i ha;rI, L .^-t' . t .. . . ' | ' r
Fieserand Fieser's
Reagentsfor OrganicSynthesis VOLUME SEVENTEEN
Mary Fieser Harvard University
PUBLICAIION A WILEY-INTERSCIENCE John Wiley & Sons, Inc. NEW YORK / CHICHESTER / BRISBANE / TORONTO / SINGAPORE
,i}-
\.
' ( ) I v li
I
ADVISORS JEFF ROHDE
MARK BIL,ODEAU
STRUCTURE COMPOSITION TIMOTHY GRINSTgweR
MIHer Azrrutoene MeRr Russerr MencaRsr Hsu
Ttu JeursoN Tee Bun SHIN Onr-euoo ScHRRBn SspBsRSaRsHe,n
PROOFREADERS MlcHRnL H. KRESS
RBssccaM. MensH RrcHenoM. GoonveN
ALEXANDER R. MucI DAVID H. RIPIN BRYAN E. R0BERTS
JAY F. LARRow
Dnsoneu EvReno
Susan L. VeNnsRvsr-op, DEBORAH T, HuNc
KARLENE A. CIMPRICH
PI ltl r{l d
F d
It
paper' This text is printed on acid-free & Sons' Inc' Copyright O 1994 by John Wiley s i m u l t a n c o u s l yi n C a n a d a A l l r i g h t s r e s e r v e t lP u b l i s h c d any part of this work beyond Reproductionor translationof r08 of the 1e76 United or r07 ;v Section ;;i';;i;;;. permissionofrhe. copyright Siut". Copyrigni Act without the or further permission for Requests owner is untu*ful to thc PermissionsDepartment' inforrnution should be addressed NY Third Avenue' New York' John Wiley & Sons, lnc', 605 I 0 15 8 - 0 0 1 2 . in Publication Data: Lihrary of Cong,ressCataloging ISBN 0-471-00074-4 ISSN 0271-616X of America Printcd in rhe United Stares 1
0
98
1
6
5
4
3
2
l
PREFACE This volume of Reagentsincludes material published in late 1990 to early 1993.As usual,this volume hasreceivedtremendoushelp from Harvardgraduate students.Mark Bilodeau and Jeff Rohde have read and correctedlarge portions of the manuscript.Other advisers have provided invaluable correction of the page proofs. Another group, for the first time, was responsiblefor composition of the chemical formulas in ChemDraw. MARY FIESER C ambridge, M assachusetts June 1994
CONTENTS
Reagents 1 Author Index 409 Subject Index 425
Acylsilanes. Review. Cirillo and Panekr have reviewed progress in the chemistry of these compounds during the last two to three years (48 references).A new synthesis involves (l)2 to form homologationof aldehydeswith methoxybis(trimethylsilyl)methyllithium enol ethersof an acylsilane(equationI). Acylsilanes can be preparedin high yield by
?rr'
(l) Liclsi(cH3)312 Tl|'n. H'
/ocHs
H.o,
?
'si1cH.;. 5t-e2'l" RCH2/ -si1cH.;.
1
o
(rr) *Asr, (ilr)
o
CuCN
+ Atlsi(cH3)313 T H F
83-98%
e, CH3CN/ H2O ---;*"-
*A.,("rr), O
*Ar,("r.).
1X3,,"r.,.
reactionof S-2-pyridyl esterswith aluminum tris(trimethylsilane)and CuCN (1 equiv.), equationII.3 A third general synthesis of acylsilanes involves anodic oxidation of 2-alkyl-2-trimethylsilyl-1,3-dithianes (equationIII)4. Acyldimethylphenylsilanesundergohighly selectivehydrogenation(Pd/C) to aldehydes without effect on benzyl or BOM ether groups, acetonides,or r-butyldimethylsilyl groups (equationIV).
(CHe)e 'l - -o Mo M
(tU CoHs-Si-'.\,CH3 i l l
o
H2,Pd lc c2HsoH
osi(cH3)3
75o/"
OMOM I H\.,r\,\..CH3
i l l o osi(cH3)3
Acylsilanesundergohighly diastereoselective reactionswith RLi and RMgX to afford s_r'n-adducts, particularly when the chiral center is substitutedby a phenyl group.5
Alanine
gt.
CHq
t -J.- -Si(CH3)3
coHs- lf o
bULI 92"/o
9t. . c"n,ft;Btrr.E',T.,4>;;
Cra" |1^'
> 100:1
asx j euor.r-r CHq
C.H.
t cuHrlY"
cl
OH
Acylsilanesarereducedtoa-alkoxysilanesbyavarietyofmetalhydrides.Reductionwith provides(R)-alcoholsin >80% ee and in 30-65Vo (-)-chlorodiisopinocamphenylborane yield.6
L-rl
su fbr ,
rrkl O
It -S|(CH3)3
(CH3)zCH-
C) - tpe2BOl
rnr,zo"60%
9H
rs
s:ndr!
"\si(cH3)3 (cH3)2cH H,98o/o ee
e rP. F. Cirillo and J. S. Panek,Or8' Prep' Proc' Intl'' 24' 553 (1992)' (1991)' 2J. Yoshida,S. Matsunaga,y. Iiicni, f' Makawa' and S' Isoe' J' org'' 56' 1307 4929 (1991'). 3 M. Nakada, S. Nakamura, s. rJuyu.r,i, and M. Ohno, TetrahedronLetters, 32, a K. Suda, J. Watanabe,and T. Takanami,ibid'' 33' 1355 (1992)' s P. F. Cirillo and J. S. Panek, ibid', 32' 45'7 (1'991)' 3l' 46'77 6J.A. Soderquist,c.L. Anderson,'E.I. Miranda, and I. Rivera, TetrahedronLetters' S' Modi' D' Williams' and Khasnis' D' Lamb' G'W' Strickland' B' (1990); J.D. Breynak, J H. Zhang,J. Org'' 56,7076 (1991)'
Alanine, CH3CH(NH2)COOH' a.Methyta-aminoacids.lTheseaminoacidsareofgenera|interestbecausesuch substituentsinpeptidescanrestricttherotationalfreedomofamidebonds'andhence A general synthesis is an extension of the secondary and tertiary structures of proteins' acids' but involves alkylation of the Seebach'smethod tbr a-methylation of a-amino the schiff baseformed from this o-amino a_methyl a_amino acid o_ or i-alanine. Thus acidandbenzaldehydeiscyclizedbybenzylchloroformatetothe(2S,4R)-oxazolidinone l.Theenolateof|'isalkylatedbyvariouselectrophilesfromthefaceoppositetothatof can be hydrolyzedby brief treatment the phenyl group. The products,such as (2S'4S)-2' derivativeof the a-methyl a-amino with LioH or NaoH in cH3oH/H2O to a protected
i \ h
t-rb Sl r-lr Ll j.rn
p-Alanine
1) C6H5CHO
.Bu ,OH
CH3, ,,H
;H2N-g-CooNa
2)ctcooBzl
305"/"
1) LDA 2) BTCH2CO2C(CH3)3
P-(o cuHu""
(*4.cHt n cbl
76"/."
(2S,4R)-1
P-
LioH,cHsoH H2O,25'
(cHg)s
(cH3)3cooccHr,.rrcH" CbzHN CoocH.
41"/"
tzs,+ni-r
lr, ::s ith acid, such as a-methylasparticacid (3). The enolateof (2S,aR)-1can also undergoMichael addition to r-butyl acrylate.The yield is low, but the adduct is obtained \n 987o ee. This reaction provides a route to a derivative of 2-methylglutamicacid (equationI). V:l
(r) (2s,4R)-1
1) LDA 2)CH2=Cx996616H.;.
P-
CoH5""1 )--Ctl"CtlrCOOC(CH3)3 ''cH^ ,N' Cbz 'zaoz. -'-
, -rI 1677 ll::-:.. rnd
:J-.i
t , ^Llun', , I
I
c H 3 o HH , 2O
(cH3)3cooccH2cH2,cH3 coznu^-coocH3
sUCh
a!:.1tcncc il(:l.l()n Of I t ,, : \ r f t h e
'8. Altmann,K. Nebel,andM. Mutter,Helv.,74,800(1991).
tr . .rmino 2,'ll,lrnone t :., thatof [::r.1tmcnt fl ir -JITllIlO
B-Alanine, H2NCH2CH2COOH. Stereoselectiveallqlation. As an extension of a method for diastereoselective alkylation of a-amino acids (14, 263-264), Seebachet al.l have convertedthis simple 2 via an imine with pivaldehyde. B-amino acid into the 2-t-butylperhydropyrimidinone
Alkylaluminum halides
(
CHs p
ll."#5$""" f-( .I".l"o!9* (cH3)3cl
e,, HoAcHzcH2NH2
44o/o
-llh"f
/
Ltt
rac-2
(CH3)3C-{
/
* l .1i
o
Hcl *;;
tl nol)(\r.rHz
NJ
Bi
R 4 (86-97%ds)
3
group has the axial of 2 show-s that the r-butyl Surprisingly, an X-ray analysis with high diastereoselectivity oii r"u"t with alkyl halides configuration. rn" .notut. (3) can be hydrolyzed to (C) (u"o axial)' These,products to give the trans-produ"t This overall processshould with 6N HCI at t60-180"' a-substitutedB-amino *td;i4; p-amino acids' oi emantiomericallypure be applicableto u tyntn"ti' (1991)' ' J' Org'' 56' 2553 andD' Seebach B' Lamatsch' 1E. Juaristi,D. Quintana, na!!1. with the Atkylaluminun " des.r Reaction of (CH3!AI with p'formylproViolalt RAIC| of Rrortion CHrAlClz with reaction but the no 'tt"ottl""tivity' ;-tffi; B-formylpropionamides cH3Ticl3 is erythro-selective' with reaction the """o"r, shows high threo-selectiiirv.'i"
o
O H ?
o
RM' .".'^+f'"t'
,.1+T-"" o I
l
cH3Alcl2
63"/"
CH3TiCl3
38"/o
o l
,,AA*'cHt r r l ' i -L -cHs CHe cH{
O H ?
. cH.tl:"t' cH3 cH3
cH3 dH3
CH3 CH3
97:3 2:8
o H O RM' cH., --.AN."tt
o H ? . cH.\'\T'"t' or'AcH?H'
"r.A"r,?tt
CH3AlCl2
62"/"
C2H5AlCl2
72"/"
(1{./ r(tl.
(xl ,i*-
CHr : / ,P / ,N1 ""*
.afftil
oq.1
99:1
Alkylaluminum halides
the cyclization of eporydienes. corey and Sodeoka2 have examined in detail acids, Lrwis several optimum conditions for cyclization of the epoxydiene 1. Of (cH3)2Alcl or cH3Alcl2 was found to increase the rate of cyclization more than is superior to chlolide (CH3)rAlOTf, but the yield was comparablein all cases.Methylene cyclization the conditions clcH2cH2cl, cH3No2, or toluene as solvent. under optimal are products -78" principal The for t hour followed by silylation. was carried out at under all formed 3, ketone the silyloxy ketone 2 and the monocyclic silyloxy methyl conditions as a minor Product
OSi(Bzl)3
1) (cH3)2Alcl, cH2clz, -78" 2) ClSiMe2-f-Bu
al t\
fY"t'ot"".
l()
rld
RsSiO -'\--l
RO
3 , 1 0- 1 5 " 6 2, f = SiR3(75 -79o/")
hc ll: ta
Deoxygenationofketones.Reductivedeoxygenationofketonescanbeeffected of diaryl with an aluminum source and a Irwis acidic aluminum reagent.In the case acidlrwis the well as as source hydride ketones i-BuAlCl2 can be used as the
2i-BuAlCl2
n
H3
CaHst
X-CuH,
h€Ptane>
(coHs)zcHz 79o/o
?ut' coHui cHsAcHs 8"/"
reduction Reductive deoxygenation of alkyl aryl ketones is best effected in two steps: addition by increased be yield can The AlBrr. with i-BuzAlH followed by treatmentwith of Cp2TiCl2 in the second steP.
)Hs 1) i- BuAIH 2) AlBr3,Cp2TiCl2
C6H5COCH3
75"/o
sequential Reductive deoxygenation of dialkyl ketones is best effected in three steps: catalyst. Ni(acac)2 a and iBu2AlH finally and AlBr3, with i-BuzAlH, treatment
AlkYlaluminum halides
1)i-Bu2AlH
O
I
nonenes
sri-au2,Lil:rN:i(acacr'n - nonane
-Bu
(32o/ol
(48y.\
CH3(CHjal
Thesereactionscanbeusedforreductionofthecorrespondingsecondarya|coholsto primary alcohols ol p:enols' alkanes, but do not reduce an alkynylmagnesium brocomplexes'a Reaction of Cyclization of oWnyiu{inium midewithdichlorobis(cyclopentadienyl)titanium'resultsinaTicomplexlinessentially and to water than is more stable to air oxidation quantitative yield' This ""rnpttl< these complexes with an alkylaluminum halide' the Grignard reagent' On i"utrntnt to a 4-' attached alkene to an exocyclic trisubstituted (n: l_3)undergo "y"rjut^i* (2)' 5-. or 6-memberedring
R
R
'l'
'l' 'l'
?'
*(cHr)i
o"l)#3iJB[."t'i'*(cHr);'t'"'"0' 5O - 79o/o
1 ,n = 1 - 3 n = 1 - 3 1) RAlCl2or R2AlCl -30' -'-78" 2) HOAo'H2O 72 '93"/o
sol+ ,*" L""r,.". 2,n=1-3
'syn-insertionto thus 3 undergoesintramolecular This cyclization is regioselective; product' give 4 as the exclusivecyclic
<;,^ CHe
-,aCH" ,r/V'/.TiClCp2
I
\,r
I CHs
1)c2H'Atct2 2) H3o- -
a31"
5:95
\,,ACHE
CHe
3 for Diels-Alder is the most effective catalyst Diels-Akler catalyst's C2HsAlCl2 reactionis a key step in a This i'*itt' silyloxy-1'3-dienes' reactionsof (S)-(+)-carvon" (S)-carvone' (5) in a0% overall yield from total synthesisot 1+1-a-cyperone
Alkyllithiums
("" (cHd3sioCHg
(+)-1
rl. t()
l ' r r tltrilr
1)CzH5AlCl2 2) H3O+
:t.ln lcri:
?
_
CHg
77"/"
CHz
2a
H CH 2b
9 1: 9
1) H3O. 2) ClSi(cH3)3,
several steos
CHg
CHz
DDO,C6H6
(cH3)3sio
CHs
87v"
CHs (+) - 5, ca +91"
'1 -.
' . - \i J c r flrna
rH. fulii, M. Taniguchi,K. Oshima, and K. Utimoto,TetrahedronLeuers,33,45'19 (l,992). 2E.J. Corey and M. Sodeoka,TetrahedronLeuers, 32,7005 (1991). 3 J . L . E i s c h ,Z . - R . L i u , a n d M . P . B o l e s l a w s k iJ, . O r g . , 5 7 ' 2 1 4 3 ( 1 9 9 2 ) . aA. E. Harms and J. R. Stille, Tetrahedron Letters, 33' 6565 (1992). 5A.A. Haaksma,B.J.M. Jansen,and A. de Groot, Tetrahedron,4S'3121 (1992)'
Alkyllithiums. with an alkyllithium(3 equiv.) 2,4-Diallqlphenols.tReactionof p-benzoquinone in 60-7074isolatedyield' followedby an acidichydrolysisprovides2,4-dialkylphenols
8
Alkyllithiums
TL r
o
I Bu. ,oH I
tl
3 BuLi
r-
)r
rHF,-78i
l . , \ l " . o ' l l t i l t - ; . |
\.,.-
It
Bu
T
|
,\
I
\"t
lr
a
I rr^ot I
o
I
" * | Ji3,lTiill:""i"Jl"1, ?u"'
,"^\
l l t --
OH
o ll
ra) v' tl
o
1) C2H5Li 2) NaH, CH3l
Lffi]
ocHs
Thealkylgloupscanalsobederivedfromdifferentalkyllithiums.2,4-Dialkyl-
."-};#,'ff
orrHF pentane, inether, co2(sorid) forms
?fi?^[:"]#]'i?:i'Jith
with lithium hydride -10' provides a product a that on treatment -40 * ketone after at RrLi or R2Li gives a (43-72% r*"ll-*""tttn alcohol' aldehyde :' .u :ith tertiary an work-up provides a tt"""O RLi to b before hydrolysis. Addition "' "
l\
[ ?'-'I ''\**.\6p,"i
|N ] + c. o z L - r r = " *
-I
,r"o | ,'^ I
o ll
z+H t\N- r l
l
l' = * -b
I
sa'2.H.oI o tl (-(-'" \N-
Allylbarium
rtagents
This protocol provides a ready accessto a fange of aldehydes or ketones with moderate to high yield. (Aminosilyl)lithiums.3 Silyl anions are unstable and are usually generatedin situ in the presenceof a quenching agent. Aminosilyl anions are more stable both to substitution with lithium and a-elimination. They can be preparedby reactionof aminochlorosilanes dispersedin THF or with lithium wire. Yields are generally in the range 80-1007o and the products are stable at 0" for 1-6 days. The reagents couple with chlorosilanes to form disilanes. They undergo conjugate addition to unsaturated esters.
(cH3)sicl
(c2H5)2N(C6H5)2SiLi
AcCl 78"k
(cH3)3sisi(c6Hs)2cl
(foHs)z
(C2H5)2NCH3C6H5SiLi TMEDA 470/o
6r.1rg'
-s'-sic6H5cH3N (czHs)z
{. 1) (C2H5)2N(C6Hs)25iLi 2) CHgl;CzHsOH
f ) r . : l k lr,': I HF f :,,rms n!
.ittcr
sl,,,hol.
(c6Hs)2sioc2H5
ar.&tooc2H5
CH3-\'-COOC2Hs
CHa HzOz KF, KHCO3 35"/o
OH I cHslAYcooc2H5 CHs
,-l t,Ul
) L l
l
3v
Bu
rF. Alonso and M. Yus, Tetrahedron, 48,2709 (1992). 1G. Zadel and E. Breitmaier,Angew. Chem. Int. Ed., 31, 1035 (1992). I K. Tamao, A. Kawachi, and Y. Ito, Am. Soc., ll4,3989 (1992).
Allylbarium reagents, CHz: Q11611rguat. These reagentscan be generatedin situ by reaction of allylic chlorides with barium(O) with retention of the double bond geometry. B,y-(Insaturated carboxylic acids.t Carboxylation of allylbarium reagents,generatedin situ,proceedswith high a-selectivity. Note that carboxylationof allylmagnesium proceedswith high y-selectivity.
4-Allylcyclobutenones
- F
-
ct
tr
Ba,THF
CsHIICHO
-82% -
n-czHrsMaacl
n-CrHtu"^\'/\Cl
llr
ll
n-crtt,u/*1cuH" OH ah =98'.2
cl M g ,T H F
-=, n-C7H15
n-C7H15
cooH
Vsct COr I
l ^ , ,
-
.,.-\.'/
99v" n-C7H.,u/'\y'wn2 1/c= 99: 1
113, 9955 rA. yanagisawa, S. Habaue,and H. yamamoto'Am. soc., (1992)' 593 Synlett' Yamamoto, H. K. Yasui and
(1991);A. yanagrsawa'
4-AllylcYclobutenones. reagents react with cyclobutenediones Bicyclo[3.2-0]heptenones't Allyl Grignard when heatedin refluxing toluene products yield' The to give 1,2-adducts(l) in moderate ring yield' The reaction evidently involves give bicyclo[3.2.0lheptenones(2) in high a and + 2]cycloaddition of a vinyl ketene opening followed by an intramolecular[2 methylene grouP. coHg \-4
CoHs ,p
ll t cH3d
CHz=CHCHzMOB'
V
------ ---58"/"
'O
t
cH3l
/o
e5"/"
l$cH,cH=cHz -
cH3o
I
oH 1a
"tnur7o
+1
flcarcH=cHz
CH3O
OCH3
1
T . o \"u"r--l"""("rr\ 0 ' c l l
l
l*r.o/focn. II L
a
""o;12o -
l
cHso_\__L_l
l
Allyl(diisopinocampheyl)borane
II
This methodologyhas been extendedto 4-alkynyl-4-(propargyloxy)cyclobutenones,' formed by additionof lithium acetylidesto dimethyl squarate(3) followed by treatmentof the 1,2-adductswith propargyl iodides.Theseproducts(4) when heatedat 135'rearrange (5), which isomerizein an acidic medium to benzofurans(6)' to methvlenebenzofurans
cHsoY4'o
CH3O. _O \__/ LiC=CBu
+ 897o
crrl{O )Hz
i l l f-f-c=cBu
CH3O
OH
3
cftoY-/'o i l l /TC=CBu cH3o d"rr"=ar,.
138.c
CH3O
75o/"
CHrO
4 5
h,,ncs r l u cn c s ring a:rJ a
I 95"/. I HrO* V -
OH
cH3o cH30 6
r s .L . Xu, H . X i a , a n d H . W . M o o r e ,J . O r g . , 5 6 , 6 0 9 4 ( 1 9 9 1 ) r s .L . Xu, M . T a i n g ,a n d H . W . M o o r e , i b i d . , 5 6 , 6 1 0 4 ( 1 9 9 1 ) .
Allyl(diisopinocampheyl)borane'
cH3YcH3 K;,1:BCH2cH=cH2
PrC=CCHzl Agzo
12
Allyltributyltin reagents
Enantioselective allylboration; (R)-y-amino'B-hydrorybutyric acid.l Reaction of with I in ether at -100'provides the (R)-bromohydrin 2 in 89% bromoacetaldehyde ee (-5OVo yield), which is converted to the (R)-epoxide 3 on treatmentwith KOH' This epoxide is a precursorto 4, (R)-(-) y-amino-B-hydroxybutyric acid (GABOB)' a
Crh{cl
neuromodulator.
BTCH2CHO
1
,r-#c
-5Oo/"
,
KoH> -70%
|
c>+-rlc
OH (R) - 2, 897oee 1) NalOa'RuClg 2) NH3
>/'\r'cH2
CXrCt{=
"^y'\cooH"N* " l OH
(R)-3
(R) - 4, 89o/oee
1Y. N. Bubnov,L. I. Lavrinovich,A. G. Zykov, andA. V. Ignatenko,Mendeleev Comn.' 86 (7992). Allyltributyltin reagents, CHr: 6g6g2SnBu3 (1). ' Allylation of dioxane acetalst (ct. 12, 375-378). Allylation of chiral dioxane acetals such as 2 has been shown to proceed with marked stereoselectivitywith allyltrimethylsilane promoted by TiCla/Ti(O-i-Pr)a. A more recent study, indicates that
cH3Y,-)....cH3
CHr:C116".t*.
Ll
rt.Gr.rd rrhrrtr
;Ldrlx r 'TT { r0
CH" CH.
i - l oYon I
fu!'r tlrr
tk-s
n-C6H134CH2CH=CH2
TiC14, Ti(O-,-Pr)4
o-t-o
CH"- CHq -
,
f 9-^--4ot
n-c6H13 H (x)-2 tL ' til
-^-
n-C5H13M=Si,R=CH3 M=Sn,R=Bu M=Sn,R=CoHs
lOOo/o 100o/o 1O0/"
ut-3
-CH2CH=CH2
58:1 27O:1 90:1
allyltributylstannane(1) is significantlymore selectivethan allyltrimethylsilaneand that phenyl groups on the metal decreasethe selectivity.The sameselectivityis shown in the case of dioxane acetalsbearing other alkyl, aryl, and alkynyl groups. B,y-Enones.2 Organic halides are known to undergo tin hydride mediated carbonylation.This reactioncan be extendedto a three-componentcoupling of RI, CO, and allyltins to form B,y-enones.
clj'
\i Lr - l.'l H . \ ra"r
Allyltributyltin reagents
Rcrctionof in 2 in 89Vo s rrh KOH. ((i.\BOB),a
* ""r=-f"' cH3(cH2)7r bH2snBu,
?r. +
o-
lcHl cH3(cH2)s
tc"=
13
".3:'i3yg -"r.(""r)r'/5cusn -ft' 74%
co CHs(CHrs "' \ Jt \-/ *CH, CH2=Ct1611rgntr. : 600/o I 0Hs
+ cHz{ cH3cH=cH(cH2)31 CH2SnBu3
r
R ?t'^"", ?t' .
O
.n (1992).
hu:l dioxane irr:r *ith alr n J r . . t t e tsh a t itl.
-oH
-i- ,.r. 6:s4 Lf '-q",
Asymmetric addition of allyltins to RCHO.3 Addition of 7-substituted allylstannanes to aldehydesto form homoallylic alcohols can proceed in high diastereo-and enantioselectivitywhen carried out in the presenceof I equiv. of the Yamamotochiral acyloxyborane| (16,314). If trifluoroaceticanhydride is used as promotor, then only catalytic amounts of I are required. Mrtually quantitativeyields are obtained if I and (TFA)2O are used in the ratio I eq:1.2 eq.
rk-3
r- 1- f-{ ^
cH.
I
OH
ul-3
H= C H z
cH3''-\,-cHo
*
cHa"'--f\snaua
(1 : 1.2), 1, (CFgCO)zO cH3cH2cN, -78" 85"/"
CHs
: rrl.'nc and that s.:r,,$n in the mrJidted caroi Rl. CO, and
CHz
cH"/ 95o/oee, syn/anti = 92 :8 r S . E . D e n m a r ka n d N . G . A l m s t e a d ,J . O r g . , 5 6 , 6 4 8 5 ( 1 9 9 1 ) . r I. Ryu, H. Yamazaki,K. Kusano, A. Ogawa, and N. Sonoda,Am. 9oc.,113, 8558 (1991). 'J.A. Marshall and Y. Tang, Synlett,653 (1992).
14
Allyltrifluorosilanes
1R--oa---.SiFe
rb
R2 Allyltrifluorosilanes, y-selective coupling with electrophilies.l In the presenceof a Pd(0) catalyst and BuaNF (1 equiv.), aryl, vinyl, or allylic halides, triflates, or acetatescouple with allyltrifluorosilanesat the 7-position, with migration of the double bond. Pd(oAc)2 and dppb in combination with TASF (tris(diethylamino)sulfoniumdifluorotrimethylsilicate)
':. 3|t
o
"rr/li
Pd(o),BU4NF T H F ,8 0 ' > 95"/.
*%' CH31-Z'.,..-.SiF3
CHs 1
=cH,
oT{
I
/^-\
to'olblltt
ff
|
|
il
I
|
\/\./
i
|
-
850/"
is particularly effective for coupling of enol triflates. Only one coupling of an allylic acetate in low yield was reported. This coupling provides a practical route to the antiinflammatoryagent ibuprofen (equationI).
CHs lld
+
1 950k | : a
Br
.x5 I
Naro4 ro%) I r; xtrlnoo, rFA (78%) z1xsi1c2nuy3, I
TL ( t
CHg
tD CHs
cooH
a r: 1l II
I Y. Hatanaka,Y. Ebina, and T. Hiyama, Am. Soc., f n'
7075 (1991).
-
(R)- and (S)-l-Amino-2-methoxymethylpymlidine
!'l .rnd I rrh al-
(1, Ramp, Samp)
Aluminum chloride. Acylation.t Acylation of 2-methylbutanewith the crotyl chloride I in CH2C|2 in the presenceof AlCl3 and CuSOa/CH3NO2provides a synthesisof cyclopentenones (equationI). A similar reactionof alkenyl chlorideswith methylcyclopentaneor methyl-
cr. and ; rI r c a t c)
o tl
cH3\
Cl.'\
cH.AcH. )H;
Arcr3 CHs
L-CHs; ;
CHs
t ?
zsz crl),1 I \ v i o \-^
r.rllvlic :,, rhe
cHs-< I ) YfvcHs cil.
cyclohexaneprovides a synthesisof tetrahydropentalenones or tetrahydroindenones. Fries rearrangement,review. Martin2hasreviewedthe rearrangement of aryl csters to o- and p-hydroxyaryl ketones,usually effected with AlCh. Thc rearrangementcan occur at room temperaturesin polar solvents(nitroalkanes).Photo-inducedrearrangement usually provides the same products as obtained by Lewis acid induced rearrangemcnt. The review lists 281 referencesto literaturemainly from 1964 to 1990. r-8".1
rC. Morel-Fourrier, J.-P.Dulcdre, andM. Santelli, Am.Soc.,ll3, u062(1991). : R. Martin, Org. Prep.Proc. Int., 24, 373 (1992).
(R)- and (S)-1-Amino-2-methoxymethylpyrrolidine (1, Ramp, Samp). Asymmetric Michael cyclization; trans-disubstituted cyclopentanecarboxylates.r The lithium enolatesof SAMP hydrazones(2) of methyl ketones react with methyl (E)6-bromohex-2-enoate(3) to form the Michael adducts (4), which are cleaved by ()zoneto give /rans-disubstitutedcyclopentanecarboxylates 5 with high diastereo-and cntantioselectivity.
Aniline and Nitmbenzene
.\ri
Thrs
er-,u
Br. )
LDA,THF -78"
I
tsd
/-coocH3
(-Jl
cH3o--'HrA"r.
(E)-3
(s)-2
I
54"/" I overall I
/ \
. *
03, CH2C|2 -78"
(:),.'coocH3 l l (F1) I
cn.
o (1S,2R) - 5
> 9 9 o / od e 97o/oAE
t s-
I D. Enders,H. J. Scherer,and G. Raabe,Angew' Chem' Int' Ed' 3O' 1664 (1991)' Aniline
r h
and Nitrobenzene.
Addition and 4-nilrodiphenylamine't . of animixture to a 2Hzos (cH3)4NoH to tetramethylammonium hydroxide dihydrate, Direct coupling
to 4-nitrosodiphenylamine
lineandnitrobenzeneresu|tsinaa-complexl,whichisthenconvertedtoamixture (3)' The ratio of 2 and 3 of 4-nitrosodiphenylamine (2) and 4-nitrodiphenylamine
oH
C6H5NH.
-. o-
C6H5NH2 + C6H5NO2
Cur,r,U"-$*O 2
I I
c6H5NO2
tol
cuHuxH$uo, 3
ratio of nitrobenzeneis increased' dependson the ratio of aniline and nitrobenzene.As the act as an intermolecularoxidizing the yield of 3 is increased.Evidently nitrobenzenecan agent of I to give 3. I M. K. Stern,F. D. Hileman,and J. K. Bashkin,Am' Soc'' ll4' 923'1(1992)'
:-t
Lr ;.r / Lr! i c
{
2-Arenesulfonyl-3-aryloxazirdin€s
)cH3
Antimony(V) chloride- Silver hexafluoroantimonate. This combinationgeneratesSbCU . SbF; (l). Beckmann rearrangemenL The antimony(V) salt I is an effective catalyst for Beckmannrearrangementof ketoxime trimethylsilyl ethersto amidesor lactams.l
lilosi(cH3)3 1 , C H 3 C NA,
\
C6H5NHCOCH3
cH,
c.Hu
/n3
t7
/
V
-----------> 77"/o
NOSi(CH3)3
l3 S-
rlc
t": ee
Pinacol rearrangement.2 This reaction is generally effected with at least one equiv. of conc.HzSOr. It can alsobe effectedwith the salt (l), preparedfrom SbCls and AgSbFr, in high yield under mild conditions.In addition only 20 molVaof I is required.
o i l n
1,CH2C|2 15-20"
rdJrnon (' l a n l -
av
ml\turc .rnd 3
OH
Hzo
{.\o2
-_Noz
Nrc.lscd,
)\rJizing
o
| 9sHs
c6H5-l\-c6H5 CnH" - - oI H
99
lcuHuy.cAcuHu
lT. Mukaiyama and T. Harada,Chem. Letters, 1653 (1991). 2lbid, idem, sl (1992).
2-Arenesulfonyl-3-aryloxaziridines,ll, 108; 12, 392-393; 13, 23-24; 14,22. Oxidative desulfunylation; d-diketones.t The potassium enolate of an d-sulfonyl ketoneon oxidationwith a typical oxaziridineof this type, 2-[(p-chlorophenyl)sulfonyl]3-(p-chlorophenyl)oxaziridine(1), is converted into an a-diketone in 78-85Vo yield. Use of lithium or sodium basesresultsin poor yields. Addition of HMPA or l8-crown6 can be beneficial.The procedureis applicableto cyclic and acyclic systemsand is compatiblewith olefins, even allenic groups.
Arene(tricarbonyl)chromium
complexes
t
o Ar-tLtX
H'
'sorAr
r il.1 :-l{r
1, Ar = 4-ClCoHa
I1r
o
TS T(
So2ror llfl#Fl|;
t-.4
81v"
i-Pr
'i-Pr
i-Pr
i_pr
I D.R. Williams, J. org.,57,3740(1992). G.S.Amato,andM.Y. Osterhout, L.A. Robinson, Arene(tricarbonyl)chromium complexes. Nucleophilic substitution.t carbon nucleophiles react with the cr(co)3 complex or of indane followed by oxidative decomplexation(iodine) to effect highly selective exclusive substitution a to the ring junction. Similar but less pronouncedselectivity Good but obtains in reactionsof the Cr(CO)3 complex of 1,2,3,4-tetrahydronaphthalene.
CN
(cH3)2c-cN 1) Lic(cH3)2cN 2) lz 90%
ra\1 \/<
(CH3)2C--.,..\,.-\ i l t
* \ N
\
9 1: 9 (' C -H a-) r Cl - C N
/,,\,,1
V')
Cr(CO)3
CN
-a) \/\..'
(CH3)2C-._..\".,\
.
l
\/\./
l
l
l
73:27
(cH3)2c-cN CHs CHs
,\ratr
l
l
V-cH.
l
cN (cH3)2c--,.1-cHs
*
l
l
\Z\cHs
l
20:80 opposite selectivity can be obtained even in substitutionof o-xylene. Evidently some steric effects are operativeas well as electronic effects. stereoselective benzylic substitution reactions.2 A novel synthesis of the phenolic reacditerpenedihydroxyserrulaticacid (6) dependson highly regio- and stereoselective tions of a tetralin(tricarbonyl)chromiumcomplex with nucleophiles.Thus the Cr(CO)3 2 on hydride reductionfollowed complex f. is convertedin high yield to the endo-acetate by acetylation.This product reacts with an (E)-crotylsilanecatalyzedby BF3 etherate to give the exo-isobutenylatedtetralin complex (3) with the desiredsyn-selectivityat
Arene(tricarbonyl)chromium
complexes
19
C11. The carbonyl group of 3 is converted to an endo-methyl group by addition of CH:Li followed by ionic hydrogenolysisto provide the complex 4. Reactionof 4 with 2Jithio-1,3-dithianeresultsin substitutionmetalo the methyoxy group to provide 5 after demetalation.This product has the desired trans-anangementof the groups at C1 and Ca as well as the precursorfor the carboxyl group at C6 for the complete synthesisof the diterpene6. The conversionof 5 into 6 was completedin four conventionalsteps.
Pr 1) LiArH4(95"6) 2) AczO,DMAP (98o/.)
.r.1 ,
c ,' n r p l c x
'o
cH3o o'
: e: l \ c 0 r :lci:ir ity r,. ,J hut
CHr
'$""t' 1) CH3L|(60%) 2) (C2H5)35iH, cF3cooH (7s7o)
(E) CH3CH=CHCH25i(CH3)3 BF3'O(C2H5)2 I 720/"
cH3o
o
exo-3
CH) i'\--.rt l 1) Lil
Fr ) SJ
2) tz
CH:
cH3o
CHs
4
un3
11.-CH3
n :I \ \ ( ) m c
severat steos
HOOC
: lhcnolic I)\ ! rcac: t :r('O)3 t f,'llrrwed , Jlhcrate e.:l\itv at
HO
CHs (t)-6
45% overall from 1
20
Arcne(tricarbonyl)chromiumcomplexes
Asymmetricreaction of the (R)4)-nluaktehyde(tricarbonyl)chromium complex' (TosMic).3 This complex reactswith TosMic in (R)-1, with tosylmethylisocyani.de at 0" to form only one(2) of thefour possibleproducts.Decomplexation K2CO3/CH3OH followed by LiAlHa reductionprovides(S)-3 in I$OVode'
cHo
K2C03 cH3oH,0' + P-CH3C6HaSOzCHzNC + 95%
Eru ;an ht
(R)-1
(CO)3Cr-
1)hv (Go7o)
/cH3
>5
t-r-*
NHCH3
z)unino
\_l^1<+e)-H H Tos
(S)-3, >99% ee
anti-Selective aldol reactions.a The racemic tricarbonyl[o-(trimethylsilyl)benz2 in the aldehyde]chromium(0) complex I reacts with the acyclic o-silyl ketene acetal -78' to form a with cAN decomplexation by followed at in cHzclz presenceof Ticl+ of is independent anti-selectivity 7l'29.The ratio in the syn-aldols mixture of anti- and itself o-trimethylsilylbenzaldehyde Surprisingly, acetal. ketene silyl the geometry of the also reacts with silyl ketene acetalswith comparableanti-selectivity.The complexed (-)-f' aldehydes,however, have the advantagethat they can be resolved to (+)- and highly also are ee and 92-98% in proceed can aldehydes complexed Reactionsof these
Po/lj< -i rTtictl i{ e cr cr. :e:=ellr r lxlrxl |]\:
anti-selective.
1i){r f\.l:rtl
r'\7cHo llr I 'si(cH3)3 (jo\"cY-z (+)-1
96"/"
: CHs si(cH3)3 (-)-2 96% ee, anti/svn = 96 : 4
t
f:'a.XriJ
?t5 rrr
Arene(tricarbonyl)chmmium
complexes
2l
omplex, 6\{lc
ln
si(cH3)3
ilc\atton
cHo
96"/o
(+l-2 94o/oee, anti/sYn= 95 : 5
(-)-1
Enantioselectiveadditionof(CzH)zZntoRCH0.5Chiralcomplexesofthetype can be effective catalysts for this reaction'
-N(cH3)2
-oH I R
CHO + (Et)zzn
hr Jc itself cr,ntplcxed rnJ (-)-1. el*, highlY
toluene,ooc
Et
I
r''\ri-oH i l l \/
S, 93% ee S, 87% ee
87o/" 98/"
+1a +lb srl\I )henzrl I in the : ( r t ( ) r ma pnJcnt of
1 a ,R = E t lb, R=CoFs
complexes are best Polycyclic arene(tricarbonyl)chromium complexes'6 These and BFr etherate'As in preparedby treatmentof polycyclic areneswith (NHr)rC(CO):7 is complexedselectively' complexationwith c(co)6, the terminal or most aromaticring However,thelowertemperaturesusedinthenewermethodareadvantageouswith for substitutionreactions thermally labile polycyclic arenes.These complexesare useful of the arenedirectly' one at positionsthat are not availableby electrophilicsubstitution suchreactionishydroxylationeffectedbysimultaneousreactionwithabase(BuLior workup' Regioselective LDA) and tributoxyborane(excess)followed by H2O2/HOAc and (cHr)rSicl with silvlation is effected by reaction of the complex with LiTMP
.ZY\ I ..\/\/
ll | YZ\/ Cr(CO)3
I t1urue,B(oBu)3
ll
2) Hzoz,HoAc ,
|
se'2.
Ho
22
5-Aza-semiconins, chiral
similaryield.Carboethoxylationiseffectedbyreactionwithethylchloroformateand abase.Sincethecarboethoxygroupissmallerinsizeandelectron-withdrawing,the mixture of 2-carboethoxypyrene'1'2reaction with the pyr"n" "o.pl"" 11; gi"t' a -ticarboethoxypyrene' dicarboxyethoxypyrene, and 1,2,3 complex of an 2-Arylcarboxylic acJds.8 a-Lithiation of a tricarbonylchromium
iffcr o Et :x-ulert ftw
Cl(
alkylarenefollowedbyreactionwithCo2providescomplexesofa-arylcarboxylicacids.
l+2 QHg | I
1)LiN(c2H5)2
Il
I ll \-Y - 'Cr(CO)3
cooH
57o/"
Tt llr lx
74,2009 (1991)' 1 E.p. Ktindig, c. Grivet, E. Wenger,G. Bernardinelli,and A.F. williams, Helv'' (1991)' 5402 113, Soc., Am. Hayashi, Y. and 2 M. Uemura, H. Nishimura, t. ilinami, A DeCian' Tetrahe3 A. Solladi6-Cavallo,S. Quazzotti' S. Colonna, A' Manfredi' J' Fischer' and dron: AsYmmetry' 3, 28'7 (1992)' a C. Mukai, M. Miyakawa, n. Minira, and M Hanaoka' J ' org'' s7 ' 2034 (1992)' s M. Uemura, R. Miyake, and Y' Hayashi,l' C' S' Chem' Comm" 1696 (1997)' 6J.A. Morley and N.F. Woolsey' J Org'' 57' 648'7(1992)' 7 G . A . R a z u v a e ve t a l . , O r g a n o m e tC ' hem',rlf' 131 (1976)' (1992)' sv.N. Kalinin, I.A. Cherepanov,and S.K. Moiseev, MendeleevComm'' 113
:rlt'
chiral' o- or t-- pyroglutamic acid' An attractive These ligands are generally prepared from and 5 aza-semicorrins such as I are known short synthesis is shown in .quuiion I. Several
5-Aza-semicorrins,
2
/Y" < l
r\
\-.'NH -a
cHs-T-oH CHs
HN[(S|(CH3)312 rsoHr
-nG
(
lr
f>..NS.-1 | ll
) \--N HN<
: \ (cH3)3sio-icH"- cHt-IoSi(cH3)3 L/n3
CHg
cH2cl2 60 - 7o'l.lcH3l,
?t' /---.-.-N
( l l \r-N -a
(CH3)35iOtCH3
osi(cH3)3
ur
{ -r *l =.I:t
r
l
Azidotrinethylsilane
nrl.
and
r rn!. the enc. I,2-
- Chromic anhydride
differ only in the nature of the substituent (R) at the stereogenic centers. Enantioselective clclopropanation and allylic allElatiot.r These semicorrins' particularly when treatedwith CuOTf, are comparableto bis(oxazoline)ligands(f6, 38-41) for cyclopropanation.
f\ ()t an 'lri rrcids.
CuOTf
'f::::
cuH,-A-H
? Nrx.AOer-;**
H-S S-COOEI 94o/o AA
r
H-A-H cuHu/Rs-cooEt
75:25
68% ee
They appearto be more useful than bis(oxazolines)as ligandsfor palladium-catalyzed allylic alkylation with dimethyl malonate/BSAIN,O-bis(trimethylsilyl)acetamide]. l^.r l()91). n
j, truhe'
OAc l coHsMcoHs
*
NaCH(COOCHs)z/
BSA
pd-2
CH3OOC--.COOCH3
ee% cuHuMcuH'
CH. t "
95oloee
al-\'1 NJ \--ru RoH2c-i L.t::rJCtlvg tn, 'rr n afld
\"rro*
R=Si(CHs)ztBu 2 I U. I-eutenegger, (1992). G. Umbricht,C. Fahrni,P. von Matt,andA. Pfaltz,Tetrahedron,48,2143
hl
Azidotrimethylsilane - Chromic anhydride. Acyl azides.t A mixture of NrSi(CH.). and CrO3 (1:1) in CHzClzeffectsconversion of aldehydesto acyl azidesin 7O-9OVoisolatedyields. In the caseof aryl aldehydes,the reactionis conductedat 25", but the conversionof aliphatic aldehydesis best conducted at -10" to prevent rearrangementof the acyl azide to the alkyl isocyanatc. N3Si(CH3)3,CrO3
coHscHo,#* {:r:
cH3(cH2)6cHo
c6HscoN3
""'-t'|:'-to'" cHs(cHz)ocoNs 74o/"
rJ. G. Lee and K. H. Kwak, TetrahedronLetters, 33' 3165 (1992).
Azidotrimethylsilane-Chmmic
anhydride
acid' Azidotrimethylsilane-TFifluoromethansulfonic acid is an efficient catalyst for Trifluoromethanesulfonic alkenes.l Azidation of also facilitated by silica gel or is reaction The alkenes. to acid addition of hydrazoic hydrolysis of alumina. A further advantageis that these adsorbentscan effect fu situ particularly useful azidotrimethylsilaneto hydrazoic acid, HNr. This new procedureis for preparationof tertiary, benzylic, and allylic azides'
Berium. r Conpl ,'f Bal: h)
A (-,,i
"t'Xt cFasogH'siozorAr2os + N3si(cH3)t ---ioo%(, No
Z-'>r'\ (-l-)
+ Nssi(cHg)s
45o/"
/ "
urlh rctcn hr a.o -cr t>l'i
r ic-ld
n-CJ 2
/
l 2 G . W . B r e t o n .K . A . D a u s ,a n d P . J Kropp. J. 0rg ' 57' 6646 ( 1992).
n-C7H.
.4llyk lrrhium trq e l l rI a l l rI r hr rJrorrlat i\ruPlct* r * rth prcsc
\ -\G cH?x
t x= 2.X=
t r s l rs t f o r [-: lcl or r L , l r : i so f rlr uscful
Barium, activated (Ba*). Coupling of altylic halides.l In the presenceof Ba+, prcpared in situby reduction of BaI2 by lithium biphenylide, cis- or trans-allylic halides undergo' a,a'-coupling with retention of the double bond geometry. Unsymmetrical dienes can be prepared by a,a/-cross coupling. Thus (E,E)-farnesyl chloride is converted into squalene in 64Va yield. Ba*,
,n-ctH*\Z\.-c,
n-c7H15
#a (cr,c'/u,y'= $$;51
?"
15-n
2
n-C7H15
v
,Br -
50/"
I n-C7H15 (o'c'/tr'1'= 77:23\
n-C7H15\r-z:._.BaCl
-"r*-
+ Br/"6C7H15-n
n - C 7 H 1 5'\/\r/V\c7H'5-n ' Allyl-allyl coupling.2 The reaction of (E)-prenyl chlorides with Bal2 2H2O and for an used been has lithium biphenylide (2 equiv.) to form allylbarium reagents allylic by preparcd I' allyl/allyl coupling to form diisoprenoids.Thus the allylic alcohol bromide This 2. bromide hydroxylationof geraniol,was convertedinto the corresponding coupleswith geranylbarium(3) to give 4 (61Voyield) with only primary/primarycoupling with preservationof the geometry of both allyl units.
CHs
OS|R3 +
1,X=OH 2,X=Br
Ba(L)
OY
THF -78" - 23" 61o/"
4, Y = SiR3 5,Y=H
26
Benzeneselenenyl chloride
Coupling of (E,E)-farnesylbromide with farnesylbariumprovides all (E)-squalene (79Vo yield). goc.,113,5893,8955(1991);A' Yanagisawa, 1A. Yanagisawa, andH. Yamamoto,AmS. Habaue, Org., 57,6386(1992)' Yamamoto,J. and H. Y. Hisada, Habane, H. Hibino,S. 2E. J. Corey and W.-C. Shieh,TetahedronLetters,33, 6435(1992).
8enz1'bhr Srillc r unsaluratcd,
coupline.: *ith an
as a l:l mr R
o )i:o
1,2-[(Benzenediolato)-O,O']oxotitanium,
Ho
o
I
(c
1 (16;19) stereoselective 1,2-cisglycosylation of tribenzJl-D-arabinofurunose (2).t The reaction of 2 with various trimethylsilyl etherswhen catalyzedby I and trimethylsilyl triflate (3). formation of 1,2-ci.s-arabinofuranosides. results in stereoselective
BzlO osi(cH3)3
Bu3SnH 8(qHJ3
1, (CH3)3siorf c*zct^--23"+ c6H5(cH2)3osi(cH3)3 92/o
BzlO O(CH2)3C6H5
+
(I - anomer
92:8
8u3snr"
I T. Mukaiyama, Chem.Letters,l4O1(1992). S. Suda,Y. Yokomizo,andS. Kobayashi, M. Yamada, Benzeneselenenylchloride. Cyclization of triethylsilyl ethers of cis-2,S-Disubstitutedtetrahydrofurans,t 3-hydroxyalkeneswith coHsSecl in thc presenceof K2cor providesci.s-2,5-disubstituted tetrahydrofuranswith high stereosclcctivity.Othcr protcctinggroups show generallylow stereoselectivity.
"utu\,
t\-"'\R
"?';i"^l'"t9,"'cuHsYo)'-t osi(c2H5)3
l
l
Y
c6H5se'
R = CHzOTBDMS
92"/o
cis / trans > 1 0 0 :1
R = CH(CHg)z
83o/"
> 1 0 0 :1
R = CHg
91To
1 5 :1
r S . H . K a n g , T . S . H w a n g , W . J . K i m , a n d J . K . L i m , T e t r a h e d r o n L e t t e r s , 3 24' 0 1 5 ( 1 9 9 1 ) '
* ith LiOH I >iX)n ricld
under 3 atm r*\ used to d or onll proi
J E. Baldru .\-(Beonld
N-(Benzyldimethylsilyl)methyl-2-(+)-methoxymethyl)pyrmlidine
le- .,ll (E)-squalene
-\ Yanagtsawa,
t-. . F:
27
Benzylchlorobis(triphenylphosphine) palladium(II). Stille macrocyclization. Several macrocylic antibiotics contain a y-oxo-a,Bunsaturatedestergroup. Macrolidesof this type can be obtainedby Stille intramolecular coupling.r The substratesare availablefrom Mitsunobu esterificationof propriolic acid with an crr-hydroxyester followed by hydrostannylationto give B-stannyl alkenoates1 as a L:1 mixture of (Z)- and (E)-isomers.Selectivesaponificationof the methyl ester R I
R o ll r{ -o- '\I
P(c6H5)3, -c_,. . , r _ o . . c rDEAD .
Hol\1cHr)ecH2coocH3
"H-COOH vvv'7/'
-1cHr)ecH2coocH3
H. lorr tll.l The reacrrr-r Jlh\ lsilyl triflate
t
Bu3SnH B(C2H5)3
o
I
Bu3Sny'v-O
lcf
s oTf t t -
(( - anOmef
F
lCHr;nCH2COOCH3 >eo"/o
R
Pd(il),co i l l /^o tcHz)ro100" i ll
Jr
cocl
Bu3Sn9 2 3
I
')(cog!fl:
'l(ZJE=1:1)
O
-
1)LioH
R
2
R=H
53"/"
R = CH.-
7Oo/"
O (E)-3
'. r\. l10l (1992).
r"' . ,.ilr I ethers of s. 1.5-disubstituted F . ,"\ rrcncrallylow
with LiOH provides the free acid which is convertedinto the acid chloride to give 2 in >9OVo yield. Intramolecularcoupling of 2 to form 3 is effected with a Pd(II) catalyst under 3 atms. of carbon monoxide at high dilution in toluenc. This cross coupling can be usedto obtain 12- to 20-memberedrings. Dimeric macrolidesare formed as the main or only products in the case of shorter precursors. I J.E. Baldwin,R.M. Adlington,andS.H. Ramcharitar, J. C.S. Chem.Comm.'94O(1991)-
,C
--R
N-(Benzyldimethylsilyl)methyl-2-(+ )-methoxymethyl)pyrrolidine.
l-
s :':.s
"rr).iT c6H5cH2 |
cH3o\,/() -r: : l5 (1991).
(S)-(+)-1
28
l,l/-Bi-2,2/'naphthol-Dichlorodiisopmpoxytitanium The anion (sec-Buli) of (S)-1 reacts with
Asymmetric synthesisof l,3-diols't
ethyleneoxidetogiveasingleproduct2.oxidativecleavageoftheC-Sibondgivesthe r,:-oiot(S>(_)-3in>ggToee.Similarreactionoftheanionoflwith/-butyloxirane which are separable by or L,2-epoxyhexane gives a mixture of two diastereomers' chromatographyandconvertedtosyn-andanti-|,3-diolsonoxidativecleavage.In the 1,3-diols have the (1S)these reactionsas in the reaction with aliphatic epoxides, configuration.
1) sec-BuLi
(S)-(+)-1
2 ) o ,/\ --r**
: CHs)Si._ CHs I
KF,H2O2 65"/"
,N.
cH3o__{_jr
C6H5--1.^---,OH : 6H (S)-t)-3 (>99o/.ee)
2
C6H5.-.-,.^-...-.Bu{ CHs-Si1)sec-BuLi ')A c1o,.1. cH;'-l (S)-(+)-1
,*
6ff
,N. rH3o__<_J
,
anti-4
+
.{t h-{s t2
1:1
lh'lr.tr
sYn-4
I 65% ltol V
C6H5-9,-..9.Bu-t : 0H 6H sYn-5
I 75./" tol I V
C6H5--9,----7.Bu{
:
l
cHzl
OH OH anti-5 .jfl
xthrl rT.H. Chan and K.T. Nwe, J. Org', 57,6107 (1992)
I (l)' 15' 26-27;16'24-25' L,lt-Bi-2,2t-naphthol-Dichlorodiisopropoxytitanium The titanium comaldehydes't unsaturated of Enantioselective ene cyclization plex(R)-lacaneffectenantioselectivecatalyticcyclizationof2and3.Substitutionof thechlorineatomsbyperchlorateimprovestheenantioselectivitysignificantly.
-naphthot- Dichlorodiisopmpoxytitanium 1,1/-Bi-2,2/
)ct\ with { t \ L ' st h e
i.r
\ li,\irane rr.rt'lc bY a\ .rqc. In
(R)-1a,X = Cl (R)-1b,x = clo4
rhc ( 1S)-
gH fi"
o \
+Atusr*"He*
a-H 5
6-)
(3R,4R)-trans
(3R'4S)-c,b
o. t
79o/oee 74o/o@e
.9H
\-H
a
47:53 80:20
70/o aa g4o/oeA
+1a +1b
ts. ee)
a1'u''\cH.
6-)
7c(cHs)z 2
gH 3"
t
rr "\----l
CHr
ru,+Aus
.lL-cH3
43"/"
l
t
l
o l \AcH, 91o/oa@
3
allylic alcoAsymmetric carbonyl-ene reaction with 1.2 The reaction of racemic asymmetric remote with hofs (2) with methyl glyoxalate catalyzedby (R)-1 can proceed components' ene two the induction,which suggeststhat (R)-1 can discriminatebetween
9H. ?H. , Bu-t
cH,/fcH' osiR3
n
CH3 CH2 OH I ll I
(R)-la' ?
QH2ct2,'^
iH'A^^^^ -COOCH3
cH'/tY'^"''-coocH3 osiR3 3, syn/anti = 99:1
2
(2) with Asymmetric glyoxytate ene reaction.3 The reaction of exocyclic alkenes ee' in 63-99% proceeds sieves molecular methyl glyoxylate in the presenceof (R)-1 and
/ f o - t
f <
3nlum comrl..lrtution of n ll r
W 2
CHr -
+Atts, 1n1-t,
* "A"oo.r,
cH2cl2 69o/"
coocH3 OH
30
Bis(acetonitrile)dichlompalladium(Il)
lK.Mikami,E.Sawa'M..l.erada,andT.Nakai,TetrahedronLetters,32,6571(1991);K.Mikami (1992) and M. Shimizu, Chem. Rev', 92, 1'021 (|992)' 2K' Mikami, S. Narisawa' M. Shimizu, and M. Terada,Am. Soc.,||4,6566 (1992). 6695 33, 3 F. T. van der Meer and ts. L. Feringa, TetrahedronLetters,
CHt'
Bis(acetonitrile)dichloropalladium (II)' orygenationofatlylicamides.|oxygenationofallylicamides(orlactams)inthe p r e s e n c e o f a P d ( I I ) - C u C l c a t a l y s t i n l , 2 . d i c h l o r o e t h a n e c o n t a i n i n g H M P A ( e s sae n t i a l ) water' the oxygenation results mainly in results in an aldehyde' In the presenceof methyl ketone.
o
o T ILB (1 il
^ ,, )'t*,'^"-r'cH2 l\
UAFIs
:T TL
cuHuAt..1"---t"cHo 02' Pd(ll)cucl' HMPA clcH2cH2cl' CHs
o
' cHs
90:10
52"/" + H2o
6:e4
GZo/o
Itir[t{ Po rrth )
O
+
tl
"uruAf-y""' cH3 o
nlrtun i,tr-tr6l : Ymrll
:trcnr I -" Plr Theal|ylacetatelisoxidizedundertheseanhydrousconditionstoanaldehyde(2) in reasonableYields'
O
o il
cHr
^,,
6/\y'"n2 1
02,Pd(r) CuCl 760/o
, CH3/
O
Jt-O- -^-._,.cHo* v L.l cH.AolcHt UHg+
2
O 65'3s
Amidationofelectron-deficientalkenes.2InthepresenceofCI2(CHTCN)zPdand COOR' COR' CHO' or CONR2 groups CuCl (1:1) amidesreact with l-alkenes bearing yield' Cyclic amides are more reactive than to form (E)-enamidesin generally good reactive' open-chainamides.Carbamatesare particularly
Bis[(allyl)trifl uomacetato]nickel(II)
o
r i. \l ikami
ot l
cat.,DMF
A -NHz+ CHt:616oocH3 CHs'
650/"
cH.AN&coocH3 H EIZ= 61:39
o
o
cat., HMPA, DME
tl A*',
+ CH2:CHCOCH3
tl
ArrycocH3
80v"
t-:a,r) in the d ' l.sential) m . 1 r n l \i n a
o tl
tl o
ttH
+ CH2:CHCOOCH3
oAru&coocH3
84o/"
rT. Hosokawa. J.C'5. Chem. Y. Yoshida,andS.-1.Murahashi, S. Aoki, M. Takano,T. Nakahira, Comm.,1559 (1'991). 2T. Hosokawa,M. Takano,Y. Kuroki, and S.-1.Murahashi,Tetrahedron Letters,33,6643 (1992).
.
_.,cH3
Fl:
O
,iJfhvdc (2)
Bis[(allyl)trifl uoroacetato]nickel(II)' 1. poly(p-phenylene),5.1 This catalyst has been used to polymerize 1,3-butadiene with >97Vo 1,4-regioselectivity.Attempts to polymerize phenylenesdirectly results in mixtures of para-, meta-, and ortho-linkedoligomers. In contrastpolymerizationof cls2 with I in CcHsCI results in exclusive 5,6-bis(trimethylsilyloxy)-1,3-cyclohexadiene 3. This polymer is convertedinto poly(pformation of the 1,4-poly-1,3-cyclohexadiene phenylene)(5) by conversionof the trimethylsilyloxy groups to acetyl groups followed by pyrolysis.
"o
1,
c6Hscl
.Jor-\J,t,,r. 3
(cH3)3sior-\ si(cH3)3
(cHs)
2
-..,.CHs
({})
93o/"
tI
1)F 2) CH3OH
{ ( \l:Pd and :( )\ R. group" r . . 1 . l i v ct h a n
(o)
+
1) Ac2O,Py 2) , -CHSCOOH
)J1;^ 4
I D. L. Gin. V. P. Conticello, and R. H. Grubbs,Am. Soc., 114,316'7 (1992).
32
Bis(1,5-cyclooctadiene)nickel-Tbiphenylphosphine
Bis(cyclooctadiene)nickel. Phenol synthesis. In the presenceof this Ni(O) catalystcyclobutenonescan couple with internal alkynesto form phenolsin 50-80% yield. Two phenolsare obtainedfrom unsymmetricalalkynes with only slight regioselectivitybased on the size of the alkyl substituents.Modest selectivity obtains with oxygen-substitutedalkynes.
R1
--/o
ill
I
.lll
CHz
f
I
CoHs
cH3ooc\ I (t)
R1
R2
0" Ni(coD)2,
products (endol diene substitue
R2
R1 C5H5
R2 75Yo
R1, R2 = CzHs R1 = CHg, R2 = (CH2)2OTHP
65:35
47o/o
cHgooc
This phenolsynthesisdiffers from the thermalreactionof cyclobutenoneswith alkynes (15, 160) in that activated alkynes are not required and the ultimate positions of the alkyne substituentsin the phenol are different.
(il) cHr:91
1M.A. HuffmanandL.S. Liebeskind, Am. Soc.,ll3' 21'71(1991)' Bis(1,5-cyclooctadiene)nickel(0)-Chlorotrialkylsilane,Ni(COD)2-ClSiR3' Conjugateadditionofalkenyltributylstannanestoa,B-enals.Thereactioncan Ni(COD)z be effected with a chlorotrialkylsilane(1 equiv.) and a catalytic amount of evidently reaction The yield.l in 48-79Vo (E)-silyl ether enol in an in DMF and results involves a 1-silyloxyallylnickel(Il) intermediate(a)'
CHr:611"tO
+
CHr:611tntr.
+
,liene with pha The preser orvnorbornadk rdduct (equalx
",|l(l),.
+ ClSiR3
(ilr)
4*.OSiR3
I CtNiT ' 2
a
-;**
z
f''\'OSiR3
("r,
EIZ=>SO:'|
rB.A. Grisso, Am.Soc',l14, 5160(1992)' andP.B. Mackenzie, J.R. Johnson,
These prclu on the regiosc tnho- and fru \t. l:utens ar
-Ttiphenylphosphine' Bis(1,5-cyclooctadiene)nickel In the presenceof [2 + 2 + 2] Homo-Diels-Alder reactions of norbornadiene,t alkenesat 80' with activated react can Ni(coD), and P(c6H5)3 (1:2) norbornadienes indicate that regioselectivity the of studies to give 12 + 2 + 2] adducts.Preliminary Thus molecules' of complex for synthesis this homo-Diels-Atder reactioncan be useful two in only results acrylonitrile with reaction of methyl norbornadiene-2--carboxylate
Bis(cyclopcrtr p-Kcto ct heramethl'ldis Jre convertd
Bis(cyclopentadienyl)chloro(hydrido)zirconium
C.1na()Uple :r:e,l from rt :hc alkYl
R1 t^
products (endof exo : 2.3:I), in which the electron-withdrawing groups are para to the diene substituent (equation I). Only two products are formed from reaction of the same
^
\
Ni(coD)2 cH3ooc. rl\
"Jgi'li,E u,"^"oo">> €
i
33
cnr:Lncrtr
6Hroocy\
Ua"*
'cN
exo-para
enoo-para Rz
2.3:1
:r."".&..r."".&
N cH3ooc\l\ r r:h .rlkvnes t r , . n .o f t h e
(tt)
SO2C6H5 C6H5S02
cHr:cHsircuHu
exo-para
exo-meta 2 : 1
t.r!li()n
can
,( \itCOD)z or: cr idently
diene with phenyl vinyl sulfone, the exo-para and exo-metaisomersin a ratio of 2:1. The presenceof a methoxy group on the diene lowers the reactivity, but 2-methoxynorbornadienecan react with methyl vinyl ketone to provide a single endo'ortho adduct (equationIII).
(ilr)
o$o"'"
+
CHr:\ po ci.
,.l\ ( YocHs 51v" *oo"r, endo-ottho
These preliminary resultsindicate that substituentgroups can exert a marked effect on the regioselectivityof this homo-Diels-Alder reactionwith a generalpreferencefor ortho- and para-isomers. I M. Lautensand L.G. Edwards, J. Org., 56,3761(1991). c lrc\cnce of l\cnc: at 80' r : r J r c a t et h a t rlriulcs. Thus , lr ()nly two
Bis(cyclopentadienyl)chloro(hydrido)zirconium,CpzZrHCl. B-Keto esters - enoales.l The enolates of B-keto esters, prepared with lithium in DME, on reactionwith the Schwartzreagent(1 equiv.) at0-2O' hexamethyldisilazane are converted into enoatesin 55-70% yield.
2,2i-Bis(diphenylphosphino)-1,1/binaphthyl
o.
.co2cH3
X
groups of the PhosPhin useful percursorto thc ,
DME 1) LiNlsi(cH3)312, 2\ Cp2Z(HQl
o
o
i l l l cH3l^focx, I -ruHcoq
o A -"or=,
CoHsNCo2Et
2
CoHs-
rA.G.GodfreyandBGanem'TetrahedronLefters'33"746'l(1992) 1'' Bis(2,6-diphenytphenoxide)tris(4-methylbenzyl)niobium(V)' aryloxide is an effiniobium This arenes'2 i)y'u't'a' All-cis Hydrogrr"tu,'tj cientcatalystforregioselectiu"t'yo,og.nutionofpolynucleararenes.Thusphenanthrene isreducedtotheg,l0-dihydrodcrivativeandanoctahydrophcnanthrenc'Anthraccneis H z ,1 C6H12,80oC
(78/o)
(22o/")
H
Z\,'\' I
l l
\-\2
|
' l
f^ff
l l \''-'/'\l
2-alkylidenecYcloPen
o
) H
(95.5%)
Asymmetric hYdroT tion can be effectc'd I regardlessof the gcom
(4.5o/o\
rH NMR spcctra indicates that Analysis of thc convertedto an octahydro derivativc' thchydrogcnatomsareallintroducedonthesamcfaceinthccascofnaphthalene' anthracene,and acenaPhthcnc' 10' 321 Rothwcll'Organometallics' f R.W. Chcsnut, G.G. Jacob,J'S' Yu' P'E' Fanwick'l'P Am Srtc''rr4'1s2'7(tssz)' an
ll o"\
o
) CH
2,2/-Bis(diphenylphosphino)-l,libinaphthyl
groups of the phosphine are replacedby 3,5-di+-butyl phenyl groups. (2S,3R)-3 is a useful percursorto the B-lactam 4.
)o:cH3
o
o
i l i l
CHs-
_\
Ru(il).1. cH2clz,cH3oH
-\ -OCH3 -a
l-NHcocuHu-
CO2EI
5
35
o H o l l l + (2R.3R)-3 cH.-^)focH. \ -NHCOC6H5
2
ee: 1
(2S,3R)-3(99%ee)
I n , : . 1 , , \ i d ci s a n e f f i F I :r. phenanthrene is rr:-- . .-\nthracene
1
OH
I
/t__\
(78/.) H
H .1.5ol")
l
?-*' 4
--\_/ _
,,
cH3-\Z: t
Asymmetric hydrogenation of 2- and 4-alkylidene-y-butyro-lactones.2 This rcaction can be effected by catalysis with Ru(ll)/(S)- or (R)-BIN Ap in 94-98o/o ee rcgardlessof thc geomctry of the olefinic group. This method is also applicable to 2-alky Iidenecyclopenta nes.
o
o
H2, CH2C|2, 500 Ru(ll)-(R)-1
o1:l.
,
Et
\__/
tl
o1n_
trI
\__/
(S), 92oloee
o
( '. . I rr
r.
\
/
CHs
ryttullics, 10, 321
(R), 94ol. ee
,l- ( 1992).
.:r \\ hich the phenyl
o1
Ru(ll)-(S)-1
/CHz
r:i .-:Jrl p-keto ester 2 h\.:' '\\ cstcr3 in 90% j1,- ,.rrrhhigh cnantio-
o tl
H2,
of
[ . : - . : r . r i n d i c a t e st h a t ! - -- rrf naphthalenc,
o tl 1t\z\ \__/
H2,
Ru(ll)-(R)-1
Bu
o tl o/\---'..^ Eu \-/
(S), 9a% ee
36
(R)-or(S)-2,2I-Bis(diphenvlphosphino)l,l/-binaphthvl
(BINAP) (R)- or (S)-2,21-Bis(diphenylphosphino)1,1/-binaphthyl triflate I with tetrabutylamvinyl of the Asymmetric Heck reaction3 Treatment and (S)-BINAP in Pd(OAc)2 of amount monium acetate(1.7 equiv') and a catalytic formed by a Heck ee, in 807o 2 pentanoid bicyclic DMSO at 20. results in the fused into 3, an convertcd be can product This process. reactionfollowed by an anion capture
Chiral sp iodoaniline(2 chiral ligand r
addedpromor of a basic tt'nt 1,2,2,6.6-pen
ffi; w
CHz Pd(OAc)2,(S)-BINAP Bu4NOAc,DMSO 89v"
CHs
2 ($O%ee) COOC2H5 I
QHg I H
s'eps(\t
several
o-
e
H
cHs 3
intermediatein the synthesisof several scsquiterpcnes' effected by a catalytic asymmetric arylation of alkenes.a This arylation can be Pd(oAc)z/(R)by catalyzed Hcck{ypc arylation of 2,3-dihydrofuranwith an aryl triflate (proton spongc)as basc. BINAP in rhc prcsenceof l.tl,-bis(dimcthylamine)naphthalcne activating factor. platelet This reactionwas used to preparean antagonist(4) of Pd(il)-(R)-BINAP base, C6H6, 40"
C6H5orf .
[)-o
tr-\
\o'2""'6u11u
(s)
(R) 46"/",>960/"a@
2-NaphthylOTf +
r-\
\o,
a
,,rNph
52o/o, >960/o ee
a
+ \o"\coH5 2 4 Y " . 1 7 Ye"e
'
Enantia pentenalssu ee by use of
\O"truPn 2 6 0 / " , 1 O o /E" €
"t.oy.\f,-Q.,,,(y) l) cat., 2-NaphthyloTl
CHsO--.1.OT{ 2)cat., ll I CH3O"-V
cHso/.v
\l^\/ p-Alll,ir,
hvdrogenatio
37 (R)-or(S)-2,2r-Bis(diphenylphosphino)l,l/-binaphthyl
ll:.:'tttVlam-
r-l.il\AP in | ^r a Heck :d lnl() 3. an
Chiral spirooxindoles.s An asymmetric Heck reaction of the acryloyl 2tand (R)-1 as the iodoaniline (2) effected with tris(dibenzylideneacetone)dipalladium upon an depending 3 spiroindole of the chiral ligand can provide either enantiomer addition whereas (S)-(+)-3, provides salt of a silver addedpromotor. Thus the presence aminc is effcctive Thc most (R)-(-)-3. of formation of a basic tertiary amine can favor (PMP). 1,2,2,6,6-pentamethylpiperidine
( B, ) - 1 ,8 0 " Pd2(dba)3 Ag3PO4,CH3CON(CH3)2
81"/o
o tl (^-ir^N"tt
( S ) - ( + ) - 3 ,7 1 o / oE a
f+--'A<' \.-o I ll \-,/
NCH3
(R Pd2(dba)3 , )-1,80'
:tl-itcd bY a 'g r I \c)1/(R)-
P M P ,C H 3 C O N ( C H 3 ) 2
)cir I lls base. .
t.
,.
(R)-(-)-3, 66% ee
. ^ \c5H5 U
S ,c-
.7oo
ee
-Noh :
'l'c
cyclization of 4Enantioselective cyclization of 4-disubstituted 4-pentenals.6 pentenalssuch as 2 to 3-substitutedcyclopentanones(3) can be effected in >997o ee by use of Rh[(S)- or (R)-BINAP]CIOa as catalyst'
9€
Rh[(s)-BTNAP]Cl04
cHo \
QH2CI2,20'
rcHz
\ 3 /
1"
R 2, R = t-Bu
o tl
87o/o
R = C(CHs)zCHzCHg 84% R=Bu
9Oo/o
3, S, >99% ee S, >99% ee S , 9 1 %e e
enantioselective B-Amino acids.T A useful route to chiral B-amino acids involves such as 1. Thus hydrogenationof (E)-1 hydrogenationof methyl B-(acylamino)acrylates
38
ll,4-Bis{diplc
(R)-or(S)-2,2r-Bis(diphenylphosphino)l,l/-binaphthvl
catafyzedby a complex of Ru(OCOCHT)zwith (R)-BINAP furnishes(S)-2 in 960/oee. Surprisingly (Z)-1 is convertedunder the same conditions to (R)-2 in 5Vo ee. Hydro-
CH3..\..NHCOCH3
H2 Ru(ll)-(R)-BINAP
cH..-fruHcoor.
o H &
(r)
I
tl cH3ooc'-
1,4-Bis(diphenylphosg Diastereoselectirc I diols.' This catalvstis alcohols (12, 426- 121 and vinylsilaneshavinc
cH3ooc'-
( E ) -1
I
c*t'',M
(S) - 2, 96% ee
oH cr flr) genation of either (E)- or (Z)-l catalyzedby Rh+(CH3OH)2CIO4 complexcd with (R)-BINAP resultsin (R)-2 but with modest enantioselectivity(45-6lqa cc). optically Asymmetric carbonylation of alkenyl hatides; a-methylene lactones.' active a-methylene lactoncscan bc preparcdby carbonylationof alkenyl halides such o/o)in the presenceof thallium acctate. as I catalyzedby PdCl2-(R)-BINAP (5 mol
CHz
cH3Fl r
P d c r 2 - ( R )- B I N A P TlOAc,CH3CN
+
Ho-
C
O 74"/"
Ho\&o
I M. Lautens, C.-H.Zhan
2,50/o ee
1
BINAP-Ru(II)
)'-,r'
CHz ,p cH" )-(
\__J
\JJ
CeHr
complexes.e
A
suitable BINAP-Ru(II)
catalyst for
asymmetric
hydrogenation of ketones (14, 40-41) can be prepared most readily by heating (R)- or (S)-BINAP with [Rucl2 (benzene)]2 in DMF at 100'to effect ligand exchange. A suitable catalyst can also be obtained by ligand exchange with RuCl2[Sb(CoHs):]., prepared from Ruclr and Sb(ccHs):, in o-dichlorobenzene at 160". Either of these catalysts gives satisfactory results in hydrogenations at 100 atm. at 25" or at 4 atm. at 100"' lK. Mashima, Y. Matsumura, K. Kusano, H. Kumobayashi, N. Sayo, Y' Hori, T' Ishizaki, S' Akutagawa, and H. Takaya,J.C.S. Chem. Conm.,609 (1991)2T. Ohta, T. Miyake, N. Siedo, H. Kumobayashi, S. Akutagawa, and H. Takaya' Tetrahedron Letters, 33, 635 (1992). 3 K. Kagechika and M. Shibasaki,J. Org., 56, 4093 (1991). a T. Hayashi, A. Kubo, and F. Ozawa, Pure Appl. Chem., 64, 421 (1992)' 5 A. Ashimori and L. E. Overman, J. Org., 57, 4571 (1992)6 X.-M. wu, K. Funakoshi, and K. Sakai, TetrahedronLetters, 33, 6331 (1992)' 7 W. D. Lubell, M. Kitamura, and R. Noyori, ktrahedron Asymmetry,2,543 (1991)' 8 T. Suzuki, Y. Uozumi, and M. Shibasaki,J. C. S. Chem. Comm., 1593 (1991)' eM. Kitamura, M. Tokunaga,T. Ohkuma, and R. Noyori, TetrahedronLetters,32,4l63 (1991).
[ 1,4-Bis(diphenylphoc nate, l(14, 44-45). Diastereoselectivc I tion of the vinyl sulfo Similar hydrogenation rate oxidation gives tlx
c6Hsso2
9H' cuHurs\cHs
o o H (R,R)- 4
R _
[1,4-Bis(diphenylphosphino)butane]norbornadienerhodium
! r:' 'l(r'i ec. Ilvdro-
i" .,
triffuorcmethanesulfonate
39
1,4-Bis(diphenylphosphine)butane(norbornadiene)rhodium(I)tetrafluoroborate, l.l Diastereoselectivehydrogenation of 7-hvdroxyvinylsilanes and -tins, Syn-l!hydrogenationof chiral allylic diols.r This catalystis known to effect diastereoselective hydrogenationof vinyltins alcohols (12,426-428). It can also effect diastereoselective and vinylsilaneshaving a 7-hydroxyl group (equationsI and II).
Bu
OH
ocH3 (l)
r
Hz,1
l
c5Hl1MSnBu3
snBu3
?t c5H11,MBu
75"/"
syn(>100:1) 2
flt) with
nrli\.d
CeHrr
?' ?'. ,/'-z'\sic6H5(cH3;
sic6H5(cH3)2 ?" c.Hrr'l\-AcH.
Hz,1
syn(>500:1) '
t )pticallY
I
I l.,li.lcs such
oo-"
ln' :!ctatc.
{-- / /. p t
I KBr, HOOAc
J
OH OH -\'z-,^ -CHs
CeHtt-
\
Honc r.raoRc,
syn - dlol
2^' to
I M. Lautens, Angew.Chem.Int. Ed., 31,232 (1992). C.-H. Zhang,andC. M. Crudden,
;=' ""
(\r .t\\'mmetfic hs.ttinq (R)- or nr:r
A suitable
1., 1,. prcpared i . . 1 l . r l v s t sg i v e s
II,4-Bis(diphenylphosphino)butanelnorbornadienerhodium trifluoromethanesulfonate, l(14, 44-45). Diastereoselectivehydrogenation of vinyl sulfones and sulfoxides.r Hydrogenation of the vinyl sulfone 2 with the Rh catalyst I proceeds in 99Vo de to give 3. Similar hydrogenationof the correspondingsulfoxide provides 5, which on perborate oxidation gives the threo-isomerof 3. Apparently the steric course of hydrogen-
9H,
lrrt' r
I
L:\.'
fdrahedron
0H anti -3,9910 de
2
.. Rhl'tt', Rh.1
pHr cuHu-s\cH.
o ) : - 1 h . r( 1 9 9 1 )
cuHusor&cH.
c6H5so2\cH3 OH
I s h i z a k i ,S .
t|,.
CH.
Rh.1H , 2,25"
(R,R)- 4
o
H
CHs oxidation cuHusor\cH.
CHr cunu-s\icH.
o
o
syn - 5,99o/ode
H
o svn - 3
H
40
Bis(dipivaloylmethanato)nickel(Il)
o
ation of sulfones is controlled by the hydroxy group, whereas the configuration at sulfuf controls the course of hydrogenation of sulfoxides.
)-''."'
I D. Ando,C. Bevan,J.M. Brown,andD.W. Price,J.C.S. Chem'Comm',592(1992)'
(,
""ol-
(TRAP)' 2,2//-Bis[1-(diphenylphosphino)ethyl]-1,1//-biferrocene
\Z^\
I rT. Yamada, K. Takah.
(s,s)-(R,R)-TRAP
( l ee1).
[N,M-Bis(4-methoxl
CHtt"'1"tt P(C6Hs)2 A catalyst prepared from RhH(co)[P(c6Hs)r]: Asymmetric Michael adilition.t ketones and TRAP can effect asymmetric addition of a-cyano carboxylatesto vinyl selectivity' or acrolein. Note that isopropyl estersshow the highest
O
NC.--.-COO-iPr
l l ^ , r + J CHs"'-\y'w'1z
CHs
3-5"
o ),,--,-,-coo-t-Pr CHs cf;\N R (B4oloee)
o ^)--,,o"^r*
Ncrcoo-i-Pr CHs
o 11A.--'-*Coo-i-Pr cH]'ctl R (84oloee)
Expoxidation ol t epoxidation with oxr'1 reductantis 2-meth1'l alkenes.
cr
cH.A
I M. Sawamura, andY. Ito, Am. Soc-,ll4' 8295('1992)' H. Hamashima, Bis(dipivaloylmethanato)nickel(ID, Ni(dpm)r. 1,3Baeyer-Villiger ox'dation.t Complexes of nickel coordinated with several aldehyde an and oxygen molecular with diketones are effective catalysts for oxidations involving or alcohol reductant(16,30-32). Such oxygenationsare much saferthan those oxygenation catalyzed a such peracid. a peroxide or the usual oxidantssuch as hydrogen can be used for Baeyer_ Yilliger oxidation of either cyclic or acyclic ketones.Highest yields are obtained with bis(dipivaloylmethanato)nickel(Il)as catalyst (l mol%) and isovaleraldehyde as reductant.
cl
' T . T a k a i ,E . H a t a , K. Y
1,2-Bis(methylene)c B,y-Enones. Rr siumprovidesa magn
1,2-Bis(methylene)cycloalkane-Magnesium
o
)ri .r: \ulfur
t
93%
l
\-.-
L)""
02, RCHO,Ni(dpm)2 ctcH2cH2ct,25"
/-'-a"'"
)
"r,o.]-
cH3oY\
-"Y
4l
CHs
o
\o\o4.,.
76%
o IT. Yamada, K. Takahashi,K. Kato, T. Takai, S. Inoki, and T. Mukaiyama, Chem. Letters, 647 (1991). I),
lN,M-Bis(4-methoxysalicylidene)-o-phenylenediaminelcobaltfl
cH3o
9CHs
; { t '(r, H s ) r ] r in\ I kctones (1)
a
COO-i-Pr
\ ^ . ,I\
Expoxidation of alkenes.t In the presence of this complex, alkenes undergo epoxidation with oxygen (oxidant) and cyclic ketones as reductant.The most useful Yields are -8OVo for trisubstitutedor exo-terminal reductantis 2-methylcyclohexanone.
\-
,r
alkenes.
COO-l-Pr
t *
1.' O,.- r-{/
CH. t cH./\--czHrs
n .lcral
1,3-
ri .'n aldehYde h,'.c involving rJ,,rrgenation 1,'xg. Highest 11 nrol%) and
"r.t).
1ao
/ \
g
\__J
/cH.\ n -v
CHa t -
cn^4-y'c'Htu -o-
#rs u*- sn.Alc,H,,
rT. Takai,E. Hata,K. Yorozu,andT. Mukaiyama, (7992). Chem.Letters,2O77 1,2-Bis(methylene)cycloalkane-Magnesium,16, 198. with activated magneB,y-Enones. Reaction of 1,2-bis(methylene)cyclohexane sium providesa magnesiumcomplex (1). This complex reactswith ethyl acetateat - 10'
42
Bis(oxazolines)
when heated to form a spiro enol containing a cyclopropane ring (a). This intermediate undergoes ring expansion and protonation to form 2'
cHz
+i..t;
r->--f I ll ,Ms
cH3cooEt
-78'-
Enantio*l t S)-phenr'lglr rs a highlv cn * ith -j-acn lor'
-10"
\-,ry
CHz
6Hs)1 ' CHs-
1
2)H3o' a>r-\ .."-ZcH" -oH I | -oMsoEt (-L-A"t' '''' ** Wcr, 2
(r) cHz
Ms/-<"" Cil"n HcH,
PTCOOC2H5
\_-^J
@K:l
overall
I H. Xiong and R.D. Rieke,Am. Soc.,ll4, 4415(1992)'
Bis(oxazolines)' 16, 38-41. r Bis(oxazolines) (1) are easily prepared by reaction Asymmetric hydrosilylation of(S).aminoalcoholswithdiethyloxalatefol|owedbycyclization.Whenpresentin cxcess,ligandsofthistypecaneffectenantiose|ectiveRh(I)-catalyzedhydrosilylation
(
Enantiml from t-leucino complex(2) *r *ith ethvl dia
P-------q l l l l) r NJ
\-N {
c6H
"
R CuHrA
The highest enanof acetophenoneto give (R)-1-phenylethanolas the major product' but using chiral results, Similar tioselectivity, 84%, obtains with l(R:CHzCoHs).1 enantioselectivity highest case, this In pyridyloxazolines,havebeenreportedby Brunner.2 obtains with the ligand bearing l-butyl as the alkyl group' in a Michael or a These chiral bis(oxazolines)effect only slight enantioselectivity ligand' this by inhibited is actually Reformatskyreaction.The latter reaction
G. Helmchen. : ll. Brunner ar 'E.J. Corel and ' D. A. Evans- X
Bis(oxazolines)
tr( ',\hcnheated
Enantioselective Diels-Alder catalyst.3 The chiral bis(oxazoline) 1, preparedfrom (2) serves (S)-phenylglycine,in combinationwith MgI2 or magnesiumtetraphenylborate of cyclopentadiene reaction for the Diels-Alder catalyst as a highly enantioselective with 3-acryloyloxazolidine-2-one(equationI). CH3 ,CH3
cH...r,ro#o\-cH. cH./Wiv ru-/-cs.
1 ' M g [ ( C 6 H 5 ) 4 8 ] 2( 2 )
'aunu
cuH{ 1
2'c*2ct2t
-oH
N
.,,=rLA.O#&":j, g
?
-Pr
\J endo/exo = 97:.3 90.4o/oee Enantioselective cyclopropanation (16, 38-39||.4 The bis(oxazoline) I, prepared chloride), forms a white, crystalline from r-leucinol and 2,2-dimethylpropane-1,3-dioyl complex (2) with CuOTf which is an effectivecatalystfor asymmetriccyclopropanation
T.1:JJhY reactron \\ hcn present in
with ethyl diazoacetate.
cH3rcH3
r.::rdrosilYlation
P--\o..
( i l i l ) NJ \.-N '-I (cH3)3c c(cH3)3 1
o\, fi
c6H5
cH, + N2cHcooc2H5
r, cHct3
-CHa i c .
c6Hs'*"\cooc2Hs I:.t highestenans. i.ut using chiral s: r nuntioselectivitY r rr .r Michael or a i. lrsand.
(1R,2R),96% ee
* "urAcooc2Hs 73 i 27
(1 R,2S), 94o/oEa
: G. Helmchen, A. Krotz, K.-T. Ganz, and D. Hansen, Synlett, 257 (1991). I H. Brunner and U. Obermann, Ber., 122, 499 (1989). 'E.J. Corey and K. Ishihara, TetrahedronLetters,33,68O'f 0,992). ' D. A. Evans, K. A. Woerpel, and M. J. Scott, Angew. Chem. Int. Ed., 31, 43O (1'992).
U
Bis(pentamethylcyclopentadi€nyl)methylyttrium
yttrium' Bis(pentamethylcyclopentadienyl) [bis(trimethylsilyl)methyl] (1)' (C5Me5)2YCH[S(CH3)31, is an effective catalyst for hydrosilylaHydrositylation of alkenes.r This lanthanide at 20' in C6H6or CeHsCH:' Hydrosilylation tion of mono- and l'l-disubstituted alkenes olefin is highly selective' of dienes with a terminal and an internal
=at, -]#At*
/YCH, (,\,^cH,
(cH2)3cH2siH2coH5 cH3cH=cH
oc(c6Hd3 cHrx,A(cH"lrr
.-Y",, ;;*
Hydrogenation ol dic' ' methane to form catall'st terminal doublebonds in tl
(\.4(cH2)3siH2c6H5
1G.A. Molanderand M' Julius,J' Org', 57' 6347(1992)' Cp;YCH3(THF)' 1' Preparation'r Bis(pentamethylcyclopentadienyl)methylyttrium' of 1 with hydrogen generates Cyclization of 1,5- and 1,6-dienes'2 Treatment ..cpjvH,,(2)withreleaseolCHa.Thishydrideisaneffectivecatalystforcyclization of1,5-and1,6-dienes,eventhosewithbulkysubstituents.Nocyclizationisobserved SO2C6H5groups' when the substratebears CN, COOCH3, or
327,3r (1e87).
F cn/\("'zcHz
' K. H. den Haan, J. L. de &r
*
(^)''cH'
R.^,y,"\'-CH3
\__/
: G.A. Molander andJ.O. H t ldem' J. Org., 57, 3266tl
R = OBzl = OC(CoHs)g
(5%)
(6: 1),84% ( 2 1: 1 ) , 9 9 %
oc(c6H5)3
CHz=rr.-rr^.-zcHz
*.
oc(c6H5)3
oc(c6Hs)3
Bis(pentamethylcyclopcr ( C s M e s ) 2 S m ' T H F( l ) . h Hydroboration v'ilh t tirr hydroborationof a u'i the order: monosubstitut rrisubstituted.
,rAr,. C5H11CH:Cl
100:1 (7O/o)
25o/o
P"' ,if"r, \),'zcHz
\r'-J 53o/"
%czHs 26o/o
W. J. Evans and T. A. Ulih K. N. Harrison and T.J. ll
Bis(pentanethylcyclopentadienyl)samarium
)r r,\ drosilylalr jr,'silylation
Hydrogenation of dienes.3 This organolanthanide when treated with H2 loses "Cp2YH," which can effect highly selective hydrogenation of methane to form catalyst terminal double bonds in the presenceof other double bonds, even those of allylic ethers.
H z ,1 , c6H6,-78"C
9H=CHz {2SrH2C6H5
tetrahydrofuran
.....'.."......................................,.-'.........................*
oc(c6Hs)3 cH2\..\(cH2)3cH=cH2
aC:Hs
. l'rcparation.i lr,,*cn generates \r 1',r cyclization alr,'n is observed
oc(c6Hs)3 ?c(coHs)s cHzxA(cH2)4cH3 , cHs\,.\(cHd4cH3 (e6%)
(1 o/o)
' K H' den Haan, J. L. de Boer, J. H. Teuben,w. J. J. smeets,and A. L. Spek,J. organo met. Chem.,
a"."-/YcH3 (5"/")
oc(c6H5)3
327,31 0981. I c.A. Molander andJ.O. Hoberg, Am.Soc.,ll4, 3123(1992). i ldem.,J. Org., 57,3266(1992).
Bis(pentamethylcyclopentadienyl)samarium tetrahydrofuran. (CsMes)zSm'THF (l). preparation.l Hydroboration with catecholborane (CB).2 This ranthanide is an efficient cataryst fbr hydroborationof a wide range of arkeneswith cB at 25". Highest rates obtain in thc order: monosubstitutedterminal ) disubstituted terminal > disubstitutedinternal ) trisubstituted.
p'Ap, 1) 1, C6H6,25o
C5H11CH:QH2 + CB
2) H2o2'NaoH
-
78o/o
CzHs
- .4^ C)-"r3 \__J 7s/"
L/--"t.
CeHs 26%
W.J. Evans and T.A. Ulibarri, Inorg. Synth., 25,2g7 (1990). K. N. Harrison and T.J. Marks, Arn. Soc., ll4, 9220 Ogg2\.
46
chiral BisPiPerazines,
CoHs Bis(phospholanes). of (3 and 4) can be preparedby reaction The C2-symmetricbis(phospholanes) L'4-diols' the cyclic sulfate (2) of chiral dilithium bis(phosphidol"tttunt1f; with
cHr--l--VcH. urP^eu,
|
1
+
o),tao
1
9
/RN
?
1tr^R\/ a*
0 0
1,n=2,a)R
\_J Rs _/ CoHs
(s,s)-3,R = CHg
R-a) ''* 1) BuLi 2\2
PHz
-=)tt
l l l
%.r-l* R,"( I
PHz
\-.,/
(s,s)-4,R = CHs
Enantioselectivehydrogenation.|Rhodiumcatalystsbearingtheseligandseffect RCH:C(COOCHT)NHAc' In general' asymmetrichydrogenationof acetamidoacrylates' enantioselectivitiesofaboutloovoareobtained,particularlywithligandsoftype(S'S)-4, R:CzHs. Highenantiomericexcesscanbeobtainedinhydrogenationofenolacetatescata|yzed b y a R h c a t a l y s t w i t h t h e s e c h i r a l l i g a n d s . l n t h i s r e a c t i o n , n o o n e l i g a n d iand s c othe n s i sR/ tent|y with R in the bis(phospholanes) superior, but the enantioselectivity;aries in the enol acetate.
CHr i l -
n'Aonc
Rh.(s,s)-4,R=czHs?"' -oAc R' '
R'= CzHsOzC
>997" ee
1M.J. Burk,Am. Soc.,113,8518(1991)' Bispiperazines, chiral. by of N,N/-dialkyl bispiperazineslinked AsYmmetric osmYlation' Chiral ligands transof dihydroxylation :2) can effect highly enantioselective two carbons (L, n disubstitutedalkenes.
Whenn:3or4.thcsc group, the enantioselectivit osmylation of mono- and < alkenes. 'K. Fuli,K. Tanaka, andH V
Bissteroidal pyrazines. A new group of steror cytotoxic, are comPosedof t
Smith and Heathcockr hav identical steroid groups arc {SchemesI and II). !
?
Bisstemidal pymzines
CoHs
CoHs ir!:l()n
Of a
il,'1.
RN, ,N-(CH2hN \-J \---J
CoHs
R II
NR CoHs CHg
1 , n = 2 , a ) R = C H 3 ,b ) C H 2 C ( C H 3o) 3 r c, p H 2 {
)--\ )-CH.
CHs 11
_
v
',CaHu
, J
OsO4,L*
CoHs
r-t
L* = la =lb =lc
",,,?t.zcaHs ""^{-[n^
84o/o 87o/o 84"/"
94o/oee 91%ee 89%ee
When n : 3 or 4, these ligands suppressthe reaction completely. If R is an acyl group, the enantioselectivityis depressed.These ligands (l) can also effect asymmetric osmylation of mono- and disubstitutedtcrminal alkenes, but not of ci.r-disubstituted alkenes. =CH3
Lrr.,n.ls cffect e In gcneral, rrpc (S,S)-4, r:;. catalyzed s ;,,nsistcntly s, .'nd the R'
I K. Fuli, K. Tanaka,and H. Miyamoto,Tetrahedron Letters,33,4021(1992). Bissteroidal pyrazines. A new group of steroidal alkaloids, known as cephalostatinsand shown to be cytotoxic, are composedof two identical steroidalgroups connectedby a pyrazine unit. Smith and Heathcockr have developed two routes to alkaloids of this type in which identical steroid groups are linked at C2 and C3 of thc A ring to the pyrazine ring (SchemesI and Il). 1) C6H5NH*Br3-HOAc
Nsr,.
2) NaN3 510/o
o
ir::. linked by ttr,'n rlf /ransSchemeI
ln contrast. I reacr l.-l-butadienc(equz
(S.S)-Bis'p-tolylsullinylmethane
HzNr,
1)cH3oNH3+cr H2o,THF 2) P(c6Hs)3,
c"H.crjaol-
a
87"h
(r)(s.s)
4 Schemell
or anunsYmmefi:iJ:t#i"i:T","u"il"ilT; a svnthesis alsoincludes rhereport at 5r are heated first ^"td-1t..'Oation
of 4' and
1) 4, c6H5cH3'9oo 2\ 1450
AcO
\. Kunieda. J \ol (i. Solladi6. F (-t ftrahedron. 32. 7
rlR.2R)'lr'f.I isoproPoxide.
p
Enantiosclctt hsdes Proceedstr irom the combina
43"/"
5 145"' the pyrazine 6 at intermediatethat forms J' Org'' 57' 6319(1992) I S.C. SmithandC'H' Heathcock'
,t
rvI oxide' -methv r-p-to (R) and ?;ff ,t"#:lf H:ffi1""T,"'.:?te '(^.9q.s (1)
C5H5Cfl(
CrHr'SJ"-tt"' The anionof this C2-symmetric withcarbonylcompoun'ds'2 in contrast reactions Asymmetric high diu'tt"oselectivity "#"U" t*nydes with with react diastereoselectivity' can (1) low reasent wt'i"tt "i"o *ttn to the anionof methyl t*l'ltt'i-'.itoxia" CoHz
c6Hitiit ?1i,,* -;-
(S,S)-1+ C6H5CHo
Ht'f,H\S';. CoHz
(s.s,s)-2 =eo:10 is,s,sln,n'n)
lligh enantiosc .ind also *ith r
ll. Takahashi1 ( le92).
9-BorabicYclol 1,4'HYdnl
or catecholkln respectiveof I
9-Borabicyclo[3.3.1]nonane
(9-BBN)
In contrast,l reactswith an d,B-enal to form a 4-substituted1,1-bis(p{olylsulfinyl)(equationI). 1,3-butadiene (E) foHz BuLi' -\-.\"-S.,*' rHF ' CH3I -o 64y" ,9_-O C6H7 ",..
(E) (l) (S,S)-1 + CH3CH:CHCHO
( S , S ) - 3 ,a s - 2 2 o
In order obtain an
{yv t l H
I N. Kunieda, J. Nokami, and M. Kinoshita, Bull. Chem. Soc.Jpn'' 49,256 (1976)' 2 G. Solladid, F. Colobert, P. Ruiz, C. Hamdouchi, M. C. Carrefro, and J.-L. Garcia Ruano, Tetrahedron, 32, 3695 (1991).
(1&2R)-1,2-N,M-Bis(trifluoromethanesulfonylamino)cyclohexane-Titanium(IV) isopropoxide. allcylationof RCHO.| The reaction of diethylzinc with aldeEnantioselective by the complex(l) obtained when catalyzed enantioselectivity high in proceeds hydes andTi(O-i-Pr)a. disulfonamide C2-symmetric active optically the of the combination from SOTCFT N
)ri1o-i-e4t
(1)
N
SO2CF3
1,coHscHs , -20"_ C6H5CHO
,'t this C2-symmetrlc .- lcctivitY in contrast ,r tlrirstereoselectivitY'
+
(C2H5)2Zn
e8"/"
C6H5yC2H5 H oH (S),98%ee
High enantioselectivitycan also be obtainedwith (cHr)2Zn, (Bu)zZn, and (csHrr)zZn, end also with aliphatic aldehydes. 5691 :H. Takahashi, Tetrahedron,4S, T. Kawakita,M. Ohno,M. Yoshioka,and S. Kobayashi,
(teez). ^ro
)F5
- ;-' F = 90:10
9-Borabicyclo[3.3.1]nonane(9-BBN). 1,4-Hydroborations of enones.t Phenyl l-alkenyl ketones are reduced by 9-BBN ()r catecholbofane(cB) (1 equiv.) in >957o yield to boron (Z)-enolates(>99/1), irwith resoective of the substituents on the alkenyl group. The reaction is more rapid
50
Bomne-DimethYl
sulfide
9-BBN undergo aldol reactions to provide CB. The (Z)-boron enolates derived from (Z)-boron enolates formed from CB show aldols in )96Vo syn-selectivity' However' : lower selectivitY(sYn/anti 3:1)'
g-aeNr -ctt --Y^%Hs oBRz 2'>99:1
cft \/yc6H5 o
jH'9!- CH3.-=.1-C6Hs
o
cH3xH3
e-
"osiR
cHss'!
osiR3
I c6HscHoI 99% V cH2cH3 CuHu*C6H5
o
(r) V'
= 99:1) @Yn/antl
1) BH
2l t+l
OH Alkenylalky|ketonesun
Borane-Dimethyl sulfide, BHj' S(CH3)2' ' of quinone ketals by BHr S(CHr)z C-Aryl gtycosides-t Reductivearomatization providesu**,out"toC-arylglycosides.Thus2-lithiodihydropyran(2)and3rcactto formaquinolketal(4).Reactionof4withBHs.S(cHj)2reducestheglyca|doub|e from p-methylanisole' bond and provides the C-glycoside5 derived
Diastereoselectivc h1 csterswith BHi 'S(CH, oxidation affords 2-alkox
9CH.
C
n'ArV I
CHg CHEO. -
\./
Li +
i
a\
l
,OCHg
r
Vll
l
9cH.
o 3
cHso. /,ocHs
r\."
Ar
!
-\Yt'\./
CHe
ll::;,:8x". A%;i1 50-60%
a"Y-ot \-/4 approachis formulatedin equationII' An alternative
\Z\OCH.
s
The diastereoseleoi \tcreochemistryof the d
K. A. Parkerand C.A. Co r J . S .P a n e ka n dF . X u .J
Borane-Dimethyl
sulfide
5t
r!*r!:l(rns to provide n..l lrom CB show
H- -y"u"t o
(tt)
CHat"'
''osin,
9e 1r
'"osiR3
1) BH3.S(CH3)3 2) H2O2,OH
11 .r rlh 9-BBN, with
al. 'r
BHr 'S(CH3)2
r r . : : rr l ) a n d 3 r e a c t t o lr. titc glYcal double rlr
.t."
(Yo"'" ao)...'\-/
R3sio^*osiR3 : OH Dinstereoselectivehydroboration.2 Hydroboration of a-alkoxy-B, 7-unsaturated esters with BH: . S(CHI)2 (1.05 equiv.) in THF at O - 20" followed by standard oxidation affords 2-alkoxy-1,3-diolswith significant diastereoselectivity.
9CH.
gCH.
1)BH3.S(CH3)2 2) H2O2, NaOH
9CH.
9CH.
o'.Y-t-\
nr-\-rVcoocH3 cHs
cH3 oH
oH
2,3-anti12,3-syn=8:1
9cHt
QCHs
coocH3 --run___*
A,
CHs
z,3-anti12,3-syn= 4:1
\ t
CHs
'OCHr
The diastereoselectivityis independentof the size of the alkoxy group and of the stereochemistryof the double bond. iK.A. ParkerandC.A. Coburn, Am.Soc.,ll3, 8516(1991). :J.S. PanekandF. Xu, J. Org.,57,5238(1992).
52
CH3rCHl
Boron trifluoride etherate
'ilanestoRCHo;tetrahydrofurans'1 trifluoride etherate' Boron ""'";;;;;'setective uddition ailditionof chirat @''*"^"":::#'ffi;;;iective acid promotorfor diastereoselectivr **" "il"*t to form rno" tf't i' aldehydes BF3 etherate (1) to a- una B-utn'yroxy B+ilyr-tei-;;lsilanes of a-substituteo
I "r,/YcozcHg
tt"d'-;o2cH3 ,15';?lB',13t, -B5%-
BzlO---...'\Orf,"r"r.
(cH3)2sic6H5
,% 6
u\<^o" l l \-/
OH
.'-<-cH2cH3 I
CHs
BF3€ i
|
: J . S . P a n e ka n d M Y a n g ' { a : G . H . P o s n e rE ' . M' Shulman' 32 Anieh, Tetrahedron Leners'
96% de
ov,,
(2s,3s)-1 5-Bromo-2'PYrone,
"r.--o..-,flo,"r.
tY;--*
Bzro
"v\
n
96% de
(2R,3R)-1
I
"t3z
cHs'--/'--'(--cozcHs
2, BFgo(czHs)z, ao%
oj
/SiR3
fa
,co2cH3
\ot1"*. Bzlo-.-,...
(cH3)2sic6H5
Diels'AldercYclu&i 15-100' to form adduo llctones.It is thereforea 1
96o/ode
(2R,3s)-1
9*'
"^"-=/?co2cH3
cozcH3
3Yuil-'-
Bzlo CHe
(cH3)2sic6H5
o\r"\
6--2L"
96% de
(2R'3R)-1
l.,''cn,:( es"u'f ziHaLx
involvel'a (1-3 rhis heterocvclization ]:1;'J::[::,'::'l^l"n u'" etherate 2,5-cis-furans' reactio":T;.;;;""0'""t0 This Burgess the tert-aliohols'2 with of Dehvilration higher'ff areusuallv could dehydrat i"ratritzs".Yields **"-i.ntotation When ffi: acid' ."rri,','" reaqent, thionyl chlori*'"tt"t' "n""".,',j" ."ril, in two different
O-
PreParation:
(cH3)2sic6H5
9H'
a
rlt "toluenesulfonic ro.. tt"rnroovnutically
stable alkene predominates'
Noepentyl,ert-alcohols'*"it''"'tl"*resofalkenes'someresultingfromacarbocatron rcafrangefirent'
t'v
o>-\'-r"' d"<
K. Afarinkra and G H Pt
5-Bromo-2-pyrone
cH3/cH3
BF3.o(c2H5)2
V
mhydrofurans.r :lrc:ir c addition dcrr Jcs to form
cHzclz ' 610/o
rt\rAoH I I
(Y
|
S R-.
,.co2cH3 I
n
1n,
t
un3
(Y"t"'""
+ 0 90:1 cH2cH3
OH ./\(
cH(cH3)2
+
-CH2CH3
+
(/
lsY"
|
99.6:0.4
f"'"
l J . S . P a n e ka n d M . Y a n g ,A m . S o c . , 1 1 3 , 9 8 6 8 ( 1 9 9 1 ) . l G . H . P o s n e rE , . M . S h u l m a n - R o s k eC s ,. H . O h , J . - C .C a r r y ,J . V . G r e e n ,A . B . C l a r k , a n d T . E . N . Anieh, Tetrahedron Letters, 32,6489 (1991).
de
o)).-r, R: ...S |
5-Bromo-2-py-n., (1)
,rCOzCHs
i \cH.
Preparation:
oY) /S,R. ,CO2CHs x 'CHs
, C l q ,A 1 ) N B S , ( C 6 H 5 C O ) z OC 2) N(C2H5)s
oY> o4",
oJ
,r-( E:E
1 Diels-Alder cycloadditions.r This pyrone undergoes Diels-Alder reactions at l-5-100" to form adducts that on radical debromination afford halogen-freebicyclic lactones.It is thereforea practical equivalentto 2-pyrone itself.
SrR3 ,co2cH3
' ir \cH.
")) o'?t*
+cH,:6116es,k
P" :e
":Y-cooH #---/ (endolexo = 100:0)
,1""r:""""o o".r^l -''"1
2) NaBH4, cH3oH,25'
rh l'it:, ctherate(1-3 *..; * ith the Burgess r Jihrdration could rl'rrnc Predominates' ! lr,16 n carbocation
ttv
csA,cH3oH
">-\tr>-cH2oH--ffi* #--_/
Br:-Z\..COOCH3
I I----,'-\CH2oH
HO-
K. Afarinkra and G. H. Posner, TetrahedronLetters, 33,7839 (1992).
(5S,6R)-4-r-Butoxycarbonyl-5,6-dipenyl-2,3,5,6'tetrahydm-4II'1,4-oxazin-2-one
54
(5S,6R)-4-t-Butoxycarbonyl-5,6-dipenyl-2,3,5,6'tetrahydro-4H'1,4'oxazin-2'one) 14, 58-59. Asymmetric synthesisof arylglycines.r These glycines are difficult to obtain in optically pure form becausethey readily undergo base-catalyzedracemization.One of the most useful routes involves the Williams glycinate (l). Bromination followed by alkylation with an arylcupfateor an afene (ZnCl2 catalysis)provides 2. Removal of the Boc group (ISiR3),hydrolysisof the lactonering, and oxidative removal of benzaldehyde provides the free amino acid. Even a furanylglycine can be prepared(equationII). 1)lsi(cH3)3
QoHs
QoHs
coHs,. aHs,,, o l]l:?";'"'o ,,"_*-cooH r.,---n f | | 111"1i".""r," -
tr ) aocN\,,\
s6%
nu
eocN-*.-\
*
o
H-"\cuH,
,i\ur,
QoHs caHs,,,.a/\o
2)(o) , zncr,
HzN H2tpd
c6Hs,,. (-o
ao"il-.,.,,\o ,{
trans- ( - ) -2-t-Buty.k1
u)-?
I
90o/"€€
This oxazinoneroute can be usedto obtain bisaryl glycines by a version of the Stille coupling rcaction (equationlll).
goHs
t'3ttli-,,o.,".
CoHs
cuH'\Ao 31il?''"*"cuHu:A. I
( I r r ,
|
BocN:o,\O
|
R. M. Williams and J
CoHs
1)NBS
(rr) eo"rl_ (o--=t-
B2%ee
zv"/o
I
I
This chiral alcoh chloroacetate(reaoio ltvcr acetonepowder :hcn be saponifiedto This alcohol w.ha r\\'mmetric induction icss effective than ti1
BocN---,,\O
s\ B ' H
P. Esser,H. Buschm ,1992\.
\
/
Tfo
r-Butyldimethylsily-l r Intramolecular .1 r rth NEtt can effec r'lvcyclic systemfuv
l-,ot
t-Butyldimethylsilyl
trifluomrnethanesulfonate
l.{
H2N\ -.COOH
-\
H
C6H5
B2/oee
90o/o€€ | . 1r J r \ i o n o f t h e S t i l l e
o
' R. M. Witliams and J. Hendrix, Chem. Rev.,92, 8gg (1gg2).
trans(-) -2-t-Butytcyclohexanol, - -" aY (1R,2s)-(-)-1 \_r.,c(cH3)3 This chirar arcohor (-)-r can be obtained from racemic l by conversion to the chloroacetate(reactionwith crcH2coou), wrriJ is saponifiedby enzyme pLAp (pig liver acetonepowder) at 4?% "onu.rrion'to g*. and the (+)-ester, which can t-Ir then be saponifiedto provide (+)_1. This arcohor when used as a chiral auxiriary in four asymmetric induction than trans-2-phenyrcyctohexan.r test reactionsshows higher or menthor. It is onry srightry less effective than g_phenylmenthol as a chiral uu"iliury.,
i;ril;:t
H' Buschmann' M. Mever-Stork, and H.-D. Scharr, Angew.Chem.rnt. Ed., 3r. ltso
t-Butyfdimethylsilyl trifluoromethanesulfonate (l), 12, g6; 15, 54_55. Intramorecurar Michaer-ardor cycrizstion.t itris sityt triflate (l) in combination with NEt3 can effect cycrization if a,B-enoates substituted by a keto group ro a polycyclic systemfused to a cyclobutane.Thus reaction of (E)-2 with 4 equiv. of l and 7
t-ButYl hydroperoxide
osiR3
/* I
I
l
I
o2'\r"
l
-
l
"'l;3il'i"
il.
coocH3
48"/.
-coocH,
(Bzt)zN, /z-CO PrcH) 1
(E)-2
AcOH, H2O 51o/"
coocH3 4
retro-aldolreaction' can be convertedinto 4 by a equiv. of NEtr provides 3, which Another examPle:
Use of m-chloroPc complete chiralitv tran
H
llf"?ii,'="*"o,"".
cH3o-",^---,'*--'H
6cH.?+
clcc|t cHg
74%
.l
I
-
H ,/t,
H
at^j^ cH3o2c"'V
?''( H
1,NEt3
--sr%-
\ \- / ' \ " H I
I
cn"orc-'\r? R3sio
/l
*-)
il
ll4' and K' Fukumoto'Am' Soc'' I M. Ihara,M. Ohnishi,M' Takano'K' Makita'N' Taniguchi' 4408 (1ee2). i M . T . R e e t za n d E . H
t-':1,:t$,::i#]'!r7.r*rn
y-dibenzvlaminoof chiraty-aminoenoates. Since since
(16, 30a) and reduced with high stereoselectivity can be 'iii-""0**" Reetzr has B_keto esters stereoselective"up'uit addition' r-BuooH with 7-dibenzylaminoenoates epoxidation substrates(1). In this case, as investigated epoxidation oi in.*" hydrolysis ester in results potut'iut t-butoxide' which requires the presence of stereoselectivity' high with epoxidation can proceed well. under these conditions with cuprate also to form is outalned and this reacts Essentially a single O'";;"; lZ; a single Product (3)'
rButyl hydroPerori Sharpless asYrst late on classicalePot dnli-epoxides,but on
r99:l). No reaction Sharplessepoxidatirx
,,
1)t-BuOOH, KOC(CH3)3, THF/NH3
- ,osiR3 -coocH3
(Bzt)2N y'z-coocH3
isopmpoxide
tartrate-Titanium(IV)
,-Butyl hydropemxide-Dialkyl
n
,*H-.._
R.--,,
+ anti-2
I
PrcH)
(Bzl)2N
3
syn-2
(CHg)zCuLi -
>96:<4
OH I
R---,,I-.--COOCH3
l
(Bzl)2N
i
CHs 3
E:: .'idol reaction'
Use of rn-chloroperbenzoicacid provides an amine oxide 4, which rearrangeswith complete chirality transfer to a hydroxyamine(5).
.,
CICoHqCOsH CHzClz,-50" -
.o-
I
(Bzt)zN+,r__Vz- COOC2H5 | . t \ I
R
-r'-\-'H
--Y /l
F.SO
il
. ,nr()to, Arfl. Soc', ll4,
l
7O-80/o
4
R"z"'rcooc2Hs H2,Pd(oH)2R ----.r,-r.COOC2H5 l - - - - - - . - - - -eoo/" --.-_ I 6ru1azt;, OH 95%ee 6
I M.T. Reetzand E. H. Lauterbach,Tetrahedron Letters,32, 4477, 4481(1991\. : :'.: 7-dibenzylamino16. 304) and since ; . ' J , l i t i o n , R e e t z rh a s
r
p,rrJ.rtionwith t-BuOOH It. :rr rrster hYdrolYsisas If ::rqh stereoselectivitY' ari- .uprate also to form
t-Butyl hydroperoxide-Dialkyl tartrate-Titanium(IV) isopropoxide. Sharpless asymmetric epoxidation of B-hydroxy acrylates.t A B-hydroxy acrylateon classicalepoxidation(alkalinehydrogenperoxide)gives a l:1 mixture ofsyn- and but on Sharplessasymmetricepoxidationgives the syr-epoxideselectively arrli-epoxides, t99:1). No reaction occurs in the absenceof the hydroxyl group. The asymmetric Sharplessepoxidationalso is possiblewith cyclic B-hydroxy ketones(secondexample).
,-Butyl hydmpemxide-Dialkyl tartmte-Titanium(IV) isopmpoxide
o H o
r t l
cHsl\y^oc(cH3)3
TBHP,Ti (o-,-P04 cH2cl2,-15' . .., v'
o H o '3
| ll -^--(}OC(CH3)3
7To/o ,.u
CHz
(syn/anti> 99:1)
o H o t t l
o H o
cH3->") "\_,
Butyllithium Diastereosela cthers(l) with Br selectivity,depex hv Petersonelim t rienes.
(CH3)35i-.tzz
(syn/anti= 99:1) Double kinetic resolution.
Davies et al.2 have noted that the enantiomeric selectiv-
ityofSharplessasymmetricepoxidationofanallylicalcoholcanbeenhancedinsome of the allylic alcohol I with casesby use of two kinetic resolutions.Thus epoxidation the epoxide2 and the less (+)-DiPT as the chiral component(58% conversion)provides
*t.-Z>
(cH3)3s
reactiveenantiomer(R)ofl,whichcanberecoveredandepoxidizedwith(-)-DiPT. I in 86% ee. This strategy is Using this technique,the epoxide 3 was obtained from
a
R=H
OH
I
l r l CHs 1
t-BuOOH, Ti(o-iP04, (+) - DiPT , 410/o
R=CHs R = CzHs
CHe
CHs ( R ) -1
eel 2 (5Oo/o t-BuOOH, I Ti(O-iP04, | 59"/. (-) DiPr I
Thus the ethcr product is reducs Jicne5. Acidic cli .clcctivity. In coo 1 7 )w i t h h i g h s e
I
OH
I
f
N^
l v " \,/,,,cHs 3 (86% ee)
on|yusefulwhentheracematesofthea|lylicalcoholdonotdiffersignificantly are available' reactivity and when both optical forms of the chiral reagent Letters'32' 2687(199-l)' I M. Bailey, I. E. Mark
tCHs)sSi V-'
Butyllithium
'oc(cH3)3 > 9 - 41 )
59
Butyllithium Diastereoselective[2.3] Wiltig rearrangement.t Treatment of allylic propargylic ethers (l) with BuLi at -85'provides either syn- or anti-B-silyl alcohols (2) in high selectivity,dependingon the R group. A variation of this Wittig rearrangementfollowed by Petersonelimination provides a stereocontrolledsynthesisof terminal conjugated trienes.
.,2/'si(cHs)s (CH3)3S|,-_z/',.(O,,,r2,r'
BuLi. THF -85" ,
I R
.,,
1 n : r , ' n r c r isce l e c t i v c:.i' .rnccdin some , l r . . r l c o h oIl w i t h rr;.1!I and the less 3; 'rith (-)-DiPT. .* I ris strategy is
I
CHs
OI H
R-.-Z--r\* l \ (cH3)3si
OH
",Fs-l ^
- -si(cH3)3
-si(cH3)3
(cH3)3si syn -2
anti - 2 R=H
90%
R = CHg
6}0/o
96:4
R = CzHs
65/o
97:3
3:97
Thus the ether 3 rearrangesto 4 with high (E)- and anti-selectivityto give 4. This product is reducedby sodium bis(2-methoxyethoxy)aluminum hydride to the (1E,58)diene5. Acidic eliminationfollowed by protiodesilylationgives sarohorneneB (6) in high selectivity.In contrast,basic elimination and protiodesilylationprovides sarohorneneC (7) with high selectivity.
(cH3)3si-Oyo)
-BuLi,
""'ill 3
-85'
CzHs
67"/"
l
si(cH3)2c6H5 anti - 4
si(cH3)2c6H5 s8%lsMEAH OH i r t l : : s i q n i l i c a n t l y in iglL.:hlC.
(cH3)3si r
'
I l()91).
Butyllithium -Potassium
t-butoxide
CHs HO/\v HO--\/-
cz+s-,-rr''\/-'-,/cH2 6
CzHs-.-Z--:.ACHz 1) KH ,0" (99%) 2) F (68%)
7 : T. Matsumoto, M Kat-sut
Scheme r
r2R)-2-r-ButYl-6mahf An imProved PrePan e r R)-3-hYdroxYbutanotc I scale I large a acid on
48' 4087(1992)' Nakai'Tetrahedron' rN. Kishi,T. Maeda,K' Mikami' andT'
c(cH3)3
"*t:#::#-,:;ffi:l-J,:J::;tll''o'^o^^'ion
suchas derivative or ananthracene
or C11; occurs mainly at Ce a problem sin-e attack o;;-;;t' alkyllithium t-BuOlJBuLi an with with 1 "un O" cffected ;; ;'' o'tho-M"tuluti"n give the instead of desired utt"tk with (CHr)lrSnCl to '"u"tion Uy at 190" follo*td treatment on (5 equiv. of each) in fHf tin-lithium exchange itris productcan undergo arvlstannanc2 in 64"yierO' at cq t)r cle' The aryllithium reaction (-ig - 30') without totu"n" in for synthesis methyllithlu. with the side chain required *i,i ura"hyde3 to introduce ,.u",, ester(5)' gencrated methyl thus 82 antibiotic uin"n*ytinone ;";-t*;" of a prccursor(4) to the
1) BuL|/KOC(CH3)3 2) (CH3)3SnCl THF, -90"
I o^o t l cH3'--"\o
Sn(CHg)a
r D . S e e b a c hU , . G1sel.
l-(/-Butylperoxy)'lJ
1) CH3L|, C6H5CH3'
-78'
OHC\/^'--z'CH2
2\
c{'"oart
- 30"
(3)
( \
l-(r-Butylpemxy)- 1,2-benziodoxol-3(lII)-one
5
rT. Matsumoto, M. Katsuki,H. Jona,andK. Suzuki,Am. Soc.,ll3, 6982(1991')' (2R)-2-t-Butyl-6-methyl-4II-1,3-dioxin-4-one(l) (14, 69 -70). An improved preparationof I from the acetal (2) obtained from pivaldehyde and (R)-3-hydroxybutanoicacid, permits preparationof this chiral derivative of acetylacetic acid on a large scale (13 g.).'
c(cH3)3
c(cH3)3 ir .r:rrc such as .': ('q or CItt
: lluOI(BuLi r( I to givc the gi \,n trcatment
2 N B S ,A I B N
o^o
f(cHs)s g^9 + l . t ercHzlt'o
oAo i I cHsl|\o
cHA--\o
Br
Br
2 - 3.5:1
2
l:. .rrvllithium :i l,rr synthesis thrI cstcr(5).
1)Al2O3 2\ H2, Pdlc, NEt3, EIOH 43o/o overall
f(cHo)s o^o
t l cH3,,..,,\\\*o 1
r
- Sn(CH3)3 I D. Seebach, U. Gysel, K. Job, and A. K. Beck, Synthesis, 39 (1992).
a
t -(l-Butylperoxy)-1,2-benziodoxol-3(lll)-one,
-'zcHz OBzl
1, stable at 25'.
OH
/-','r-i,, t i l \-.4-/
o \
o
l-BuOOH BF3.OEt2 85%
/ooc(cH3)3
y'-':r-\,,
w t
l
t
1
o
o
1-(t-Butylpemxy)'1,2-benziodoxol-3(1IO'one Oxidation.
reagent'r is a versatile oxidizing This new iodinane
1,cH2Cl2'25o-t;;c6Hu/s-cH
"
a)
txt
! c6H5l"-cH3
rtr-gf S.r.d :rr*rtutc
o
"t#r"-
cuHuAcH.
C5H5 CH3
Soc'' ll4' IM. ochiai, T' Ito' and Y' Masaki' Am'
,
i;rc
{
'( (.'F{ ':rr'Cn:' I
\,,v'
6269 (1992)'
:c.l-ts
. :r lt$tr
(Y\
cHe-o cn.H
t({c\1t I
o tl
61"/"
:a-.rnlx
: i
{
i IJI\I
: a:.,rr I
. . ( . (
?*' OH
l}rr-
-l
Cr+
t.r I
t.-l
T\T
CH: ''
-4oH
u-Camphor dimethyl acetal (1). Selectiveprotection of myo-inositok.) lnositol derivatives, particularly various phosphates,are involved in various biological processes,but are difficult to prepare in enantiomericallypure form. A useful expedient is to use o-camphor not only as a protective group but also as the chiral auxiliary. Thus o-camphor dimethyl acetal (l) reacts with rnyo-inositol (2) to give the 2,3-protectedtetrol 3 in 3l7o yield. The l-hydroxyl group of 3 reacts selectively with the bulky t-butyl-dimethylsilyl chloride to give 4 in 88% yield. This product reacts selectivelywith pivaloyl chloride to form the C4-protectedester in 78o/oyield. The tetrol 3 reactswith the bifunctional silylating reagent,1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane, to give a protected5,6-diol. By use various of acylatingreagentsit is possibleto obtain derivativesof rzyo-inositolsin which hydroxylgroupsare free at C1; C1 and Ca; Cr, C:, and Ca; Cr, C+, and C5; C1, C3, and C,ri Cr, Ca, and Cs; Cr, C2, and Cr,i Cr, Cz,Cq, and C5; and C1 and C6.
"X,
cH3\K.cH3
t\ + /-11 4y'ocH"
HO
(cH3)3sioTf 31o/"
o
OH
C H-A I
ocH3
",oH
2
1
' K. S. Bruzikand M.-D. Tsai,Am. Soc.,ll4, 6361(199r.
Camphor-derived oxazinone (l). The oxazinone I is preparedin severalstepsfrom ketopinic ethyl ester
CHs--o,Ctto a\\
c,Huo3-(o
)e
CHo Several steps
LI--L)'tH
1 m.p. 242",cre-155'
64
(fR)-or(1S)'10-Camphorsulfonamides derivative of I The enolate of the N-propionyl
Asymmetric aldol reactions'.
CaHs'
canundergohighlysylr-selectivealdolreactionstoprovidethe..non-Evans''syn-aldols (16, 48).
1) LDA,-78" 2) clTi(o-t-Po3 3) c6H5cHo 1
-
751"
o q H l l , xJ'\i^cuHu =
*
CHs
? ? '
(c6H..)2
x-l\',^c6Hu CHs
99:<1
(1992)' 1K.H. Ahn, S. Lee' andA' Lim' J' Org'' 57' 5065
(1R)- or (1S)-10-Camphorsulfonamides' realcohots' The a-chloro-a-nitroso Chirat a-nitro'" ";;;;;;-;;1i-p-omi'o oximation by yield I tn 78% l0-camphorsulfonamide agent2is preparedtio'n-tf'e zinc cnolate(a) of an ethyl the with reacts '"ug"nt followedby chlorinatio"'int'
a ( k{\'lrc:. (
ll(
eopborr (hilal P-
.r .i 'n\ CnCd I
:f :sir\-C (rf r.t( *:-s.rx'lcr.ltr I
cH3-.v.cH3 \
/l-)> a\
(C6H11)2NSO2-
o
cH3\'cH3 1)NH?oH
2)(cH3)3cocr, 1ao/o
l\
/) t
2 ", I
(C6H11)2NSO2-
N--O
I (HtO*) of 4 .provides a single nitrone (4)' Hydrolysis and ketone 3 to form essentially reduction converted by hy-drochloride5' which is general and a B-keto N-ttyd'o*ytu*ine This sequenceprovides a hydrogenolysisinto (-)-noreptrlOrl-(O]^i \:Y:" in 96-99'|J"k ee" ,out. io aflti-p-amino alcohols
10-Camphomultam (l)
r .:ltrC Of I
;" . \ n-aldols
1) LiNlsi(CH3)312 2) ZnCl2
o c6Hs-A\7cH3 3
OZnCI l
2
^\,6n5 ,, .\-CHs a
o Hso*
"uruy'ytt'
-2
+NH20H
'-H'l t'
cl5
1 ) N a B H 4C , H3OH 2\ Zn, HCIIHOA: 68% from 3
OH t c.Hu-\icH' : NHe 6, 960/" €e (anti/syn=95:5)
'(t -nltroso fe-
lW. Oppolzer,O. Tamura, G. Sundarababu,and M. Signer,Az. Soc., ll4, -5900(1992).
h.r irrimation | ,,1 an cthYl
(
l0-Camphorsultam (1), 13, 62; 14, 71-72. Chiral B-hydroxy esters,t The N-acetyl derivative I of Oppolzer's auxiliary can bc converted into the O-silyl-N,O-keteneacetal 2, which reactswith aldehydesin the presenceofTiCla to afford aldols3 or 4. Theseare hydrolyzedto B-hydroxy esters5. The stereoselectivitydependsupon the steric demandsof the aldehydegroup R mainly, with
CH.
"t'*"t'
'iLCt
''--o
NI
2
,.11
?#'."o"r,
I OSiMe2-t-Bu
O2 1 = X*COCHg Tict4 FCHO, CH2C|2
rf { provides 1 ' :iJuction and rrJt: a general
X*-,?,CH2
2
X*\..^-r-R
+
l
l I o o H
p-Carboxybenzenesulfonyl
azide
91 : 9 610/o R = CoHs = i-caH7 75o/" 96.4 : 3.6 = c-CoHl 73o/o 95 : 5
-
?-*
I ',o",*,o,
+ 5
/FN.
slight dependenceon the silyl substituents'
o
I W. Oppolzerand C. Starkemann, Letters,33' 2439(1'992)' Tetrahedron
(10-Camphorylsulfonyl)oxaziridines, 13, 64- 65; 14,'72; 16' 6l 62' (LDA) of (+)-3Kinetic resolutionof a lactone.t Hydroxylation of the enolate yield and 6OVoee' methylalerolactone(2) with (-)-1 (0.5 equiv') provides 3 in 58%
cHr.-(c '
t \l (ia1ur
.#
-l>=-
('etcciolbon
Catal-Jur a Rh(l) and
O2
c)-1 CH.
CH.
t -
1) LDA,TMEDA 2 ) ( - ) - 1 , T H F ,- 7 8 '
t l \oAo ( x )- 2
t thc \-hr< --:hrlamirrc.
A,.o' t l \oAo
\$antag6 i:J
I
thc rcgro
i rr-rclic atr 'rl: t{xencd
3, (60% ee)
provides (2S,3R)-(-)-verruFlash chromatographyfollowed by two crystallizations carinolactone(3) in >95Vo ee. I F.A. Davisand A. Kumar'J. Org., 57,3337(1992)'
(l)' 2' 62' p-Carboxybenzenesulfonyl azide, p-HOOCCoH+SOzN: Azi'dationofN-hydroxyp.lactams.|ReactionoflwiththeN-hydroxyp-lactam 2doesnotprovidetheexpecteda-diazo-B.ketoesterbutcompound3,formedbyazide resultsobtain in reaction transfer to Cr with cleavageof the N-hydroxy bond' Similar
Hzc\
I
Catecholbomne
o Trisylazide,2 N(C2Hs)3
,(""^O.^-.--Si(CHs)s
/-"o^
rt l)A) of (t)-3r r : l . i a n d 6 O %e e
5 of the N-hydroxy B-lactam (4) with trisyl azide in the presenceof 2 equiv. of tricthylamine. 1C.M. Gasparski, M. Teng,and M.J.
Miller,Am. Soc.,114,2741(1gg2\.
Catecholborane (CB), 16, 65-66. catalyzed hydroboration r Hydroboration by cB can be catalyzed by a number of Rh(I) and Ir(I) catalysts,particularly RhCt[p(C6H5)3]2and Ir(cod)(pCyr)(pylpFo. Advantagesare that selective hydroborationowing to steric factors can be improved and the regioselectivitycan be enhanced.Moreover, the Rh(I)-catalyzedhydroboration of acyclic and cyclic allylic alcoholsproceedswith high diastereoselectivity, oppositeto that observedwith 9-BBN (equationsI and II).
OH
OH
(r)t"*"H. :..iR)-(-)-verru-
i|.
"#k#;- Ho'^+cH3+ Ho-^\r 9-BBN el%
|
i-:rJroxY B-lactam I -1.ltrrmedby azide ls ,,[1xipin reaction
SOn
|
rHF,2oo
8 1: 1 9 '17:83
,,.-U.CHzOH
cB.Rhfl)g3% |
e-BBN ris"/"
Pr
Pr
syn
/"
OH
\
anti
^.-CH2OH 'l
|
OR
V.On 91:9 54:46
I
I
cH.
68
s1
Cesiumfluoride Inadditionat.ewgroupscandifectRh(I)-orlr(I)-catalyzedhydroboration.Thusan
amidegroupcandirecthydroborationofcyclohexene-derivedalkenes(equationIII),
CONHBzI
coNHBzl 0il)
,\ t
\'2
cB 1) rr(r),
p{hlorol
( tirrnirr IJ.Di :anat1ckrb lnt(\ th€ tf
2\ Ac2O
i --i{renc I
l OAc sYn/anti= 91:9
G C' Fu' and I D. A. Evans,G.C. Fu, andA. Hoveyda , Am. soc.,ll4, 6671(1992);D. A. Evans, (1992)' 114,6674 ibid., B.A. Anderson,
r. ftrrmcd
,b) rs forn JccomFxl
NaNr)' Ceric ammonium nitrate-Sodium azide (CAN, enol ether in cHjcN with NaNr triisopropylsilyl a of Reaction a-Azid.o ketones.r -20" results in an a-azido ketone and (4 equiv.) followed by CAN (3 equiv') at
cpzT
triisopropylazide.Othertrialkylsilylenolethersarelessusefulforthisazidationbecause of their readY hYdrolYsis.
o
-Pr)s
d
NaN3,CAN cH3cN,-20"
.\r'r. (-J
+
(t-P03siN3
72o/o
1P. Magnusand L' Barth, Tetrahedron Letters,33' 2777 (1992)'
CotrTi
CH
Cesium fluoride, CsF. AllcylationofRCooH.|InthepresenceofCsF(1.5equiv.)carboxylicacidsreact withalkyliodidesinDMFatl0-15.toformestersin.To-g|voyield.DMSOcanalso effective' be used as solvent, but less polar solventsare not
!
o * gr1 -c'!'Dvl* 1cH313cAoeu (cH3)3ccooH o il ThisreactioncanalsoconvertBulSnCoRintocarboxylicesters(equationl). (l) coHscooH
Bu3snosnBu3 > Bu3sncooc6Hs
czHsl'csF
riifirrdr r ri\rl
I
r:-f,,rnlrc Ltu -
Tcttx
:r
r rli
r":-: hrnd :: e..llrtIl
'
coHscooczHs
94V" I T. Sato, J. Otera, and H. Nozaki' J' Org', 57' 2166 (1992)'
\v : ii
ft P.
titanium (Tebbe reagent)
p-Chlombis(cyclopentadienyl)(dimethylaluminum)-p-methylene
tr':.i:tttn. Thus an ri-urrtion III).
9 1 . . , - - .G . C .F u ,a n d
69
p -Chlorobis(cyclopentadienyl) (dimethylaluminum)-p'methylene titanium (Tebbe reagent). 1,3-Dienes.l Reaction of the Tebbe reagentwith 2-butyne provides the dimethyltitanacyclobutene1. Aldehydesreactwith I to provide a complex (a) formed by insertion into the titanium-vinyl bond. This complex is unstable and at 60" decomposesto a 1,3-diene(2) and Cp2Ti:O. Ketonesreact with 1 to give two insertion products.One is formed by insertion into the titanium-vinyl bond and correspondsto (a); the other (b) is formed by insertion into the titanium-alkyl bond. This latter complex does not decomposeinto a diene when heated gently. The trend to formation of the undesired
cH2YcH3
( ll ('N with NaNj r - . ! . / l J ( )k e t o n e a n d
Cp2Ti,.ry'CH3
r\ .:./rJation because
I
- CP2T|=O
cH3cHo
cH3 -
tYt.r,
98Yo
CHs
CHs 2
1
o ,SN:
cH.A
CHe
[
,tt' I
cH2\"'cH3
, l"o,'f).r, I - *-* CHs arh,,\\'lic acids react e l.-t I)MSO can also
b .34"/"
- Cp2Ti=O
| 3il.'. ]
I
"tt-4"".
I CHs
o OBU
n r':quationI)'
t':
intermediateb increasesas the size of the alkyl groups of 1 increasesand as the size of alkyl groups on the aldehyde or ketone increases.Even so, this route is useful for preparationof l,3-dienes from simple alkynes and unhinderedaldehydesor ketones. Ketone methylenation 2 A comparison of methylenation of about 10 ketones using indicatesthat the Tebbe reagentor the Wittig reagent(methylenetriphenylphosphorane) rhe yields are consistentlyhigher with the former reagent,and that the yield improves with hindrancein the substrate.Another advantageis that the Tebbereagentis available commercially (Strem and Alfa), but expensive. I K. M. Doxseeand J. K. Mouser,Tetrahedron Letters,32, 1687(199f). rS.H. Pine,G.S. Shen,andH. Hoang,Synthesis,165 (1991).
70
Chlorobis(cyclopentadienyl)methylzimonium
Br
Chlorotris(cyclopentadienyl)hydridozirconium(IV) (zirconium hydrochloride, Schwartz reagent). Conjugate addition of alkenes.t Hydrozirconation of alkenes followed by addition of a catalytic amount of CuBr'S(CH3)2 results in in situ pteparationof alkyl cuprates
OCHz I
N,. Bzl
that undergo l,4-addition to an enone.
I
i
CpzZr(H)CI
rHF'((((
>
CH2=611611r)2OTBS
] [cp2zncr(cH2)4orBs
o ,,\ (/
tcH'
f-V.. l l t
)
\Z^-tri
tazr 3
o
, CuBr.S(CH3)2
CH2:N-(C2H5)2\ 85'
\
G,.r2)4orBS
\
I
,^
fit'
1) Cp2zr(H)Cl 2\ , CuBr S(CHg)z ( FO
-
tl
o
0-o
v
with various active enop
I J.H. Tidwell,D. R. Senn (Z)-Vinylstannes.2 (Z)-Mnylstannanes can be prepared by hydrozirconation of followed by proton quench. stannylacetylenes
B-Chlorobis(iso-2-ethg I Preparation:
1 ) C p z Z r ( H ) CTl ,H F
CH3:SnBu3
\-at'{
2\ H2O. +
92"/"
CHs
SnBu3
\- I
cH3"-'\c t P. Wipf andJ.H. Smitrovich, J. Org., 56, 6494(1991,). 2 B. H. Lipschutz,R. Keil, andJ.C. Bafion,Tetrahedron Letters,33,5861(1992).
Chlorobis(cyclopentadienyl)methylzirconium,Cp2Zr(Cl)CH3,15, 81 Indole synthesis.t A novel route to 4-iodoindoles involves reaction of N-allyl-Nbenzyl-2-bromoaniline(1) with this zirconoceneto form the zirconacycle2, which is converted into 3 by iodination and elimination. This product undergoesene reactions
Asymrnetric reduai campheylborane(lpclB( ketones:they show link alkyl groups are similar i 1l). Thus acetylcyclohe rcduced in 95Voee (6-5
B-Chlombis(iso-2-ethylapinocampheyl)borane
Br .i
:.rincS followed bY addition
OCHz I
f-BuLi Cp2Zr(CH3)Cl
N,. I Bzl
[r :',r.rration of alkYl cuprates
CpzZt,-7
-CH+
/
1l t2,cHzcl2 2) DBU
)
'ezt
,
|
C : - Z " C l ( C H z ) 4 O T B]S
.cH,
..<-J( i l t \ \zL"
C2H502CHC:CHC02C2H5 85"
tgzr
i
r--<'...-co2c2H5
6o,c,Hu
fm \-4N Bzl
3
4 CH2:N+(C2H5)2 85"
-
:-i,)oorBS
N(C2H5)2
Bzl 5 with variousactiveenophilesat 85' to form 4-iodoindole derivativessuchas 4 and5. 1J.H. Tidwell, D. R. Senn,and S.L. Buchwald, Am. Fc:.:'-J hv hydrozirconationof
Soc.,ff3, 4685(1991).
B-Chlorobis(iso-2-ethylapinocampheyl)borane, Eap2tsCl(l). I Preparation: | - - H2Bcr.s(cH3)2 cH2c,2,25" ;fftr,r.,
-C"H.
C H3
snBu3
F6 cHrAcH,
v- , .t-t.5tt6l ( 1992).
( ( . ( H , . 1 5 ,8 1 r -r,'lrcs reactionof N-allyl-Nrr :rc zirconacycle2, which is F1 \:ret undergoesene reactions
H
cn"Ac"l CHe (1)
Asymmetric reduction of ketones.2 Both Arpine-Borane and B-chrorodiisopinocampheylborane(Ipc2BCl) have one main defect for asymmetricreductionof prochiral ketones:they show little enantioserectivity in reductionof diarkyr ketonesin which the alkyl groups are similar in size. This probrem is now sorvedby reductionswith Eap2BCl 1l)' Thus acetylcyclohexaneis reducedby l in 97% ee and isopropyrmethyl ketone is reduced in 95Vo ee (65Vo yield\.
Chlomcyclopentadienylbis(triphenylphosphine)ruthenium
1) 1, cH2cl2'-25"
O
ll
-:1-$i9I'c!:9IL:-
(CH3)zCHACH3
65"k
FL .OH
r..H3)zcH)\cH3 (c|
CuHrA
(e5% ee)
Letters' Tetrahedron and S Swaminathan' A'V' Teodorovic' I H.C. Brown,P.V. Ramachandran' 32, 6691(1991). Acc'Chem Res''25' 16 (1992)' 2H.C. Bro*n, P.V. Ramachandrtn'
Chlorobis(triphenylphosphine)palladium' 1 can be preparedin -fi"-:'+'S{ri-o-(triisopropylsilyl)-o-glucal C-Aryl glucats' f
TIPSO-\
TIPSO-\
rrpso-trVot \ ,'TIPSO
1) t-Buli; ClSnBu3 2\ l'2,QH2C!2
TIPSO-]-Z.-l
85"/o
cl2PdlP(C6H5)312 C5H5ZnCl(excess) 9OY"
rrpso-\-vot
TIPSO-\
\-o
TtPso--\--+' \ ',PSO_\z-c6Hs 2
of a protectedo-glucal' If Ol high yield by stannylationfollowed :tt/t01":^:--change the same converused for prote:ti:n of the o-glucal' t-butyldimethylsilyloxygroups are in low yield (12-30Vo)'l sion to an iodo glucal p'o""td' with iodide pi CiralrlCoHs):lz' this vinyl tutatyst' 'couPles u ln the presenc" or
q
CH B. \1. Trtxt alxl ('hloro(cYcloPa l. preParedtn r
[2 + 2]Ctc irnvlamine2 r ()n additionof ..rn undergo rc: .rcrlation occur rlwr be used tc
ANHz
\---s-\\\ -q 2
m e t a | a t e d a r o m a t i c s , p a r t i c u l a r l y a r y l z i n c c h l o r i d e o r a r y lglucals b o r o n can i c a cbe i dconverted s.ArylGrignard lo* yield. The resultingC.aryl reagents,however,couplein u",y of the enol ether double bond'2 to C-aryl glycosidesby functionalization (1991) rR.W. Friessen and R W' l-ao'J' Org'' 56' 4821 (1990)' 5808 55' ibid'' tn.W. fti".."n andC'F' Sturino' CpClRu[P(CoHs):]z (1)' Chlorocyclopentadienylbis(triphenylphosphine)ruthenium' compounds.t ln the pres,trrt oirio ,oiuroteil carbonyl Isomerizp.tion "t "t'ii saturatedaldehydesor allylic alcohols reafrangeto ence of this ruthenium'""rnpt"-, double bond' with highest nunrL.. of substituentson the ketones.The rate dependson ,h" ratesinthecaseofmonosubstitutedalkenes.l,l-Disubstitutedalkenesrearrangefaster than 1,2-disubstitutedalkenes'
P t- \lc(iru
Chloro(cyclopentadienyl)dimethyltitanium
IH
1, NH4PF6
OH
O ll
d i o x a n e1, O O ' , 2h
CH:
----';-
cut-tu/\2"'r'CHz
73
c6Hs(cH2)2""\c2H5
t€
c:' .".,,lron Letters,
8h
cuHr&cH20H CH2
CHq
3.5 h
i l cH3(cHd8-'\cHo
rf: .c preparedin
c6HscH2cH2cHo
9O/o
t -
cH3(cHr8"'\cHo
I B. M. Trost and R. J. Kulawiec, TetrahedronLeuers, 32,3039 (1991).
I ,,^----,
Chloro(cyclopentadienyl)dimethyltitanium, CpTiCl(CHr)2, l, preparedin situ from CpTiCl3 and 2CHrLi. [2 + 2]Cycloaddition of allcynylamines; heteroannelations.t Reaction of the alkynylamine 2 with I leads to a titanacycle(a) with evolution of mcthane (2 equiv.). On additionof CHrOH the A1-pyrroline3 is formed in 96% yield. The intcrmediatea can undergoreactionsat either carbon or nitrogen with appropriateelectrophiles.Thus acylation occurs exclusively on nitrogen (4). Intramolecular[2 + 2]cycloaddition can also bc used to obtain tetrahydropyridines.
.l
..ilrJ
t)-glucal. If
. l'J \amc COnVefurJi i;.
1-rr, \"ur,;;
1,2s"I fryli(cp)cr "".o" ,f-N q"r,"ur, *".r. nu.o L ] a
II
couPles with -\rvl Grignard
88% | cHsococl
,l
^ ,coocH3 A N -l (
l.,.rn bc converted )c.l
\--\
\
I CoHs
4 CpTiCl3, C6H5N(CH3)2 c6H5cH3,80'
, u t ' r ( . , H s ) r l z( l ) . In the Presnd;. r.r:rJ aldehYdesor 1 \,nti. with highest nc. r.arrangefaster
88o/"
r
r.r
(--.\.-coHs
CoHs I P. L. McGrane, M. Jensen, and T. Livinghouse, Am. Soc., ll4,
5459 (1992).
74
4-Chlom-2,3'disutrstituted-2-cyclobutenones
(-)-B-Chlorodiisocampheylborane, (-)-Ipc2BCl (1), 13' 72; 14' 82'
'utt-/
o tl
ill ,uAc,
Red'uctionofacetylenicketones,RC=CCR.|Alpine-Boranecaneffectthisreducto steric effects' Thus tion in high enantioselectivity,but this borane is very sensitive In contrast' asymmetric it fails to reduce a carbonyl group adjacentto a /-butyl group' reductionofalkylarylketoneswithlisincreasedbyahinderedalkylgroup.The as the steric bulk of Rr same effect obtains in reduction of actylenic ketones(2). Thus increases.the enantioselectivityalso increases'
CHs
l. rCH3)2CHO
OH
,o
n-Oct-----:-{
n-Oct------(
Rr
R1
3
2
I
(cH3)2cHo R1 = iPr
g6k
26o/o @e
R1 = C(CHs)zCzHs
760/o
>99o/o @a
R1 = t-Bu
72o/o
>99% ee
l). K. Krysan.A. (it , Chloromethyl)dir
r P. V. Ramachandran,A. V. Teodorovic,M. V' Rangaishenvi,and H C Brown' J ' Org" 51' 2379 (1992).
Stereoconlrollt .ritutcd 1,3-diener {t para. This int
:hc diene with a d "r a (P-hydroxrc
, chloromethyl)dinx formaldehyde.Thc precusor(4) for an
^t\--/o (1)
4-Chloro-2,3-disubstituted-2'cyclobutenones' ll I
underthe condition :csults in a singlc
'Cl
R2 cH3 ,cHe Regiospecificsynthesisofphenols'|Thesesubstrates,obtainedbyreactionof4si(cHd cH2\.hydroxycyclobutenoneswithP(C6H5)3/CCla'undergoPd-catalyzedcoup|ingwithvari-f transformed are that products form to vinylzirconiums and arylstannanes and ousvinylI \cH, phenols' (100")to tri- andtetrasubstituted on thermolysis
"""Y(
2 (CeH+PdCl)z P(C6H5)3
*
CHltSnBu3
(cH.)rcHoAct CHs -\./
(
i l t A-{
(CH3)2CHO'
,P \,/)t'\
1oo" ,
-SnBu3
CHs
670lo overall
(CH3)2CHO
"T
(Chlommethyl)dimethylsilyl chloride
Bu :11..1this reducni etTccts.Thus
Pd cat. 1) Bu3Sn(EIO)C=CH2, 2) 100"
,o
,14",
"*Y(
rr.l. ]symmetric l\r I grouP. The tcrre bulk of Rl
Cl.-r-1.-Bu cPz
1o-r.yrcHo,^cr ,H
I
I'
t
P(c6H5)3 PdlP(c6H5)314,
(E)
I
100"
>
41o/"
(cH3)2cHo
It.t.,,"tot;Nr,]
CHs
I D. K. Krysan,A. Gurski,andL. S. Liebeskind, Am. Soc.,ll4, 1412(1992).
n | ( )rq., 57, 23'19
tChloromethyl)dimethylsilyl chloride, ClCHrSi(CH3)zCl (1). Stereocontrolled Diels-Alder reaction.l The Diels-Alder rcaction of a 2-substituted 1,3-dienewith acrylatesgives mainly the cyclohexcnein which the substituents {e para. This intrinsic para effect can be revcrsed by joining the dienophilc and rhe diene with a disposabletether. Thus the chloro group of chloropreneis replaccd by a (B-hydroxyethyl)dimethylsilyl group by reaction of the Grignard reagent with lchloromethyl)dimethylsilylchloride (1) followed by a second Grignard reaction with formaldehyde.The product (2) is then coupled with the acrylic acid (3) to form the precusor(4) for an intramolecularDiels-Alder reaction.The product(5) is then oxidized underthe conditionsof Tamao(12,243-245) to the cyclohexenone(6). This methodology "meta" addition. rcsults in a single adduct that is formed by
i.r rcaction of 4ouplinqwith varia: .1ri transformed
CH3 ,CH3 cH3/cH3 ? HOOC-....CH3 tt'Y'---^o\tt' cH2\r-si(cHz)20H Dcc> ll -cH. I \ar, \"r, \cH,
o
2 Fre icl)2
fj'''
CHs
,
180' 6sol.1
o\.^._i"oocH3 -cHe I I $cH.
?CHo
1) cleavage 2) oxid
tt3,'-Yor-o
c4)f-icH. t$CHs 5
m-Chlomperb€nzoic
CH3 ,CH3
acid
CHs Si
?
"t'V'--,,^o\"t.
c4
o.
>o CHg
CHZ
CHs
.\
(,
Chloro(phenylethynyl )dir Stereoselective C-sy4 to styryl C-glycosidesbr r as a silyl ether to an a- ot of the 3,4,6-tribenzylerhc the tetheredsilyloxy preo desilylation(BuaNF) pror.
I J. Shea,A.J. Staab,and K.S. Zandi, Tetrahedron Letters,2715(1991').
m-Chloroperbenzoic acid. Stereoselective epoxi.dation of enoates.t The final step in the synthesis of (+)aphidicolin (4) requires a stereoselectiveconversion of the cyclic norketone (l) to a vic-'1.,2-diol,>C(OH)-CH2OH. Methylenation of the ketone followed by a Sharpless asymmetricdihydroxylationprovides a 1:1 mixture of epimeric 1,2-diols.Reactionwith a chiral oxaziridinealso providesa 1:1 mixture of epimeric epoxides.The transformation is effected successfullyby conversion of the ketone to the enol triflate, which is converted to the enoate(2) by Pd-catalyzedcarbonylationin methanol(13,234).Epoxidationof 2 with ','-CPBA in buffered CH2CI2with a radical scavenger(4,85-86) resultsin a single epoxy ester Q) in 90vo yield. This product is reducedwith lithium aluminum hydride (excess)to aphidicolin (4) in 67Vooverall yield from the ketone l.
.coocH3 1l rtzo, c{zct2, 1oo% 2) Pd(o),co, cH3oH,75%
CHsQ
2
so7"I crcuFqco.H
I
L|AIH4,THF, A
100%
AoocH3
i'q )-,) H
3 (+)-4 1C.J.RizzoandA.B. Smith,III, J.C.S.Perkin1, 969 (1991)
CHo \" C6H5---9i-O-' / CHs
/ '
cH3o !
In contrastcyclization a linkedto the 3 B-hydroxrI I 6. The styryl group of .f ar .i carbinol. Note that a frc uscful for subsequenttrans This overall processis tcquationsI and II).
Chloro(phenylethynyl)dimethylsilane
\-n
-cH. 1-\cHs n
77
Chloro(phenylethynyl)dimethylsilane, C|(CH3)2SiC=CC6H5(l). StereoselectiveC-styryl glycosidation. Storkt has developed a stereoselectiveroute to styryl C-glycosidesby a radical intramolecularcyclization of an ethynyl group linked Thus reaction as a silyl ether to an cr- or B-hydroxyl group of a phenylselenoglycoside. 2 with 1 provides of the 3,4,6{ribenzyl ether of the 2-hydroxyphenylselenoglucoside the tetheredsilyloxy precursor3. Reaction of 3 with Bu3SnH and AIBN followed by desilylation(BuaNF) provides the a-C-styryl glucoside4 in 83% yield.
OBzl .\llhesis of (+)n('ikctone(1) to a 'ci f'\ a SharPless
1)Bu3snH, AIBN 2) BuqNF
BzlO 83o/"
or' CHs-J,
h,,1. Rcactionwith 1 rc rransformation . ir hrch is converted It I poxidationof 2
SeC6H5
"risi-:-..H.
ir r.r.ultsin a single r rluminum hYdride
o
BzlO
coocH3
0
/-1
tr1?cHcuHu
1) Bu3SnH,
c1.
I,
C6H5:3 CeHaCOsH
o COOCHo
2\/
,,/-1
ocH3
ocH3
AIBN 2) BuaNF
,Si-g CHs SeC6H5
F ct1?crcuru 6
In contrastcyclization and desilylationof 5, in which the phenylethynylsilylgroup is linked to the 3 B-hydroxyl group ofa phenylselenoglucoside, providesthe B-C-glucoside 6. The styryl group of 4 and 6 is useful as such and as a precursorof an aldehydeor r carbinol. Note that a free hydroxy group is liberated in this cyclization and can be uscful for subsequenttransformation. This overall process is also an efficient route to C-furanosidein the ribose series ,cquationsI and II).
<>
1-Chlom-1-phenylsilacyclobutane
cH3. /cH3 BzlO (t)
-Si----C6H5 O-
[-.----o-l-t-sec6H5 \-7I BzlO
C\srCHs coHs-bl-o.
ou,)
BzlO
l--o-lJ
OH CH=CHCoHs
?-t'-""' (il) cH.o-lYH
H
CHg
BzlO
"o\
cH=cHcoHs
rN. Auner and J. Grobe. J (i I A.G. Myers, S.E. KePhan. ' ' K. V. Brown et al., J. Ory'.
80% V"-sec6H5;fJ h<"1,
i;.-"l.
the presenceof ClSi(CH,) 'hows significant 1,4-as1
r c . S t o r k , H . S . S u h , a n d G ' K i m , A m ' S o c ' '1 f 3 ' 7 0 5 4 ( 1 9 9 1 ) '
C l .'Si l -Chloro-1-phenylsilacyclobutane' CoHs
C hlorotrimethYlsilane. 1,2-Adtlition of R2Cd .rdditionof cuPratesto eno
(1)
OI M O M
";::"i;:;i;"
of a catalvst' silvl enol ethersordiof atdot reactions'2 In the absence Thus the dimcthylphenyleven at high tem-peratures' narily do not react with aldehydes the silacyclobutane CoH'CgO at 150'' In contrast' silyl ether 2a does not react *itt' and anti-aldols with C6HsCHO at27" to form 'syzanalog(2b), preparedtrorn f, reacts in12:lratio.Thisstereosele",iui.yi.theoppositeofthatobtainedbytheTiCla-cata|yzed effective CH'(CDSi(CHz)r' is even more reaction. 1-Chloro-1-metnyrtiru"i"foUutu*
c-c6H11McH
oMo I
c-C5H11N
thanlforthisaldolreaction.Itispreparedr,oml:-ctrto,opropyl)dichloromethylsilane.3 Itisparticularlyusefulforaldolreactionswithacyclicsilylketeneacetals(equationll).
*"i"
R R
o'"'-coHs o i l l /fcoHu
o'si-cuH,
(t)
A
26, fl = CH3 2b,R=(cH2)3, 100o
+
C6H5CHO
\-,' Qo/o
84"/"
3b(12:1)
\1. Arai, T. Nemoto.\'. o
(' hloro(triPhenYlPhocPl
Preparation.l Stereoselective reocl -tecto provide either Pvn
Chloro(triphenylphosphine)copper
CH=CHCoHs
?-t'-"r, trr)cH3o'/Y
+ C6H5CHO-
tetmmer
230 1000/"
CHs
(syn/anti=19:1)
CH=CHCoHs
I N. Auner and J. Grobe, J. Organomet.Chem., 188,25 (1980). r A. G. Myers, S. E. Kephart, and H. Chen, Am. Soc., 114,7922 (1992) t K.V. Brown et al., J. Org., 56,698 (1991).
7 Chlorotrimethylsilane. 1,2-Addition of R2CuLi to y-alkoxy enals.t ClSi(CH3)? is known to facilitate 1,4additionof cupratesto enonesand enals,but reactionsof cuprateswith 7-alkoxy enalsin the presenceof ClSi(CHr)3 results in exclusive 1,2-addition.Remarkably,this reaction shows significant 1,4-asymmetricinduction.
2 CtSi(CH3)3 THF, _78'
OMOM I
+
cn,'l cthersordiJ rnrcthylphenYl: . rIucvclobutane r- .rntlanli-aldols e I r('11-catalYzed n nt()rc effective or,'mcthYlsilane.3 trl. tcquationII). R , R S i- c o H s
+
(CHg)zCuLi
c-cun,,,Mcno
640h
OMOM
OMOM
I
c-c6H1()\y''\acHs
+
c-c aH.,.,')\'y''-''1cHe osi(cH3)3
osi(cH3)3 78:22
V. Arai, T. Nemoto,Y. Ohashi,and E. Nakamura, Synlett,309 (1992).
o. '
'CuHu
2 '\
Chloro(triphenylphosphine)copper tetramer, ICuCl(CoHs)rP]+(1). I Preparation. Stereoselectivereactions with oxaziridines.2 This reagent can effect N-O cleav.rscto provide either pyrrolinesor aziridineswith markedselectivity(equationsI and II).
Chmmium
aminocarbenes
1) BuLi 2) C6H5CH2X
.CH2C6H5
9t'
iia
1 ,T H F
(r) CoHsAt',1'^ lr\)
(co)5
(R)-1
B:
cuHur
c6Hs/l(cH2)2cH=CH2
>95% de
o C H q-
1,rHF
I
(lr)
--;*
Tlo-"utu 1...t"
cuHu
coHs
lcHi2cH=cH2
Chem'' f f' l8-18^(1972)' r M.R. Churchill, S.A' Bezman, and J'A' osborn' J Inorg' ll4, 5466 (1992)' soc., Am. 2 J. Aub6, X. peng, v. w-g, ""J F. Takusagawa'
(R)-1 can also be convertedtnto ester of (S)-alanine(2) to form th CycloProPanation.t Chromiu gt with unactivated l,3-dienes as vinylcycloProPaneswith high rcg result in a alkylmethoxYcarbenes
occurs selectivelywith the least I with 1,3-dienesthat can adoPt thc Chromium aminocarbenes pentacarThe chromium amino-carbene I' Asymmetric synethesisof tlipeptides't (methyl)carbene]chromium(0)' bonyl [(R-1-az a-2,2-dimelhyl-:-*u-S-pf'"nylcyclopentyl) with amino esters under coupling carbonylative derived from (R)-alanin", und"'go"t (S'S)-dipeptideswith high diastereoselectivity' irradiation (visible lighQ at 0' tolorm
*
cn/6cru,
"^r,
l$o(Co)5
erAocH.
o
CoHs / p
\
(co)scr\ ni;b tcH. cil. cHl (R)-1
H t l * cHog'\o(cHe).
C O ,h v , 0 " THF
H
88V"
I NHz
F- /
B"{'z\c,',
(s)-2
O
CHs
ocH3
cH.JAru\o,"'.t.,. cuHul4N-*-Bn. -cHa \.
o_J
b
i
(R,S,S)-3(s8:2)
Cr(C
c.HrAo
Chromium aminocarbenes
)H:c5Hs
CuHu,,
1) BuLi 2) CoHsCHzX
(R)-1
BzCH2 CH3
R-4
t€
'
(S)-2,CO, hv THF
/:--f
(co)5cr\_ il-" .b / X
CH3
? 9t. ,.-\iAN4-..,1o(cH3)3 b CoHs1,'N;-Bt. -cH' [J
1 ,NfH3
( R , S , S ) - 5( 8 7 : 1 3 )
o€
li.
CoHs
.,tal).
(R)-1 can also be convertedinto the (R)-chromium4, which coupleswith the t-butyl ester of (S)-alanine(2) to form the protecteddipeptide5. Cyclopropanation.r Chromium and molybdenum carbene complexes can react with unactivated l,3-dienes as well as electron-rich or -poor dienes (14,91) to form vinylcyclopropaneswith high regio- and diastereosclectivity.In fact' reactionswith alkylmethoxycarbenesresult in a single diastercomer.In addition, cyclopropanation occurs selectively with the least hindered double bond of the diene and more readily with 1,3-dienesthat can adopt the s-cis conformation.
rr,. ::hcnc l, pentacar5 ,:^rnclchromium(0), f .1nlinocstersunder d.r.,.rcrcoselectivity.
Cr(CO)s
+
cH/6crnu
THF 1000
cH34ocHg
"^"1-^",'u ocH3
Mo(CO)5
Bu
ocHg
H
8€'
,ul'z-",r, o
cHs
- ^,J-- -.o1atr;. :: lt o *-Et. ,
CHS
S S '3 (98:2)
ocH3
Cr(CO)s cuttu^ocH,
92o/o
er"r.
82
Chromium
arninocarbenes
time for synthesis carbeneshave been used for some o-Alkoxyphenols'| Chromium dienylcarbenes' chromium to o-alkoxyphenols employs ofp-alkoxyphenols. A novel route under carbon irradiated when prepared as shown, Thus the chromium carbene r, yield' 90% in 2 to cyclizes *t"pt""ed ketene (a) that monoxide is converted t'" " Cr(CO)s 1)BuLi 2) cr(Co)6 3) cH3orf>
rt orovides the oxazinone 2 in good b-v.ch Optically pure 2 can be obtained the chiral auxiliary, effected by h1'drq Reaction with ketene ketak'! Tt ortlx acyclic ketene ketal 2 to give two In 5' and 5 acid to the butyrolactones I rather group selectivity with an ethyl
.ocH3 (co)scr{ 'CsHs *
cHz-
2 CsHs-
n,,"o I rHF I
CHr-
I
ocH3 I .'r,-.. \
-Z\t l l \,,'
c
ocH
[,.o,0.,
eo%
l
x\.
--o
Le
cslls
cl{:
complex active chromium-carbene arylglycines'3 The optically
Optically activl canbe-used Preoaration lo1 rr.. trs,zn'l]z-ffi"" t''-oto'nt"ttethanol' DMAP l, prepared of 1 in CHrCN containing
Thus irradiation of opticallyactivearylgtyJnes' 1) AcBr
t)cu,'-,'. cuH.
N(CH3)4* /.O (CO)sCra^ ,, \'6n5
HzN oH 7e"/"
CoHs
rcgi The reaction was used for a
rCuHu ,O(CH2)2CH=C(Cl.
,uf,ao'.
(CO)sCr< 'CHs
, (CO)sCr{ 'CoHs 1
I nu,"n."*
81% DMAP I CoHs I
1\ chromatograpny
H2N---,COOH ' "H _ cuntu
,i ilr. r0",, 23oloov€rdll
coHs ),,4o
t*Y^o CeHs
(R)-3 (94'l"ee1
2 ( 8 8 : 1 2)
(CO) sCr-- C (OR) R comPkx a carbene I and the stabilized Phc H'Ovield. HYdrolYsisof 3 with (Z)-l'3dr ellene3 rearrangesto a catalystfor this rearrangement'
Chromiumaminocarbenes 83 mc :rmc for sYnthesis nrunr.lienYlcarbenes. drrlcJ under carbon r I ir 907r yield. (COt5
'ocH3
provides the oxazinone 2 in good yield, but modest diastereoselectivity(76% ee). optically pure 2 can be obtainedby chromatography.The final step involves removal of the chiral auxiliary, effected by hydrogenation. Reaction with ketene ketak,a The chromium carbene complex I reacts with the acyclic keteneketal 2 to give two orthoesters,3and 4, which are convertedby aqueous acid to the butyrolactones5 and 6. In the example cited the carbenereactswith high selectivity with an ethyl group rather than a methyl group.
,ocH3 (CO)5Cr{ 'CeHs *
PCzHs
CHz{
C O ,T H F
OCH3 2
coHs---.-1
.:: ;
,oCHs
I Y cHr)-d'ocH,
coHs--lroczHs * l--6^ocn,
76V" )
CH,
4
( <'lo/o )
\r-
"'-o
| ".o.
Hso*
I
coHs--r1
coHs\r-1
l F o ru::: carbenecomPlex : :..rJ for PreParation ( \ i()ntainingDMAP C;Hs
'CoHs
x
11
f
NH
OH
CHs'/-O
l-oF o 6
5
The reaction was used for a regioselectivesynthesisof eldanolide(6)' 1) THF,co, 80" 2) HCI P(CH2)2CH=C(CH3)2 /OCH3
(Co)sCr{ 'cH.
*
CHz={ 'ocH3
,::{, CeHs
o tl ( ' o
1 hr',CH3CN DMAP
1",
L_/
r
cH;
CoHs I {=r. Ao I
'u _Ao I CoHs 2 t 88:12)
\-cH=c(cHr),
6 (trcnslcis = 24:1\ (CO)sCr:C(OR)R complexes; allenes.s Photolysis of a mixture of the chromium in 6jo/a carbeneI and the stabilized phosphorusylide 2 under CO gives the allene 3 4. The (Z)-enone rield. Hydrolysis of 3 with Hro+ in ether provides the B-substituted effective is an allene3 rearrangesto a (Z)-1,3-diene(5). Pyridiniump-toluenesulfonamide catalyst for this rearrangement.
Chmmium(Il) chloride
(Co)sCrl
hv, CO C6H6,25'
,oc2H5
(c6H5)3Pz\ co2Bzl
c(cH3)3
2
1
C2H5O, Cr(CO)6
selectivity. Reactionsof chiral r configuration of the bromide car can provide accessto compler c
(c6Hs)3PO
fOzBzl
Fcl (cH3)3c
o
H
CHs
-sv"2/PYHrs
HCl, ether
i
-\.-o CHs
4
reactionsinto nephromopsinicr
CzHs? CO2Bzl (aHs)sc-,or'-,-?
CO2Bzl O i l l
K;nd"c)J
I J. Mulzer,L. Kattner,A. R. Strcct Soc., 113, 4218 (1991).
4 IJ.R. Miller, S.R. Pulley,L.S. Hegedus' andS' Delombaerr'Am'Soc''ll4'5602(1992)' 2 D. F. Harveyand K. P. L;und,Am. Soc.,113,8916(1991)' 3 C.A. Merlic and D. Xu, ibid., ll3' 7418(1991)' 4J.-M.Vernier,L.S. Hegedus, andD.B. Miller' "/' Org', 57,6914(1992)' Am' Soc''114'10665(1992)' 5S.L.B.Wang,J. Su,W.D. Wulff,andK. Hoogsteen, 6 M. R. Sestrick, ibid', ll4, 40'19(1992)' M. Miller, andL. S. Hagedus, Chromium(Il) chloride, CrClz. fo crotyl Asymmetric addition of allylic bromides to aldehydes.t The 1,2-addition homoallylic provides reaction) (Hiyama bromides to aldehydes promoted by crcl2 ofbenzaldehyde alcoholswith anri-selectivity(8,111-112). A model study ofthe reaction that this center indicates position 6 the group at with allylic bromideswith a stereogenic give as the major to (7 and centers Bt) controls the configuration at the generated centers' An chiral three at arrangement all-.syn product the diastereomer(2) with the the all-syn increases merely bromide allylic of the at the e position additionalstereocenter
c6H5cHo+ eztolj,Ver
products.)Ester, cyano, or chlo a-substituentcan favor formatr
CzH5OOC(CHj3C=CCH2
c c"Hu/
CrCl2
fl)
Chromium(Il) chloride - Lithi Allenic alcohols. Proparg rn c n c eo f C r C l z ' L i l ( 2 e q u i r ' . 1 (Use of other solvents increas
8O"/"
CHs c[
//',CHc = i
(""
a , ^ , ,
o.,^-N,'1--!-t6t5 o L t v : Y :
en, 6H
+
82:18
Bzro'->aVC6H5 cH3 oH
Addition of y -disubstitutcd halidesadd to RCHO when catr srereoselectivityobtains in add addition of LiI and use of DM? In contrast,addition of 7{isut .rnd stereodivergent(equations
Chromium0l)
iodide
chloride-Lithium
selectivity. Reactionsof chiral allylic bromides with chiral aldehydesindicate that the configurationof the bromide can override that of the aldehyde.This reaction therefore can provide accessto complex chiral adductssuch as 4, which is convertedby standard
I : C
t.25 65'.
oBzt -/cH2
CO2Bzl
CrgHzz
q j )-o
H
CHs
4 steps
Hooc\
.SHt
,,7
c,.Hrr4oAo
CHs
c)-s
rcactionsinto nephromopsinicacid, (-)-5.
CO2Bzl I J. Mulzer,L. Kattner,A. R. Strecker, andP. Luger,Am. C. Schrdder, J. Buschmann, C. Lehmann,
r'
Soc.,113,4218(1991). . ... ,t t 1992),
i
,,,/l).
,l'.'JJition fo crotYl r.r rJes homoallYlic i.'r,,t bcnzaldehyde :;t: ' that this center ril\c itsthe major : .lir.rl centers.An r:.:.ilscs the all-syn
Chromium(Il) chloride-Lithium iodide (l:1). Allenic alcohols. Propargylichalidesreact with carbonyl compoundsin the prescnce of CrCl2 'Lil (2 equiv.) in DMA to form allenic alcohols as the major products.r (Use of other solvents increasesthe formation of homopropargylicalcohols as minor products.)Ester, cyano, or chloro groups have no effect on the regioselectivity,but an a-substituentcan favor formation of propargylic alcohols.
C2H5OOC(CHj3C-CCH2Br+
CrCl2.Lil DMA
C6H5CHO
84"/"
OH | ^.,cHz
c^H^/^'V"
+ CeHsOOC(CH2)3C=CCH2OH
I
(cH2)3cooc2H5 98:2
(""
. Y*tu
cH3 oH 3
Addition of y-disubstituted allylic phosphates to RCHO.2 Both (E)- and (Z\-allylic halidesadd to RCHO when catalyzedby CrCl2 to form anti-homoallylicalcohols.Similar \tcreoselectivityobtains in additions of (E)- and (Z)-allylic phosphates.In this case rddition of LiI and use of DMPU as solvent are usually requiredfor satisfactoryyields. ln contrast,addition of 7-disubstitutedphosphatesto aldehydesis both stereoselective rnd stereodivergent(equationsI and II).
Chromium(Vl)
oxide
I ll (t) HexCHO * er'-,,/VOP(OC2H5)2 I Bu
---
crcl2,Lil 25'
effected with CrO3 in 90% aqueous: dichromate(Na2CrO3)in aqueousH; are obtained with CrO: in CHrCO(
OI H
nr..y'VH.*
"**
vtr2
, \
Bu Pr 99:1
o tl (lf) HexCHO + B]'\a/."'-,'OP(OC2H5)2 I Pr
pr "\
/
OH aoY"
r'^4'{Hex Pr' Bu
v t t /
/
-
CHs
I
'
.-.CHz
1) HBr2B.S(CH3), 2) H,O I
\
rH.C. Brown, S.V. Kulkarni,V.\'
Xl
(ree2).
9B:2 rK. Belyk,M.J. Rozema,andP. Knochel,J' Org'' 57' 40'10(1992)' I. Antes,C.E. Tucker,andP' Knochel'J' Org" 57'6384 2C. Jubert,S. Nowatny,D. Kornemann, ('t992).
Chromium(Il) chloride-Nickel(Il) chloride' lb' when treated with CrClz Cycloenediynols.t The r,r-iodo enediynals la and (14'98)' undergo an intramolecular (5-8 equiv.) and a catalytic amount of NiClz additionofthealkynyliodidetothealdehydegrouptoproducel0-and1l-membered cycloenediynols,isolatedastheacetates2aandZb'Theseproductsareunstable'but2b wasshowntoundergocycloaromatizationto3whentreatedwithl,4.cyclohexadiene. and is believed to be responsible This reaction is typical of .oln" antitumor antibiotics for thc biological activitY.
Cobalt([) acetylacetonate, Co(ace I ntrarnole cular homo D ie Ls- A I a tetheredalkyne group at C2 underg treatedwith 8 mol% of Co(acac):.((
is particularly facile when a 5- or 6 on thermal treatmentof I at l{0-
\
R
Co
\-,.r6na^ (bH,)"cHo lli"i;:)i"'',
,t^\.'t\
i l t l
\/"'aI
OAc
3 1 a ,n = 1 1 b ,n = 2
34o/o 760/o
2a 2b
Letters'32' 31'11(1991)' I C. Cr6uisyand J.-M' Beau,Tetrahedron
Chromium(Vl) oxide (CrOr)' This conversion can be effected in )80% overall RCH:CHz-RCH2COOH'1 H2BBT S(CH3)2' thexylyield by hydroboration of l-alkenes with HBBrz'S(CH3)1' followed by hydrolysis to form torun" lUrefhx), or dicyclohexylborane(HBChx2)' to RCOOH' which can be RCHrB(OH)2. The final step is oxidation of RCHzB(OH)2
1 R=H,n=1 R=H,n=2 R=CHs,n=1
W. Tam,and L.G. Edrl M. Lautens,
Copper(I) iodide-Tetrabutylenr Skipped diynes and triyncs. I rropargylic halides or tosylatess rt
:n DMF or CH3CN.I This reaction
Copper(I) iodide-Tetrabutylammonium
"u^/{Uex . , \
Bd
Pr
99:1
t'F.r, OH
t
87
effected with CrO3 in 90% aqueousacetic acid, pyridinium dichromate (PDC), or sodium dichromate(Na2CrO3)in aqueousHzSOa.In generalthe highestoverall yields (80-92%) are obtained with CrO3 in CH3COOH/H2O.
OH e t t z
chloride
CrO3,
[.ur,.r1ory, ]
CHs
cH,Z)(\He' Pr Bu
cH3cooH, Hzo
1) HBr2B.S(CH3)3 2) H2O
86/"
t'pr"oo,.., CHs
rH.C. Brown, S.V. Kulkarni, V . V . K h a n n a ,V . D . P a t i l , a n d U . S . R a c h e r l aJ, . O r g . , 5 7 , 6 7 7 3
(reez).
98:2 lq.--
J. Org.,57,6384 Knochel,
I l h .\ hcn treated with CrCl2 ::Jcrqo an intramolecular t ..c l0- and 1l-membered ..jucts are unstable,but 2b l( :'.r 1,4-cyclohexadiene. ith rt.l ..licvcd to be responsible N .
Cobalt(I! acetylacetonate, Co(acac)2 Intramolecular homo Diels-Alder reaction of dienynes.t Norbornadienesbearing a tetheredalkyne group at C2 undergoan intramolecularhomo Diels-Alder reactionwhen treatedwith 8 mol%oof co(acac)2,(c2Hs)2Alcl (4 equiv.),and dppe at 25". This reaction is particularly facile when a 5- or 6-memberedring is formed. No reactionis observed on thermal treatmentof I at l4O-170".
\
R
CHz)n
R
Co(acac)2, (C2H5)2AlCl, dppe, benzene, 25'
\.---.16r,r
1s i l
l
7
l
OAc 3
1 R=H,n=1 R=H,n=2 R=CHs,n=1
76/" 64o/o
69/"
\f. Lautens, W. Tam,andL.G. Edwards, J. Org., 57,8 (1992).
rr. ^, rffccted in )80% overall ( l1 , . H:BBr S(CH3)2,thexYl1, .. ,.rcd by hYdrolYsisto form l ( ) l i , l o R C O O H ,w h i c h c a n b e
Copper(I) iodide-Tetrabutylammonium chloride. skipped diynes and triynes. A new route to skipped diynes involves coupling of rrtrpargylic halides or tosylateswith l-alkynes catalyzedby cul, Nacor, and Bu+NCl :r DMF or cH3cN.' This reactioncan be extendedto skipped triynes (equationII).
Copper(I) iodide-Tliphenylphosphine
C u l ,B u a N C l NaCO3,DMF
(l)
Et-----CH2l
,Zuco2cH3 co2cH3
Cyanotrimethylsilane. Cyanosily lation of ald ehy d cs acid catalyst such as Znll or A ethyldiisopropylamineare alst.rh methylsilyl ethers in 90-100'i r tavalent silicate, (CHIIS(CN )\-(( amine. The reaction can proceedi the chiral tin(Il) kwis acid l. pn ( l2-l and 1,1'-dimethylstannocene
H------cH20H
F-cHroH
-;
(tt)
L-CBH1,
CaHrz+CH2Br
T'OS
cBrc/ P(cons)s I
t
7"'"''
11+(CHz)gGOzCHg
-co2cH3
E-QsH17
5'lo/"
--c8H17
The skippeddi- or triynesare reducedto skipped(z,z)-dienesor (z,z,z)-trienesby 4H2O(equationIII)' partialreductionwith NaBH+/Ni(OAc)2' (lll) CsHrz--:\-.-CH2OH
+ (CH3)39(
90o/o
crH,rfficH20H
r S . K o b a y a s h iY , . T s u c h i y a ,a n d T t
fT. Jeffery,S. Gueugnot, Letters,33,5757(1992)' Tetrahedron andG. Linstrumelle, Cyclam (1,4,8,1 1{etraazacvclotctr
Copper(I) iodide-Ttiphenylphosphine. This coupling has been effectedwith Pd catalysts, Coupling of I-allcynes and ArX.t 80-120'. but can also be effectedwith cul/P(C6H5)j (1:2) in the presenceof K2cor at
C6H5l
+
Cul/P(C6H5)3 , K2CO3 DMF,120"
HC=CC6Hs
--;C6H5CH:CHBr + HC=CC5H11-n (Elz=ss'.1)
C6H5C=CC6H5
CoHsCH:Cl-lC=CCsHtr-n (E/Z= 99:1)
1K. Oku.o, M. Furuune,M. Miura, and M' Nomura,TetahedronLetters,33,5363 (1992)'
Epoxidation.t An iron comp of I is an effective catalyst for r or CH3CN. Thus reaction with cr
Cyclam
Cul,BuaNCl D,M F NaCO3
.CC:CH3
82v"
Cyanotrimethylsilane. cyanosilylation of aldehydes.t This reaction has been effected by use of a Lewis acid catalyst such as Znl2 or AlCb (4,542-543). Amines such as triethylamine or ethyldiisopropylamineare also highly effective catalysts, providing cyanohydrin trimethylsilyl ethers in 90-100% yield. Presumably,the reactive intermediateis a penTributylphosphineis as effective as a tertiary tavalentsilicate, (CH3)3Si(CN)N(C2H5)5. amine. The reaction can proceedin high enantioselectivity(907oee) in the presenceof the chiral tin(Il) lrwis acid 1, preparedby reaction of (+)-cinchonine with triflic acid and 1.l/-dimethylstannocene(12,20I -202).
cHz:\i\
7""o^
TfOSnO,,. ttf
---CBHl7
carc/ e(coH5)3 |
-1-.H-
V-CH2Br
/ L-caHrz
: +
.rrcncsor (Z,Z,Z)-trienesbY
I
.llr
l:
osi(cH3)3 /..',-.,..CHO I |
1,c12cl2, -28" + (CH3)3SiCN 630/"
\-/
O^"(90o/oee)
-cH20H
rS. Kobayashi,Y. Tsuchiya,and T. Mukaiyama, Chem Letters, 537,541 (1991)'
-r-r.57s7(1992). Cyclam (1,4,8,1 1-tetraazacyclotetradecane), l.
- , " ' Jrn cffcctedwith Pd catalysts' ts ;.cncc of K2COI at 80-120''
t ' -
l
NH HN
c!-
C6H5C=CC6H5
-
tr.
.) NH HN
CoHsCH:Cl-lC=CCsHrr-n (ElZ=99:1) : ' ' , 1I ( \ t e r s , 3 3 , 5 3 6 3 ( 1 9 9 2 ) '
(1)
(, Epoxidation.t An iron complex preparedby reaction of Fe(CF3SO3)2with 1 equiv. of I is an effective catalyst for epoxidation of alkeneswith Hzoz (30vo) in cH3oH product or cHrcN. Thus reaction with cyclohexeneprovides the epoxide as the main
(RRF erd t!
Cyclobutenediones
OH
I
HzOz Fe(1)(CF3S03)2 -
o"+ 40/"
t i l 17"/o
cHs\--/'o
1) C6H5L| GHs 2) CH3l,Ag2O
"A"
s
6't"/"
o
cHlcH'
CHs
1
cHs
o ceHf\coH,
CeHs
'CoHs + frans-isomer
,Bu
[\-"u^,
o.
bH
3
26%
I L. S. Liebeskind, K. L. Granberg,and J. Zli
high stereoselectivity with only tracesof the allylic alcohol. cis-stilbeneis oxidized with tothecis-epoxide.Iodosylbenzene,CcHolo'cana|sobeusedastheoxidantforthis reaction.
ls,2S-cyctohexanediot. a'])'"o"
\ho"
rW. Nam.R. Ho, andJ.S.Valentine, Am' Soc',f 13' 7052(1991)'
Asymmetric allrylation of P-kao whenprotectedas the acetal2 with tlS selectivealkylation(equationl). Cyclic sulfates,sulfites,15, 105-107; 165' they are now Review.t These products have become of special interest since In addition' of alkenes' dihydroxylation availablc in optically pure form by asymmetric and epoxides of that from differ can the regioselectivityin reactionswith nucleophiles (104 1991 through 1863 from literature covers the yields can be superior.The reference
(t)
p
o$.oo.r.
references). rB.B. t-ohray,Synthesis, (1992). 103-5 2 RX Cyclobutenediones. -98;209-I2O;' 14' 253-254:16' Naphthoquinones from cyclobutenediones (13,9'7 to 2,3-disubstituted t02). Liebeskind et al.\ have devcloped a stereocontrolledroute quinonesfrom2-alkyl.3-alkoxycyclobutenediones(l).ThusadditionofArLitol 2 with RLi followed followed by methylationprovides 2 in 5O-757o yield. Reactionof byaquenchwithtrifluoroaceticanhydrideandNHqClprovidesthccyclobutenone3. followed by oxidaThese products are convertedinto quinones4 by pyrolysis at 140" tion (CAN).
= CH3l = CrsHlgBr
I K. Kato,H. Suemune, andK. Sakai.Icrrd
t R,R)- and (S,S)-1,2-CyclohexaocditL Asymmetric olefination of mahyi cthylidenationof 4-methylcyclohexans
(R,R)- and (S,S)-1,2-Cyclohexanedi(2,2-dimethylprcpyl)amine
""'\1o
OH
I
ll
H
BuLi
61"/"
^/*tutu
oAo
17o/o
cH, Bu,pH
cHs\--/P
1) C6H5Li 2) CH3l, Ag2O
i
bcH.
)L+c6H5 o\ bcH.
87v"
cHf.-cH'
,,|""
cHf.-cH'
1
cHg
c a -r.lv ^ , , 5
2€
1)140' 2) CAN
,Bu
CHg
l\-cu,,
+ trans-isomer
Bu
o b H <27"
3 'L.S. LiebeskindK , . L . G r a n b e r ga , nd J. Zhang,J. Org.,57,4345 (1,992).
c,r .',.1s ith high stereoselectivity - .:.cd as the oxidant for this s
"Ot lS,2S-cyclohexanediol. ab
\)\o|r
Asymmetric allqlation of p-keto esters.l The a-carbomethoxycyclopentanone, when protectedas the acetal2 with (lS,2S)-cyclohexanadiol,undergoeshighly stereoselective alkylation (equationI). x. , l:rtcrcstsince theY are now rc' \ . .,r1()n of alkcnes.In addition' that of ePoxidesand .r :lrr irom t: through1991(104 1863 -.-I r(,m ra:
(t)
p f
LDA, THF, HMPA,RX
coocH3
q- .. lo9- 120;14, 253-254-16, c. -.' ll;J route to 2,3-disubstituted I hus addition of ArLi to I I ilJ :-.r.rr()n of 2 with RLi followed 3. H.t :.r(r\idcsthe cyclobutenone o x i d ab y . . r . at l-10'followed ^-
o /
\,,,\
p \-coocH" R
3
2 RX
H
= CHsl
57o/o
92o/ode
= CrsHrsBr
66/o
>99% de
' K. Kato, H. Suemune,and K. Sakai,Tetrahedron Letters,33,24'7 (1.992). rR,R)- and (S,S)-1,2-Cyclohexanedi(2,2dimethylpropyl)amine. Asymmetric olefination of methylcyclohexanones (12, 396). The asymmetric with the chiral phosphonamideR,R-1, derived cthylidenationof 4-methylcyclohexanone
92
(&R)-and(S,S)-1,2-Cyclohexanedi(2,2-dimethylpropvl)amine
providesthe (S)-ethylidene2 in from (R,R-1,2-cyclohexanedi(2,2-dimethylpropylamine)' highenantioselectivity.Thisproductundergoesanenereactionwith2,3.di-o-benzyl.oglyceraldehyde(3)toformthetriol4(>90:l0selectivity),withtwonewchiralcenters. ozonizationof4providestheopticallyactiveacyclic5with|,5-anti-selectivity.
o
o
CHzC(CHg)s
r-YN. l l \-2,,,(
P/zO ' -cHrcH.
A
+ l
Y
cH2c(cH3)3
"\CHzoBzl OBzl r
1) BuLi 2) HOAo
(-) -tran s -Cy clohexane-(l\2R)-disulfoort
Enantioselective cyclopropanation d propanationof allylic alcohols is possiblc ' by this C2-symmetricdisulfonamide l. R '
(CzFl.)i
CaHs,'/-.-zOt
SnCl4, CH2Cl2
I
63%
t
T
IH. Tokahashi, M. Ohno,andS I M. Yoshioka,
CHs
CHs
(S)- 2, crp+ 23'
( R , R ) -I
(Cyclooctadiene) (cyclooctatriene) ruthcri Coupling of l,3-dienes with acrybc most efficient catalyst for this coupling to the absenceof the Ru catalyst,Diels-Aldt
CH3 QBzl
OCH39H3 : | cH3o'--yv\
),,__,.,.-_.OBzl =
/",zCH, .u ll112'
*
cH/\coN((
o o H 5, (rD- 2.6" 4 (>90:10)
Asimilarreactionwith(R)-6and2,3-o-dibenzyl-l-g|yceraldehydefol|owedby yield'l oxidative cleavageprovides, 1,6-anti-7 in 600/o
o il
+ "'CHs
(\/"'.'con CHs
-\
-.2\
H' Y: 6gzt
-OBzl
[2 + 2]Cycloadditions.2 In the prcrr acrylatesundergocycloadditionto give c1c The reaction involves prior isomerization, undergoesthermal cycloaddition with thc
1)SnCl4 2) os
(R)-6
CHr:6116t2N(C2H5)2
r*
[*r:r
1 T Mitsudo, S.-W. Zhang, T. Kondo. and \. I l T Mitsudo, S.-W. Zhang, and N. Satake.T
x
t S. Hanessian and S. Beaudoin, Tetrahedron Lefters' 33"7659 (1'992)
(CyclooctadieneXcyclooctatriene)rutheniun llD(
2 in c :' '\ idcs the (S)-ethYlidene -. 2,3-di-O-benzyl-owith :.ritrfl ! centers' N;i. * ith two new chiral . i .r:th 1.5-anli-selectivitY'
o CHg
\-cHroezt H A oBzl 3
HSo2R 16'ro2- ro3' (-)-trans-cyclohexane-(1R,2R)-disulfona-ia"', flN --./""ttHSOzR Enantioselective cycloEnantioselective cyclopropanation of allylic alcohols't the Simmons-Smith reagent catalyzed propanationof allylic ut"oiot, is possiblewith : CoH+NOz-P' ty ili. Cr-.y.metric disulfonamidel, R (C2H5)2ZnlCH212
cH#i*" * .-}--.-.oH ---l-,,,..o+ :' caHs c6H5
SnCl4'CH2cl2
'
637"
760/" ee rH.Tokahashi,M.yoshioka,M.ohno,andS.Kobayashi,TetrahedronLetters,33,25'15(1992)'
I i J
v '
*< 2 'ts+23"
Ru(COD)(COT)' (Cyclooctadiene)(cyclooctatriene)ruthenium' the acrylamides't Ru(COD)(COT)is or acrylates with l,3-dienes Coupling of mostefficientcatalystforthiscouplingtoprovidederivativesof3,5-dienoicacids.In areobtained' of the Ru catalyst,Diels-Alder adducts the absence Ru(coD)(coT) 8oo
t", ] i:
cH /YcHz
*
cH/tcoN(cH3)2
-
51"/"
o 5 rro - 2.6"
coN(CH3)2 Z'\Z'\/CON(CH3)2 I CHs
x-
bY : -rllvceraldehYdefollowed
lcl.
+ CHs
80:20 and catalyst and a base' allylamines this of In the presence [2 + 2]Cycloaddilions'z derivatives' to give cyclobutane-B-amino:ttb:Y:"-::O acrylatesundergo cycloaddition which then of the allylamine to an enamine' The reaction involves orror'tro..iration wilh the acrylate' und.r*o", thermal cycloaddition CH2:CHCOOCH3 (
NCHg, 70"
-\*s*r9* cHz:cHCH2N(C2H5)2 [cnacH:cHN(CzHtrtl /coocH3
--1
!r
l
cH;
I
7
'N(czH5)2
^*: y111^o-'; r Kondo' Zhang' rr Mitsudo, 11'"lttltiiil;' S'-w' arf{"!,;:,::^::'',iil: andN' Satake'T' Kondo' t r. rr,ritruAo'S'-W' Zhang'
-^
l
94(Cyclopentadienone)(cyclopentadienyl)dicarbonyImo|ybdenumhexafluomphosphate(1)
Acylation.r These complexes read rc amides or dipeptidesin high yield. The rc:
(Cyclopentadienone) (cyclopentadienyl)dicarbonylmolybdenum hexafluorophosphate (1). Preparation:
o ,\ \ \ / \
(CoHs)gC*PFo
1) Mo(CO)3(CH3CN)3
cH2cl2
2) LiCp
rl
1 , m . p .1 9 0 ' d e c ., air-sensitive
cis-4,5-Disubstituted-2-cyclopentenones.t Although nucleophiles react with uncomplexedcyclopentadienoneB to the carbonyl group, 1 reactswith nucleophilesa to the carbonyl group of the terminus of a diene group. Thus reactionof I with a Grignard reagent provides 2, which undergoesdecomplexationby protonation with TFA to 3. Oxidative decomplexationof 2 with C6HsI(OCOCF3)2providesthe cis 4,5-disubstituted cvclooentenone4.
CpMo(CO)2 CHsMgCl THF. -78"-*25" 1 + 92"/"
.l-zo
cF3cooH
U-.r. 2
o tl rA--cHs \J 3
I
CsH5l(OCOCF3)2 -66.7^ "'- | lcH"cl,. -78'
t
CpTa(O)Cl2
+
I
.Alo, PFo\t=)
CpMo(CO)2
+
Cptvto-(Co)z
o< Br
CpTaC|3[OCOCH(CH3)2]
- -
o tl
A--cH.
\_l
bcocr. 4
I L. S. Liebeskind and A. Bombrun,Am' Soc.,ff3' 8736(1991).
Cyclopentadienyltantalum(V) carboxylates' CpTaCl3(OCOR)' These chemicalsare preparedby reactionof a carboxylic acid with cpTacla.
amides in 75-81Vo yield with little racrmi
1K. Joshi,J. Bao,A. S. Goldman,andJ. Kohr .
Cyclopentadienyltantalum(V)
hr\afl uoroPhosphate(l)
-m
CpTaC|3[OCOCH(CH3)2] + CpTa(O)Clz +
^-9tr.
./=lo, pFo-
o< rl \t4
1 , m.p. 190"dec. , air-sensitive
ruclcoPhiles react with unwith nucleophilesd to :r.rcts ! a I T ' _ :r.rction of 1 with a Grignard to 3' tr lr()tonation with TFA 4,5-disubstituted cis . the rtlcs : ): 0{:i^
- -
C6H5CH2NH2 +
C6H5CH2NHC(O)CH(CH3)2
cptvto-(Co)z ' t
t- J:
f . -
95
Acylation.t These complexes reacl readily with amines or amino acids to form amides or dipeptidesin high yield. The reaction with amino acid complexesprovides
olr Menum
. -
carboxylates
o ll /^-CH3
l
\__,/ 3
.(. ()(OR). ci:\,\\lic acid with cpTacl4'
9Oo/o amides in 75-81% yield with little racemization. I K. Joshi,J. Bao, A. S. Goldman,and J. Kohn,Am. Soc.,ll4, 6649(1992).
rtE
coocH3
a\ t Cp2ZrRz' Dialkylbis(cyclopentadienyl)zirconium'. by reaction of reagents are available These Hydrosilylation of 1-alkenes't -78'' of l-octene with Reaction THF at c'u'Yel'.in cpzztclzwith excessBtM;;;;t n-octSiH(ccHs)z in ot cp2ztBu2results ci'z(c;H5)' HzSi(coHs)z catalyzed W-Iitn"' in13-T5Toyieldwith}ggZaregioselectivity(equationl).
- Hzsi(coHs), #
1) LDA ruEDA 2i t(caHs)clPdl2,
l
84%
coocH3
1) LDA 2) [(cH3caH4)clPdl2 TMEDA,CO
,\
n-Hex-cH2cHzsiH(coHs)z
CH
o ll
and E' Negishi' C' J' Rousset'P' E Fanwick' l T. Takahashi'M' Hasegawa'N' Suzuki' M' Saburi' A m . S o c . ,f 1 3 , 8 5 6 4 ( 1 9 9 1 ) '
t,"i|1:11n[,fids
to but ignitewhenexposed arerelativelystablein sealedtubes,
a i r ; t h e y a r e v e r y " n ' i t l u " t o t o i ' t u ' " ' O n l y d i e t h y l z i n ccan isre a dgenerated i l y a v a i l arelatively b l e i n s o safely lutions be hazardous"otpoundt These nitrogen' under packaged (equationI)'1 Zncl2 ;ith in ether by u'";;;i;tion in siru from Grignard reagents as a complex with MgX2' which is precipitated and reaction *"nt'ut"t-it'n This ether
(l) 2RzMgX + 7nCl2
=:
R2Zn+MgX2+MgCl2
cH.-rrAorr,
L^
I CHe
cl
can be isolated after osmylation to thc l'
) H. M. R. Hoffmann,A. R' Otte'andA \ArLJ
( lR,2R)- or (1S,2S)-/rans'\,2-Diaminal Asymmetric epoxidation't Jacohtn (ll or (S,S)-diphenyl-1,2-diaminoethane alkeneswith NaOCl, but the enantioscl
in the case of cis-alkenes.Subsequcntlr
| ''o""n"
{
X2Mg'dioxane CaHso. ,CoHs further a solution of R2Zn for an inert atmospheregives under Filtration dioxane. Grignard reagents' is slow in the caseof hindered reactions'This transmetalation Chem'Int' Ed'' 3O'1008(1991)' rD. Seebach, L. Behrendt'andD' Felix' Angew'
-J
z:N- .Nr Mn ;-
cn-4 !o'cio{ ts.", t-Bu
l-Bu 1
Di-p-allylpalladuim chloride)' [(C3H5)ClPd]z'- -, and carbon of TMEDA (large excess) 'ft" p"t"n"" a'Cyclopropyl esters-j--in esters to carboxylic of complex reacts with enolates n-allylpalladium this monoxide, minor products of allylic alkylation u' itt" rnulo' product' The form 2-cyclop,opyt t"t'* 96
Jerived from the readily available rra solved by crystallizationwith tananc r
(lR,2R)- or (lS,2S)nrazs-1,2-Diaminocyclohexane
coocHs
o t:
It ;
coocH.
A
" l t
coocH3
84y"
.
::! atailable bY reaction of -\". Reactionof 1-octenewith , z'-llu; rcsultsin n-OctSiH(C6H5)2
1) LDA 2) [(CaH5)CrPd]2, TMEDA,CO
1) LDA 2) [(CH3CaH4)CrPdl2 TMEDA,CO
CH=C1166.
x
COOCH3 +
,Xoor"
\J
,
(14"/") (83olo)
' - Hex-CHzCH25iH(C6H5)2
I
o
9H' I
"t.1Aor,
.,:. P.E. Fanwick, andE. Negishi,
CHe
.'-\. hut ignite when exposedto ri. - :. rcadilyavailablein solutions nrj. ::r hc gcneratedrelatively safely ::r\,n with ZnCl2 (equationI).r n-,cipitatcd . as a comPlex with : r i:
l:Z^-MgXe+MgCl2 t . I Oloxane
O
A/or., cHs
'cHg
can be isolated after osmylation to thc 1,2-diols. ' H. M. R. Hoffmann,A. R. Otte,andA. Wilde,Angew.Chem.Int. Ed., 31,234(1gg1).
( lR,2R)- or (lS,2S)-trans-1,2-Diaminocyclohexane. Asymmetric epoxidation.t Jacobsen'ssalen-basedcatalyst l, derived from (R,R)or (S,S)-diphenyl-1,2-diaminoethane (16,157) can effect asymmetric epoxidation of alkeneswith NaOCl, but the enantioselectivityis generally only moderate(-70% ee) in the case of cis-alkenes.Subsequently,this group has examinedsalen-basedcatalysts
I
X2Mg.dioxane
caHso. ir-. , .,rlution of R2Zn for further r : - :rJcrcdGrignardreagents. -
i-
; -10.l(X)tt(1991).
7:N. .Nr Mri ,--(\ \ l/r\ //
//
6Hs1
cto{ :\ )-o t-Bu
f-Bu 1
t\ll I)..\ (large excess)and carbon s:'- :n()latesof carboxylicestersto k -r 'r,\rproductsof allylic alkylation
a)
,coHs
H,')--(.H i' 7:N. ' Mr .N:.
\\
)-cH.
A r-4,-( !o'cio{ :\l-Bu
\-
_F t-Bu
)-t-a,
2
derived from the readily available trans-1,2-diaminocyclohexane, which can be re:olved by crystallizationwith tartaric acid. Of these new catalysts,2 proved to effect
(l&2R)-
or (lS,2S)-lrazs-l'2-Diaminocyclohexane
epoxidation of cis-alkenes with >907o ee. Thus it effects epoxidation of cis-Bmethylstyrenein92% ee and of a ketal in 94% ee. Even an a,B-unsaturated ester can be epoxidizedinsgVo ee, but in this casethe reactionwas conductedin the presence of 4-phenylpyridineN-oxide.
c6H?_/cH3 847o,92o/oee
aY"l \--J
coHs_rcoocHs
b-'-
63/o,94"/o a@
c6HsscH3+ H2Oz
65%. 89o/oee
3 C
,
Br I
Asymmetric epoxidation of l,3-dienes and eynes. Jacobsen has extended his methodfor effectingasymmetricepoxidationof alkeneswith a chiral (salen)Mn(II) complex (16, 157-158) to conjugateddienesand enynesby use ofthe chiral (salen)Mn(Ill) complex 2.2 Epoxidation of l,3-dienes with Naocl catalyzedby S,S-2 provides only monoepoxideswith only moderateenantioselectivity(-45Vo ee). In the caseof (Z'E)-dienes' epoxidationoccurswith high selectivity(10:1) at the (Z)-alkene(equationI). In contrast, high enantioselectivitycan be obtainedwith cls-enynes(equationII)'
tiYt-.H3
+ Hzoz
\2
I E.N. Jacobsen, W. Zhang,A. R. Muci.J. R [.ri, I N. H. t-ee and E. N. Jacobsen,TetrahedronLcu I M. Palucki,P. Hanson,and E.N. Jacobscn. rlv
(DBU l. 1,8-Diazabicyclo[5.4.0]undecene-7
(D rerora,,y'J
CHs
NaOCI 2
tsBrorc-_ZylcH. = 7: l),66%ee (trans/cis
(cHs)ssi\__ortt' 1rr;
(CHg)sSi.\---. Y,,6 oHs
a-Ailql a, B-enones.t Theseprodrrt: a Michael acceptorwith DBU (0.20 equir I i
o
l l l .
CHr:6g"OOC2H5
(trans/cis= 2.5 : l), 90%ee
E
o tl \,rr3
Asymmetric ortdation of ArsR wilh H2o2.3 The chiral (salen)MnCl complexes derived from this diamine can effect asymmetric oxidation of alkyl aryl sulfides' The highest enantioselectivityis obtained with (R'R)-3.
DAJ rl
| r(
+CH,:CHCN-CHs
60
1,8-Diazabicyclo[5.4.0]undecene'7 (DBU)
ct:-.i\ epoxidationof cis-Bir r: .rn a, P-unsaturatedester I q.1. .()nductedin the presence
:N.
/ Mn
(R,R)-3
dir
c(cH3)3
coHs_rcoocHs
q
3, CH3CN
c6H5scH3+ H2o2 -- **-
65"/",89o/oee
.s'
cuHui5-cH. (-)-S' 47% ee
o\\ ts'
t-ar. + H2o2-r"**
his t!. J.rcobsenhas extended com(II) '' (salen)Mn ., chiral * chiral (salen)Mn(Ill) ! .--, "i the mono1 -. :.S-2 Providesonly (Z,E)-dienes' of case i r-, ln lhe ln contrast' [,-.: renc (cquationI)' I I ) . F -.:u.ttion
,1x1s-cH.
\z-s,
(-)-S, 68% ee
(1991)' I E.N. Jacobsen, W. Zhang,A. R. Muci, J R' Ecker,andL' Deng'Am' Soc''1f3' 7063 r N. H. Ire and E.N. Jacobsen, Letters,32,6533(1991)' Tetrahedron r M. Palucki,P. Hanson,andE.N. Jacobsen, ibid',33,'7111(1992)' (DBU)' 1,8-Diazabicyclo[5.4.0]undecene-7 can be preparedby additionof an enoneto products These a, a-Atlql B-enones.t
uo,o.-Z-
---6"t'
aMichaelacceptorwithDBU(0.20equiv')in1,3-dimethyl-2-imidazolidinone(DMEU)'
o
II
.\. \-/
CH2:611aOOC2H5
CHs-
)a l.l
rhiral (salen)MnCl comPlexes The :r\rn of alkyl arYl sulfides'
185' 80v"
-
,)',-.cn"cH2cooc2Hs
I r l \-/
o A
1a
o
D B U 'D M E U '
o I '\"r. + CHz:CHCN
60"/.
ar.&"H2CH2CN ll-cH,
Diazomethane
Diborane. Diastereoselective reduction of 4-Lc'to. be effected with several reductants.but thc with BH3.THF at -78' in THF.'
o
2l
ll
85o/o
tlt-a", 1,8-Diazabicyclo[5.4.0]-7-undecene hydrobmmide,l.
/ \
\ \\-// / \
oH
-2
N+ 'l-
R1
"lt-"",
' N- - ) t l \
?1"".
B-o^c".
Er
H
R2
o{
_CH.
*'/-;=,d-oX"r, anti - 2
1, m.o. 120- 122"
Preparedby reactionof DBU with Br2 in HOAc in the presenceof HBr. Bromination of arenes.2 This reagent brominates activated arenes at room temperature in DMF/H2O (phenol * tribromophenol, 89Vo yield). Less reactive aromatics are brominated by I in the presenceof HgCl2 as catalyst (mesitylene* 2-bromomesitylene,76Vo yield). Polycyclic arenes are brominated by 1 in refluxing acetic acid (naphthalene- l-bromonaphthalene,65Voyield). rJ. R. Hwu, G. H. Hakimelahi,and C.-T. Chou,Tetrahedron Leuers,33, 6469(1992). 2 H. A. Muathen , J. Org., Si , 2740(1992). Diazomethane. Cyclopropanation.l This reactioncan be conductedwith diazomethanegenerated in situ ftom N-methyl-N-nitrosourea(excess)with KOH in CH2CI2/O(CzHs)2. A number of Pd compoundscatalyzethe cyclopropanationand are equally effective for ex situ and in siln reactions.
R1= CHs,R2= CHg
71%
gt = cHe, R2= i-Pr
8996
R1= iPr, R2= CHs
92:%
:
I G.A. Molander,K. L. Bobbin,andC. K- Murrr
Dicarbonylbis(triphenylphosphine) pelht I,4-Silylstannation of l,34ienes.) T reaction,which can be highly regio- and tE silyl)tributylstannanewith butadiene prorx organosilylstannanes with more bulkr gru obtained in lower yields.
(l) Bu3snsi(cH3),* " 4Yc',
\ /f> r\/
?
+ cHs--*Arr,
(c6H5cN)2Pdct2, KOH,CH2C|2
| NO
I O. M. Nefedov,Y. V. Tomilov, A. B. Kustitsyn,U. M Dzhemilev, and V. A. Dokitchev, Mendeleev Comm., 13 (7992).
(CH3)3SnS|C6H5(CH3)2 * CH Z",ZQ
r Y . T s u i i a n d Y . O b o r a ,A m . S o c . , 113.g-Vs rt
Dicarbonylbis(triphenylphosphine)palladium
Diborane. Diastereoselective reduction of 4-ken-2-alkylborate esters (1). This reaction can obtained be effected with several reductants,but the highest diastereoselectivity(anti) is -78' 'THF in THF.' at with BH:
Ct1. ",_,^
9{-Ci
.!.
x
BHs.rHF
'
rHF'-78' >
o-o'tcH. L I
tlt-,,tt.
,"t3t.*
B-/tcH.
Rr
,,
9H l" ?1"r. -
Ri ///\\,//\"\./t
OnC r,
syn-2
anti - 2
a
'rc of HBr. rr .Prcsence x:r-.::.\ activated arenes at room rf - - l. sqc''r Yield). lrss reactive o: f li( l- as catalyst(mesitylene :r .-. hrominated bY I in refluxing l:
.rcld).
l, - . ::, ,,. 33. 6469 ( 1992).
generated n.:...:rJ wirh diazomethane A number l.li{ rr CHrClr/O(C2Hs)2. nc .,', rquallv effective for ex situ and
Rl = CHg, R2= CHg
71o/o
34:1
R1 = CHg, R2 = iPr
89%
62:'l
Rr = !pr, R2= CHs
92/"
>50:1
I G.A. Molander,K. L. Bobbitt,andC.K. Murray,Az. Soc',ll4, 2759(1992)' (1) Dicarbonylbis(triphenylphosphine)palladium, Pd(CO)2[P(C6Hs)3]2 catalyst for this effective most is the I,4-silylstannation of l,3-dienes.l This of (trimethylreaction the Thus (E)-selective. reaction,which can be highly regio- and I). Other (equation (E)-alkene single a provides silyl)tributylstannanewith butadiene are products the and reactive less groups are with more bulky organosilylstannanes obtained in lower yields.
(CO)2Pd[P(C6H5)312
(l) Bu3snsi(cH3)s+ cHNct'
--ffi-
r
(;
(E)
ti(cH3)3
- (E)
(cH3)3Snsic6Hs(cH3)2 *cn/v"',
D..-
1cr. and V. A. Dokitchev,Mendeleev
-"*-
rY. Tsuji and Y. Obora, Am. Soc., f n, 9368 (1991).
ffitic6H5(cH3)2
102
Di-p-carbonylhexacarbonyldicobalt
Dicarbonylcyclopentadienylcobalt, CpCO(Co)2' presenceof CpCo(CO)z' the mono[2+2+2]Cycloaddilion (cf. 12,163).1 In the mixture of epimers' cyclic enyne (Z)-l cyclizesto the tetracyclic diene (2) as a 2:1 (3), and can be The product has the carbon skeleton present in the diterpene stemodin the diterpene'This converted in three steps to an intermediatein a total synthesisof cycloaddition fails with (E)-1'
The yield of the carbonylation-erpan catalyzed by both Co2(CO)s and Ru.tCC (equationIII).
/^-r-\ l
(il) \.,\ru'
l
)
\
d
+ co
CHzCOOCzHs + Ru3(CO)12
This combined catalyst can also effcrt tones to tetrahydroindolizines(equationllll rearrangement(equationIV).
CpCo(CO)z 55"k
(rrr) cH.-Q-cH,
2 (2:1)
@(col
cH2coc(cH3)3
co | (lv, CH3..\N,'
CHs
Co2(CO)e. Rua(COr. | -----;;CH2COC5H5
I J. Germanas, Am' Soc',ll3' 4006(1991)' C. Aubert,andK.P.C- Vollhardt, Di-p-carbonylhexacarbonyldicobalt, Co2(CO)a' by to Ring expansion-carbonylation.t The ring expansion of aziridines BJactams piperidones to a Rh(I) catalyst(r5,82-83) hasbeenextendedto expansionof pyrrolidines by cobalt carbonyl-catalyzedcarbonylation(equationI)'
(r) +R,.
Co2(CO)6 c6H6,02, 220'> co
R1 R1= CHs, R2= CHzCoHs R l = C H s , R 2= C o H s
(-'{^'
.)
nr AttAo Rr 24o/"
Cyclic enediynes. The realization thr an enediynecore which is essentialfor tlx svnthesisof this ring system.One approa'h eldehydeprotectedas the Co2(CO)6adduc conventionalstepsfrom cyclopentene-l--i{ and N(C2H5! cyclizesto 2 in 69% rield
o
* t\ttAol R1 15"/o
oHc
\cotcor.
i
I
t-BuMe2SiO
cH2oH 56"/"
e{
Di-p-carbonylhexacarbonyldicobalt
r :---.nce of CpCo(CO)r,the monoir:- lr as a 2:l mixture of ePimers. hr .r :Jrpcnestemodin (3), and can be ' ' : \\ nthesisof the diterPene.This
103
The yield of the carbonylation-expansionreaction is generally improved when catalyzed by both Co2(CO)s and Ru3(CO)12, dodecacarbonyl-tri-tr iangulo -ruthenium (equationIII).
/^>-1
t t (ll) \-,^-t'
)
an
tt--AttAo t
Co2(CO)8
+ CO
\ cH2cooc2H5
l
I
CHzCOOCzHs
+ Ru3(CO)12 79/o
c: \
This combined catalyst can also effect cyclization of 2,6-dimethylpiperidinylketones to tetrahydroindolizines(equationIII), and this cyclization can predominateover rearrangement(equationIV).
co
2 (2:11
(lll)
Co2(CO)6, Ru3(CO)12 cH.Af^ar. cH2coc(cH3)3
r
| (lv) c H ". A N 2 t
|
r
c
o
l
a^) l
Ru3(co)12, | co2(co)s, \ruA 77yo ,.-1)
cH2coC6H5 -\ .
I l-r. .l(x)6(1991).
t-
c\: :-.rrrnof aziridinesto B-lactamsby c\: :'r\r()nof pyrrolidinesto piperidones Ir s:
lttt
F:
-* " R1 24o/o
-
t
tR'
o
\rAo
-
CeHs
oHc \colcolu
Bu2BOTf NEt3
t-BuMe2SiO l-BuMe2SiO
cH20H 56o/o
*cH.
1o:1
/-\ lll lII ttt^o
|rr.rrCur, l
Cyclic enediynes. The realizationthat a number of antitumor antibiotics contain an enediynecore which is essentialfor their activity has led to extensivemethods for synthesisof this ring system.One approachinvolves an aldol reactionwith an acetylenic aldehydeprotectedas the Co2(CO)6adduct.Thus the keto aldehyde1, preparedin five on treatmentwith dibutylboron triflate conventionalstepsfrom cyclopentene-1,3-dione, and N(CzHs)r cyclizes to 2 in 69Vo yield. Attempted decomplexationwith N-methyl-
l
R1 15"/o
c(cH3)3
Didlt
104
Di-p-carbonylhexacarbonyldicobalt
o9l R3S|CTCCHO + CHoCH-, Coz(CO)o sc
Q,*'*o
1
2(ElZ= >%
CH2OBBu2 3 to 3' Such morpholine N-oxide (NMNO) in cyclohexene results in aromatization agents'2 aromatizationis characteristicof compoundsof this group of antitumor the antibiotic (6) of structure enediyne tetrahydroquinoline the A synthesis of propargylic alcohol with an dynemicint involves condensationof a co(co)6-protected enol.3 Thus treatment of 4 with triflic anhydride and 2,6-di-t-butyl-4-methylpyridine
The uncomplexedpropynal underqocsI Intramolecular Pauson - Khanl alkynyl allylaminochromiumor lung intramolecularPauson-Khand reac-tx
inCH2CI2/CH3NO2resultsin5in52%yie|d.(Useofnitromethaneiscrucialfor iodine provides 6, which satisfactoryresults.) This product on decomplexationwith undergoesaromatizationwhen heatedto form 7'
(co)sM -coocH3 Tf2o, cH2cl2,cH3N02 43o/o
l,M=Cr,W
M.D. Wang and H. Alper,Am. Sr. ll, r P . M a g n u sa n d T . P i t t e r n aJ, . C . S . C h d ' P. Magnus and S. M. Fortt, ibid.. 5JJ t I 'C. Mukai, O. Kataoka, and M. Hanaob ' F. Camps,J. M. Moret6, S. Ricant. arxl J
52o/"
Dichlorobis(cyclopentadienyl)hrhi c ' p l H f C l 2 - A g C l O 4 , 1 5 , 11 9 - 1 2 0 : l C l
7
6
complex I ofProPYnal Diastereoselective aldol reactions of propynals'a The cobalt almost exclusivelY' aldol syn the form (2) to reacts with O-silyl ketene O,S-acetate
Aryl C-glycosides.t This C-gl1c - )-gilvocarcin (a). An unusual feel ('-glycosidation of the A ring. folk Ihus reaction of the t--acetylfucosc,
t'plHfCl2/AgClOa (2 equiv. each) rn ! in 877ayield. This product was cor
Dichlombis(cyclopentadienyl)hafnium-Silverperchlorate
*"'tI::::,
I
+ cH3cH<
Coz(CO)o
I
1)TiCl4 2) CAN
psiR3
1
sc(cH3)3 2 (Elz = >98: <21
'cH2oBBu,
105
o' Hl ol -\ -\ -SC(CH3)3 R3S|C=C' \a CHg 3 (syn/anti= >98 : <2)
J
rr-.'. ::r aromatizationto 3. Such S ' l , ' t a n t i t u m o ar g e n t s ' 2 n. .::ucture (6) of the antibiotic p:-.'-.1 propargylicalcoholwith an
(95:5). The uncomplexedpropynalundergoesthe samereactionwith high ar?/i-selectivity Intramoleculnr Pauson-Khand reaction. Addition of Coz(CO)a (1 equiv.) to alkynyf allylamino chromium or tungstrum carbenecomplexes(l) at 25" results in an intramolecularPauson-Khand reactionto provide 2 in 7O-75% yield.
r: .: 1.,'-di-r-butyl-4-methylpyridine I nitromethaneis crucial for t.' ,.rlh iodine Provides 6, which l
H
/--CHz
NJ
(co)5M
Co2(CO)8, THF, 25' 70 - 75v"
I,M=Cr,W
:M.D. WangandH. Alper,Am.Soc.,114,7018(1992). : P. Magnusand T. Pitterna, J.C.S. Chem.Comm.,541,(1991)'P. MagnusandS.M. Fottt,ibid.,544 (1991). 'C. Mukai.O. Kataoka,andM. Hanaoka, Letters,32,7553(1991). Tetrahedron ' F. Camps,J. M. Moret6,S. Ricant,an
520k
6
T'
I :rccobaltcomPlexI of ProPYnal - 'rn aldol almost exclusivelY.
Dichlorobis(cyclopentadienyl)hafnium-Silver perchlorate, Cp2HfCl2-AgClO4,15,119- 120; 16'120-121. Aryl c-glycosi.des.l This c-glycosidation was used for synthesisof the antibiotic 1+)-gilvocarcin (4). An unusual feature of this synthesis is that the first step is the c-glycosidation of the A ring, followed by addition of the remaining three rings. Thus reaction of the t--acetylfucosederivative 1 with the iodophenol 2 promoted by -78 - -20'provides the c-glycoside Cp2Hfcl2/Agcloa (2 equiv. each) in cH2clz at five stepsto 4 in 38% overall yield. in 3 in 87Voyield. This product was converted
Dichlorobis(cyclopentadienyl)zirconium
Cp2HfCl2 AgClOa
OBzl
Ethylmagnesiation of alkenes.'' In thc nesium chloride adds to alkenesto sivc.an electrophiles(equationI).
bH. 1
fl)
OBzl
n-CsH17CH=CH2 +
C2H5MgCl
OH
o
OBzl
Hr,,
c,
n-CaH.,z^
1T. Matsumoto,T. Hosoya,and K. Suzuki,Am. Soc.'114,3568(1992)' Dichlorobis(cyclopentadienyl)zirconium. Coupling of |-alkenes with Grignard reagents, TWo laboratoriesr'2have reported that Cp2ZrCl2 can catalyzecoupling of l-alkenes with C2H5MgBr or (CzHs)zMg' Thus l-decene reactswith c2HsMgBr in the presenceof cp2zrcl2 to form the bisGrignard reagent (a) that on quenching with HrO+ provides 3-methylundecane(l) The high
This carbomagnesiationcan also he ag caseof the free alcohol, the reactionafftxd
OR
CH2:CHgH17
+
C2H5MgBr
CP2ZrCl2 rHF
C,H^ -
arrrrro---l.-*,
1) C2HsMgCl. W& Hp2 2) B(OCH3)3:
ncsH2o)\r'cHz R=H R=CHs
70q 8G
**i".o. I
i'"'
CgH17
CH3 1
regioselectivity is notable. Another advantage is that the intermediate is a Grignard reagent subject to further functionalization.
Protectionof the alcohol with a t-bul)ldrrnc ncsiation.The actual catalyst in these rcxt dc, Ethylmagnesiation of homullylic can add to the double bond of homoalllh high stereoselectivity.In the cas€of the aar proceedswith high anli-selectivityin thc cr ln contrastto the reaction of the sln-txrnrq
107
Dichlombis(cyclopentadienyl)zirconium
of Cp2ZrCl2Qnol'%)'ethylmagEthylmagnesiationof alkenes.3 Inthepresence (a) that can react with various intermediate an give to nesium chloride adds to alkenes electrophiles(equationI).
Cp2HfCl2 AgClOa t
87o/"
OH
?T'!i;+ c2H5Mscr (r) n-c6H17cH=cH2 L-"-r,,j]"n''l t t
'y*
ocH3
a
uur"I "*.""o
I
?"'?t
QzHs ,-crHrr/'--'-oH
n-csHlrMcH3
4 ll
:'',. (1992).
Thiscarbomagnesiationcana|sobeapp|iedtoallylicalcoholsandethers.Inthe cascofthefreealcohol,thereactionaffordsthesyn-diolwithg5:5diastereoselectivity. . Irro laboratoriesl'2have reported Thus :':' (';H.MgBr or (C2Hs)2Mg' : ( r-Z-rclr to form the bisGrignard (1) The high 'rJ,- :-mcthylundecane 6
oR
j" oH
ll 3,,5#:;i;i6t'": ?" ?'*r-c"nro)1., r-""rrol
)--=-zcHz#
lzHs l t'"n'c'H"l
n-Cs{2s'
R=H R=CHg
CzHs
CzHs 7O"/o 80o/"
95:5 11:89
I
se'u.n.oI I
?"u CH3^CgH17 1
t\
rhe intermediateis a Grignard
blocks carbomagprotectionof the alcohol with a l-butyldimethylsilyl group completely "Cp2Zr'" be may nesiation.The actual catalyst in these reactions (ethers)'a Ethylmagnesium chloride Ethylmagnesiation oi homoallylic alcohols on catalystswith cp2Zrclz with alcohols can add to the double bond of homoallylic highstereoselectivity.lnthecaseofthearrli-homoallylicalcoholl(R:H)thereaction proceedswithhighanli.selectivityinthecaseofboththealcoholandthemethylether. lncontrasttothereactionofthesyn-homoallylicalcohol3,thereactionproceedswith
Dichlorobiscyclopentadienylzirconium
- Butyllithium
t
2)B(ocH3)3/H2o2,-78' CHz
l
\.^1r-
9H'
l n-Non--1
n-Non-\,cH2oH
r
| L
Bzt 1
3 +svn-4
o\-
5* b,Hu
l
CHZ
anti-4
less in the case of the methyl the anri-selectivityis markedly less cnri-selectivity,and ether (3, R:CHI)' , ..- .^) ^*.-6ac proceeds -.ncee6s sluggishly' slueeishly,the reacof disubstitutedalkenes Although carbomagnesiations regioselectivity'However' pro"."o, in high yield and .'onof endo_5_noruorn"n-z-oi1iy of the methyl ether of 5' ur. O."r.ured in ttr" reaction the reactivity unO ,"gio..tlO"iui(
1)C2HsMgCl,CPzZtCl2 2) H3O*,-40"
,,.\
ZCHz
I I ( tt \.,A^r/
I
97o/o 75"/"
>99:1 97'.3
l\'cPlr'
z)x"o' , 8'*
Bzl
"o'zr s+z"lrr o\-
_AczHs+"&"r,
RO
-'--,
85:15 65:35
55-/o 38o/o
3,R=H R = CH3
s,R=H R = MEM
,,n l\l'""""e s i ( c H 3) 3 [.&"
>99:1 97:3
CHs
l
6rH, 6n anti-2
75o/o 65%
1,R=H R=CHs
OR
+svn-2
" *on-.-,[cH2oH
I
\[!' l t t\-'tN
)
H Bzl
Am' Soc'' ll.3'6266 C'J Rousset'and E' Negishi' rT. Takahashi,T' Seki' Y' Nitto' M' Saburi'
(reel).
'btd'' 113'6268'^(1eel) t)i.s.'il,*n, and R'M' Wavmouth' 'Am' Soc''ff3' 5079(1991)' , e,.*t. tt"i.VA^ and Z' Xu' ibid" 113'8950(1991)' aA.H. Hoveyda,Z'xtt'''t'fr"'"*"] ^Je'u Houri' 14' 122-1'23' "ZtCp2" Dichtorobiscyclopentadienylzirconium-Butyllithium"'ZrCp2"' Reaction of dienes;^p-erhydroindoles't or enynes of is Reductive coupling in a zirconacycle (a) that i in THF at 25" results with the cyclohexenylat;
;"';',ll*:1.11: byHc,(10%;; hydro,yzed I,flil;,Jj ll];ffifi'.;*!i:::,'."#, to gtvesu electrophiles other various i" "r"uu.A by ketone3' oi a wittr Co gives the tricyclic
t Triquinane sYnthesis'2 A highlr zircontu the :.rlenic acid (6) employs group :nyne I with an allylic hydroxyl C I the of Addition :o the A-B rings. e This group' ,'f an allylphosphonate oxidat by followed rinylphosphonate t0 shich is hydrolyzed by a mild base (Z)-crotylphxp rnion (BuLi) of diethyl
Dichlorttliscyclopentadienylzirconium
- C p
CHs '-.,,-,CH2OH + syn-2 cR
si(cH3)3
| .+N'/
31ti-2
si(cH3)3
Cp-)r
lll 't'"0," -
,, 1 ! *.\ 1
czHs
H
Hso* 75o/o
I
H Bzl
>99:1 97:3
Bzl 1
I 30%lco
CHs ,-\--,,.CH2OH
- Butyllithium
+ syn-4
o\-----
I OR CzHs
XIj( l t
anti-4 8 5 : 15 65:35
--\--tN
)
H Bzl 3
. s.s in the case of the methYl . - rroceedssluggishlY'the reaci l r .: .'nd regioselectivity.However, x' - ,.tion of the methYletherof 5.
cHo
4CH, I
.--.1 | (tt \Anr/
1l"Cp2zr" 2)H3O* .
8eo/o
Bzl
I
H 9H'
-^-bt l l \,1-N
)
H Bzl "CP2ZI"
94o611l
l2)co
I o\-
i
H. I H I
a-K \-]-- i
R >99:1 97:3
H Bzl
t
Negishi, Am. Soc., ll3'
6266
f.
!-_ I l.r se50 (1991).
bm. lrCP:"' 14,122-123' "ZrCP2" Fdr,,indoles.tReactionof '(a) that is rn a zirconacYcle F, r-i
ricld). The Zr-C
bonds can
l h - : ' . : : c d p e r h y d r o i n d o l e s .T r e a t m e n t
Triquinane synthesis,2 A highly stereocontrolledsynthesisof the triquinane penralenic acid (6) employs the zirconium promoted bicyclization-carbonylation of an cnyne 1 with an allylic hydroxyl group to provide the bicyclic enone 2, corresponding ro the A-B rings. Addition of the C ring was effected by a novel Michael addition of an allylphosphonategroup. This approach is useful becausehydroboration of a vinylphosphonatefollowed by oxidation provides an (a-hydroxyalkyl)phosphonate, which is hydrolyzed by a mild base to an aldehyde(equationI). Thus addition of the to 2 provides3, which, after protection anion (BuLi) of diethyl (Z)-crotylphosphononate
110
- Butyllithium Dichlombiscyclopentadienylzirconium
(r'
ot l
1) BH3THF
ol l
CHs
2) H2o2,NaoAc> RCH2_.,,,P(OC2H5)2
R'\,-P(oCzHs)z
OH
NaHC03, cH3oH,H2o> 80 - 85% overall
CHs
RCH2CHO several sleos 467o ov€r3ll
Reaction of 3 with pyridinium of the carbonyl group' is convertedto the aldehyde3' p-toluenesulfonateeffectsdeprotectionofthecarbonylgroupfollowedbyaldolization. Dehydrationofthealdolfo|lowedbyhydrogenationprovidesthetricyclicketone5. Thisproductisconvertedinto(+)-6bystandardreactions.Thiscyclopentannelationto providetheCringproceedswithhighstereo-andregiocontrol'Sinceallylicalcoho|s canberesolvedbySharplesskineticasymmetricepoxidation,itshouldbepossibleto prepare optically active triquinanesby this route'
si(cH3)3
3:ii'"'' sr.
CHa CHs
84"/o
followed by protonolysisand cartrx was used for a synthesisof (*)-tn A lle ny lzirc oniu m reage nts.t allenylzirconiumreagent(a) that rt ctherate to form anti-B-acetvlenic . and anti-p-acetylenicalcohols.a si tbrmed.
CHS
OBzl
1, R = CHzCoHaOCH3-P
coHs4 cHs.-1^cHo Li
t
t
o
:;:tpfi
l
1) CH3CHCH=CHP(OEt)2' 2) BU4NF 94o/"
1) 2) 3) 4\
PyHTs MsCl DBU H2,Pdlc
58%
CHsCHs CHs
CHs
o -so.z.*
CHs CHg
Bicyclizationofl,6.heptenynes.3Treatmentofthechiral3-methyl-1'6-octenyne formed from Cp2ZrCltlBufi $:Z)' t, preparedfrom (+)-citronellene, with the reagent
V. Mori. N. Uesaka,and M. Shihas r{;. AgnelandE. Negishi, Am.Su . I 'G. and E. \q Agnel,Z. OwezarczYk, 'll. Ito, T. Nakamura, T. Taguchi.and
Dichlorobis(triphenylphospine)pc Carbo ny latio n of o-allY Ibc aad :hloride (1) in the presenceof tr ralladiumcatalyst(5 mol %) prorr
Dichlorobis(triphenylphospine)palladium(II)
CH.
o !-
lll
1) "ZrCp2"
acHz-.-.,.i51ocrHu;t
lAI
2 ) H a O * :C O , 73"k
I
\
'rfi
OH
F o
2. >9o%de
CHe H : -
1*:
- severalsteps 46o/o overall
d. .r Rcectionof 3 with PYridinium ir',,uP followed bY aldolization' :':,,rides thc tricYclic ketone 5' h r. This cyclopentannelationto t.:. d --- 'crrntrol.Since allylic alcohols (:. \:.:.lii()n.it shouldbe possibleto
si(cH3)3
o HU
c _
F'
(+) - 3, >99o/oee
2. This product followed by protonolysisand carbonylation,providesthe bicyclic ketone was used for a synthesisof (+)-iridomyrmecin (3)' "Cp2Zr" reacts with propargylic ethers to form an Allenylzirconium reagents.a presenceof BFr allenylzirconiumreagent(a) that reacts in sia with aldehydesin thc to the sy'?addition In ctherateto form anti-P-acetylenicalcoholsas the major product. is usually alcohol nd anti-p-acetylenicalcohols, a significant amount of an a-allenic tbrmed.
OBzl
"Cp2zl' THF.-78"
coHs-{
cHs..1^cHo
3::>epfi RJil
t{''
H-,o
cH'. H
H 2
t{Y
- CHs CHs
:hc chiral 3-methYl-1'6-octenyne rmcd from CPzZrClzlBuL\ (1:2),
o
c-CsHrrCHO BF3O(C2H5)2 76"/"
CHs
CoHs
CoHs ?
49:l
J' Org'' 57, 3519(1992) V. Mori. N. Uesaka,and M. Shibasaki, I c. Agnel and E. Negishi,Am. Soc.,ll3,'7424 (1991) 'c. Letters'33' 1543(1992)' and E. Negishi,Tetrahetlron Alnel, Z. Owezatczyk, 'H. It;, T. Nakamura, ibid'' 33' 3769(1992)' T. Taguchi,and Y' Hanzawa,
Dichlorobis(triphenylphospine)palladium(II)' (600 psi) of o-allylbenzyl Carbonylation of o-attylben4yl halides't Carbonylation in the presenceof this and (2 equiv') ;hloride (1) in the presenceof triethylamine (2) in 78o/oyield' lactone enol benzoannelated the ralladium catalyst(5 mol %) provides
rtz
Dichlombis(triphenylphosphine)palladium(II)
.Z\\.,//\r\r
r
t t *cHz
iT
,-,
l
- Copper(I) iodide
CO'N(C2H5)3
Pd(il) 780/"
(') u
Bu2MePy 9 o H Tf2O, cH2ct2,25' _
63v"
orf (D )-.,o,
=cH,
.orf
t_/
c
a
+ Hl
(E)-1
cl
HO-----.
sevefal steps
?tt orr
tr
.
,)fJ:,
(z)-1
of theantiulcer in a synthesis A similarreactionwith 3 gives4, whichis an intermediate agentu-68,215(5).
and 2 equiv. of diethylamineto givc thc tl ,nd (Z)-2 exhibit comparablecytotoxitr K. Arai, K. Yamada, andS. Tcrr K. Nakatani,
rG. wu, I. Shimoyama, J. Or9,56,6506(1991)' andE. Negishi, -Copper(I) iodide' Dichlorobis(triphenylphosphine)palladium(II) be coupling of dienol tlitriflates and propargylic alcohols.t This coupling can dicyclic the used to obtain open-chain (E)- and (Z)-dienediyne diols, analagousto enediyne system of the neocarzinostatinchromophore,responsiblefor the cytotoxity prepared of the antitumor antibiotic. Both (E)- and (Z)-dienol ditriflates (1) can be couple ditriflates from 2-formylcyclopentanoneas shown in equation(I). The dienol of cul, lo% catalyst, with propargylic alcohols in the presenceof 5 mol vo of the Pd
Dichlorodimethylsilane, (CHr):SiCl:. Reductive coupling of RCHO aad cll. uracil (5) involves a novcl coupling of u * ith dichlorodimethylsilane.Thus treatnrr bcnzeneselenoland (CHr)2SiCl: (cxccs:s n 927a yield as a mixture of epimcrs tl *ith Bu3SnH and (C2H5)BI follo*c'd br
ll3
Dichlorodimethylsilane r
I
,dide
-'-\.-O. ^-'--,ry
l F o
(l) tr
nv (cH3)2c=o
Tf2O,Bu2MePy
? o H cH2cl2,25' 63"/"
oTf
?tt orr
tr
(z)-1
( E ) -1
oTf
. X:;" (t)2-.€\^-. 'orr \--l HccH3
P d ( l l ) ,C u l , DMF NH(C2Hs)2, 91"/"
(E)-1
9Hs HO CHs CHe
{
- -oH '{
?tt orr
tr
.,x::"
CHs CHs ,CHs CHs
(z)-'l
rc-- . .:r.llcin a synthesisof the antiulcer
and 2 equiv. of diethylamineto givc the (E)- and (Z)- dienediynesystem 2. Both (E)tnd (Z)-2 exhibit comparablecytotoxity. (1991). :K. Nakatani. andS. Tcrashime,TetrahedronLetters,32,3405 K. Arai,K. Yamada,
y-(,,pper(I) iodide. coupling can be 13tltc alcohols.r This cyclic ditr.'- .lr,,ls.analagousto the cytotoxity trl : :i. rcsponsiblcfor the prepared ir-.:.:r,'l tlitriflates(1) can be dienol ditriflates couple luj' :: rl). The rrf the Pd catalYst,107oof Cul' :'
Dichlorodimethylsilane, (CH1)2SiCl2. Red.uctivecoupling of RCHO and allylic alcoholst A synthesis of tunicaminyluracil (5) involves a novel coupling of an aldehydewith an allylic alcohol, effected s ith dichlorodimethylsilane.Thus treatmentof the alcohol I and the aldehyde2 with benzeneselenoland (cHr)2Sicl2 (excess) in pyridine at 23' provides the product 3 n 92Vo yield as a mixture of epimers (1:1). Radical cyclization of 3 in acetonitrile *.ith Bu3SnH and (C2H5)B3 followed by siloxane hydrolysis provides the protected
ll4
Dichloro(ethylene)platinum
dimer
D
\HAC CH3O,,,./,,--y'lOMEM t l o-r.t\^,.
R3S|O\
/D
A]-'
lCt
(,
l l " "
rBSd brrso
CHz 1
2
o
C6HsseH (cH3)2sicl2 Py,23"
t(
R3S|O\A
,r7c"^u
*'r",
92"/"
CHs
1 ) B u s S n H(, C 2 H 5 ) 3 8 2) oH
AcNHz,,.
oH oH
>
o
o
indicatesthat rearrangementinvolves inre
*'rt,
I K. Ikura,I. Ryu,N. Kambe,and N. SoncJr .
CH3O"''\O : TBSO
t O OTBS
a ( 3- a : 1 )
o 'PMB
Diethylzinc-Chloroiodomethane, (C:H. I Cyclopropanation ofalkenes.t Thc ! from diethylzinc and CH2I2,and presuma reagentpreparedfrom (C2H5)2Znand (l
the usual Simmons-Smith reagent. pan rclvent. Moreover,cyclopropanationof alh t equationI).
OH derivate 4 of tunicaminyluracil (5). rA.G. Myers,D.Y. Gin,andK.L. Widdowson, Am- Soc.,f13' 9661(1991)'
Dichloro(ethylene)platinum dimer, IPt(C2Ho\Clr]2, Zeise's dimer (l)' Isomerization of silytoxycyclopropanes to allyt silyl ethers.t This Pd(lI) complex effects isomerizationof silyloxycyclopropanesto allyl silyl ethers. The last example
(t)
'-\
rc,/{ m
(/
S . E . D e n m a r ka n d J . P . E d w a r d s J. . O r e . . *
Diethylzinc - Chloroiodomethane
D R3S|O\ ]l--D
-"vo \- "J.."-'(. PMB
/
: o ores
lsa
1 , C D C | 32, 0 "
R3S|O. ,H
/-Y"o'
rK]-t (-J
\-,
2 SeC;Ht
?siR3
1,cHcl3
R3S|O-n Pr/
-czHs
11s
,,/tY'"^'
8a"/"
CzHs
) - -: :-\ ^,
cH3\Y.cH3
t\
"tr>_l\
H l osiR3
2v
OH
l . '--r,
-
n -^^/i
:
nssio)-,,'--r. H
indicatesthat rearrangementinvolves inversion of the silyloxy group.
o
rK. Ikura,I. Ryu,N. Kambe,andN. Sonoda, Am. Soc.,ll4,1520 (1992).
'-- o OTBS
4 3 - 4 1)
) F ^
cH3-y'cH3
o 'PMB
rc
Diethylzinc-Chloroiodomethane, (C2Hs)2Zn-ClCHzl (l)' Cyclopropanation of alkenes.r The Simmons-Smith reagentis generally prepared from diethylzinc and CH212,and presumablyis (iodomethyl)zinc,lCHzZnX. The related reagentprepared from (C2H5)2zn and clcHzl in the ratio 1:2 is more reactive than the usual Simmons-Smith reagent, particularly when used with dichloroethaneas solvent.Moreover,cyclopropanationof allylic alcoholscan show high diastereoselectivity (cquationI).
5
OH l H
OH (C2Hs)2Zn- ClCH2l,
(t) r
l l - r . ) 6 f r (l 1 9 9 1 ) .
t r l
ctcH2cH2ct,0'
a'Y.\,{
H
(99% de) r ' u ' 't . c ' . d i m e r ( 1 ) . hl ,tltl erhers.r This Pd(II) complex I , . i . i l r l c t h e r s .T h e l a s t e x a m P l e
1 S . E . D e n m a r ka n d J . P . E d w a r d s ,J . O r g . , 5 6 , 6 9 7 4 ( 1 9 9 1 ) .
116
(BINOL) 2,2/-Dihvdmxv-1,1/-binaphthyl
(Simmons-Smith reagent)' Diethylzinc-Methylene iodide allylic alcohols Cyclopropanation of substituted Asymmetric cyclopropanation't
1)f.41 2) Cfi/
(1)attachedtoacarbohydratederivedfromo.glucosewith(C2H5)2ZnandCH2I2(excess) canproceedwithhighoius",.o,"t""tivity.Thetriflateoftheproduct(2)whenheatedin
OBzl
(C2H5)22n,CH212 -35' - 0" >97"/o
(,?u'u oJ"'
1) t-BuLi(3 equiv.)
"roH OBzl
\/
\.,,
2 (>50:1 de)
1
r* a
OBzl 1) Tf2O,PY 2) DMF, H2O,
Ho,-,..yzcaas 4 (90%,98.4%ee)
3,3/-DiarYl BINOLs can be obtaincd * BINOL followed by Suzuki coupling rth (equationI)'
: 1) BuLi (3 equiv.) 2\ BTF2CCF2BT
(t) 4
\
of the cyclopropylto the aldehyde3 with release aqueousDMF undergoescontraction methanol4.NotethatthepresenceofthefreehydroxylgroupatC2oftheglucopyranoside of the product 2' I is essentialfor the high diastereoselectivity lA.B.Charett,B.C6t6,andJ.-F.Marcoux'Am.Soc.,rl3,8166(1991).
(BINOL)' 2,2/-Dihydroxy-1,1''binaphthyt 3-and3,3I-Substitution.Thedirectedortholithiationroutecanbeusedtoeffect3or carbamates' by use of the MOM or SEM ethers and 3,3'-functionalization of BINOL (THF, -78')' t-Buli of equiv. 2.2 is best lff.",.d with Generation of the monoanion G e n e r a t i o n o t t h e d i a n i o n i s b e s t e f f e c t e d w i t h 3 . 0 e q u i v . o f Bconfiguration' uLi(ether,25").This proceedswith retention of method when applied to lS;-sfNOf-
OMOM
4,4-Disubstitutedbutan4-olidcs'by additionof Gngna cnantioselectivity .ruxiliaryBINOL.The reactioncan prtx
(BINOL) 2,2i-Dihydroxy-1'l/-binaphthyl
tt7
i. :.- ill I
o:' ' "f substitutedallylic alcohols rr .\ '- | ('1H.)2Znand CH2l2(excess) n-.'. : ihc product(2) when heatedin
1) l-BuLi (2 equiv.)
,l qd-
710/o
6,?u'u oJ''' 'rroH
2 ( > 5 0 :1 d e )
HO-=//>.C6Hs 4 (90o/.,98.4"h ee)
of 3,3/-Diaryl BINoLs can be obtained by conversion to the dibromo derivative Pd[P(C6H5)3]a by mediated BINOL followed by Suzuki coupling with arylboronicacids (equationI).
Br 1) BuLi (3 equiv.) 2l BIF2CCF)BI
OMOM
84y"
OMOM
(t) tr ..- -r * irh rclcaseof the cyclopropylh \ . ir(rup at C2 of the glucopyranoside i ',:':,rduct2' nr 11991)
":t.'tion routecan be usedto effect 3'-- \1o\1 or SEM ethersor carbamates' -78")' q I I cquiv. of l-Buli (THF' This 25")' (ether, r: : rquir'. of BuLi 'rl(nti()n of configuration' s
c6H5B(OH)2 Pd(0)
Br
tsi(cH3)3 cH3cN
I
in high 4,4-Disubstituted butan-4-olides.2 Products of this type can be obtained the chiral (R)-1, of esters, inantioselectivityby addition of Grignard reagentsto 7-keto induction. .iuxiliary BINOL. The reactioncan proceedwith high 1,7-asymmetric
ll8
2,2tDihydroxy'1'l''binaphthyl
(BINOL)-Triphenylborate
o&o-cH. o'?o o
"11dll, ry*
+
B(OC5H5)3
(S) - 2' 95% ee
(A".ru
(R)-1
CH2\,,C to the use of 1'1/-binaphthyl is a general introduction Review.3 This review from 1974 to 1992' uu*iUu'lt'; 86""f""n"t' derivatives as chiral
*':?.it;?"it , retrahedron andv. Snieckus 1p.J.cox,w. wang, MiYano"J.t S and 2 y. Tamai.M. Akiyama'A Okamura' 3c. Rossini,L' Franzini'" #;;;;';Jp'
(l)
C6H5CH=NBz|
+
ocH3
ou un rl. l)1,)]).,
s03 (19e2)' sutuuao'i'svnthesis'
ta srnr Jienc promotedby (R)-1' generated ': fhis asymmetric Diels-Alder reaoion comof this organoaluminum
2,2/-Dihydroxv-1,1/'binaphthyl-TFimethvl".t:1tl:l;"
j.""1',"".##*'?i"J"'"hvdes'. *";r::Ixxfx::;;'::::;;[, -2- oxai form cis-4-alk oxY
CH2\,.OS .
( ocH3
)-l A)^o\ocH'
C6H5CHO
1' CH2C|2'CH3CN 0" ---;;;-
cH3o'^\y'
cis-3
,lkaloid derived from nicotinic acid' lbata' Tetrahedron I H. Suga, S. Shi, H. Fujieda, and T
(1991)' Leners' 32' 691 I
',''";:l:::li::;i:::l;I,:Hl:l"Tl"-reac,ioncanbeeff
ectedinT2-e0v.
with reactionof (R)-BINOL io'on reagentr' p'"pJuy "n'J the with Danishefsky and the eeby catalysis Thu-sreactionoi un uldinlin" (jt'ii)"^ii':' triphenylboratein
J' Ort 57 K. Hatltoriand H. Yamamoto'
t)ichloroketene. Ct Indolizidines; quinolizidines't gent'ntt (l) \-bcnzyl-2-vinylpiperidine
Dichlomketene
o
"\Yill,
r9a t: -
ll9
+
B(OC6H5)3
B-CnHq
o
(S) - 2, 95% ee ( R ) -I
l l L . .-l
z
-l-l
( ' t .-
' thc use of 1,1/-binaPhthYl r r r1 9 9 2 .
C6H5CH=NBzl
.
rr5.r(1992).
l r l Bzl
2, B5o/oee
dienepromotedby (R)-1, generatedin situ, providesthe adduct2 in 85o/oee (equationI). This asymmetric Diels-Alder reaction can be used to prepare (-)-anabasine (5), an
r(-'
L.C-o
o
ocH3
:
cH3cN 1, cH2cl2, 0"
1 , 4 4M . S . c{zct2, -78"
cuHu4f-
:tnr. Comm., 687 (1992). , 503 (1992).
!m. F- -. - rrf this organoaluminumcomto ;\, 'JJition with arYl aldehYdes lt:
(l)
cH2Y'oSi(CHs)s /
1
o
71v"
Bzl/N
77.7"/"
poocH3 -\ {:C
)1 oA"uru
'".a) trans - 3
. r 2 .6 e lI ( 1 9 9 1 ) .
5, tts = -79.2"
:lkaloid derived from nicotinic acid. J. Org., 57,3264(1992). K. Hatltoriand H. Yamamoto,
: Ir\ '- i!ri()ncan be cffectedin72-90Vo ;p.--.1 hv reactionof (R)-BINOL with | , : ,:r .tldimine and the Danishefsky
Dichloroketene. Indolizidines; quinolizidines.r Generation of dichloroketene in the presence of \-benzyl-2-vinylpiperidine (l) generatesan intermediate(a) that cyclizes on warming
l2O
Dichlomketene
to the 10-memberedlactam 2. A silnilar reactionwith the N-benzyl-2-vinylpyrrolidine (3) provides the 9-memberedlactam 4' 2,6-Dichloropyridine N-oxide,
CtA
X
o
i'tl
(^l^"t,
25"
cl2c=c=o
Oxidation.l In the presence of ruth RuTMPOz, and a trace of HBr or HCl. 1 secondary alcohols at 25" in high I ield Adamantaneis oxidized mainly to the l-hrt (15-25Vo) and adamantanone-2(7-21 '1zn
\....,.N-.._..C6H5 1
,"--rAcH" t
l
cl
60'
\.--rya"cctt
CI
Bzl I
oCH.
a
t "
z--zl\CH, ( l \--N..,-CuHu
ct2c=c=o
cl cl
25" 64"/"
..) t
l
RuTPP(CO).H& benzene.20'
+
1
*1
ft""u cyclization and Exposureof either 2 or 4 to 12or c6H5SeBr triggers a transannular quinolizidines(5) from 2 or dcbenzylationkr providc iodo- or phcnylseleno-substituted the analosousindolizidines from 4.
OH .\
t
2
-
12,50" 857"
I E . D . E d s t r o m ,A m . S o c . ,f 1 3 ' 6 6 9 0 ( 1 9 9 1 ) .
cl
l
Il. Ohtake,T. Higuchi, and M. Hirobe. .{a .S
CI
ldisilou I J- Dichloro-1,1,3,3-tetraisopropy t(cH:):cHlzSi(cl)osi(cDcH(cH.):l:I lt Regio- and stereoselectivedihfiranl I exclusivelywith the isolatedcvcloallc \\'hereasdirect osmylationof 2 providcs
1,3-Dichloro-1,1J"3-tetraisopmpyldisiloxane
\ -benzyl-2-vinYlPYrrolidine
,-\
/\i -l-l ClN-o*id", 2,6-Dichloropyridine
l2l
l-Cl
o
(1) Oxidation.r ln the presence of ruthenium porphyrin oxo complexes' such as RuTMPOz, and a trace of HBr or HCl, pyridine N-oxide I can oxidize alkanes to secondary alcohols at 25' in high yield. The reactive intermediate is not known. Adamantaneis oxidized mainly to the l-hydroxy derivativc (68Vo);adamantane-1,3-diol (l-2%) are minor products. (15-25Vo')and adamantanone-2
cl cl
CHa
I '
cl cl
.^> l
l
R u T P P ( C O )H, B r benzene,20'
+
1
'x"* (,
94o/o
ri\
",A*A",
o
*1
ft""u cyclizationand t : - - :. .r transannular u--
C6H5COCH3
o
OH
.:rd quinolizidines(5) from 2 or
.\
t
l
a\ t
l
I
H
.-\
l ^ l I z9l
N -.-4.,
:H. Ohtake, T. Higuchi,andM. Hirobe,Am.Soc.,114,10660(1992).
l " ' o 5
I J-Dichloro-1,1,3,3-tetraisopropyldisiloxane(TIPDS-Cl2), 1' [ (CH: ):CH]zSi(CI)OS(CI)CH(CH:)zlz $6,r2s 126). Regio- and stereoselective dihydroxylation.t This reagent adds to the oxepin ! exclusively with the isolated cycloalkene double bond to provide 3 (84Vo yield) Whereas direct osmylation of 2 provides a mixture of diols in low yield, osmyla-
(Diethylamino) (phenyl)oxosulfonium
methylide
CoHs
1
.<;rCHz
1 ) N B S .C O r 2) (CHgO)rP
coHu:A^ t i
86.3%
f-BocN-_,,\O
84V"
2
--CHz
CoHs
""'lA?
1, NaH, DMSO C6Fl5 18- 25'
l-Bo
t-eocll--r.\O Hnn
R = CHs R = CoHs
82/" 96o/o
I usually gives a single product {. tcl dimethyloxosulfonium methylide results l-3:1. Use of diazomethanealso result arc converted into the desired amino rr dcprotectionof the amino grouP' I R.M. williamsandG.J. Fegley, An. -Sa. I tionof3resultsinalmostcxclusiveattackoftheterminaldoublebond.Whenthe presenceof (S,S)-N,N/-dineohexyl-2,2/-bipyrrolidine osmylation is carried out in the but (867o)is(2S)-5' Howevt:'l*:t-: ieaction' (4) (16,i50-151), the rnu3o'p'oOutt yield(1lVo)' (2S)-5 as the major product'but in lower catalyzedby(R,R)-a' ut'o f'ouidtt by and the regioselectivityare controlled These resultsshow that th; diastereosclcctivity group' the sterically demandingTIPDS
705 (1992)' rO. SatoandM. Hirama,Synlett'
Diisobutylaluminum hYdride. a-Trimethylsiloxy aldehydes'i Ttrc r icld by addition of cyanotrimethvlsilanc rcducedby DIBAH (1.5-2 equiv.)in hcu hv dilutesolutionsof 1-1.6N HISO. at l5 can be hydrolyzed by dilute HCI to a-ht
(cH3bsicN
CoHs -CN X -os
?
cuHrAcH.
cH(
I (Diethylamino)(phenyl)oxosulfonium
methylide'
5' 23r' (1),3' 10s-,106: iGr"ir* (c6Hs)l*so(cH1)BF; o,;ia''t Thesecyclopropyl aminoacidscanbe I-Aminocyclop'ooo'-'--iniuoty'ti'' the a, B-dehydro with ylide
yield by rcactionof this obtainedin high chemicuiun.topti"ui lactones(3) preparedtin'n 1SS,On;-4-t-butoxycarbonyl-5'6-diphenyl-2'3'5'6{etrahydroderived from The reaction of 3 with the ylide 4H-1.,4-oxazin-2-one(2, 1+,SS-SO)'
+
1)NH4C| 2 ) 1 . 3N H C I
C6H5r_-Qg(r
63"/"
cH/\orc 2
Diisobutylaluminum
,-rr\..,_r, P-"''o -o ,si-i-Pr \-Pr
CoHs CoHs
cuHrr-J-^
I
1 ) N B S ,C C t 4 2) (cH30)3P
Y
2
I osoo,(s,s)- q
".t'yA?
cuHu:A^ I Y
'"'-
I
| C H-' C |-, ,- 7 8 o Y
,"'in,j'' pi-iPr -o \i_p,
x .-"rtnal double bond' When the 5, r. r Jincohexyl-2,2t-bipynolidine but |.5 il,,scvcr. thc samereaction, yield(7lVo)' ,Juct. lower in but rr :^. -- Ltosclcctivityare controlledby
CoHs 1 , N a H ,D M S O c u H r : - \ o 1 8- 2 5 "
I
t-eocru:rz\O
I
r-eocru-.*,.\o
1 ) L i ,N H 3 H3N*-.--COO2)H3O-_
H, H
4 1 : 0 1:0
82% 960/o
I usually gives a single product 4, rcgardless of R. Cyclopropanationof 3 with dimethyloxosulfoniummcthylide results in two diastereomericproducts in the ratio l-3:1. Use of diazomcthanealso resultsin a diastereomeric mixture. The products arc converted into the desired amino acids by reduction with Li in NH.r followed by dcprotectionof the amino group. : R.M. Williamsand G.J. Fegley,Am. Soc.,ll3, 8796(lggt). Diisobutylaluminum hydride. a-Trimethylsiloxy aldehydes.t The a-trimethylsiloxy nitriles I, obtained in high r icld by addition of cyanotrimethylsilaneto ketoncs catalyzedby Znl2 (4,542-543), are :cducedby DIBAH (1.5-2 equiv.) in hexaneat 0" to imines (a), which can be hydrolyzed rv dilutesolutionsof 1-1.6N H2SOaat 15" to a-silyloxy aldehydes (2). Thesealdehydes ;an be hydrolyzed by dilute HCI to a-hydroxy aldehydes(3).
(cH3hsicN coHs.-.cN Ri""l,*, n ? :.rr^cH.----------.------* cH/\osi1cH.).-------------* 1
: - . . , ).
:.
-.'l.
T'-.- lclopropyl amino acidscan be tr, " I :his vlidewith the a, B-dehydro t' r
r.o-diphenyl-2,3,5,6-tetrahydro: -l rvith the Ylide derived from
R
"K"
R 3
R=CHg R = CoHs
:St -5(majorProduct)
82 - 96Vo
(H3CO)2P.-:O
CoHs
qAo/^
1) NAH 2) ROH
t-eocN\_,.\O :
86.3ol.
t-BocNr_.\O
=CHz I
123
hydride
1) NH4CI
2 ) 1 . 3N H C r 63v"
CoHs.-.OSi(CH3)3
cH/\cHo 2
HCt,H2O
CoHs._-oH
cu/\cno 3
(lsrR-'sJ 124
DiisobutYlaluminumhydride
By appropriatechoice of i-Bu2AlH of terrninal eno1u11.' Regioselectivereduction regioselectivity to the primary "un be reducedwith marked or i-Bu3Al, terminal "po*lO"t i-Bu2AlH mainly ePoxides ate ted"ted by or the secondary alcohot'"i"tufi-J"uttto to the primary alcohol' use of i-Bu3Al favors reduction to a secondary alcohol' **;; epoxides' Phenyl-substituted in the cure silyl-substituted This regioselectivity is ,.;;; Reduction of theseepoxides mainly to primary-alcohols' epoxides are reducedby i-Bu3Al in THF' best effected with LiAIH+ to secondary alcohols is
nYcHs
'
H- P\ R>-
RCH2.H2oH
+
OH
R = (C6Hs)3Si
fl = C6H5
i-Bu2AlH
95"/"
l
o
..ng n-C16H2'1N-oTt
i-Bu3Al
93"/"
iBu2AlH
90o/o
i-Bu3Al
90o/"
LiAlH4
95"/"
i-Bu3Al
90o/o
1 0 0 :1 0:100
?-CtoHrl l
0: 100
:\"^ors o'
18:82
base
l + ..."tD-OMen ' cHa CzHt
2 DIBAL -78" 85"k
o
O H ? ? cH."\'^---"t*i't'", 1
q H 9
(CH3)4N- HB (OAc)3
A
HOAc
cn/-/)1"t;i,
9O"/o
l
l
.
2. >95"/"de
O H 9 H 9 I ' A
CH{/"*"t';'", 3, 88"/. cle
n-C,olf
ss'/"
Reductive cleavage of hbutyUinahy ion' but thc eenerallycleavedby fluoride to )ield th hours 1-2 in CHrClz at23" in
97'.3
oll l
-
65:35
sulfoxides(1)' preparedby of 1'3-diols3 tT.(*) q: 6-diketo by Asymmetric synthesis arereduced p-toluenesulfinate' with (S)-menthyl of thedianionni BlAit"ton"' reaction
l cH.'/\'
I DIBAH cnzCtz,o..p-( s7%
>98o/oae
R = n-CeHrz
o
(2s)-hydroxl keto DIBAH (2 equiv') to the to the 'rt converted be can de). The products (Evans n ammonium triancetoxyborohydride of 2'3-epry Regioselectivereduction pure 3-all enantiomerically "on r"r*d into -15 - l at CH2CI2 in equiv.) (3 oi"O"
Raney Ni
oH 9H l . cH.McH. (R'R) - 4
andN' Ogunr'Srd I M. Hayashi. T. Yoshiga' : t,t. gisct,,Z.-R.Liu, and M' Singh'J t)rt ' La ti. sorruaieandN. Ghiatou'Tetrahedma 'J. M. Chong,ibid', 33, 33 (1992)' t i.'1. cor"ylnd G' B' Jones'J' org" 37' ltt ( I S,2R,4S,5R)-2,5-Diisopropylcyclobcr PreParation.r'
(cH3)2cH\, HO
(D Ior ct Chiral titanium catalYst ansa-bis{tr chiral titanium catalyst,an of I T ith reaction of the dimesylate
(1) 125 (1s,2R,4s,5R)-2,5-Diisopmpylcyclohexane-l'4-diol
a:-
^llopriate choiceof i-BuzAlH ::rioselectivitY to the PrimarY -rJuced bY i-Bu2AlH mainlY
0:
.-.li()nto the PrimarYalcohol' .: :norides. PhenYl-substituted . Rcductionof theseePoxides
Ir lc.
I
2 with high diastereoselectivity (>95Eo DIBAH (2 equiv.) to the (2S)-hydroxy ketone anti-l'3-diol4 by reduction with tetramethylde). The products can be converied to the reagent) followed by desulfurization' ammonium triancetoxyborohydride (Evans These epoxy alcohols can be Regioselective reduction of 2,3'epory alcohols'a by reduction of their tosylates with converted into enantiomericalli pure 2-alkanols -15 - 25"' DIBAH (3 equiv.) in CHzClz at
Illl
I
9H
DIBAH
CHr +
..nQ
RCH2CH2OH
n-C16H21,.MoTs
CH
-/.\ "illBilt, n-crcH21,"-ycH3 + n-C'roHx' ) I s7"^ 6t ,, : 3 CHs >98o/oee
>98% ee
OH
100:1 0: 100
t-"ttlt ^\.,^ors o '
0: 100 65:35
18:82 bY : \fto sulfoxides(1), PrePared bY reduced are :,,lucncsulfinate,
=-
O H ? ? cHa*tti't'* 1 (CH3)4N.HB (OAc)3 HOAC
l:-
.-n-c,0H2.,^-] n-c1oHz1"'\Y,,ltt
sso/'
6H
94:6
cHs
ethers are ethers's /-Butyldimethylsilyl Reiluctive cleavage of t-butytdimethylsilyl DIBAH by cleaved reductively Uut they can also be generallycleaved by fluoride lon' yield' in84-917o alcohols to yield the corresponding in CHzClz at23'in1-2 hours
97:3
h\
---^: +
9O"/"
I M. Hayashi, T. Yoshiga'and N Oguni'Synlat'-41,9 .(1991)' ';;, 57' 1618.(1ee2)' t;.; Z.-R.Liu, andM' Singh'J' org'' 1605(1992)' 33' r G. Solladi6andN' Ghiatou'Tet'ih"d'onLetters' (1992)' t J.M. Chong,ibid', 33, 33 J' Org'' 37' 1028(1992)' ti.l. co..y1nd G B' Jones' (1)' ( I S,2R,4S,5R)-2,5-Diisopropylcyclohexane'l'4-diol , PreParation.r
(CH3)2CH6...OH
t
l
Ho"'\^cH(cH3)2 OH 9H I ' cn3,McH3 ( R ' R )- 4
of alkenes'z The enantioselec.tivekomerization Chiral titaniun catallst Q) for the dichloride (2)' is preparedby conchiral titanium catalyst,t"l"'-OOtt"denyl)titanium is that product form a of r wiih indenytlithium to rcaction of the dimesyrut.
DimethYlsulfoxonium
methYlide
cH30
o
CH3O
Hs o.(
1
cH3o
v e r t e d i n t o 2 b y r e a c t i o n w i t h B u L i a n d t h e n w i t h T i C l l i n Tfrom H F athe t - . isopropyl 7 8 . 6 5 . . Agroup' single indenyl groupsare placedaway product is formed in which the the isomerization of the LiAiH; (4 equiv ) can catalyze This reagent, when rcduced by in 767o ee' product only 1i1 to 1S;-l as the meso-trans-4-butyf-f-uinyf"ytiohexane
NHCOCH3 (! 4)
(""
a\ t YI
1, L|AIH4 mesitylene,23'
l
c(cH3)3 3
(cHt ll
100"/.
-
I
c(cH3)3 (s)-4, 76ol"
l-"tr--.
I (A , ll . I
l
"t"t.,] (R)-4
r M . G . B a n w e l l ,J . N . L a m b e r t ,M . F \ l e c l r t
(teez).
Dimethyl sulfoxide-Triphosgen€' Triphosgene(CCIIO)2C:O. is a rcad Ofidation.3 This combination(l t rs rmall- and large-scaleSwern oxidatttns
H H
crHr-+cH2oH 1Z. Chenand R.L. Halterman,Synleu'142(1990)' 2ldem,Am. Soc.,114,2216(1992)'
DimethYlsulfoxonium methYlide' C y c l o p r o p a n a t i o n ' , T h e k e y s t e p i n a b i o m i m e t i c s y n t h e s iin s oseveral f ( + ) . c osteps l c h i cffom ine(4) reactionof the tricyclic l, prepared is a regio_and stereoselective 5-bromo-2-methoxyphenol,withdimethylsulfoxoniummethylidetogiveasingleproduct ( 2 ) i n l 5 a o y i e t d . W h e n t r e a t e d w i t h t r i f l u o r o a c e t i c a c i d a tproduct 2 5 " , t h i sisp rconverted o d u c t f e a into rlanges O-methyl ether 3' This in 897o yield to the a-tropolone (+)-colchicine (4) in four known steps'
/-*'r*,
H. EckertandB' Forster,Angew'Chen It .tldrichimicaActa, 21, 47 (1988)' C. Palomo,F. P. Cossio,J.M Ontoria'arrJ
l2-Diphenyl-1,2-ethanediamine. lG l: Asymmetric sYnthesisof l)'dbJt rcactionof (R,R)-l with a l,2-dione to
1,2-Diphenyl- 1,2-ethanediamine
127
H2CSO(CH3)2 D M S O ,1 8 '
ltt
*, c
I
I'HF at -78 -. 65". A single :'.\av from the isoProPYlgrouP' :.rlrzcthe isomerizationof the
cH3o
,'nl)' product in 76Voee'
NHCOCH3
cH30
(1 4)
t.\
r M . G . B a n w e l l ,J . N . L a m b e r t ,M . F . M a c k a y , a n d R . J . G r e e n w o o dJ, . C . S . C h e m .C o m m . , 9 7 4
tl
(tee2).
n: 72' ..
I c(cHs)s (R)-4
Dimethyl sulfoxide -Triphosgene. (CClrO)2C:O, is a readilyavailablersubstitutefor phosgene.2 Triphosgene Oxidation.3 This combination(1) is comparableto DMSO-oxalyl chloride for both small- and larqe-scaleSwern oxidations.
H H
czHs#cH2oH
1, N(C2H5)3 -78-0'
l l /FN. O' PMP
(4) n '- -' . .\nthcsisof (a)-colchicine l. prcparedin severalstepsfrom 1. n:.-- 'le th\ lidc to give a singleproduct :rr. ,-rJ et l5', this product rearranges b(' .r lhis product is converted into
H H
c2Hs+_j-cHo l l /FN, OPMP
ll. Eckertand B. Forster,Angew.Chem.Int. Ed., 26,894 (1987). - .lldrichimicaActa, 21, 47 (1988). (1991). J. Org-,56,5948 F.P.Cossio, J.M. Ontoria, andJ.M. Odriozola, C. Palomo,
lJ-Diphenyl-1,2-ethanediamine, 16, 153-158. Asymmetric synthesis of 1,2-diamines.t This synthesis involves as the first step :!'actionof (R,R)-l with a 1,2-dioneto form a dihydropyrazine(1,2-diimine,a), which
lza
1,2-Diphenyl-1,2-ethanediamine
can be reducedto a piperazine2 by various hydride reagents.The highest diastereoselectivity obtainswith NaBH:CN and an acid catalyst,pyridinium p-toluenesulfonate,in CH3OH at -30', which affords the diaxial product (2). Reductionof the C-N bonds can be effectedby acetylationand cleavagewith lithium/NHr. Somewhatbetter results can be obtained by conversion of 2 to the biscarbamate3 by reaction with isobutyl chloroformateand cleavagewith LilNH3. This 1,2-diaminederivative is cleaved to the
-;
cH3"\"'\oi'--t" (E)-2
I
(S, S)-1,N(C2Hs)3 | hexane I C6H5CH3,
bishydrobromidesalt 4 in 68% yield and 99Vo ee.
I
9BR'* I
c6Hs\ NH,
faoHsn-ru1-cHsl | | | \ll CH.l LauHru"
+ C H 3 C O C O C H 3+ l
|
CoHu."'\*r, ( R , R )1 -
PPTS NaBH3CN, cH3oH,20' _ SSYo
1)CICOO-l-Bu 2)Li/NH3
o\ | \
a
H C6H51.-N--7rCHs | I C6Hur..'\;r1l",rata H 2
NHCOO-l-Bu I
cHs\-AcHs : NHCOO-r-Bu (R,R)- 3
1)-2oo | CH"^
ll-cH,
2) H2o _ 650/o
H{
"'
ery
(E,z)_3 H
coHsr..-N._acHs + 15:1
HBr,AoOH 80"
l
l t'-t'-at. CoHs"" H
of allyl alcohol itself, but rearrangemcnrof r: proceedswith high enantioselectivin..
Enantioselective Darzens reaction.-' Rr hvdeswhen promotedby (R,R)-l resultsin ar can be debrominatedby Bu3SnH/AIBN or err
HBr.H2N
tttfcH. t : HBr.H2N (R,R)- 4, 99o/"ee
Asymmetric lreland-Claisen rearrangement.2 The chiral diazaborolidine S,S-1 rearrangementof allylic esters.This can effect highly enantio- and diastereoselective reagenthas previously been used to convert (E)-crotyl propionate(2) into the (E)- or (Z)-enolate(3) dependingon the solvent and the base(16,155).Thus 2 is convertedinto (E,E)-3 by reactionwith I and ethyldiisopropylaminein CH2CI2in CH2C|2at -78". On standingat -20" for severaldays it rearrangesto the threo-acid4 in >97% ee. Reaction of 2 with I and triethylamine in toluene-hexane results in (E,Z)-3, which rearranges at -20' to the erythro-acid 4 tn >967o ee. The by-product of rearrangement is the bis-sulfonimide precursor of 1. Lower enantioselectivityobtains in the case of esters
d
o CnHqCHO +
N'Q
ll
BrcH2
oc(cH3)3
KOC(CH3)3 HOC(CH3)s
CoHs
OC(CHJ3 3, oe-140o
rith base.Theseepoxidesare easill con\cno irc easily reducedto B-amino a-hvdrorr cs
1,2-Diphenyl-1,2-ethanediamine
-l'he highest diastereose:..," 'rum in t\- : P-toluenesulfonate. honds C-N I R-.:rcrionof the rr \ ll,. Somewhatbetterresults r:'. .r hr reaction with isobutYl n: -. .icrivativeis cleavedto the
(S,S)-1,1-Pr2NC2Hr, ?8R.2 cH^cr,.-78o , 6-\.-cHs
o -
t
l
o'A\"-cH3
cH.,.\.,.
%CHs
(E)-2
(E, E)-3
I( S ,S ) - 1 ,N ( c 2 H 5 ) 3 |
I
r,-ro" I ,rr,ol'u"'"
hexane C6H5CH3,
i
l. Hs
3.Hs
OBRr*
t
*Y"'1
-
?- "" )l -cH,
ru^cH'l a
129
1) -20o 2) H2O > 65o/o
I
o
o
,o\.""t.
,o\c"
cHzx-/',rcHs
cHzx2.,rcHs
erythto-4 (>960/"ee)
threo_ (>g7o/oeel
(E,Z)-3
H C6Hs1.N-"eCHs
t
\*'-"t. CoHs*'' H
6r
of allyl alcohol itself, but rearrangementof various allylic propionateand butyrateesters proceedswith high enantioselectivity. Enantioselective Darzens reaction.s Reaction of l-butyl bromoacetatewith aldehydcswhen promotedby (R,R)-l resultsin an anti-adduct(2) in >91Va ee. The product can be debrominatedby Bu3SnH/AIBN or convertedto a glycidic ester(3) by treatment
H B r . H 2t N
e'
l
-
cH.-=AcH. : (R,R) - 4' 99o/oee
(RR , )-1,
o
HBr.H2N C6H5CHO+
Jl-oc1cH.;.
BrcH2/
N(CcH<)r. -78o
ff
O
9H :
cuHrl-y^oc(cH3)3 Br 2 (98o/oee)
l - ;hiral diazaborolidineS,S-1 l : - , . i - n r c n t o f a l l y l i c e s t e r sT' h i s xi '" rpionate(2) into the (E)- or : 16 . 97Vo ee' Reaction c\- '. rn (E.Z)-3, which rearranges is the lr,:: 'Juct of rearrangement trr '. ',htainsin the case of esters
N . O
KOC(CH3)3 HOC(CHds
82/"
f" ll cuHu-^)i^oc(cH3)3 75"/" :
NaN3
coHs
oc(cH3)3 3, ct6-140o
OH 4
with base.These epoxidesare easily convertedto B-azido a-hydroxy esters(4), which are easily reduced to B-amino a-hydroxy esters.
130
(S)-(+)- or tRx - r
(&R)-1,2-Diphenylethane-1,2-diol,dimethylether
Asymmetric synthesis of B-amino acid esters.4 The chiral diazaborolidine I (16,155) also effects diastereo-and enantioselectivereactions of (S)-r-butyl thioproponoate (2) with N-benzyl or N-allyl aldimines 3 to form B-amino acid esters 4, precursors to chiral trans-B-lactams (5) in 9O-99Vo ee.
"r.? lf-*
r--Y -'-O'-O
+ rY'\ \--\,2 I
LJ 2,R=c-CoHrr
C6H5CH=NCH2CH=CH2 3
*
(s,s)-1, N(c2Hs)s
o tl
C6H5CH3, hexane, -78"
cH.cHrAsc(cH3)3
CH2=61611'N O t t l ceHs/-lAsc(cH3)3 = CHs
r-BuMgX
R'N4 ,
O
L_l'cn, c"(,
4 (antilsyn = >99:1)
5 , 9 0 %e e
I M. Shindo, K. Koga, and K. Tomioka. .{r I M. H. Nantz, D. A. Lee, D. M. Bender, and A. H. Roohi, J. Org., 57, 6653 (1992)' 28.J. Corey and D.-H. I e,e,Am. Sac., ll3, 4026 (1991). 38.J. Corey and S. Choi, TetrahedronLetters,32,2857 (1991). a E. J. Corev. C. P. Decicco, and R. C. Newbold, TetrahedronLeuers, 32, 528'7 (1'991)
(&R)-1,2-Diphenylethane-1,2.dio|, dimethyl ether (1)
c6H: CH3O
,cuHu
(S)-(+)- or (R)-(-)-Diphenyl(l-merbla E nantios elective cyanomethy latiu-l action of BTCHzCN with ZnlCu. adds t cquiv.) to give B-hydroxy nitriles in t{'. the optical yield is markedly decreascd 7U7o).Therefore, I servesboth as a licz
qi
( R , R )- 1 ( 1 6 , 1 5 8 - 1 5 s ) .
i
OCH3
CHr
c6HscHo Asymmetric aromatic allqlation; binaphthyls.t The reaction of l-naphthyllithium with a naphthylimine (2) catalyzed by I provides 3, which is hydrolyzed (H2O' CFTCOOH, NazSO+),with recovery of 1, to the aldehyde 4 in 85% ee. The stereochemistry can be improved by use of a bulky R group in 2.
+
BTZnCHfN
K. Soai. Y. Hirose. and S. Sakata.Tetralx$
(S)-(+)- or (R)-(-)-Diphenyl(1-methyl-2-pyrrolidinyl)methanol (1)
c ,.rrrl diazaborolidineI o.. ,,t (S)-t-butyl thiopron: j-.tmino acid esters 4,
cH.?
liu't
r)r.4. r)v'\/ :-a
l3t
(R,R)-1 c6H5cH3,-45'
Li 2,R=c-Q.11