactionsof enolethers ! rn reactionsof enol ethersof ethyl of the geometryof the c. regardless rclrent-dependent,being higher in
No reaction occurs with vinyl ethers, silyl enol ethers, or ketenesilyl acetals, usuallyusedin thermal12*2)cycloadditionreactions,but thepresentcaseis the first exampleof the preparationof a chiral cyclobutanoneby a cycloadditionroute. Asynmetric intramolecular Diels-Alder reaction.T This chiral Ti catalystsystem 4 is also effective for enantioselectiveintramolecular Diels-Alder reactions (equationI). In this particular case, a dithiane group acceleratesthe rate and enhancesthe endo-selectivity,and is comparableto the gem-dialkyl effect. CH"
L
', \ 'rr
-
/,,^\,'' r
|
lL,\ -ry
\
9t +r- ils.zs" &%
\-/
S
,,.\
S
\-,
hrral titanium reagent4, PrePared ad irom r-tartaric acid and known to l:-:-33), can alsopromoteasymmetN-acyloxh1leneto c,p-unsaturated $67o ee\
)l.Tl O-i-Pr)t (4)
' B. SchmidtandD. Seebach, Angew.Chem.Int. Ed.,30,99 (1991). 2D. Seebach, He|v.,70,954 A. K. Beck,R. Imwinkelried,S. Roggo,and A. Wonnacott, (1987). 3 K. Furuta,S. Shimizu,Y. Miwa, andH. Yamamoto, J. Or8.,l48l (1989). a K. Furuta,T. Maruyama,and H. Yamamoto,Am. Soc.,ll3, 1041(1991). 5 T. Mukaiyama, Org. React., 28, 203 (1982). 6 Y. Hayashiand K. Narasaka,Chem.Letters,793(1989). 7 N. Iwasawa,J. Sugimori,Y. Kawase,and K. Narasaka,ibid.,1947 (1989).
3f6
2,4,{,6-Tetrabromo-2,S-cyclohexadienone
Tellurium(IV)chloride. in (1) selectively 1-alkyl-l-silyloxycyclopropanes a,$-Enones.rTeClacleaves yield' quantitative ketones(2) in essentially CHrCi;at 0o to form p+richlorotelluro to give ainducesdehydrotelluration bases) of (or variety a DMSO Additionof
pMso,o" >,-sulcH:cH, -
(cH3)3siot.ifi:'0", !-T"t s6% usrlcJ ,-e,fl
78%
unsaturatedchlorohydrin2 with I re becauseof the preferencefor an cl analogof 2 is cyclizedbY I to r I bromotetrahydrofuran.The melor I monoterpene aplysiaPYranoidD chlorovinylation. ' M. E. JungandW. Lew,J- Org-.{.
;
I
od-o&*' when TeClr is replaced methyleneketones. similar reactionshave been observed SnCL(13,124),butdehydrotellurationproceedsmuchmorereadilythandehydrostannation. Letters'32' 229 Tetrahedron t H. Nakahira, I. Ryu,L. Han,N. Kambe,andN. Sonoda, (1991).
Tetrachlorosilane,SiCL. Dithioacetalizttion.t Tlris rd Moreover, it is useful for cooPlcr aldehydesin the presenceof aroori of aliphatic aldehydesin the prescr I B. Ku andD. Y. Oh, SYn. Conn-.l)
Tetrakis(triphenylphosphinc)rictl ArC=N.t Aryl triffates ral Ni(0) (5 mole %), generatedia ria nitrilesin 69-78VoYield.This o@ becauseof couplingof KCN witb d I M. R. I. Chambers andD' A. sidtbt
2 141416-Tetrtbromo-2 rS-cyclohexadienone(1)' of Brominative cyclizntion,r Even though brominativecyclization Y,6-unsatuof the reaction (12, 457-458), tetrahydrofurans in rated alcoholsusually results CH. -o
-CH,
H'c-*-Br
fr'1, ^^- "#"'Q4:",oSiR,+d"' ur
fCHrOSiR, cl cH.
H,C6U, rr3v\-n3
Tetrakis(triphenYlPhmPhiDc)Ff Biphenyls.t Pd(0)-caulyzcdo videsa usefulrouteto substitutcdd able yields; it inhibils decomposi groups is tolerated on both coogo triflates have someadvantagesbccr
z:l g1."-)(,_ iHr'CH'oSiR'
.,*lll[, crcL,cHcll J3)
CH, n
w/--1r/" ft--ffcH:cHCr H,C CH,
Under the sameconditions.rrJ biphenyls.2 Coupling of alkYlsilaacs it triflatesis possiblewith fluoridc i
Tetrekls(triphenylphoephine)pelladium(0)
(1) selectivelyin ,r) c! clopropanos yield' quantitative 2) rn essentially give ato rcs dehydrotelluration
tl7
3, probably chlorohydrin2 with I resultsmainly in the tetrahydropyran unsaturated becauseof the preferencefor an equatorial chlorine atom. Indeed the des-chloro and a analogof 2 is cyclizedby I to a l: I mixture of a bromotetrahydropyran The major product (3) was convertedinto the cytotoxic bromotetrahydrofuran. monoterpeneaplysiapyranoidD (5) by desilylation, Swern oxidation, and chlorovinylation. I M. E. JungandW. Lew,J. Or9.,56, 1347(1991). Tetrachlorosilane,SiClq. Dithioacetalizttion.r This weakLewis acid is a usefulcatalystfor this reaction. of aromatic Moreover, it is useful for completeselectivityin dithioacetalization preferential dithioacetalization aldehydesin the presenceof aromaticketonesand for of aliphaticaldehydesin the presenceof aliphaticketones' I B. Ku andD. Y. Oh, Syn.Comm.,19, 433(1989).
I observedwhen TeCL is rePlaced b much more readilYthan dehYdroLetters,32, 229 Stnoda.Tetrahedron
Tetrakis(triphenylphosphine)nickel(0). ArC=N.t Aryl triflatesreactwith KCN at 60o in CH3CNin the presenceof and zinc, to form aryl Ni(0) (5 mole %), generatedin situfrom Br2Ni[P(C6H5)3]2 case of haloaryltriflates nitrilesin 69-78%yield. This couplingis not usefulin the are becauseof couplingof KCN with the halo groups.Pd catalysts not useful' rM. R. I. ChambersandD. J.C.S.PerkinI, 1365(1989)' A. Widdowson,
l.
of 1,6-unsatucyclization Dmrnative rns (12, 457-458),reactionof the Hrc---B,
r -o '/"
n
/ rlcH' tcH.osiR3+ | )o-
Z:l 61"'tX iH'-cH'osiRt
H. n'
4
,/-\
cH^o-( - r-
\:/
1. c{
Tetrakis(triphenylphosphine)palladium(0). couplingof aryltributyltinsand aryl triflatesproBiphenyls.r Pd(0)-catalyzed biphenyls.Lithium chlorideis requiredfor reasonvidesa usefulrouteto substituted able yields; it inhibits decompositionof the catalyst.A wide rangeof functional groupsis toleratedon both components.Aryl halidesundergothis coupling,but phenols. becauseof the manyavailablesubstituted triflateshavesomeadvantages
cHcl,
\J
4eq.
"",o$.$*o,
l n '2,u
/rn:ct >1,
Pd(o).Licl'
\Foso,cR, -+-
\-snBu. + o,N{
t
Underthe sameconditions,aryl triflatescouplewith arylboronicacidsto form biphenyls.2 Coupling of alkylsilaneswith aryl triflates.3 Coupling of organosilaneswith triflatesis possiblewith fluoride ion (2 equiv.) and a Pd(0) catalyst.The striking
3lt
Tetrskis(triphenylphosphine)pslladium(0)
Tfo
QH, :
c#5
2F , Pd(o) THF ---------+ 3l -51%
+
siF3
(S)-1 (347o ee)
cocH3
52" 900
:", c"HrAc6H4cocH3 (S),32-34Vo e (R\, -207oe*
featureof this reaction is that even alkyltrifluorosilanescan participate, as well as alkenyl- and aryltrifluorosilanes. Presumablya pentacoordinatedsiliconate is the effective participant. The stereochemistryhas been examined in the case of the opticallyactivesilane1. The reactionproceedsin THF in3l-517o yield. At temperaturesof 50o,thereactionproceedsmainlywith retention.The opticalyieldsdecrease >75o, inversionpredominates. is increased,andat temperatures asthe temperature The effectof solventsis evenmore striking.Additionof HMPA resultsin inversion, whereasDMF or DMSO favor retention. l,l-Dibromoalkenes and E-vinylboronic acids (Z,E)-2-Bromo-1,3-dienes.a in the presenceof this Pd(0)catalystandTIOH (Z,E)-2-Vomo-1,3-dienes to couple for coupling of vinyl bromideswith vinylearlier developed base, conditions as
Ho(cHr)r&B(oH)'
(Z)-2-bromo-l-phenylthio-l-alkencs to r tively.
+ Br'c:cHB" tt'llh??I' ' "o,"trrr.__4ru Br
boranesto give 1,3-dieneswith retentionof configurationof both partners.Basecouplingsobtain sensitivegroupsare not affected.rMost efficientandstereoselective whenthe l,l-dibromoalkeneis substitutedby an allyl alkoxy group. are of interestbecausethey can show high These (Z,E)-2-bromo-1,3-dienes biin intramolecularDiels-Alder reactionsresultingin substituted stereoselectivity cyclicsystems.5 Alkenyl sulfides.6 An attractiveroute to vinyl sulfidesinvolves crosscoupling catalyzedby Pd(0)in of a primary9-alkyl-9-BBNwith l-bromo-l-phenylthioethene of a base,NaOH or K2HPO4.This couplingcanbe extendedto (E)- and the presence
t-/
l1 J
Br "'-a:o
*
c.ES-
ArOTf + Al& + ArR.1 This cor0 catalyzedby a Pd(0)catalyst.Thusrhc rc i-butylaluminum(2 equiv.) catalyzcd! 67% yield. 1,2-Diene-$yzes.t Propargylicca reactas allenyl complexes.Thus cutat Pd(O)results in 2,3-dienylcarborylucr Similarly, coupling of 2-alkynyl c.rbc of CUI and LiCl and catalyzd by Pd(0) (equationII).
!uH" -ryo).c''r (I) CH3-I:H + CO'
cJ
oco2cHs
a L
luH''
+ HC=CCH.mHP UI) CH3-f-Bu ocorcH3 Indole synthesis.e A new roorc to coupling of alkynylstannaneswith 2{n alkynylanilines.Intramolecularcyclir-i catalystsprovides substitutedindolcs.
Br + Bu"Sl€=C NHAc
Tetrakis(triphenylphosphtne)palladium(O)
PJ lxr +
-' i t:' n'
3f9
(Z)-2-bromo-l-phenylthio-1-alkenes to afford(E)- and (Z)-vinylsulfides,respectively.
CH, t' |
coHr"'\c6H4cocH3 (S),32-347o e.e (R),-20Voee
-A
t-) *
illanes can particiPate,as well as siliconateis the pcntacoordinated cen examinedin the caseof the IH F in 3 I -5 I Voyield. At temPeratntion. The opticalyieldsdecrease ' es > 75o, inversionpredominates ion of HMPA resultsin inversion, lenes and E-vinylboronic acids cc of this Pd(0)catalystandTIOH ng of vinyl bromideswith vinYl-
tl
"
fffr..",
8t%
cuHss"
J
cH" ll
Br o'-.:.",3qj'I9\,
ArOTf + Al& + ArR.1 This couplingproceedsin generallyhigh yield when catalyzedby a Pd(0)catalyst.Thusthe reactionof l-naphthyltriflatein THF with triin i-butylaluminum(2 equiv.) catalyzedby Pd(0) provides l-isobutylnaphthalene 67% yield. lr2-Diene$yzes.t Propargyliccarbonatesin reactionscatalyzedby Pd(0) can catalyzedby reactas allenylcomplexes.Thuscarbonylationof2-alkynyl carbonates as the major or only product(equationI). Pd(0) resultsin 2,3-dienylcarboxylates in the presence with terminalacetylenes Similarly,couplingof 2-alkynylcarbonates of CuI and LiCl and catalyzedby Pd(0) provides | ,2-diene-4-ynesin 60-83% yield (equationII).
ll]al
coH,, !uH,, (t) CH,-f:H + CO-rg)rcH,o5 Fs:sHsoocH3 ee% cH, oco2cH3
4 I
HO(Cnz)::rArABu
Pd(o)' cul. CuH,r.
Br
tuH,, -#(rr)CH3+Bu + HC=CCH,OTHP
dgurationof both Partners.Basecouplingsobtain ld stereoselective elll I alkoxygrouP. resl becausetheY can show high bir.'rronsresultingin substituted 1l sulfidesinvolvescrosscoupling rykhioethenecatalyzedby Pd(0)in ruplingcanbe extendedto (E)- and
pd(o),c6H,cHl
Br
+ BurSnC=C
, X r) i l + t+
'C-CCHTOTHP
Indole synthesis.e A new route to 2-substitutedindoles is basedon the Pd(0) with 2-bromoanilines or 2-trifloxyanilinesto give 2couplingof alkynylstannanes Intramolecularcyclizationoftheseproductswith a varietyof Pd(II) alkynylanilines. catalystsprovides substitutedindoles.
NHAc
>( H.
^..'Fa:a'
CH,
ocOrCH3
,/B'
ctztn
77%
NHAc
*.1!",ir"^i,i:9"r CHt
sc6H5
320
Tctrskis(triphenylphosphine)palledium(0)
with sulfonyl chlorides Sufones.ro Pd-catalyzedcoupling of organostannanes particularly vinyl and allyl sulfones. of sulfones, providesa direct synthesis (E) (E) *JoS'1r". CHTSOTCH:CHC6H5 + Bu.SnCH-CHC6H5...ff CH3SOTCI p-cHrocuHrsorcl + BursncHrcHgcHcH3 +
p-clroc6H4so2cH2cH9cucrt,
Carbonylationof aryl and vinyl iodides.rr Pd-catalyzedcarbonylationin a basic mediumof aryl or vinyl iodidescontainingenolizablecarbonylgroupscan result in reactionwith the in situ generatedenolateto form enol estersor enol lactones.
cH. CTI. 3
Intramolecular H ccL clclizlhtcontaining one alkenyl and onc vhyl bicyclic products(14, 291-29t: 15. 301 ucts is possiblewhen the substnrc cc Pd(0) catalystand 2 equiv. ofuicrhyL
of.ocH3+coff+ofr o
H,C:rryCOOC2Hs I |
t
o4"",
CH'-,/',,
l t l
+ C O -----) 569o
|
\2
yield. This "zipper" tyPe rcrtid b stratecontainingtwo triplc boo&. Th the major product.
coocHs
coocH, -,^!r,^\"
I (E = COOCJLI
f'o--a", /r\.\
ll
|
rAau
. Co------> u'" | l.n I
"ff"u J-o
BenZylpalladation.r2 Benzyl halidesdo not undergousual radical cyclizations alkenes effectedwiih organic halides,but do undergoPd-catalyzedcyclization with group can andalkynes.A typicalreactionis formulatedin equation(I)' The leaving I with cyclize alsobe Br, I, or oMs, but not ocoocH3 or ococH3. Attemptsto
y',-,\(cH,ct (I)l ll
.o3l;,fl:,1,t ---r*-
ll! Intramolecular enc rcabtf chiral unsaturatedcyclic allylic a
CHt
\,r^cH,cH:cHz I
hydroBu3SnH(AIBN) fail, but the correspondingbromide or iodide doesundergo not a probably 2 is to of I cyclization the stannationin moderateyield. consequently, other several paper includes The radical reaction but involves benzylpalladation. suchas the conversionof 3 to 4' examplesof this cyclic carbopalladation
I (1046 cc)
Tetrekis(triphenylphosphine)pallsdium(0)
with sulfonylchlorides Eoslannanes larlr rinyl and allYl sulfones.
CI t ^
/'l
,
,
(cH' --::+l Pd(o)1y'\'r(1zc*' | ll I
tI \ " - ll' - c H . 7 2 % \ " - ' - c H , F
,c' a ' > cH.so,cH=cHC6H5
3
E
;+
p-CH,OC6H4SO2CH2CH9CHCU,
carbonylationin a baPd-catalyzed enolizablecarbonylgroupscanresult o form enol estersor enol lactones'
4
Intramolecuhr Heck cyclizntions.r3 Pd10)-catalyzedcyclizationof substrates containing one alkenyl and one vinyl iodide group is a well-establishedroute to bicyclicproducts(14,297-298;15, 301-302).Tandemcyclizationto tricyclicproducts is possiblewhen the substratecontainsa triple bond. Thus, in the presenceof a Pd(0) catalystand 2 equiv. of triethylamine, 1 undergoestricyclization to 2 in high
CH, Pd(o),N(c,H5)l cH"cN, d --------:---+ 95%
cooc2H5 -cH,
I (E = COOCTHT)
2
yield. This "zipper" type reaction has been extendedto tetracyclizationof a substratecontainingtwo triple bonds.Thus 3 underthe sameconditionscyclizesto 4 as the major product.
CHt :Q\1,
76%
mt undergousualradicalcyclizations cyclizationwith alkenes Pd-catalyzed io equation(I). The leavinggroupcan OCOCH3.Attemptsto cYclizeI with
fr-rn"", t
>E E
4
3
cyclizationof Intramolecular ene reactionsrr (15, 302). The Pd(0)-catalyzed chiral unsaturatedcyclic allylic acetatessuch as I proceedswith high transfer of
cH3oocfTocHl
\-'V 2
romrdeor iodidedoesundergohydro: ;r clizationof I to 2 is probablynot a on The paper includes several other r as the conversionof 3 to 4.
\J
I o"",
Pd(o), HOAC,75"
cH3ooc, H..
67%
CHt
AcO l (l00Voee\
2 (>92Vo ee)
322
Tetrskis(trlphenylphosphine)palladlum(0)
chirality to give 2. The overall result implies displacementof the acetategroup with inversion. This ene-typecyclization has beenextendedto chiral unsaturatedacyclic allylic acetates suchas (s,E)-3 and (s,Z)-3.tsPd-catalyzed cyclizationof (S,E)-3resultsin the (s)-pyrrolidine 4 in high optical purity by apparentdisplacementof the acetate Boc
HO11
,13'R /*\ vt G;t""!'o" ,zN:.
(
"
6in-
Boc
I
(E) \\
eicosanoidswith a conjugatedtctra of geometryof the vinyl halidc, er r provides 3, a convenientprecufl(r I ester(4).
+ HC:C Br
-io
t
: osiR.
--tt
2
osin.
HOCH2,,Z\._. t L:Lv/^.(cH:\cr
CHr/ (S,E)-3(98.6%ee)
(S,E)-4(>967oee)
Boc
Boc
I
I
N:.
yt .z
----------J
--t"' ( " (z)\-g11.
/*\
"5"". \^
I
,t,\
CH( (R,E)-4(>96ee)
(S,Z)-3 (98.6Vo ee\
groupwith inversion.cyclizationof (s,Z)-3 underthe sameconditionsoccurswith netretentionat the acetoxycenterandZ - E isomerization to give (R)-4alsoin high opticalpurity. Evidently,in this casethe n-allyl complexintermediatecan undergo isomerization. Actually the acetoxydiene (s)-5 lackingthe terminalmethylgroupof 3 cyclizesto a racemicproduct (6). Boc I N.
Boc
I
N
Pd(o) / ------------) \ 7\qo
,/
..
: osiR'! 3
> /
\-aLI
1 \"",
CH"
(s)-s (R,S)-6 Coupling of l-alkynes and vinyl halidesr6(6, 6l). This coupling reactionhas beenusedextensivelyfor synthesisof isomersof lipoxin Aa andBa, linear trihydroxy
t A. M. EchavarrenandJ. K. Srillc. ir , ren, R. M. Williams, andJ. A. Hdn 2 J. Fu and V. Snieckus,Tarahe&a La 3 Y. Hatanakaand T. Hiyamt, dtdd..!1. 1 W. R. Roush,K. J. Moriarty, rd B- | 5 W. R. RoushandR. J. Rive.t. Ot..l 6 Y. Hoshino,T. Ishiyama,N. Miyrr (1988);T. Ishiyama,N. Miyrun. rd, 7 K. Hirota, Y. Isobe,and Y. Mrti. J.CEJ. Tsuji, T. Sugiura, and I. Mialri. li Nakata,H. Murayama,H. Yrmrti. ll (1990). e D. E. RudisillandJ. K. Stille, J. O4., r0 S. S. Labadie, ibid. , g, 2496 ( l9t9). ttI. Shimoyama, Y. Zhang,G. Wo. d I '2 G. Wu, F. Lamaty,and E. Ncgidi..l. t3 Y. Zhang,G. Wu, G. Agncl, rd E. t{ 'a W. Oppolzer,J.-M. Gaudin,rld T. N. W. Oppolzer, T. H. Keller, M. Bcdotr 15W. Oppolzer, T. N. Birkinshry, rd G t6 K. C. Nicolaou.B. E. Marroo.C. A. V s527 (1989).
Tetrakis(trlphenylphosphlne)pelladium(0)
ccmentof the acetategroupwith acyclicallylic ihrral unsaturated I clclizationof (S,E)-3resultsin rcnr displacementof the acetate Boc
t\" lI
l - 1 ' > 9 6 V oe e )
323
eicosanoidswith a conjugatedtetraenesystem.One valuablefeatureis the retention of geometryof the vinyl halide, as well as the high yield. Thus coupling of I and 2 provides 3, a convenientprecursor to optically active 7-cis,ll'tans-LXAa methyl ester(4).
pd(o),cut,
QSiR?
HO"\a I
I + Hc=cv''^t(cHr)3coocH Br : osiR3
3
rc,rij,un, Bs%
t
OSiR" HC/.Cfir-,gZ'.'.-. I L:Lv'/\(cHr)3coocH3 : osiR3
Bcrc
(cHr)3coocH3
3
/'\
-.+{-cHz
, I
I
4 r > 9 6e e )
[,.{
the sameconditionsoccurswith rizationto give (R)-4alsoin high can undergo mplex intermediate ing the terminalmethylgroupof
&x* N'.. -1t CH, CH, ts-6 6l r This couplingreactionhas Drrn\ andBa,lineartrihydroxy
I A. M. EchavarrenandJ. K. Stille,Am. Soc.,l09, 5478(1987);I. K. Stille'A. M. Echavarren, R. M. Williams, and J. A. Hendrix, Org. Syn.,[submitted(1990).] 2 J. Fu and V. Snieckus,Tetrahedron Lctters,3l, 1665(1990). 3 Y. Hatanakaand T. Hiyama, ibid.,3l,2719 (1990);Am. Soc., 112,7793 (1990\. 1W. R. Roush,K. J. Moriarty, and B. B. Brown, Tetrahedron Letters'3f ' 6509(1990). 5 W. R. RoushandR. J. Riva,J. Or9.,53,710 (19E8). 6 Y. Hoshino,T. Ishiyama,N. Miyaura, and A' Suzuki, TetrahedronLetters, 29, 3983 (1988);T. Ishiyama,N. Miyaura, and A. Suzuki,Org. Syn.,submitted(1990). ? K. Hirota, Y. Isobe,and Y. Maki, J.C.S. Perkin1,2513 (1989). 8 J. Tsuji, T. Sugiura,and I. Minami, TetrahedronLetters,2T' 731 (1986);T. Mandai' T. Nakata,H. Murayama,H. Yamaoki,M. Ogawa,M' Kawada,andJ. Tsuji, ibid.,3l,7179 (1990). e D. E. RudisillandJ. K. Stille,J. Org., 54,5856(1989). r0S. S. Labadie,ibid., 54,2496 (1989). rr I. Shimoyama,Y. Zhang,G. Wu, and E. Negishi, Tetrahedron I'etters,3l' 2841 (1990). 12G. Wu, F. Lamaty,andE. Negishi , J. Or9.,54, 250?(1989). t3 Y . Zhang,G. Wu, G. Agnel, and E. Negishi,Am. Soc., f n, 8590(1990). raW. Oppolzer,J.-M. Gaudin,and T. N. Birkinshaw,Tetrahedronktters,29,4705(1988); W. Oppolzer,T. H. Keller, M. Bedoya-Zuritaand C. Stone,iDid.,30, 5883(1989). '5 W. Oppolzer,T. N. Birkinshaw,and G. Bernardinelli,ibid',31' 6995(1990)' 16K. C. Nicolaou,B. E. Marron, C. A. Veale,S. E. Webber,andC. N. Serhan,J. Org.' 54,
s527(1989).
324
2,2,6,6-Tetrcmethylpiperidinyl-1-oxyl
cH3\ f-l
/'cH3 dichloride, Tetramethylethylenediaminezinc - H, C Cnr. -\ril cl cl additionof RMgXto enones.r Thiscomplexcanserveasa catalyst Conjagate for this rcaction.The relatedcomplexin which onechlorineis replacedby methoxy by useof I aresimilarto thoseobtained morereactive.Yieldsof adducts is somewhat equiv.of trialkylzincates. ' J. F. G. A. JansenandB. J'C.S.Chem.Comm.,74l(1989). L. Feringa,
t{cL
t
ctrs/ 'Horl
cH3cHoH(cHr)rcHpH
cH3cHoH(ctL\calg of primary/secondarydiols to bydl diols is best conductedwith ddcd I
' P. L. Anelli,S. Banfi,F. Moourn' t 2 R. Siedlecka, eodK- I J. Skarzewski. Tetramethylammonium triacetoxyborohydride, (CH3)4NHB(OAc)r(f ). Reductionof a chiral imi.dc(2).t Highly selectivereductionis possiblefor the chiral protectedcis-dihydroxytartarimide2 with this reagent(equationI)' Lithium (22Vo),anduseof SMEAH aluminumhydrideshowsonly slight diastereoselectivity triacetyxyborohydride provides3 in about64% de. However,tetramethylammonium
o
tt
,o\r-\
(D( " X \Jt"\
|
cH.oH
lW. P. GriffithandS. V. l*y. AUhcl
1..."s -'------+ r
,N-c -au",
-1o%
o
[
Tetrapropylammonium PerrrOcl Oxidation ol alcohok. Grifril of this reagentfor catalytic oridri morpholineN-oxide as reoxider. h than thoseobtainedby thc Swen rt
9" cH.oH
l^
f
sH,oH
. lo]4"_l:t"-cuH' l"-f'\._1.::H' -cu""n"
Thallium(Ill) acetete. Dehydrogcnation of etor,et- I selenenicanhydridefor dehydrqcl in somecasesthe reactioninvolver I to catechols.as in the oxidetioo of
lo*1"
|o-1 3
4 cHt
doesnot reducea silyl-protected2. In contrast,t-butyldimethylsilyl-2is reducedby to 4 in >98/o de. Note that the MEM ether of 2 lithium tri-sec-butylborohydride showsonly slightselectivitywith eitherLiAlHa or lithium tri-sec-butylborohydride. t S. A. MillerandA. R. Chamberlin, J. Org.,54'2502(1989\.
n
o o
C.HV
t
f# 2,2,6,6-Tetramethylpiperidinyl-l-oxyl(TEMPO, l) and the 4-methoxyderivative (2), 12, 479-480;13, 183. Oxiilation of diols,r,2 Both I and2 can serveas effectivecatalystsfor oxidation of diols by NaOCIin aqueousCH2CI2.This methodis usefulfor selectiveoxidation
t I CHt I
I A. K. Banerjee,M. C. Carrasco.td
Thallium(III) acetate
H'.- f-l
325
NaOCl,2
,rcH,
,N- -CHl H' /zn\ CI CI [s complexcanserveas a catalyst r chlorineis rePlacedbY methoxY imrlarto thoseobtainedbYuseof I -\
cH3cHoH(cHr)tcrlroH
cH'ct/Ho'KBt,
cH3cHoH(cH2)scHo + cHrco(cH2)rcHo lOVo
687o NaOCI' I
g:FcH3cHoH(cH2)2cH2oH
cH,-ao)Fo \__J
diols to hydroxy aldehydes.Oxidationof very hydrophilic of primary/secondary diols is best conductedwith addedLiCl to provide a pseudo-solid-liquidsystem.
C o n m . . 7 4(l1 9 8 9 ) .
I P. L. Anelli,S. Banfi,F. Montanari, andS. Quici,J. Org., 54' 2970(1989)' 2 R. Siedlecka, Letters,3l,2177(1990). Tetrahedron andK. Mlochowski, J. Skarzewski, (l). , rCH.)aNHB(OAc)r ccti\ e reductionis possiblefor the thrs reagent(equationI). Lithium srrttry (22%), anduseof SMEAH lammoniumtriacetyxyborohydride
Tetrapropylammoniumperruthenate,14, 302. oxidttion o! atcohols. Griffith and Leyr report various improvementsfor use of this reagentfor catalyticoxidationof alcoholsin combinationwith N-mithylmorpholineN-oxideas reoxidant.In general,the yieldswith this oxidantare higher than thoseobtainedby the Swern reagent. ' W. P. GriffithandS. V. Lev.Aldrichim. Acta,23,13(1990).
)H H + C . H . q g' I
I B cH.oH 1...1n Lo\-'\ { t N - c
f"a I o
Thaltium(Ill) acetote. Dehydrogenationof enones. Tl(oAc)l can be as effectiveas DDQ or benzeneHowever, of c,p-enonesto 1,4-dienones. selenenicanhydridefor dehydrogenation aromatization and acetylation, in somecasesthe reactioninvolvesdehydrogenation, to catechols.as in the oxidationof I to 2.
-cu",
H 4
n
o
cH'w
o: ,1989).
e aseffectivecatalystsfor oxidation nJ rs usefulfor selectiveoxidation
o
c
H
"
A"o\zr!A 38% I ll Aco-ry
n(oAc)r,
.? O. I r andthe 4-methoxYderivative
CH,
CH,
'but) ldimethylsilyl-2is reducedby de Note that the MEM ether of 2 rr I rthiumtri-sec-butylborohydride.
CH,
o I
CH,
I A. K. Banerjee,M. c. carrasco,and c. A. Pefra-Matheud, Rec. Trav., r08, 94 (1989).
t26
Thellium(Ill)nitrete
Thallium(IlD nitrate (TTN)' antibiotics are polypeptides Oxidative phenolic coupling.r The vancomycin in modelsystemssuch shown al-have et Evans with bridging diphenylether groips' peptides(2) canbe accomplishedby oxidation as I that cyclizationto o_halolphenolic followed by crcl2 with thallium(Ill) nitrate in iHr-methanol or cH2Cl2-methanol reductionofapara-qlinolintermediate(a).Inthreecasestheyieldofcyclicproductswas40-487o.
Thexylborane (ThxBHJ. Intramolecular hYdroboratiot ot oxidationof allyl vinyl ah subsequent with almostexclusivesyn selectivity- | bulk of Rr, but is loweredwhenR.ris pl importantfor stereoselectivity.
9H, *'lA'*'
ql:9"'#*a"'L*,yl o-"":"",
*[-
*::ClL L
I,Rr=Bu,R2=H R' = Bu, R2 = CHr R' = CoH", R' = H R' = CoHs,R' = H
**'r.oor, J CI
OH
Av"/v*
[-z\"'Y \,"tu*p,,0"
/
of cu Hy droboration-reductioa can be used to induce asymmetric ifltt a cyclic transition state. Thus ratrr followed by oxidation provides thc l.t reaction with the homologous cnoc P tivity (synlanti = 6.6: l).
?",
H,cl\.,'tcrt' with TTN in methanol/chloroform Isoflavones.zTreatmentof the flavanoneI isoflavone(2) as the major prod.on,uining perchloric acid (essential)results in an of a halogengroup at the parauct, formed via aZ,3-aryl migration' Substitution the isoflavone' position of the phenyl group increasesthe yield of
.afoy.."' (yr\".", Til,Ji,:,&#;., ay"l \4-''"'*-'
W
o
6
,
'
o
siti d Reductionof 1,4-diketoncs with atti-selectivityof 17-47:l- Ro but reductiooof 1.3 stereoselectivity, tivity. ' T. Harada. J. Uchimln' r Y. Matsuda, 2T. Harada, S. lmudr' r Y. Matsuda,
0
2 (659o)
3 (r3Vo)
I D. A. Evans,J. A. Ellman,andK' M' DeVries'Am' Soc''f ll' 8912(1989)' Letters'31, 7355(1990)' 2 T. Kinoshita,r. tcninose,and U. Sankawa,Tetrahedron
Thiophenol. p-Lactones;alkencs.t A rr c fact that the enolatesof phenylthiolcr
ThloPhenol
tnc(rmycin antibioticsare polypeptides ct al. haveshownin modelsystemssuch by oxidation ilcsr2 ) canbe accomplished by CrCl2 followed CHzCl2-methanol or prodcyclic yield of the cases three . ln
Thexylborane (ThxBHz). Intramolecular hydroboration of allyl vinyl ethers.t The hydroborationand oxidationof allyl vinyl ethersI with ThxBHz(2 equiv.)leadsto 1,3-diols subsequent with almostexclusivesyn selectivity. High syn selectivity obtainsregardlessof the bulk of Rr, but is loweredwhenRr is phenyl.Apparently,electroniceffectsof Rr are important for stereoselectivity.
-y\--' -""':t"' **,",,t--,e-,-l*l o-"":"", 9H,
!','fd:al-; \*ou*0*"1t"] a
42% lc'ct, OH
Cl
a\""-'A..ta''
*,,y 2
CH" t
-.--O-..
tl
"^-.1fc'H' o ) 165%o)
*(YoY"'"' \ry o
-
R'--',,\aR'
t
L J-l*J
OH
83Vo 30Va 90Vo 897o
l , R r= B u , R 2 = H R r = B u ,R 2= C H : R' = CuH,,,R' = H R'=CuHyR'=H
l
OH
synlanti >200:I 1 6 :I >200:I 1 6 :I
Hydroboration-reduction of enones.2 Hydride reductionof a carbonyl group of a doublebondvia canbe usedto induceasymmetricintramolecularhydroboration a cyclic transitionstate.Thus reactionof the enonel with thexylborane(l equiv.) followedby oxidationprovidesthe I,5-diol 2 with high 1,4-synselectivity.A similar reactionwith the homologousenoneprovidesa 1,6-diolwith modest1,5-synselectivity (synlanti = 6.6: l). 9H' u r - ) * C H 'HzL
pne I with TTN in methanol/chloroform hs rn an isoflavone(2) as the major prodntrturionof a halogengroup at the parar l reld of the isoflavone.
327
Il
o t
r) rhxBH! zln'o''o" ' u%
OH = 15:l) 2 (sYnlanti
with thexylborane(l equiv.) is also stereoselective, Reductionof 1,4-diketones showsno of 17-47:1. Reductionof 1,5- and 1,6-diketones with anri-selectivity 4nti-stereoselecmodest show can 1,3-diketones but reductionof stereoselectivity, tivity. (1989)' tT. Harada, Comm.,1429 andA' Oku,J.C.S.Chem. J. Uchimura, Y. Matsuda, 2T. Harada. (1990). ibid.,164l A. Oku, and Imanaka, S. Y. Matsuda.
3 (r3%o)
r r : c . .. { m .S o c . ,1 1 1 ,8 9 1 2( 1 9 8 9 ) ' Letters,3f,7355(1990)' . Ti:,ahedron
Thiophenol. p-lactonesis basedon the $-Lactones;alkenes.r A newone-steppreparationof to form pfactthatthe enolatesofphenylthiolestersreactwith carbonylcompounds
TboD rl
Thiophenol
provide alkenes. This new syn6crir t variety of tri- and tetrasubstiotcd dta ' R. L. Danheiser andJ. S. Nowicl,.l. &1 -Lisc6H' J0',
o4
o
" r l R' -fl, R'
i3
cyclizationis not observedwith lactonesdirectly (equationI). This spontaneous aliphaticthiol esters.This p-lactonesynthesisshowsmoderateto goodstereoselectivity for formationof thelesssterically hindereddiastereomer.The stereoselectivity
Tln(II) chloride. Diastereoselectivc cartotyl d;&, hydeswhen carried out witb SnClr (3 G addition,y-additioncan be sya- tillq t tivity can be controlledby thc solvcl- / of (E)-2-butenol-l with C6Iff,HO ir I -20o and resultsonly in y-additito ri can be controlled by the amountof rr + C.HTCHO
CH..,,Z',,,,.OH
hlr i
can bc improued by ase of eslen of26-dimehr/JbetzcrelhtoJ. P-Lactones are known to lose co2 stereospecilfcally when heated (90-160) to
a CH,CH:Cl{CllrCa
o il
c2H5csc6H5 * /--\ \---o ry
I
c
all"
'"",
THF,25" THF + H2O,-20" DMSO + HrO(l: l) DMSO + HrO(l:5)
(, -co, ro*Jtzo",
72% 35% U% 70%
' Y. Masuyama,J. P. Takahen, lad Y. Irr
CH.
?
?
(CH3)2CHCSC.H,+ C.HTCHzCHTCCHT-'--+
CHr-l
o_/o |
^__
Tin(II) trifluoromethencsulforaFlh Aldol reactionsr(15, 314-315). b t a chiral diaminesuch as (S)-l-ahyl-2{e and Sn(OTf)2and Bu2Sn(OAch,eldefr& loxy thioestersto form anri-c,p{ihydmrrl
"r"r,""rrrftt"'
**f^
os(cltrl
RCHO +
,<
BzlO
""" cF5(cHr),
scJt
,"" cH
rT. Mukaiyama,H. Uchiro, I. Shilu, rrd S. I
329
Tln(II)trifluoromethoneEulfonlte-Dlbutyltlndiscetrte
.oLi o l'll
I
provide alkenes. This new synthesisthus provides an attractive route to a wide variety of tri- and tetrasubstitutedalkenes.
I
r'^)^sc.n'l R
'
I R. L. Danheiser andJ. S. Nowick,J. Org., 56, 1176(1991).
I
Tin(II) chloride. Diastereoselectivecarbonyl allylation.r Pd(Il)-catalyzed allylation of aldehydeswhencarriedout with SnCl2(3 equiv.) can resultin o- and/or1-addition.In addition, y-additioncanbe syn- andlor anti-selective.The regio- and diastereoselectivity can be controlledby the solvent.All threeproductsare obtainedfrom reaction of (E)-2-butenol-l with C6II5CHOin THF. Addition of H2O permits reactionsat -20' and resultsonly in 1-additionwith cnti-selectivity.Reactionsof DMSO/HzO can be controlled by the amountof water to provide either syn- or anri-1-addition.
| 0",-.,r".", I
.
o4 t
o l
R-fl, i, R, clclrzationis not observedwith rs moderateto good stereoselecbstereomer.The stereoselectivity Enzenethiol. hcalll whenheated(80-160")to
cH^-/"'...oH
+ cuHrcHo
Pd(lD' sncl' > OH
t
CoH,
J
** | ,r0",-"o,
+
THF,25' THF + HrO, -20' DMSO + HrO (l: l) DMSO + HrO (l:5)
* ^1,anti-
CH,
o
CH,
l
+ cHt:cH-rAcuH,
CH,CH:CHCH,C.
' o 4o * r'-'-L--l t \
oH
9H,
'1/,syn' 53:22:25 0:6:94 0 : 8 6 :1 4 0:16:84
72Vo 357o 84Vo TOVo
t Y. Masuyama, Letters,30,3437(1989). J. P. Takahara, andY. Kurusu,Tetahedron CH,
o
+ I
o4 t"'*--l-.",
Tin(II) trifluoromethanesulfonate-Dibutyltin diacetate. ofa complex(l) obtainedfrom Aldol reactionsr(15, 314-315). In the presence (13, 302), a chiral diaminesuch as (S)-l-ethyl-2-[(piperidinyl)methyl]pyrrolidine and Sn(OTf)zand Bu2Sn(OAc)2, aldehydesreactwith silyl enol ethersof a-benzyloxy thioestersto form czti-c,p-dihydroxythioestersin high diastereoselectivity.
c^H,(cH2)2 cH]
**Jo
osi(cH3)3 RCHO + BzlO
cH'\-Jc cuH5(cHz)z
sc2Hs
oH
?
#AlsqH, oBzl anti-2 (96Vo de\
cH
'T. Mukaiyama, H. Uchiro, I. Shilna, and S. Kobayashi, Chem. Letters, l0l9 (1990).
330
Titanium(Ill) chloride-Potassium/Grrphite
Titanium(Ill) chloride. u,p-Dihydroxy ketones.r Reduction of l,2-diketones with aqueousTiCl3 (2 equiv.)in HOAc or CH3OHresultsmainlyin an a-hydroxyketoneor thedimer. The samereductionin the presenceof an aldehyderesultsin (syn, anti)-a,p-dihydroxy ketonesby reactionof a ketyl radical from the diketonewith the aldehyde(equation I). The yields decreasewith increasein the size of R3; the synlanti ratio also is dependenton the bulk of R3.
successfulcoupling of enonceldc sensitiveto the C3K/TiCl3ratio r reagent,but consistentlyhigh ykl low-valenttitanium obtaincdfru
I'T
(I) Rrc-cR' + HCoR31""',1'tn'c-i-i-n' 3o-rm% ll ll ll | |
o o
O
OHOH
c6H5cococ6H, + cH,cHo-,*{-
?
tuH'tH'
c.n,8-[-lHoH OH
CJt-..
(synlanti= 60:,10)
I
'A. ClericiandO. Porta,J. Or9.,54, 3872(1989).
cll Titanium(Ill)chloride-Lithiumaluminumhydride(14,307-308). Trienols. Solladi6 hasextended his reductive elimination of allylicdiolswith TiCl3-LiAlH4(2: l) to a synthesis of opticallyactivetrienolsfrom chiralallylic diols.
osiR3
,,*Jl ;il..i;.,'-','
I D. L. J. Clive,K. S. K. Mofllt. Majewski, P. C. Andersoo. C. F. Er S o c . , 1 1 2 , 3 0(1189 9 0 ) .
Titanium(Ill) chloride-Sodr I Reduction of a-oxinho cu imino esters(l equiv.) to o-rmir acid is a useful buffer; it does u cleanreactions. NOH
CH,
CH.
l
OH
t
CH.
l
ll
RCfoocH
CH.
IC. Hoffman,R. S. Tankc.rod M. ,. rG. SolladiCand C. Hamdouchi,Synlett,66(1989).
Titanium(IlD chloride-Potassium/Graphite, 14, 308-309. Enone-aldehyde coupling. A recentsynthesis of thering system2 of mevino lin (3),ta fungalmetabolite usedfor treatment of hypercholesterolemia, depends on
Titanium(Ill) chloride-Zix/crg McMurrycoupling.t This rcr a low-valentTi reagentfrom TiO fromTiClllZnCu(8, 483;9, 465
Titanium(Ill) chloride-Zinc/copper
!{rketones with aqueousTiCl3 (2 !-hrdroxy ketoneor thedimer.The ssultsin (syn,anti)-u,p-dihydroxy iletonewith the aldehyde(equation n of R3; the synlanti ratio also is
l t H t ]-C-R,
331
successfulcoupling of enonealdehydessuchas 1. The McMurry coupling is highly sensitiveto the CsK/TiCl3ratio and to the relative amountof substratesand titanium reagent,but consistentlyhigh yields can be obtainedby use of a large excessof the low-valent titanium obtainedfrom TiCl3 and CsK in the ratio 2: 1. (crH5)3si9
-
I
)H OH I
9uH' QH,
\:- . ) , l l l " " l r
C^H
"'"'YAg
(synlanti= 60:40)
CH, CHr"
lride (14, 307-308). ire eliminationof allylic diolswith active trienols from chiral allylic
'
9H' I
,.."--J/\CH1
.-. .:5'
3 ' D. L. J. Clive,K. S. K. Murthy,A. G. H. Wee,J. S. Prasad, G. V. J. da Silva,M. Majewski, P. C. Anderson, L. D. Heerze, andJ.R. Barrie,Am. C. F. Evans,R. D. Haugen, S o c . , l l 2 , 3 0 l 8( 1 9 9 0 ) . Tltanium(Ill) chloride-Sodium borohydride. Reductionof u-oximino esters,t This combination(3.15:2.8) reducesa-oximino esters(l equiv.) to c-amino estersin a bufferedsolution(pH 7). u-Tartaric acid is a useful buffer; it does not induce any enantiomericselectivity, but affords cleanreactions.
ilo"
ricrr/I{aBH.T"'
RCcoocH, #
nCHcoocH,
CH, f C. Hoffman, (1989). R. S. Tanke,andM. J. Miller,./.Org.,54,3750
l{. 108-309. csrsof the ring system2 of mevinodependson rf hr percholesterolemia,
Titanium(Ill) chloride-Zinc/copper. McMurry coupling.r This reactionhasbeencarriedout by McMurry et al. with a low-valentTi reagentfrom TiCl3/LiAlH+in THF, TiCl3/K, TiCl3/Li, and finally from TiCl3/ZnCu(t, 483; 9, 466). In addition,TiClalZnlPy and TiCl3/K/graphite
Titrniun(IV)
chlorlde
G"#:Oe oHc(cH2)',cHo ;;' tQi"-n \.-cn
?
?
, :c\tt: E cu,c
cn,c1cu,),,ccH,d
t(CH,),! havealsobeenusedinotherlaboratories.Thenow-preferredTireagentisthe solvate,preparedby refluxingTiClr in refluxingCH3OCH2CHzOCHT TiCI3(DME)r.5 for2days.Thecouplingr""g"n'fromthissolvateofTiClrandZn/Cugivesconsistently high Yields. of a have reviewed the reagentsobtainedby,reduction Betschartand Seebach2 probably are All reductants. of number of Ti(III) and Ti(IV) salts with a variety for organicsynthesis(195 potential similar have and Ti(0), soluble metallic, forms of from 1971to 1989). references I t. E. McMurry,T. Lectka,andJ. G' Rico,J' o!s'l5a'3748 (1989)' 2 C. Betschart Chimia,43'39 (1989)' andD. Seebach, Titanium(IV) chloride. beenpreparedby transmetTitanium enolates. Theseenolateshave generally talationofalkali-metalenolatesorsilylenolateethers.surprisingly,Evanse'cl.l from the oxazolidinoneI by find that a titanium enolatecan be pripared directly with ethyldiisopropylthereafter reactionwith TiCla (l equiv.) in CHzClzand shortly amine(ortriethylamine)at0..Theenolatemayactuallybeanatecomplex(2e)
cl'
l'
o
o
/*A-t"' \
/
a*o I
fi .....^\
o i
i
"An!""' , J.'f;!.". \ i --\^
o
t
l
o
'Tiel' \
o
t
-.,.-qA|,/=-t"' "\--i -*ct \"r,
-Bzl.
2h
2a
t*J'"'*",t'
o ll
-,\-,ocHroBzl
+
l
CH, 3 (>100:l)
rather than the expectedtrichlorui an electrophile in the ssrnc rry I lates.TiCL canbe replacedby i-h as base and can be added st th tl In additionto the simplified qt has someadvantagessuchrs iry patibility with a wider rangc of d for unhinderedketones,bcceslc t of chin The tetrachloroenolatcs reactionswith aldehydes.2la frcr, that obtainedwith the analqoos bt adductis often higher. Thc Ti dl the ketone in CH2CI2at - l7'. CzHsN(iPr)2. O TBSO t i l cHr-_A-,A'-cH,
t
+ 1(]1.
l
CH,
CH,
o
o
l l r l
oAruA-cH' \ /
a
+ (CH.)r
Bzl
Disubstitatedo,,l'utra,rr. (l) to actwith silyloxyacetylencs UCllBr.; Hr
oLl RCOOC2H5 Tl-,
Titaniun(IV) chloride
-\
l1
/
'-in t., I <el i-CH H.C:CCH, ' r C H , )), 1 oo*'-preferred Ti reagent is the 11in refluxingCH3OCH2CHzOCHT of TiCl3 andZnlCt givesconsistryentsobtainedby reduction of a y of reductants.All are ProbablY (195 ptential for organicsynthesis
333
ratherthan the expectedtrichlorotitanium enolate(2b), but in any caseit reactswith an electrophilein the sameway as shown for 2b generatedfrom alkali-metal enolates.TiCl4 canbe replacedby i-PrOTiClr, and in this casetriethylaminecanbe used as baseand can be addedat the sametime. In addition to the simplified operation,this direct generationoftitanium enolates has someadvantagessuch as improved yields and enantioselectivities,and its compatibility with a wider rangeof electrophiles.One limitation is that it is less useful for unhinderedketones,becauseof self-condensation. The tetrachloroenolates ofchiral ethyl ketonesundergohighly diastereoselective reactionswith aldehydes.2In fact, the syn/antidiastereoselectivityis comparableto that obtainedwith the analogousboron enolate,but the isolatedyield ofthe syn-aldol adductis often higher. The Ti enolatesare generallypreparedby additionofTiCla to the ketone in CH2CI2at -l'7", followed by dropwise addition of N(C2H5)3or C2H5N(i-Pr)2. TBSO O l t l
+ (cH,),cHcHo-]j#
cH,\y'\/\_-cH,
t
CH,
l
CH,
3.. 3748(1989).
TBSO
OH
"",y\A,AcH(cH3), CH, rrally beenpreparedby transmetahers. Surprisingly,Evanset cl.r nl1 from the oxazolidinoneI by 11thereafterwith ethyldiisopropylp actuallybe an ate comPlex(2a)
9
o
oA*\,.",
CH, CH, (96:4)
? ? "
*'TtH(cH3)'
gg% + (cH,),cHC"o
(94:.6)
....riq, o o
'cH' -
i l l -cr oANAtcH' , +cr- \ a 'Bzl I
t
t
2
e9%JBzlocH:cl
Disubstituted ar$-unsaturatedesters.t In the presenceof TiCla, aldehydesreact with silyloxyacetylenes(1) to form o,p-unsaturatedesters(2) in moderateyield. LiCHBrr; Bul-i;
Rcooc.H.-#( 5 0 -
Rc=c-osiRl |
r,.,. J*'."o,
b
l-n
o
tl ^-.,\,OCHtOBzl p l CH, 3 (>100:1)
lH ['-o
R COOCH. \./ c
osiR;l
lift.
-j
i;5r
R'l
tl c
\H t
334
Tltanium(IV)chloride
The silyloxy acetylenescanbe preparedin one stepin moderateyield from estersaby sequentialreaction with dibromomethyllithium, BuLi, and a chlorotrialkylsilane, usuallychloro(triisopropyl)silane.A valuablefeatureofthis reactionis the high (E)selectivity, which could result from an oxeteneintermediate(a). Diastereoselectivereaction of allylsilanes with s,-amino aldehydes.s The diastereoselectivityofthe reactionofallylsilane with the protectedc-amino aldehydeI dependson the quantity of TiCl4 used. Thus cnti-selectivity predominateswhen I equiv. of TiCla is used,Du! syn-selectivityobtainswith lessthan I equiv. The aamino aldehyde3 showssyn-selectivitywith stoichiometricor catalytic amountsof TiCl+. Theseresultssuggestthat aldehydessuchas I can form both l:l and 2:l complexeswith TiClr.
d-{"'o
+ + CH,:CHCHTS(CH3)3
""\l'"0,
?"
Titanoxycyclopropotrct ; /caa boxylate (1) provides thc pden NMR. Reactionsof 2 with bc homoaldol (3). Reduction of 3 r Cl.fr
coocH. (cH3)3sio\
I A
rio.. -78+-3(r ) -crs(clr,)'
l-Bu'
t
I
t(
syn-2
UOlA.nCHr+ I HNCbz
anti-2
l-1
+ TiClo(l equiv.) + TiClo(0.5 equiv.) + TiClo(2 equiv.)
20:l l:8 l:l
844o 45Vo 69Vo
?" (cH3)rcHcHCHo + CHr:cHcHrs(cH3)r +
(CH3)rcHcH+CH,
l
+ syn-4
l
(4). Reaaiooof t tetrahydrofuran in 79%yicld.TL of two isomers noneto giveessentially oncprot
HNCbz
HNCbz
t-Br
anti-4
+ TiClo(l equiv.) + TiClo(0.6 equiv.)
l:14 l:1.5
82Vo 46Vo
Dihydropyrans.6 The silyl ethersofhomopropargyl alcoholsin the presenceof TiClacondensewith aldehydesto form dihydropyrans.This reactionis highly dependenton the substituentsofthe silyl group, with bestresultsobtainedwith the bis-silyl ether (1) of 4-pentynol-2.Use of AlClr as catalystor of the free alcohol resultsin at
products. acyclic leastthree CH, a/\./9rH5
L
% cH+ cH,cH,cso
A-{'-t
C.H.N-"C I
CH, I
ricr
CI I ^ c,H,"'\9/"'cH, 2
Oxepanes.t Addition of I 2. penyl ether suchas I to a diluc r allylic metal on the epoxideto Jrro
'r
h.R H H.C BurSnJ
> I
Titenium(IV) chloride
p rn mderate yield from esters4by BuLi, and a chlorotrialkylsilane, ture of this reactionis the high (E)Itermediate(a). 3h a-amino aldehydes.s The diaI the protectedc-amino aldehydeI n-selectivitypredominates when I ins with lessthan I equiv. The achiometricor catalyticamountsof t as I can form both l: I and 2: I
Titanorycyclopropanes;tetrahydrofurans., Methvl 2-siloxycyclopropanecarboxylate (l) provides the pale-yellow titanoxycyclopropane2, identified by rrcNMR. Reactionsof 2 with benzaldehydeat low temperaturesprovides a single homoaldol (3). Reduction of 3 with a silane and BF3 etherateprovides a single
cl.lTi-...o. ,ocH, \ \.2
coocH3
(cHr1r51O n
\
-,J5!i0",
?"
c
c6H,cHo.-78.>oHo\acuH,
\l
-cls(cHr)'
t-Bl/
58%
,-,,ut I
2 (dec.90- 100")
,-B"AlcoocH3 3
",Jlil,."atall,,.
syn_2
to-ffCH2+
33S
HNCbz
'-BuYoTc6Hs
anti-2
a"oo"",
20: I l:8 l:l
?" ]}l,r.CHCHnACH, ' l
+ syn-4
4
tetrahydrofuran(4). Reactionof 2 with isobutyric aldehydeprovides5 as a mixture of two isomersin 79%'yield. The titanoxycyclopropane also reactswith acetophenoneto give essentiallyone product.
HNCbz
r) t-Bu:.2-\zCH(CH3), \ /
anti - 4
l;li pargylalcoholsin the presence of ns. This reactionis highlydepenresultsobtainedwith thebis-sityl or of the free alcoholresultsin at
coocH, 5 (79Vo,90:10) Oxepanes.t Addition of a 2,3-epoxypropyl2-[(tributylstannyl)methyl]_2_pro_ penyl ethersuchas I to a dilute solutionof riclr in cH2cl2 resultsin attackof the allylic metalon the epoxideto providethe oxepane2 in95vo yield. Similar cycliza-
cl
I{l-,r. ___--____) 6
t
I
Z\ |
| * t l crHr"'\o/"'cH, 2
h 'l-\' .R-H u'
\
-F/
H"C. BurSnJ
I
I O
rict. cH,cl,,0. es%
336
Titanium(IV) chtoride
n
tion obtains when sn is replacedby Si. of a variety of Lewis acids incruding Ti(o-i-Pr)a, Snclr, AlClr, only Ticta is generally useiur for this cyciization.of firrther interest,the processis diastereosp"Jifi.ir th" substrateis addei slowry to the Lewis acid (l equiv.). Theprecursorsare availableby alkyrationof substituted 2,3-epoxyarkoxideswith methyl 2-l(tributylstannyl)methylJ-2-propenesulfonare (3)e fofiowej Uf .t ro..tog_ raphy.
*'..,/o\..'" H
cH"
il'
.^) LiO
* CH3SqCHrCCHrSnBu, *5 3
,
conjagate propynyration of enones.t, In the presence of ricla (l equiv.) alIenyltriphenytstannanes add1,4 to cyclic andacyclico,p-enones.other Lewis acids are ineffective.Use of Znl2 canresultin 1,2_ajdition.
7 H.-U. Reissig,H. Holzinger.lod G. I 8 G. A. Molanderand D. C. Shubcn.,tr Andrews,J. Org.,54, 3l t4 09t9f . e B. M. Trost, D. M. T. Chan.end T, ! r0J. Haruta,K. Nishi, S. Marsudr.y.
(1e89).
Titanium(IV) chloride-Nunirn. Allylation of imines.t A lor-v TiCla with aluminumfoil in THF ca even when usedin catalytic anxxrr.r amountof TiCla with I equiv. of dul which reactswith the allyl hali& ro I
N tl
,Bzl
^,,)
+ CH.:Cl{Cll
Lohs
CH,)-CH,
p,^coocH, "u"r) + CHrCH:C:CHSn(CuHrt
+ cH':cl
;-
CH, CH_C:CH
lD.A..Evans,F.Urpf,T.C.Somers,J.S.Clark,andM.T.Bilodeau, Am.Soc.,ll',g2ls (1990). 2 D. A. Evans,D. L. Rieeer,M. T. Bilodeau,and F. tJrpi,ibid.,ll3, 1047(1991). 3 C.
J. Kowatski andS. Sikdarat, t. ors.,ii',fiti
Useof an opticallyactiveimim frq allylamine. I H. Tanaka, K. Inoue,U. pokonti. lf I 3023(1990).
Titanium(IV) chloride-Til-niurfiy) 12* 2lCycloadditions.t Acyclk a [2+2'lcycloaddition with alkenes.bot r cloadditionin the caseof methoxymcttr vinyl ketone.Usually2 equiv. of I a r
Titenium(IV)chloride-Tltsniun(IV)isopropoxide 337 I a r ariety of Lewis acids including nlll useftrlfor this cyclization.Of if rlre substrateis addedslowly to the rubsriruted2,3-epoxyalkoxideswith lfonare(3)e followed by chromatog-
7 H.-U.Reissig, H. Holzinger, andG. Glomsda, Tetahedron45, 3139(19g9). 8 G. A. Molander andD. c. shubert, Am. soc.,rog, 576(r9g7);G. A. Moranierands. w. A n d r e wJs., O r 9 . , 5 4 , 3 l 1 (41 9 8 9 ) . e B. M. Trost,D. M. T. Chan,andT. N. Manninga, Org. lyn.,62,5g(19g4). loJ. Haruta,K. Nishi,s. Matsuda, y. Tamura,andy. Kita,LC.s. chen. comm..1065 ( | 98e). Titanium(IV) chloride-Aluminum. Allylation of imines.t A low-valent Ti(O) speciesgeneratedby reduction of Ticla with aluminumfoil in THF can effectallylationof imineswith allyl bromide, evenwhenusedin catalyticamounts(0.05 equiv.). This combinationof a catalytic amountof ricla with I equiv. of aluminumpresumablygenerates AI(III) andri(0), which reactswith the allyl halideto form an allyltitanium,the reactivespecies.
l.r"r,.*''o, r 86%
be presenceof TiCla (l equiv.) alclic c,p-enones. OtherLewisacids lrtion.
)
^
--.8'l N tl
,Bzl HN'
+CH":Q11gH"sr-lLTl+ ' vrr2-Lrrv"2sr 'C.HT
%$CuHrt
cH'\-CH,
cH2-c:cH
p "u'r)
fi. r, --+ tl%
CHTCH:CH,
cH'
cH' , qp^coocH,
coocH, + CHr:Q11gHrBr i!f:g*
cuHr\ACH, (20:1\
''*J NH, I
CH,
cH-c:cH
I
CH,
cuHr-Acs, Useof an opticallyactiveimine from r-valineresultsin an opticallyactivehomoallylamine. I H. Tanaka, K. Inoue,U. Pokorski,M. Taniguchi, ands. Torii, Tetrahedron Leuers,3r, 3023(1990\.
d \{ T. Bilodeau, Am. Soc.,ll2,82ls trpi. ibid., l13, 1047(1991). 1r 990). io(- . l0t, 7127 (1986). t . J O r g . , 5 4 . 5 4 0 9( 1 9 8 9 ) . r o o 5r 1 9 8 9 ) .
Titanium(IV) chloride-Titanium(IV) isopropoxide(1, I : l). f2+2lcycloadditions.t Acyclic enonesdo not usuallyundergophotochemical [2+2]cycloadditionwith alkenes,but this Ti(IV) Lewis acid doespromotethis cycloadditionin thecaseof methoxymethyl vinyl ketoneand,to a lessextent,of methyl vinyl ketone.Usually2 equiv. of I or of TiClr(O-i-pr)2is required.
Tr-
Titanium(IV) chloride-Titsnium(IV) isopropoxide
tl
cuHr.. C.HTCH:CHCH,
o i
l
+ CH,:CHCCHTOCHt
_ *d
\
/ccH2ocH3
)
CU(
Titanium(IV) chloride-Zinc/cop a,$-Dihydrory esters.t Tbc I Cu convertsalkyl glyoxylates iato poundsto form a,P-dihydroxycsra -45' in CH2CI2/DME, sirrceDM compound.
(l: l)
"n,o" J*,.o,, cuHr...
BZIO"CCHO+ A'CII
o ll /ccH2ocH3
I_l
BzIOTCCHO+ Cfl
cH(Pterocarpans.2This Lewis acid (l) effects12*2lcycloadditionof 2H-chroto form cyclobutanes,which rearrangein menswith 2-alkoxy-1,4-benzoquinones situ to the pterocarpanskeleton.
CH3o\Zyo\
\A/.
Z'yo
r,cltcr,
tT. Mukaiyama, H. Sugimun.T. fr
Tltanium(IV) isopropoxi&. Halohydrins. In the presc convertsepoxidesof trazs-dlylic c high yield with markedregiocclai essentialfor regioselectivity.
o ot{
J---o\o,,-
o+l
,r-; J cH3o
.\
I
'(
I E. Alvarez,M. T. Nuflez,end V- S.
Titanium(IV) isopropoxldc-r{ + Enantioselectivctrinalyldl in theprescncc ofn benzaldehydes
Titanium(IV) isopropoxide-l-( + )-Diisopropyl tertrste
il
CoHr..
t-I + 14
,
/ccH2ocH3
/ CH,
(l:l)
Titanium(IV) chloride-Zinc/coppercouple. u,$-Dihydroxy esters.r The low-valent Ti compoundformed from Ticla-Znl cu convertsalkyl glyoxylatesinto a Ti enediolatethat reactswith carbonylcompoundsto form a,p-dihydroxyesters.The reactionis generallyperformedat -23 to -45" in cH2cl2/DME, since DME alonepromotes self-couplingof the carbonyl compound.
o CuHr...
OH
ricl.-znrcu,
| *,.o,,.".o"
J
Bzlo,ccHo+ ArCHo##
tl
nao,cCH-Cuar = 72- 82: 28- 18) (syn,anti OH
/ccH2ocH3
1-1
OH
t
BzIOTCCHO+ C.HTCOCH.' ;
OH
l
BzIOTCCH-CC'H,
CH'
CH, (syn,anti= 30: 70)
l? * 2fcycloadditionof 2H-chroIclobutanes,which rearrangein
cHlo
lT. Mukaiyama, H. Sugimura, T. Ohno,and S. Kobayashi, Chem.Letters,l40l (19g9).
Titanium(IV) isopropoxide. Halohydrins- In the presenceof I equiv. of ri(o-i-pr)r, bromine or iodine convertsepoxidesof trans-allylic or homoallylic alcoholsto halohydrinsat 0-25o in high yield with markedregioselectivity.The presenceof the free hydroxyl group is essentialfor regioselectivity.
OH I
o luSl:fl;;, a-'yo" 80% V"'t
OH -\
(rE"o I E. Alvarez,M. T. Nufrez, and V. S. Martin, J. Org., SS,3429(lgg}\.
m lztters,30, 176l (1989). S Chem.Comm.,454(1989).
Titanium(IV)isopropoxlde-r.-( * )-Diisopropyltartrate (DIPT). Enantioselective trtmethylsilylcyanation.r The addition of (cH3)3sicN to benzaldehydes in thepresence of anequimolar or catalyticamountof a Sharpless-like
p-Toluenesulfonylhydrozine OSi(CH3)3
ri(oi-Pr)..DIPI
C6H5cHo+ (CH,),SiCN-##-
RCHCN G90Vo ee\
catalyst(A) preparedfrom Ti(O-i-Pr)aand I-DIPT (l: l) proceedswith only moderate enantioselectivity,which is not improved by addition of molecularsievesor by removalof isopropanolfrom catalystA by freeze-drying.However, additionof l-2 equiv. of isopropanolper Ti to this freeze-driedcatalyst provides a catalyst (D) which is highly effective, both in equimolar and catalytic amounts. 'M. Hayashi, (1990). Comm.,1364 T. Matsuda, andN. Oguni,J.C.S.Chem.
Alkenes can also be oheinod saturatedaldehydeswith a vioylli at centersadjacentto the aldciy& of both di- and trisubstiotcd dh
Ts I ..NSiR3
R.SiO ry " l J i --.'-t:..,, : CH,
n
Li
I
r
]
+ '
{
><
tRr= (CoHr)zC(CHJrl
pToluenesulfonylhydrazine. Alkenc synthesis. A modified version of an earlier synthesisof alkenesfrom the tosylhydrazonesof aldehydesand certain alkyllithium reagents(9, 472-473) of c,p-enals, employsthe N+-butyldimethylsilylderivatives(l) of tosylhydrazones o which undergoonly I ,2-additionof an alkyllithium at - 78 . The adducts(2) decom-
cH.
c:
cH.A..a-/ Ts
Ts
I
I N
/,NSiR3
N
tl
CuHt
I CH, I
BuLi
H
Iqt-"-siR, I
c.H.\4su I H CH, 2 ^^I so*, cr,cupx uor
' o
I A. G. Myers and P. I. Kultolr. ,tr
| _20.
cst(\/\nu it,
Tributyl[(methoxymethoxy)r.r l) LD^. nf
BurSnH
'"*rol
r I
3 GIZ = l2:l) with elimination of pposeat -20. when treatedwith acetic acid and cF3cH2OH rearrange1'5-sigmatropic a with ioluenesulfinicacid, the silyl group, and nitrogen in high 12:1, ratio (3) the in (Z)-alkene mentto providea mixture of-an 1e1-ana overallyield (88%).
Hydrorymethyl anion cgitd transmetallationon treatmcntviti I ing lithium reagent(2) which eddr t gem-diol.The methoxymethylgrc acid.
Tributyl[(methoxymethoxy)methyUtin
1'r
r t{
os(cH.). -|
341
Alkenes can also be obtained by reaction of the silylated p+osylhydrazoneof saturatedaldehydeswith a vinyllithium. of further interest,no epimerizationoccurs at centersadjacentto the aldehydegroup. The (E)-configurationis favoredin the case of both di- and trisubstitutedalkenes.
' RCHCN (-9OVo ee)
T rl : l) proceedswith onlYmoderrddition of molecularsievesor bY :{ry ing. However,additionof l-2 d catalystprovidesa catalYst(D) catalyticamounts. (1990)' tr Comm.,1364
Ts
I
R3sio il t l
/,NSiR3 R3SiO
>Y""'
Y'-t CH,
CH, H ( E l Z= > 2 0 : l )
[Rr= (CoHr)rC(CHr),]
n earlier synthesisof alkenesfrom rlkrllithium reagents(9, 472-473) of c,p-enals' I t of tosylhydrazones m at -78o. The adducts(2) decom-
Ts /,NSiR3
CH. l "
CH. ry I
l l
Li
CH"
--------) CH,
H
83%
cnr\'-\-\-C-H
i 1 "1't*-r,*,1 ,-=l,f"" I CH, ,
CH, (ElZ= >2O:l)
I
I A. G. MyersandP. J. Kukkola,Am. 5oc.,112, 8208(1990).
.** I 1l^1"'cF,cH:oH J * H
'-11,/\.,/\nt '
Tributyl[(methoxymethoxy)methylltin,
Bu3SnCH2OCH2OCH3(l). Preparation:
I
l
CH, = 3'ElZ 12:l) ICF.CH2OHwith eliminationof Prearrangeo *ith a 1,5-sigmatropic I' in high (3) 12: ratio in the Itcne
I) LDA, THF
cHrocHlocH,,
2)(HcHo)" > [BurSnCHroHlgAT#4 BurSnH
t
Hydrorymethylanion equivalent(cf., t,495).2 This tin reagentundergoes transmetallationon treatmentwith LDA or BuLi at - 78' to providethe corresponding lithium reagent(2) which addsto ketonesto form a monoprotectedderivativeofa gem-diol.The methoxymethylgroup of the adductis cleavedon treatmentwith dilute acid.
Tributyl(isoprenyl)tin
a\ I
'u'',
LicH20cHro"",#' t
9H, I
CHr:C-Ctt:CHr
ut"H20cH3 ,,*flfJ'"",o"'
+ llCl
Atlylation of quinotcs.t la t tyltins add to benzo- and nePhtog quinonesor hydroquinoncs.An err
cH30
trfl
a 1 5
I
cH30 r R. L. Danheiser,K. R. Romines,H. Koyama,S. K. Gee,c. R. Johnson'andI' R' Medich' Org. Syn.,submitted(1990). 2 C. R. Johnson,J. R. Medici, R. L. Danheiser,K. R. Romines,H. Koyama,andS' K' Gee' iDid., submitted(1990).
Tributylarsine, Bu3As. ylides' Ar3As+CHX-' are useful Catdytic Wittig'type reaction'r Arsonium be more reactive than the correcan l7O), and Wittig-type reagen; in, nl;14, spondingphosphoniumylides.onedisadvantageisthetoxicityofarsenicsalts. and can be used in catalytic However, arsonium ylides can be generatedin situ amountsinthepresenceoftriphenyl-phosphite,whichregeneratesBu3Asfromtribuwith methyl bromoacetatein tylarsineoxide. Thus tfre reactionof various aldehydes (l equiv') and BurAs (0'2 KzCOr (l and equiv') iirc pr"r"n"" of triphenyl ptt"-pftrc yield and in E/Z ratios of 97"q-oi".l provideso,0-unr",ot*"d estersin ffi-87% 99:3-1. Bu,As
+ KPO' =#L + (CuHrO)rP RCHO+ BCHTCOOCH, ncu9cgcoocH, + (cuHrO)rP:O 'L.Shi,W.Wang,Y'Wang,andY'-Z'Huang'J'Org''54'2027(1989)' (1)' Trlbutyl(isoprenyl)tin, Bu3SnCH2CH:C(CH:)z of hydrochloric acid (36%) to addition by p"pttta' This allyl trialkyltin can"i" which undergoesan ultrasoundBarisopreneto form 4-chloro-2-mitt'yt-Z-Uut"ne' methodis usefulfor preparationofother bier-typecros, "oupring *itt' iurSnCt' This allylic tributYltins.
rY. Naruta,Y. Nishigaichi. ud K- Ir 2 Y. Narutaand K. MaruYarna.Ory SY
Tributyltin hydride. Radicalring cxpansiorr(ta. 3 (3) fromcyclodo thesisof muscone
ff
343
Tributyltlnhydrlde
HxH,ocH2ocH3
"..i
.(e' I HCl,CHTOH,
cH" I CHr:g-"t:CHz
tu'tl8'."' -----+ --------t (CHr)rC:CHCHTCI + HCI
I
Allylation of quinones.2 In the presenceof BF3 etheratevarious allyl tributyltins add to benzo-and naphthoquinones to form a mixture of the corresponding quinonesor hydroquinones.An exampleis the synthesisof ubiquinone(2).
lrt HO
CH"OH
.1
cHrovA/cHrcH:c(cHr), r)BF,.o(clr!)'
cHro\-A
-;-=
cH,o{AcH,
-cH' cH,o\}cH, cH3oY 2
Gee.C. R. Johnson,andJ' R. Medich' andS. K. Gee' H. KoYama, I Romines,
r llides, Ar3As+CHX-, are useful u be more reactivethan the correge is the toxicity of arsenicsalts. r situ and can be used in catalYtic Bu3Asfrom triburhich regenerates in chrdeswith methylbromoacetate DdKrCO3(l equiv.) andBu3As(0.2 B:{ yield andin EIZ ratios of 97-
I Y. Naruta,Y. Nishigaichi,and K. Maruyama,Org. Syn., submitted(1990). 2 Y. Narutaand K. Maruyama,Org. Syn., submitted(1990).
Tributyltin hydride. (14,317-318). Thisreaction hasbeenusedfor synRadicalring expansiont (3)fromcyclododecanone. with3-chloroAlkylationoftheketone thesisofmuscone
o cH, ,,"".,," |
CH,
2) N8I, _--)
Arr^C H , /o\ \-,^=/
t Bu.As :1{F - cH.cN, 25' )
tn -vqo
ICH:CHCOOCH, + (C,H,O),P:O Ore . 54,2027(1989).
ernn ,*Jnu,snn,
oh',.-"", t
l
/,-.. , ; -r l ) . dirion of hydrochloricacid (36%)to rhich undergoesan ultrasoundBarhod is usefulfor preparationofother
\
\ ' / (, 3
34
Tributyltin hYdride
provides1, which on additionof hydrogenbromideand replace2-methylpropene mentof Br by I providesthe iodide2. This producton treatmentwith Bu3SnH(AIBN) underhigh dilutionprovidesmuscone3 (l4Voyield) andthe productof directreducby tion of 2 (63Voyield). This sequencewas usedfor a synthesisof (R)-muscone (available from with (S)-3-bromo-2-methylpropanol alkylationof cyclododecanone Aldrich) to give a product that can be convertedinto an optically active form of 2' also in low yield (l'Vo). Conversionof this chiral iodideprovided(R)-muscone, reductionofp-alkoxyRadical radicalreduction orallylation.2 Stereoselective with Bu3SnH(AIBN) at o-haloesterssuchas I showsmarkeddnti-stereoselectivity irradiation photochemical 50., which is markedlyimprovedwhen conductedunder tetrahythe of reduction obtainsin at -78o. Similarbut evenhigherstereoselectivity drofuranderivative2.
?"",
crH,/Xcooc2H5 Br cH,
AIBN Bu,SnH, lrv.-78"
-t
*------
I
85% 90% EE%
syn-Hldrostannylation of oltyrct.t 1 in the presence of Pd[P(Co]I5)3la rr 25' to; alkyne, both possibleadductsare usuelly fr ally observedin hydrostannylatiooof ircr A.OC
'@.. HOCHTC=CCHr +
t
a'. I CH3
I
t
cooc2H5
Bl5.
BurSnH
o
93%
Allylation of these p-alkoxy-a-haloesterswith allyltributyltin initiated with which canbe improved AIBN at 60oalsoshowsgoodto impressivestereoselectivity, -78o. reactionsaregenerally these However, by useoftriethylboraneas initiatorat slowerthan radicalreductions.
*r.#f 2 + CHr:Q11CHrSnBu,
syn-1,&Diols.s The radicrt forocd frr homoallylic alcohols with rnom- or diexclusivecyclization to 6-membercdcird diols on oxidationwith H2O2(3Ot) n L ever, the samereactionwhenapplbl to r r terminusresultsin cyclizationto r ssverr H3C\^./'CH!
($r"ooc,H5 CH''
CH'CH:CHt ( > 3 0 :l )
?"r, i
d/1, a, R = CHc b,R=OCHr c,R=F
, a.rq,
Bu,SnH
2,R=TBS
cuHr&coocHi
*n'*
AcOCHTC=CCHTOAc #
C.HTAyCOOCTHs : CH, (32:l)
( no)l-.- -COOC.H. ------) \----J
H.
Bu,rs1{.;?r
Rtn 9CH, I
^ H
(,
"tr*
(I) c6H5Lcooc2H5 /\ HrC Br
+ cH,:eflgHrsnBu,=#=, t)aa
?tn'^^^ '
.."'^Y,::"
cH'cH:cH' (antilsYn= ITll)
reduction o! acyclic a'bromo esters.r Highly diastereoselective Stereoselective radical reduction of c-bromo estersobtains when an electronegativegroup (F or OCHI) is presentat the P-position,particularlyat low temperatures'
(1,
ar-tt-cHJ.
i c-c.n,,\A1H{ cllr
rt
Tributyltin hydilde
droeenbromideand replacelatrnentwith BusSnH(AIBN) d rheproductofdirectreducsr nthesisof (R)-muscone by lhr ipropanol(availablefrom rn optrcallyactiveform of 2. r . r l . o i n l o w y i e l d( 1 5 % ) . ladrc.ilreduction of p-alkoxytir rtr * ith Bu3SnH(AIBN) at irradiation kr photochemical rnsrn reductionof thetetrahy-
"rr* HrC Br
2:l 32:l Z0:l
syn-Hydrostannylntionofalkynes,a This reactioncan be effectedwith Bu3snH in the presence ofPd[P(c6H5)3]a at 25o to providevinylstannanes. In the caseofa lalkyne,bothpossibleadductsareusuallyformed,but someregioselectivity is generally observedin hydrostannylation of internalalkynes.
AcOCHTC=CCHTOAc
Pd(0), c.H.,25. 93%
AcOCH, CH"OAc \ . / C:C H
ll: l)
SnBu,
HocH'\
.rcH'
HOCH2C=CCH3 ----+
\. cooc2H5
,ZC:C\ BurSn
t
Bu,SnH
71I' illr ltrrbutyltininitiatedwith ir rtr . whichcanbe improved rhe.ereactionsaregenerally
H3c\^./,cHi
t'..
CH.CH:CH,
>:tt:l)
+
H
H
g-tt-cHrBr .u
c-cuH,,\A/t
?.", c^H.t\\,-coocH3 l CH,CH:CH,
.rcH'
/c:c\ (t4%)
CHr-^.r.CH, Bu,snH
H'
{"t)
.-cuH,,\.A.,-cH,
cH. *.-*.* | H,q,KHco] * *'-JrHFrcHloH, ^
(antilsyn= lTll) -OH
i.-' Highly diastereoselective electronegative group (F or temperatures.
SnBu,
syn'1,$Diols.5 The radical formed from (bromomethyl)dimethylsilylethersof homoallylicalcoholswith mono- or dimethyl-substituted doublebondsundergoes exclusivecyclizationto 6-memberedcis-siloxanes. Theseare convertedto cis-I,4diols on oxidationwith H2o2Q0%) in the presenceof KHCo3 (equationI). However, the samereactionwhenappliedto a substratelacking a substituentat the olefin terminusresultsin cyclizationto a seven-membered ring, which is oxidizedto a 1,5-
\>-.COOC2H5
.\
"*"'a. +
(74Vo)
CH
l,
H3C H
85Vo NVo 884o
BurSnH
CH,
+ cour/-ycooc2Hs /...
H CH3
d/1,a,R = CHr b, R = OCH: c,R=F
OCH. ,'^.r.,/.COOCrH5
H R
Bu,srH,-78. 1 r* i'tgN' a" r crHr/'',cooc2Hs /...
(r) c6Hr&cooc2Hj /\
345.
o H r
t l c-Cutt,r\,A''cHr (crs)
36
Tributyttin hydrid€
-';)''i
CHr._^.rrCHl
CH3--^.rrCH: - 5 1 - -cH,Br
(Il)
6 I
i szqo
c-CoH'rMCH,
oH ("'P" t )
t
c-cuH,r1.--_-)
diol.Thiscyclizationprovidesaroutetosteroidswithdihydroxylatedsidechains (equationIII).
CHtoH -..CHt
l) BurSnH (95%)
DEp,(g't%)
>
CH,
cH
Treatmentof the epoxythionoimidazCyclizationvia epoxidefragmentation'6 of the an alkoxy radical by fragmentation olide I with BurSnHuno miln-g"nerates (2)' cis-fusedbicyclic system "po*ygroup with cyclizationto u S
\
tl y^g \-/
,\
acoocHr
I-o) L \,r^\-/ t
n,s"n.
H /coocH3
reactioncan bc usodI phenylselenocstcrs oo
(' cfl
---.UV oH , rr.r,t,
of secondary (11' 550)' Radicaldeoxygenation Deoxygenationof R2CHOH? More Mccombie' and *u, introdo."d by Barton alcohorsvia thiocarbo";i;;; deoxyradical the for havebeenrecommended recently,phenoxythioc""i""yf esters obtained andquantitativereductioncanbe rapid genation(f0, 306-307)'fu'titutu'ty esters' ot pentafluorophenoxythiocarbonyl using2,4,6-trichlorophenoxyBu:SnH/ of alkyl or aryl radicalsgenerated'with RX' RCHO.s Carbonylation is more alkane the to reduction useful AIBN from halides i' "'""fiY not tt::* in effected vields be can of RX to RCHo facile. However,this ;;;it;;"";sion with 15-90atm' and M) ( 0'05 concentrations of 40-'10%ifBurSnHis usedin low "t a,?",
CJrS.
radicalsgeneratedfrom phenylselenoradicalsfrom Rcosecals.e Acyl The latter tandem lntru*ot"cular alkeneaddition. esterscan participatei" i;;r- una
Intermolccttbtfi reactionsof acrylooi trolled by adjaccnrrl whereasan equsurria beredcyclic radicdr. tutedproducts(tt: l2
(cH3)!ca
+ O cq: r
Trlburylfin hydrldc
:H
+
oH
l
l
acH.g
c-C6Hrr^v/
til_HdcH,:cHcoocH,, a-n $% v o^s"cuH, L\aryj
ur:r dihvdroxvlated sidechains
H
a-'l--\
oH
\.+-/ b
"",*""d","
cH2oH
H imc'ntof the epoxythionoimidazy radrcalby fragmentation of the c . r . t e m( 2 ) .
reactioncan be usedfor macrocyclizationunder standardhigh-dilutionconditionsof phenylselenoesters containinga terminalunsubstituted alkenegroup.
o ll
o
}il, 6d-.o-,tcH,\fisecoH, An o cH, Vo",,"
I I
l:;'
OH 2 (2.7: l) kal deoxygenation of secondary t Banonand McCombie.More for the radicaldeoxyommended trtatr\e reductioncanbe obtained rr throcarbonyl esters. with Bu3SnH/ radicalsgenerated reductionto the alkaneis more RCHO can be effectedin yields r -0.05 M)andwith15-90atm.
,;3"
Intermolecularfree radicar reactions.ro Giesenotes the diastereoselectivity of reactionsof acrylonitrilewith cyclic 5- and 6-membered ring radicalscan be con_ trolled by adjacentsubstituents. Thus an axial p-substituent can favor axiarattack, whereasan equatorialp-substituentfavorsequatorial attackin the caseof 6_mem_ beredcyclic radicals.Glucosylradicals,t.g.rdl"r, of the precursor,yierd c-substitutedproducts(88: 12). OH
(cH ,),c1_ \
-
' lr l
( cH,) - c- - .l-
\ \_---\\
from phenylselenoils senerated Iteneaddition.The lattertandem
+ CH2:CHCN eq:ax = 27:73
+ CH2:CHCN eq: ax = 79:21
-. CH,
34t
Tributyltin hYdride
Acyl radical cyclization to cyclohexanones.tt Acyl radical cyclizationto fivememberedrings is well known, but this reactionis also useful for synthesisof as shownby a recentsynthesisofthe c-methylenecyclocyclohexanones substituted hexanone 3. Thustreatmentof the selenolesterI with Bu3SnHandAIBN in C6H6at 2 in 9l% yield. Oxidationof 2 with 80' providesa 1:1 mixtureof cyclohexanones
-OBzl
nzrc\qi-.-'-o, nzto\--ff\scx,
t
Al
J'
ocH! I
o R3sio
tl
osiR3
Bu,snH, AIBN
/\-CH,SC6Hs
-#t-
c.H,S/$CoSeCuH'
t
Rlsio"
1' R,= 1-9u14",
l
\-osiR3 2 (l: l)
u*Jllx"",",",o" CH.-
"-\ osiR3
BulOvitaprovides3, a unit presentin 14,25-dihydroxy monoperoxyphthalate magnesium 5 in provides cyclohexanones 4 of I min D3. The samecyclizationof the syn-isomer 8l/o yield.
o
R3SiO
cnHrs'\z^v!
OSiR3
-=> coSecuH5
tl /Ar\,,'CHrSC6H5
t
l
RrSiO.,,,,yosiR3 5
$-Glycositlcs.r2Hemithioorthoesterssuchas I are reducedby Bu3SnH(AIBN) mainly to p-glucosides(2). The methodcan also producethe maltosedissacharide4 is not clear. as a l0:l mixtureof anomers.The effectof anomericCz-substituents Desulfunylationof }-keto sulfones.rs Radicalreductionof thesesulfoneswith Bu3SnHand AIBN can be more efficientthan the conventionalmethodwith Al/Hg. An excessof initiator is necessaryfor ready and completereduction, but yields of equiv.of AIBNin 4equiv. of thestannaneand2 80-95%canbeobtainedbyuseof refluxing toluene.
t P. Dowd and S.-C. Choi, Tetralvdta L 2 Y. Guindon,J.-F. Lavallde, L. Eoisvcrr.
Lemieux, and B. Simoneat, Taralu*a 3 Y. Guindon,C. Yoakim, R. Lcnku. L hedronl*tters,3l, 2t45 (1990). 'H. Miyake and K. Yamamun, Clcr la s M, Koreedaand L. G. Hamrno, /l] b. 6 V. H. Rawal,R. C. Ncwron,.d V. fri 7 D. H. R. Barton and I. C. Jerzbcreryi. f 8I. Ryu, K. Kusano,A. Ogawt, N. X.dr Ryu, K. Kusano,N. Masumi,H. Yrd 6887 (1990). e D. L. Boger and R. J. Marhviot, /r & r0B. Giese,Angew.Chem.Int. H..t.fr rr D. Batty, D. Crich, and S. M. Forn. .l.C
Trlbutyltln hydrlde
lcr I radicalcyclizationto fiveis also useful for sYnthesisof the.rsof the a-methYlenecyclofr Bu,SnHandAIBN in C6H6at 9l I vield.Oxidationof 2 with
scH3
BurSnH, AIBN
BzlO
8't%
2 (pla= 12:l)
o ll
BzlO
/,\-cH'sc6H5
t
l
scH3
R sio"'^--./'\osiR,
+ 75%
2(1:l) I t"tuen'c'uPx oo* | ;t I Y
OAc
CHt
osiR3
R sio" 3
vitapre\entin 14,25-dihYdroxY 5 in f I providescyclohexanones 4 ( 1 0 :l )
ot l ,r'Jt'-.*/'cHrscuHs t t
l l
R,,SrO"--osiR3 5
I arereducedbY Bu3SnH(AIBN) roducethe maltosedissacharide4 is not clear. crrc C2-substituents I reductionof thesesulfoneswith pn\entional methodwith Al/Hg. rompletereduction,but Yieldsof nannaneand2 equiv.of AIBN in
' P. Dowd and S.-C. Choi, Tetrahedron Letters,32, 565 (1991). 2 Y. Guindon,J.-F. LavallCe,L. Boisvert,C. Chabot,D. Delorme,C. Yoakim, D. Hall, R. Lemieux,and B. Simoneau,Tetrahedron Letters,32,27 (1991). 3 Y. Guindon,C. Yoakim,R. Lemieux,L. Boisvert,D. Delorme,andJ.-F. Lavall(e, TetrahedronLetters,3l, 2845(1990). a H. Miyake and K. Yamamva, Chem.Lctters,98l (1989). 5 M. KoreedaandL. G. Hamann,Am. Soc.,ll2, 8175(1990). 6V. H. Rawal,R. C. Newton,andV. Krishnamurthy, I. Org.,55,5181 (1990). 7 D. H. R. Bartonand J. C. Jaszberenyi, Tetrahedron l*tters,30, 2619(1989). t I. Ryu, K. Kusano,A. Ogawa,N. Kambe,and N. Sonoda,Am. Soc.,ll2, 1295(1990);I. Ryu, K. Kusano,N. Masumi,H. Yamazaki,A. Ogawa,N. Sonoda,TetahedronLetters,3l, 6887(1990). e D. L. Bogerand R. J. Mathvink,Am. Soc.,1l2, 4003, 4008 (1990). r0B. Giese,Angew.Chem.Int. Ed.,28, 969 (1989). f f D. Batty, D. Crich, and S. M. Fortt, J.C.S. Chem.Comm.,1366,1696(1989).
350
TributYltinlithium
Am' Soc''f10' 8716(1988)' 12D. Kahne,D. Yang,J. J. Lim' R' Miller' andE'-Paeuaga' larcrs' 30' 55?9(19E9)' r"rt6uofty r' 'h'1e;ahedron 13A. B. smith,Iu' r. l. naf";uidi' chloride' Tributyltin hydride-Copper(I) iodide-Lithium of Bu3SnHandCuI solucombination The Coniugatereduction;I a,}'"non"' (l) thatreduces.o,0-enones bilizedwith LiCl (2.s equiv') result,in a hydridocuprate be beneficial' can to the ketonesin 67-9E%yield. Addition of clSi(cH3)3 O
O
.{i\.,,\,," u I
I
t--------+
o)-'-y'"'-2
.l.l\ |
"2W
C6H5COOC2HT+ Bufali
|
I rK. C. Nicolaou,D. G. McGarry, ald P. f 2 A. Capperucci,A' Degl'Innocenti' C. Fi! Seconi,J. Or9.,54,2966 (1989).
(cisltrans= 12:l)
nco:,'1r:-1cHo r.c.fl!gn,r, r
nco:-z:5.r.--,A/cHo
quilt'
|
|
CH'
CH'
CH,
CH.
rB. H. Lipshutz,C. S. Ung, and S' Sengupta'Synlen'64 (1989)'
Tributyltin hydride-Triethylborane' (10 mole 7o) car-initiate reduction of Hydrodehalogenation' hriethylborane Bu3SnHevenat -78'' Alkenyl organichalides,particularlyiodidesor bromides'.by Aryl halidesrequire room temperaiiioes are also reducedundertheseconditions. obtainedby radical initiators' turc or higher. Yields are comparableto those rK.Miura,Y.Ichinose,K.Nozaki,K.Fugami,K.oshima,andK'Utimoto'Bullchem'soc' J a p a n , 6 2 , 1 4( 1 39 8 9 ) . Trtbutyltinlithium, Bu3SnLi' Cyclicethersfromlactones.|ThereadyadditionofRLitothec:Sgroupof thionolactones(14,9)hasbeenusedtopreparefunctionalizedcyclicethersfrom lactonesofthesameringsize.ThefirststepinvolvesLawessonthionationoflactone
,
k/ \
l
-.F", .F", \ ;;;ili'"',Y )
f--\ /
l
-
x\oA* I,x=O 2,X=S
(l) to provide a thionolactone(2). Additit methylthioether(3), which eliminatcsu triflate to provide a vinyltin 4. This plt transmetallationto a vinyllithium, rtid electrophiles.The sequencefrom thioml Acylstannanes.2 These tin rergca esterswith Bu3SnLi(1) and BF3 ethcrLewis acid is not necessaryin the rai chloridesare inferior to estersin this sF
l) Bu'snLi
|
B
%
s
/
\
/
{-o-frn"u, cH3s 3
/
\
,'lTn',Y
/--\
4
)
%
\
) ,
1
ri-o^snBu,
Tributyltin
methoxide, Bu3SnOCHl. $
Snnnylquinones.r The quinoc sn to substitutedcyclobutenedioncs(Ll, 2! Thus thermolysisof the alkynylcycloh ment to the stannylquinone2. As crpa dium-catalyzedcross-couplingwith oqr larly with allylic halides.
""t\-zo Lic=cBu
i-p.oAo-;
,:4 I
t L. S. Liebeskindand B. S. Fostcr, /r
Sc
Trl-p-carbonylhexacarbonyldbn,R Alkyne- alkene carbonylzrir.c $ by Fe(CO)rprov of dialkynescatalyzed carbonyluivertr more difrcult The t). (Pauson-Khand reactioo)ca d tenones yield. In an improvedcouPling,a
Trl-p-corbonylhcxecarbonyldliron
.2. .1m.Soc.,110,8716(198E). 'ohedron ktters,30, 5579(1989)' Dride. Mrion of Bu3SnHandCuI solurte ( l) thatreduceso'P-enones l:). caobe beneficial.
o
35f
(1) to provide a thionolactone(2). Addition of Bu3snli followed by cHJ providesa methylthioether(3), which eliminatesmethyl mercaPtanon treatmentwith copper(I) triflate to provide a vinyltin 4. This product can be used as is or can undergo transmetallationto a vinyllithium, which undergoesready reaction with various electrophiles.The sequencefrom thionolactoneto vinyltins is general. Acylstannanes.2Thesetin reagentscan be preparedby reactionof carboxylic esterswith Bu3snli (1) and BF3etherate(2 equiv. of each)in THF at 78', The Lewis acid is not necessaryin the reaction of 1 with thiol esters,RICOSR2.Acid chloridesare inferior to estersin this synthesis.
C H .I I
/^.-l l t
z
A''t
cflscooc2H, + BurSnLi#
t
CuHrCoSnBu,
H r o a , = 1 2 :l )
CHO
I --,,r1ar^r--r'^--a, l
CH,
l
CH,
I r1 9 8 9 ) .
le %) can initiate reduction of Bu.SnHevenat -78". AlkenYl 'l halidesrequireroom temPerained by radicalinitiators. Soc. r. andK. Utimoto,Bull.Chem.
Tributyttin methoxide, Bu3SnOCH3.Supplier: Aldrich. Stannylquinozss.r The quinonesynthesisbasedon additionof alkynyllithiums to substitutedcyclobutenediones(13, 209-210,284) can provide stannylquinones. resultsin rearrangeThusthermolysisof the alkynylcyclobutenolI with Bu3SnOCH3 ment to the stannylquinone2. As expected,these stannylquinonesundergo palladium-catalyzedcross-couplingwith organichalides(Stille reaction,14, 35), particularly with allylic halides.
o C"r..
"Hr'P fl
l l
- ^/\^ i-PrO'
Lic=cBu l -
'O
e4%
li-I
l l
/P I
' ^ ^fr.-'" i-PrO' OH
Bu,snocH! CH, AclcH,cHrcl'
u%
j-Pro
Bu SnBu,
I
bn of RLi to the C:S grouPof InctionalizedcYclicethersfrom thionationoflactone s Lawesson ,CH,
-F*
13 rTfl,
Io{r"r",
' L. S. Liebeskindand B. S. Foster,Am' Soc., f 12, 8612(1990).
Trl-p-carbonylhexacarbonyldiiron' FedCO)q. Alkyne-alkenecarbonylativccoupling. Intramolecularcarbonylativecoupling (equation ofdialkynes catalyzedbyFe(CO)sprovidesa route to cyclopentadienones provide cyclopenI). The more difrcult carbonylativealkyne-alkenecoupling to tenones(Pauson-Khandreaction)can also be effectedwith Fe(CO)s,but in modest yield. In an improved coupling, acetone is treated with FedCO)e to form Fe-
Tri-p-cerbonylnonacarbonyltetrarhodium
I I. Matsuda,K. Takahashi, andS. Sato,Icol
Fe(CO),
Fe(CO)r,
+ COt
C'H'CH"135" 87%
\ f ' 6T}o CH,
CH,
(CO)r(acetone).This complexreactswith an enynesuchas I in tolueneat 145" under 55 psi of CO to form a cyclopentenone(2) in high yield.
2,4,6Trlchlorobenzoyl chloridc' ), 178' Macrobctoniwtion.r High diluti
o
,tu"t
f-4/cuH'
o
h*L
+ Fe(co)o(cH3cocH3) # 81% or-lzlo
I I A. J. Pearson J.C.S.Chem.Comm.,202(1991)' andR. A. Dubbert, Tri-p-carbonylnonacarbonyltetrarhodium' Rhr(CO)rz. Three-componentaldol synthesis.r This rhodium carbonyl can promotealdol couplingofenol silyl etherswith aldehydesor ketones.It can also effectcoupling of an enone,an aldehyde,and a trialkylsilaneto providea silyl aldol. In the caseofan enolizablealdehyde,yields are improved by addition of a phosphineligand suchas
t"""Y^""rll ^..[^.,-^,r+. (crH,),cH,siH ,^rr\ as9L' cu,icu:cH, L
oRhsiR3 J
,* fififs,1,;"Jfl ;,".",,, J 9H, (CH2)4cH3 cH, -*r1-.i l l osi(c2H5)2cH3 o = 68:32) (synlanti The reactioninvolveshydrosilylationof the enoneto furnish an interCH3P(C6H5)2. mediateenol ether (a), which then undergoescoupling with an aldehyde.
-
l
o4
I
aminopyridine.Lactonizationof 2 ir dr but in somewhatlower Yield.
I
rM. Hikota,H. Tone,K. Horite,rd O- Yc Sakurai.K. Horita,andO. Yoocmirrr'Icol
CllTi(H Trlchlorolsopropoxytltrnlun' l-cti This F-Alkoxy cyclic cthen.r g dlyhir molecularreactionof a 1-alkoxy ut t tootc ss ' reaction hasbeendeveloped
Trlchloroisopropoxytitanium t I. Matsuda, K. Takahashi, and S. Sato, Tetrahedron Leners,3l,
b as I in tolueneat l45o under :ld.
5331 (1990).
2,4,6-Trichlorobenzoyl chloride, 9, 47g_479: lf . 552. Macrolactonizltion.r High dilution is usuallyessentialfor macrolactonization, but the l4-memberedlactone, 9-dihydroerythronolideA (3), can be obtained in almostquantitativeyield by lactonizationofthe seco-acid2 via the mixed anhydride formed with 2,4,6-trichlorobenzoylchloride (r) with triethylamine and 4-dimethyl-
oYo Mes
o
DMp
2, Mes = C6H3(OCH,),-3,4 D: ,1991).
I rl t, *r",41.,DMAI,25" I
xytcre (96%) H,, Pd(oH),/c (e8%)
J2) ll:
r carbonylcan promotealdol . h canalsoeffectcouplingof r silrI aldol.In thecaseof an of a phosphineligandsuchas
...CH, 7
o"r""ll _
OH .'CH,
'oH
oRhsiR3 J CH, 3 -^. | .nu.",,.""o,
Rh.(co),,. cH,P(qH,),
J CH, v/\.(cHr)4cH3 I o OSi(CrHs)rCH3 r srqanti = 68:.32) the enone to furnish an inter1 *rth an aldehyde.
aminopyridine.Lactonizationof 2 is also possiblewith mesitylenesulfonyl chloride, but in somewhatlower yield. rM. Hikota,H. Tone,K. Horita, andO. yonemitsu, J. Org.,55,7 (1990);M. Hikota,y. Sakurai,K. Horita,andO. yonemitsl, Tetrahedron ktteri, n, e]fJl OgtiOl. Trlchloroisopropoxytitanium, Cl3TiO-ipr (l). p'Alkoxy cyclic ethers.r This Lewis acid is particularly effectivefor an intramolecularreactionofa 7-arkoxyallyltin group with an acetalgroup (cl 14, l6). This reactionhasbeendevelopedasa route to p-alkoxy cyclic ethers.Thus in the presence
Triethoxysilane-Pellsdium(II) scetrte
7(cHzL:, \ / o-y'o
HO(CH,)4O...r,,^) l.cH.cr. *;=
| --.^o1 LsnBu,
H,cs.\o/
Water is essentialfor this reduction.Thi high stereoselectivity.Addition of mcd reactivity and can effect reductionof dl rJ. M. Tour,I. P. Cooper,andS. L. Fcrd
3 (translcis= 1.3:l)
p-alkoxy of l(2 equiv.), the o-trialkyltin ether acetal(2) cyclizesto an c-vinyl, are ones, or 7-membered cyclic ether(3) in goodyield. Cyclic acetals,particularly 5can cyclization This more usefulthan acyclic acetalsor the correspondingaldehyde. cyclic ethers,as well as c,c',p-trisubstitutedcyclic resultin 6-,7-, or 8-membered synthesisofa [6,8] bicyclic ether(4). ethers.It was usedfor a stereoselective
Trlethylgallium, (C2H5)3Ga. Itctams trom a-amino corbrylic t be formed from co-aminocarboxylic ri absenceof high dilution. Triethyldnni position.
HrN(CHr)rCmll .
o_.,| l, cH,cl!I CH,). - - --r*Q-----:
I Y. Yamamotoand T. Furuta, Ctv;- It{l
SnBu, = I I : l) 4 (a,P+ransla,P-cis fJ. Yamada,T. Asano,I. Kadota,and Y. Yamamoto,l. Org',55' 6066(1990)' I Trichloromethyl carbonate, (ClrCO)zC: O. Preparation' phosa-chloro chloroformates.2 This reagent can be used as a substitute for gene in a synthesis of c-chloro chloroformates from aldehydes'
PY,CClr
+ (clrco),c:o t?# cH,(cH')scHo
?
Trlethyl phenylsulfinylortbrcttc, obtainedby reaction of 2,2,2-trkblcq phenyl sulfoxide with sodiumetho*b. Claisen reorrangcmcnl of dlylt t ranSementof allylic alcohols witt u , homologatedy,6-unsaturatedestcrs(5. , orthoacetateI is accompaniedby u ir I homologateddienoateesters(cqutin I)
cHr(cHr)rcH(cl)occl (D CHr:gg6"tH,+15 I
! H. EckertandB. Forster,Angew.Chem.Int. Ed.,26' 894(1987\' 2 M. J. Coghlan Letters,30,2033(1989)' andB. A. Caley,Tetahedron Triethoxysilane-Palladium(Il) acetate. Polymerizationof triethoxysilane in water catalyzedby Pd(OAc)2results in a catalystfor reducsiloxanethat can be usedas a heterogeneous palladium-deposited
tionswithhydrogen.
can Hyilrogenation.l Alkenes, including o,P-unsaturatedketonesand esters, bereducedbytriethoxysilaneand5mole%ofPd(oAc)zinTHF/Hzo(5:l)at25".
OH
OH
+l
rt ^ / l R3sio'\ (-\ 2
osin,
Triethyl phenylsulffnylorthoscetste
locHr)0o.../,,-\
^.r"\/
Ltl-
!
t |
\o,,'
|
l
355
Water is essentialfor this reduction.This systemreducesalkynesto cis-alkeneswith high stereoselectivity.Addition of methyl propynoate(10 mole %) increasesthe reactivity and can effect reductionof alkynesto alkanes. fJ. M. Tour,J. P. Cooper, J. Org.,55'3452(1990)' andS. L' Pendalwar,
: , a n s l c i s= 1 ' 3 : l )
lizes to an c-vinyl, P-alkoxY ones'are 115- or 7-membered can cYclization This rltlehyde. cYclic ts o,o',P-trisubstituted r [6.8] bicYclicether(4).
Triethylgallium, (CzHs)sGa. lactamscan Itctams lrom 4o-aminocarboxylicaci.ds. Five- to eight-membered (CzHshGa even in the with treatment by acids be formed from or-aminocarboxylic decomof thermal because less useful is absenceof high dilution. Triethylaluminum position. (CrH!)rca,
HrN(CH2)5COOH
c6H'cH'4 )|
tso
8t%
\_N' H
I Y. Yamamotoand T. Furuta, Chem.Letters,797 (1989).
o
tl
te . 55,6066(1990).
ltlon.
I
usedas a substitutefor Phosaldehydes.
o
tl
CH,rCHr)'CH(CI)OCCI
(l)' The reagent is Triethyl phenylsulfinylorthoacetate, C6H5SCH2C(oC2H5)r 2,2-dichlorovinyl or sulfoxide phenyl obtainedby reaction of 2,2,2-trichloroethyl phenyl sulfoxide with sodiumethoxide. Claisenrcafiangement of attytic alcohols to ethyl dienoates. Claisen rearrangementof allylic alcohols with an orthoacetateis known to provide 2-carbon homologatedy,6-unsaturatedesters(6, 607-608). Reactionwith the phenylsulfinylby an in situ sulfoxideeliminationto provide 2-carbon orthoacetateI is accompanied (equation I). This novel reagentwasusedto convertthe homologateddienoateesters
(D CHr:g11gg"H, + I !#-
l r r1 9 8 7 ) . . : 0 3 3( 1 9 8 9 ) .
c'Hrooc,\-A-zcH'
OH
/cooc2Hs II
OH
yzed by Pd(OAc)zresultsin a ierogeneouscatalystfor reduc-
a\,
Nratedketonesand esters,can r A c ) :i n T H F / H 2 O( 5 : l ) a t 2 5 ' '
R,sio'\-AosiRj (-) 2
t
l) H', 100'
l
+l')o'
89%
,
aY"' R.sio'\*osiR, 3
356
Triethylsilane-Pelladlum/C
allylic alcohol( - )-2 into theprecursor(3) for theA-ring of Ig,25-dihydroxyvitamin D3. ' G. H. Posner andC. M. Kinter,.1.Org., 55,3961(1990).
Triethylsilane-Trifl uoromctlea Hydrogenation ol alLetct.t k conductedwith a trialkylsilea u
(CHr)'C:CHCJ{.' Triethylsilane,b. p. 108'. Trifluoroaceticacid deprotection. Trialkylsilanesin combinationwith an acid DuPontchemistsrecommend as a hydridedonorare usefulfor ionic hydrogenation. by-productsformed in for carbocationic as scavengers or triisopropylsilane triethylmore effectivethan can be In fact, triethylsilane acids. of amino TFA deprotection scavenger. used a commonly ethanedithiol, r D. A. Pearson. Letters,30, Tetrahedron M. L. Baker,andc. A. Guindon, M. Blanchette, (1989). 2739
Actually hydrogenationwith thc lh yield at -75' in 5 minutes.Simi! CpMoH(CO)3as the hydridcdooor reducedto alkanes. ctl
(CHr)rC:C(CHr; -
I R. M. BullockandB. J. Rappolr..lC (C2H5)3SiH-CH3(CH2) r rSH. Triethylsilane-Dodecanethiol, Reductiono! RX to RH.t In the presenceof di-t-butylhyponitrite(initiator) and a thiol,2triethylsilanereducesalkyl chlorides,bromides,or iodidesto alkanesin >9lVo yield by a chain reactionin which the thiol effectstransferof H from the silaneto an alkyl radical.This reductionis generallyeffectedwith a RlSnH,which is toxic and more difficult to removefrom the products. l R . P . A l l e nB , d C .R . W i l l i s , J . C . SC.h e mC. o m m ' , 1 3 8( 179 E 9 ) ' , . P . R o b e r tas n 2 H. KieferandT. G. Traylor,Tetrahedron l*tters,6l63 (1966)'
Trifl uoroethyl trifl uoroecctdc, Cl d-Diazo ketoncs.r Dircct dir productive,and a-diazoketos rre with c-formyl ketoneswith elirnir finds that c-diazo ketooesare obrri acetatesof ketones,particulerly if d
o
ll n'iCH.Rt Triethylsilane-Palladium/C. in two steps:conversionof RCOOH+ RCHO.| This reactioncanbe conducted RCOOHto the ethylthiolester,which is reducedby triethylsilanecatalyzedby Pd/C to an aldehyde(equationI). This methodis suitablefor conversionofoptically active aminoacidsto aminoaldehydeswithout racemization. l) clt,ococl, N(c,H!),
(D RcooH aE#..--
o L ncsc,H,
,,_rojs:k,",.*. RCHO + (C2HJ3SiSC2H5 I T. Fukuyama, S.-C. Lin, and L. Li, Am. Soc.,ff2' 7050(1990).
rrr.rxs.cru 2)cF'oo{r'r
disilazidein THF at -78". Triiut roacetic anhydride for trifluoru reagentfor diazotransfer, mcthrr preparedin >90% yield by rata
' R. L. Danheiser, R. F. Miller.R. GTrifl uoromethsnesulfoniculyfi a-Glycosybtion.r Triflic uty 2,3,4,6-tetrabenzyI -p- o-glucopfrr TiFa, AgOTf/SnCl2,or trimahylsil tivitv.
Trifl uoromethanesulfonicanhydride
bc A-ring of 1c,2S-dihydroxyvitamin I r 1990).
Triethylsilane-Trifl uoromethanesulfonicacid. Hydrogenationofalkenes.r Ionic hydrogenationofalkenes hasgenerallybeen conductedwith a trialkylsilaneand an acid no strongerthan trifluoroaceticacid. (crHr)rsiH, cFrsosH
(CHr)rC:CHCrg, --ffi ylsrlanesin combinationwith an acid Datlon.DuPontchemistsrecommend carbocationicby-productsformed in th1lsilanecan be more effectivethan Leuers,10, Tetrahedron C {. Guindon,
(CH3)2CHCH2C,H5
Actuallyhydrogenation proceedsin almostquantitative with the silaneandCF3SO3H yield at -75" in 5 minutes.Similar resultsare obtainedby use of CF3SO3H and CpMoH(CO)3as the hydridedonor, and in fact eventetrasubstituted alkenescanbe reducedto alkanes. CpMoH(CO)r, CF,SOTH
(cHr)rc:c(cHr), ---j!:JJ!L----
(cHJ2cH-cH(cH3),
I R. M. BullockandB. J. Rappoli, (1989). J.C.S.Chen.Comm.,1447 H,rCH:)rrSH. (initiator)and of dr-r-butylhyponitrite to alkanesin or iodides . bromides, H from the of transfer r rhrol effects which is R3SnH, with a :rall1 effected oducts. . S C h e mC. o m m . , l 3 8(71 9 E 9 ) . . 6 1 6 1( 1 9 6 6 ) .
(1). Trifluoroethyl trifluoroacetate, CFTCOzCH2CF3 u-Diazo ketones.r Direct diazo transfer to ketone enolatesis generally not productive,and c-diazo ketonesare generallypreparedby reactionof sulfonyl azides Danheiser'sgroup with a-formyl ketoneswith eliminationof a sulfonylformamide. finds that c-diazo ketonesare obtainedin significantly higher yield via o-trifluorowith lithium hexamethylacetates ofketones,particularlyifthe enolateis generated
o
ll R'icH,R' conductedin two steps:conversionof d br triethylsilanecatalyzedby Pd/C rt le ior conversionof opticallyactive uzatlon.
o ) RCSC2H5
.r:{
Pdrc' c.H,)JsiH' ffi
*a"O |:
* (C2H5)3SiSC2H5
-050 (1990).
o
r )L i N t s i ( c H , ) , tl,l . . . . - ._ . . 2)cFrcorcH?cFr > n'CcHR' -q*,#" cocF3
o
ll R'icR' N2
is superiorto ethyltrifluodisilazidein THF at -78'. Trifluoroethyltrifluoroacetate roacetic anhydride for trifluoroacetylation. Although tosyl azide is the traditional reagentfor diazo transfer, methanesulfonylazideis a convenientreagent,andcan be preparedin >90% yield by reactionof MsCl with NaN3in acetone. ' R. L. Danheiser, R. F. Miller,R. G. Brisbois, andS. Z. Park,"I. Org.,55, 1959(1990). Trifl uoromethanesulfonicanhydride. a,-Glycosylation.r Triflic anhydride is highly effective for c-glycosylation of 2,3,4,6-tetrabenzyl-p-o-glucopyranosyl fluoridewith a dissacharide. It is superiorto TiFa, AgOTf/SnCl2,or trimethylsilyltriflate, listedin the orderof decreasing reactivity.
35t
Trifiuoromethenesulfonic anhydride
Glycosylationofphenolsandevenhinderedalcoholsis possibleby reactionwith (1, excess)and triflic anhydride^t -78o an O-proticted l-phenylsulfinylglucose protectivegroups and the solvent. lequationI).2 The c/p ratio is influencedby the p-glycosylation, whereastoluenefavors cuse of cH2cl2 or propionitrilefavors
Triisobutylaluminum, [(CHr)zCHCH:lI Annelation of acetals. A few yeerst trialkylaluminumconvertsthe acetd 2 to the reactionhas been shown to bc epplrc
'r
cHr..
glycosylation.
!', (D RoH+Bzt\<;--o\ Bzlo\/G\
oJ I ]-o1.",
l) c#'cH3' -78 + -6oP
-OBzl
[
+rr,ok
\-/
'sc^H. il-o
l, -7E"
-''"-(/ 3
,OBzl
",to-1\(/\
a
nzfO\--fr\ OR ( o ' l F= 2 ' l : r )
Dehydralionof formamides to isonitrilcs.s This reaction can be effectedin It high yield at -78o with the combinationof triflic anhydrideanda tertiaryamine' formamides' vinyl of case is effectiveevenin the
CH, ' ll
fi",
(cFlso!)ro,
frA*"."o-Ir$4ry*
ketonesandto provide a generaland gcrr (4) oo ttq ether3 cyclizesto a hemiacetal type ut of this propylamine.Hemiacetals and photolysiswith CeHsI(OAc)z l:. Tl inversionat the hydroxy groupsas sbr reductionwith Bu3SnH. This novelannelationnot only prorrd to a synthesisof a diol (t) from tbe ra
cH3o'
cH,o\./
tHr! o-1
cH'
"VB?i*'
a ,(>
\
NC
scvcnl+)
nV o1 /\
CH.
O-\-{
NHCHO
1
crr,.
-.'cH,
CH, 7
cH. cH, cH, ' H. P. Wessel,Terrahedron Letters,3f' 6863(1990)' 2 D. Kahne,S. Walker, Y' Cheng,and D. Van Enges Am' Soc" lll' 3 J. E. BaldwinandI. A. O'Neil, Synlerr,603 (1990)'
6881(1989)'
,ogo*
cH.
Triisobutylaluminum
kohols is possibleby reactionwith ssr and triflic anhydrideat -78' protectivegroupsand the solvent. ylarion.whereastoluenefavors c-
(l). Triisobutylaluminum, [(CH3)2CHCH2]3AI Annelation of acetals. A few yearsago Mori and Yamamotorreportedthat this trialkylaluminumconvertsthe acetal2 to the enol ether3 in high yield. Sincethen, the reactionhasbeenshownto be applicableto 1,3-dioxanes of acyclicand cyclic
cH3"'rYcHl
!",
- Tf:o
O
-A-
l) c6HrcH!,-78 -> -60" 2) NaHCOI
-"\
I|
5E-86%
359
\-/
O
)
F^n |
|
OH
l.-78.
-#
OH -z{-o-..'cH,
rrzo,
**,
>95%
,
I
I
t
t
\.4..//
'cH.
I
l
: CH, 4
,**J;:l{o^"' o
o
&oa....", \-^'--' |
OR
|
a-=lj-o\....", €\-Nl Bu.SnHl
I
: cH-
(alP=27'11
I
5
6
Thrs reactioncan be effectedin c anhrdrideanda tertiaryamine.It
ketonesandto providea generalandstereoselective routeto lactones.2 Thustheenol ether3 cyclizesto a hemiacetal(4) on treatmentwith triflic anhydrideandethyldiisopropylamine.Hemiacetals (5) on of this type are readilyconvertedinto iodolactones photolysiswith C6H5I(OAc)2 and 12.The cyclizationstepproceedswith complete inversionat the hydroxygroupsas shownby formationof a singlelactone(6) after reductionwith Bu3SnH. This novelannelationnot only providesa routeto chiral lactones,but wasapplied to a synthesisofa diol (8) from the acetal7 as a precursorto (-)-lardolure (9).
cHr.. 'f-V"f
+ ti
: CH,
' ..cH,
o t",'..f---ll-o)..'t", r-_-_,.,--.
\ A ) ' i c v e n r s t c p s > ( - ^ - " ,
O--(
,H CH,
tH,
DIBAH --------t 92%
I i CH, CH,
7 CH,
r) 1 . . { , ' r S o c . .l l l , 6 8 8 1( 1 9 8 9 ) .
)
"ogo"
CH.
CH.
CH.
CH,
CH.
*go""o
CH,
CH"
TrimelhylimineN-oxide
360
'A. Mori and H. Yamamoto,J' Org" 50' 5444(1985)(1990)' H. Yamamoto,J.org.,55,5814 2 M. Kaino,y. Naruse,x. tstritraraland Triisopropyl phosphite, P(O-i-Pr):'
\
Trimethylsilyldiazomah (Z)-l - Trt n etht I silYl'l < pared by reaction of Primr diazomethane,decomPosct caseto rhodium(Il) aceurcl
hydrocarbons Aldehydes and ketones are reduced to aCHz'r triisopropyl phosphitewith continuous when heatedfor about 24 hours in refluxing higher from aldehydesthan from ketones' removalof acetone'In general,yields are and highly hinderedketonesare not reduced' C:O
\ --'--+
R'R2c:o
+ P(o-i-Pr),ffi
RCHJ I
R'RtcH' + 2(cH')'c:o
(1990)' I G. A. OlahandA. Wu, Synlett,54
TrimethYlamine N-oxide' N-oxide2in DMSo can oxiRCHzBT' RCH;.; Anhydroustrimethylamine at 25' in yieldsof about to.aldehydes dize primarybromideslbut notihe chlorides) are oxidized go%(shours reactioni.ailyri. and benzylicchloridesand bromides DMSO/CHzCIz' more rapidly at 0o in a mixed solventof of the c1s-hydroxyl group into introduction Direct Benzslic hydroxylations with (CH)3NO' Thus I is convertedinto anthracyclineglycosidescan be effected DMF' The yield is only 53% when oxaunomycin(2) inSzi" VitfOftot reactions-in (34vo)in the absenceof the c11-hydroxyl acetoneis the solvent,uno i, also lower group.
o
OH
I T. Aoyamaand T. Shioin. (
0-TrimethylsilYlethorYAklol-type rcactb.t.l kctoc in a-hydroxymethYl undergodeProtectionwith Dire cted mctallation.t methyl) ethers for dirccro addedadvantageof remov lithiationof hydroxYPYri
' D. CrichandL. B. L. LiD. 2 S. Sengupta andV. Sniect
,-o I
(i",)
HorNHt
, L:':'*.11:4825 (1990)' A. G. Godfreyand B' Ganem,Tetrahedron 27' 3961(1986)' ibid" t.'e-. SoO.rquirtand C' A' Anderson' ibid'' 30' 4857 (1989)' Sakakiba:a' M' and Kawai, H. S. Nakajima,
(2-Trimethylsilyloxy)ellY Preparation:
cHscocl
g
(2-Trimethylsilyloxy)sllyltrimethylsilane
Jr ?o.! Org.,55,5814(1990).
(CH)35iCHN2. Trimethylsilyldiazomethane, (Z)-l-Trinethylsilyl-l-alkenes.t The a-trimethylsilyl diazoalkanes(2), preparedby reactionof primary halides(1) with the lithium anion of trimethylsilyl on treatmentwith rhodium(Il) pivalate[superiorin this diazomethane, decompose caseto rhodium(Il)acetatelto (Z)-l-trimethylsilyl-l-alkenes.
one\ are reducedto hydrocarbons N, (cHr)rsic(LDNr> ncHrlsltcu,l, RcH2x
rcpropyl phosphitewith continuous thanfrom ketones, r frtrmaldehydes
t 'R'cH. + 2(cHr)rc:o
2 - e6% Rh,(ocoi-Bu)4 J
R \
Si(CH"). /
H H (ZlE = 80-97:20-3) hmrneN-oxide2in DMSO can oxir al,iehl'des at 25" in yieldsof about b[rrrdesand bromidesare oxidized
I T. Aoyama (1989). andT. Shioiri,Chem.Pharm.8u11.,37,2261
) cH:cl:. ion t.rfthe C1s-hydroxylgroup into CH,r,NO. Thus I is convertedinto r D\tF. Theyield is onlY53% when of the C11-hydroxyl r rn the absence
o
OH
OH
p-Trimethylsilylethoxymethylchloride (SEM-Cl), CICH2OCH2CH2Si(CH3)3. Aldol-typereactions.t Reactionof lithium enolateswith SEM chlorideresults in c-hydroxymethylketonesprotectedas the p-trimethylsilylethylethers,which can undergodeprotectionwith BuaNFor TFA. Yields are in the rangeof 55-80%. Directedmetallation.2 SEM ethersof phenolsare as usefulas MOM (methoxyof aromaticsystems,and have the methyl) ethersfor directed ortho-metallation of removalby fluorideion. This group is also usefulfor directed addedadvantage lithiationof hydroxypyridines. I D. CrichandL. B. L. Lim, Synleu, 117(1990). 2 S. Sengupta Letters,Sl, 4267(1990). Tetrahedron andV. Snieckus,
H O o
o H c r-O
(in )
Ho|NH, t
r . - r l . 1 8 2 5( 1 9 9 0 ) 96r 1986). . -q) 1857(1989).
I
(2-Trimethylsilyloxy)allyltrimethylsilane,CHr:C,
/,os(cH3)3 'cHrsi(cH3)3
Preparation:
o cH3coclgg-#ry
cu,Acu,si1cH,y,
(f).
362
2-(Trimethylsilyl)thlazole
Whenactivatedby TiClr (1 equiv.) I reactswith acetalsor Doubteawotion.t --r carbonyl compoundsto give productsof double alkylation, probably via a 1,3-C O Si rearrangement.Thus I can function as the o,o'-dianion of acetone.
qcH.9
* r J*#! c6H5cH(ocH,),
9CH,
..",1""",1cu'lucoH, o H o
+ r -IffE C6H5cHo
OH
tA. Dondoni,G. Fantin,and M. Fog4mlo.
Trimethylsilyl trifl uorometbrncsutrc Cyclic u-amino acids.r The uosrtnr ment with TMS triflate (l equiv.) cyclu markedpreferencefor the former cyclk r the solvent.It is highest(33: l) in rdu reaction is obtainedin t-butyl mcrhyl cd lower (18: l). Lewis acidsdo not ioiti*
crH,JncHrlcH2cHc6H5
I A. Hosomi,H. Hayashida,and Y. Tominaga,J. Org., 54' 3254(19E9).
cH'
l )
r l NH,+ HCocootu {
CH,
(1), b.p. 73-75'lr5mm.)
2-(Trimethylsilyl)thiazole, q\r,(cH,),
The reagentis preparedby treatment of 2-bromothiazole(Aldrich) with BuLi followedby ClSi(CHr)3(85% yield). Formyt anion equivalenl.r This reagentcan be used as the equivalentof the formyl anion. Thus it reactswith an aldehydesuchas2 in the absenceof a catalystto form mainly the cnti-adduct. After protection of the hydroxy group, the thiazole groupcanbe convertedto a formyl group by N-methylation,reduction,andhydrolysis.
cH"
I "-l-o
CH.
CH,"
/CH' -l-o
*1r,crro-25_-' J--A/J o-f-cHo t
l
s --1
3
The doubly activatedimirrcsI cen be r provide the cyclic amino acid derivrtrve !
, 3 (a5So de)
cH.-Y |
*oJ"""..",r, CH. CH," - Y - 'I- ^ I
I
|
q ,,\ \./
5
Hro
*--3) Hgcl?, -cHo 62%: OBzl
CH, 4
CH" I
t
"l-o
CH" r)cHrl 2) NacNBH'
'O
']., -[ ^'\c(coon,.
.s-\
o'..",A *) OBzl
Conjugate addition of alkynykitc ht nationwith I equiv.of a trialtylsilyl rn0t acyclico,p-enonesat -40o in THF or a formed from p-disubstitutedo,$-cnom.
Trimethylsilyl trifluoromethanesulfonate 363 I r I equiv.)1 reactswith acetalsor rlkllation,probablyvia a 1,3-C+ o.o'-dianionof acetone.
ocHr
fr ?""'
I.CHCH,ccH2cHC6H5
O H O O H
l l l
f A. Dondoni, G. Fantin,andM. Fogagnolo, (1990). Org.Syz.,submitted Trimethylsilyl trifluoromethanesulfonate, TMSOTf. Cyclic a-amino acids.r The unsaturatedimine 1, preparedas shown, on treatment with rMS triflate (l equiv.) cyclizesto a mixture of trans- and cis-2, with markedpreferencefor the former cyclic amino acid. The selectivityis dependenton the solvent.It is highest(33: l) in toluene,but the highestyield (55/o) andcleanest reaction is obtainedin r-butyl methyl ether even though the diastereoselectivityis lower (18: l). Lewis acidsdo not initiatethis cyclization.
{.cHCH,CCH2CHC6H5
gurJ I
Mssq, a} cur,.,) NH, + HCocooBu #-
.^)
5{. 325a(1989).
>etYa
CH,
il.--cHcooBu
f CH,
I
5m.) I r . b . p . 7 3 - 7 5 ' l 1m lnr,rsorr, 49-55% orcoH,CH, J,-BuocH,
romothiazole(Aldrich) with BuLi n be used as the equivalentof the of a catalYstto b as2 in theabsence f rhe hydroxy grouP, the thiazole rrhr lation, reduction,and hydroly-
a^Nn |
|
-
f^Nn .
\/A.ooH cn/cu,
9
"
-
Jr#3
3
9
H
l
-^NH
i
l
\*cooBu
|
cuf\cu,
|
|
+ fcooeu cu/cu,
trans-2
cis-2 lg-33: r
cH,, --o a
l
o.-,r\,A*)
.s --1 \
\
The doublyactivatedimines4 can be cyclizedby Lewis acidsor TMS triflateto providethe cyclic aminoacid derivative5 after saponification anddecarboxylation.
-l
: OH 3 t857o de\
c "Y H , l "\c(coon), *
%* lc"H(cH?Br
CH, 4
CH.
l . t
\o
1
.s--l
o...A,A*) OBzl
'lI r^*" \x:331 1l-y,"^.", J
CH, 5
Conjugateaddition of alkynylzinc bronides.2 Atkynylzinc bromidesin combinationwith I equiv.ofa trialkylsilyl triflateundergoconjugateadditionto cyclic and acyclicc,p-enonesat -40o in THF or ether.A mixtureof 1,2- and l,4-adductsis formedfrom p-disubstituted c,p-enones.
?t
Trimethylsulfonium methylsulfste
o
OTBS
;B:-'ff", n..^-^a-D-# +. Buc-cZnt' A $"*.""
A (/
I L. F. TietzeandM. Bratz,Synthesis,439 (1989). 2 S. Kim andJ. M. Lee,Tetrahedron lztters, Sl,7627 (1990). Trimethylsilyl trifluoromethanesulfonate-Titanium(IV) chloride. Spiroannelation of silyl enol ethcrsr (15,237-238). Spiroannelationcan be effectedby reactionof a silyl enol ether with an alkyltin reagentbearinga terminal acetalgroup in the presenceof trimethylsilyl triflate and TiCla. An intermolecular reactionis followed by intramolecularring closure to provide a spiro ring system, bestisolatedafter oxidationofthe secondaryalcohol groupto a ketone.This method providesaccessto [4.41, [4.51, [4.6], [5.5], and [5.6] spirocyclicsystems.
(Yt"s(cH3)3 CH"
Furan synthesis.r The original syr methylidc(4. 19 usingdimethylsulfonium phase-transfer conditions. tM. E. PriceandN. E. Schore,./. Org..9.
Triphenylcarbenium hexechlorufr a-Substitutedcyclic cthcn.r ln thc atrdSnl: ( 15. systemof SbCl5-ClSi(CHr)3 (l) lod I methylsilyloxy)-l-ethoxyethenc form s-substitutedcvclic ethers.
(cH2)" (
)
\oAo
tt"*i"io' + (cH,o)rcH(cH'),Sn(cH,r,
osiMc& + CH.:C/
t*Jr.
(n = 2-4)
|
/
t-
cHlo'
,s(cHJl li;s'
ILc"Yarr.J'"'I r,*-cH, Similarreactionof a bifunctionalalkyltinreagentwith the enolsilyl etherof a (cf. 13,ll8; 15' 237). cyclicketonegivesriseto fusedring systems I T. V. Lpe andJ. R. Porter,Org. Syn., submitted(1990).
(
f"t,
+CH3SO4-(l). Trlmethylsulfonlurn methylsulfate' (CH3)3S
ayycHSBu :i,Hi,lCfXcHsBl V+o L\-x--rvo J st*
This reaction can also be uscd to cq from p-hydroxy carboxylic acids,: ro qr
|
?^?
+ r ' oorc+ 4,
?' a"5
cn.AAo
f"',
oAo
"",A/cH,coocr.
DrlJt 4.B\
u
365
Triphenylcorbenium hexachloroantimonrte
,^\
Furan synthesis.r The original synthesisof 3,4-disubstitutedfurans by Garst using dimethylsulfoniummethylide(4, 196-197)can be improvedby useof I under phase-transfer conditions.
J"*""u
' M. E. PriceandN. E. Schore, ./. Org., 54,2777(1989).
OTBS
il990r rE(IV) chloride. can be t-l-18). Spiroannelation llltrn reagentbearinga terminal le and TiCla. An intermolecular I ro providea sPiroring sYstem, rl groupto a ketone.This method l.6l spirocyclicsYstems.
Triphenylcarbenium hexachloroantimonate, TrSbCl6. a-Substitutedcyclic ethers.r In the presenceof this Lewis acid or of a mixed systemof SbCl5-ClSi(CH3)3 andSnI2(15, 14-15),the silyl keteneacetall-(t-butyldi(1) and a silyl nucleophilereact with lactonesto methylsilyloxy)-l-ethoxyethene form c-substitutedcyclic ethers.
l-tcH,)" I osiMerBu+ JCHr)" rrsbcl' + CH,:c/ f ) ( toa,", \oAo | o^'Ltncooc'H' I bsiuer-r-nu L J (n = 2-4\
(cH])rsioTf
rCH.t.
I
THF
75_e5%l(c,4),siH
"l
(cH2)"
r\o4",.oo.,", )
| ) TiCl. l) PDC
----------) 54%
CH,
pnt with theenolsilYlether of a 13. ll8; 15,237).
available This reactioncan also be usedto convert6-alkyl-1,3-dioxan-4-ones, p-hydroxy carboxylicacids,2to syn-1,3-diols. from
ccl.
f""
Ir
I
oAo
L S O . -( l ) .
I
cHa+o
r''
e3%
cHr-$oSiMer-t-Bu
oAo t
l
cHr/-+cH2coocrH5 l
(crH5)rsiH,
ccl.
\r.'--tzCHSnu-l
-^-=r==" I
_ rlsrcL
+ l -
t
oAo Tict. | [...cH?cooc,H592%
BursnH, AIBN '10%
f",
crHrsH, Ticl.
oAo t l cHr^\-
87%
cH2coocrH5 OH
OH
c",A-l'---cooc2H5 syn-2
16
Trlphenylphoephlne/Carbontetnbromldc
the reactionof ketenesilyl $-Amino csterc.r A numberof metal saltscatalyze mixture of syn- and antip-amino a as usually esters, acetalswith imines to form yield are observedwith trityl chemical and isomers. The highest azri-selectivity iodide is equally iron(Il) but of N-phenylimines, in the case hexachloroantimonate N-diphenylmethylimines' or effectivein the caseof N-benzyl/osi(cH3)r
cuHrcH:NR'* a"floa""
Triphenylphosphine/Crttc El Bischle r-N apicmlsli crdd. ally effectedwith P2O5or ZoCll. I (C6H5)3P and CCla(equationI). cH30
(D
NHR'
+ svn-l
-gt c.nr\coocH3
cH30
CH, anti-l
Rt= CeHs
FeI, TrSbClu
92Vo 95Vo
8 2 :l 8 92:8
Rr= Bzl R'= Bzl
FeI, TrSbClu
77Vo Tl%o
9l:9 93:7
R'=c#s
rK.Homma,H.Takenoshita,andT.Mukaiyama,Butl'Chem'Soc''63'1898(1990)' 2 D. Seebach, R. Imwinkelried,and G. Stucky,Ilelv',70' 448 (1987)' 3 T. Mukaiyama,H. Akamatsu,and J. S' Han, Chem'Letters'889 (1990)'
tetrabromide' Triphenylphosphine/Carbon 'bn)ono_l-alkynes.t Theseproductsareformedin g2-96%yield by reaction (6 equiv')in CHzClz' of terminalalkyneswith CBra(3 equiv.)andP(CoIIs): THP or of cycliwtion of ansaturaledethers.2Reaction Y- or d-unsaturated to in cyclization results 25o reagentin cH2cl2at MOM etherswith this phosphine
This versionalso PermirsI c lines from 2-arylethYlamin d
cu'oy1zl Nq
cH3o^,/
o(n ,.*,,",o).G ]
tetrahydroPyrans.
C"r....t,
,
ocH2ocH3
f"'
-><" cH; (78Vo\
CH,
><: CH, CH, (r0%)
H
Wittig-tYPe cYctizttios-t 2' zation to 3-chloroflavoncsor 2 andN(CJ excess(CoHs)3P/CCL bly involves formation of e cllt
c*t"l-g11'
/-orrp
\
cHr
cooH
a
cH,
(1990)' TetaheilronLctters'31' 3141 I A. Wagner, M. P. Heitz,andC' Mioskowski' 2 lden..-ibid.,30, 19?1(1989)'
(c#5)'P.ccrN(CJT\
ococH3
Triphenylphosphine/Carbon tetrachloride
ntallze the reactionof ketenesilyl dly as a mixture of syn- and,antikal l ield are observedwith trityl rines.but iron(Il) iodide is equally mcth.v"limines.
167
Triphenylphosphine/Carbon tetrachloride (1). Bischler-Napieralski cyclodehydrationof amides.t This reactionis traditionally effectedwith P2O5or ZnCl2.It can also be effectedunderneutralconditionswith (C6H5)3P and CCla(equationI).
NHRI
I -\../-COOCH, C-H. I CH,
+ syn- I
78% l^
anti-l 8 2 :1 8 92:B
cH30
9l :9 93:7 it Chen. Soc.,6t, 1898(1990). . 7 0 . 1 4 8( 1 9 8 7 ) . t Iztters,889(1990).
Drmed in 92-96% yield by reaction CJ.t. (6 equiv.) in CH2CI2. bn of y- or 6-unsaturated THP or {l;
cH3o CH, This versionalsopermitsa one-potsynthesisof dihydroisoquinolines or p-carbolines from 2-arylethylaminesand carboxylic acids.
cHro ,l I cH3o^,/
.. |
NH'
I'4, + c.H.cooH4s
cH3o cH.o
at 25" results in cyclization to Zt'.*-----/t\
tr
l
9H,
9*/
I
\-
l
l
l
l trH, l + cH'cooH--------+
'4*
+ l 'l \l \ - , / l l\ ._ o \.o l. e
* ll
cHr
cH,
cH,
(to%)
Wittig-typecyclization.2 2-Acyloxy- or 2-benzoylbenzoicacids undergocyclization to 3-chloroflavones or 2-chloroindenones, respectively,when treatedwith excess(C6H5)3P/CCI4 andN(C2H5)3 in CH2CI2in 40-60Voyield. This reactionprobably involves formation of a chloro ylide (a) via the acid chloride.
:CH
0
t --rt^\.Ana ]H hed,onLctters,3l, 314l (1990).
-----Io'-."J':r,".",,,1 -.
cl
\4o"o.", -l
CH,
368
Trl
Triphenylphosphineoxide-Trifluoromethanesulfonicanhydride
I A. Bhattacharjya, M. Bhaumik,and S. C. Pakrashi,J. Chem.Res.(5)' P. Chattopadhyay, 228 (1989). 2 H. Vorbriiggen,B. D. Bohn, and K. Krolikiewiez,Tetrahedron, 46, 3489(1990).
chloride. Triphenylphosphine-Titanium(IV) a'-Alkylidenation of clclic enones.r The combination of P(CeHs)3and I equiv. of TiCla or of a mixture of TiCl4 and Ti(O-i-Pr)4 activates cyclic o,p-enones for an aldol condensation with aldehydes to form c'-alkylidenocycloenones.
Alkynes.r In combination wi6 tn activatedketonesto alkYnes. I J. B. Hendrickson andM. S. Hutsil' I
Triphenyltin hydride-TrlcilyDrr ( CyclopropylcarbinYl rldirrb-t pyl group is attendedbY clcev4e d availableby cyclopropanatiooof r cyt
d. *."o-f,il'*r'*ld^I T. Takanami, Letters,Sl'677(1990). K. Suda,andH. Ohmori,Tetrahedron Triphenylphosphinehydrobromide, (C6H5)3P'HBrGlycosylationo! glucalsJ Preparationof 2-deoxyglycosidesby glycosylation of glucalsis diffcult becausethe usual Lewis acid catalystsprovokeallylic rearhydrobroglycosides.Triphenylphosphine rangementresultingin 2,3-unsaturated acids phenols, and carboxylic ofalcohols, promotes addition direct however, mides, high with generally yield, good to moderate in give 2-deoxyglycosides to glucalsto c-selectivity.
9A'
9A. :
Aco\a\ ,.H,p.HRr (coHlol'HBr' I I I il+ c"H.oH 88% A.o..-..\oAoc,H, Aco\..\^,,!J u (u"F='18:221 Aco*r1
clGrlsR
cJtpurcJug O'
CHt
r ,t\ I
CH,J cH,^'/
the hydroxyl grouPbY a grouPtir t andan initin leno)with a stannane is shownin aFi 337).An examPle AnotherexamPle:
ot .* t
l
C.ffrSe$
rV. Bolitt.C. Mioskowski, S.-G.Lee,andJ' R' Falck'J' Org" 55'5812(1990)' (C6H5)3i)20 Triphenylphosphine oxide-Trifluoromethanesulfonic anhydride 2Oif- (1). The reagent(l) is preparedin situin 1,2-dichloroethane'
?l
?
l
r.N(c:Hi).
l CPTCCuPC6H' -h-
o tl
l
CH3CCHTCOOBzI
a
?
C6H5C-CCC6H5
--'---->CHrC=CCOtBzl
I D. L. J. Clive and S. J' Daigmolt' Jand D. L. J. Clive, Org' SYn" suhl
Tris(4'bromophenYl)amlnlur b 338). l GlYcosYlation Whentredcd lationwith PrimarYandseconde Acetonitrilcil linkeddisaccarides'
3 rnhrdride
Tris(4-bromophenyl)aminlum hexahalosntimonste
d S C Pakrashi,J. Chem.ftes. (S), |tn4.dron, 6, 3489(1990).
369
Alkynes.r In combinationwith triethylamine,the reagenteffectsdehydrationof activatedketonesto alkynes. fJ. B. Hendrickson andM. S. Hussoin,Synthesis,2lT (1989).
brnationof P(C6H5)3 and I equiv. crr\atescyclic 0,p-enonesfor an lidenocycloenones.
o //
Triphenyltin hydride-Triethylborane. Cyclopropylcarbinylradicals.r Generationof a radical adjacentto a cyclopropyl group is attendedby cleavageof the cyclopropanering. The precursorsare availableby cyclopropanationofa cyclic allylic alcohol followed by replacementof
,l
,-J
\22\^
OH
K
OH CHCI} NaOH,
tttz,s.31,677(1990). ir m\\ _slycosides by glycosylation I catalystsprovokeallylic rearT ri phenylphosphine hydrobrols. phenols,andcarboxylicacids goodyield, generallywith high
9A"
AeO-
i
\/-\ t| l /-f) | ^-'-"\oAocrH,
CH,
bnic anhydride (C6H5)3i)rO l -drchloroethane.
l) Tscl,ry, DMAP(78%) 2) NaSf"H,(91%)
cr ''"Ji8:ilil;1"
s---?;fi;!=-lili', the hydroxyl group by a group that undergoesready homolysis(such as phenylseleno) with a stannaneand an initiator, photolysis, AIBN, or triethylborane/air(15, 337). An exampleis shownin equation(I). Another example:
cH.
cH"
al-Biatrt;i,, 85%
t a ; P= 7 g ' 2 2 7 I O r s . , 5 55, 8 1 2( 1 9 9 0 ) .
cl cl
c^H.cH,N(C,H.),OH ---dcH' CH, CH,
(r) cH3
c.H,se$
\{/
I D. L. J. CliveandS.J. Daigneault, J. Org.,in press(1991); S. Daigneault, C. J. Nichols, andD. L. J. Clive,Org. Syn.,submitted (1990).
o
tl
lC:CCC6H5
:CCOrBzl
Tris(4-bromophenyl)aminiumhexahaloantimonate,(BrC6IIa)3fr-:SbXo(1; 14, 338). Glycosylation! Whentreatedwith l, RS- or ArS-glycosides undergoglycosylation with primary and secondaryhydroxyl groupsof O-glycosidesto give p-Olinkeddisaccarides. Acetonitrileis the only suitablesolvent.
Tris(F-chloro)hexakis(tretrehydrofuran)divanadium hexachlorodizincate
Tris(F-ch loro)bcrrtHtnrrlf
I, CHrCN 4-A MS
---------------) 83%
Crosspinacol coupling of ileayh general method for stereoselectivepir vanadium(Il) reagent. Aryl aldeiydcs o >90% yield and with high diastcrccd aldehydesunder similar conditionsoorfl
BzlO
oB, O il | il R'cHo+ HiYNBzt.
g. -
t,
ocH3
2
Vinylcyclopropane+ clclopentene.z This one-electronoxidant permits rapid in CH3CNat ambient rearrangement of somevinylcyclopropanes to cyclopentenes temperatures.
CH,O ):\
\1414#o'.",o..",-@ 'r"4\)
fi"'
4-cH3oc6H4 n/icH,
r,cH,cN
/---JcHt
-#---- 4-cH3oc6H4 il"",
Isomertufion of epoxidesto ketones.t This radical cation [as well as trityl (C6H5)3C+SbClo-l effectsthis reaction. hexachlorostibnate,
,zo..
-'C(C6H5)2 (C6H5)2C
|
--+
-?
(C6H5)3C-CC6H5
lA. Marra,J.-M. Mallet,C. Amatore,and P. Siniiy,Synlett'572(1990)' 2 J. P. Dinnocenzo andD. A. Conlon,Am. Soc.' 110' 2324(1988)' 3 L. Lopezand L. Troisi, Tetrahedron Letters,30' 3097(1989).
o
(I)
95Vo yield by reduction of VCI3(THF)3 with zinc dust.r
{ I t
ture, can showmarkedlydifferentrucs. ( lar couplingof aliphaticaldehydeswhcr t vanadium(Il) center of the reagcot. TL simple aliphaticaldehydesto form 1.2 selectivity increaseswilh c-branchi4 it diastereoselectivityby use of los rcry the chelatedaldehydeprevails ovcr cfin 3,3-Disubstituted allylic alcd.lt.t (2) (diphenylphosphinoyl)aceuldehydcs allylic alcohols.A ger 3,3-disubstituted from (c-chloromethyl)diphenylphoepii chelating aldehydesundergo vanadiur nonchelatingaldehydesto provide oaly r over, this crosscoupling is effectcdrid centerevenwhen the substituentsare c selectivityincreaseswith branchingof isopropyl.Thesepinacolson Winig-llo stitutedallylic alcoholswith high *cro
il
hexachlorodizincate [VzTris(p-chloro)hexakis(tretrahydrofuran)divanadium cl3oHF6)6llznzclel (1). This green, dimeric vanadium(Il) reagent is obtained in
6 't
R'=CoHsCHzCHz R2.Rr=H = i-Pr R2,Rt = H = r-Bu R2,R!= H = i-h R2 = CH.,Rr = H = i-Bu R2 = H.R, = CH.
o
llll'-:^", I 2)cH'coR > (c#r\i. (c6HJrPcHrq
I lcrrchlorodizincate
Tris(F-chloro)hexakis(tretrshydrofuran)divenadium hexachlorodizincate
.OBzl
(-------o\ _-,---\.1 BzloI
r, cHpN +A MS 83%
ocH
.OBzl r,,1--\-(--..-.---o\
--,-o-\=-1\-\ ' Bzlo J"", rc-electronoxidantpermitsrapid lopentenesin CH3CNat ambient
cross pinacol coupling of aldehydes. Pedersenet al.z havereportedthe first generalmethodfor stereoselective pinacol coupling of aldehydesby use of this vanadium(Il)reagent.Aryl aldehydescouple in the presenceof I to pinacolsin >907o yield and with high diastereoselectivity (dllmeso = 12-100:l). Aliphatic aldehydes undersimilar conditionscoupleonly slowly, but dependingon the struc-
o oB' il| ll RrcHo+ HiTNBzr, i3
= i-Pr = i-Bu
/----.cHt
ll
hcH,
radrcalcation[as well as trityl reaction.
o tl
H.rC-CC.H, aie::.572(1990). !:r r988). r1 9 8 9 t .
oH R2 o | | ll R'A1A.aNBzr, oH il
+ anri-3
syn-3 67% 73Vo 42Vo SlVo 80Vo
R2,R'= H R2,R3= H R2,R3= H R2=CHI,R3=H R2=H,R3=CHr
4:l 8:l > 1 0 0 :I 1 4 :I 4:l
ture, canshowmarkedlydifferentrates.ofgreater interest,I caneffectintermolecular couplingof aliphaticaldehydes whenonealdehydeis activatedby chelationto one vanadium(Il)centerof the reagent.Thus 3-formylpropanamides (2a) couplewith simple aliphaticaldehydesto form 1,2-diolswith syn-selectivity(4:l). The synselectivityincreaseswith c-branchingin either aldehyde.Attemptsto improvethe diastereoselectivity by useof low temperatures fails becausethenhomocouplingof the chelatedaldehydeprevailsover crosscoupling. 3,3-Disubstituted allylic alcohols.s Pinacol coupling of aldehydeswith a(diphenylphosphinoyl)acetaldehydes (2) can be usedfor a stereoselective route to 3,3-disubstituted allylic alcohols.A generalroute to the phosphinoylacetaldehydes from (c-chloromethyl)diphenylphosphine oxide is formulatedin equation(I). These chelatingaldehydesundergovanadium(Il)-promoted pinacol cross-couplingwith nonchelating aldehydesto provideonly syz-diolsin high yield (equationII). Moreover, this crosscouplingis effectedwith diastereofacial selectivityat the prochiral centerevenwhenthe substituents are only methylversusethyl. This diastereofacial selectivityincreaseswith branchingof the R2 group and is highestwhen Rr = isopropyl.Thesepinacolson wittig-Horner syn-elimination provide(E)-3,3-disubstitutedallylic alcoholswith high stereospecificity.
o ll
lum hexachlorodizincate[V2rdrum(ll)reagentis obtainedin ust
... ii15
2 R' = CcHsCHzCHz = i-h
= r-Bu
r,oc^n, {
371
r) BuLi
o ll
2)cHPoR'> (D (c6H5)rttHrcl (cuHr)rF_A-*, H
.Il:%, CH"
ffe
lc.H,LPrln in''n' ,
Tris(dibenzylideneacetone)dipalledium(chloroform)
o
?
o
H
oD z +HJn'l- 1".",y,$--I1n'
'B. M. TrostandY. Shi,An k.
'"*, ntln'
/",'*'5"
cH,
oH
ds ratio Rr= CzH: R'= Bzl Rr= i-h
14:I 9 9 :I 1 4 :I
R 2 = B z l C H z 82Vo R2= CHr 94Vo R2= lBu 82Vo
92Vo 9lvo 92Vo
Ac
I
N-protected reagent, of thisvanadium(Il) ln thepresence 3-Amino-lr2-diols.a provide syn, to pinacol with aliphatic aldehydes coupling undergo aldehydes c-amino (5-50:l). product major as the syn-3-amino-1,2-diols NHCbz
NHCbz
* "_.(", R'cHo l o
^ l
?"
n#o
Tris[2-(2-methoxyethorY)ct Hydrogenationconlyt.t 1 substnrcsri tionof unsaturated ashighasthoseobtaincdsi6 c
*'T*'
O*+Brcr 8 N-Arylation of ani/rlt.' e n c eo f T D A - I a n d C u C l ( l : J )
I D. Villemin and M. l,etullc. 5n 2 A. Greiner,Syntftcsis,312 (lg|9l
H
l F . A . C o t t o nS , . A . D u r a j ,a n d W . J . R o t h ,l n o r g .C h e m . , 2 4 , 9 l 3( 1 9 8 5 ) ' 2 J. H. Freudenberger, Am' Soc.,lll' 8014(1989)' A. W. Konradi,and S. F. Pedersen, 3 J. ParkandS. F. Pedersen, J. Or9.,55, 5924(1990). 4 A. W. KonradiandS. F. Pedersen, ibid',55' 4506(1990).
Tris(methoxyethoxYProPYl)th from methoxyethylallYl ctbcr. Rdical reductions ol &.Yl to organicsolvcrr. I limited are bromidcs c i alkYl to reduce organic solvents.
Tris(dibenzylideneacetone)dipalladium
(chloroform),
(dbahPdz'CHCl3 (f)'
with a phosphine Potyotefincyclizntion.rThis Pd(0)catalystin combination to polycyclic substrates ligandandaceticacideffectscyclizationof polyunsaturated for initiais required bond a triple However, (zipper reaction). pioductsin onestep pentaspirocycles, and prepare tetrato used has been iion. Thispolyolefincyclization asa mixtureof onlytwo stereoisomers.
' J. Light andR. Brcslow ' Tar*
Trls(2-methoxYmctborYPb
PrePrr. cis-SrilDcncs.2 with arYleldcl arylmethanides asa mixtureof cis-andrrcrr-i in Plu of t phenyl)phosPhine in rerti
H
^ r---H EV CH, 14 '-CH"
\-J
CH,
CH,'r'---r ll
.--....--, A( ) 8s-8e% E+-/ Y
E,
CH,
-,ocH:ocll,
Q,,;-.'
I S. Ieganathan,M. Tsukrmo. t 2 M. Tsukamotoand M. Schlc
37, Tris(2-methoxymethoxyphenyl)phosphlne
l,
I B. M. TrostandY. Shi,Am. Soc.,f f3, 701 (1991). tn .
^\.2\-K-
t
CH,
l
OH
2+ la
(TDA-I ) , 13, 336-337 . Tris[2-(2-methoxyethoxy)ethyl]amine ; 14, 341-342 Hydrogenation catalyst.r TDA-l canserveasa catalyticligandfor hydrogenaat 20". Yieldsaregenerally withPdCl2or RhClr.nHzO tionof unsaturated substrates of Pdor Rh. complexes ashighasthoseobtainedwith expensive
z+
Ac I
Ac I
'anadium(II) reagent,N-protected ilrphaticaldehydes to providesyn, .lt. OH
r
NHCbz
--\21p,I t OH
"
t m . 2 4 , 9 1 3( 1 9 8 5 ) . c n . { m . S o c . ,l l l , 8 0 1 4( 1 9 8 9 ) . )9Ltr
+BrcoHncF,_ ^ wo.u"*
o*
arylateamidesin the presN-Arylationof amides.2 Bromo-or chlorobenzenes enceof TDA-I andCuCl (l:5). ' D. VilleminandM. Letulle,Syn.Comm.,19,2833(1989). 2 A. Greiner,Synthesis,3l2 (1989r. (l), prepared Tris(methoxyethoxypropyl)tin hydride, [CH3O(CHt2O(CHz)r]sSnH :CH2. from methoxyethylallyl ether,CHTOCH2CH2OCH2CH Radicalreiluctions ol alkyl hali.desin water,r Radicalreactionswith Bu3SnH are limited to organicsolvents,but this tin hydride (1) is sufficientlysolublein water to reduce alkyl bromides or iodides under free-radical conditions in water or in organic $olvents.
rm), (dba)rPd2.CHcl3(l). ! combination with a phosphine rrurated substratesto polycyclic mple bond is required for initia?are retra- and pentaspirocycles,
' L LightandR. Breslow,Tetrahedron Letters,3l,2957(1990).
-,ocH2ocHl 'F,p .Preparation.r
( Tris(2-methoxymethoxyphenyl)phosphine, \-./ cis-SfilDeres.2 Preparationof stilbenesby reaction of (triphenylphosphino)arylmethanideswith aryl aldehydesunderusualWittig conditionsresultsin stilbenes 1:1. Useof tris(2-methoxymethoxyasamixtureof cis-andtrcns-isomerscloseto phenyl)phosphine in place of triphenylphosphineincreasesthe cis/trans ratio markedly, particularlyin reactionscarriedout at -75o.
_,ocH2ocHl
9H, il /---a
.,,,\/
'=--^L E
O'r,;--HcuH, \:/ \
cH,
+ coH,cHo#l '
"u",a":cHCuH, ,t=ro.u
t S. Jeganathan, 109(1990). M. Tsukamoto,and M. Schlosser,Synthesis, 2 M. Tsukamotoand M. Schlosser,Synlett,605(1990)
374
Trls(trimethylsilyl)silene
Tris(2-methyl-2-phenylpropyl)tin hydride (trineophyltin hydride), HSnlCHz(1), m. p. 50-51'. The hydrideis preparedby boranereductionof C(CH3)2C6II5]: bis(trineophyltin)oxide in refluxing THF. radical reductions of halfules.r This hydride when exposedto Stereoselective
BrH
nrfr ")<"", -cu, o
,*-N--1 'corcHroclcHr;,
H
I, AIBN ether, 25o -+ 75%
H
BTH
Bri-i ty"", - H...i-i tO"", * cH, ,)-;,
-/-
o/_N-*/-cH, co2R
co2R 4:l
AIBN selectivelyreducesthe a-halo group, whetherCl, Br, or I, of pivaloyloxymethyl 6,6-dihalopenicillanates.The order of reactivity is I > Br > Cl > F. tE. G. Mata,O. A. Mascaretti, Tetrahedron A. E. Zuniga,A. B. Chopa,andJ.C. Podesta, lztters,30, 3905(1989).
(f ). This reagentis genTrls[(trimethylsilyl)methyl]aluminum,[(CH3)3SiCH2]3AI erated in sirn by reaction of AlCl: with [(CH:)rSiCH2lLi. The neat reagent is pyrophoric. this alanereactswith Allyltrimethylsilanes.r In the presenceof Pd[P(CoH5)3]a, yield with transferof vinyl or aryl triflates to form allyltrimethylsilanesin 60-85/o group. one (CH3)3SiCH2
/-'Ytu'' (rloro,cF.
.'.".10,1?,...". /YQH' ---;(zL.",ri(cH3),
t M. G. Saulnier, andD. M. Vyas,z{m.Soc.'lll' J. F. Kadow,M. M. Tun,D. R. Langley, 8320(1989). Tris(trimethylsilyl)silane,15, 358-359. In combinationwith an initiator, this R4dicalreductionswith Kcruhsilrsiff.r silane(l) reducesnot only alkyl halides,but also thionoesters(usedfor deoxygenaHowever,cleavageofC-S bondsis ineffition ofsecondaryalcohols)and selenides.
cient. It is more efficient thrn BoS spondinghydrocarbons. The silanealso can be uscd for I trile.
( DG o - , ' : This silanecan also bc usodro d addedslowly to a solutionof thc pru
(ID c-Cull,,l + CIL:
ll Catalytic rcductbt of ll.r if hdidct I of alkyl radical reduction (CH3)3Sil3SiXformedon rcdoctb genationprocessare only sligttly b amountof the silane.
I M. Ballestri, C. Chatgilido/u.K. EO r g . , 5 5 , 6 7(81 9 9 1 ) . 2 M. Lesage,C. Chatgilialoglu. erd D.
Trltyl bromide (triphenylmcrhylh N-Trityl a-amino acidt.t TrBl amino acids. The reaction of thc r aminein CHCI3/DMF(2:l) Provil hydrolyzedin situ with merhrrcl r I M. MutterandR. Hcrspergcr. S.ria
Trltyl perchlorate. Mukaiyama-Michoel & addition of enol silyl ethcrs of qd trityl perchlorate can procccd rirl ether (2) ofthe ketone(R)-l rd
Trltyl perchlorete
ineophyltin hydride), HSnlcHzs preparedby boranereductionof t.r This hydridewhen exposedto
BrH o\-cH, H"'f
I
- s
'-cH, * r-- AcH, 'co2R oAN-t/-cn,
co2R
4:l
lher Cl, Br, or I, of pivaloyloxyFtrritv is I > Br > Cl > F.
375
cient. It is more efficient than Bu3SnHfor reduction of isocyanidesto the correspondinghydrocarbons. The silane also can be used for hydrosilylation of dialkyl ketonesand acrylonitrile.
.u
G".'#G*irs(cH3)3r3
This silanecan also be usedto effect addition of alkyl radicalsto alkenesif it is addedslowly to a solutionof the precursorto the radical andthe alkene(equationII). I, AIBN
-#-0D c-CuH,,I + CH2:CHC*
c-CuH,,CHrCHrCN
Tetrahedron ihooa.andJ. C. Podesta,
SiCH:lrAl(l). This reagentis genl.r,SiCH2lLi.The neat reagentis this alanereactswith i[P(C6H5)3]4, s rn 60-85% yield with transferof
,-ry"ut, . l
t\z\cHrsi(cH3)3
4ley. andD. M. Vyas,Am. Soc.,lll,
with an initiator,this n combination (usedfor deoxygena, thlonoesters 'er. cleavageof C-S bondsis ineffi-
Cdalytic reduction of RX.2 This silanecan be usedin catalytic amountsin the radical reductionof alkyl halidesif NaB& is addedto regeneratethe silanefrom the [(cH3)3sil3six formedon reductionof RX by l. Yields in the catalytichydrodehalogenationprocessare only slightly lower than thoseobtainedby use of an equimolar amountof the silane. I M. Ballestri, J' K. B. Clark,andD. Griller,B. Giese,andB. Kopping, C. Chatgilialoglu, Ors.,55,678(1991). 2 M. Lesage, ktters,30' 2733(1989). andD. Grillet,Tetrahedron C. Chatgilialoglu,
Trityl bromide (triphenylmethylbromide). N-Trityl u-amino aci.ds.r TrBr is markedlysuperiorto Trcl for tritylation of aaminoacids.The reactionof the acidswith TrBr (2 equiv.) and (excess)triethylaminein cHcl3/DMF (2:l) providesthe N-tritylaminotrityl ester' which is then hydrolyzedin siru with methanolat 50o. Yields are 80-86Vo. I M. MutterandR. Hersperger, 198(1989). Synthesis,
Trityl perchlorate. Mukaiyama-Michael reactionr (13, 339-340; 14' 344-345). The conjugate addition of enol silyl ethersof optically active ketonesto c,p-enonescatalyzedby trityl perchloratecan proceedwith high diastereoselectivity.Thus the (Z)-enol silyl ether (2) of the ketone(R)-l reactswith enone3 to give the l,5-ketone 4 with high
Trityl perchlorete (cH3),sicH,cooc,H, Bu.NF -----_-+cH3v{r''cH3
O ll cH3v"l!,cH3
OSi(CH.)" I
l
l
SiMer-r-Bu (R)-r
SiR3
2
lt
t
ol
% lcqAz-cH, rflq I
(3)
o cn,-r\...cn,
i l l
HBF.
?cn.
cHrl\.AcH, = 80:20) 5 (antilsyn
4 (antilsyn= 88: 12)
anti-selectivity.Removalof the silicon substituentwith aqueousHBF4 resultsin an intramolecularaldol reactionfollowed by dehydrationto give a cyclohexenone(5). I B. B. LohrayandR. Zimbiniski,Tetahedron ktters,3l,7273 (1990r.
Ultresound, ))>, . Review.r This review ir-h& generators:whistlers, clcening bd efficient,but the most expensivc.c1 the temperature range to thet of ft cludesthat sonicationis moo urfrl organometallics.The rcfererc (21 in the last l0 years. Luche er ol.2 point out thrr iab to mechanicaleffects such u rgir mechanismof a reaction.Tbcy mc ation of single electron tnrrfcrt I obtained in the absenceof sooit-ir ultrasound.
Oxymercuration.t Coorrci reaction,althoughhighcr yicldr u sive mercury(Il) trifluorolcanc. A sonicationof a mixture of HgO ril CHzClz,hexane,and aqueousTHI curation,in which caseonly I q;n is formedon oxymercuratioo.Ad t tivity in monooxymercuntiooof r
osi(cH3)r -V"-ZCHt I siRs
o tl
t:+
(3)
"'\,4cH, to'o' ,
CH,
cH,
siR3
; . r = 8 8 :1 2 ) I aqueousHBF4resultsin an b grvs a cyclohexenone (5). ll--: r1990).
Ultresound, )>:. Reviev.r This review includes a discussionof the three types of ultrasonic generators:whistlers, cleaning baths, and probe disruptors. The last is the most efficient, but the most expensive.cleaning bathsare inexpensive,but are limited in the temperaturerangeto that of the liquid used, generally water. The review concludesthat sonicationis mostuseful in heterogeneous reactions,particularly thoseof organometallics.The references(235) datefrom 1953to the presenttime, with most in the last l0 years. Lucheet al.2 pointout that sonicationcan result in an overall rate increaseowing to mechanicalefiects such as agitation, but that sonicationcan also influencethe mechanismofa reaction.They notethat in the latter casesonicationleadsto acceleration of single electron transfers and can result in a difierent product than that obtainedin the absenceofsonication. In general,ionic reactionsare not sensitiveto ultrasound.
ll
(Y**,'
'/
w%
o
\-\.^cH,
Z\A
\r*, 95%
(.-jL-/-""'
oxymcrcuratioz.l commercial mercury(Il) acetateis the usualreagentfor this reaction,althoughhigher yields and greaterselectivity obtain with the more expensive mercury(Il) trifluoroacetate.A variety of mercury(Il) saltscan be prepared by sonicationof a mixture of Hgo with a carboxylic acid (2 equiv.) in solvlnts such as cH2cl2, hexane,and aqueousTHF. They can also be preparedin situby oxymercuration, in which caseonly I equiv. of the acid is requiredsince I equiv. of the acid is formed on oxymercuration.And this oxymercurationcan result in increasedselectivity in monooxymercurationof a diunsaturatedsubstratesuch as limonene(l).
"p'""'
Ultrusound
QH,
rAr \../
!"'
l) Hgo'cF3cooH
I
A
,ffi8i'li?"ff -
I I
vI
+h CH,
(4Vo)
cr,frcn,
cH.AcH, I
(76Vo)
Hydrostannylation.aThisreactionwithatinhydridenormallyrequiresaninitiator,usuallyAIBNbutalsoB(CzHs):(14,314)'Itcanalsobeinitiatedwithhigh rate acceleration(100-600times) intensityultiasound,and suchreactionsshowlarge -50o. Sonicationis also effectivefor radical andtake placeevenat temperaturesof reductionsand cyclizations(last example)' (coH,),SnH'Bur_rSn(coHs)r
BuC:CH 4;-
(cis,929o) (C6H,)rSnH' -64"
-+#_-) cH3(cHr),ocHJ fu"t
Ao."r.":cHr CH,
cHi(cHr),ocH3
Bu,SnH, C.H.--,/O\
B
t-/-
t -
I
.CH,
= 94:6) (translcis
of l'4- to l'6-diesters acAcyloin condensations The acyloin condensation and highly dispersed cording to the Riihlmann version using chlorotrimethylsilane sodiumismarkedlysimplifiedbysonochemicalactivation'Technicalgrade be used' ClSi(CH3)3and small cubic piecesof sodium can
( |
-COOC,H.
-coocrH,
+ CtSi(CHr)j
Na.rHF --o - 5 ' . > > r*-'-
osi(cH3)3
osi(cH3)3
787 (1989)' I C. Einhorn,J. Einhorn' and -Bi"r,orn, J. L' Luche,Syntlresis' l*^tters,3l, , Tetrahedron and i. v. Sinisterra-Gago 2 J. L. Luche,C. Einhorn,i. 4125(1990);C.Einhorn,J.Einhorn,M'J'Dickens'andJ'L'Luche'iDid"31'4129(1990)' 3 J. Einhorn, C. Einhorn, and J. L' Luche, J' Or8" 54' 4419(1989)'
a E. Nakamura, D. MachiiandT. loubortri'' 5 A. Fadel,J.-L. Canet,andJ. Sdr[n. S-dr
Urea-Hydrogen Peroxide, H2NCONH solid is formed on crystallizatioo of rn availablefrom Interox Chemicds l-rd. o Alternative to anhYdtols fltQ..t 1 acetic anhydride or trifluoroacctic ril1 alternativeto anhydrousH2O2for cpori version of nitrogenheterocyclcsto Nor it shouldbe usedwith care. The comPlexconvertsN'N-bi{trid in 86% yield.z rM. S. Cooper,H. Heancy, ^. 1' lftrtol4 2 W. P. Jackson, (1990). SYnlett,536
peroxide Urea-Hydrogen
'|'""'
r p (4%)
ll
dnde normallyrequiresan initican also be initiatedwith high (100-600times) re acceleration nron ls alsoeffectivefor radical
SnrCuHs): = u. vlQ r
}|,
CH:)roCH3
r) fi.--rl"\
J
I
.CH,
ttd4(,rr = 94:6)
ion of 1,4- to 1,6-diesters achrlsrlaneand highly dispersed actnation. Technicalgrade used. .osi(cH3)3 'osi(cH.)l ( I9 8 9 ) . n-Cago,Tetrahedron Letters,31, . L Luche, ibid.,3l,4129(1990). l'9 r1989).
a E. Nakamura,D. Machii and T. Inubushi,Am. Soc.,ffl, 6949 (19g9). 5 A. Fadel, J.-L. Canet,and J. Sala0n, Synlett,Bg (1990\.
Urea-Hydrogen peroxide, H2NCONH2-HzOz, (!, m.p. 90-93.). This crystalline solid is formed on crystallization of urea from aqueousH2o2. It is commercially availablefrom Interox ChemicalsLtd. or Aldrich. Altemative to anhydroas Hzoz.r This addition complex in combinationwith acetic anhydride or trifluoroacetic anhydride (0.25-0.50 equiv.) can serve as an alternativeto anhydrousH2o2 for epoxidation,Baeyer-villiger reactions,and conversionofnitrogen heterocyclesto N-oxides. The complex is reasonablystable,but it shouldbe usedwith care. The complexconvertsN,N-bis(trimethylsilyl)ureato bis(trimethylsilyl)peroxide in 86% yield.2 ' M. S. Cooper,H. Heaney, A. J. Newbold, andW. R. Sanderson, Synteu, 533(1990). 2 W. P. Jackson, (1990). Synlett,536
r-Valinol. Knetic re solationof ( t )-b-anisahlehyile)Cr(CO)t 0).t This arenechromium carbonylhas beenresolvedby chromatographyof a derivative, but a more convenient methodinvolves reactionwith r-valinol to form two imines (a, b) with widely differentRlvalues.The fastestmovingfraction(a) is a precursorto (-)-1' whereas the slowermoving fractionprovides(+)-1 on hydrolysis.
Vanadium oxytrichloridc, VO( Oxidative dccartory lain< When heatedin refluxing chlort undergodecarboxylationrnd dcr cessis useful for preparatiood limitations, includingdehydnir formation of ketonic by-prodrr
o otl l t l
Ho)a( 'cll, cHr
o
o
"o51 CttCOlr{
cH, cll
z^\,/.cKo L-(cHr)'cHcHcHoH ^..^..i1..^.. ll
>
o oll l l t
VOCH.
Ho)ac
(r)-I
cH, cH. Pr-j
proved by use of ldshlsro( prol ton Sponge(l equiv.) can bc d
il'1oH
t I. K. MeierandJ. Scbwertz. ,h
I
(io"'
t.tl "Bn--r"" Z\.)
: n-i
)\iocH, c(co)3
(a)
""Jh?,
(b)
,o*f",o' cHo
ocH3
ocH3
l
cHo
cr(bo), (-)-r
I S. G. Davies and C. L. Goodfellow, Org, Syn., submitted(1989). 3&)
Vsnadlum oxytrifluori&, VOF Asymmetric phcnohc ori/ I with VOF3 resultsin eficicu 1
"::"Dd:
-coocHSr
(2R,5S)-1, c"+ 32'
Vanadium oxytrifluoride
CO)\ tl).t This arenechromium I denvative,but a more convenn r*o imines(a, b) with widely is a precursorto (-)-1, whereas t o l rs r s .
3tf
Vanadium oxytrichloride, VOCI3. ortdativ c decarboxylatio n-de oxyge nation o! p-hydroxy c arboxylic acids,l when heatedin refluxing chlorobenzenewith vocl3, B-hydroxy caiboxylic acids undergodecarboxylationand deoxygenationwith formation of an alkene.This processis useful for preparationof tri- and tetrasubstitutedalkenes,but it has some limitations, includingdehydration,isomerization,migration of the doublebond, and formation of ketonic by-products.In general, yields of the desiredalkeneare im-
o o H tl
I'qH'cl'^'" An" tun' -? HoA (cH')'c:CHCuH' ""'\"' o o H
| J I "o--)(aiT'
8s?(cH,),c:c(cH,),
CH" CH. i
l
OH l
"o$cuH,,-c CH, CH,
h-t .-{
,') t.tl .yocH"
OH
{
6"
c(co)3 (b)
h-,
,*J",o. ('\Y'cHo
il.
$Ao*r.
c(co)3 (+)-r
GH3\2c{) 77%>
provedby useof trichloro(p-tolylimino)vanadium(V), CH3C6HaN:VCIr(l). pro_ ton sponge(l equiv.) can be addedto preventisomerizationof the doublebond. I I. K. MeierandJ. Schwartz, Am. Soc.,llf, 3069(1989);iden,J. Org.,55,5619(1990). Vanadium oxytrifluoride, VOF3. Asymmetricphenolic oridativc coupling.r oxidation of the chiral oxazolidine 1 with voF, resultsin efficientpara-para coupling to a spirodienone2. The trans-
cHsoY\
cH,o)J"ro>.'-l\
- -r-
LJ
V-o" -coocHrccl,
"'+1i^, eBEo
(2R,5S)-1,ao+ 32"
2, (a"+ 34") d rl9E9).
,*J^,"n,o"
Vengdium oxytri6uoride
w Wster.
o 3 isomerof I doesnot undergocoupling. Reductiveremovalof the trichloroethoxycarbonyl group resultsin the pentacyclicamine3. I J. D. White,R. J. Butlin,H.-G.Hahn,andA. T. Johnson, Am. Soc.,112'8595(1990).
Chisen rearrullitc.c)t. I acceleratethe rate ofClaisca rc rearrangementat lower tcryt H2O at 60o in 85% yicld. Rc benzeneat 60o requires > l(I) The paperpresentsscvenl orl cosolvent. The rate accclerri transition state.
o'
NaOOClCHrt.A t
rP. A. Grieco,E. B. Braod6, S. I
Wittig and Wittig-Horr ru Review.r This revicw cor ons, and phosphineoxidc cutt and (E)-selectivities(558 refcrr IB. E. Maryanoffand A. B. nc-
CH.O
w Water.
3 tmo! al of the trichloroethoxycarlon .,l'a.Soc.,ll2,8595 (1990).
claisen reanangemenf. Grieco et ar.t have found that water as solvent can acceleratethe rate ofclaisen rearrangementofseveral substrates, and therebyallow rearrangementat lower temperatureswith higher yields. Thus I rearrangesto 2 in Hro at 60o in 85% yierd. Rearrangementof the corresponding methyt ester in benzeneat 60o requires > 100 hours and gives the rearranged ester in 64% yierd. The paperpresentsseveralother examplesof the advantages of water as solventor cosolvent. The rate accelerationmay be associatedwith stabilization of a polar transitionstate.
9AcH, |
Naooc(cHr)u/\zcH, I
- - _n,o.*. -l
8s%
acHo \Z\(cH,)ucooNa t
f P. A. Grieco,E. B. Brandes, S. McCann, andJ. D. Clark,.f.Org., S4,5g49 (19E9). Wittig and Wittig-Horner reagents. Review.t This review covers use of phosphoniumylides, phosphoryl carbanions, and phosphineoxide carbanionsin synthesiswith particularemphasis (z)on and (E)-selectivities (558 references). ' B. E. Maryanoffand A. B. Reitz,Chem.Rev.,g9, g63(19g9).
3t3
Ytterbium(0). Chiral |,3-diols. Coupling of diaryl ketoneswith chiral epoxidesmediatedby yb (15, 366)provideschiral 1,3-diolsin high opticalyields.Generallytwo diols are formed by coupling at both carbon atoms, but coupling with styreneoxide occurs mainly at the more-substitutedcarbon.
rHF l-cu",. " "Xpl_-_____-_+ I A'...:-'
"o"ta. C:O
"".o,1 + yb
Lc'H;ib I
crH(
OH
OH t
r
cuH,-9-9H-cHroH t l c6H5 cH3
l
OH
l
.
+ C.H'-C-CH2-CH l l CH, CUH' (377o,9O7o ee)
(46Vo,9OVo ee)
chem.ktters,1421(1990)' r K. Takaki,s. Tanaka, andY. Fujiwara, F. Beppu,Y. Tsubaki, Ytterblum(Ill) chloride' YbCl3. Reversalof diastereoselectivityol rcactions with RM9X and RLi'r The chiral addition of | (12, 237-239) undergoesdiastereoselective 2-acyl-1,3-oxathiane
cH'A
,4-yv", o t-----/4------{
re"
I
+ RMgBr ----+ (R=PrC=C) + YbCl3 + CeCl,
787o 99Vo 4r6vo
:7Y;:'.Yry;'"' 8 4 :l 6 0:100 38:62 3t4
Grignard reagentsbecauscof Crrm r sorsto optically activetertiary dcob reagentis addedto a suspensiooof I resultantspecies,RMgBr.YbCl3.ree quantitativeyield. Ytterbium(Ill) chloride can rlso n with alkynyllithium reagents.Cerirr lowered. I K. Utimoto.A. Nakamura. rld S- Xr
Ytterbium(III) chloride
nth chiral epoxidesmediatedby I l ields.Generallytwo diols are plrngwith styreneoxide occurs
OH
OH
CH OH + CuHr-C-CHr-F t CuH,
l CH,
(37Vo,9OVo ee)
r
ibara. Chem.Letters,1427(1990\.
L RItgX and RLi.t The chiral drastereoselectiveaddition of
lr --------rC -8qr rDqc !6qt
\r.C,H.
l
l o H
-s' /
- ^//-'.7CzHs
t..
* - d H o R 84: 16
0:100 38:62
Grignard reagentsbecauseof Cram chelationto provide mainly adducts2, precursorsto optically activetertiary alcohols.However, if a THF solutionof the Grignard reagentis addedto a suspensionof YbCl3 in THF and storedat 0o for 2 hours, the resultantspecies,RMgBr'YbCl3,reactswith I at -78o to provide3 in95.4% dein quantitativeyield. Ytterbium(Ill) chloride can also reversethe diastereoselectivityof reactionsof I with alkynyllithium reagents.Cerium(III) showssimilar effects,but yields are also lowered. rK. Utimoto,A. Nakamura, andS. Matsubara,Am. Soc.,ff2, El89(1990).
(II) Br(CHr)uCN
INC(CH,)6Cu(Cl
.,rI a cH,
Zlnc. Luchc allylation (13, 298). One unusualfeature of Luche allylation of aldehydesis the useof HzO/THF as solvent.More recentlyWilson and Guazzaronirhave effectedthis allylation with allyl halidesand zinc dust in an aqueousNH4CI solution c-18 with a solid organicsupportin placeof THF. The supportcanbe reverse-phase on (Bio-Red), or OV-101 silica gel (CustomChem. Laboratories),biobeadsSX8
zn NI{.cr, n - C.H,TCHO+ CHrCH:CHCH2CI -P
\ / NC(CH.|.
In the presenceof a Pd(0) cetdyl. , aryl and vinyl halidesto form novel rr (Itr)
ft' n - C.H'TCHCHCH:CHz I OH
C\OOCrH5 \, \
( \:/
Fz's'
+ p-BCJ
( 1: l )
OH
+ cH':cHCHzBr;
(-h"
t-,X.",cH:cHz \- -_ OH
OH
cis-Reduction of proparglic M CH3OH/H2O(7:5: l) reducessiny'c pr also reducesconjugateenynols and dr group permits selectivereductionof n
"o.. of this newsystemis that a hydroxylgroupdoesnot chromosorb.one advantage reagentis probablynot involvedsincesuchsperequireprotection.An organozinc ciesareunstablein water. by reduco! activatedzincwithf,x.2 Activatedzinc,Zn*, obtained Rcactions tionofZnCl2withlithiumnaphthalenideinTHForDME,canaddoxidativelyto alkyl,aryl,andvinylhalides.Thisreactiontoleratesawidevarietyofsubstituents' Theresultingspecies,RZnBr(I),ontreatmentwithCuCN'2LiBrisconvertedintoa reTheseorganocopper-zinc .opp", aeriiatineRuCu(CN)inBr(I)(15' 225-226)' agentscoupledirectlyo,in""iachloridestofurnishketonesingoodyield(equation of thecopperadditionto enones(15' 229-230)'Reaction conjugate tior unOergo zincreagentswithatlylichalidesresultsmainlyinSx2,substitution(equationll).
/CHC=C CH;
(CH,)2C:C (CH:).CH.
Reformatslcyreaction. Ftrstrr' reaction,both inter- and intramolccuh the reactionsuggeststhat metal preFn (13, 348) is the most satisfactorY.
I S. R. WilsonandM. E. Guazzarooi' .l- t 2L.Zhl, R. M. WehmeYer, andR. D- Li 3W.-N. Chou,D. L. Clark,andJ. B. sl a A. Ftirstner, 5?l (19t9). Synthesis,
l) Znr
(I) Br(CHr)TCOOC#5
2)cucN'2Licr, ' \-2n5wL\vrr, cfl5ooc(cHr)rCu(CN)ZnBr soe' lc;nPoct
c;n'cotcJ,lcooc,Hs 3t6
Zinc-Copper couPle. Pinacol reductive couPling.r A CuCl2 in acetonc-water(4:l) Prm unsaturatedvic-diols. The reactioai
Zinc-copper couple
(II) Br(CHr)uCN ---+
[NC(CHr)uCu(CN)ZnBr] 9l% lcH,\Z\cH.cl Y C H ," \
t of Luche allYlation of aldey r*'ilsonandGuazzaronilhave I in an aqueousNHcCI solution C-18 port canbe reverse-Phase iX8 (Bio-Red),or OV-l0l on
/
In the presenceof a Pd(O)catalyst,organozinchalidescan coupledirectly with aryl and vinyl halidesto form novel arenesor biaryls.
(rr)"fl,", (:Xr""r
OH
-<.
CH'CH:CHt
CH;*(CHr)6CN
S n2 '
> a-C.H,TCHCHCH:CHz
(l: l)
+ 9'7:3
NC(CHr)6
9*r,
-ruroH
CHCH:CH,
319+ p-B,cuHocN
cis-Reductionof propargylic alcohols.s Rieke zinc (5, 753; 6,679) in THF/ CH3OH/H2O(7:5: l) reducessimplepropargylicalcoholsto cr's-allylicalcohols.It also reducesconjugateenynolsand diynols to dienols. Activationby the alcohol group permits selectivereductionof nonconjugateddiynols.
OH zn*
HO
bat a hydroxYl grouP does not 11 not involvedsincesuchsPe6 zrnc.Zn*, obtainedbY reducr DVE. can add oxidativelYto I a * ide varietYof substituents. luC),J.2LiBris convertedinto a ter. TheseorganocoPper-zinc lctones in goodYield(equation L:-10). Reactionof the copPerl.l substitution(equationII).
\
cH,oH. H,o. A
.cHc=c (cH?),c=c (cH,)rcHr+ / CH;
(\.=c(cH2)3cH3 )-oH CH,
Reformatskyreaction, Ftirstnedhas reviewedliterature(1887-1988)on this reaction,both inter- and intramolecular.A comparisonof differentforms of zinc for the reactionsuggeststhat metal preparedby reduction ofZnCl2with silver-graphite (f3, 348) is the mostsatisfactory. 'S. R. WilsonandM. E. Guazzaroni, J. Or9.,54,3087(1989). 2 L. Zhn,R. M. Wehmeyer, andR. D. Rieke,ibid.,56,1445(1991). 3W.-N.Chou,D. L. Clark,andJ. B. White,Tetrahedron (1991) Letters,32,299 a A. Fiirstner,Synthesis,57l (1989).
DoCrCH,),Cu(CN)ZnBr m+f cJt'coct H.CO(cHr)3coocrH5
Zinc-Copper couple. Pinacol reductivecoupling.r A couplepreparedby sonicationof zinc dust and CuCl2in acetone-water(4: l) promotescoupling of enonesand acetoneto c,0vic-diols.The reactionis slow in the absenceof sonication. unsaturated
o:"'
Zinc borohYdride
ZrBll.v$r
OH
398 (1989)' rP. Delair and I.-L' Luche' J'C'S' Chem'Comm''
reducedto the correspondingpnml ( reducedmainly to 2-phenylethaml regio- and stereoselective' Selectivereductions'2 Zinc bo and o,p-enalsat l5o without cft ol Reduction azomcthitcs't Z arv aminesor the amine'BH3cooPl aliylation-reduction of nitriles to 1
r
couple'14' 350-351'- .^ ^ Zinc-Copper/silver stereoselecCu(oAc)2andAgNo3effects s.t (8,E,Z)-Trienc [* ^"it" ^"dby Catalytic i to tte (n,n,z1-rri"nez ii cttrotllH2o' tive reductionor trreoie-nyne but only in 30%yield' uring Linii'u;L "ut"tytt gives2' hydrogenation
GHrLcooclr3
c"4MsB') Prc=N I LC t B. C. RanuandA' R' Das't'C'S' d t D. C. Sarkar, A. R' Das' ad B' C l 3 H. Kotsuki, N. Yothimura' I- Kea'
Zinc bromide. Dlels-AtdercalalYst't A novel hid Diels-Alderreactionbetweena
'0* r,,,, f3i,BH},1o \./\
:1
-(CH2)3COOCH3
OH
/-,zCH,
o>A'
!al-,,.".. \Ao
CH, CH, 1
4951 (1989)' Tetahedronktters' 30' I M. Avignon-Tropisand J' R' Pougny'
,r"*Yirirll"!1li;r*
bv hvdtide reduced arc usualty Epoxides of eporides.' the provide to carbon
less-substituted particularlyLiii'nt' ly:"ttack aithe r€agents, on sioz in with zn(B{r)zadsorbed at.onor.Howwer, reductions. more-substituted
THFat25ocanshowtheoppositeregioselectivity'Thustheepoxideofal-alkeneis
+ 7nBr,
?t.l
Zinc bromidc
H (cH,):
I
zn(BH.),/sio, * (Y""' >fit"' \+oH
aT:".
V'..on
\,./
cis,85Vo
'a ,OH
\o" 1CH3)z
lNOr effectsstereoselecCH.OH/H2O.CatalYtic 30% Yield.
oocHl
trans, l0%o
about 90% yield' Styreneoxide is reducedto the correspondingprimary alcohol in oxidesis ol (-g5% yield). The reductionof cyclic reducedmainlyto z-ptrenylelhan regio- and stereoselective' Selectivereiluctions.2ZincborohydrideinDMEcanreducesaturatedketones ando,p-enalsat-15owithouteffectono'p-enonesorsaturatedaldehydes' reducesSchiff basesto secondReductionof azomethine.r.3ZnlBHn;, in ether aryaminesortheamine'BH3complexinhighyield.Thisprocedurecanbeappliedto alkvlation_reductionofnitrilestoyieldl-phenylalkylamines. Pr
prc=Nc.H,MsBr, Lri:*|
CHNH'
HC.H,
rB. C. RanuandA. R. Das,J.C'S'Chem'Comm''1i34(1990)' (1990)' 2 D. C. Sarkar, A. R. Das,andB' C' Ranu'J' Org'' 55'5799 401(1990)' 3 H. Kotsuki,N. yoshimural-i. iuaotu,Y. Ushio,andM' ochi, Synthesis' Zinc bromide. Diels-Atdercatalyst.|Anovel'generalroutetotricyclicditerpenesinvolvesa as I and a 1,4-benzoquinone' Diels-Alder reactionbetweena hindereddienesuch o\,,\
'
:oocH3
+ cH,
| \Ao
|
-
r2kbar
21%
t . 1 e 5 l( 1 9 8 9 ) .
ually reducedbY hYdride nltedcarbonto Providethe BHr)z adsorbedon SiO2in ilreepoxideofa l-alkeneis
+ ZnBr,
't570
3
CH, CH, 4 2 . 4 :I 8 . 4 I:
390
Zinc bromide
by use of high The steric difficulty inherent in a hindered diene is partly solved reactions,but pressure.Lewis acidscan also acceleratethe rate of high-pressure reactionof I the more importantly, can improve stereo-and regioselectivity,Thus undesired latter, The with theluinone 2 underhigh pr"rtut. resultsin both3 and4' productisaresultofpre*sure-promotedoxidationof3'UseofZnBr2improvesthe catalystsin yi.ta of I anddecreasesformation of 4. Yb(fod)r and Eu(fod)3are useful
t-L Reactionol urybttuile grls ud the solvent,ketencsilYl foru tion with acrylonitrile. Tbc CH2CI2with ZnIz, with no intcrcu this way, but substitutedacryloott
reactionsof the enol ether 5. ocH3 I 2 kber
/ocH'. (cHr)rC:c_
{
os(cH,) I
ocH3
CH, + Yb(fod),
CH' (26Vo) Q'|Vo)
rT. A. Engler,U. SamPath' S. Nrg J. Org.,54,5712(19t9). 2 D. deOliveiraImbroisird N. S. ! 3 A. QuendoandG. Roussceu. S-n I (234o) (129o)
ZnBrzisanemcientcatalystforreactionofdieneswiththedihydropyridinone9to reactionsprogive cis-hydroisoquinolinessuch as 10.2The correspondingthermal vide adductsin onlY 15-25% Yield.
Zinc chloride. (S)-}-Amino acids-t Tbc Xr 2,3,4,6-tetra-O-PivaloYl-P-oOPiv
coocH3
v
OPiv
i"'"'
""\
6vgJ-z
'* tr")G
CH3OOC/
Zinc chloride
nnll solvedby use of high reactions,but hrgh-pressure rtr . Thus the reactionof I tir and 4. The latter,undesired I l. Useof ZnBr2improvesthe ur it:rlJ)1 areusefulcatalystsin
391
Reactionof acrylonitrile with keteneacetals.s Dependingon the zinc salt and the solvent,ketenesilyl acetalsundergo[2 * 2]cycloadditionor a Michael-typeaddition with acrylonitrile. The former reactionoccursin CCla with ZnBrz, the latter in CH2Cl2withZnI2,with no interconversion.2-Chloroacrylonitrilecanalso be usedin this way, but substitutedacrylonitriles are inactive.
cH. ocH" ZnBrr.CCll(80%) .
cn,$ositcu,l, !_
I (CHr)rC:Ct-
/ocH3
CN
+ CHr:Qt1gY
osi(cH3)3
CN I Znl,, CH,Cl,(90%) #
I
(cHJrC-CHTCHS(CH3)3
,OCH.
I
coocH3
'o
' T. A. Engler,U. Sampath, S. Naganathan, D. V. Velde,F. Takusagawa, andD. Yohannes, J. Org.,54,5712(1989). 2 D. deOliveiraImbroisiandN. S. Simpkins, Tetrahedron Letters,30,4309(1989). 3 A. Quendo andG. Rousseat, Syn.Comm.,19, l55l (1989).
1l (23Vo) (127o) 9 to nhrhedihydropyridinone odrngthermalreactionspro-
Zinc chloride. (S)-p-Aminoacids.t The Mannich reactionof the Schiff basel, preparedfrom 2,3,4,6-tetra-O-pivaloyl-p-o-galactosylamine, reactswith the silyl keteneacetal2 in OPiv
sd>.\
^/,OS(CH3)3 + (CH")"C:C -ocH,
Pivo\---ffi+\"-cuH,
)
OPiv
cHr'..cH, H *{"-"", sc6H5
3 ( 1 5 0 :l )
coocH3 cH,oH JHcr,
zncr,,rHF, _30"
8e%
Zinc trifl uoromethanesulfonate
Cbz
CH: CH" eo'> H,o'. "r*_._)Xaoo"
OPiv
"CuH'
V-N,/
"COOBzl
t c
H
HJ
(s)-4
(959o)
(907o)
I
<-'r-----*" \ . I ll ll*
I K. SatoandA. P. Kozikowski.Tetohe*a -30o to give essentiallya singleproduct(3)' which the presenceofZnCl2inTHF at (4)' can be convertedto (S)-p-phenyl-p-alanine methides'z In the presenceof p'quinone with l3+2lCycloaddition oI ,'y"" thisLewisacid,p-quinonemethidesandstyrenesundergoaformal[3*2]cycloaddishowssomestereoselectivity.Thus tion to form dihydro-lr1-indenes.The reaction retained(17: l) and only two of the four the geometryof the (E)-sty'"n" i' largely possibleproductsu,"fo,."d.Presuma=bly,anyelectron-richalkenecouldparticipate in this cycloaddition'
Zirconocene-4-DimethyhminopyrlCp2Zrl(CH)2NPylTHF, lb. Tbc coq|c with I or 2 equiv. of DMAP in THF r 25 than the cherry red lb and can bc sro,rcd Rcductivc coupling ofalkytct.' Tl reaction of l-trimethylthioalkyncs rit alkyne to form coupledproducts.
""T*,,,'b -20"'
ocHl ZnCl,
+ C.HTCH:CHCH.
67Va
[."[^-]'
(E)
,"lllff=" OH
OH
cH,or\ocH,
u
|
\f)'cuH'
crHi
I
cH,oy\ocH,
'cH'
* r7'r
ot{ I
Wa.n,
\ c,H,
I
CH3SCH:C-C(Cll I C"H,,
cH'
rH.KunzandD.Schanzenbach,Angew'Cllery'-l:' .!!''2E'1068(1989)' '^n. i.-e"gf. andD. O. Arnaiz,J' Org'' 55'3708(1990)'
Zinc trifl uoromethanesulfonate' Lewis acid of a large numberexamined Amidoethylation.r Zn(OTf )z is the only with indolesto obtain that promotesreactionof (2R)- oi (zs)-z-uritdinecarboxylates yield' moderate "pii*ffy pure tryptophans,albeit in only
I B. C. VanWagenen andT. Livingborc. li
Zlrconocene dichloride-Dlbroocct Methylenation.r These threc rce3r methylenylatesaldehydes,ketones,or cr be replacedby CH2I2but not by CHfll
Zirconocenedichlorrde-Dibromomethane-Zinc
"tf .P", "'*J<X.oorI '"u"'
"t
GJ.A.o*'c#*Oqrx;' (l00%o ee)
(s)-4
I K. SatoandA. P. Kozikowski, Tetahedron Letters,30,4073(1989). 11a -.rngleProduct(3), which of cthides.zIn the Presence *2]cYcloaddi3o r formal[3 Thus somestereoselectivity. ' l , and only two of the four r-nchalkenecouldParticiPate
Zirconocene-4-Dimethylaminopyridine complexes, CpzZrl(CHs)zNPyl2,la, or CWZII(CH)zNPy]THF, lb. The complexesare preparedby reactionof Cp2ZrBu2 with I or 2 equiv.of DMAP in THF at 25'. The burgundycomplexla is morestable than the cherry red lb and can be storedfor severalhours. Reductivecoupling of alkynes.t The reactioncan be effectedin good yield by reaction of l-trimethylthioalkynes with la or lb followed by addition of another alkyne to form coupledproducts.
cH"s 'l
rll
l) crHrcrcclH, 2) CH,OH
rb-20'>["['",'']
"t'tcH\c
gzcHc'H'
t
8t%
l
Hr3C6 C2H5
CuH,,
^ro I l) tcHr)rc:o '-'"12)
cH,oH
cHsO
OH
I
cHrs\
+ CH,SCH:C-C(CH.)" l l-
CoH,,
C:CHC.H,,
(cH,),c/ "-l OH
C,H,
l:1.3 :t
1 0 6 8( 1 9 8 9 ) .
rcr,jof a largenumberexamined borr lateswith indolesto obtain rreld
t B. C. VanWagenen andT. Livinghotse, Tetahedron lztters,30,3495(1989).
Zirconocene dichloride-Dibromomethane-Zinc. Methylenation.r These three reagents form a complex, possibly 2, which methylenylatesaldehydes,ketones,or enonesbut not estersor lactones.CH2Br2can be replacedby CH2I2but not by CH2CI2.
Zirconocenedichloride-Dibromomethane-Zinc
--> CprZrCl, + CHrBr,+ Zn
t
/ -CH,ZnCll l " ! l ,oq' l""rc,oH,cH:cH. -cl I SOrr, )
r^t'\* al\
?\/J
cH,z'€-J
Letters,30' 3927(1989). I J. M. Tour, P. V. Bedworth,and R. w]u, Tetrahedron
AUTHOR INt Aalten,H. L., % Abdel-Magid,A. F.. 3O9 Abdullah,A. H., 159 Abe,H.,242 A b e l m a nM , . M..7E Abenhaim,D., 203 A b i k o .A . . 3 9 Ablenas,F. J., 120 A b o o d ,N . , 2 Abraham,W D..242 A c h i w a ,K . , 2 1 5 Acklin, P., 55 Adam, W., 142. 143 A d a m s .J . . 2 5 1 . 2 9 Adler, M. E., 149 Adlington,R. M.,233 Afonso. M. M.. l,l0 A g e r ,D . J . , 2 0 9 A g n e l ,G . , 3 2 1 A h u j a ,J . R . , 2 5 0 Akai. S.. 163 Akamatsu.H..375 Akbulut. N.. lm Akutagawa,S., 33. 126 A l a m i ,M . , 9 7 , 2 4 3 Alauddin,M. M.. % Alexakis,A., 159,253 Ali, M. H.,337 Ali. s..207 Allen, R. P., 356 A l f o u m .A . 8 . . 2 8 2 Alper,H.,25,228 Alvarez. 8.. 339 Alvarez. R. M.. l.l4 Amatore.C..369 Amedio,J. C. (Jr.). la2 Amer.1..228 Andersen,M. W.. 270 Anderson.B. A.. 90 Anderson.C. A.. 360 Anderson.C. L..n Anderson.D. A.. 215 Anderson,L. G., 189 Anderson.P. C.. 330 Anderson.P. G.. 261
CH
AUTHOR INDEX A a l t e n .H . L . . 9 6 Abdel-Magid,A. F., 309 Abdullah.A. H.. 159 4be.H..242 Abelman.M. M..78 Abenhaim.D..203 A b i k o .A . . 3 9 Ablenas,F. J., 120 A b o o d .N . . 2 Abraham.W. D..282 A c h i w a .K . . 2 1 5 Acklin. P.. 55 Adam, W., 142, 143 A d a m s ,J . , 2 5 1 , 2 8 9 A d l e r ,M . 8 . , 1 4 9 Adlington,R. M.,233 Afonso.M. M.. 140 Ager, D. J., 209 A g n e l ,G . , 3 2 1 Ahuja, J. R., 250 Akai. S.. 163 Akamatsu.H..375 Akbulut. N.. 100 Akutagawa,S.,33, 126 A l a m i .M . . 9 7 . 2 4 3 A l a u d d i nM . . M..98 Alexakis,A., 159,253 Ali, M. H.,337 Ali. s..207 Allen. R. P..356 A l l o u m ,A . 8 . , 2 8 2 Alper,H.,25,228 Alvarez. E.. 339 Alvarez. R. M.. 144 Amatore.C..369 Amedio,J. C. (Jr.), 142 Amer. I..228 Andersen,M. W.,270 Anderson,B. A.,90 Anderson.C. A..360 Anderson,C. L.,77 Anderson,D. A., 215 Anderson,L. G., 189 Anderson.P. C.. 330 Anderson.P. G..261
Ando, K., 135 Andrews,M. A.,87 Andrews,S. W.,206, 335 Anelli, P. L.,324 A n g l e ,R . S . , 3 9 2 Annoura,H., 307 Aoi, T., 131 Aoki,Y.,37 A o y a m aT , .,361 A r a k i ,S . , l 8 l Arase,A., 66 A r c a d i ,A . , 2 6 3 , 2 6 7 Armstrong,J. D. (III), 146 A r n a i z ,D . O . , 3 9 2 A r n o l d ,L . D . , 2 1 3 Arseniyadis, S., 48 Arya, P., 334 Asano,T., 353 Asao,N., 95, 194 A s s i l ,H . I . , 2 1 3 A t w o o d ,J . L . , 3 6 Audin, C., 237 Avignon-Tropis,M., 388 Aznar,F.,227 Baciocchi,E., 66 Biickvall,J.-8.,261 Bacquet,C., 107 Bagheri, Y. , 292 BaileyM , .,53 B a i l e yW , . F.,56,57 Baker,B. E.,262 B a k e r ,M . L . , 3 5 6 B a k i a p kK , . A.,73 Bakshi,R. K., 71, 254 Balakrishnan, P.,257 B a l d w i nJ, . 8 . , 1 6 , 2 3 3 , 3 5 8 Ballabio,K. C., 106 Ballestri,M.,374 Bal-Tembe,S., 128 Banerjee,A. K., 325 Banfi, S., 199,324 Banno,H., 134,209,210 Baptistella, L. H. B., 106 B a r c i n aJ, . O . , 1 4 4 395
396
Author Index
B a r i ,S . S . , 3 1 1 Barltrop,J. A., 99 Rarltenga,J.,227 Barney,C. L., 305 Barrie,J. R., 330 Barton,D. H. R., 16, 160' 164,346 B a s k a r a n5,. , 2 3 , 2 8 4 Batty,D., 20, 348 Baum,J. S., 290 B a u t a ,W . 8 . , 9 2 Baxter, E. W., 305 B e a l ,R . 8 . , 2 1 0 B e a t t i eM , . S.,74 Beau,J.-M., 237 Beaucourt,J.-P.,251 B e c k ,A . K . , 1 7 8 , 3 1 2 B e c k e rD , . A.,282 Bedoya-Zurita,M., 321 Bedworth,P. V.,393 Behling,J. R., 73, 235 Beifuss,U., 190 B e l l ,A . P . , 7 5 M.. 307 Bellassoued, Bellesia,F., 202 B e n b o wJ, . W . , 2 8 5 Beppu, F., 384 Bergh,C. L., 71 Berglund,B., 187 Bernard,A. M., 194 Bernardi,A., 191 Bernardinelli,G., 322 M., 28 Bernatchez, Bernocchi,E., 263,26'l N., 260 Berrios-Pefra, Bertrand,M. P., 200 Bestian,H., 150 Betancor,C., 20 Betschart,C., 332 Bharathi,P., 25 B h a t ,K . S . , 6 A., 366 BhattacharjYa, Bhaumik,M.,366 Bhedi,D. N., 128 Bianco,A.,269 Bierer,D. E., 85 Bisi,F.,216 Bilodeau,M. T., 332,333 Birkinshaw,T. N., 321,322 B l a c k ,T . H . , 1 1 5 Blacklock,T. J',254 Blagg,J., 58 M., 356 Blanchette,
Block,E., 5 Block,H., 255 Boger,D. L., 96, 310,346 B o h n ,B . D . , 3 6 7 Boireau,G.,203 Boisvert,L., 344 Boivin,T. L. 8., 268 Bold, G., 137,246 Boldrini,G. P., 135 Bolitt, V., 368 Bonsignore,L., 63 Bortolini,R.,276 Boruah,R. C., 11 Boschelli,D., 62 B o s eA , . K.,311 Bossler,H., 196 Boubia, B., 277 B o u c h e rR , . J.,67,139 Bougauchi,M., 166 Boukouvalas,J., 301 Boulanger,R., 28 Boumendjel,A.,207 Bowles,S., 273 Brandes,E. B., 383 Brandvold,T. A., 88 Bratz,M., 363 Braun,M., 180 Breitschuh,R., 178 Breslow,R., 373 Bringmann,G., 119 Brisbois,R. G.,357 Britton,T. c., 255 Broida,N., 142 Broka,C. A., 168 BrownB , . 8.,318 B r o w n ,D . S . , 2 4 7 BrownH , . C.,6,71 Briickner, R., 278 Bruno,M., 247 Buchwald,S. L., 72"1 5, 7'7 BullockR , . M.,357 Bunnelle,W. H', 129 Burini, A., 267 Burkhardt, E. R.' 248 Burkholder,C. R.' 106 B u t l i n ,R . J . , 3 8 1 Butsugan,Y., 181 Bzowej,E. I., 150 Cabal,M.-P.,227 Cabiddu,S., 63 Cabral,J., 167
Cabri, W.. 29 C a c c h iS, . . l Cahiez,G.. 9 Caley,B. A.. Campbell. M. Canet,J.-L.. Canonne,P.. Cantrell,W. I Capdeviellc.I Caple,R.. tt, Capperucci./ Carlstrdm. A. Carpenter. N. Carpino, L. I Carrasco,M. Carrefro, M. ( Carson,K. G Carter-Petillo Casnati,G.. 2 Cassidei,L.. I Castro,J.. lli C a s u ,A . , 6 CaubCre,P.. 3 Cederbaum. t Cerero,S. & Cha,J. S., 2& Chabot,C.. 3 Challener.C. Chamberlin./ Chambers,M. Chan, C.. 263 Chan,D. M. I Chan,T. H.. i Chandrasckan Chang,H. S.. Chang,M. HChang,V. H.Channon,J.. t Channon,J. A Chao,H. G.. Charlton,J. L Charpin,P., l( Chatani,N.. I Chatgilialoglu Chattopadhye Chemburkar. ! Chen, B.-C. 6i Chen,8.,215 C h e n ,H . , 2 4 9 Chen,H. G.. I C h e n ,J . S . . 2 [ Chen, L., l,lt
Author Index Cabri,W.,294 Cacchi,5.,263,267 C a h i e zG , .,97,243 C a l e y ,B . A . , 3 5 4 Campbell,M. M.,273 Canet,J.-L., 378 Canonne,P., 28 cantrell,w. R. (Jr.),290 Capdevielle,p., 95 Capfe,R., 114, tB7 Capperucci,A., 351 Carlstrcim, A.-S..261 Carpenter,N. E.. 265 Carpino, L. A., l0l Carrasco,M. C., 325 Carrefro,M. Carmen,134 Carson,K. G.,309 Carter-Petillo,M. 8., 43 Casnati,G.,276 Cassidei,L., 224 Castro,J., 113 C a s u ,A . , 6 6 CaubCre,P..308 Cederbaum,F. 8., 109,l2l Cerero, S. de Ia Moya, 144 C h a ,J . S . , 2 8 2 Chabot,C.,344 Challener,C. A.,88 Chamberlin,A. R., g3,324 Chambers, M. R. I.,317 C h a n ,C . . 2 6 3 Chan,D. M. T.,336 Chan,T. H.,208,334 Chandrasekaran, S., 23, 2g4 Chang,H. S.,284 Chang,M. H.,296 Chang,V. H.-T., 147 Channon,J., 139 Channon,J. A.,62. 13g Chao,H. c., 101 Charlton,J. L.,219 Charpin, P., l0 Chatani,N., 115 Chatgilialoglu,C., 374 Chattopadhyay,p.,366 Chemburkar,S.,255 C h e n ,B . - C , 6 2 C h e n ,E . . 2 1 5 Chen,H.,249 Chen,H. G.,239 C h e n ,J . S . , 2 0 4 Chen,L.. 148
Chen,M.-H., 174 Cheng,Y.,358 Chiara,J. L.,294 Chidambaram, N.,23 Chikashita, H.,21.3 C h i n n ,R . L . , 2 8 9 Cho, I. H., 18 Cho, W. J., 13 Choi, S.-C.,343 C h o p aA , . B.,373 Chou, T.-S., 239 Chou,W.-N.,387 Choudary,B. M., 25 Chowdhury,p. K., 199 Chrdtian,F., 308 Christensen,B. G., 62 C h u ,K . S . , 2 6 5 Chung,J. Y. L.,263 Chung,S., 18 Cirillo, P. F., 8, 250 Ciufolini,M. A.,44 C l a r k ,D . L . , 3 8 7 CIark,J. D., 383 Cfark,J. E., 176 Clark,J. S., 332 C l a r k ,K . 8 . , 3 7 4 Classon, B., 77 Claus,V. K., 150 Clerici, A., 330 Clive,D. L. J., 330,368 Coffen,D. L.,73 Coghlan,M. J.,354 Cohen,T., 195,232,282 Combrink,K. D.,338 Comins,D. L., 159 Commergon,M., 159 Concepcion, A. 8.,212 Conlon,D. A.,369 Connell,R. D., 157 Cooper,J. P.,354 Cooper,M. S.,379 Corbett,W. L.,310 Corey,E. J., 40, 153,154,156, 157,t6Z, 178,254,26 Corley,E. G.,269 Cossy,J., 200 Costanza,C., 193 C o t a ,D . J . , 5 2 C o t t o n ,F . A . , 2 7 , 3 7 0 Cowen,K. A.,305 Crabtree,R. H., 205 C r a i g ,S . L . , 9
lyl
Author Index
Enholm,E. J.. 29 Enomoto, S.. 22? Ensley,H. E.. 2f, Erben, H.-G.. X) Erickson,B. W., Evans,C. F.. 3I) Evans,D. A.. !9. 326.332.3t3 Evans,J. F.. 251
Fadel, A., 37E Fagan,P. J.. lZ Faggi,C., 351 Falck,J. R.. m. Faller, J. W.. 2aa Fang,F. C..2S Fang,F. G.. 37 Fantin, G., 362 F a u l ,M . M . . 3 9 Faulkner,P. .t.. 2 Fauq,A. H.. lA Feigelson,G. 8.. Ferguson,R. R.. Feringa,B. L.. I Fernandez.P.. Z Fevig,T. L.. 2S Finet, J.-P.. 16 Finkelhor,R. S. Finney,N. S.. X Fiorentino.M.. I Fitak, H., 162 Fitsimmons, B. 1 Flippin, L. A.. { Fogagnolo,M.. I F o k t , 1 . ,1 6 2 Ford, M. J.. 6f Forster,8., 351 Fort, Y.,3,G Fortt, S. M., 3ll Foster,B. S.. 35 Fowley, L. 4.. I F o x ,D . N . 4 . . , Fraile,A. G.. l, Francisco,C. G Freire, R., A) Frejd, T., 261 Frenette,R., U Freudenberger Fried, C. A.. X Friedrich.E. C. Fringuelli,F., &
Author Index
!-:. I
!^
- :is
t 3 :.r5. 236
)L
l. i.9
Enholm,E. J.,295 Enomoto, S., 227 Ensley,H. E., ZS7 Erben,H.-G.,90 Erickson,B. W., 162 Evans,C. F.,330 Evans,D. A., 39, 47, 65, 86,2ZS,255,2g4. 326,332,333 Evans,J. F..251 Fadel,A., 378 Fagan, P. J., 122 Faggi,C., 351 F a l c k ,J . R . , 2 7 7 . 3 6 8 Fafler,J. W.,244 Fang,F. C.,290 Fang,F. G., 32 Fantin,G..362 F a u l ,M . M . , 3 9 Faulkner,P. J., 255 Fauq, A. H., 128 Feigelson,G. 8., 32 Ferguson,R. R., 205 F e r i n g aB, . L . , 3 2 4 Fernandez.P.. 235 Fevig,T. L.,298 Finet,J.-P.,16 Finkelhor,R. S., l9l Finney,N. S.,98, 129,223 Fiorentino,M.,224 Fitak, H., 162 Fitsimmons, B. T.,251 Flippin,L. A.,46 Fogagnolo,M.,362 Fokt. I.. 162 F o r d ,M . J . , 6 4 Forster.8..354 Fort, Y.,308 Fortt, S. M.,348 Foster,B. S., 351 Fowley,L. A.,lt7 F o x ,D . N . A . , 3 0 2 Fraile,A. G.,144 Francisco, C. G.,275 Freire, R., 20 Frejd, T., 261 Frenette,R., 289 Freudenberger, J. H., 370 Fried,C. A.,259 Friedrich,E. C., 107 Fringuelli,F., 82
Froen,D., 114 F r y x e l lG , .8.,289 Fu,G. C.,65 Fu,J.,317 Fugami,K.,350 F u h r y ,M . A . M . , 9 8 Fuji, K., 132 Fujimura,O.,93,94 Fujinami,T.,68 Fujioka,H.,307 Fujisawa,T., 68, 300 Fujita, E., 186 Fujiwara,Y.,384 Fujiyama,R.,334 Fukami, S., 170 Fukushima, M.,68 Fukuyama,J., 281 Fukuyama,T.,356 Fukuzawa,S., 68 F u n k ,R . L . , 7 8 Furber, M., 288 Ftirstner,A., 387 Furuta, K., 314 Furuta,T., 145,355 Fusco,C., 224 Gage,J. R., 47 G a g n €M , . R.,41 G a i ,Y . , 5 7 Gallagher,T., 302 Ganem,8., 273, 291, 308, 360 G a n o ,J . E . , 2 W Gante,J., 174 Gao, Y., 102 Garcia,E., 55 Garcia-Ruano,J. E., 134 Garrido, M., 134 G a t e sB , . D.,274 Gaudemar,M.,307 Gaudin,J.-M., 321 Gawley,R. E.,255 G e e ,S . K . , 3 4 1 Geffroy,G.,230 G e o r g ,G . I . , 7 8 Georgiadis, M. P.,22 Germani,R., 82 G h a z a lN , . 8.,9l Ghelfi, F., 202 Ghiani,M. R., 194 Ghosez,L., 148 GhoshA , . K.,22
399
400
Autbor Index
Gibson,F. S., 182 Giese,B., 148,347, 374 Gigou,A., 251 Gifheany,D. G.,249 Girard, Y., 251 Glass,R. S., 278 Glomsda,G.,335 Gmeiner,P., 232 Godfrey, A. G.' 291' 360 Goldsmith,D.,269 Gdebiowski, A.' 163 G o n g ,L . , 3 6 Gong,W. H.,259,262 Goodfellow,C. L.' 15' 380 Gosmini,R., 159 G o t t l i e bH , .8.,142 Goudgaon,N. M.' 310 G o u l d ,G . L . , 8 7 Goyal,S., 179 Grabowski,E' J. J., 254' 269 Granja,J' R.' 83 G r a y ,R . A . , 3 0 8 Graziani,M.,200 G r e e ,R . , 5 1 G r e e ,R . , 2 5 1 Greene,A. E', 113' 124 Greiner, A., 373 Grenier, L., 289 Grieco, P. A., 2, 191' 383 Griesgraber,G.' 303 Griffith, W. P.' 325 Grigg,R., 88,264,26 Griller,D.'3'14 Grim, S. O.' 184 Grob, C. A.' 186 Grossman,R. B.' 75 G r o v e ,D . M . , 9 6 Grover, P. T'' 135 Groves,J. T'' 151 Griindler, H.' 196 G.,162 Grynkiewicz, G u , J . - H . '2 1 9 Guan,X., 78 Guazzaroni,M' E" 386 Guindon, C' A'' 356 Guindon,Y', 344 CuirY,P. J'' 16 Gulino' F., 142 Gung, B. W'' 133 Guo, C., 132 GuPta,V., 23
Gybin,A. S., 114 Gyorkos,A. C.,26 Habaue,5.,246,248 , L., 142, 143 HadjiaraPoglou A.,137 ' 246 Hafner, Hahn, C. S., 18 H a h n ,H . - G . , 3 8 1 Halcomb,R. L.' 142' 143 H a l e ,K . J . , 3 4 8 H a l l ,D . , 3 4 4 Hallberg, A',245 Halterman,R., 135 Hamanaka,N., 127 Hamann,L. G.' 345 Hamdouchi,C.,330 H a m e l ,N . , 2 5 H a n ,J . S . , l 8 l , 3 7 5 H a n ,L . , 3 1 6 Hanack,M., 144 Hanaoka,M., 13 5.,235'294 Hanessian, Hannon,F. J.' 178 Hansen,H.-J-' 32 Hansson,S., 225 Haque,M. S.' 334 Hara, R., 19 Harada,T., 204,248, 327 Haraguchi,K.' 152 Harasawa,K.' 170 Harayama,T., 69 Harms, K., 90 Haroutounian,S. A'' 22 H a r p e r ,D . l - , 2 7 2 Harring,S. R.' 214 Harrington,P. M'' 52' 98 Harrowven,D. C.' 94 Hart, H., 23 Hartsough,D.' 100 Hartung, J. B. (Jr')' 229 Haruna, S., 292 Harusawa,S', 296 H a r u t a ,J . , 2 7 4 ' 3 3 6 Hashimoto'S., 193 Hatajima, T.' 67 Hatanaka'M.' 162 Hatanaka'Y., 317 HataYama,Y., 115 Haugen,R. D'' 330 Hayami,K.,l'14 HaYasaka,T', 230
Hayashi,M., 339 Hayashi,T., 33, 35, 169.216 Hayashi,Y., 314 H.,X2 Hayashida, Heaney,H.,379 Heathcock.C. H., 46. 48 Heck. J. V.. 62 Heeren,J. K., 184 Heerze.L. D.,330 Heffer, J. P., 43 Heffner,T. A., 60 Hegedus,L. S.,26 Heitz, M. P.,366 Helquist,P., 103 Hendrickson,J. 8., 290. 36t Hendrix.J. A.. 317.3lt Herbert, J. M., 288 Herndon. J. W., 80 Herold,P.,137,245 Hersperger,R., 375 High, K. G.,292 Hikota, M.,353 Hildebrandt.8.,270 Hilty, T. K.,2Y2 Himeda. Y., 162 H i n m a n ,M . M . , 3 9 Hipskind,P. A.,263 Hirama. M.. 150 Hirano. M.. 285 Hirashima,T., 201 Hirayama,N., 212 Hiriguchi, Y., 80 H i r o t a ,K . , 3 1 9 Hiyama, S., 69 Hiyama,T., 185,317 Hoffman,C., 331 Hoffmann,H. M. R..261 Hoffmann,R., 278 Hoffmann,R. W.,270 Hogan,C.,257 Hojo, M., 169 Holmes.S. J., 121 Holmquist,C. R., 163 Holsworth,D. D.,23 Holzinger,H., 335 Homma,K.,365 Honda, T., 149 Honek. J. F., 129 Hopkins, T. 8., 186 Hoshi, M., 66 Hoshino,Y., 319
AuthorIndex Hayashi,M.,339 Hayashi,T., 33, 35, 169,216 Hayashi,Y.,314 Hayashida, H.,362 Heaney,H.,379 Heathcock,C. H.,46,48 Heck, J. V., 62 Heeren.J. K.. 184 Heerze,L. D., 330 Heffer,J. P.,43 Heffner,T. A., 60 Hegedus,L. S.,26 Heitz, M. P..366 Helquist,P., 103 Hendrickson,J. 8., 290, 368 Hendrix,J. A., 317,318 Herbert, J. M., 288 Herndon,J. W., 80 Herold, P., 137,245 Hersperger,R., 375 H i g h ,K . G . , 2 9 2 Hikota. M..353 Hifdebrandt.8..270 Hilty, T. K.,292 Himeda, Y., 162 H i n m a n ,M . M . , 3 9 Hipskind,P. A.,263 Hirama,M., 150 Hirano,M.,285 Hirashima.T.. 201 Hirayama,N., 212 Hiriguchi,Y.,80 H i r o t a ,K . , 3 1 9 Hiyama,S.,69 Hiyama,T., 185,317 Hoffman.C..331 Hoffmann,H. M. R.,261 Hofmann. R..278 Hoffmann,R. W.,270 Hogan, C., 257 Hojo, M., 169 Holmes,S. J., 121 Holmquist,C. R., 163 H o f s w o r t hD, . D . , 2 3 Holzinger,H.,335 Homma.K..365 Honda, T.. 149 Honek,J. F.,129 Hopkins, T. 8., 186 Hoshi,M.,66 Hoshino.Y..319
Hosokawa,T.,26 Hosomi,A.,362 Houben,S., 180 Houpis,I. N.,266 Houston,M. E. (Jr.), 129 Hoveyda,A. H., 65,294 H u a ,D . H . , 2 0 4 Huang,Y.-2., 111,342 H t i b e l ,M . , 4 Huber,E. W.,305 Hughes,M. J., 152 Hughes,W. R., 184 Hulshof, L. A., 96 Hiimmer,W.,224 Hunter,W.,36 Hussoin,M. S., 368 H w a n g ,C . - K . , 5 8 , 3 0 0 Hwang, J. P., 86 Hwang,l.-T.,296 Hwang,T. S., 19 H w u ,J . R . , 2 1 5 Ibragimov,I. I., 114 Ibuka, T., 234 Ichinose,K.,326 Ichinose,Y., 350 Ife, R. J., 149 Iguchi,S.,2M Ikariya,T., l3l Ikeda, T., 33 Ikegami,S., 193 Ikemura,Y.,204 I m a i ,N . , 4 0 Imamoto,T., 67, 69,294 Imanaka,S., 327 Imanaka,T.,292 Imbroisi, D. de Oliveira, 390 Imwinkelried,R., 154, 312,365 Inaba,M., 17 Inanaga,J.,296,297 Inoki, S., 27, 203 Inoue, K., 213,337 lnoue, M.,227 I n o u e ,S . , 3 3 Inoue,T., 7 Inubushi,T., 378 Inui, N., 35 I q b a l J, . , 9 5 , 9 9 Ireland,R. E., 146 Irie, R., 158 Irifune, S., 86
{l
Author Index
Isaacs,L. D., 90 Isaka,M., 85 Isayama,5.,27,203 Ishibara,K., 359 Ishii, H., 69 Ishii,Y.,86, 131,178'272 Ishikawa,T., 69, 176' 177 Ishimoto,N., 213 Ishiyama,T., 319 Ishizone,H., 149 Isobe,Y., 319 Ito, K., 79 Ito, S., 150 Ito, T., 116 Ito, \., 27, 29, 33, 35, 51, 158' 169' 298 Itoh, K., 41, 213 Itsuno, S., 79 Iutiano, A., 154 Iwaki, S., 186,249 I w a s a w aN, . , 3 1 5 I w a t a ,C . , 7 Iwata,K., 214 Iwata,S., 190 Jackson,R. F. W.' 246 Jackson,W. P., 379 Jacobsen,E. N., 158 Jaeger,R., 4 Jiiger,V., 143,224 James,K., 23, 246 Jamison,T. F., 49 Jang,D. O., 160 Jansen,J. F. G. A.'324 Jansen,J. R., l19 Jardine,P. D. S.' 157 Jarvi,E. T., 130 J. C., 160' 346 JaszberenYi, Jaurand,G.,237 A', l1 Jaxa-Chamiec, Jefford,C. W., 283' 301 lefrrey,T.,98,262 A', 201 Jeganathan, S.,373 Jeganathan, Jellison,K. M.' 78 J e n k i n sT, . 8 . , 2 9 Jensen,M., 109 Jeong,N., 184 Jeroncic,L. O.,272 Job, K., 178 J o h n ,J . A . , 2 4 4 Johnson,A. T., 381
Johnson,C. R., 341 Johnson,E. P., 112 Johnson,M. R., 166 Johnston,M. I., 210 Jolly, R. S., 87 Jona,H., 120 J o n e sE , . T.T.,254 Jones,T. K.,254 Joseph,S. P.,99 Jozwiak,A., 21 J u ,J . , 1 1 4 J u l i a ,M . , 5 7 Jung,K.-Y., 105,188 J u n g ,M . 8 . , 3 1 6 Jurczak,J., 163 Kabalka,G. W., 77' 85, 183'310 Kadota, I., 353, 389 Kadow, J. F., 374 Kaesler,R' W., 92 Kagan,H. B., 160 Kahne,D., 348,358 Kaino,M.,359 K a j i ,N . , 1 3 1 Kalish,V. J., 73 Kaller, B. F., 279 Kalosa,A. N., 179 Kambe,N.,316, 346 K a m e i ,K . , 7 Kametani,T., 149 Kameya,Y.,127 Kamio,C., 191 Kamiya, Y., 67 Kamiyama,T.,227 Kanai, T., 86 Kanda,F.,99 Kaneda,K.,292 Kang, H.-Y., 296 Kang,S. H', 19 Kannangara,G. S. K.' 172 Kaspar,J., 200 K a s p e rA , . M.,310 Kataoka,Y.,93, 107' 312 Katayama,H., 208 Katayama,S., 84 Kato, K., 27, 203 Kato, S., 115 KatritzkY,A. R.' 21, 177 Katsuhira,T., 248 Katsuki,M., 121 Katsuki.T., 158
Katsuki, T. M., 120 Kawabata,T., l&5 Kawada,K., 170 Kawada,M., 319 Kawai,H.,360 Kawai, K., 141 Kawakita,T., 102 Kawamoto,K.,2Y2 Kawamoto,T., 216 Kawamura,H., 166 Kawano,T., 298 Kawasaki,Y., l15 Kawase,Y.,315 K e i l ,R . , 7 2 Keinan,8., 134 Keiner, P., 278 Keitz. P. F., 140 Keller,T. H., 321 Kelner, R., 142 Kende,A. S.,297 Kennedy,R. M., 147 K e p l e r ,K . D . , 9 J., 164 Kervagoret, Khan, M., l14 Khetani,V., 2 Kibayashi,C., 19 Kiefer, H., 356 Kierkus, P. C., 218 Kiji, J., 309 K i m ,B . H . , 4 Kim, B. M.,249 Kim, D., 174 Kim, I. J., 13 K i m , J . - I . , 3 0 ,l f l ) Kim, K.,57 Kim, K. S., 18 Kim, S., 199,363 Kim, S. S., 154,156 Kim, W. J., 19 Kim, Y. H.,57,2U K i n g ,S . M . , 7 2 , n Kinoshita,T., 326 Kinter,C. M.,356 K i r a ,M . , 9 Kita, Y., 163.274, 3O7.3L Kitamura,M.,33,3.{. l4l Kiyooka,S.,334 K l a d e ,C . A . , 6 Klaeren,S. A., 87 Knapp, S., 182 Knochel,P., 184,239.l{0.
Author Index
-. .5 183.310 h! I t:
0 J5.
! !6
)
, K t72 llr l tr - .
t
Katsuki, T. M., 120 Kawabata,T., 185 Kawada,K., 170 Kawada,M., 319 Kawai,H.,360 Kawai,K., 141 Kawakita,T., 102 Kawamoto,K., Zg2 Kawamoto,T.,216 Kawamura,H., 166 Kawano,T., 298 Kawasaki,Y., l15 Kawase,Y.,315 Keil, R., 72 Keinan,E., 134 Keiner, P., 278 Keitz. P. F., 140 Keller,T. H.,321 Kelner, R., 142 K e n d e ,A . S . , 2 9 7 Kennedy,R. M., 147 K e p l e r ,K . D . , 9 Kervagoret, J., 164 K h a n ,M . , 1 1 4 Khetani,V.,2 Kibayashi,C., 19 Kiefer, H., 356 Kierkus,P. C.,218 Kiji, J., 309 K i m ,B . H . , 4 Kim, B. M.,249 Kim, D., 174 Kim, I. J., 13 K i m , J . - L , 3 0 ,1 0 0 K i m ,K . , 5 7 Kim, K. S., 18 Kim, S., 199,363 Kim, S. S., 154,156 Kim, W. J., 19 Kim, Y. H., 57,284 K i n g ,S . M . , 7 2 , 7 7 Kinoshita,T., 326 Kinter, C. M.,356 K i r a ,M . , 9 Kita, Y., 163,274, 307, 336 Kitamura,M., 33, 34, l4I Kiyooka, S., 334 K l a d e ,C . A . , 6 Klaeren,S. A., 87 Knapp, S., 182 Knochef,P., 184,239,240,241
4{13
Knors, C., 103 Ko, S. Y.,54 Kobayashi, K.,2i,29 Kobayashi,S., 144, t 8t, 220, 221,32g. 33g Koch, S. S. Canan,83 Koga, K., 110, 158,249 Koh, K., 219 Koide,K., 144 Koide,Y..69 Kolb, M., 198 Komazawa,S.,213 Komissarova,N. G., 149 Kondo,H.,307 K o n d o ,M . , 4 l Kondo. T.. 126 Kondoh, H., 149 Konishi,H.,309 Konoike. T.. 178 Konopelski,J. P.,265 K o n r a d iA . . W,370,371 Konwar,D., l1 Koo, S., 146 Kopping, B., 374 Koreeda,M., 105,146, 188,345 Korita, K.,353 Koser,G. F., 179 Kdster. G.. 270 Kotani,Y.,248 Kotsuki,H.,389 Kottirsch,G., Z6i Koumoto,N.,300 Kowalski,C. J., 333, 334 K o y a m aH , .,6,341 Koyama,T.,32 Koyano,M.,230 Kozikowski, A. p., 128, 392 Koz'min. S.. 187 Kraft, T. E., 119 Kramer,S. W.,73 Krass.N.. 310 Kreager,A., 114 Kress,T. J., 82 K r i m e n ,L . 1 . , 5 2 Krisch€,M. J., 49 Krishnamurthy, V., 346 Krishnan,L., 311 Krohn, K.. 171 Krofikiewiez.K..367 Kropp, P. J.,9 KruseL , . L,11,152 Ku.B..317
Author Index
Ku, J.,215 K u b o ,A . , 3 5 Kucera,D. J.,265 Kudo, T., 228 Kuilman, T., 96 Kukkola, P. J., 341 Kulkarni, S. U., 7l Kulkarni, S. V., 4 Kumar, T. K. P., 95 Kumobayashi,H., 33, 126 K u n z ,H . , 3 9 1 Kunz,T.,2l7 Kuo, E. Y., 52, 129,223 Kuo, G.-H., 103 Kurihara,T., 296 Kurosawa,H., 115 Kurusu, Y., 164,329 Kusano,K., 346 Kusche,4.,278 Kusuda,K.,297 Kuwabara,T., 128 Kuwajima,I., 37, 80, 81, 85, 167 Kuznetsov,O. M., 149 K w a k ,K . H . , 8 6 Kwass,J. A., 210 Kwon, T.,66 Kwong,H.-L.,249 Labadie,S. S,, 320 Laboue,8.,243 Lacher,B., 147 L a l , G . S . , 6 1 ,3 3 4 LaMaireS , .J.,72 Lamaty,F.,320 Langley,D. R.,374 Lankford,P. J.,92 Lappert,M. F.,36 Larock, R. C., 259, 260,262 Larsen,R. D., 269 Laszlo,P., 167 Lathbury,D.,302 Lauher,J. W., 103 Lavall€e,J.-F., 344 Lavigne,A., 95 Leanna,M. R., 82 Leblanc,C.,zffi Leblanc,Y., 251 Le Corre,M.,222 Le Coz, L., l0 Lectka,T., 331 L e e .A . W . M . , 5 4
Lee, C.-H.,42 Lee, D.-H., 157 L e e ,J . G . , 8 6 Lee, J. M., 363 L e e ,S . - G . , 3 6 8 Lee, T. V., 67,138,139,140,3U Lee-Ruff,E.,120 Lellouche,J.-P.,251 Lemieux,R.,344 Lenarda,M., 200 Lennick, K., 304 Le Nouen, D., 230 Lenz,G. R., 193 L e 6 n ,E . I . , 2 0 Le Roux, J., 222 Lesage,M.,374 Lesimple,P.,237 Lessor,R. A., 193 Letulle,M.,372 Leuck,D. J., 305 Leung,W.-Y.,260 L e w ,W . , 3 1 6 Lewis,E. J., 107 Lewis,P. J.,292 Ley, S. V., 64,247,325 Li, c.-s., 152 Li, L.,356 Li, s.-w., 111 Li, x.-Y., 50, 286 Li, Y.,283 Lieberknecht,A., 261 Liebeskind,L. S., 102,225, 351 Light, J., 373 Lim, J. J., 348 Lim,J. K., 19 Lim, L. B. L.,361 Lim, S.C.,284 Lin. K.-C.,279 Lin, S.-C.,356 Lin, X., 135 Linde,R. G. (ll\,272 Lindner,H. J., 148 Liotta, D.,269 Liott^, L. 1.,273 Lipschutz,B., 73 Lipshutz,B. H., 55, 72, 232, 235, 236' 350 L i t t l e ,E . D . , 5 0 Lin,2.,77 Livinghouse,T., 87, 105, 109,214, 393 Livingston,D. A.,71 Liz, R.,227
Lodge, B. A.. lE3 Loebach.J. L.. 158 Loganathan,V..261 Lohray, B. B., 102.l5 Lohse,P., 55 loner, H., 55 L o n g ,Q . - H . , 2 l Lopez,L.,370 Lottenbach,W.. 137. Lourak,M.,3{B Lowenthal,R. E..39 Lowinger,T. 8.. 74 Loy, G., 63 Lu, X., 127. 132 Lubell,W D..,19 Luche,J. L.,175. !n. L u e ,P . , 2 l Luedtke. G.. E7 Luh. T.-Y.. l18. 12{ L u k e ,G . P . , 8
Ma, D., 127.l3?. McCann.S..383 McCarthy,J. R.. lI). McCauley,J. P. (Jr.l. . McCormick,M..20 McDermott,P. J.. l19 McDermott,T. S.. l15 McDonald,F. 8..217 McGarry,D. c..350 McGettigan,C.. 175 Machii, D., ,f6, 37E Machinaga,N.. 19 M c K e e .B . H . . 2 4 9 McKee,S. P.,22 McKinney,J. A.. 93 McKinnis, B. R.. 129 Mclaughlin,K. T..73 McMurry,J. E..331 McPhail.A. T.. l,ft McSwine.D..50 M a e d a ,K . , 5 l Maeta, H., 120 Magnin,D. R., 147 M a h .R . . 2 7 5 Mah6.L.. 167 Mahon,M. F.,3O2 Maiti. S. N.. 177 Majetich,G., 2 Majewski,M.,330 Majid, T. N.,2,lO
AuthorIndex
t . l - r e .1 4 0 , 3 6 4 5l
D
.,'.
1)S ?<1
I
i. !5 B-
-1.232,235,236,350
lw,214,393 ,1r)5.
Lodge,B. A., 183 Loebach.J. L.. 158 Loganathan,V., 264 Lohray,B. B., 102,250,375 Lohse.P.. 55 Loner. H.. 55 L o n g ,Q . - H . , 2 1 Lopez,L.,370 Lottenbach, W., 137, 245 Lourak.M..308 Lowenthal,R. E.,39 L o w i n g e rT, . 8 . , 7 4 Loy,G.,63 Lu, X., 127, 132 Lubell.W. D..49 Luche,J. L., 175,272, 377, 387 L u e .P . . 2 1 Luedtke.G..87 Luh, T.-Y., ll8, 124 Luke, G. P., 8 Ma. D.. 127.132 McCann.S..383 McCarthy,J. R., 130,225,305 McCauley,J. P. (Jr.), 3a8 McCormick,M.,269 McDermott. P. J.. 119 McDermott.T. S.. 115 McDonald,F. E.,237 McGarry,D. G.,350 McGettigan,C., 175 Machii,D., 46,378 Machinaga,N., 19 McKee.B. H..249 McKee,S. P.,22 McKinney,J. A., 93 McKinnis.B. R.. 129 Mclaughlin,K. T.,73 McMurry,J. E., 331 McPhail,A. T., 148 McSwine.D..50 M a e d a .K . . 5 1 Maeta.H.. 120 Magnin, D. R., 147 Mah, R., 275 Mah€.L.. 167 Mahon.M. F..302 Maiti. S. N.. 177 Majetich,G.,2 Majewski,M.,330 Majid, T. N.,240
M a k i .Y . . 3 1 9 Mallet,J.-M., 369 Mancini,F., 135 Mandai.T.. 319 Mangeney,P., 159,253 M a n h a sM , . S.,311 M a n n ,T . A . , 1 7 6 Manna. S.. 277 Manninga,T. N.,336 Manogaran,S., 95 Marchon,J.-C., 151 Marinelli,F.,263,267 Marino. J. P.. 235 M a r k 6 ,L 8 . , 4 9 , 5 3 Marks,T. J., 4l Marolewski.A. E.. I Marra. A.. 369 Marron.B. E..322 Marsaioli.A. J.. 106 Marshall,J. A., 8, 133 Martin. O. R.. 118 Martin,V. S.. 339 Martinelli. M. J.. 82 Martinez.A. G.. 144 Maruoka,K., 134,209,210,211,212 Maruyama,K.,7, 166,342,343 Maruyama,T.,314 Maryanof, B. E., 383 Maryanoff,C. A.,309 Masamune,S., 39, 54, 147 Mascaretti, O. A.,373 Mashava.P. M..78 Massiot.G..207 Masuda.H..298 Masuda,Y.,66 Masuyama, Y.,164,329 M a t a .E . G . . 3 7 3 Mathre.D. J..254 Mathvink,R. J., 346 Matsubara.S.. 384 Matsubara.Y.. 201 Matsuda.I.. 352 Matsuda.S.. 336 Matsuda,T.,167.339 Matsuda.Y..327 Matsumoto,N., 158 Matsumoto,T.,l2O. 121 Matsumoto,Y.,33 Matsuura,Y., 249 Matsuzawa,S., 85 Matthews.B. R..304
M
Aulhor Index
Matthews.D. P.. 130 Mattson,R. J.,305 Maumy,M.,95 Mazziei, M. R.,244 Medich, J. R., 341 Meier. I. K.. 381 Meister,P. G., 10 Mekhalfia.A.. 49 Mello. R..224 M e n d o z aJ, . 5 . , 2 9 7 Mertes,K. B., 160 Meurs,J. H. H., 286 Meyers,A. G.,52 Miao. S. W..204 Micetich,R. G., 177 Mickus,D. E., 195 Midland.M. M.. 140 Miftakhov, M. S., 149 Mikaelian,G. S., 114 M i k a m i .K . . 2 5 Miller, J. A., 121,242 Miller, J. F., 225 M i l l e r .M . J . . 3 3 1 Miller. R..348 M i l l e r ,R . A . , 9 2 Miller, R. F.,357 Miller. S. A..324 M i n a m i .L . 3 1 9 Minato,M.,249 Mioskowski.C., 277, 287,3ffi , 368 M i r a n d aE . . 1.,77 Mitani, M., 125 M i u r a .K . . 3 5 0 M i w a .Y . . 3 1 4 Miyachi, N., 99 Miyake,H.,345 Miyasaka,T., 152 Miyashita,M.,309 M i y a u r aN , .,66,319 Miyazaki,K.,214 Miyazaki,Y., 193 Mizuno,M., 131 Mlochowski.J.. 8l lvl/ochowski.K..324 Mocerino.M.,142 Mohamadi.F., 82 Mohan,I. J.,253,254 Molander,G. A., 206, 248,335 Molloy, K. C.,302 Moloney,M. G., 16 Monahan,R. (III), 269
Montanari,F., L99,324 Montaufier.M.-T., 167 Morehouse,S. M., 43 Mori.A..359 Mori, W., 149 Mori. Y.. 197 Moriarty,K. J.,318 Moriarty, R. M., 179, 186 Morikawa. Y., 251 Morimoto. T., 285 Morin. C.. 113 Morita, T., 125 Moriwake,T., l7, 176, 177,251 Motherwell,W.8.,276 Moustrou.C..200 Moyano,A., ll3 Mozaffari,A., 166 M u c h a ,B . , 2 6 1 Muchmore,C. R., 91 M u d r y k ,8 . , 1 9 5 , 2 3 2 Muedas.C. A.,205 Mukai, C., 13,93 Mukai,T., 126 Mukaiyama,T., 19,27, 30, 31, 100' l8l' 2$. 2n, 221, 3r4, 329, 339,365, 375 Miiller, D., 39, 40 Mulliken.M., 187 Mtinster,I., 278 Murafuji, T., 214 Murahashi,S.-I., 26, 126,l3l M u r a i .S . , 3 2 ,l 1 5 Murai. T.. 115 Murakami.K.,7 Murakami,M.,298 Murata,S.. 21 Murayama,H.,319 Murphree,S. S., 107 Murphy,B. L.,176 Murray, C. K., 89, 92 Murray, R. W., 142, 143 M u r t h y ,K . S . K . , 3 3 0 Mutter, M.,375 Myers,A. G.,98, L29,223,302,341 Nagahara,5.,211,212 Naganathan,S., 389 Nagao,Y., 186,249 Nakahira.H., 316 Nakai,S., 12 Nakai,T., 25, 219 Nakajima,H.,2U
Nakajirne Nakajirnl, Nakajim:. Nakamun Nakamun Nakamun Nakamun Nakano.I Nakata.T Nakayarn Nally,J.. Nantermc Naota.T.. Narasale. Narayane Narayarur Narayane Narusc, Y Naruta. Y. Naruto, SNavarro. I Neeson.S Negishi.E Negrete.( Nerz-Stor Nestler,B Newbold. Newton. R Newton. F ' Ng,J. S.. Ni, z.-J.. Nicholas. I Nichols.C Nicolaou. I Nielsen.R Nierlich.I Nikolaidcs Nimura, Y N i s h i ,K . . . Nishigaiti Nishiguctr Nishigucfir N i s h i i ,S . . Nishikawa Nishimura Nishimura Nishiumi.! Nishiyama N i t t a ,K . . , Niwa, N.. I Noda, K..
AuthorIndex
tt
t-
:51
_ 1 r. i l . 1 0 0 ,l 8 l , _1:.r..139.365,375
6 . t - rI
I
Lr
-102.341
Nakajima,M.,249 Nakajima,S.,360 Nakajima,T., 32 Nakamura,A., 384 Nakamura,8., 46, 80, gl, g5. 379 Nakamura,K.,67 Nakamura,T., 4l Nakano,M.,334 Nakata,T., 319 Nakayama,O.,35 Nally,J., 148 Nantermet.P. G..247 Naota, T., 126, l3l Narasaka, K., 314,315 Narayana,C., 183 Narayanan, B. A.,lZ9 Narayanan, K.,260 Naruse,Y., 359 N a r u t aY , .,7,342.343 Naruto,S., 109 Navarro,8.. 124 N e e s o nS, . J . , 8 8 Negishi,E., 57, 109, l2l, 242, 320. 321 Negrete,G. R., 265 Nerz-Stormes, M.,257 Nestler,B., 143 N e w b o l dA , . 1.,379 Newton,R. C.,346 Newton,R. F.,52 N g , J . S . , 7 3 ,1 4 6
Ni, z.-J.,rr8. r24 Nicholas,K. M., l14 Nichols,C. J., 368 N i c o f a o uK, . C . , 5 8 , 3 m , 3 2 2 , 3 5 0 N i e l s e nR , . B.,72 Nierlich,M., 10 Nikolaides,N.. 291.308 Nimura. Y.. 164 N i s h i ,K . , 3 3 6 Nishigaichi, Y.,7,342 Nishiguchi,I., 201 Nishiguchi,T., l9t Nishii,S., 234 Nishikawa.T.. 17 Nishimura,S., 294 Nishimura,T.. 181 Nishiumi,W.,309 Nishiyama, H.,41 N i t t a ,K . . 9 3 Niwa, N.. 177 Noda, K., 158
Node, M., 132 Nomoto,Y.,66 Nonoshita,K.,209 Normant,J. F., 107, 159,253 North, M., 16 Nose,A., 228 Nowick J. 5., 327 N o y o r i ,R . , 3 3 , 3 4 , 3 6 , 1 2 7 ,t 4 1 Nozaki,H., lt1, tlZ,216 Nozaki, K., 350 N u d e l m a nA, . , 1 , 4 2 Nugent,W. A.,74, 122 Nunez,M. T.,339 Nunokawa,Y.,66 Nuzillard,J-M.,207 O c h i ,M . , 3 8 9 Ochiai, M., 186,249 Oertle,K., 137,245 Ogawa,A.,346 O g a w aM , . , 8 6 , 1 7 8 ,3 1 9 Ogawa,T., 174,214 Ogino,Y.,249 Oguchi,T., 178 O g u n i ,N . , 3 3 9 oh, D. Y.,317 O h e ,K . , 1 1 5 O h k u m aT , .,33,34 O h m o r i ,H . , 3 6 7 Ohnishi,T., 204 Ohno, M., 102, 144 Ohno, T., 181,339 Ohnuki,T.,304 Ohrai,S., 280 ohta, H.,272
Ohta,T., 33 OhtakeH , .,127 oi, R., tol Oishi,T., 150 ok, D.,23 O k a b e ,M . , 7 3 Okada,S., 141 O k a m o t oM , .,277 Okamoto,S., 116 Okano,T.,309 Oku, A., 204,248,32j O k u d o ,M . , 2 7 7 O l a h ,G . A . , 5 0 , 2 8 6 , 3 1 0 , 3 6 0 O l l i s ,W D . , 4 9 , 5 3 O ' N e i l ,I . A . , 2 3 3 , 3 5 8 Ono, N., 166
{6
Arthor Index
Oohara,T., 80 Ooi,7.,211 Ooka, Y., 26 Oose,M.,285 Oppolzer, W., 58, 321, 322 Osakada,K., l3l O s h i m aK . .,350 Otera, J., lll, tl2.216 Ouimet,N..289 Oumar-Mahamat, H.,2@ Overman,L. E., 25, 219, 265 Owen,T. C.,99 Ozaki, S., 125 Ozawa.F.. 35 Padmanabhan, S., 183 Padwa,A., 107.289 Page,P. C. 8., t6t Pagnoni,U. M.,202 Paguaga,E., 348 Pahuja,S., 179 Pakrashi,S. C., 366 Palkowitz,A. D., 135 Pandiarajan, P. K.,71 Panek,J. S., 8, 25, 45, 250 Paquette,L. A., lO,71.216 Parekh,S. I.,209 P a r k ,J . . 3 7 1 Park,J. H., 199 P a r k ,S . 2 . , 3 5 i P a r k ,Y . J . , 5 7 Passacantilli, P., 269 Patricia,l. J.,57 Pattenden,G., 94 Pearson,A. J.,352 Pearson,D. A., 356 Pearson,M. M.,292 Pearson,W. H.,279 Pedersen,S. F., 229. 370.371 Pellon.P..208 Pena-Matheud,C. A., 325 Pendalwar,S. L., 2U, 354 Periasamy,M., 182 Perichs,M. A., 113 Petasis,N. A.. 150 Peterson,G. A., 88 Petre,J. E., 7l Petty, C. M., 99 Pfaltz,A., 39, 40, 55 Pflieger,P.,287 Pham,K. M..305
Philippo,C. M. c.,71 Piantini,U.,137,246 Piekstra,O. G.,96 Pieters.R. J.,292 Pietroni,8.,267 Pikul,S., 153,154 Pilarski,8.,177 Pinetti,A.,202 Pini, D., 154 Piras,P. P., 194 Pizzo, F., 82 Plant, A., 199 P l u m b ,J . 8 . , 2 7 2 Plumet,J., 199 Podesta, J. C.,373 Pokorski,U.,337 Poon,Y.-F.,279 Porta, O., 330 Porter,J. R., 67, 138, 139,140,364 Porter, N. A., 1.47 , 149 Posner,G. H., 356 Pougny,J. R.,388 Poupaert,J. H., 13 Poupart,M.-A.,289 Powell,A. R.,43 Powers,D. 8., 135 Pradilla,R. Fernandezde la, 235 Prakash,G. K. S., 50, 310 Prakash,O.,179 Prandi,J ., 237 Prange,T., 20 Prasad,C. V. C., 58, 300 Prasad,J. S.,330 Price,M. E.,365 Pridgen,L. N., 257 Prodger,J. C., 161 Pulley,S. R., 110 Punzalan,E. R., 56, 57 P u t m a nD , .,5 Qian, L., 160 Q u e n d oA , .,391 Querci, C., 199 Quici,S., 199,324 Quinn, R., l5l Racherla,U. S., 6 Raczko,J., 163 RajanBabu,'1. V.,74 Ramasseul, R., 151 Rambaud,M.,164
Randad Randria Ranu.B Rao, S. , Rapopor Rappoli. RaSmrrs Ravindn Rawal. V Reamer. Rebiere. Rebrovk. Reddy. B Reddy.C Reddy.J. Reddy. V. Reed, L. , Reetz.M. Reginaro Reicbelr.I Reider.p. Rein, K.. i Reissig.H. Reitz, A. I Relenyi.A Retherford Reuter. D. Revis.A.. . Rezenka.D Rhode,O,. Ricci,A.. I Ricci, M.. t Rich,J. D.. Richardsoo Rico,J. G.. Riediker, M Rieger,D. I Rieke, R. D Riera,A., I Rigby, J. H. Righi,G.. Z Rigollier, p.. Rihs,G., lii Rink, H.-p.. Rishton,G. I Riva, R. J.. J Rivera, I., Zl Rivoldini, A., Roberts,B. p Roberts, F. E Robins,M. J.
Author Index
410
AuthorIndex
Salazar, L A.,20 Salvadori,P., 154 Samano,V.,272 Sampath,U., 389 8., 77 Samuelsson, S a n c h e zR, . , 3 0 W. M.,22 Sanders, Sanderson,W. R., 379 S a n d h uJ, . S . , 1 l Sankawa,U.,326 Sano,T., 115,221 Santelli,M., 43 Santhakumar,V., 264 Santiago, B., 221 Sarkar,D. C., 389 Sartori,G., 276 Sasaki,I., 131 Sasaki,M., 280 Sashiwa,H., 280 Sato,F., 116 Sato,J., 210 Sato,K., 9, 392 Sato.S., 352 Sato,T., 1ll, ll2,216 Sato,Y., 35 S a t o hM , .,66 Satoh,T., 80, 283 Satomi,H.,216 Saulnier,M. G., 374 Savelli,G., 82 Savignac,P., 3 Sawhney,S. N., 179 Sayo,N., 33, 34 S., 112 Scapecchi, Schaller,C., 289 D.,391 Schanzenbach, Schlosser,M., 373 S c h m i dM , .,45 S c h m i dR , .,32 Schmidt,8.,312 Schmidt,U.,261 S., 180 Schneider, C.,233 Schofield, Schore,N. E., 365 Schultz,P.,64 D. P., 176 Schumacher, Schuster,G. B., 30, l0O J., 73,381 Schwartz, Scolastico, C., 191 Scott,R., 88 Screttas, C. G.,144
Secci,D., 63 Seconi,G., 43, 351 S e e b a c hD, . , 1 7 8 ,1 9 6 . 3 1 2 . 3 3 2 , 3 6 5 S e g i ,M . , 3 2 Seidel,B., 143 M. F.,268 Semmelhack, Sengupta,S., 350, 361 Seong,C. M., 183 Serhan,C. N., 322 J. L., 166 Sessler, J., 10 Seyden-Penne, Seyferth,D., 184 Shah,V. P., 1l Sharma,G. V. M.,25 Sharma,S., 232 Sharpless,K. 8., 54, l0l, 102,249 D., 87 Sheehan, Sheldon,R. A., 96 S h e n ,W . , 6 0 A. C.,6l Sheppard, S h e p p a r dG, . S . , 8 6 , 2 2 5 shi, L., 342 s h i ,L . - L . . 1 l l shi, Y., 372 Shibasaki,M., 14, 35, 99 Y., 280 Shigemasa, Shiina,I., 220 S h i l n aI,. , 3 2 9 S h i m ,S . C . , 2 9 6 Shimizu,S., 314 I.,320 Shimoyama, Shindo,M., ll0, 158 S h i n k a iI,. , 5 0 Shinoda,T., 193 Shinohara,T., 26 Shioiri, T., 361 Shiota,F., 334 Shipton,M. R.,286 Shipton,S. G., 15 Shirai,F., 219 S h i r o ,M . , 2 4 9 J., 283 Shishikura, Shoda,S., 196 Shone,R. L., 73 ShookC , . A.,232 Short,R. P., 147 Shoup,T. M., 310 Shubert,D. C., 335 Shundo,R.,201 Siedlecka,R., 324 B.,344 Simoneau,
Simon Simpk Simps Sina!. Sinny. Singan Singh Singi. Singh. Singh. Singh. Siniste Sinou. Sivik. I Skalird Skarze Sledcs Smit.I Smith Smith. Snider Snieck Soai. X Sodeot Soderh Soderq Soga.I Sohar. Solladi Somers Somcn Somnr Song.l Sonodt Sophcr Sorato. S
AuthorIndex Simonyan,S. O., 114 Simpkins,N. S.,390 Simpson,p., 50 Sinaii,P.,237 Sinay,P.,369 Singaram, B., 7l Singh,A., 36 Singh,G., 184 Singh,M., 142 Singh,O. V.,275 Singh,R., 177 Sinisterra-Gago, J. V., 377 Sinou,D., 17 Sivik,M. R., t0 Skalitzky,D. J., 303 Skarzewski,J., 81,,200, 324 Sledeski, A. W.,301 S m i t ,W . A . , 1 1 4 S m i t h ,A . B . ( I I I ) , 6 2 , 3 4 8 S m i t h ,R . A . J . , 2 3 5 , 2 3 6 S n i d e rB , . 8.,66,210 Snieckus,V., 56, 317, 361 S o a i ,K . , 2 3 0 , 2 7 7 Sodeoka,M., 14, 35 Soderberg,R. H., 27 Soderquist, J. A., 77, 221,299,360 Soga,T., 100 Sohar,P.,254 Solladi6,c., 134,330 Somers,P. K., 58 Somers,T. C.,332 Sommers,P. K.,350 Song,H., 262 S o n o d aN, . , 3 2 , l 1 5 , 3 1 6 , 3 4 6 Sopher,D. W.,286 Sorato,C., 249 Scirenson, H., l13 S o r i a J, . , 2 6 9 Spanton,S. G., 255 S p a r k sM , . A.,25,45 S p e e sM , . M.,82 Spencer,G. O., 44 Spileers,D., 230 Spivey,A. C., 233 Sridharan,V., 264, 266 Steele,B. R., 144 Stemerick,D. M., 130,225 Stephenson, T. A., 43 Stern,A. J., 212 Sternfeld,F., 55 Stevenson, P., 88,266
S t i l l e J, . K . , 2 6 , 3 1 7, 3 1 8 , 3 1 9 S t i l l e J, . R . , l 1 7 Stone,C., 321 Stoner,E. J., 6 Stork,G., 140,184,275 Streiber,J. M., 166 Streith,J., 230 Streitwieser,A., 36 Stryker,J. M., 175 Stucky,G., 365 Sturm,T.-J., 1 Stiirmer,R.,270 S u d r e zE, . , 2 0 S u a r e zE, . , 2 7 5 Subramanian, L. R., 144 S u d a ,K . , 3 6 7 Suemitsu, R., 241 S u g aS , . , 3 2 ,1 4 1 Sugano,Y., 109 Sugimori,J., 315 Sugimura,H., 339 Sugiura,T., 319 Sukirthalingam,S., 266 Sumi,K., 185 S u n ,R . C . , 7 3 S u n ,2 . , 1 6 0 Surzur,J.-M., 200 Sutowardoyo, K., l7 Suzuki,A., 66, 319 Suzuki,H., 12, t74,208,214 Suzuki,K., 120, l2l Suzuki,M., 69, t27, 197 S u z u k iS , ., 115 Suzuki,T., 21, 309 Suzuki,Y., 149 Swann,E., 148 Swanson, D. R., 57, l2l S w e e n e yJ ,. 8 . , 2 3 3 Swenton,J. 5., 21.2,274 Sy, W-w., 183 Syper,L., 177 Szeja,W., 162 Szymonifka, M. J.,62 Taber,D. F.,122, 142 T a d d e iM , .,43 Tagliavini,E., l3-5 Tahbaz, P., 176 Takacs,B. 8., 189 Takacs,J. M., 189,266 T a k a h a r aJ,. P . , 3 2 9
4tl
4t2
Author Index
Takahashi, H.,215 Takahashi. K..352 Takahashi.N.. 176 Takahashi,T., 109,121 Takai,K., 93,94, 107,312 T a k a i ,T . , 2 7 , 3 0 , 3 1 Takaki.K..384 Takanami.T.. 367 Takaya,H., 33 Takeda.H..215 Takeda.S.. 69 Takenoshita.H.. 100,365 Taketomi.T.. 33 Takeuchi.T.. 272 Taki, H., l3l Takiyama,N.,67 Takusagawa, F., 389 Tamao, K. , 27, 29, 35, 5l Tamaru.Y..97 Tamioka.K.. 158 Tamura.R..208 Tamura,Y., 163,274, 336 T a n a k aA . ..68 Tanaka,F., 132 Tanaka,H.,152,337 Tanaka,K., 12, 190 Tanaka,M., 178,234 Tanaka.S..384 Tanaka,T., 7 Tanigawa,H.,97 Taniguchi,M., 163,337 Tanino.K.. 167 T a n k e ,R . S . , 3 3 1 Tarakeshwar. P..95 Tarasov,V. A., 114 Tashika,H.,241 Taylor,R. J. K.,288 Taylor, S. K., I Teasdale. A..2& Tejero, T., 159 Terada.M.. 25 Terashi.H..2'14 Teulade,M.-P.,3 Tezuka.M.. 107 Thavonekham,B., 235 ThimmaReddy,R., 120 Thompson,A. S.,50 Thornton.E. R..257 Tian. W.-S.. 105 Tidwell, T. T., 150 Tietze,L. F., 190,363
Tius,M. A., 172,207 Toda, F., 190 Togni, A., 137,246 Tohma, T., 35 Tolstikov,G. A., 149 Tominaga,Y.,362 Tomioka,K., 110,249 Tomita,K., 170 Tomizawa,G., 170 T o n e ,H . , 3 5 3 T o o l e ,A . J . , 9 0 Torii, S., 337 Totleben,M. J., 298 Toupet,L.,251 T o u r ,J . M . , 1 2 1 , 2 & , 3 5 4 , 3 9 3 T o w s o nJ, . C . , 5 8 , 6 1 T o y ,A . , 9 1 Traylor,T. G.,356 Trippet, S., 142 Trivellas,A., 295 Troisi, L., 370 Trombini,C., 135 Trost,B. M., 43, 83,263,267,336,372 Trovarelli,A., 200 T s c h a e nD, . M . , 5 0 Tsubaki,Y., 384 Tsuda,T., 216 T s u j i ,J . , 2 4 9 , 3 1 9 Tsukamoto,M.,373 Tubergen,M. W.,9 T u b u l ,A . , 4 3 Tucker,C. E.,240 T u n ,M . M . , 3 7 4 Tykwinski,R., 187 Uchida,Y., l3l Uchikoshi,K.,79 Uchimura,J., 327 Uchiro,H.,220,329 U e d a ,1 . , 1 6 2 Ueda,Y., 80 U e k i ,S . , 6 9 Ugajin,S., 230 Ujikawa,O.,296 Ukaji, Y., 68, 300 Ukita, T., 186,249 Umani-Ronchi,A., 135 Umbricht, G., 39, 40 Umemoto,T., 170 U n g ,C . , 2 3 6 U n g ,C . S . , 3 5 0
Ura, T.. 178 Urogdi,L.. l7l Urpi, F.. 332. 3 U s h i k i ,S . . 2 1 Ushio,H.. ll Ushio, Y.. 3tD Utimoto.K..91 Uyehara.T.. l{
Vaid, B. K.. 16 Vaid, R. K.. 17 Valdes.C.. ll? Vanderesse . R. Van der Vecn. . Van Draanan.! Van Engen. D. Van Hijfre. L . Van Koten.G,. Van Niel. M B Van Wagencn. Varie,D. L.. & Vasapollo. G.., Veale,C. A.. f Vederas.J. C . Velde, D. \'.. 3 Verhoeven.T I Verpeaux.J.-rVest,G., 30 Vilar, E. T.. 14 V i l l a ,R . . l 9 l Villemin,D.. Z Villieras,J.. lO Virgil, S.. 157 Viso, A., 135 Vo,N. H..71 Vollhardt, K. P Von ltzstein, M Vorbriiggen. H. Vostrikov,N. S Vu, C. 8.,2E5 V y a s ,D . M . . 3 1
Wagner,A.. 3fl Wailes,P. C..71 Wakahara,Y.. I Walker, C. B. (. Walker,D. M.. Walker, F. J.. ! Walker,S..35t Wallace,M. A.. W a n gN , .,215
Aulhor Index Ura, T., 178 Urogdi, L., 177 Urpi, F., 332,333 Ushiki,S., 221 Ushio,H., 12 Ushio,Y.,389 Utimoto, K., 93, 94, 107,312,350, 384 Uyehara,T., 194
l. i9.i
ln- i36. 372
Vaid, B. K., 186 Vaid, R. K., 179,186 Yaldes,C.,227 Vanderesse, R., 308 Van der Veen,J. M., 311 Van Draanan,N. A." 48 Van Engen,D., 358 Van Hijfte, L., 198 Van Koten,G.,96 Van Niel, M. B., 161 Van Wagenen,B. C.,393 Varie,D. L., 82 Vasapollo,G.,228 VealeC , . A.,300,322 Vederas,l. C.,213 V e l d e ,D . V . , 3 3 7 , 3 8 9 Verhoeven, T. R.,50 Verpeaux,J.-N., 57 V e s t ,G . , 3 0 Vilar, E. T., 144 Villa, R., 191 Vilfemin,D.,282,372 Villieras,1., 107, 1fu Virgil, S., 157 Viso, A., 235 Vo,N. H.,7l Vollhardt,K. P. C., 112 Von ltzstein,M.,142 Vorbrtiggen,H.,367 Vostrikov,N. S., 149 Vu, C. B.,285 V y a s ,D . M . , 3 7 4 Wagner,A., 366 Wailes,P. C.,75 Wakahara,Y., 112 Walker,C. B. (Jr.), 167 WalkerD , . M.,142 Walker, F. J., 54 Walker,S., 358 Wallace,M. A., 167 W a n g ,N . , 2 1 5
W a n g ,Q . , 3 1 0 W a n g ,S . , 2 7 4 Wang,S. L. B., 89 Wang,W.,342 Wang,X.,57, 142 Wang,Y.,283,342 Wannamaker, M. W.,75 Ward,D. E.,2'19 Warner,B. P., 89 Wartski,L., l0 Wasserman, H. H., 271, 281, 285 Watabe,K.,208 Watanabe, M.,230 Watanabe, T.,84 Watanabe, Y.,125,126 Watson,8.T.,72,75 W a t t ,D . S . , 2 0 1 W a t t e rW , .,58 Webber,S. 8.,322 Weber,8., 39, 40 W e e ,A . G . H . , 3 3 0 Wehmeyer,R. M., 386 Weigold,H.,75 W e i l e r ,L . , 7 4 Weinig,P.,248 Weismiller,M. C., 58, 61,62, 120 Weissbart, D.,287 WelchW , M.,308 Welmaker,G. S., 133 W e n ,X . - Q . , 1 1 1 Wender,P. 4., 29, 93, 237 Wenger,R., 196 Wessel,H. P., 357 Wettach,R. H., 179 white, A. w.,237 White,J. 8., 387 W h i t e ,J . D . , 3 8 1 Widdowson,D. A.,317 Widdowson,K. L.,302 W i d h a l mM , .,33 Wierda,D. A., 178 wild,J.,261 Wilkinson,G.,43 Williams,D. R.,285 W i l l i a m sJ, . M . J . , 5 2 Williams,R. M., 317,318 Williard,P. G.,88 W i l l i s ,C . R . , 3 5 6 W i l s o n ,S . R . , 1 5 8 , 3 8 6 Wilson,V. P.,9 Wipf, P., 146
48
Auttor Index Wittman, M. D., 142 Witz. P.. 198 Woerpel,K. A.,39 Wojitowicz,H., 106 Wolf. W. A..290 Wonnacott.4.,312 Wood.A..246 Wright,M. E., 110 Wu.A..360 Wu.C..80 Wu, G., 320,321 Wu.R..393 W u l f f ,W . D . , 8 8 , 8 9 , m , 9 2 Wythes,M. J.,246 Xavier,L. C.,253,254 Xiang,Y. B., 154 Xiong, H., 198 Xiong, Y.,42 Xu. Y.-C..88 Yakura, T., 274 Yamada,H.. l4 Yamada.J..242,353 Yamada.M.. 100 Y a m a d aT, . , 2 7 , 3 0 , 3 1 Yamago,S., 46 Yamaguchi, M.,296,297 Yamaguchi,T., 5l Yamakawa,K.,80,283 Yamamoto,A., 169 Yamamoto,H., 134,209, 210,211, 212,
359 U6,3/i/7,314, 24f,, Yamamoto,K.,249 Yamamoto,M., 163 Yamamoto,T.,97 Yamamoto,Y., 45, 95' 145,194,208'234, 242,353,355 Yamamura,K.,345 Y a m a o k iH , .,319 Yamasaki,Y., 115 Yamashita,A., 9l Yamashita,D. S., 6 Yamashita,M.,241 Yamashita,S., 17 Yamauchi,M.,84 Yanagisawa,A., 246, 248
Y a n g ,D . , 3 4 8 Yang,D. C., 89, 92 Yang, P.-F.,124 Yasui,E., 115 Yasui,M.,280 Yatagai,M.,3& Y e h ,M . C . P . , 1 8 4 , 2 3 9 Yeoh,H., 138,139 Yeoh,H. Y.-L.,67 Yeske,P. E., 107 Yoakim,C.,344 Yohannes,D., 96, 389 Yokoyama,H.,177 Yokoyama,Y., 17 Yoneda,R.,296 Yonemitsu,O.,353 Y o o n ,M . S . , 2 8 2 Yoriguchi,Y.,8l Yoshida,Z'., 97 Yoshikawa,S., 131 A.,309 Yoshikoshi, Yoshimura,N.,389 Yoshioka,M., 102, 178 Young,J. R., 117 Yu, C.-M., 156,157 Yuen,P.-W.,157,178 Zaidlewicz,M.,6 Z a r d ,S . 2 . , 1 6 4 Zefirov, N. S., 188 Zehnder,M., 148 zeitz,H.-G.,148 Zeller, S., 303
Zhang,H.'G.,40 Zhang,1.,60 Z h a n g ,N . , 2 6 8 Zhang,W., 158 Zhang,Y.,242, 320,321 Zhao, K., 184 Zhao, S.-K., 103 Zhdankin,V. V., 187 zhi,L.,289 Zhu, J ., 266 Zhu, L., 386 Zibuck, R., 166 Zimbiniski,R.,375 Zuniga,A. E.,373 ZydowskY,T' M.' 255
SUB.
Acetalizeti O,S-Aceu P-Acetem Acetoaccfr Acetonc , Acetophcr 4-Ac€tory Acetoxyb 4-Acctory. anhld l-Acefor-v Acetylatir N-Aceryle Acetyl cilr N-Acetyl r N-Acetyt-l l-Acety'-2. 45 Acrolcin. I Acrylonitri 3-Acryloyl 3-Acryly'-l Acyloxybo Acyl broo Acyl(carto (tdptl Acyl iodil Acyloin a 2-Acyl-lJ" 2-Acyloxyt c'-Acylor| Acyl rlcri Acylsilaru Acylstanor
u,4lAddi
o-Alaninel Alcohols. i Alcoho$n Aldimincs. Aldol cod Aldot rel l3?. l: 329 Seealso aldol t
SUBJECT INDEX Acetalization,199 O.S-Acetals.278 p-Acetamidobenzenesulfonylazide, 290 Acetoacetylation,142 Acetone glucose,245 Acetophenone,187 4- Acetoxy-2-azetidinones,127 Acetoxylation, 127 4-Acetoxy-5-methoxyhomophthalic anhydride, 307 1-Acetoxy-2-propenylsilane, 45 Acetylation, 205 N-Acetylation,214 Acetyl chloride,&, 107 N-Acetyl l-threonine, 33 N-Acetyl-l-phenylethylamine, 52 l - Acetyl-2,3,4,6-tetrabenzylglucopyranose, 45 Acrolein, 166 Acrylonitrile, 14, 347,391 40 3-Acryloyl-1,3-oxazolidin-2-one, 154 3-Acrylyl-1,3-oxazolidinone-2, Acyloxyboranes,314 Acyl bromides,49 Acyl(carbonyl)cyclopentadienyl(triphenylphosphine)iron, I Acyl iodides,134 Acyloin condensation, 378 2-Acyl-1,3-oxathianes, 384 2- Acyloxybenzoic acid, 367 a'-Acyloxylation,201 Acyl selenides,20 Acylsilanes,77 Acylstannanes, 133,351 [1,4]Addition,167,243, 26r o-Alaninals,163 Alcohols,23,273, 325 Alcoholysis, 292 Aldimines, 158-159 Aldol condensation,302-303,367 Aldol reactions, 46-47,l00, lW, l3l-132, 137, 154-156,2r8-2r9, 220, 257, 314, 329 Seeabo Mukaiyama aldol reaction; Nitro aldol reaction
Aldols,71 anti-Aldols,155-156 135,154,155,194 syn-Aldols,58-60, Aldol-type reactions,15-16,221-222,272,
36r Alkynes1 , 75,368,393 1-Alkynes,198 Alkenes,327-329 crs-Alkenes,175 Alkene synthesis,340-341 o-Alkenyl ketones,193 Alkenylchromiumcarbenes,92 Alkenyllithiums,196 Alkenylsilanes,106 Alkenyl sulfides,319 1-Alkoxyallyltins,8 c-Alkoxy carbonyl compounds,287-288 o-Alkoxy hydrazones,287 p-Alkoxy cyclicethers,353 Alkoxycarbonylation,200 Alkoxylation,26 Alkoxy(phenylthio)acetonitriles, 83 ( l -Alkoxypropen-3-yl)tributylstannanes, 44 c-Alkyl o-aminoacids,255 Alkylaluminumhalides,1-3 o-Alkylation,'132-133 C-Alkylation, 196-197 Alkylation of phenols,276-277 Alkyl benzyloxyacetates, 109 Alkyl chloroformate,200 Alkylchromium(III) reagents,93-94 4-Alkyl-1,3-cycloalkanediones, 145 3-Alkyl-1,1-dichloro-2-propene, 93 43 1-Alkyl-2,5-divinylcyclopentanols, 152 3-Alkyl-3-hydroxyazetidine-2-ones, Alkylidenation,367 c'-Alkylidenocycloenones, 367 Alkyl iodides,182 Alkyllithium/Cerium(III) chloride,4-5 Alkyllithiums, 3-4, 56-57 Alkylmanganese chlorides,243 Alkylmercurychlorides.4-5 2-Alkyl-1,3-propanediols, 204 1-Alkyl-1-silyloxycyclopropanes, 316 Alkyltetracarbonylferrates,241 415
4L6
SubjectIndex
2-Alkyne-1-ol,129 Alkynylhydrazine. 129 1-Alkynylleadtriacetates,193 l-Alkynyllithiums, 193 Alkynyl silyl ethers,140-141 Alkynylzincbromides,363 Allenes. 130, 175,223, 267 Allenyl chloromethYlsulfone, 5-6 Allenylsilanes,6 90-91 Allylaminocarbenes, Allylation, 6, 137,337 of aldehydes,156 of quinones,7, 343 6 B-Allylbis(2-isocaranyl)borane, 6 B-Allylbis(4-isocaranyl)borane, Allylcoppers, 236-237 6 B-Allyl(diisopinocampheyl)borane, Allylic acetates,269 Allylic alcohols,86, 200, 260, 261,262' 272, 3r2, 355-356,371 Allylic amines,75-76 Allylic boronates,66 Allylic iodides,86 Allytic silanes,250-251 Allylic ureas,20 Allylmagnesiumbromide,245 Allyl methyl ethers,120 298 l-Allyloxy-2-iodobenzene, Allyl propargyl ethers, 43-44 Allylsilanes,67 7 Allyltitanium triisoProPoxide, Allyltitanium triPhenoxide,7 , 235, 344 Allyltributyltin , 7-9, ffi, 156-157 Allyltrifluorosilane,9 Allyltrimethylsilanes, 204, 3'l4 Allyl vinyl ethers,209 Alumina,9-10,190 Aluminum chloride, 10-12 Aluminum enolates,I Aluminum(Ill) iodide, 1l Amberlyst,2, 15 Amides,30,49 Amidoethylation, 392-393 Amination, 305, 309-310 Amine arylation,16 Amines.225,255 c-Amino acids,233, 255,363 B-Amino acids,205, 232,265' 391-392 1-Amino acids,204-205 1,2-Aminoalcohols,44-45 1,2-crs-Aminoalcohols,22-23
Amino-acid synthesis,16 Amino acylations,64 Amino alcohols,102,250 Amino aldehydes,356 163 c-Amino aldehYdes, c-Amino esters,331 p-Amino esters,365-366 cr-Aminoketones,214 1-Aminobenzo$iazole, 23 90 2-Amino-1-butYrolactones, e-Amino carboxYlicacids,355 Amino cyclization,302 3-Amino-1,2-diols,3'71-372 1l-12 3-Amino-2-hydroxybornanes, acids,140 4-Amino-3-hydroxycarboxylic I(S)-I -Amino-2-methoxymethylpyrrolidine,12-13 Amino sulfates,102 Angelateesters,128 Angelic acid, 128 380 (o-Anisaldehyde)Cr(CO).' -280 [3 + 3]Annelation, 279 Annelation-ringcleavage,139-140 [3 + 2]Annelations,67 Anodic oxidation,202 Anthracene,13 120 AnthraceneP-C-olivosides, Anthracycline antibiotics, 249 360 AnthracyclineglYcosides, Anthracyclinones,171 Anthraquinone,56 Aplysiapyranoid,317 Arachidonicacid,252 ArenechromiumcarbonYl,380 Areneseleninicacids,177 complexes, Arene(tricarbonyl)chromium 13-16 Arsoles,122 Arsonium ylides,342 Arylamines,228 p-Aryl-P-aminoacids,265 Arylannelation, 259-260 N-Arylation, 373 C-Aryl glycosides,120-121 3-Arylcycloalkenes, 262 Aryl ethers,194 367 2-ArylethYlamines, Aryllead triacetates,16 ArylmethYlketenes, 269-27O Aryl methYlketones,275 215 3-Aryloxy-2-oxo-1-propylamine,
Aryl proPargYl eth 2-ArylProPionrcri Aryl triflates. 317'3 Aryl-vinyl couPb4. Asparagine.265 Asymmetric cPord of alkenes'157-l Asymmetric SherPl Atom-transfer ec Atom-tramfer qrcl Azaamino acil. l'l 1-AzabicYcld5-3. 1-Aza-1,lbutedir 2-Azetidinonc. lll l,2-Azido alcohotr cr-Azido acirts. 255 Azidotributvltin. lt Azidotrimcthyldr 2-Azirdinccartorfi Aziridines' l@ N-Aziridimhvdru Oto.",6i6s. 3[I) Azulenes' 282
Baeyer-Villiger o Baeyer-Villigcr rt Barbier additirnBarbier-tYPccoq Barbier-tyPccra Barium mangrtrl Benzamidirr. l0l Benzannelatirn' BenzazaPim'3t 1,2-Benzencdic [1,2-Benzencd-l Benzenes,Et ' Benzeneselcml Benzenesclcu! 2G2l BenzhYdrYtam4-BenzhYdrYlo BenzocYclobur 2,4-Benzodkrrq Benzofurans'99 BenzonaPhtbry 1,4-Benzoquim BenzoquinorsBenzothiazolinr Benzotriazolc.I
Subject Index
f
i
Nr.i.. l.l0
I :crr. t. | \cs.
Aryl propargYlethers, 69-70 2-ArylproPionic acids' 269 Aryl triflates,317-318 Aryl-vinyl couPling,265 Asparagine,265 AsymmetricePoxidation.54 of alkenes,157-158 Asymmetric Sharplessdihydroxylation, 153 Atom-transfer annelations,6l Atom-transfer cYclization,174 Azaamino acids, 175 275 1-Azabicyclo[5.3.0]decanones, 310 1-Aza-1,3-butadienes, 2-Azetidinone, 127' 152 1,2-Azidoalcohols,17 ct-Azido acids,255'256 AzidotributYltin, 16-17 17 AzidotrimethYlsilane, 2-AzirdinecarboxYlates,392 Aziridines, 102 N-AziridinohYdr azone,290 Azomethines,389 Azulenes,282
2-Benzoylbenzoicacid, 367 Benzylacetates,115 Benzylamine/Potassiumcyanide, 22 Benzylation, 273 Benzyl(chloromethyl)dimethylsilane'209 Benzyl chloromethYlether, 298 O -BenzylhYdroxYlamine,22-23 Benzylic hYdroxYlation,360 namides' 204N-Benzyliiene-p-toluenesulfi 205 Benzylmagnesiumbromide, 172 N-Benzyl aldimines' 4 Benzylpalladation,320 BenzyliriethylammoniumborohydrideChlorotrimethYlsilane,23 Benzyne,23-24 Bicyclicenones,122 100 Bicvclo[2.2.2loctenes, StNnL-H. See2,2' -DihYdroxY-l'l'binaphthyl-Lithium aluminum hydride 1,1' -Bi-Z,2'-naphthol-DichlorodiisoproPoxYtitanium,24-25 -diyl hydrogen 1.1'-Binaphthyl-2,2' phosPhate,25 BINiP. iee 2,2'-Bis(diphenylphosphino)1,1'-binaPhthYl BTNOL, 132-133 BIPHEMP. See2'2-'Bis(diphenylphosphino)-6,6'-dimethYlbiPhenYl Biphenyls,119,317, 319 2,2'-Bipyridine,308 Bipyridine-Palladium(II) acetate,25 189 2,2-BiPYridYl, 2,2'-BiPYtidYl,230 -26 nirf "."tbnitilt")dichloropallad ium, 25 26-27 Bis(acetylacetonate)cobalt(II)'
Baeyer-Viltigeroxidation' 81, 177 Baeyer-Villigerreactions,71, 379 Barbier addition,312 Barbier{YPe couPling,298 Barbier-tYPecrosscouPling,342 Barium manganate,18 Benzamidine,101 Benzannelation,172 BenzazaPins,38 l8-19 1,2-Benzenedimethanol, Bis(acetylacetonato)nickel(Il)19 [1,2-Benzenediolato-o,o']oxotitanium' Diiiobutylaluminumhydride' 27'28,, 88 Benzenes, N,N'-Bis(benzylidene)ethylenediamine'.263 19-21 chloride, BenzeneselenenYl 1,3-bistrimethylsilylcyclopentadienyl)Benzeneselenenyltrifluormethanesulfonate' Bis( chloroYtterbium(IIl)' 36-37 20-21 ?A-29 1,4-Bis(bromomagnesio)pentane' -,, 305 Benzhydrylamine, nischter-Napieralskicyclodehydration'36654 4-Benzhydryloxy-(E)-2-butene-1-ol' 367 102 BenzocYclobutenediones, 29 Bis(cyclooctadiene)nickel, 2,4-BenzodioxePines,l8 30 Bis(dialkYlamino)magnesium' Benzofurans,99 30 t. t' -nis(i,+-oicyanonaphthalene), 18 1 BenzonaPhthoPYranones, complexes' Bis(1,3-diketonato)nickel(II) 1,4-Benzoquinones,389 30-32 Benzoquinones'102' 338 32 Bis(dimethylaluminum)selenide' 213 Benzothiazolination' 309 Bis(diphenylphosphine)ethane' Benzotiazole,2l-22
41E
SubjectIndex
2,2'-Bis(diphenylphosphino)-1, l'2-Bromothiazole.362 binaphthyl,32-36 Bromotrimethylsilane, 50 2,2'-Bis(diphenylphosphino)-6,6'1-Bromovinyldimethylsilyl chloride,51 dimethylbiphenyl,32 Brook rearrangement.146 Bis(dipivaloylmethanato)cobal t(il), 27 Butadiene-Ironcarbonylcomplexes,51-52 Bis(iodomethyl)zinc, 185 Butadiene-tricarbonyliron, 251 Bis(N-isopropylsalicylaldiminato)Butadienylsilanes, 118 copper(Il), 37 Butane-2.3-diol.159 2,4-Bis(4-methoxyphenyl)(R,R)-(--)-2,3-Butanediol, 1,3-dithia-2,452-53 diphosphetane-2,4-disulfi de. 37-38 1,4-Butanediones, 188 1,2-Bis(methylene)cyclohexane, 5 3-Butene-2-ol,86 Bis(3-methyl-2,4-pentanedionato)nickel(II), Butenolides,116-117 31 l-rButyl 4-methylN-benzyloxycarbonyll, 1-Bis(methylthio)ethylene, 314 aspartate,16 Bismoles,122 Butylboronicacid,254 1,1'-Bis(2-naphthoic acid), 30 t-Butyldimethylsilane,292 Bis(oxazolines), 38-41 -2-one,152 N-t-Butyldimethylsilylazetidin Bis(oxazolinyl)pyridines, 4 1-42 Butyldimethylsilyltriflate, 59-60 Bis(pentamethylcyclopentadienyl)sec-Butyllithium,56 lanthanumhydridedimer, 42 t-Butyllithium,56-57 Bis(salicylidene)ethylenediaminatoButyllithium-Sodiumt-butoxide,55 copper(Il), 37 Butyllithium-Tetramethylethylenediamine, Bis(2,2,6,6)-tetramethylpiperidino)55-56 magnesium,42 t-Butylsulfonylmethyllithium, 57 Bis(tributyltin),279 t-Butyl acetate,137 Bis(trifluoroacetylacetonate)cobalt(II), 27 t-Butyl alkyl sulfoxides,160 Bis(trimethylsilyl)acetamide, 285 t-Butyl hydroperoxide,53-54,126 1,4-Bis(trimethylsilyl)-2-butene, 43 t-Butyl hydroperoxide-Dialkyltartrate-1,8-Bis(trimethylsilyl)-2,6-octadiene, 43 Titanium(IV) isopropoxide,54-55 Bis(trimethylsilyl)peroxide, 43 r-Butyl hydroperoxide-VanadylacetylN,N-Bis(trimethylsilyl)urea, 379 ^cetonate.273 Bis(trineophyltin),373 t-Butyl methyl sulfone,57 Bis(triphenylarsine)palladium(II) acetate, t-Butyl thionitrate,57 43-44 t-Butyl (S)-N-tosylaziridine-2-carboxylate, Borch reduction, 305 233 Boron enolates,109 t-Butyl (triphenylphosphoranylidine)Boron trifluoride etherate, 44-47 acetate,285 Brevicomin,289 2-Butyne-1,4-diols, 280 Brominative cyclization, 316-317 1-Bromo-1-alkynes, 366 2-Bromo-1,3-dienes, 318-319 Calomelanolactone, 88 N-(Bromomagnesio)-2,2,6,6Camphorbenzenesulfonimine, I 19 tetramethylpiperidide, 48 Camphorsulfonic acid, 59 2-(Bromomethyl)acrylate, 164 10-Camphorsulfonic acid, 61 Bromomethylation,79 ( 1O-Camphorsulfonyl)imine, 58 (Bromomethyl)dimethylsilyl ethers,345 1O-Camphorsultam, 58-61 3-Bromo-2-methylpropanol,3zl4 ( l0-Camphorylsulfonyl)oxaziridines, 6l 9-Bromo-9-phenylfluorene, 49 62 2-Bromopropionicacid, 289 CAN. .SeeCerium ammoniumnitrate N-Bromosuccinimide, 49 Carbenoids,248 N-Bromosuccinimide-Pyridinium 2-Carboalkoxycyclopentenones, 247 poly(hydrofluoride),50 367 B-Carbolines.
Carbomcthor 62-63 4-Carborrrtl dioritcr, Carbon subo Carbonyl ui Carbony' r$ Carbony'atir Carbonylatir 1,1'-Carbmtriflatc. ( Carbonylcbh rhodiur I,l'-Carbct Carboxanil Carboxy'ic r Catecholban Cephalocpon Cerium anr Cerium(IlI) r Cerium(lll) r 68 Cerium(Ill) r 69 Cerium(M) t Cesium firs Cetyltrinrcrl Chileninc. 2! Chiral amir Chirald. 133 ChloramirChloranil. l( Chloroaccty 2-Chloroacrt c-Chloroaltl o-Chloro chl c-Chloro Lct 1,4-Chloroa o-Chlorobis( (dimcQ methy'c B-Chloro9l 4-Chloro-3t 3-Chlorobuu Chloro(chh 72 Chlorodi(cyr conium. Chlorodi(qt conium. Chlorodi(c.v
7+75
SubjeciIndex
chl,rride,5l I
o m p l c r e s5, 1 - 5 2
a:-:.r
ylorr carbonyl-
drn-l-one,152 5e-rt I
r r r J c .5 . 5 !hr !cnediamine, lr.l.
sj::6 ili\ r tartrate-lrr.ic.5{-55 4 . . : \l . i c c t v l -
- i - i . rr h o x y l a t e , rnr lrJine)-
r.
.19
rl :. i. Dn.trncs.6lurn nrtrate nc.. l-17
419
r ane, 77 B-Chlorodiisopinocampheylbo chloride, Carbomethoxymethanesulfonyl Chlorodiphenylphosphine,77-78 62-63 c-Chloroenolacetates,124 1,14-Carbomethoxy-1,2-thiazetidine 124 c-Chloro-c,B-enones, dioxides, 62 3-Chloroflavones,367 Carbon suboxide,63 Chlorohydrins, 80 Carbonyl activation, lll-ll2 367 2-Chloroindenones, Carbonyl allylation, 329 Chloromethylation,79 Carbonylation, 228, 320, 346 (c-Chloromethyl)diphenylphosphineoxide, Carbonylativecoupling, 351-352 371 1,1'-Carbonylbis(3-methylimidazolium) iodide, 78-79 2-Chloro-1-methylpyridinium triflate, 63-64 p-tolyl sulfoxide,79(R)-(--)-Chloromethyl Carbonylchlorobis(triphenylphosphine)80 rhodium(I), 87 Chloromethyltrimethylsilylether, 79 l,l'-Carbonyldiimidazole,63, U, 251 n-Chloroperbenzoicacid, 71, 80-83,199, Carboxamidation,1rg 273 Carboxylicacids,216 m-Chloroperbenzoicacid-Trifluoroacetic Catecholborane,65-6f, 86, 254 acid, 83-84 Cephalosporin,178 3I 1 3-Chloro-3-(phenylthio)-p-lactams, Cerium ammonium nitrate, 66 Chloropropionic acid, 280 Cerium(III) chloride, 67-68 sulfide,84Cerium(IIf chloride-Chlorotrimethylsilane, N-Chlorosuccinimide-Dimethyl 85 68 334 Chloro(triisopropyl)silane, Cerium(III) chloride-Tin(II)chloride,6879, 85; l1-5,243 Chlorotrimethylsilane, 69 iodide, 86 Chlorotrimethylsilane-Sodium Cerium(IV) trifluoromethanesulfonate,69 nitrite or Chlorotrimethylsilane-Sodium Cesium fluoride, 69-70 nitrate, 86 Cetyltrimethylammoniumbromide, 228 Chlorotris(triphenylphosphine)rhodium(I), Chilenine,291 86-88 Chiral aminals,159 65 Chlorotris(triphenyl)rhodium, Chirald, 133 Chlorox, 308 Chloramine-T.213.214 2H-Chromens,338 Chloranil, 166 Chromiumcarbenecomplexes,88-92 Chloroacetylchloride, 207 Chromium(II) chloride,93-94 2-Chloroacrylonitrile,391 Cinnamylaldehyde,216 c-Chloroalkyl phenyl sulfides,240 Citronellal,190 c-Chloro chloroformates,354 Citronellol,243 o-Chloro ketones, 202-203,283 Claisenrearrangement,69, 71, 134,147, 261 1.4-Chloroamidation. 209-210,355-356,383 o-Chlorobis(cyclopentadienyl )(dimethylaluminum)-oCleaningbaths,377 Cleavage 70-71 methylenetitanium, of acetals,300 3.1]nonane,71 B-Chloro-9-borabicyclo[3. -ol, 93 of alkenes,178 4-Chloro-3-butene-1 of epoxides,17 annelation,115-116 3-Chlorobutenolide 7lof oxiranes,7 Chloro(chloromethyl)dimethylsilane, 362 1,3-C-OSirearrangement, 72 Cobaloxime(I),94-95 Chlorodi(cyclopentadienyl)-hydridozirCobalt(Il) acetate,95 conittm, T2-74 93 Cobalt phthalocyanine, Chlorodi(cyclopentadienyl)-methylzirComplexationof ethers,212 conium,75-77 Chlorodi(cyclopentadienyl)titanium(III), Conjugateaddition,73, 97, 208, 231, 363 Conjugate reduction, 65, 263-264,350 74-75
4m
Subjec{lndex
2, 338 Cyclobutanes, Copper,95 148' 315 Cyclobutanones, Copper azide,95-96 102 Cyclobutenediones' 216 Copperhydride, l'17 CyclodehYdration, Copper(I) bromide,96 220 Coppe(I) bromide-Dimethyl sulfide',96-97 B-Cyclodextrin, 343 Cyclododecanone, Coppe(t) chloride-Chlorotrimethylsilane' 134 1,4-Cyclohexanedione, 97 102 Cyclohexanedisulfonamide' Copper(I) cyanide-Chlorotrimethylsilane' 1R,2R)1--)-trazrs-Cyclohexane-( 97-98 102-103 disulfonamides, Copper(Il) acetate,16 132 Cyclohexanes, 98 Copper(I) iodide, 348 Cyclohexanones, Copper(I) iodide-Tetrakis(triphenyl376 Cyclohexenones, 98-99 phosPhine)Palladium, 126 I i-O-Cyclohexylidene-lnyo-inositol, Copper(I) oxide, 99 methYlketone,254 CyclohexYl 99 Coppe(f ) trifluoromethanesulfonate, 116 Cyclopentadecanone, Corey aldehYde,149 es, 92, 162 Cyclopentadien 84-85 Corey-Kimreagent, 351 CvcloPentadienones. 71-72 Corticosteroids, trichloride' Cyclopentadienyltitanium(IV) Cross-couPling,169-170 245 See alsoPinacol cross-couPling Cyclopentaneannulation'103-104 166 CrotonaldehYde, 145 CycloPentane-1,3-diones' 184 Crotyliodomalononitrile, 43' 295 Cyclopentanes, Crotylsilanes,251 88 CycloPentenediones, crotyltributyltin, 99-100 0 369-37 Cyclopentenes. acid CSA. SeeCamPhorsulfonic es.261'262.351 Cyclopentenon Cyanation,100 38-39,57, 107,191-192 Cyclopropanation, 100 Cyanoarenes, 281 CycloproPanone, Cyanocuprates,235-236 Cyclopropylcarbinylradicals, 368-369 Cyanohydrin acetonide,303 CycloproPYlesters,39 Cyanotrimethytsilane-Di-o-chlorobis2 100-101 [4 + 2]Cycloreversion, (cyclooctadiene)dirhodium' Cyanuricfluoride, 101 Cyclic acetals,354 DABCO, 43. r42, r85 Cyclicethers,350, 365 diene, 163 DanishefskY's l0l-102 Cyclicsulfatesof 1,2-diols, DAST. SeaDiethylaminosulfur trifluoride Cyclization,188 DBU. See1,8-Diazabicyclo[5'a'0]of alkenes,117 undecene-7 of dienes, 122-123 SeeDichlorodicYano-oDDQ. 1 14 [2 +2 + l]CYcloaddition, benzoquinone 1l2-l 13 88' + ZlCycloaddition' + Z lZ 106' 307 DeacetYlation, 149,314[2+2]Cycloaddition,2, 88, 89' Deacylation,107 391 315.337-338, DealkoxYcarbonYlation,142 247' 392 [3 + 2]Cycloaddition,68-69, 193 DebenzYloxYcarbonYlation, [3 + 4]Cycloaddition' 68-69' 206 198 Debromination, [3 + 5]CYcloaddition'206 cn-Decalins,35 163' 25'l, 3lr [c + zicyctoaoaition,23, 100, 87 DecarbonYlation, Cycloaddition, 218 Decyanation.214' 303 Seealso DiPolar cYcloadditions Dehalogenation,11 Cycloalkenones,2-3 Dehydration,163,l9l' 358' 368 CycloalkenYllithiums,196 105-106 1.3-Dehvdrochlorination, 109 CycloalkYlhYdrazides,
DehydrogeoetSee aho Trl' Dehydrohalqe Dehydrotcllur 4-Demethor-vd Demethy'atir Deoximadn. I 2-DeoxYaldcc Deoxyaldccr. Deoxygenatir %y7 ePoxidcs' 7{ 2-DeoxYglYo l-DeoxYrciilr DepolYmcra DeProtcctioo ' Deprotonau Deracemizli DesulfonYleu Desulfuradr gem-Di*tzl Diacetor-o1 1.6Did&h!( N,N-Didlcq 3,4-Didlory{ 2,2-DialkYl-l 4,5-DialLvfr N,N-DidrYl 1,2-Diamir vic-Diamir c,a-Diary!2 2,5-Diary'u 1,8-Diazabr Diazenes.ll Diaziridincr. Diazirincs. I Diazoaccur a-Diazo ka l-Diaza-25 l-Diazo$ Diazo trad N,N'-Dibcr N,N-Dibct 1,1-Dibro Dibromodil Dibromoc lo? Dibromoo 1,5-Dibra 2,3-Dibrq lm-10
S'UGd lr&a
ll I
t.,
l{)]
(iR lR)c-.,l
126 -r:. ,-rnositol, onc l5{ ll"
ri: rum l\') trichloride' k,n 103-104 |.- i15 F. ;r, l - 1 " 1 .. r 5 1 ; l ' : 1 . 1 0 7 ,1 9 1 - 1 9 2 raJr.rls.368-369 p
.: L< mrno.ulfurtrifluoride b r r rc l o [ 5 . 4 . 0 1 dr;r.rno-o-
x.n. l{2 r l a t r o n .1 9 3 l ? !'l l.r: 158,368 ptrrrn.105-106
109 Dibutylboryl triffuoromethanesulfonate' roe
130-l3l' 149' 325 "Dehvdrosenation, il i, "tt-t Transfer dehydrogenation Dehvdrohalogenation'308 Dehydrotelluration'316. 249 I-o J."trto*voaunomYcinone' 214 DemethYlation, Deoximation' 86 2-DeoxYaldoses,87 Deoxvaldoses'87
;i;;;;iffir;nentadientlzirconium' Di-t-butYlhYPonitrite'l:o . 110 i.i:iiifi"iir-+-methoxvphenor' -z.i-oi-t-ut,ir-l-methvlphenol' 39 110 i-r.r i-"pi-t-i"ivr+-methvlpvridine' 230 -oiuurvinorephedrine' ]r.r
ree'2e7' 160'188-18e' ;.*y;;;;i;;, 346'347 ePoxides.74 3682-DeoxYglYcosides' 3U) 1-DeoxYnojirimycin' 178 DePolYmerization' 149 P.iroi..,ion of acetals' 307 Deprotonation, Deiacemization' 204 DesulfonYlation'348-349 Desulfuration, 214 183 sem-Diacetates' "oiu..ton.-o-glucose' 136-I 37 294 1,6-DialdehYdes'
zzr 2.6-Di-r-butYlPYridine' lll telluride' DibutYl DibutYl telluroxide'111. t I 1-112 oil",tr,i" bistriflate' 112 oxide' DibutYltin "oi.ui6onvrttvtlopentadienyl)cobalt' .. I l2113 I 13-115 oi-o-Tiruonytrexacarbonyldicobalt' 16 15.-1 I acid' 6i.t totou"tilt I l6Dichlorobis(cyclopentaorenyl)titanium' ll'l
oictrioroui,(cy:r"o:"j:^oJiJrll::il;:li; dtcn Ethvlaluminum
oi.ir""J#i"if rrenvrprrosptrine)nickel(II)'
200 N.t'l-Oiutt"nyt-p-oxoamides' 105 3.4-DialkoxYfurans' 'zi-oi"iivr-i'l-cvclohexanediones'
145
302 +,i-oi"irvrrttn-21514-ones' 19-200 r.i.ll'oiurlyrttvdrazones' 1,2-Diamines,l0l'294 vic-Diamines'4 ;-";;;;tlpYrrolineme
ttll
118 pichioiobis(triphenylphosphine)l18 oalladium(Il)' --t-J'ol-oi.rtrorocamphorsulfonylr 119-120 oxaziridine' 124 o.o-Oi.ntototyclobutanones' l2o
ffi;ffi6;o-o-benzoquinone' nium-Silver
thanols' 253
5o i.i-oi".ir",iuttYdrofurans' 106 105s'l'o]unoecene-7' i i;i;;ilt.v'to[ 130,223 Diazenes, Diaziridines, 149 Diazirines, 149 Diazoacetates,38-39 ct-Uiuto ketones, 282' 35'l 289 i-oiazo-z,s-trexanedione'
28e ; -iffi -!-pnenvl-2'5-pentanedione'
il'i.'r,i.iotoi.v.lopentadienyl )haf oerchlorate'120-121 oi.irotoJii.vtlopentadienyl)zirconiumButvllithium' l2l-lz4 i38 Dichlorodimethyltin' "o'rc'i'r.t"iiL.t-oiphenvlphosphino)ethanelnickel(Il), 124 Dichloroketene'124 "oii'fi"toprrenvlphosphine' -. 22
t i.;:fi;il;;- i ' i '3'3-tet'ai'opropvrdisnoxane,125-126 oicr,ioioiri.( trlphenylphosphine)ruthenium(II)' 126-128
355 Diazo "N.N transfer'290'35.'l #;il;l;Yl'PhenYl sulroxide' ,,, -Di.hlorotittonocene' 233 iPiu"nrvrasPar.agine' l2l -D-valine ' ,304 N.N-OiU"ntYf DictYoptereneB' 283 318 Ioo i.i-oiutotourkenes'198' Ll--6i.vunonuPhthalen-e' / Zinc' 106 I 28 iiiul*"Jin""romethane "oiut"t"t"tt"ne-Zinc I ) chloride' i i-"oi.v.i"tt"-vlcarbodiimide' / Copper( 7l 107 107 OiUro"momettryl(trimethll)silane' 2'17 ntane' 1.5-DibromoPe l -propene' z,i-Oiuro.o- r -phenylsulfonyl107-108
oiwroiexyrctrtoroborane'271 t'2-ethanediol' i;ilft'h;-Yltriflate'109 oi.vloP.ntYruorYl 261 acids' Oia.nYatoutino ts4'389-390 87-88' catalvst' 6i.i.-iro.'
4n
SubjectIndex
Diels-Alderreactions,5, 10, 14, 24,28,32' 40.92. 100,105,218,2r9,230'3r0311,314,315,319 SeealsoTriplex Diels-Alderreaction 1,3-Dienes,198, 259-260,zffi 1,4-Dienes,236,259 319 1,2-Diene-4-Ynes, 325 1,4-Dienones, 267 1,5-Dien-3-Ynes, Dienynes,29 Diethylaminosulfur trifl uoride, 128-129 , 223 Diethyt azodicarboxylate, 129-130 Diethyl malonate,13 13 Diethyl methylidenemalonate' idate, 296 Diethyl PhosPhorocYan 166 3,4-DiethylPYrrole, Diethylzinc, l4l, l'18, 277, 312-313 130 1.1-Difluoroalkenes, a,c-DifluoroalkYl ethers, 129 Difluorocarbene, 106 DifluorocycloProPanes,106 Difluoromethyldiphenylphosphineoxide'
o.B-DihYdroxythioesters'329 132-133 2,i'-OitryOrory-1.1'-binaphthyl. 2,2'-Dihydroxy-1,1'-binaphthyl-Lithium aluminum hYdride' 133 1'-bis(triphenylsilyl)-1' 2,2'-Dihydroxy-3,3' binaphthyl-Trimethylaluminum,133134 Dihydroxylation,150-151,249' 250' 251 Dihvdroxytartarimide.324 to,is-oitryoroxYvitaminD-J' 356 Diiodosilane,134 Diisobutylaluminum hydride, 134-135 135 DiisopinocamPheYlborane, Diisopropyl (E)-1-[cyclohexyloxy)dimeth135-136 ylsitYllboronate, DiisoproPYlethYlamine,109 1,2;5,6-Di-O-isopropylidene-c-o, 245 glucofuranose,136-137 1,4-Diketones,327 vic-Diketones,298 Dilithiodichloroacetate, 115 Dilithium tetrachlorocuPrate,50 l '31,3-Di(p-methoxYPhenYl)30 orooanedionate, I4.4-Dimethoxy-2-trimethylsilylmethylbutene,138 3,3-Dimethoxy-2-trimethylsilylmethyl-1 138-140 ProPene, 1,3-DimethoxY-1(trimethylsilyloxy)butadiene,140
130 Dihydridotetrakis(triphenylphosphine)ruthenium,130-132 89 Dihydrobenzenes, Dihydrobenzofut ans,Zffi , 274 2,3-Dihydrofuran'35 Dihydrofurans, 202, 280 392 Dihydro-1H-indenes, 5,5-Dimethoxy-2-trimethylsilyl-1-pentene' 193,367 Dihydroisoquinolines, 138 l0 1 DihydronaPhthalenes, 119 N,N-DimethYlacetamide, 20 Dihydro-1,3-oxazines, 210 chloride, DimethYlaluminum 5,6-DihYdro-2H'PYrans,226 140Dimethylaminodimethylchlorosilane' DihydroPYrans, 25-26,334 l4l t,+-bitryOropyridine-3-carboxaldehydes' Dimethylamino-1,2-diphenyl-3-methyl-2159 butanol, 133 ( 1,2-Dihydropyridine)tricarbonyll4l (--)-3-exo-(Dimethylamino)isoborneol' chromium,286 ip-Dim"thytuminophenyl)-diphenylphosDihydroPYrimidinone,265 Phine,142 Dihydroquinidine 4-chlorobenzoate'249 42' 353 4-Dimethylaminopyridine,'l 153 p-chlorobenzoate' Dihydroquinidine 142 N,N-DimethYlaniline, 153 Dihydroquinine p-chlorobenzoate' 5, 198 2,3-DimethYl-1,3-butadiene, 91 t,4-bihydrothionaphthoquinones, 224 1,2-DimethYlcYclohexane, vitamin D-3' 348 lct,25-DihydroxY DimethYldioxirane, 142-144,291 274 DihydroxYacetones. DimethYlformamide,144 Dihydroxyacetoneside chain' 80-81 Dimethylformamide dimethyl acetal' 37 274 comPounds, DihydroxYacetonYl Dimethylgallium chloride; dimethylgallium o,c'-DihYdroxYimines,298 triflate' 144 o,c'-DihYdroxYketones,81, 298 145 1,1-DimethYlhYdrazine, c,P-DihYdroxYesters,339 109' 145 N,N-DimethYlhYdrazones, 330 ketones' c,P-DihYdroxY
O,N-DimethYlhY 1,3-DimethYtind DimethYlkctcr n DimethYl m.lor DimethYlmalmYl DimethYl mcthYt 3,3-Dimcthylorcr DimethYloxcdft 2,4-DimethYl-!9 1,4-DimethYSE 2,6-DimethYPta DimethYlPhcs.te DimethYl(PhctY N,N'-DimcthYldimethvlor 196 2.5-DimethYf:n 2,5+rans'Did DimethYlsulfcr DimethYl sullc DimethYl suilc Dimethyl (R.Rl DimethYldrec
(s,s)-N.N'-t
l5Gl5l Diols, 12!126 1,2-Diols.t. 2{ 1,3-Diols. 2Or1,4-Diols.l9'. 1,5-Diols.327 anti-1,2-Diob cis-I,3-Diob. syn-1.3-Diob.' 1,4-Diones.6 DIOP,35 1,3-Dioxats. 1,3-Dioxan4< Dioximincs. 5 Dioxiranes. ll 1,3-Dioxolar traru-Dioxo(r rutheniut Diperoxohcrr molYbda 1,2-DiPhenY trimctby' 1,4-DiPhcnY 1,4-DiPhenY diylmagr DiPhenYldb DiPhenYldb hvdri&.
Subjec'tIndex
hIurr. h !- . . r. .ll).:4.
l-:l drmcth-
thrl-1t h rI ' l -
l! lcn:cnc.
n(' . +()3 1 [ rl - l nc.'1.l-ll | rI n n , t r -
s,i l.
ItrL
-i7
lr lralltum
l.
421
153-158 1,2-Diphenyl-1,2-ethanediamine, 20? O,N-DimethYlhYdroxYlamine, (S,S)-1,2-DiPhenYl-1'21,3-DimethYlimidazolidinone,164 159 ethanedimethYlamine, Dimethylketene trimethylsilyl acetals,292 dimethyl (R,R)-1,2-Diphenylethane-l'2-diol Dimethyl malonate,107' 190 ether, 158-159 39 dichloride, DimethylmalonYl 153-154 1,3-Diphenylethane-1,2-diol, 145 Dimethyl methYlPhosPhonate' 254 (Diphinylhydroxymethyl)pyrrolidine' 232 3,3-DimethYloxetane, 178 esters, DiphenylmethYl Dimethyloxosulfoniummethylide' 146 366 N-DiphenYlmethYlimines, 213 2,4-DimethYl-3-Pentanone, 371 a-(Diphenylphosphinoyl)acetaldehydes, 188 1,4-DimethYlPhenanthrene, azide, 160-161 Diphenylphosphoryl 29 isocYanide, 2,6-DimethYlPhenYl 159-160 (Sj-r,r-blpnenylpropane-1,2-diol, DimethylphenYlsilane'292 160 Diphenylsilane, 146 Dimethyl(phenyl)silyllithium' 160 N,N' -Dimethyl-N,N'-propyleneurea(1,3- Diphenylsilane-Triethylborane, cycloadditions'13-14,105-106 t,3-Dipolar 146-147' dimethyloxohydropyrimidine)' 42 Directedmagnesiation, 196 Directed metallation, 361 148 2,5-DimethYlPYrrolidine, -149 Disiamylborane,86 2,S-trans-Dimethylpyrrolidine, 147 Disparlure, 80 365 Dimethylsulfonium methYlide, "Y-lactones, 2 2,4-Disubstituted Dimethyl sulfoxide, 149 cYcloPentanes,122 Disubstituted 149-150 chloride, Dimethyl sulfoxide-Oxalyl 16l 1,3-Dithiane, Dimethyl (R,R)-tartrate'312 317 Dithioacetalization, 150 Dimethyltitanocene, ll8' 124 (S,S)-N,N'-Dineohexyl-2'2'bipyrrolidine' Dithioacetals, DitosyloxYlationof alkenes, 179 150-151 Divinyl ketones,227 Diols, 125-126 Divinylmethanols'234 1,2-Diofs,8,242,3'11 DMAP. See4-Dimethylaminopyridine 384 365, 327, 294-295, 204, 1,3-Diols, DMI. See1,3-Dimethylimidazolidinone 1,4-Diols, 194, 345-346 DMPU. SeeN,N'-DimethYl-N'N'327 1,5-Diols, propyleneurea( 1,3-dimethyloxohydroanti-L,2-Diols,I 35-136 pyrimidine) 94 cis-1.3-Diols' syn-1,3-Diols,65 1,4-Diones,66 Electrooxidation,202 DIOB 35 c,P-Enals,127 359 300' 149' 1,3-Dioxanes, Enamines,2l'22' 32 365 1,3-Dioxan-4-ones, dihydroxylation,157 Enantioselective 57 Dioximines, 127' 188-189 EndoPeroxides, Dioxiranes,143 Ene cyclization,190 149.300 1,3-Dioxolanes, Enediones,199 rrcns-Dioxo(tetramesitylporphyrinato)Ene reactions, 24, 210-211,212, 321-322 ruthenium(Vl), RuOt(tmP), 151-152 Enol borinates,71 DiperoxohexamethylphosphoramidoEnol silyl ethers,47, 6, 112,216,314'3'15 152 molYbdenum(Vl), couPling,330-331 Enone-aldehYde 1,2-bis(2,4,61,2-DiphenYl126,131, l':-5,2Cf ,216'222' a,P-Enones, 157 trimethylbenzylamino)ethane, 243, 254,272, 292, 316,363,375 198 1,4-DiPhenYl-1,3-butadiene, P,1-Enones,200 1,4-DiphenYl-1,2-butene-1'4Enyne cYclization,263 diylmagnesium,198 1,4-Enynes,98 309 diselenide' Diphenyl Enynones,132 aluminum Diphenyl diselenide-Lithium 127 1,4-Epiperoxides, hvdride' 152-153
4U
Subject Index
Epoxidation,31, 53-54,71,82, 143, 151, 199,207,227,273,379 Seealso Asymmetric epoxidation Epoxide fragmentation,346 Epoxiderearrangement, 211 Epoxides,80, 277 deoxygenation,74 2,3-Epoxyesters,176-177 to-Epoxyalkenes,74-75 Epoxy silanes,242 Epoxystyrene,l7 Esterification,128 Esters,83,163 Ethanedithiol,356 Ethanolamine,162 Ethoxycarbonylation,309 3-Ethoxycarbonyl-2-methylallyltriphenylphosphoniumbromide, 162-163 Ethoxytrimethylsilylacetylene, I 63 1-Ethoxy-3-(trimethylsilyloxy)1,3butadiene,163 Ethyl acetoacetate,202 Ethyl acrylate,148 Ethyl 4-bromo-3-methyl-2-butenoate, 162 Ethyl cyanoacetate, 131 Ethyl diazoacetate, 163-164 Ethyl (Z)-2,3-dibromopropenoate,98 Ethyl 3,4-diethylpyrrole-2-carboxylate, 164 Ethyldiisopropylamine, 359 Ethylene glycol,297 Ethyl (S)-N-(ethoxycarbonyl)pyroglutamate,178 Ethyl cr-(hydroxymethyl)acrylate, 164 Ethyl 3-hydroxy-4-pentenoate, 166 Ethyl isocyanoacetate, I&-166 Ethyl lactate,219 Ethyl (S)-lactate,159 Ethyl 3-oxo-4-pentenoate, 166 I -Ethyl-2-[(piperidinyl)methyl]pyrrolidine, 329 2-Ethylpyridinechromiumtricarboynl,15 Ethyl trifluoroaceticanhydride,357 Ethynylcarbinols, 274 Ferric chloride, 167-169 Ferrocenylphosphines, chiral, 169-170 Fischercarbenes,88 Flavanones.179 9-Fluorenylmethoxycarbonyl groups,101 Fluorination, 170-171, 276, 286-287 o-Fluoro ketones,283
6c-Fluoro-4-cholestenone-3, 276 69-Fluoro-4-cholestenone-3, 276 Fluoro-zyo-inositol, 128 Fluoromethylhomocysteine, 129 4-Fluorophenol,160 p-Fluorophenols,286 N-Fluoropyridiniumtrifluoromethanesulfonate,170-171 9c-Fluorosteroids, l7l FMOC. See9-Fluorenylmethoxycarbonyl groups Formaldehyde,166, l7l, 212 a-Formylalkylphosphonates, 4 Formylation,144 c-Formylcyclopentenone, 52 3-Formylpropanamides, 371 Friedel-Craftsalkylation,l1 Furan annelation.6. 107-108 2(5fl)-Furanones,186 3(2fO-Furanones, 289 Furans,199,290,365 Germoles,122 Gilvocarcinantibiotics,1l8-l 19 Glucals,368 Glucitol, 306 Glycals,143 Glycerolderivatives,109 Glycopyranosylfluorides, 144 C-Glycosidation,45 Glycosidation,64, 120, 144 p-Glycosides,143,348 C-Glycosides, 237 Glycosylation,357-358,368, 369 Glycosylfluoride, 120 Grignardreagents, 4,37, 48, 50,67, ll7, 122,t72-173,2r2, 246,247,248,253, 270,324,385 Grob fragmentation,186-187 Grubbsreagent,150 6-Halohexapyranosides, 308 Halohydrins,339 Heck coupling,245,26l Heck cyclizations,32l Heck intramolecular cyclization, 264-265 Heck-typearylation,35 Heck-type cyclization, 265-2ffi Hemicaronicaldehyde,192 1,6-Heptadiene, 122 2,5-Heptanedione,206
Heptapeptida Hexaburykfri Hexadieoab. i Hexamerhyld HexamcthylC 174 2,4-Hexaul r-Hexccs. Sl HMPA. Sc?l triamb Hofmann dca Homoalllt r Homophtb* Hydratioo. l7 of allc6. Hydrazim. 17 Hydrazobeu Hydridoni{u hexarr. Hydroac.vbrx Hydroaminri Hydrobontn 1,4-Hydrobcr Hydrobontn Hydrocarborl Hydrodchelol Hydrodimrir Hydrofruort r Hydrogcoatir
357.3'n
Seeaho Tn Hydrogenatio Hydrogcn azi
nGln
Hydrogen ird Hydrogenolyr Hydrogen pcr Hydrogen pa 177 Hydrogen pcr Hydrogcn pcr Polyphoq Hydrogen pcr Hydrohalogcr Hydroiodic r cr,s-Hydroisoq Hydromagrc Hydrosilylatio Hydrosilylatir Hydrostannl Hydrosrannyl
SubjectIndex
on\ I
. il-. t:al
425
Hydrovinylation, 51, 267-268 c-Hydroxy aldehYdes,209 olhreo-p-Hydroxy-c-amino esters' 137 3-Hydroxyazetidine-2-one,152 c-Hydroxy benzYloximes,23 3-Hydroxy butanoate' 34 (R)-3-HydroxYbutanoicacid' 178 219 3-HydroxY-2-butanone, c-Hydroxy carboxYlicacids, 203 p-Hydroxy carboxylic acids, 180' 381 c-Hydroxy carboxYlicesters,203 134 4-Hydroxy-2-cYclohexenones, 26I 6-Hydroxy-2,3-dihydro-6H-pyranones, (2SJR)-(--)-2-Hydroxydiphenylmethyl-5(dimethylamino)methylpyrrolidine' 178-179 Hydroxy dithioketals, 300-301 p-Hydroxyesters,19, 137,246 c-Hydroxy ketones, 22 p-HydroxY ketones, 65 1-Hydroxy ketones, 230 80-81 17-Hydroxy-20-ketopregnane, Hydroxylamines,142 Hydroxylation, 6l-62, 257-258,310 2-Hydroxymandelicesters,276 171 HydroxymethYlation, ketones,172 2-HydroxymethYlene 2-HydroxymethYlPYrroles'165 268 5-Hydroxy-1-Pentenes, l7c-HydroxYPregnanes,72 63 4-Hydroxy-2H -PYranones-2, Hydroxypyridines, 361 3-Hydroxypyridines,89 Hydroxyquinone annelation, 207 219 o-Hydroxy-o-quinonedimethanes, -Hydroxy1,2,3,4-tetrahydronaphthalenes' 1 219 ne, 779 IHydroxy(tosyloxy)iodo]benze (R)-( + )-2-Hydroxy-1,2,2-triphenylethyl r77 acetate,180 Hydrogen peroxide-Dimethylsulfoxide, 177 73 Hydrozirconation, acidHydrogen Peroxide-Formic 330 Hypercholesterolemia, PolyphosPhoricacid' 177-178 178 acid, peroxide-Tungstic Hydrogen Ibuprofen,25 Hydrohalogenation,9 Illudol, 112 182 Hydroiodic acid, Imidazole,77 390 cr,s-Hydroisoquinolines, l-Imidazolylcarbonyl glycosides'64 17 I 16-1 Hydromagnesiation, halides, 105 Imidoyl Hydrosilylation, 4l-42, 292, 352, 374 -28 294 Imines, 27 cy clization, Hydrosilylative 29 IminocycloPentadienes, Hydrostannation,320 90-91 Indanones, 378 345' HydrostannYlation,
Heptapeptides,101 Hexabutylditin, 174 Hexadienals,230 Hexamethyldisilazane,305 Hexamethylphosphorictriamide, 146-147, 174 2,4-Hexanedione,2A6 l-Hexoses, 54-55 HMPA. SeeHexamethYlPhosPhoric triamide Hofmann degradation,291 Homoallylic alcohols,200, 244 Homophthalic anhYdrides'307 Hydration, 177 of alkenes,26-27 Hydrazine, 174-175 Hydrazobenzene,22S Hydridotris(triphenylphosphine)copper hexamer,175 Hydroacylation,51 Hydroamination, 42 Hydroboration,33, 86, 205,327 1,4-Hydroboration,66 Hydroboration-reduction,327 Hydrocarboxylationof styrenes,25 Hydrodehalogenation,350' 375 Hydrodimerization, 205-206 Hydrofluoric acid-Boron trifluoride' 176 Hydrogenation,33, 34' 215, 264,354-355' 357,372 See alsoTransfer hYdrogenation Hydrogenation catalYsts,25 Hydrogen azide-Diisopropylethylamine' 176-177 Hydrogen iodide, 86 Hydrogenolysis,269 Hydrogen Peroxide, 250, 379 Hydrogen peroxide-Areneseleninicacids,
425
SubjectIndcx
Indium, 181 Indium(IID chloride, 181-182 Indole-3-acetaldehyde,308 Indoles,319 myo-Inositol 4-phosphate,126 myo-Inositol phosphates,125 zyo-Inositol tetrakisphosphate, 126 rnyo-Inositol 1,3,4-trisphosphate,126 Intramolecularbiaryl coupling,118-119 Intramolecular hydrosilylation, 35 Invictolide, 271 Iodination. 182. 183 Iodine, 182 182 Iodine-Borane:N,N-diethylaniline, Iodine-Silver nitrite, 183 1-Iodoalkanes, 93 184 1-Iodo-1-alkenes, Iododiphenylphosphinate,77 Iodohydrins, 199, 272-273 Iodolactamization, 182 Iodomalononitriles,183, 183-184 fl84 Iodomethylenetriphenylphosphorane, Iodomethyltriphenylphosphoniumiodide, 184 lodomethylzinciodide, 184-185,239 N-Iodosuccinimide. 183. 185-186 Iodosylbenzene, 158, 186 Iodosylbenzene-DicyclohexylcarbodiimideBoron trifluoridediethyl ether, 186-187 Iodosylbenzenetetrafluoroborates,187-188 Iodotrimethylsilane, 188-189 Iodotyrosine, 96 9-Ionone,65 Iron, 188-189 Iron(III) chloride, 190-l9l Iron(II) iodide, 366 189 Iron(III) 2,4-pentanedionate, Iron(III) sulfate,191 bromide, ll6 Isobutylmagnesium 3l9 1-Isobutylnaphthalene, p-Isobutylstyrene, 25 Isoflavones,1'19,326 Isoindolobenzazepine,290 Isoindolobenzazocine,37-38 Isomerization of allylic amines,32 of epoxides,370 Isonitriles,358 Isoprene,94 1-Isopropylidene-2-indanone,257
191Isopropylidenetriphenylphosphorane, 192 Isoxazolidines,14 Jatrophone,26 Jones'soxidation,166 Julia synthesisof alkenes,297 Kadsurenone,274 Ketene acetals,391 [2 + 2]Ketene-allenecyclization, 78 Ketene silyl acetals,19, 221 B-Ketosulfoxides,134-135 1-Keto aldehydes,230 'y-Keto amino acids,2z16 p-Keto esters,305 5-Keto-o-fructose,306 5-Keto-o-glucose,305 c-Keto-pJactams,311 c-Ketols, 178 c-Ketomethylaryliodoniumsalts,187-188 Ketones,370 71 17-Ketosteroids, 65-l7-Ketosteroids.l5 I Khellactones,128 Kinetic resolution.33. 35. 380 Kjellmanianone,62 Knoevenagelreactions, 190 Koser'sreagent,179 Lactams, 2W-201,275-276,355 p-Lactams,78, 99, 127, 185-186 1-Lactams,182 Lactones,130-131,163,283-284,285, 359 P-Lactones,116, 327-329 "y-Lactones, 34, 201 6-Lactones,25 Lactonization, 200 Lardolure,359 Laweson'sreagent,37-38,350 Lawessonthionation,350 LDBB. 195-196.232 LDMAN, I95 Lead tetraacetate,193-194 Limoncne,377 Lindlar hydrogenation,193,388 Lipoxin AaandBa,322 Lithiation, 195 ortho-Lithiation, 56 r-Lithioalkoxides,195
cr-Lithiodkyt 2-Lithio-l-}d 2-Lithiorcrel Lithium di{-l Lithium alur Lithium N-br Lithium boro Lithium chlcr Lithium dieD Lithium dirso Lithium dic Lithium hcr| Lithium }lid Lithium nepl Lithium tn-F Lithiuo Lithium tn-r Lithium rta Lithium trir Loratadinc. l Luche alhla
McMurr_vo Macroc.vdr Macrocyrdizr Macrolrrc Macrolidcs. I MAD. Sc?t butyl-|r Magallanes Magnesium MagnesiumI Magnesiumr Magnesiumt Magnesium Manganescr
2u2-m
Manganesc Manganesc dionatc Mannich rer Markovniko Marschalk n MCCPM. S 4diqd phocph Menthol. !) Menthonc.i /-Menthyl
SubjeclIndex fr..rane.191-
rn.
-S
slrr.187-188
i*" lFr :r15.359
Ir.
4n
Menthyl phenylglyoxalate,203 Menthyl p-toluenesulfinate,135, 204-205 Mercury,205-206 Mercury(Il) acetate,377 Mercury(II) trifluoroacetate, 99, 377 Metal acetylides,52-53 75 Metallapyrrolines, Metallation.SeeDirectedmetallation; Transmetallation Methacrolein,166 chloride, 172 Methallylmagnesium Methanesulfonylazide, 357 Methanetricarboxylicesters,2(X) Methioninesulfoxide,129 1-Methoxy-1,3-bis(trimethylsilyloxy)-1,3butadiene, 206-207 25 l-Methoxy-1,3-butadiene, 2l 7 Methoxycarbonylmethylation, 2,3-Methoxy-1,5-dihydro-3H-2,4l8 benzodioxepine, Methoxyethylallyl ether, 373 207 (Methoxymethoxy)allene, N-Methoxy-N-methyldiethylphosphonoMcMurry coupling, 331-332 acetamide.207-208 2-(Methoxymethyl)pyrrolidine, 208-209 Macrocycliclactams,160-161 Methoxymethylvinyl ketone,337 Macrocyclization,184 25 78, 353 1-Methoxy-1,3-pentadiene, Macrolactonization, Methoxy(phenyldimethyisilyl)methyllithium, Macrolides, 83-84 209 MAD. SeeMethylaluminumbis(2,6-di+Methylal, 166 butyl-4-methylphenoxide) Methvlaluminumbis(2.6-di+-butyl-4Magallanesine, 37-38 methylphenoxide), 2ll, 212 Magnesium,198-199 Methylaluminumbis(2,6-di-r-butylphenMagnesiumbromide,8-9, 116, 199 Magnesiumiodide, 199 oxide). 209 -2,6-di-tMagnesiummonoperoxyphthalate,199-2W Methylaluminumbis(4-bromo Magnesiumoxide, 200 butylphenoxide), 209-212 Manganesedioxide-Chlorotrimethylsilane, Methylaluminumbis(2,6-diisopropylphen202-203 oxide\,212 Manganese(Ill) acetate,2W-202 Methylaluminumbis(2,6Manganese(II)tetramethylheptane-3,5diphenylphenoxide),209-210,212-213 212 dionate,203 o-(Methylamino)benzenethiol, 44 Mannichreaction.391 Methyl 4-aminobenzoate, Markovnikovaddition, 182 Methylation,225,275 213 Marschalkreaction,171 Methyl azodicarboxylate, MCCPM. See(2S,4S)-N-Methylcarbamoyl- Methyl benzenesulfenate, 214 4-dicyclohexylphosphino-2(diphenylc-Methylbenzylalcohol,15 phosphinomethyl)-pyrrolidine 214 Methyl bis(l-naphthyl)bismuthinate, Menthol,203 N-Methyl-N,O-bis(trimethylsilyl)hydroxylMenthone,204 amine,215 /-Menthyl diazoacetate, 39 Methvl bromoacetate.342
cr-Lithioalkylphosphonates, 3-4 2-Lithio-1.3-dithianes. l6l 2-Lithiotetrahydropyrans,195 Lithium di-r-butylbiphenylide,195-196,232 Lithium aluminum hydride, 109 194 Lithium N-benzyltrimethylsilylamide, Lithium borohydride, 66 194 Lithium chloride-Dimethylformamide, 236 Lithium diallylcuprates. Lithium diisopropylamide,196-197 Lithium dimethylcuprate,124 Lithium hexamethyldisilazide,16, 357 Lithium 3lithioalkoxide,232 214 Lithium naphthalenide, Lithium tri-t-butoxyaluminumhydrideLithium iodide, 197 Lithium tri-sec-butylborohydride,324 Lithium triethylborohydride,72, 110 75 Lithium trimethylsilylbenzylamide, Loratadine,176 Luche allylation,386
4A
Subjec'tIndex
(3-Methyl-2-butenyl)triffuorosilane' 9 (25,4S)-N-Methylcarbamoyl-4-dicyclohexylphosphino-2(diphenylphosphinomethyl)-PYrrolidine,214, 215-216 Methyl chloroformate, 159 alcohol,216 cr-MethylcinnamYl Methylcopper-Diisobutylaluminumhydride' 216-217 16o-Methylcortexolone,81 Methyl crotonate, 194 Methyl cYanoacetate,200 2-Methylcyctohexanone,248 MethylcycloPentane,l17 l0 2-Methyl-1,3-cyclopentanedione, 1-Methylcyclotridecene'124 Methyl diazoacetate, 217 Methyl 2,2-dimethyl-1-cyclopropenecarboxYlate,217-218 Methylenation,150,393-394 cr-Methyleneketones,316 c-Methylene-1-butyrolactones,164 143 1-Methylene-1-butyrolactones, 279 MethylenecYclohexanes, 210-21| Methylenecyclohexanols, 208 MethylenecYclohexanones' 279 MethylenecYcloPentanes, c-Methyl-B,yenoates,234 Methyl 6cr-fluoroshikimate,273 Methyl glyoxalate,24 80 6-Methyl-1-hePtanal' Methyl (R)-3-hydroxybutyrate,218-Tq Methyl ketones,219 219 Methyllithium-Chlorotrimethylsilane, Methyl (R)-(-)-mandelate, 180' 219-220 Methyl (S)-mandelate,219-220 Methyl c-methoxyarylacetates,275 N-MethylmorPholineN-oxide' 325 Methyl l-naPhthYlsulfide, 220 (S)-l -Methyl-2-[(N- I -naphthylamino)methYllPYrrolidine,220 N-Methylnitrones,215 N-Methyl trifluoromethanesulfonamide,225 o-Methyl deoxYbouvardin,97 l0-borabicyclo[3.3.2]l0-Methyl-9-oxadecane,22l Methyl 3-oxobutanoate,34 l-ol, 2zl4 2-Methyl-1-phenyl-3-butene(S)-l-Methyl-2-[(piperidinvl)methvl]pyrrolidine,221-222 2-Methyl-P-ProPiolactone,222 Methyl proPYnoate,355
(2-Methylpyridine)tricarbonylchromium, 286 35 1-Methyl-2-PYrrolidinone, N-Methyl-2-PYrrolidinone'87 Methyl 2-siloxycyclopropanecarboxylate' 335 (S)-(-)-Methyl 1-naphthylsulfoxide,220221 MethylthiofurYlcarbene,91 Methyl thioglYcolate,62 Methyl triacetylshikimate,105 dione,223-224 4-Methyl-1,2,4-triazoline-3,5Methyl(trifl uoromethyl)dioxirane, 224 46 3-Methyl-2-(trimethylsilyloxy)-2-pentene, 4-Methylurazole,223 Methyl vinYlketone, 112,337 N-Methylviologen,2T6 Mevinolin,330 Michael reactions, 19, 97-98' ll2' l3l-132' 164,237,286 Michael-typeaddition,391 Midland'sreagent,280 Mitomycins,230 Mitsunobureaction, 142,169,213,225 MK-927,254 Molybdenum carbonYl,225-226 Molybdenum(VI)oxide-Bis(tributyltin) oxide,227 MonoacYlation,112 MonoperPhthalicacid, 273 H-Montmorillonite'25 2-Morpholinobutadienes,227 MTAD,223 , 46 Mukaiyama aldol reaction, 36-3'1 reaction,375-376 Mukaiyama-Michael Mukaiyamareactions,l1l' 314 Mukaiyama'sreagent,78 Muscarine,289 Muscone,124,343 144 1-NaphthalenacarbaldehYde' acid' 1l0 1-Naphthalenecarboxylic 77 Naphthalenes, NaphthalYnezirconocene,77 p-Naphthol,lq) Naphthols,229 77' 102 Naphthoquinones, I l9 Naphthylisoquinolines, Naphthyl ProPargYlether, 69 Naproxen,25,133 Nazarov cyclization, 16'l-168
Naz Neq Ned Ni.t Nid Nim Nid
Niu Niu Niu 2-N 2-(t Ni! N-f Nin Ni! Nit No
(lr (ls
No
l.? Oc G
ol q
Or ol
o o o
o o o o o o o o c c c
C
( ( ( ( (
Subjec{Index
nr
Nazarov reagents,lffi , 227 Neocarzinostatin,52 Neolignans,274 Nickel boride, 228 Nickel cyanide, 228 Nimbidiol, 214 Niobium(III) chloride-Dimethoxyethane, 229 Nitriles, 95, l3l-132, 177,282,296'317 Nitro aldol reaction, 164 Nitro alkenes,241 acid, 82 2-Nitrobenzeneseleninic 2-(Nitromethyl)-2-cyclohexen-l-one'208 Nitrones, 142 291, 308 N-Nitrosoamides, Nitrosobenzene,230 Nitrosolactams,291 Nitryl iodide, 183 Norephedrine, 230-231 ( lR,25)-NorePhedrine, 191-192 ( I S,2R)-NorePhedine, 277 Nozaki reaction, 93 123 1,7-Octadiene. OctaethylPorPhYrin,166 O-Glycosidationof Phenols,121 Olah's reagent,283 Oppolzer'sauxiliarY,58-61 O rganobis(cuPrctes), 237-238 310 Organoboranes, Organocerium reagents,232 OrganocoPPerreagents,232-238 reagents,184-185'238Organocopper/zinc 241 235 OrganocyanocuPrates, Organoiron reagents,241 Organolead reagents,242 Organolithium comPounds,242 bromides, 243 Organomanganese halides, 243-244 Organomanganese iodides, 243 Organomanganese OrganomolYbdenumreagents,244 OrganoPalladiumreagents,245 Organotitanium reagents,245-246 Organoytterbium reagents,248 Organozincreagents,203' 246-248 Osmium tetroxide, 157' 249-253 Osmylation, 249-250,253 Oxapolycycles,289 Oxaspirolactones,232 OxaunomYcin,360
4It
Oxazaborolidines,178, 253-255 Oxazolidinones,chiral, 255-257 2-Oxazolines,20 Oxepanes,335-336 Oxetanes,152-153.195-196 224 Oxidation, 69, 81-82, 143-1.43, Oxidative decarboxylation-deoxygenation' 381 Oxidative phenolic coupling, 190, 326 N-Oxides,379 ct-Oximation,57 cr-Oximinoesters,331 o-Oximino ketones, 57 Oxiranes,45,199 Oxiranyllithium reagents,55 206 1,5-OxoaldehYdes, p-Oxo esters,34 Oxocenes,300-301 Oxoindolizidines,275 Oxolanes,152-153 Oxone,285 l2-OxophYtodienoicacid, 2 261 1,4-Oxyamidation, Oxygen,singlet,257-258 Oxymercuration, 37'l-37I OxymethYlation,115 Palladium(II) acetate,259-263 Palladium(II)acetate-N,N' 263 Bis(benzylidene)ethylenediamine, formate' acetate/Potassium Palladium(II) 263-26/. Palladium(II) acetate-Triethoxysilane'264 Palladium(II) acetate-Triphenylphosphine' 2&-268 Palladium(II) chloride, 268-269 Palladium hYdroxide,269 (R)-Pantolactone, 269-270 ParaformaldehYde,212 bicyclization,113-114 Pauson-Khand reaction,351 Pauson-Khand Payne's rcagent,273 Penicillin,178 372 PentasPirocYcles, (Z)-PentenYlboronates,270 4-Pentynol-2,334 Peptides,163 Peracetic acid, 127' 220 PerfluorobutYric acid, 292 Periodic acid-sodium bisulfite, 272-273 Periodinaneof Dess-Martin,27l-272
43{f
Sobjec'tIndex
Peroxybenzimidic acid, 273 Perylenequinones,168-169 Pfitzner-Moffatt reagent, 186 Phase-transfercatalysts,86 I 44 3-Phenanthrenecarbaldehyde, Phenanthridinones,23 I,lGPhenanthroline,231 p-Phenethylalcohols,115 Phenolic oxidative coupling, 381-382 Phenols,310 Phenoxythiocarbonylesters,346 l-Phenylacetylene,76 Phenylcyclohexanol,113 thane, 273 Phenyldiazome 2-Phenylethanol,33, 389 118 2-(2-Phenylethenyl)-1,3-dithiolane, l-Phenylethylamine, 186 l-Phenylglycine, 257 Phenylglycinol,40 Phenyliodine(III) bis(trifluoro acetate),274' 275 Phenyliodine(III) diacetate,275 Phenyliodine(III) diacetate-Iodine, 275-276 Phenyliodine(III) difluoride, 276 8-Phenylmenthol, 276-277 8-Phenylmenthylglyoxylate, 276 Phenyl-2-oxazolidinone,257 (1S,2R)-(+ )-[-Phenyl-2-(lpiperidinyl)propanol-|, 277 (S)-l-Phenylpropanol, 179 py nyl)hydr azine,223 (3-Phenyl-2-pro cation, 19-21 Phenylselenoetherifi 8-Phenylselenylalcohols, 153 1-Phenylselenylalcohols, 153 Phenylsulfonylallene,107 c-Phenylthio ketones, 277 3l I 3-(Phenylthio)-2-azetidinones, 279 2-(Phenylthio)-1,3-butadienes, Phenylthioenol ethers,277 (Phenylthiomethylene)triphenylarsorane, 277-278 2-(Phenylthio)tetrahydropyrans,195 Phenylthiotrimethylsilane,278 ( l -Phenylthio-I -trimethylsilyl)allyl'9borabicyclo[3.3.l]nonane, 278-2'19 3-Phenylthio-2-(trimethylsilylmethyl)propene, 279-280 Phenylzincchloride, 264 Phleichrome,168 Phosphineoxide carbanions,383 371 Phosphinoylacetaldehydes,
Phospholes,122 Phosphoniumylides, 383 Phosphorylcarbanions,383 Phthalic dicarboxaldehyde,229 Phthalides,34 Pinacol coupling, 294 Pinacol cross-coupling,370-371 Pinacol reductive coupling, 387-388 1]nonane, B-3-Pinanyl-9-borabicyclo[3.3. 280-281 Piperazine,231 Piperidine synthesis,305-306 l-PiperidinocycloproPanol,281 Pivalic acid, 297 Polyenecyclization, 214 Polyenemacrolide antibiotics, 303 177 PolymethoxyacetoPhenones, Polyolefi n cy clization, 372 1,3-Polyols,197 Polyols, 45-46 Polypeptides,96, 196-197 Polyphosphoricacid, 176, 177 Poly(4-vinylpyri dine), 282 Potassium9-sec-amyl-9-boratabicyclo282 [3.3.1]nonane, PotassiumdiisoproPYlamide,175 Potassiumfluoride, 282 Potassiumhexamethyldisilazide,282-283 Potassiumhydrogen fluoride, 283 Potassiumpermanganate'Copper(II) sulfate, 283-284 Potassiumperoxide-Phenylphosphonic dichloride, 284-285 Potassiumperoxymonosulfate,285 PPA. SeePolyphosPhoricacid Probe disruptors, 377 Proline,253 Prolinol propionamide, 302 Propargyl acetates,175 Propargylation,246 Propargyl esters,280 Propargylicalcohols,387 Propargyliodomalononitriles,183 (S)-Propranolol,215 Propynylation, 336 Proton Sponge,381 Pterocarpans,338 Pummererreaction,54 Pummerer-typereaction, 311 2H-Pyran,225-226 159 Pyridine-3-carboxylaldehyde,
Pyridinct ([pilu-Pwl Pyridiniu Pyridiniot 2E62 Sridiniu Pynoh-2. Pyrrohs. Pynolc q Pynoliln 4-hrrrolid SrrolirAt-Pynol Pyrrolizil
furrokir \ryliun Quebrrd P-Quitu Quinor
Radfu:l r asymE Radical r of dty of hel Radizl t Rambc4 l,+Rcd Reducrx Redrrrn Refornr Rhodiu Rhodiu Rhodic Rhodir r-Rhofi Rhodr D-Rih* Rielc ri Ring cq Rincr n Robim Rocc bc Ruttrri Ruttrri
Saliclpf Samari sill Samarir
SubjectIndex
B nane.
Pyridine-2,6-dicarboxylicacid chloride' 41 ([pi]qPyridine)tricarbonylchromium,286 Pyridinium betaines,230 Pyridinium poly(hydrogenfluoride)' 286' 286-287 Pyridinium p-toluenesulfonate, 287-288 Pyrrole-2-carboxylates,165 Pyrroles,281 Pyrrole synthesis,89-90, 164-16f,229 Pyrrofidines, 302, 306, 322 4-Pyrrolidinopyridine, 128 Pyrrolines, 281 At-Pyrrolines,106 Pyrrolizidines,281 Pyrroloindoles,230 Pyrylium perchlorate, 288 Quebrachitol,128 p-Quinone methides,392 Quinone synthesis,102
Cl0-
f :-llt3 ll t pntc
(
Radical reactions, 147-148 asymmetric,60-61 Radical reduction, 373, 374 of alkyl halides, 374 of halides, 373-374 Radical ring exPansion,343-344 5 rearrangement, Ramberg-Blackland 1,4-Reduction, 65, 216 Reduction of carbonyl compounds'360 Reductive cleavageof epoxides,388-389 Reformatsky reaction, 387 Rhodium(II) carboxylates,289-292 Rhodium(III) chloride,291 Rhodium(Il) perfluorobutyrate, 292 Rhodium(II) pivalate,361 1-Rhodomycinone,307 171 Rhodomycinones, o-Ribulose, 298 Rieke zinc, 387 Ring expansion,167, 193-194 Ritter reaction, 52 Robinsonannelations,ll2 Rose bengal, 257 Ruthenium(Vlll) oxide, 292-293 Ruthenium tetroxide, 292-293 Salicyaldehyde,255 Samarium(III) chloride-Chlorotrimethyl' silane, 300 Samarium(II) iodide, 294-300
431
SAMP. See(S)-1-Amino-2-methoxymethyl1-pyrrolidine Sarcosine,196 Schwartzreagent, 73 Selenoesters,20 Selenoetherification,21 32 Selenoketones, Selenolactonization,2l 122 Selenophenes, Selenoxideelimination, 62 120 Selenoxides, Sensitizers,100 dihydroxYlation,153 Sharpless reagent,120 Sharpless Silicagel, 191 Siloles,122 Silver-graphite,387 Silvernitrate,84 Silverperchlorate.300-301 Silver trifluoroacetate,301-302 Silver trifluoromethanesulfonate,302 Silyl dienol ethers,14-15 Silylenol ethers,31,48,111' 146'364 Silyl ethers, 292 Silyf keteneacetals.146-14'1 O-Silyl keteneN,O-acetals,302-303 333 Silyloxyacetylenes, 21I B-silyloxyaldehYdes, I 67 Silyloxycycloalkanecarbaldehydes, ales, 217 Sifyloxycyclopropanecarboxyl 14 (Silyloxy)methYlbutadienes' reagent,'107,184,239 Simmons-Smith Singletoxygen,285 Sodium-Ammonia,303-3M Sodium borohydride, 304, 304-305 Sodium cyanoborohydride'305-306 184 SodiumhexamethYldisilazane, Sodium hexamethyldisilazide'307 Sodium hydride, 307-308 Sodium hydride-sodium t-amyl oxide' Nickel acetate,308 Sodium hypochlorite, 308 Sodiumnitrite, 57, 308-309 Sodium perborate, 310 Sodium phenylselenotriethoxyborate,309 309 Sodiumtetrachloropalladate(II)' Sodium triacetoxyborohydride,309-310 Sonication, 107, 377, 387 Seealso Ultrasound Spiroannelation,364 Spirocycles,138
432
SubiectIndex
SpirocYclization,266 Spiroketals,232 Siirolactams' 200 Stannoles,122 StannYlcuPration'232 StannYlquinones,351 (3S,4S)-Statine,304 Statine, 45 SterePolide'263 SterPurene,104 Stiboles, 122 Stilbene,Lsl,l53'249 Stilbenediol, 101 cis-stilbenes,373 Stille couPling,261, 35t 22 Si.""t- "'"rnino nitrile synthesis' Styrene, 38-39 Styrene oxide. 384' 389 55 2-Substituted1,3-dithianes' 181 Sulfides, Sulfines,284 4 N-iofnnyf -puoluenesulfonamide' Sulfones,320 310-311 N-Itii""vf -f *za'1,3-butadienes' Sulfoxides, 120 Sulfuryl chloride, 83' 3lr Sulfur Ylides,84-85 B-Sultams,62-63 Suzuki reaction' 221 Swern oxidation, 317 Swernreagent,149'325
sulfate' 262 Tetrabutylammoniumhydrogen 317 Tetrachlorosilane, loo ii.s, lGr."u.Yanoanthracene' i.iii. "' ^" i!,zo-r"ti-2,6-dichlorophenvlpor199 piinu,.tunganese(Ill) acetate' 266 Tetraenes, Tetrafluoroboric acid' 273
21'58'95'196' i"rtJvii"tt."ns, 19-20' 33s 268-269,316' 21'.58' 366 TetrahYdroPYrans,
3l I i :.r,+-r"tiirtvdropyridines' 3l7 ii,t"r.r.?iitpn.nvlphosphine)nickel' i.it"liti,tibrt"nylphosphine)palladium' 317-323 1-Tetralone,41 TetramethYlammonium.. triaceioxYborohYdride'324 146 TetramethYleihYlenediamine' dichloride' i.it"rn.irttr.nylenediaminezinc 324 256 fetramethytguanidinium azide' 42' 48 ;5' 'Z.z.i,i-i"**ethylpiperidinvliii,i';^ethYlPiPeridine' l-oxyl' 324-
Tantalum(V) chloride'Zinc' 312 (r-)-Tartaricacid' 304'305 15 iri,R)-r.ttuti. acid' 312-3 Tartaric acid, 331 SeeTris[2-(2'methoxyethoxy)rie-r. ethvllamine Tebbereagent.70-71'150 Tellurium(IV) chloride' 316 Tellurium-Wittig reactions' l1l TEMPO. See2,2,6,6' I -oxYl TetramethYlPiPeridinYlTestosterone,71 ii,i,t't*rur"nzyl-p-glucopyranosyl fluoride, 357 2,4,4,6'Tet abromo-2'5-cyclohexadienone' 316-317 262 TetrabutYlammoniumchloride'
325 lactosylz S,i,Z--r etr^ -o'pi valoyl' 9-D- Ba 391 amine, 325 f.tru'propyf u*monium^perruthenate' JZ) acetate' Thallium(Ill) Thallium(Ilt) nitrate' 326 ThexYlborane.327 237 i-ftti*vf (.Vuno)copperlithium' 199 Thioacetals, Thiomidization, 37-38 Thionoesters,374 Thionolactones'350 ThioPhenes,122 -329 ThioPhenol, 196' 327 195 Z-fttioptt"nVrt"trahydropyrans'
352-353 inri"-i"*ti,r".nt aldolsynthesis' l-Threonine' 234 Tislate esters.129 tii(tl) ctrtoriae,164' 329 tin(It; triflate, zzt ii;iiii,t'il";"methanesulfonate'Dibutvl' tin diacetate,329 294 Tishchenko-tYPereaction' Titanium enolates,332-333 Titanium(Ill) chloride' 330
aluminum iii""rt.irui chloride-Lithium 330 hYdride,
Titaniuo
3vL
TitaniuD 331 Titaniun 332 Titaniul Titaniu! Titaniul isoP Tilaruul 339 Titaruur Titanrur pro Titaniu Titanc Titanor TMED p-Tolu a-T6.V Trans& Transfi Transa Trialll Tri.o{ Tribur Tribril Tribul
]
1-Tnt Trih! Trih! l Trib{ I Tribit Trib{ Tribr 1.23 Tri{ Tri<
vtc-| vic-" 2.4.
,,)
Trr Trk Tri
SubjectIndex
l-
n t
l:1-
tt
l--i: l
trr\ l-
433
p-Trichlorotelluroketones,316 / Graphite, Titanium(III) chloride-Potassium 381 Trichloro(p-tolylimino)vanadium(V), 330-331 borohydride, Trienols,330 Titanium(III) chloride-Sodium Trienones,132 33r. Triethoxysilane,264 33lTitanium(III) chloride-Zinc/copper, acetate,354Triethoxysilane-Palladium(II) 5JZ 355 Titanium(IV) chloride,36, 44, 107,332-337 Triethylaluminum,355 Titanium(IV) chloride-Aluminum,337 Triethylborane,60, 160, 344, 350 Titanium(IV) chloride-Titanium(IV) Triethylgallium,355 isopropoxide,337-338 couple, Triethyl phenylsulfinylorthoacetate, Titanium(IV) chloride-Zinc/copper 355-356 339 Triethylsilane,356 Titanium(IV) isopropoxide,339 356 Triethylsilane-Dodecanethiol, + )-DiisoTitanium(IV) isopropoxide-r--( 356 Triethylsilane-Palladium, propyl tartrate, 339-341 Triethylsilane-Trifluoromethanesulfonic Titanium(IV) isoproxide,313 acid, 357 Titanocenedichloride,150 Trifluoroacetic acid deprotection, 356 335 Titanoxycyclopropanes. 357 TMEDA. SeeTetramethylethylenediamine Trifluoroacetylation, Trifluoroethanol, 88 p-Tofuenesulfonylhydrazine,340-341 Trifl uoroethyl trifluoroacetate,357 of ketones,179 o-Tosyloxylation anhydride,144, Trifluoromethanesulfonic Transfer dehydrogenation,130 3s7-358 Transfer hydrogenation,40 l, 1,I -Trifl uoro-2-propanone,224 73, 239,257, 341 Transmetallation, 359 Triisobutylaluminum, Trialkylzincates,324 Triisopropyl phosphite, 360 Tri-o-biphenylphosphite,29 TrinrethylamineN'oxidc, 360 Tributylarsine, 342 Trimethylboroxine, 253 nyl)tin, 342-343 Tributyl(isopre Trimethyl orthoformate, 275 341Tributyl[(methoxymethoxy)methy|tin, Trimethyloxoniumtetrafluoroborate,104 342 1,3-butadienyl)silane, Trimethyl(4-phenyl1-Tributylstannylalcohols, 186 118 Tributyltin fluoride, 221 triflate, 170 . Tributyltinhydride,20,147,160,181,184, 2,4,6-Trimethylpyridinium 292 Trimethylsilane, 343-349,344 Trimethylsilylacetylene,98 Tributyltin hydride-Copper(I)iodidel-alkenes,361 TrimethylsilylLithium chloride.350 Trimethylsilylcyanation,339-340 350 Tributyltin hydride-Triethylborane, Trimethylsilylcyanide,303 1 Tributyltinlithium,350-35 361 Trimethylsilyldiazomethane, Tributyltin methoxide,351 Trimethylsilylesters,85 compounds,299 1,2,3-Tricarbonyl p-Trimethylsilylethoxymethylchloride, 361 351-352 Tri-o-carbonylhexacarbonyldiiron, Tri-o-carbonylnonacarbonyltetrarhodium, 1-Trimethylsilyl propargylic alcohols, 1l6 (Trimethylsilyl)methylmagnesiumchloride, 352 118 vic-Tricarbonylcompounds,27l-272 O-Trimethylsilyl monothioacetals,181 vic-Tricarbonylsystems,285 (2-Trimethylsilyloxy)allyltrimethylsilane, 2,4,6-Trichlorobenzoylchloride, 353 361-362 2,2,2-Trichloroethylphenyl sulfoxide, 355 186,301 2-(Trimethylsilyloxy)furan, Trichloroisopropoxytitanium,353-354 2-Trimethylsilyl-2-propenylmagnesium Trichloromethyl carbonate,354 chloride, 172 Trichloromethyl chloroformate, 257
434
SubJectIndex
2-(Trimethylsilyl)thiazole,362 Trimethylsilyl trifl uoromethanesulfonate, 49, tl2, 138, 278, 363-3& Trimethylsilyl trifl uoromethanesulfonateTitanium(IV) chloride, 364 Trimethylstannylcuprates,232 Trimethylsulfonium methylsulfate,364-365 Trimethylsulfoxoniumiodide, 146 l-Trimethylthioalkynes, 393 Trineophyltin hydride, 373-37 4 1,2,3-syn-Triols, 7-8 Tioxane,79,2l2 Triphenylcarbeniumhexachloroantimonate, 365-366 Triphenylmethyl bromide, 375 Triphenylphosphine/Carbontetrabromide, 366 Triphenylphosphine/Carbontetrachloride, 36-367 Triphenylphosphinehydrobromide, 368 Triphenylphosphineoxide-Trifl uoromethanesulfonic anhydride, 368 Triphenylphosphine-Titanium(IV)chloride, 367 Triphenyltin hydride, 20 Triphenyltin hydride-Triethylborane,368369 Triplex Diels-Alder reactions,30, 100 Tris(4-bromophenyl)aminiumhexahaloantimonate,369-370 Tris(o-chloro)hexakis(tetrahydrofuran)divanadium hexachlorodizincate,370372 Tris(dibenzylideneacetone)dipalladium (chloroform), 372 Tris[2-(2-methoxyethoxy)ethyl] amine, 372373 Tris(methoxyethoxypropyl)tin,373 Tris(2-methoxymethoxyphenyl)phosphine, 373 Tris(2-methyl-2-phenylpropyl) tin, 373-374 Tris( l-naphthyl)bismuthine,214 Tris[(trimethylsilyl)methyl]aluminum,374 Tris(trimethylsilyl)silane,374-37 5 Trityl bromide, 374 Trityl hexachlorostibnate,370 N-Trityl c-amino acids,375 Trityl perchlorate,375-376 Tryptophans, 308,392 TTN. SeeThallium(Ill) nitrate
Two-carbon ring expansion,71 B-Tyrosine-O-methylether, 265 Ubiquinone,343 Ullmann coupling, 308 Ullmann reaction, 96-97 Ultrasonic activation, 149 Ultrasound, 377-379 c,p-Unsaturatedacids,228 Unsaturatedepoxides,94-95 o,P-Unsaturatedesters,333-334 p,1-Unsaturatedesters,309 to-Unsaturatedfatty acids, 291 c,B-Unsaturatedlactones,140 Urea-Hydrogen peroxide, 379 6-Valerolactones, 131 l-Valine, 337 Valinol, 255 l-Valinol, 15,41,380 Vanadium oxytrichloride, 381 Vanadium oxytrifluoride, 381-382 Vancomycinantibiotics, 326 Vedejs hydroxylation, 152 Vilsmeier rcagent, 144 Vineomycin 82, 120 Vinylation, 259 Vinyl cuprates,73 2-Vinylcyclopentene-1,3-dione, 88 Vinylcyclopentenediones,88-89 Vinylcyclopropane,369-370 Vinyl iodides,184 2-Vinylnaphthalene,25 Vinyloxyborane, 135 Vinylsilanes,25-26 Vinylstannanes, 26-267, 345 Vinyl sulfides, 174 Vinyl sulfoxides,235 Vinyl triflates, 26, 110,26-267 Vinylzirconates,73 Vinylzirconiums, 73 Visnagan,9l VitaminBr2,93 VitaminK,33 Water, 383 Wharton reaction, 175 Whistlers, 377 Wilkinson'scatalyst,88, 302 Wittig conditions,373
Wirrig-ll winig-lk Wirtig-ll Winig rez Wittig r.: Wittig-r1 Wittig-n1 2,6Xvhl
Ytterbiun Ytterbiul
Ziegler-N Zinc. 3E6
SubjectIndex Wittig-Horner elimination, 371 Wittig-Hornerreaction,130' 145 Wittig-Horner reagents'206' 383 Wittig reactions,15, 55' 142 Wittig reagents,295' 383 Wittig-typecYclization,367 Wittig-typereaction,342 2,6-Xylyl isocYanide,298 Ytterbium,384 Ytterbium(III) chloride,384-385 Ziegler-Nattapolymerization,1l7 Zinc.386-387
435
Zinc in acetic acid,7'l Zinc borohydride, 388-389 Zinc bromide,64, 389-391 Zinc chloride, 391-392 Zinc-CoPPercouPle,387-388 Zinc-CopPer/silvercouPle, 388 Zinc iodide, 105 e, 392-393 Zinc trifluoromethanesulfonat Zirconaaziridine,75 ZirconabicYcles,122 Zirconocenedichloride, 72 Zirconocenedichloride-DibromomethaneZinc,393-394 Zirconocene-4-dimethylaminopyridine complexes'393 ZrCp2,121-122
