General and Synthetic Methods Volume 12
A Specialist Periodical Report
General and Synthetic Methods Volume 12
A Review of the Literature Published in 1987 Senior Reporter G. Pattenden, Department of Chemistry, University of Nottingham Reporters
K. Cooper, Pfizer Central Research, Sandwich, D. J. Coveney, University of Nottingham T. Iu. Dank, University of Warwick C. W. Ellwood, University of Nottingha T. Gallagher, University of Bath D. C. Harrowen, University of Notting D. W, Knight, University of Nottingham T. V. Lee, University of Bristol K. E. 8. Parks, Roche Products Limited, Welwyn Garden City, Herts. G. M. Robertson, Glaxo Group Research, Ware, Herts. N. Simpkins, Queen Mary College, University of London S. E. Thomas, University of Warwick C. J. Urch, lCl Agrochemicals, Bracknell, Berks. P. J. Whittle, Pfizer Central Research, Sandwich, Kent
SOCIETYOF HEMISTRY
ISBN 0-85 186-934-3 ISSN 0141-2140 Copyright 0 1990 The Royal Society of Chemistry All Rights Reserved No part of this book may be reproduced or transmitted in any form or by any means-graphic, electronic, including photocopying, recording, taping, or information storage and retrieval systems-without written permission from The Royal Society of Chemistry Published by The Royal Society of Chemistry, Thomas Graham House, The Science Park, Cambridge CB4 4WF Printed and bound in Great Britain by Bookcraft (Bath) Ltd
Introduction T h i s r e p o r t c o v e r s t h e p e r i o d J a n u a r y t o December 1987.
The b r o a d
a i m s of o u r s u r v e y of ' G e n e r a l and S y n t h e t i c Methods' remain a s s e t o u t i n l a s t y e a r ' s Report.
W e welcome a number o f new c o n t r i b u t o r s
t o Volume 1 2 which h a s an i d e n t i c a l l a y o u t t o t h a t f o l l o w e d i n Volume 11. As always, comments and s u g g e s t i o n s from o u r r e a d e r s h i p r e g a r d i n g t h e coverage and f o r m a t of t h i s R e p o r t a r e v e r y h e l p f u l . March 1 9 9 0
G. P a t t e n d e n
Contents
Chapter 1
Saturated and Unsaturated Hydrocarbons
1
By N. Simpkins 1
2 3 4 5 6 7
Chapter 2
1
2
3 4
Saturated Hydrocarbons Olefinic Hydrocarbons
1 1
Conjugated l13-Dienes and Non-conjugated Dienes Allenes
19
Alkynes Enynes and Dlynes Polyenes References
25 27 32 32
Aldehydes and Ketones By K.E.B. Parkes
37
Synthesis of Aldehydes and Ketones Oxidative Methods Reductive Methods Methods Involving Umpolung
37 37 40 44
Other Methods Cyclic Methods Synthesis of Functionalised Aldehydes and Ketones Unsaturated Aldehydes and Ketones a-Substituted Aldehydes and Ketones
45 49
Dicarbonyl Compounds Protection and Deprotection of Aldehydes and Ketones Reactions of Aldehydes and Ketones Aldol and Other Reactions of Enolates Conjugate Addition Reactions References
14
58 58 63 68 72 75 75 78 84
...
Contents
Vlll
Chapter 3
1
Carboxylic Acids and Derivatives By D . W K n i g h t
91
Carboxylic Acids
91 91
General Synthesis Anhydrides Diacids Diacid Half Esters Hydroxy-acids Keto-acids Unsaturated Acids Aromatic Acids and Esters Arylacetic Acids and Esters 2
3
4
5
Carboxylic Acid Protection Carboxylic Acid esters Esterification General Synthesis of Esters, Thioesters, Dithioesters, and Selenoesters Diesters Hydroxy-esters Keto-esters Unsaturated Esters Lactones Butyrolactones a-Methylenebutyrolactones Butenolides Phthalides Tetronic Acids Valerolactones Macrolides Carboxylic Acid Amides Amide Bond Formation React ions Amino-acids a-Amino-acids f3-Amino-acids Y and Other Amino-acids Asymmetric Hydrogenation of Unsaturated Amino-acid Derivatives Amino-acid Protection References
93 93 93 95 98 98 101 101 102 104 104
105 112 115 124 132 142 142 151 153 155 157 159 162 165 165 167 170 170 177 179 181 182 186
Contents
ix
Chapter 4 1
2
3 4
5
Chapter 5
1
Alcohols, Halogeno Compounds, and Ethers By C.J. Urch Alcohols Preparation by Addition to Alkenes
Preparation by Reduction of Carbonyl Compounds Preparation by Nucleophilic Alkylation Preparation by Opening of Epoxides Miscellaneous Methods Protection and Deprotection Oxidation Halogeno-compounds Preparation from Alcohols Preparation from Alkenes Interhalide Conversions Miscellaneous Preparation of a-Halo Carbonyl Compounds Preparation of Vinyl Halides Preparation of Other Unsaturated Halides Ethers Thiols Thioethers References
203 203 203 205 208 218 219 224 226 228 228 229 23 1 231 232 233 234 235 236 236 241
Amines, Nitriles, and other Nitogencontaining Functional Groups By G . M . Robertson
249
Amines Acyclic Amines Aromatic Amines Allylic, Homoallyic and Allenic Amines Cyclic Amines Protecting Groups Enamines Aminoalcohols Azo Compounds Nitriles and Isocyanides
249 249 256 259 259 266 266 270 270 273
Contents
X
6 7 8 9 10
11 12 13 14 15
Nitro- and Nitroso-compounds, and Nitramines Hydrazines and Hydrazides Hydroxylamines Imines Amidines Oximes Carbodimides Azides and Diazonium Compounds Isocyanates and Isothiocyanates Nitrones References
276 278 278 278 281 281 285 285 289 289 289
Chapter 6
Organometallics in Synthesis By T . N . Danks, S.E. Thomas, and T G a l l a g h e r
293
PART I:
The Transition Elements By T.N. Danks and S . E . Thomas
293
1
Introduction
2 3
Reduction Oxidation Isomerisations and Rearrangments Carbon-carbon Bond-forming Reactions v i a Organometallic Electrophiles
4 5
v i a Organometallic Nucleophiles v i a Coupling and Cycloaddition React ions
v i a Carbonylation Reactions 6
Miscellaneous Reactions References
PART 11:
1
293 293 295 297 297 297 305 315 324 330 330
Main Group Elements By T . G a l l a g h e r
333
Group I General Aspects
333 333
xi
Contents
4
5
6
Chapter 7
1 2 3
4
5 6
Selective Lithiations Di and Trianions, Alkenyl, and Alkynyl Anions Sulphur Stabilized Anions Group I1 Magnesium Zinc and Mercury Group I11 Boron Aluminium and Thallium Group IV Silicon - General Aspects Ally1 and Vinyl Silanes Other Silicone-containing Reagents Germanium, Tin, and Lead Group V Phosphorus Arsenic, Antimony, and Bismuth Group VI Sulphur Selenium and Tellurium References
335
Saturated Carbocyclic Ring Synthesis BY T.V. Lee
407
Three-membered Rings Four-membered Rings Five-membered Rings Generated Methods Fused Five-memered Rings Six-membered Rings Diels-Alder Reactions Other Syntheses of Six-membered Rings Severn-membered, Medium, and Large Rings Ring Expansion Methods References
407 407 407 407 412 412 412
339 344 354 354 354 356 356 362 365 365 365 369 374 379 379 383 385 385 390 394
415 415 417 420
xii
Conten ts
Chapter 8
Saturated Heterocyclic Ring Synthesis Whittle
423
By K. Cooper and P.J. 1
Oxygen-containing Heterocycles 423 Three-membered Rings 423 Four-membered Rings 423 Five-membered Rings Tetrahydrofurans 4 2 5 Dihydrofurans and Benzofurans 431 Five-membered Rings With More 431 than One Oxygen Six-membered Rings - Tetrahydropyrans 4 3 4 Dihydropyrans 434 Six-membered Rings With More 436 than One Oxygen Medium- and Large-Ring Ethers 439 Sulphur-containing Heterocycles 439 Heterocycles containing More than 442 One Heteroatom Nitrogen- and Oxygen-containing Rings 4 4 2 Five-membered Rings 442 Six-membered Rings 445 Nitrogen- and Sulphur, and Sulphurand Oxygen-containing Rings 445 Nitrogen-containing Heterocycles 449 Three- and Four-membered Rings 449 451 Five-membered Rings Six-membered Rings 463 Six-membered Rings containing Two Nitrogens 471 Seven- and Eight-membered Rings 474 p-Lactams, Penicillins, Cephalosporins, and Related Compounds 474 References 481
-
2
3
4
...
Contents
Xlll
Chapter 9
Highlights in Total Synthesis of Natural Products By C.W. Ellwood, D . C . Harrowven, and
486
G. Pattenden 1 2 3 4 5 6
Terpenes Alkaloids Spiroacetals Macrolides Ionophores Other Natural Products References
486 490 501 504 509 509 515
Reviews on General and Synthetic Methods 518 Compiled by K. Carr, D.J. Coveney, and G Pattenden Fluoroorganic Compounds Carbonyl Compounds Peptides Organometallics I
General Main Group Elements 5
6 7 8 9 10 11 12 13 14 15 16
Transition Elements Cycloaddition and other Pericycle
518 518 518 518 518 519 519
Processes Macrocycles
520 520
Heterocycles Natural Products Asymmetric and Selective Synthesis
521 521 522
Sugars Photochemistry, Electrochemistry, and Radicals Reagents Oxidation and Reduction Resolution Methods General Miscellaneous
522
Author Index
527
522 523 523 524 524 524
1 Saturated and Unsaturated Hydrocarbons BY N. SIMPKINS number of cyclic and bicyclic hydrocarbons can be formed by The cyclisation of suitable unsaturated alkyllithiums(Scheme 1) in situ formation of the initial alkyllithium is carried out at -78 "C using tBuLi. Quenching at low temperature provides simple non-cyclised products, whereas warming to room temperature (and in some cases addition of TMEDA) effects cyclisation. Benzylic alcohols are reduced to the corresponding hydrocarbons by means of the familiar Me3SiC1 - NaI combination in CH3CN.2 The method gives very good yields, and tolerates other functionality. The combination of M O ( C O ) ~and phenylsilane comprises a powerful reagent for conjugate reduction of Michael acceptors, including ketones, esters and amides, usually in near-quantitative yield. 3 Hydrogenation of organic compounds can be carried out effectively using soluble polyethylene-bound Wilkinson's catalyst,4 and using a new biphasic reduction system. Electrocatalytic hydrogenation, using specially prepared cathodes, is also an effective method for reducing carbon-carbon double bonds. Other functionality can also be reduced by the system, such as aromatic aldehydes and nitro compounds. A
.'
2
Olefinic Hvdrocarbons
Deoxygenation of epoxides to the corresponding olefins can be The reaction requires the use of effected by treatment with Sm12.' HMPA and/or other additives for high yields in reasonable reaction times, especially for non-terminal epoxides. A report has detailed the use of titanium on graphite as a highly effective reagent for McMurry coupling of carbonyl compounds to give alkenes.8 Methylenation of enolisable carbonyl substrates is a common problem in syrlthesis, due to the basicity of the reagents employed. The combination of CeC13 with the Peterson reagent Me3SiCH2Li offers one solution to this problem(Scheme 2) The combined Li/Ce reagent proved superior to Li reagents, Mg reagents or combined Mg/Ce reagents in all cases.
.'
2
Gcnneml und Synthrtic Methods
Scheme 1
i, Me3SiCH2Li ii. bk$iiCH2~/CeC13
SiMe, i , 6% + recovered starting material ii, 83% Scheme 2 ,C02Me Ph3PCHC02Me
\I
CH3CN. E13N
86%
Scheme 3
- XR *rxH Ar
i or ii
Mes2BCHLiR + ArCHO
+
H e.g. A r = Ph,
R = n - Heptane
H i,16
H :
R
84
ii,90 : 10
Reagents: i , -78OC. THF; Me3SiC[ TFAA. - l l O ° C ,
;
HF, CH3CN,-95%; i i , -78OC. THF; Me3SiCL;
- 77% Scheme L
I: Saturated and Unsaturated Hydrocarbons
3
An interesting study of the elimination of stabilised phosphorus ylide adducts brings into question the reversibility of the addition step as an explanation for (El-olefin selectivity in such Wittig reactions. l o A variety of a-hydroxy ketones undergo accelerated Wittig reactions with stabilised phosphoranes to give trisubstituted alkenes with good (E) -selectivity, e.g. Scheme 3 As indicated in Scheme 4, the boron-Wittig reaction of aromatic aldehydes can be effected to give either (E) or (2) products.12 The initial erythro boron adduct with the aldehyde is thought to undergo selective syn (TFAA), or anti (HF) elimination, to account for the overall stereoselectivity. Palladium catalysed cross-coupling reactions provide a powerful means of synthesising alkenes, as indicated by the examples in Scheme 5. Thus, the use of manganese compounds adds to the ranks of coupling partners which can be used for enol phosphonates or triflates. Trisubstituted systems, e.g. ( 2 1 , are available by coupling of vinylalanes such as (l), which are themselves readily available from acetylenes.I4 The formation of the substituted vinyl silane (3) contrasts with previous palladium-catalysed couplings of CH2:CHSiMe3 with aryl iodides, in which aryl-desilylated products were obtained. The N-nitroso-Ij-arylacetamide acts as a source of ArPdOAc. l 5 More ambitious processes along the same lines allow sequential introduction of two groups. Thus, both 1,l- and 1,2-disubstituted ethenes can be prepared, as indicated in Scheme 6 . Both methods are one-pot procedures and have the advantage of using readily available starting materials. Piers has further extended the chemistry of bis-stannylesters such as (4). I 8 A series of metallation-alkylation reactions allowed these compounds to be efficiently converted into differentially tetra substituted alkenes (Scheme 7; see also Scheme 54). The sequence is highly stereoselective, either isomer of (4) giving the same product in the first step. Surprisingly, direct metallation of ( 5 1 , as a protected derivative, was not efficient, hence the need to convert to the corresponding iodide. What amounts to an intramolecular version of this chemistry has been used by Negishi et al.in another solution to the exocyclic alkene problem, e.g. Scheme 8. 19 The use of a new alkylidenation reagent derived from a 1,l-dibromoalkane, zinc and TiC14 allows conversion of esters and
General und Synthetic Methods
4
?IX = OP(O)(OEt )2 or OSO,CF, M
= Li or MgBr
Ar N(NO 1COC H
Ar
m
si Meg
Pd (dbaI2
O S i M c g
(31 Scheme
5
i. C O , v z n c l .
BBr,
HCECH
+
BBr,-
M Br
pd(O) ii, Phl, LiOH
*
c-
’ 61*/o Ref .16
i, R ’ M ~ X ,THF 5
ii, R2MgX, NiClq(dppp)
-
63 91% Ref. 17
Scheme 6
Ph
5
1: Saturated and Unsaturated Hydrocarbons
i
SnMe3
I Reagents:
i, MeLi. THF,
- 90 *C;
I /\//;
ii, LiAlH,
;
iii
i i i , I , , CH2ClZ; MEMCl,
(Pr'),NEt, CH2C12; iv, BuLi, THF; -78OC. Me1
Scheme 7
Br
I
Bu"Li, THF
- 7 8 ° C to 22°C
.5-,
OSiBu' Me,
Scheme 8
.
lactones to the corresponding vinyl ethers (Scheme 9 ) 2o Both chemical yields, and & / E selectivity are, on the whole, very good, and the method looks operationally quite simple. Vinyl ethers derived from lactones suffered partial hydrolysis to hydroxyketones as indicated in the Scheme; some isomerisation of a cis double bond incorporated into one starting substrate was also observed. A study of the Heck arylation of vinyl ethers describes factors responsible €or regiocontrol in the reaction.21 Vinylic chlorides are available from alkenes by reaction with PhSeC13, followed by hydrolytic selenoxide elimination(Scheme 10) .2 2 In many examples regiochemical problems arise, the most useful application of the method being the preparation of 2-chloro-1-alkenes (7) by oxidation of the selenide (6) to the dichloroselenide using S02C12, followed by elimination. The reaction of 1,l-dichloro-1-alkenes with Grignard or organozinc reagents in the presence of [PdC12(dppb)I allows replacement of just one chlorine group with high stereoselectivity, e.g. Scheme ll.23 In each case a new group is introduced trans to the existing substituent, to give the vinyl chloride in good yield. By changing the catalyst to [PdC12(PPh3)21 the second chlorine could also be substituted, resulting in a very elegant route to trisubstituted alkenes. Vinyl sulphides and selenides have been prepared by free radical addition to suitable unsaturated starting materials(Scheme 12). The addition o f PhSeH to allenes was found to require the presence of oxygen, and presumably takes place via attack of PhSe at the central carbon atom.24 The use of Et3B allows addition of thiols to acetylenes, although with very poorastereoselectivity.25 Analogous reactions of acetylenes with Ph3GeH,26 and with R3SnH,2 7 have been reported by the same group of workers. A variety of vinyl sulphoximines can be prepared by a simple two-step sequence involving dehydration of B-hydroxyalkyl sulphoximines (Scheme 13) 28 Alternative dehydration conditions could also be used to furnish the corresponding N-formyl or N-acetyl derivatives. Optically pure ( g ) - or (Z) - vinyl sulphoxides can be obtained straightforwardly from the corresponding chiral acetylenic sulphoxide.2 9 Back et al. have described further details of the reactions of 6-(phenylse1eno)vinyl sulphones leading to substituted vinyl sulphones.30 Stereoselective access to either ( g ) or (Zl-vinyl sulphones can be achieved via iodosulphonisation of alkenes or acetylenes
.
7
I: Saturated and Unsaturuted Hydrocarbons CH3CHBr2.TiC14. Zn, TMEDA
Ph
OMe
Ph
Z: E 9 2 : 0
R
Scheme
Reagents: i. PhSeCl,;
9
ii. benzene, NaHC03(Qq), 100°C; iii, PhSeCl ; iv, SO,Cl, Scheme 10
H
XCl
Me
CI
PhMgBr [ PdCIZ(dPPb
11
- ,XPh Cl
Me
9 0 OO/
Scheme 11
GetI i w 1 uti d Sy ti tli et ic Meth ocls
8
/='= +
Ph
-
02
PhSeH
AePh JP +
Ph
Ph
8 8 *lo
1 2 O/O
Ref. 24
1
Ref. 2 5 Scheme 12
0 II
.
0 II
..
OH
H N-
Me3Si N
0
I
K
Reagents: i , BuLi; ii, RCOR'; iii, H + C D I = carbonyldiimidazole Scheme 13
I
Reagents: i . TolSOzNa. 4 H 2 0 / I Z , AcOEt-HzO; ii, pyrrolidine, CH,CN; iii, MCPBA/Na,CO,,
CH,CI,;
iv, H2, 5% P d K , AcONa, CH30H
Scheme 14
R'
1: Saturated and Unsaturated Hydrocarbons
9
respectively(Scheme 14) .31 Thus Cope elimination of (8) gives the (g)-product, as does a related selenoxide syn-elimination. The corresponding (Z)-isomer is obtained using a very high-yielding hydrogenolysis reaction. Additional chemistry concerning isomerisation of these vinyl sulphones to allyl sulphones is also described in the same report. A detailed paper describes the preparation and reactions of alkenes having vicinal silyl and stannyl substituents.3 2 Two new methods for the preparation of vinyl silanes are illustrated in Scheme 15. The direct silylation of vinyl iodides such as ( 9 ) using the Me3SiSiMe3/TASF/Pdo system gives good yields, and also works, although less efficiently, with aryl iodides.33 The reaction also tolerates ester and nitrile functional groups. The other procedure produces (g)-vinylsilanes exclusively, presumably via gem dichromium species.34 Methods for the incorporation of single fluorine atoms or of perfluorinated alkyl groups into unsaturated systems continue to be of interest. Three recent examples of this type of chemistry are shown in Scheme 16. The production of (10) in 6 3 % yield illustrates the efficiency and flexibility of the first process, in which the four substituents ending up on the alkene each come from different fragments.35 The phosphonate (11) is cleanly produced in stereoselective fashion by cuprate-induced reduction of the corresponding enol derivative (12).36 Lastly, Scheme 16 indicates how a-fluorothioethers can be oxidised to the corresponding sulphoxides, and pyrolysed to give simple vinyl fluorides.37 The electrochemical oxidation of ethyl silanes has now been extended to silyl dienes.38 The major products are oxygenated, unsaturated acetals resulting from 1,4-oxidation(Scheme 1 7 ) . Allylic azides are produced in good yield by reaction of the corresponding allyl silanes with a cocktail of iodosylbenzene, Me3SiN3 and BF3 .0Et2.39 Unsaturated nitriles are amongst the products available using a new hydrocyanation procedure(Scheme 18).40 The method has the prime advantage of using isocyanides (trimethylsilylcyanide is in equilibrium in solution with the isocyanide) in place of HCN, which has obvious attractions. Several new methods for the synthesis of allylsilanes have appeared this year, along with improvements and modifications of previous methods. Scheme 19 highlights some of these developments. Two research groups have described the advantages of using
Geiierul und Synthetic Methods
10
(91
R e f . 33
R
Mc3SiCHBrZ. CrC12
RCHO
H
X
THF, 25'C
Si Me3
H
Ref. 3L Scheme 15
+
BrCH3
Ph3P
PhLi
Ph3P=CHCH3
-
I-
PhLi
CH,
H Ph
PhLi
Z ' F5
CH3
+
+
-
I
Ph3P
( C2FiC0),O
0 %
Ph3P=C (CH3I2
2 F5
(101 63%
0
II
xi
CF3
OP(OEt12
BuLi,
CuI
THF, TMEDA
F
P(OEt 1,
F
P(0Et 1,
(11) 65%
(12 1
RCH=CHF
Scheme 16
I : Saturated and Unsaturated Hydrocarbons
11
CeC13 in combination with Me3SiCH2M (M = Li or Mg) for reaction with acid derivatives (13) ( X = OR or Cl). Whilst reagents derived from CeC13 and Me3SiCH2Li work very well with acid chloride^,^' better results are obtained with esters by using the CeC13/Me3SiCH2MgC1 ~ o m b i n a t i o n . ~The ~ versatile species (15) is produced by electrophile-initiated migration of an alkyl group from boron to carbon.43 Subsequent protonolysis gives the allylsilane, whereas H202/NaOH work-up gives a B-silylketone. A rather more laborious route to simple allylsilanes uses the unusual synthon (16).44 Combination of (16) with a Grignard gives (17) which on treatment with methanesulphonyl chloride undergoes Reich-type elimination to give the final product. No alternative elimination (to give allyl selenides) is observed, and the products are obtained solely as (El-isomers. Two new methods for the synthesis of allyl stannanes both rely on the introduction of tin into a preformed allylic functional group (Scheme 20). In both methods the tin group ends up at the least substituted end of the allylic system, with mixtures of stereoisomers resulting where possible. Allylic sulphides also act as electrophilic partners in a new Mo(CO)~- mediated reaction with certain carbon nucleophiles such as malonate or enolates of 6-ketoesters(Scheme 21) .47 In addition to substitution, reductive desulfenylation was also observed in some cases. Similar allylic substitution using soft carbon nucleophiles is possible using novel n-ally1 palladium complexes incorporating a phosphonate group(Scheme 22) .48 Since the starting materials e.g. (18) are easily available from a,B-unsaturated aldehydes the method offers a useful entry into functionalised phosphonates. Alternatively, amino-substituted phosphonates can also be prepared by substituting a secondary amine for the carbon nucleophile.49 Simple homoallylic alcohols are available by coupling of allylic halides with aldehydes using a BiC13-metallic aluminium combination in aqueous THF,50 The scope and limitations of the Wenkert coupling of substituted dihydrofurans with Grignard reagents using nickel catalysis have been examined.51 Providing care is taken on work-up the reaction provides excellent stereoselective access to a variety of homoallylic alcohols(Scheme 23). The reaction gives by-products due to competing reduction, i.e. (191, with Grignard reagents bearing 6-hydrogens. Homoallylic fluorides are formed on treating cyclopropylmethanols with a
General and Synthetic Methods
12
OMe &iMe3
4 - 2 F/rnol Et4 NOfs, McOH
OMe
4 7 /'o
Scheme 17
Scheme 18
LiCfCR
R3B
:F3S0,vSiMe3
1
R2B
H
d
CH$OZH
Li+[ R 3 B l C - C R
1
____.)
__c__..)
R
0
-
SiMe,
SiMe3
R
OH
RMgBr
Me@+
H
Me3Si
/
Me3Si
R
Se Ph
SePh (16 1
(17) Scheme 19
-R
R'nsR
OAc
+
RiSnCL
SrnIZ,THF cat. Pd ( 0 )
m
R-SnR,
1
Ref. 45
Bu3SnLIlCuBr THF, HMPA
SnBu3 Scheme 20
Ref. 46
13
1: Saturated and Unsaturated Hydrocarbons
75 /o'
Scheme 2 1
0
0
'E
II
o'*pF II
C02Me
OAc
COzMe
( E t O ) Z P 4 C 0 z M e &
THF, reflux
6I
(181
BSA = bis(trimethylsilyl1acetamide Scheme 22
Scheme 23
9L% Scheme 2 4
Generril urtd Syrithrtic Mc.thods
14
specially modified HF-pyridine reagent.52 The reaction of allylstannanes with in situ generated immonium salts provides a high-yielding route to various homoallylic amines(Scheme 24). 53 The outcome of this reaction using allylstannanes contrasts to earlier results using allylsilane, in which cyclisation to form N-substituted piperidines occurred. A novel two-carbon homologation reaction converts amides into enaminones (vinylogous amides) by reaction with lithium triphenylacetylide (Scheme 25) .5 4 The use of other silyl acetylides (e.9. tBuMe2 Sic= CLi) gave only the expected, "normal" product, i.e. the silylylated acetylenic ketone. A simple stereoselective preparation of (2)-a-fluoro-a,B-unsaturated esters involves reaction of aldehydes with methyl dichlorofluoroacetate (20) using zinc powder(Scheme 26) . 5 5 The starting ester (20) was itself prepared from methyl trichloroacetate by the action of antimony (111) fluoride and bromine. Finally, a full report has appeared describing the palladinum-catalysed decarboxylation-allylation reaction of allylic esters of various B-ketocarboxylic (and other) acids. 56 3
Conjugated and Non-conjugated Dienes
Two new reports further demonstrate the usefulness of the Peterson olefination in the synthesis of 1,3 dienes(Scheme 27). Although both syntheses involve a series of at least four steps, they each solve problems of regio- and/or stereo-chemistry, and are reasonably efficient. A number of THP-protected dienyl alcohols were found to undergo smooth nucleophilic substitution reactions with allyllithiums to give conjugated (g,E) -dienes (Scheme 28) . 5 9 Other nucleophiles such as R2NLi, R3SiLi and R3SnLi also effect substitution, although a lower degree of stereoselectivity was obtained in some cases. Another route to variously substituted dienes involves the Ireland Claisen ester enolate rearrangement of propargyl esters, followed by decarboxylation(Scheme 2 9 ) . 60 Temperatures for the decarboxylation range from 140OC-250°C, and some limitations to the combinations of ester and alkynyl groups useful in the process were noted. a-Lithiation of alkoxy-substituted dienes is possible using sec-butyllithium in THF, as evidenced by quenching with Me SiC1.61 3
15
1: Saturated and Unsaturated Hydrocarbons
Ph3Si
- -L i
m
+NMe2
$NMe2 OSEM
OSE M 80 /'a
SEM = CH20(CH212SiMe3
Scheme 25
Zn powder, c a t a l y t i c CuCl, Ac 20,
0
CFCl$O,CH,
+
R
A
4 A Sieves
*
H
(20 1
RxF H
C02CH3
Scheme 26
Ref. 57
-
Me3Si
Me3Si
V
R
I
vii
Ref. 58
t----------
R Rcagtnt s:
R
16
CL
-
Getirrul a d S v ~tlii rtic Methods
i, ii,iii
,YR
iv
OTHP
Reagents: i , Mg, ZnCI2; i i , R'COR';
R2
iii, dihydropyran, PPTS; i v , R3Li Scheme 28
'Bun
Ph Scheme 29
Bn 0
. . t o0 & - c ~ [ B n o ~ c ]
B\n-:
__..)
LHMDS
BnO'
OBn
BnO
OBn
Bn = CH,Ph
(211
CN
Scheme 30
Me,Si
Me3Si
RMgX
Me3Si-
*
MezN
LiZCuC14, THF
BunMezN+
I-
(23) Scheme 31
R
>
1: Saturated and Unsaturated Hydrocarbons
17
Two unusual, chiral alkoxy dienes can be obtained from a protected arabinose by a Wittig-elimination sequence, e.g. Scheme 30.62 The diene (21) was shown to undergo Diels-Alder reaction with N-phenylmaleimide. The diene (22) was highlighted previously in connection with Diels-Alder reactions. Further studies now show that the corresponding ammonium salts, e.g. (231, undergo reaction with Grignard reagents to give substituted isoprenylsilanes(Scheme 31).63 Yields are quite good providing an excess of Grignard (2-8 eq.) is used, the use of Li2CuC14 as catalyst being preferable to several other cuprous salts tried. Another process which uses the migration of a group from boron to carbon allows the synthesis of alkyl- and alkylthio-substituted 1,3-dienes(Scheme 32) .64 Two interesting steps occur in the reaction, the first involving migration of an SBu (or secondary alkyl) group as shown, the second being elimination of the B-chloroborane using MeLi. The paper includes some interesting results concerning the relative migratory aptitude of various groups in the first step. Two methods for the preparation of 1,3-dienes substituted with an SePh group are outlined in Scheme 33. The Wittig preparation using (24) proved troublesome, largely due to the instability of (24).65 An alternative scheme was also investigated by incorporating the SePh group into the aldehyde rather than the phosphorane. The use of the Grignard ( 2 5 ) allowed efficient preparation of either tin or selenium derivatives, which were then examined as partners for Diels-Alder reactions66 Another stannyl diene synthesis involves introduction of the tin group by free radical hydrostannylation of an acetylene, followed by a 1 ,4-elimination to give the product (Scheme 34) .67 Yields overall are moderate, with (E)-isomers predominating in the final mixture. Details of some new and interesting reactions of ketenes, using palladium catalysis, include syntheses of certain 1,3 dienes, e.g. Scheme 35.68 The reaction involves the insertion of the ketene into the initially formed ally1 complex, to give an acyl complex, followed by decarbonylation. The coupling of vinyl halides, particularly iodides, with other vinylic partners under transition metal catalysis now appears to be the most powerful method available for conjugated diene synthesis. Three examples of this method are indicated in Scheme 36. The reactions are characterised by mild, neutral conditions, high stereoselectivity,
General and Synthetic Methods
18
R = 1,2 - dimethyl propyl Scheme 32
Ph3P
Br
PhSe-
Ph
*OH PPh3 PhCHO +
PhSe-
-
x-
PhSe-
PhScCl
CI
CIMg
PhSe
(25)
Scheme 33 SnBu,
A
+xO"
BugSnH b
AIBN,
A
Me3S i+OH
R
R'
R'
R
DMAP~Ac20 Et3N
+'
SnBu,
SnBu,
*
T BAF
Me3Si
++R
R
R' Scheme 34
Ph \ Ph'
~
c=c=o
O
A
C
b
Pd ( PPh3Ir, Ph
Scheme 35
R'
I : Saturated and Unsaturated Hydrocarbons
19
and ready accesibility of starting materials. Interestingly, in the coupling leading to the complex product (26) modification of the original Suzuki procedure, by addition of TlOH was vital for efficient reaction.71 Cyclisation of unsaturated starting materials using nickel, titanium or zirconium reagents provides access to cyclic dienes, as illustrated in Scheme 3 7 . A special polymer-supported nickel catalyst gave the best results in cyclisations of substrates such as (27). 7 2 Ester, sulphone and unprotected hydroxyl functions are all tolerated in the reaction. The diyne cyclisations were examined with both zirconium and titanium based reagents, the products having ( E , E ) stereochemistry. Both 1,3- and l,4-dienes are available by oxidative coupling of alkenyl-tin partners, using palladium catalysis(Scheme 38). 7 4 Homocoupling products are obtained as minor contaminants in the cross-coupling reactions. Finally, two methods for the preparation of 1,5-dienes are outlined in Scheme 3 9 . Conversion of the pyrrolidine ( 2 8 ) to the pheromone ( 2 9 ) required the synthesis of an intermediate diazene (via N-nitrosation) which underwent elmination to give the all-trans product. 75 High yields of a number of dienyl alcohols are obtained by regioselective attack of a1 lylstannanes onto vinyl epoxides.76 Either 1,2- or 1,4-attack on the epoxide is observed, depending on the substituents present.
4
Allenes
A full account of the palladium - catalysed hydrogenolysis of propargylic carbonates to give allenes has appeared.77 The allenyl palladium species involved in this process can alternatively be converted to the corresponding samarium derivatives, which undergo coupling with carbonyl compounds(Scheme 4 0 ) .78 In some cases competing alkyne formation is observed. Attempts to obtain chiral allenic alcohols via lipase catalysed sterification of racemic compounds gave very poor results, the configuration of the preferentially transformed alcohols also being unpredictable. 7 9 Both alkynoic and allenic esters are formed on treatment of certain substituted pyrazol-3 (211)-ones with PhI (OAc) (Scheme 41) .80 The method offers an alternative to the use of thallium reagents
General and Synthetic Methods
20
(CH3CN lz PdClZ
+
B u"
~~n
DMF, 25.C
6ujSn
OH
7 4 % Ref. 6 9 ""8"17
x
H
A1 Bu' l2
H
zo
02
..oz Pd ( PPh3)4
+
TLOH
'02 OMe
.oz OMe
Z
=
( 2 6 ) 94%
Si(Me)2But
Ref. 71
Scheme 36 10% nickel catalyst
30°/0 chromous chloride THF : ethanol
OH
-
32
OH
53 */o
(27)
+
+/
OSi,
- -CH3 - -CH
?sic
3
7 82
Scheme 37
O/o
I : Saturated and Unsaturated Hydrocarbons
21
Ph
Ph
-SnEt3
Ph 80 '10
72 O/e
Scheme 38
(28)
I
several st cps
OAc
% \ (29)
91 O/O
Scheme 39
Ph Pd(PPh3I4. Sm+, THF . )
d Scheme 40
22
General mid Synthetic Methods
reported previously for this process. Chloro-substituted, and vinylic allene carboxylates can be prepared from silyl ketene acetals by treatment with a carbene, followed by Bu4NF(Scheme 42) .81 Depending on the amount of Bu4NF used the initially formed chloroallene product could all be converted through to the other product, presumably via a butatriene. Allenic amides are available, albeit in moderate yield by a Horner-Wittig reaction of certain ketenes.82 A preparation of allenyl silanes has been reported which involves very brief treatment of stannyl alcohols such as (30) with CF3S03H (Scheme 43) .a3 Surprisingly, protiodesilylation of the product only causes problems when R=H. Carbanions derived from allenic ethers have been the focus of several reports this year. Firstly, the configurational stability of anions derived from certain allenic carbamates has been studied.84 The anion (31) produced by metallation, following a silicon migration of ( 3 2 ) , undergoes a variety of useful reactions, as outlined in Scheme 44.85 Thus alkylation and conjugate addition reactions can be effected regioselectivey at C-3 to give allenic intermediates which are then hydrolysed to the products shown. Reaction of (31) with benzaldehyde occurs with contrasting regioselectivity, to give the propargylic product. Metallated allenol ethers feature in a new synthesis of spiroketals which allowed the preparation of known precursors of the natural products Talaromycins A and B. 86 Spiroketals are also amongst the products produced in cyclisations of certain hydroxyl-substituted alkenyl sulphoxides(Scheme 45) .8 7 Alternatively, the same intermediate can be transformed into a 1,5-dioxadecalin structure, another compound-type relevant to natural products. Two methods for the preparation of allenic sulphones are outlined in Scheme 46. The Horner-Wittig reaction of ketenes with the anion of sulphones (33) ( R can be varied) suffers from lack of flexibility - only the stable ketenes diphenylketene and ethylphenyl ketene were used.88 By contrast,manipulation of the readily available selenosulphone (34) provides a variety of 1- and 3- substituted compounds in good to excellent yield.89 Thus, straightforward selenoxide elimination of (34) (the oxidant being usually mCPBA) gives 3-substituted products. Alternatively, the regioselective alkylation of (34) as an ally1 sulphone carbanion, using various electrophiles (MeI, Me3SiC1, ~~0etc), followed by
I: Saturated and Unsaturated Hydrocarbons H
23
H
\
/
COzMe
H pC =C =C
t
o+
, ,
PhI(0AC)p
MeOH
Me
R
5 9 -66%
R Scheme 41
Scheme 42
SnBu, CF3S03H, THF m
0.C. 1 min
Me3Si+R
A
Me3Si -yC
R
OH (301
Scheme 4 3 0
/ catalytic BuLi
*
R&SiMeZBut
R
2-
OSi
/-
BuLi
c,\
R (31)
(321
F;2
I
0
R Scheme 44
R3
R
ii, H ~ O +
R3
Getierul arid Syrithrtic Methods
24
SOph
0
ii, iii
~
II
X
Me
= SiButMe2
C
\
Me &OH
X = H
Ph
Ph \
's=o
s=o
~
i
Me
~
Me
Reagents: i. NaH, THF; ii, HF, MeOH; iii, CSA, CH2C12; i v , PTSA. C6H6 Scheme 4 5
0
NaH,THF
II
I EtO),P-SO,R
Ph Ph
MH
Ph
>C=C=O /
(33 1
SO, R
Ph
R e f . 88 S0,Ar
b c l ~electrophilc . (€+I w
PhSe
E
PhSe
(34)
I
oxidize (- PhScOHl
I 1
oxidize
R
H
>c<so2Ar Ref. 89
Scheme 46
E
1: Saturated and Unsaturated Hydrocarbons
25
m-elimination gives disubstituted products. Sulphonyl allenes have been used by Denmark et al. to construct sulphonyl-substituted ally1 vinyl ethers for carbanionic Claisen rearrangement 90 reactions. A new route to the relatively unknown fluoroallenes involves acetylide alkylation with freon (35), followed by reductive displacement of chloride using A1H3, e.g. Scheme 47. The method allows the preparation of fluoroallenes substituted with other functional groups such as hydroxyl, amino and carboxylate. Finally, azabicyclic allenes can be prepared by cyclisation of suitably set-up propargylic ~ilanes.'~ 5
Alkynes
A full report has appeared on the preparation of alkynyl tosylates and mesylates via alkynylphenyl iodonium sulphonates. 9 3 Moderate yields of l-aryloxyperfluoro-l-alkynes can be obtained via a Wittig elimination under conditions of vacuum pyrolysis (Scheme 48) .94 A series of chiral acetylenic ethers can be prepared in good overall yield by a one-pot procedure involving several steps(Scheme 49). 95 Compounds (36)-(38) illustrate the kind of product available. The acetylenes could also be converted to stereochemically pure chiral enol ethers.96 A chiral 3-phenyl-l-alkyne is amongst the products prepared by reaction of bromoallenes with organocuprates. 97 An improved procedure for the reaction of acetylenic silanes with acetals or aldehydes involves the use of a SnC14/ZnC12 combination as catalyst(Scheme 50).98 In the reactions of acetals, only 10% each of SnC14 and ZnC12 was needed, whereas 2 0 % was used in the reactions with aldehydes. The new catalyst combination was also useful in promoting the reaction of allylsilane with products such as (39) to give 1,5- eneynes. Although l-nitro-2-(trialkylsilyl)acetylenes can be prepared by treatment of bis-silylacetylenes with nitronium tetrafluoroborate, the reaction cannot be extended to prepare alkyl-substituted acetylenes. 99 A simple and high-yielding synthesis of l-iodoacetylenes involves treatment of the corresponding acetylene with CH30Na and I(pyI2BF4 in methanol .'O0, The method appears more convenient than earlier alternatives, especially with acetylenes having additional functionality. Finally, O-substituted propiolic acids can be prepared in
26
General and Synthetic Methods
III
I
-
FYc' Ill
ii
AOTHPfsio I
LOTHP HO
/
Reagents: i , 6u"Li. CHFCI,; (35)
HO
~
B u ~ N F ;ii, AlH3, O'C, l h r Scheme 47
+
+
CI-
Ph3PvOAc
i, PhLi
ph3pH0250- 270.C
_____)
ii, RCOCl
)
R-
ArO
R
-
6 2 -78% e.g. R =
C=C-OAr
10 Torr
2 8 4 0%
C2F5.Pr" Scheme 4 8
ROH
K H ; CIzC=CHCL BunLi; R'1 M H 2 0
Scheme 49
RO- c
C-
R'(H I
H
I : Saturated and Unsaturated Hydrocarbons
27
reasonable overall yield from the phosphonium salt (40) by the sequence shown in Scheme 51 . I o 1 The sequence appears operationally straightforward, the starting compound ( 4 0 ) being available by iodination of the corresponding simple phosphonium bromide. 6
Enynes and Diynes
Conjugated diynes are generated when an appropriate brominated phosphacumulene ylide is condensed with aldehydesfscheme 52). 102 Benzyltrimethylammonium methoxide can be used as the base for both steps. Alternatively the use of lithium bis(trimethylsily1)amide allowed isolation of the intermediate bromocumulene. Liotta has described an extension of the well-known oxidative rearrangement of tertiary allylic alcohols which uses starting materials derived from acetylide addition to enones, e.g. Scheme 53.1°3 The method provides varied, and usefully functionalised enyne and dienyne products, providing the tertiary allylic alcohol has a :-double bond. Treatment of l-trimethylsilyl-1,3-diynes with 2.5 eq. of Me3SnCuSMe2LiBr results in trans-distannylation to give products of type (41) (Scheme 5 4 ) . l o 4These products act as attractive precursors to a host of enynes and derived products since controlled transmetal lation-electrophilic quench (El and E2 are typically alkyl halides) of each tin group can be carried out. Another attractive route to enynes involves coupling of alkenylcopper reagents with alkynyliodoniurn salts. The starting materials for this process are readily available, and the method is highly stereoselective. As previously, important contributions to this area of synthesis have been made using palladium coupling processes. Scheme 55 illustrates two new examples which provide functionalised enyne products. The formation of ( 4 2 ) illustrates this latest reaction from Trost's group, which is favoured by using bulky ligands on phosphorus. The reaction has the attractive feature of allowing homo- or cross-coupling to give products which correspond exactly to the addition of the two starting materials (i.e. no halogens or other metals involved or expelled). The other method highlighted utilises iodoalkynes as reaction partners, and requires the use of a large excess of the reacting a,B-unsaturated ketone (or ester). l o 7 A full report of Stille's palladium-mediated coupling of alkynylstannanes with vinyl iodides to give enynes has appeared. l o *
28
General and Synthetic Methods OMe
+
9"'Y
I Co2Et (40)
K2C03'CH30H
b
ph3p~c02Et
I
Scheme 51
RCHo
I__)
[
I R 4 c 0 2 E ]
29
I : Saturated and Unsaturated Hydrocarbons
R-C=C-C=C-Si
Me,
Me3SnCu. W e 2 . LiBr R # S n M e 3
*
T HF
MeGn
+
; 'HLi ~
+
Me397
\
\
IE1 ,
El
R
E
H+ \
\
Si Me3
SiMe,
SiMe,
( 4 11
R = n-alkyl
Scheme 5 4
OH I
+*H
OH ( 4 2 ) 64% Ref. 106
ii
+
R-CCfC-I
R'
1
R
R
= a l k y l or SiMe,
-
40 60% Ref. 107
R'= CH, o r OCH3
Reagents: i, Pd(0Ac 12, t r i s ( 2 . 6 - dimethoxyphenyl lphosphine, benzene ii,
Pd(OAcI2, K2CO3, ButNCl, DMF
Scheme 55
GrrieruI and Sy ri t h rtic Meth 0d.s
30
L,i
PhS
Et
Et
Ii Et
Reagents: i, LDBB; CeCt3; P C H O (LOBB = l i t h i u m . p,p’-di butylbiphenylide) ii, Bu,P, PhSSPh
-
- tcrt
Scheme 57
R
i, LDA
i,AcZO, DMAP Et3N
ii,MoOPh
ii, NaH
BuMgCL
* R
OH
N i ( oOacl2 R
(44) Scheme 58
* R
/=.7
R
31
I : Saturated and Unsaturated Hydrocarbons
W
H
O PhJ;&
base
OH
OH major isomer Ref, 112
n = 0, 1 or 2 Reagents: i , P h 3 P T o M e ; ii catalytic I * , CH,CI,;
Ref. 113
iii, Ph3P-OMe
0
0
CONHBU'
Ref. 114
I
Scheme 59
L
X = 6Ph
Ref. 115
32 7
Polyenes
Trienes including the pheromone (43) can be prepared by deoxygenation of the corresponding terminal mono-epoxide via the thiirane(Scheme 56) .log The epoxides can also be diverted, to produce (Elg)-2,4-dienalsby reaction with NaI04. Non-conjugated dienes and trienes are amongst the products available by use of allylcerium reagents. lo These organometallics undergo regioselective reaction with aldehydes including enals and enones(Scheme 57). As can be seen, the process can be repeated to build up a "skipped diene" chain. The use of LDBB gave better results than LDMAN. On treatement with Mo05pyHMPA (MoOPh) sulphone carbanions can undergo oxidative coupling to give intermediate 6-hydroxysulphones, which can then be further transformed to alkenes (Scheme 58).ll1 The newly formed double bond is predominantly ( g ) ; (44) is typical of the trienes available by starting with unsaturated sulphones. Wittig and palladium-mediated coupling reactions continue to dominate target synthesis in the polyene area, and some examples are illustrated in Scheme 59. Thus, the well-established protocols for constructing trans-double bonds via stabilised phosphoranes and for incorporating *-double bonds via partial hydrogenation of triple bonds remain faithful favourites.
References 1. 2. 3. 4.
5.
6. 7.
8. 9. 10.
11.
W.F.Bailey, T.T.Nurmi, J.J.Patricia, and W.Wang, J. Am. Chem. Soc.,1987, 109, 2442. T-Sakai, K.Miyata, M.Utaka, and A.Takeda, Tetrahedron Lett., 1987, 28, 3817. E.Kein=.and D.Perez, J. Or . Chem., 1987, 52, 2576. D.E.Bergbreiter and €I.Am. ChemTSoc., 1987, 109, 174. C.Larpent, R.Dabard, and H.Patin, Tetrahedron Lett., 1987, 28, 2507. L.Coche and J.-C.Moutet, J. Am. Chem. SOC., 1987, 109, 6887. M.Matsukawa, T.Tabuchi, J.Inanaga, and M.Yamaguchi, Chem. Lett., 1987, 2101. A-Furstner and H-Weidmann, Synthesis, 1987, 1071. C.R.Johnson and B.D.Tait, J. Org. Chem., 1987, 52, 281. E.Vedejs, T.Fleck, and S.Hara, J. Org. Chem.,1987, 52, 4637. P.Garner and S.Ramakanth, J. Org. Chem., 1987, 52, 2629.
1: Saturated and Unsaturated Hydrocarbons 12. 13. 14. 15. 16.
33
A-Pelter, D-Buss, and E.Colclough, J. Chem. Soc., Chem. Commun., 1 9 8 7 , 297. K.Fugami, K.Oshima, and K.Utimoto, Chem. Lett., 1 9 8 7 , 2203. M.I.Al-Hassan, Synth. Commun., 1 9 8 7 , 1 4 1 3 . K.Ikenaga, K.Kikukawa, and T.Matsuda, J. Org. Chem., 1 9 8 7 , 52 , -
1276.
17.
S.Hyuga, Y.Chiba, N.Yamashina, S.Hara, and A.Suzuki, Chem. Lett., 1 9 8 7 , 1 7 5 7 . V-Fiandanese, G-Marchese, F.Naso, and L.Ronzini, Synthesis,
18. 19.
E.Piers and R.T.Skerlj, J. Org. Chem., 1 9 8 7 , 52, 4 4 2 1 . E.Negishi, Y.Zhang, and V.Bagheri, Tetrahedron Lett., 1987,
1987,
20.
28, -
1034.
5793.
T.Okazoe, K.Takai, K.Oshima, and K.Utimoto, J. Org. Chem., 1987,
52,
4410.
21.
C.-M.Andersson, A-Hallberg, and G.D.Daves Jr., J. Org. Chem.,
22 *
L.Engmz, J. Org. Chem., 1987, 52, 4086; L.Engman, Tetrahedron Lett., 1 9 8 7 , 2, 1 4 6 3 . A.Minato, K.Suzuki, and K.Tamao, J.Am.Chem.Soc., 1 9 8 7 ,
1 9 8 7 ,. 52,. 3 5 2 9 .
23.
109,
1257. 24. 25.
26. 27. 28.
T-Masawaki, A.Ogawa, N.Kambe, I.Ryu, and N.Sonoda, Chem. Lett., 1 9 8 7 , 2 4 0 7 . Y.Ichinose, K-Wakamatsu, K.Nozaki, J-L.Birbaum, K.Oshima, and K.Utimoto, Chem. Lett., 1 9 8 7 , 1 6 4 7 ; for an alternative preparation see also B.Bartels, R.Hunter, C.D.Simon, and G-D-Tomlinson,Tetrahedron Lett., 1 9 8 7 , 2,2 9 8 5 . Y.Ichinose, K.Nozaki, K.Wakamatsu, K.Oshima, and K.Utimoto, Tetrahedron Lett., 1 9 8 7 , 28, 3 7 0 9 . K.Nozaki, K-Oshima, and K ~ t i m o t o ,J. Am. Chem. SOC., 1 9 8 7 ,
109 , -
2547.
K-J.Hwang and E.W.Logusch, Tetrahedron Lett., 1 9 8 7 ,
28,
4149.
35. 36.
H.Kosugi, M.Kitaoka, K.Tagami, A.Takahashi, and H.Uda, J. Org. Chem., 1 9 8 7 , 52, 1 0 7 8 . T.G.Back, S.Collins, M.V.Krishna, and K-W.Law, J. Org. Chem., 1 9 8 7 , 52, 4258; see also T.G.Black and M.V.Krishna, J. Org. Chem., 1 9 8 7 , 52, 4265. T.Kobayashi, Y.Tanaka, T.Ohtani, H.Kinoshita, K.Inomata, and H-Kotake, Chem. Lett., 1 9 8 7 , 1 2 0 9 . T.N.Mitchel1, R.Wickenkamp, A-Amamria, R.Dicke, and U-Schneider, J. Org. Chem., 1 9 8 7 , 52, 4868. Y.Hatanaka and T.Hiyama, Tetrahedron Lett., 1 9 8 7 , 28, 4715. K.Takai, Y.Kataoka, T.Okazoe, and K.Utimoto, TetraEdron Lett., 1 9 8 7 , 28, 1 4 4 3 . Y.Shen ad W.QE, Tetrahedron Lett., 1 9 8 7 , 28, 449. T.Ishihara, T.Maekawa, Y.Yamasaki, and T.Ando, J. Org. Chem.,
37.
S.T.PuEington and J.H.Pittman, Tetrahedron Lett., 1 9 8 7 ,
29. 30. 31. 32. 33. 34.
1987,
52,
300.
28,
3901. 38.
J.Yoshida, T.Murata, and S.Isoe, Tetrahedron Lett., 1 9 8 7 ,
39.
XArimoto, H-Yamaguchi, E.Fujita, M.Ochiai, and Y.Nagao, Tetrahedron Lett., 1 9 8 7 , 28, 6 2 8 9 . S.L.Buchwald and S.J.LaMaGe, Tetrahedron Lett., 1 9 8 7 , 28,
28, 40.
295.
211.
34 41. 42.
General and Synthetic Methods M.B.Anderson and P.L.Fuchs, Synth. Commun., 1 9 8 7 , 6 2 1 . B.A.Narayanan and W.H.Bunnelle, Tetrahedron Lett., 1 9 8 7 ,
2,
6261.
44. 45.
K.K.Wang and K.E.Yang, Tetrahedron Lett., 1 9 8 7 , 3,1 0 0 3 ; K.K.Wang and S.Dhumrongvaraporn, ibid., p . 1 0 0 7 . T.K.Sarkar and S.K.Ghosh, Tetrahedron Lett., 1 9 8 7 , 3,2 0 6 1 . T.Tabuchi, J-Inanaga, and M-Yamaguchi, Tetrahedron Lett.,
46.
T-Takeda, S.Ogawa, N.Ohta, and T.Fujiwara, Chem. Lett., 1 9 8 7 ,
47.
Y.Masuyama, K.Yamada, and Y.Kurusu, Tetrahedron Lett., 1 9 8 7 , 28, 443. J.Zhu and X.Lu, Tetrahedron Lett., 1 9 8 7 , 28, 1 8 9 7 . J.Zhu and X.Lu, J. Chem. Soc., Chem. Commun., 1 9 8 7 , 1 3 1 8 . M.Wada, H.Ohki and K.Akiba, J. Chem. Soc., Chem. Commun.,
43.
1987,
28, 2 1 5 .
1967. 48. 49. 50.
1987, 708. 51. 52.
S.Wadman, R.Whitby, C.Yeates, P-Kocienski, and K.Cooper, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 2 4 1 . S.Kanemoto, M.Shimizu, and H.Yoshioka, Tetrahedron Lett., 1987, 28, 663.
53. 54. 55. 56. 57. 58.
P.A.GrGco and A.Bahsas, J. Org. Chem., 1 9 8 7 , 52, 1 3 7 8 . K-Suzuki, T.Ohkuma, and G.Tsuchihashi, J. Org. Chem., 1 9 8 7 , 52, 2929. T.Ishihara and M.Kuroboshi, Chem. Lett., 1 9 8 7 , 1 1 4 5 . J.Tsuji, T.Yamada, I.Minami, M.Yuhara, M.Nisar, and I.Shimizu, J. Org. Chem., 1 9 8 7 , 52, 2 9 8 8 . P.A.Brown, R.V.Bonnert, P.R.Jenkins, and M.R.Selim, Tetrahedron Lett., 1 9 8 7 , 2,6 9 3 . S.Kuroda, T-Katsuki, and M.Yamaguchi, Tetrahedron Lett., 1987, 28, 803.
59. 60. 61. 62.
T.IshiX N-Kawamura, S-Matsubara, K.Utimoto, S.Kozima, and T.Hitomi, J. Org. Chem., 1 9 8 7 , 52, 4 4 1 6 . J.E.Baldwin, P.A.R.Bennett, and A.K.Forrest, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 2 5 0 . P.G.McDouga1 and J.G.Rico, J. Org. Chem., 1 9 8 7 , 52, 4 8 1 7 . A.B.Reitz, A.D.Jordan Jr., and B.E.Maryanoff, J. Org. Chem., 1987,
63.
52,
4800.
64.
A Hosomi, K.Hoashi, Y-Tominaga, K.Otaka, and H. Sakurai, J. Org. Chem., 1 9 8 7 , 52, 2 9 4 7 . M.Hoshi, Y.Masuda, and A.Arase, J. Chem. SOC., Chem. Commun.,
65. 66.
J.V.Comasset0 and C.A.Brandt, Synthesis, 1 9 8 7 , 1 4 6 . G.S.Bates, M.D.Fryzuk, and C.Stone, Can. J. Chem., 1 9 8 7 ,
1987, 1629. 2612. 67.
C.Nativi, M.Taddei, and A.Mann, Tetrahedron Lett., 1 9 8 7 ,
65,
2,
347. 68. 69. 70. 71. 72. 73.
T.Mitsudo, M.Kadokura, and Y.Watanabe, J. Org. Chem., 1 9 8 7 , 52 , 1695. J.K.Stille and B.L.Groh, J. Am. Chem. SOC., 1 9 8 7 , 109, 8 1 3 . E.Negishi, T.Takahashi, S.Baba, D.E.Van Horn, and N.Okukado, J. Am. Chem. Soc., 1 9 8 7 , 109, 2 3 9 3 . J.Uenishi, J.-M.Beau, R.W.Armstrong, and Y.Kishi, J. Am. Chem. SOC., 1 9 8 7 , 109, 4 7 5 6 . B.M.Trost and J.M.Tour, J. Am. Chem. SOC., 1 9 8 7 , 109, 5 2 6 8 . W.A.Nugent, D.L.Thorn, and R.L.Harlow, J. Am. Chem. S O C . , 1987,
2, 2788.
1: Saturated and Unsaturated Hydrocarbons 74. 75. 76. 77. 78. 79 * 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101 102. f
103.
104. 105.
35
S.Kanemoto, S.Matsubara, K.Oshima, K.Utimoto, and H.Nozaki, Chem Lett., 1987, 5 . J.J.Tufariell0, A.S.Milowsky, M.Al-Nuri, and S.Goldstein, Tetrahedron Lett., 1987, 28, 263. Y.Naruta and K.Maruyama, Chem. Lett., 1987, 963. J.Tsuji, T.Sugiura, and I.Minami, Synthesis, 1987, 603. T.Tabuchi, J.Inanaga, and M.Yamaguchi, Chem. Lett., 1987, 2275. G.Gil, E-Ferre, A.Meou, J. Le Petit, C.Triantaphylides, Tetrahedron Lett., 1987, 28, 1647. R.M.Moriarty, R.K.Vaid, and P.Farid, J. Chem. SOC., Chem. Commun., 1987, 711. N.Slougui and G.Rousseau, Tetrahedron Lett., 1987, 28, 1651. H.Fillion, A.Hseine, and M.-H.Pera, Synth. Commun., 1987, 17, 929. C.Nativi, A-Ricci, and M.Taddei, Tetrahedron Lett., 1987, 28 , 2751. D.Hoppe and C.Gonschorrek, Tetrahedron Lett., 1987, 28, 785. R-Matsuoka, Y.Horiguchi, and I.Kuwajima, TetrahedronLett., 1987, 28, 1299. R.Whitby and P.Kocienski, J. Chem. SOC., Chem. Commun., 1987, 906. G-Pairaudeau, P.J.Parsons, and J.M.Underwood, J. Chem. SOC., Chem.Commun., 1987, 1718. H.Fillion, A-Hseine, M.-H.Pera, V.Dufaud, and B.Refouvelet, Synthesis., 1987, 708. T.G.Back, M.V.Krishna, and K.R.Muralidharan, Tetrahedron Lett., 1987, 28, 1737. S.E.Denmark, M.A.Harmata, and K.S.White, J. Org. Chem., 1987, 52, 4031. xL.Castelhano and A.Krantz, J. Am. Chem. Soc., 1987, 109, 3491. W.J.Klaver, H.Hiemstra, and W.N.Speckamp, Tetrahedron Lett., 1987, 28, 1581. P.J.Stang, B.W.Surber, 2.-C.Chen, K.A.Roberts, and A.G.Anderson, J. Am. Chem. SOC., 1987, 109, 228. Y.Shen, W.Cen, and Y.Huang, Synthesis, 1987, 626. A.Moyano, F.Charbonnier, and A.E.Greene, J. Org. Chem., 1987, 52 , 2919. F.Charbonnier, A-Moyano, and A.E.Greene, J. Org. Chem., 1987, 52 , 2303. A.M.Caporusso, C.Polizzi, and L.Lardicci, J. Org. Chem., 1987, 52, 3920. M-Hayashi, A-Inubushi, and T.Mukaiyama, Chem. Lett., 1987, 1975. R.J.Schmitt, J.C.Bottaro, R.Malhotra, and C.D.Bedford, J. Org. Chem., 1987, 52, 2294. J.Barluenga, J.M.Gonzalez, M.A.Rodriguez, P.J.Campos, and G.Asensio, Synthesis, 1987, 661. J-Chenault and J.-F.E.Dupin, Synthesis, 1987, 498. C.B.Ziegler Jr., S.M.Harris, and J.E.Baldwin, J. Org. Chem., 1987, 2,443. D.Liotta, D.Brown, W.Hoekstra, and R.Monahan 111, Tetrahedron Lett., 1987, 28, 1069. G.Zweife1 and W.Leong, J. Am. Chem. SOC., 1987, 109, 6409. 7561. P.J.Stang and T.Kitamura, J. Am. Chem. SOC., 1987,109,
General and Synthetic Methods
36 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116.
B.M.Trost, C.Chan, and G.Ruhter, J. Am. Chem. SOC., 1987, 3486. T.Jeffery, Synthesis, 1987, 70. J.K.Stille and J.H.Simpson, J. Am. Chem. S O C . , 1987, 109, 2138. M.Goldback, E.Jake1 and M.P.Schneider, J. Chem. SOC., Chem. Commun., 1987, 1434. B.-S. Guo, W.Doubleday, and T-Cohen, J. Am. Chem. SOC., 1987, 109, 4710. n a p e t , T.Cuvigny, C.H. du Penhoat, M.Julia, and G.Loomis, Tetrahedron Lett., 1987, 28, 6273. A.Hosoda, T.Taguchi, and Y.Kobayashi, Tetrahedron Lett., 1987. 28, 65. S.Hane=ian and M.Botta, Tetrahedron Lett., 1987, 28, 1151. R.J.Blade, J.E.Robinson, R.J.Peek, and J.B.Weston, Tetrahedron Lett., 1987, 28, 3857. G.Pattenden and D.C.RobsoC Tetrahedron Lett., 1987,%, 5751. For two further examples of palladium-catalysed cross coupling reactions which furnish trienes see T-Ishiyama, N.Miyaura, ,andA.Suzuki, Chem. Lett., 1987, 25; T.L.Gilchrist and R.J.Summersel1, Tetrahedron Lett., 1987, 28, 1469.
109, -
2
Aldehydes and Ketones BY K. E. B. PARKES
1
Synthesis of Aldehydes and Ketones
Oxidative Methods. - This year has seen an important new development in oxidation methodology with a publication from Ley's group on the use of tetraalkylammonium perruthenates as catalytic oxidants for alcohols.' The recommended reag,ent, tetra-npropylammonium perruthenate, is used in dichloromethane at room temperature in the presence of 4A molecular sieves with Nmethylmorpholine-N-oxide as co-oxidant. Both primary and secondary alcohols are cleanly oxidised to aldehydes or ketones respectively in the presence of a wide variety of other functional groups, including silyl and tetrahydropyranyl ethers, alkenes, epoxides and esters [equation (111. The reagent has the additional advantage of not epimerising the position Q- to the ketone being formed. In interesting contrast to the tetraalkylammonium perruthenate catalysts, catalytic potassium ruthenate, used under phase transfer conditions, with potassium peroxydisulphate as the regenerating oxidant, oxidises benzylic and allylic alcohols with high selectivity over saturated alcohols. Procedures have also been reported for the phase transfer catalysed oxidation of alcohols to ketones with either catalytic ruthenium tetroxide and periodate as regenerating oxidant, or with potassium permanganate. The full paper describing the use of 3-carboxypyridine dichromate (1) (previously called nicotinium dichromate) as an oxidant for alcohols, and comparing the results with those obtained with pyridinium dichromate,has been published. A system using catalytic chromium trioxide in the presence of 70% t-butyl hydroperoxide for the oxidation of benzylic alcohols and of both allylic and benzylic methylene groups has been reported. While on the subject of the oxidation of unactivated C-H bonds, papers describing the use of pyridinium chlorochromate, or less effectively pyridinium dichromate, for the allylic oxidation of A 5 steroids' and of permanganate under phase transfer conditions for benzylic
GejiLW 1 mid Syti th e t k Methods
38
HO __c.
OTBDPS
Qco2H
cr*o; -
H
& I
0'
?
(2) 0 TMSO
R e a g e n t s : i , DMSO, (COC112
;
i i , MeOH , HCI
Scheme 1
R e a g e n t s : i , PhCHO
Scheme 2
2: Aldehydes and Ketones oxidation8 should be mentioned.
39
The latter reagent may also be used for the hydroxylation of doubly or triply benzylic tertiary C-H. Peracetic acid, an oxidant that appears only rarely in this section, has, in the presence of sodium bromide, been found to oxidise a variety of allylic, benzylic and secondary but not primary alcohols to the corresponding carbonyl compounds in high yields. The authors suggest that the actual oxidant is acetyl hypobromite (AcOBr) and emphasise the cost and environmental advantages of their method.’ Alternatively sodium hypochlorite may be used for the oxidation of alcohols, this time with the nitroxyl ( 2 ) and potassium bromide as co-catalysts.10 Perhaps the most mild and versatile group of oxidants are those based on activated DMSO; the Swern and Pfitzner-Moffatt oxidations. One potentially valuable property of these systems that has been highlighted by two research is their ability to oxidise 1,2-diols to diketones without any carbon-carbon bond cleavage. Despite the rather different activants, G. trifluoroacetic anhydride in one case and dicyclohexylcarbodiimide in the other, comparable results and yields were obtained. Another interesting oxidation, that of the trimethylsilyl ethers of primary or secondary alcohols to aldehydes or ketones, may be achieved by treatment with the DMSO/oxalyl chloride system at - 3 0 ° C for 30 to 45 min - conditions that are considerably more vigorous than the below - 6 0 ° C for up to 15 min used in a conventional Swern oxidation. t-Butyldimethylsilyl ethers are inert to these reaction conditions and the reaction of highly hindered trimethylsilyl ethers is inhibited, making selective oxidations possible (Scheme 1) . 1 3 Also of interest is a report of the use of phosphorus pentoxide in the presence of triethylamine to activate DMSO, a reagent mixture which avoids the chlorinated by-products which are 14 occasionally seen in some Swern-type oxidations. A type of oxidation that is perhaps too infrequently seen outside undergraduate textbooks is the Oppenauer oxidation. One most interesting development of this reaction is its extension to halomagnesium alkoxides, the immediate products from the reaction of Grignard reagents with aldehydes. Thus a variety of ketones were prepared by addition of a solution of a Grignard reagent in an acyclic ether to an aldehyde followed, in the same pot, by benzaldehyde as hydride acceptor (Scheme 2). Alternatively the halomagesium alkoxide could be prepared from an alcohol and
40
Gemv-al utrd Synthetic Methods
ethylmagnesium bromide. Yields were rather variable with the lowest yields being obtained from simple primary alkoxides and the highest with secondary and allylic alkoxides. I 5 Japanese workers have also reported on the use of zirconocene complexes to catalyse the Oppenauer-type oxidation of allylic alcohols to conjugated carbonyl compounds.16 Other reagents reported for the oxidation of alcohols to aldehydes or ketones include the stoichiometric molybdenum reagent (3) ,I7 the use of iridium pentahydride to catalyse the dehydrogenation of alcohols in the absence of any hydrogen acceptor,18 and of the Dess-Martin periodinane (4) for the oxidation of di- and trifluorocarbinols [equation (2)I . 19 The Nef reaction has been the subject of several publications this year,2 o and particularly interesting were those applying the reaction to more functionalised substrates. Thus the treatment of a solution of a nitroalkane in dichloromethane with triethylamine followed by cetyltrimethylammonium permanganate gave respectable yields of aldehydes or ketones, with, surprisingly, olefin, ketone and alcohol functionalities being tolerated [equation (3)I .21 The traditional Nef conditions, in which a sodium nitronate is treated with sulphuric acid, have now been found to be applicable to allylic nitro compounds, thus allowing the preparation of unsaturated aldehydes.22 Palomo's research group has reported on the use of the oxidative Nef reaction of ~ i l y l and ~ ~ t a n n y lnitronates ~~ to prepare both ketones (Scheme 3 ) and a- alkoxyketones (Scheme 4); again the method is tolerant of other functionality such as ester and olefin groups. Finally in this section, two electrooxidations have been described, both of which use electrochemistry to regenerate a chemical oxidant which is therefore used catalytically. Curiously both are also carbon-carbon multiple bond oxidations, one the Wacker oxidation of a terminal alkene with palladium(I1) acetate and benzoquinone as an electron transfer catalyst,2 5 and the other a ruthenium tetroxide oxidation of non-terminal alkynes to adiketones.2 6 Reductive Methods. - This year has seen the publication of a remarkable number of papers on the one-pot reduction of carboxylic acids to aldehydes, not something that is widely regarded as a simple transformation! The majority of these reagents are based on boron.
41
2: Aldehydes and Ketones
OAc
OAc
(3)
F
F
- & Me
Me
Reagents: i, B u g n H ; ii, MCPBA
Scheme 3
Reagents: i, CH2=CHCH20Na,DME
ii, M e 3 S i C 1 , DBU.CH2CI2; iii, MCPBA
Scheme 4
(3)
Me
42
General and Synthetic Methods
Thus H.C.Brown's group has reported the use of thexylchloroborane dimethyl ~ u l p h i d e ,and ~ ~ J.S.Cha's group in Korea has published several papers on the use of thexylbromoborane - dimethyl sulphide; this has the advantage of tolerating alkene functionality and allowing the reduction of a@- unsaturated carboxylic acids, but the disadvantage of requiring carbon disulphide as solvent.2 8 ' 2 9 In both methods the isolation of the aldehyde product from thexylboronic acid requires either distillation, or the preparation and decomposition of a bisulphite adduct. The Korean research group has also published an alternative boron based method in which an acyloxyborane, prepared by reaction of the carboxylic acid with 9 - borabicyclo[3,3,llnonane, is treated with either lithium 9boratabicylo [3,3,1]nonane3' or tert-butyllithium followed by 9 31 borabicyclo[3,3,lJnonane ; isolation was again by distillation or via a bisulphite adduct. A totally different method of one-pot carboxylic acid to aldehyde reduction uses the pentacoordinate silane (5) and gave good results with a variety of aromatic, heteroaromatic , aliphatic and unsaturated acids. 32 The related reduction of esters to aldehydes may be achieved with lithium aluminium hydride in the presence of excess diethylamine in pentane as solvent.33 In refluxing tetrahydrofuran and with molybdenum carbonyl as catalyst, phenylsilane cleanly effects the conjugate reduction of a variety of a@-unsaturated carbonyl compounds. Unfortunately the reaction fails for a@-unsaturated aldehydes, which were chiefly reduced 1,2- and for cyclic ketones which cannot attain a cisoid conformation. The reagent transfers hydride regioselectively to the 6-carbon of the substrate and a proton from water is incorporated at the a-position during work-up (Scheme 5) . 3 4 A modification of the traditional dissolving metal conjugate reduction of ketones has been reported, in which ultrasound was found to markedly improve the reduction of unsaturated ketones by nickel chloride activated zinc dust in aqueous media.35 Two related, and unlikely, reducing agents have been reported for the conversion of B-phenyl-a,@-unsaturated ketones to the corresponding saturated carbonyl compounds,k t-butylchloride - sodium iodide36 and chlorotrimethylsilane - sodium iodide - water.37 The two systems give similar, good results and are postulated to proceed by related mechanisms, depicted for the latter system in equation (4). Probably the most valuable group of reductive ketone syntheses
43
2: Aldehydes and Ketones
D
O
A04 Ph iii, iv
Ph+ D
Reagents: i, P h S i D 3 , M o ( C 0 ) 6 ; ii. H20
;
iii,PhSiH3,Mo(CO)G; i v , D20
Scheme 5
General and Synthetic Methods
44
are those involving the reaction of a carboxylic acid derivative with an organometallic carbon nucleophile, and as usual there have been a variety of interesting publications on the topic. Firstly acid chlorides; these have been found to react, in the presence of tris(acetylacetonate)iron(III), with Grignard reagents to give ketones free of any of the alcohol product of over-reaction. The conditions are compatible with nitrile, ester and aromatic methoxy and chloro functional groups, although only simple - alkyl and phenyl Grignards were tried.38 Tertiary amides react with alkyl and aryllanthanum triflates [RLa(OTfI2], prepared by the reaction of an alkyl- or aryl-lithium with lanthanum(II1) triflate, to give ketones in very high yields.39 Respectable yields of ketones may also be obtained from the reaction of tertiary thioamides with alkyllithium reagents, followed by acidic hydrolysis of the intermediate thioketones, which may themselves be isolated if a milder hydrolytic work up is used. 40 The reaction Gf a non-enolizable or slowly enolizable ester, o r diethylamide, with a combination of lithium diisopropylamide and a Grignard reagent forms a ketone which is protected from further reaction by enolate formation. Although previously known for allylic Grignard reagents the reaction has now been shown to be far more general and is even extendable to the use of alkyllithium 41 rather than Grignard reagents as nucleophile. Despite its long and respectable pedigree, ketone preparation by the addition of a Grignard reagent to a nitrile can be a capricious process. However, it has now been found that copper(1) salts effectively catalyse this reaction and allow the preparation of quite hindered ketones.42 Lastly in this section, sodium formaldehyde sulphoxylate (HOCH2SO-2Na+) 43 and phenylsilane with a molybdenum ( 0 ) catalyst in the presence of triphenylph~sphine~~ have been reported as reagents for the dehalogenation of a-halo ketones.
.
Methods Involving Umpolunq. - An extensive study of the bis (benztriazo1e)anion ( 6 ) as a potential acyl anion equivalent has been reported. Although the deprotection, with 10M hydrogen chloride in tetrahydrofuran for 15 min, is claimed to be milder than the conditions required for the corresponding dithiane, the system is clearly less general and only in special cases would it offer advantages over better established methodology.45 An
2: Aldehydes and Ketones
4s
interesting new type of acyl anion equivalent, the oxazolidine anion [eg (7)3, has been described. They are generated by the electroreduction of oxazolinium salts, which are easily synthesised from the corresponding carboxylic acid. As yet the range of electrophiles used is limited but include benzylic halides, aqueous acid,46 and, in the presence of chlorotrimethylsilane, Michael acceptors47 (Scheme 6). Reports have appeared on the use of the lithiostyrylsulphone (8) as an equivalent of the acyl anion (9); the sulphone apparently migrates to the styryl a- position by rearrangement of an epoxy-sulphone intermediate formed during the unmasking by treatment with m-chloroperoxybenToic acid. 48 Also described in 1987 are the anion (lo), equivalent of the 6-acylvinyl anion (11),49 and (12) used as an equivalent of the acetone electrophile (13).50
-
Other Methods. The discovery that acyl radicals may be generated by the homolysis of acylcobalt salophens (14) and that they can be trapped, without any decarbonylation, by a wide variety of Michael acceptors, forms the basis of an interesting new approach to ketone ~ynthesis.~ A ~wide range of acylcobalt species can be prepared by the reaction of a carboxylic acid chloride, or mixed anhydride with 2,6- dichlorobenzoic acid, with cobalt(1) salophen formed by the sodium amalgam reduction of the readily available cobalt(I1) Photolysis, trapping, and elimination of salophen (Scheme 7 ) . cobalt hydride is then achieved in the one pot by irradiation with a 300W sunlamp of a refluxing dichloromethane solution of the acylcobalt complex in the presence of excess olefin [equation (5)l. The reaction may also be carried out intramolecularly to give cyclic products [equation (611. A radical mechanism may also underlie a new preparation of masked hydroxy aldehydes by the samarium iodide mediated coupling of 1,3-dioxolane with ketones or aldehydes in the presence of iodobenzene [equation (7)]. 5 2 H.C.Brown's group has described how enantiomerically pure boronic esters, which are available from the asymmetric hydroboration of alkenes with monoisopinocamphenylborane,may be converted to a-chiral acyclic ketones of greater than 99% ee. Thus, treatment of the boronate (15) with an alkyllithium reagent followed by chlorotrimethylsilane forms a borinic ester (161, which on treatment with dichloromethyl ether in the presence of lithium t-butoxide gives a boronate (17) and hence, after oxidative work up,
G m i w l arid Synthetic Methods
46
I
[
iv __t
Ph
Ph
\
lv
1
1
iv
iv
0
0 Ph
Ph
Reagents: i, H z N C M ~ ~ C H ~;Oii.H Met
v,PhCHtBr
;
;
iii, +(el. D M F , EtbNOTs
v i , M e 3 S i C l , cyclohcxcnone
Scheme 6
;
i v , H3O+;
2: Aldehydes and Ketones
47
W
*
Me M e
Ts
O
Ts
0
OMe
(10)
i ,ii ,iii __c
Reagents:
i , lo/. Nal Hg
;
i i , RCOX
;
iii, p y r i d i n e
Scheme 7
0 R *Co(solophe")p
y.
Getieml utid Syrtrhetic Method
48
O
l
'
H
+
i,ii
J ii i
Reagents: i, 2
- furfuryllithium
;
ii, Me3SiCL ; iii, CHCIzOMe, L i O But
Scheme 8
;
i v , Me3NO
2: Aldehydes and Ketones
49
the chiral ketone (Scheme 8 ) . 5 3
An alternative approach to a-chiral ketones by hydroformylation of olefins with the platinum catalyst (18) has been reported. Although the enantiomeric purities were often good, only poor control of the regiochemistry of hydroformylation was obtained.54 Diary1 ketones have been prepared by the palladium(I1) catalysed coupling of arene diazonium salts with aryl tin reagents pressure of carbon monoxide. Yields were under a 9 kg cm'2 generally good, with the main by-product (up to 2 5 % ) being the symmetrical ketone in which both aryl groups were derived from the tin reagent [equation ( 8 ) ] . 5 5 Aromatic ketones have also been prepared in high yield by the use of zirconium chemistry. Thus, heating a solution' of diphenylzirconocene in benzene in the presence of one equivalent of a nitrile gives, by trapping of a zirconium-benzyne complex, a novel metallocycle which, surprisingly, is isolable as a crystalline solid. The metallocycle is then coverted to the ketone in a second, hydrolytic, step (Scheme 9). The reaction is tolerant of a wide range of functionality, although the benzyne-complex trapping reaction takes a different course with dinitriles and w - h a l ~ n i t r i l e s . ~The ~ preparation of nitrobenzaldehydes from nitroarenes by an application of the vicarious nucleophilic substitution reaction,5 7 and a method for ketone p-hydroxy- or p-amino- arylation by sifane reduction of the products from the reaction of tin(I1) enolates with p-benzoquinone or its mono N-tosylimino derivative,5 8 have both been reported. Lastly in this section, mention must be made of the dithiolane reagent (19), which provides a convenient means for the one carbon homologation of aldehydes and ketones (Scheme and also of an improved and more direct method for the use of synthon (20) for the preparation of y- hydroxyketones 6 o
.
Cyclic Ketones. - Probably the most popular method for the preparation of cyclobutanones is by the [ 2 + 21 cycloaddition of ketenes to alkenes. Unfortunately extension of this reaction to the preparation of simple cyclobutenones by substitution of an alkyne for an alkene in the cycloaddition is rendered impractical by the poor ketenophilicity of simple acetylenes and the difficulty of reductively dechlorinating the adducts obtained with the far more reactive dichloroketene. However, the publication by two groups of zinc based dehalogenations should do much to improve the
General and Synthetic Methods
50
Reagents : i, bctitene , 80 *C ; ii, hydrolysis
Scheme 9
2: Aldehydes and Ketones
51
4 Reagents: i, HBF4 . E t 2 0 , M e C N . r . t . ; ii, NaBH6; iii. HgO, a q . H B F 4 , THF
Scheme 10
H
I
Ill I
-
Bun
H q o c l Bun
CI
-
BU"
Reagents: i , CCl3COCl , Z n ( C u ) ; i i , Z n ( C u ) , AcOH, pyridine.or zinc dust2 EtOH AcOH, TMEDA
Scheme 11
52
General and Synthetic Methods
availability of these interesting compounds (Scheme 11) .61 Chiral a,a-disubstituted cyclobutanones may be prepared by the reaction of the anion from a chiral cyclopropyl tolyl sulphoxide with ketones, followed by ring expansion of the resulting 6-hydroxy sulphoxide, reduction and vinyl sulphide hydrolysis (Scheme 12) 63 The entantiomeric excess obtained clearly depends heavily on the ketone used, although too few examples are reported to permit any generalisations. The intramolecular insertion of a rhodium carbenoid into a carbon hydrogen bond has proved to be particularly valuable for the preparation of five membered carbocycles. Different research groups have now described the application of the reaction to a-phosphory1€I or a- pheny 1su 1phony 1 cyc 1opentanone synthe sis [equation (9)I . The former products are of particular interest as precursors of a-alkylidenecyclopentanones. The reaction has also been applied to the synthesis of 2-indan0nes.~~ Last year Matsuyama et al. described the use of the Ramberg-Bkklund reaction for the preparation of 3-alkyl-3cyclopentenones. They have now published full details of their method and also of its extension to 2-alkyl-3-cyclopentenone synthesis (Scheme 13) .67 An enzymic approach to chiral 4-alkyl cyclopentenones68 and an application of the Parham cyclisation to the synthesis of 7-metho~y-l-indanones~~ have also been reported. Cyclopentenone ring annelation has been a popular area of research with a variety of new reagents being reported for the purpose. These methods are conceptually similar in that the reagents are equivalents of the acetonyl cation and allow access to a 1,4-diketone which is cyclised by means of an aldol or Wittig reaction to give the required cyclopentenone [equation (lo)]. The reagents (21),70 (22),71 and (23)7 2 vary considerably in their reactivity and method of deprotection and cyclisation, and should serve a wide variety of annelation requirements. A mechanistically very different, if conceptually related, approach to the same annelation is by the manganese(II1) promoted addition of 6-keto esters to enol ethers or esters.73 The reaction has a rather nice symmetry in that the annelation of a particular cyclic ketone may be achieved by either the condensation of its vinyl ether derivative with ethyl acetoacetate or condensation of its a-ethoxycarbonylated derivative with an enol ester or ether [equations (11) and (12)l. An isomeric cyclopentenone annelation
.
53
2: Aldehydes and Ketones ...
0 F S a T o I
9
P h - -Me ~ b S d ' l O l
111,
-iL ii c
i
**
*.
Reagents: i , B S L i Pb(OH12
**
S- Tol
;
,
i i , P h C O M e ; iii, T s O H , P h H , A
1. i v , M e C O C I , C H Z C I Z ; v , TiC14,
H 2 0 , MeCN
Scheme 12
i,ii __c
Reagents: i, PhCH2Br , K2CO3,MqCO; ii.LiC1, HMPA,8O0C; iii, HOCH2CH20H,p-TsOH,PhHs iv, Na1O4; v, ButOK ,CCl4, B d O H ; Vi,p-TsOH.pyridinc.MqCO
Scheme 13
54
Gerieml wid Sviithetic Methods
0 II
( E t 0)2P,
I
CI
4
(23)
(22)
+"-p COZ Et
a0
c02 Et
COzEt
Do Me02C $*Me
\
OMe
OLi
+
But-CZC-CO2Ph
Me02C
0
(12)
2: Aldehydes and Ketones
55
has been reported to occur in a single step by the reaction of the dilithio derivative of dimethyl ~-4-cyclohexen-1,2-dicarboxylate with a substituted propiolic acid phenyl ester [equation (1311. 7 4 The Robinson annelation continues to take pride of place amongst methods for cyclohexenone ring synthesis. This year sees the disclosure of another methyl vinyl ketone equivalent, the sulphone (24)75, and most surprisingly, the first example of a Robinson annelation on a carbohydrate derivative [equation 14) ] .76 The aldol closure of 1,5-diketones to form cyclohexenones has been reported to occur on treatment with alumina in hexane. The method is particularly attractive in its avoidance of both strong acid and strong base allowing the preparation of compounds containing the sensitive iso-propenyl group [equation ( 1 5 ) 1 . 7 7 The tandem Michael-Claisen condensation provides a new method of cyclohexenone ring annelation which is formally equivalent to the Diels-Alder reaction but allows the use of notoriously poorly dienophilic substrates such as cyclohexenones and cyclopentenones. The synthetic value of the reaction is nicely illustrated by its application to the synthesis of the natural products (2)-aristoline and ( 2 )-fukinone (Scheme 14) .78 The Diels-Alder reaction, although possibly proceeding by a double Michael addition mechanism, has also been used in both an i n t e r m o l e ~ u l a rand ~ ~ intramolecular8' sense for the cyclohexanone annelation of the trimethylsilyl enol ethers of 1- acetylcyclohexenes. The intramolecular variant provides remarkably direct access to highly substituted decalones of defined regio- and stereo-chemistry (Scheme 15). Cyclohexenones have also been prepared by the Diels-Alder reaction of alkenyl ketenimines with acrylates,81 in a chiral form by an extension of the Meyers bicyclic lactam chemistry,82 and benzannelated tetralones by the manganese(II1) mediated coupling of aroylacetates with styrene derivatives.8 3 A free-radical cyclisation forms the key step in a new ring annelation (Scheme 16) ,84 with the selenide radical precursor being prepared by an application of the now well established Yamakawa chemistry of phenyl sulphinyl oxiranes. Although in principle the method is applicable to the annelation of a variety of ring sizes, the reaction was most successful when forming six membered rings. Ketone preparation by ring expansion has received considerable attention this year. One particularly interesting method involves the rearrangement of a radical generated by treatment of an a-(halo-
56
Grnrral arid Synthetic Methods
H
(2)
H
- fukinone
Reagents: i , TiC14, Ti(OPri 14
;
ii, LiSPh
;
iii, several steps
Scheme 14
SPh
2: Aldehydes and Ketones
57
ceo&C02Et
iii
'@CO*
Reagents: i , H9Cl2
Et
, ii, toluene , 190 'C,
48h
;
8c0 CO2Et
iii, Na2C03 , EtOH
Scheme 15
0 II
P
SePh
SePh
0 II
Reagents: i, PhSCHCI(CH2)3SePh, base
;
ii, LiC104, Bu3P=0,toluene; iii, Bu3SnH,
AlBN
Scheme 16
58
General and Synthetic Methods
alkyl) B-keto-ester with tin hydride [equations (16) and (17)] . 8 5 , 8 6 Although very successful for one, three or four carbon ring expansions, the reaction unfortunately fails for two carbon expansion. Several research groups have reported studies of cyclic ketone formation by the cationic rearrangements of B-hydroxy sulphur or selenium derivatives. Thus, Krief et al. have reported on the regiochemical preferences of the ring expansions of B-hydroxy selenides [equation (18)I ,87 and Trost et al. have extended the reaction to allow the preparation of a-methoxy or a-phenylthio cycloalkanones by the Lewis acid catalysed rearrangement of a-phenylthio or a-methoxy - B-hydroxysulphones [equation (1911.88 Closely related in terms of the transformation effected, if not in mechanism, are the carbenoid ring expansions. Thus, the treatment of the adduct from the reaction of a a-lithioalkyl 2-chlorophenyl sulphoxide and a cyclobutanone with potassium hydride gives a modest yield of the ring expanded cyclopentanone. Unfortunately the reaction is only satisfactory for cyclobutanones bearing at least one phenyl or alkenyl substituent at C-2 [equation (20)1.89 Interestingly carbenoid-ring expansions have also been extended to allow the preparation of a-phenylthio ketones by treatment of the adducts of bis(pheny1thio)methyllithium and a cyclic ketone with two equivalents of an alkyllithium [equation (21)I The reaction also has the advantage of being successful in cases where the cuprous triflate induced (cationic) rearrangement of the intermediate (25) fails. Finally in this section, the importance of macrocyclic ketones to the perfumery industry continues to inspire some interesting chemistry with syntheses of large ring ketones by twog1 or threeg2 carbon ring expansions being reported. 2
Synthesis of Functionalised Aldehydes and Ketones
Unsaturated Aldehydes and Ketones. - Several oxidative approaches to unsaturated aldehydes and ketones have been reported; these include the oxidations of allyl B-oxoesters or allyl l-alkenyl carbonates with palladium(I1) phosphine complexes in nitrile solvents of [equation (22)] the chloral oxidation of B-phenylthioketones to B-phenylthioenones,94 and the palladium (11) oxidation of Mannich products to enaminones. 9 5 Particularly
59
2: Aldehydes and Ketones
H
TkOEt ,CHCl3
6
Me
&H
HO
?Me
-& H
H
76 'lo
(19)
60
General and Synthetic Methods
=&o 0
Reagents: i , DIBAL. MeCu,HMPA,THF
;
ii, McLi
;
iii, BrCHZCOZEt
S c h e m e 17
OTMS
fJJ$-& 90 O/*
2: Aldehydes and Ketones
61
impressive, in view of the delicate nature of the products, is the preparation of a variety of polyunsaturated acetylenic ketones by pyridinium dichromate induced 1,3-oxidative rearrangement of 96 enynols [equation (23)1. The conjugate reduction of af3-olefinic ketones with diisobutylaluminium hydride using methylcopper catalysis in HMPA containing solvent mixtures has now been extended to allow conjugate reduction-trapping via the 'ate' complexes; unfortunately, this is only successful with quite reactive electrophiles (Scheme 17) .97 The reagent mixture has also been found to effect the partial reduction of as-acetylenic to aB-olefinic ketones, a method which is noteworthy in allowing the reduction of a conjugated acetylene in the presence of an isolated alkyne function [equation (2411.9 8 The a-methylenation of ketones has been achieved by reaction of their enol silane derivatives with bormomethyl methyl ether with tin(I1) bromide catalysis followed, in the same pot, by DBU treatment. The yields, although very variable, can be good [equation (25)1. 99 Although the preparation of enones by cycloaddition strategies involving nitrile oxides is well established, less use has been made of nitrone cycloadditions for this purpose. However it has been found that treatment of the A4-isoxazolines, formed by the reaction between acetylenes and nitrones, with m-chloroperbenzoic acid gives enones in very high yields. Most of the reported examples contain an electron withdrawing substituent at the enone a- position to give regioselectivity in the cycloaddition [equation (26)I . 100 a,@-Unsaturated ketones have been prepared by the palladium(0) catalysed coupling of aroyl chlorides with ketenes which were usually generated in situ from an acid chloride and tertiary amine. The mechanism is complex and involves the palladium mediated decarbonylation of the acid chloride [equation (27)I .lol Sulphoxide chemistry has been exploited in several ways for the synthesis of enones. Thus, 4-hydroxyalk-2-enones have been found to be readily available by the reaction of an aldehyde with a l-(phenylsuphinyl)alkan-2-one in the presence of diethylamine [equation (28)I . lo2 Yamakawa et al. have continued their exploration of the chemistry of phenylsulphinyl epoxides. This year they have described the preparation of enones by the lithium
Cenerul und Synthetic Methods
62
wo t PhSOCHzCOMe
----C
OH
b
0
-
II
I
0
I
SPh
iii , iv c--
PhS
Reagents : i , PhSOCH(CI)CH2CH2SPh, b a s e
;
0
ii, P h S N a , EtOH; iii,MCPBA; i v , A
Scheme 18
2: Aldehydes and Ketones
63
perchlorate - tributylphosphine induced rearrangement of these substrates,lo3 and their use as precursors of divinylketones (Scheme 18) .lo4 One very flexible approach to aO-unsaturated ketones is by Wadsworth-Emmons olefination of an aldehyde with a 6-ketophosphonate. Japanese workers have increased the flexibility of this approach by developing a new synthesis of a'6'-unsaturated-a-phosphinylketones by a Favorskii type rearrangement of a,a'-dihaloketones induced by the enolate of ethyl (diethoxyphosphinyl)acetate.lo5 The use of the product in the Wadsworth-Emmons reaction for the preparation of divinyl ketones was also described [Scheme 191. lo5 The rearrangement may also be induced by other active methylene enolates such as those from malonic esters or O-cyanoesters. WadsworthEmmons chemistry has also been extended to the preparation of a,Bunsaturated aldehydes by using a phosphonate in which the aldehyde group is protected as an enamine. 106 The preparation of B -unsaturated ketones has attracted considerable interest with perhaps the most remarkable approach being the discovery of the 13-cleavage of bis(homoally1ic) potassium alkoxides. In this route a carboxylic ester is treated with an excess of an allylic Grignard reagent to give the corresponding tertiary alcohol, which on warming with potassium hydride loses one allyl group to form, after work-up, the unsaturated ketone, often in very respectable yields (Scheme 20).lo7 The authors have studied the relative rates of cleavage of differently substituted allyl groups and extended the reaction to lactone starting materials . I o 7 other routes to By-unsaturated ketones include the reaction of acylstannanes with allylic halides,lo8 the palladium catalysed coupling of vinyl iodides with O-aminovinyl zinc reagents"' and by an application of the ene reaction.110 a-Substituted Aldehydes and Ketones. - The preparation of both a-hydroxy' l1 and a-methoxyketones112 by hypervalent iodine oxidation of silyl enol ethers in the presence of boron trifluoride etherate has been reported. The product obtained is dependent on whether water or methanol is used as solvent; indeed the use of other alcohols as solvent permits the preparation of a variety of a-alkoxyketones [equation (2911. The same authors have also reported that lead(1V) acetate may be substituted for iodosobenzene in these reactions, although with some reduction in ~ie1d.l'~ The
Grrirml arid Svtitlwric. Methods
64
ii
R=Y
4ph -
0
CO*Et
0 Reagents: i , (EtO)2POCHNaC%R
;
iii, PhCHO , N a H , DME,
ii , p -MeC6H4CH0, N a H , diglyme,13O0C ,
A
Scheme 19
- B"4---$ OH
Me
i
B u C 0 2 Me
Me
I
ii ,iii
0
+
Bu
Bu
5 : 1 Reagents: i , CH2C(Mc)CH2MgCI
;
ii, KH , HMPA
iii, aq. NH4CL
Scheme 2 0
2: Aldehydes and Ketones
65
use of 2-sulphonyloxaziridines (26) to convert silyl enol ethers to a-hydroxyketones has also been described. Impressively this reagent is sufficiently mild to allow the isolation of the intermediate a-silyloxy epoxide which is converted to the a-hydroxyketone by treatment with either acid or f1~oride.l'~ An interesting carbon-carbon bond forming approach to the preparation of hydroxymethyl ketones is by the reaction of the methanol dianion synthon (27) with esters, tertiary a i d e s , nitriles or, rather less successfully, acid chlorides. Although only applicable to non-enolizable carboxylic acid derivatives the convenience of this one pot procedure should make it a useful alternative to the electrophilic hydroxylation reactions (Scheme 21) .l15 The preparation of fluorinated ketones has received considerable attention this year. Trifluoromethyl ketones have been prepared by the reaction of Grignard reagents with ethyl trif luoroacetate, and perf luoroalkyl ketones by the reaction of In both perf luoroalkyllithium reagents with esters and lactones.'17 cases the stabilization of the tetrahedral intermediate by electronwithdrawing fluorine substituents prevents over-reaction and carbinol formation. Fluoromethyl ketone enol ethers, and hence fluoromethyl ketones, have been prepared by the reaction of 1,2,3-triols with tetrabutylammonium fluoride and methanesulphonyl fluoride. Particularly when combined with a Claisen rearrangement, the method shows considerable potential for the synthesis of complex f luoromethyl ketones (Scheme 22) .11* The monof luorination of 6-diketones has been achieved by treatment of their silyl enol ethers with 5 % gaseous fluorine in nitrogent1l9 and either mono or difluorination of benzylic ketones may be achieved by their anodic oxidation in acetonitrile and triethylamine trihydrofluoride; in the latter reactions the extent of the fluorination is controlled by the oxidation potential selected.120 The regioselective monochlorination of the less substituted side of a ketone, often a difficult transformation, has been achieved by the use of a methoxycarbonyl as a removable Lastly on the subject of regiocontrolling group (Scheme 23) .12' halogenation, tetrabutylammonium tribromide has been used to prepare a range of phenacyl bromides from the corresponding acetophenones, 22 and a-iodo ketones have been prepared conveniently and in high yield by the meta-chloroperoxybenzoic acid oxidation of
66
General und Synthetic Methods
(26) Me3Si CHzOH
i.ii _ 1 ) 1
1
iii
iv
OH Ph Reagents: i, BunLi
;
i i , C02; iii, Bu’Li,
THF,
- 25’C
;
iv,PhCONMe2
;v
. H30+
S c h e m e 21
Reagents : i , base
;
ii, PhCHO; iii, LiAlHb; i v , TBDMSCL, imidazole; v , BubNF, MeSO2F;
vi, A
Scheme
22
67
2: Aldehydes and Ketones
Cl
0
Reagents : i, (Me0I2CO, NaH,PhH
;
ii, SOC12, CH2CL2 ; iii , 5 0 % H2S04 ,A
S c h e m e 23
i
H
SPh
...
Ill
42
e.e. p
4
y
o
H Reagents: i , L D A , Et20
; ii,
P h b N Y P h H
( P h S ) Z ; iii, (COzHI2, H 2 0
Scheme 24 OL i
4k B ut
xs
0
__F
Ph
Ph T e a
Ph
General and Synthetic Methods
68
enol silanes in the presence of sodium iodide and 123 hexamethyldisilazine. Chiral a-sulphenylated ketones of modest enantiomeric purity have been prepared by the sulphenylation of ketone imines derived from R (+) -a-phenylethylamine (Scheme 24) ,124 and a convenient largescale, one-pot synthesis of sulphonylated propanones from chloroacetone has been described. 125 Since sulphur functionality is often introduced next to a ketone for reasons of activation or regiocontrol, its removal is a reaction of some importance and the discovery that activated zinc in a mixture of THF and saturated aqueous ammonium chloride can achieve, not only the desulphonylation, but also the desulphinylation or desulphenylation of a-sulphur substituted ketones, should prove valuable. 126 a-Telluroketones have hitherto been a virtually unknown class of compound: however two preparative methods are now available. In the first, telluration of a lithium enolate is achieved by treatment with phenyl tellurium iodide [equation (30)1,127 and in the second the reaction of a ketone, or preferably its silyl enol ether, with 4-methoxyphenyltellurium trichloride gives a tellurium(1V) derivative [equation (3111.128 Finally, the preparation of B-ketophosphonates by the base catalysed rearrangement of vinylic phosphates,12' and the use of the Enders chiral hydrazones for the synthesis of homochiral a-silyl ketones have been reported (Scheme 25) .130 Dicarbonyl Compounds. - Several syntheses of monoprotected forms of the simplest possible dicarbonyl compound, glyoxal, have been reported. The methods include the Swern oxidation of 2,2-diethoxyethanol where the product could be used, without isolation, in Wittig or Grignard chemistry,131 and a preparation of the same diethylacetal from the commercially available 6-ethoxyacrylonitrile (Scheme 25) 132 More complex 1,2-dicarbonyl compounds are also often more useful in a monoprotected form and much recent work in the area has addressed this point. Thus a-keto acetals may be obtained by treatment of a solution of the sulphone (28) in an alcohol, with mild base; the reaction probably involves a cyclopropanone intermediate. The starting sulphone (28) is readily available by the acylation of methylthiomethyl p-tolyl sulphone with an a-alkoxy ester (Scheme 2 7 ) . 1 3 3 a-Keto acetals have also
.
been prepared by the reaction of a-cyano acetals with Grignard or
2: Aldehydes and Ketones
69
J SiMezBu'
Reagents : i , SAMP; ii , L D A
;
-A iv
ii ,iii
N /O 'M ,.SiMe2But e
iii , MegSiOTf ; iv , 0 3
Scheme 25
-
EtO
i,ii
1,
CN
Reagents : i , NBS, EtOH
;
EtoxoAc EtO
EtO
CN
ii , KOAc , 18 - c r o w n - 6 , MeCN
S c h e m e 26
PhCHzO Reagents : i, NaH
;
CHO
111
ii, H 3 0 + ; iii, PhCH20H , DABCO
Scheme 2 7
EtO
;
iii,K2C03 , MeOH, H 2 0
alkyllithium reagents (Scheme 28),134 and Fetizon et al. have adapted their chemistry of 1,4-dioxen-2-yllithium to allow the preparation of a-keto thioacetals. 1 3 5 Free a-keto aldehydes, which generally exist in the a-hydroxy-a,B-unsaturated aldehyde tautomer, have been prepared by an interesting two step rearrangement of a-cyano-a-hydroxymethyl epoxides [equation (32)1 .136 The preparation of monoprotected 1,3-diketones has also inspired some novel chemistry. In particular Japanese workers have studied the reaction of 1,3-dioxolan-2-ylium cations (291, species that are readily prepared by the reaction of trityl tetrafluoroborate with a dioxolane and which are isolatable, with carbon nucleophiles. Although a wide variety of nucleophiles were tried, the authors have chiefly studied the reactions with silylketene acetals and morpholine enamines, with the latter providing a remarkably high yielding route to mono-protected 1,3-diones [equation (33)3 . 13'
The preparation of either a- or $ - keto acetals
by the regioselective reduction of a 2,3-epoxy acetal followed by oxidation to the monoprotected diketone has also been described. 138 Several new methods have been developed for the synthesis of 1,4-diketones. Perhaps the simplest of these, although only applicable when symmetrical compounds are required, is by the iodosoben~ene'~~ or lead (IV) acetate14' mediated oxidative dimerisation of silyl enol ethers [equation (3411. Unsymmetrical 1,4-diketones have been prepared by an analogous oxidative approach in which ceric ammonium nitrate is used to effect the coupling of a ketone with an enol acetate.14' Another enolate acetonylation method uses the synthon (30) which, with palladium(0) catalysis couples, in rather variable yield, with a variety of tributylstannyl enolates and a-tributylstannyl ketones [equation (35)1.142 A totally different approach to 1,4-diketones is by the reaction of alkyllithium or Grignard reagents with the iron tricarbonyl complexes of a,$-unsaturated ketones [equation ( 3 6 ) 1 .143 The preparation of both 1,4- and 1,5- diketones by the palladium(I1) catalysed hydration of alkynones has been studied.144
Lhst year the rather curious methylene insertive dimerisation of ketones in the presence of dimethylformamide and potassium was reported. Mechanistic studies in which N-phenyl-N-methylformamide was substituted for dimethylformamide have led to the isolation of an enaminone intermediate which suggested the modification of the reaction so as to allow the preparation of unsymmetrical
2: Aldehydes and Ketones
71
-
.. ...
i
EtC(0Et l 3
Reagents : i , M e C O C N
;
Et C (OEt ) 2 COMe
EtC(OEt),CN
ii , "Me-" ; iii, H3O +
Scheme 28
(32)
pyridine ___c
CHO Br
% 4 "4 n
n
[:I
+
Ph
BFi-
Ph
(29)
/
Me
Ph-0
MeLi
Fe
oc'
I 'co co
Ph
(33)
.
1 ,5-diketones (Scheme 29) 145
1,4-Diazabicyclo[2.2.2]octane
(DABCO) has been found to catalyse the self condensation of aB-unsaturated ketones to form 2-methylene-1,5- diketones [equation ( 3 7 )I
Also of interest is a study of the conjugate addition reactions of the allenic cuprate (31) to form 2-alken-1,5-dione~,'~~ and a series of publications on the preparation of a wide variety of dicarbonyl compounds by Michael additions to 2-(N-methylanilino)acrylonitrile (32).148 Di-ketone or keto-aldehyde monodimethylacetals have been prepared by the electrooxidative cleavage of cyclic B-hydroxy sulphides. The method is applicable to a wide range of ring sizes and allows the preparation of quite remotely difunctionalised Similar long chain diketones may be compounds [equation ( 3 8 ) 3 .14' prepared by the palladium catalysed reaction of a ketonic alkylzinc reagent with an acid chloride [equation (39)I .150 Palladium catalysed coupling of these reagents with enol triflates and vinylic or allylic halides also appears to be feasible, although as yet these reactions are only exemplified by a very few examples. 150 3
Protection and Deprotection of Aldehydes and Ketones
The value of that pre-eminent carbonyl protecting function, the acetal, has now been increased by the development of a functionalised derivative modified so as to allow the deprotection to be carried out under basic conditions. In this the initial dioxolanation is performed with 2-(2-pyridy1)propane-l13-diol using conventional Dean and Stark conditions, but deprotection is effected by N-methylation followed by treatment with potassium carbonate or sodium hydroxide. The method's chief weakness appears to be the introduction of another chiral centre into the protected molecule (Scheme 30) .151 A very comprehensive study of the scope of the Noyori dioxolanation of aldehydes with 1,2-bis((trimethylsilyl)oxy) ethane in the presence of trimethylsilyl trifluoromethanesulphonate has been published. This exemplary study systematically examines the range of functionality tolerated and the effect of introducing unsaturation, the only limitation encountered being for aldehydes containing amine functionality. The extreme mildness of this method is well illustrated by equation (40).152 Also of relevance to acetal protection are reports of the use of a polystyryl
2: Aldehydes and Ketones
73
Ph
BU'
Me Reagents:
i , N a H , HC02Et
; ii,
PhNHMc
;
iii , K . THF , PhCOEt
Scheme 29
-
Ph
Ph
(37)
0 OMe
__c
(38)
OMe
J Et
n
(39)
General and Synthetic Methods
74
OH
Reagents : i ,
PhH, TsOH, Dean-Stark
;
i i , acetonc.Mc1; iii, lequiv. NaOH
Scheme 30
78 ‘10
2: Aldehydes and Ketones
75
diphenylphosphine - iodine complex to catalyse their formation,153 and the use of iron(II1) chloride dispersed on silica gel to effect their deprotection [equation (41)I .154 Polyphosphoric acid trimethylsilyl ester has been reported as a catalyst for the preparation of thioacetals from carbonyl compounds and t h i ~ l s , ' and ~ ~ the deprotection of diphenyl and diethyl thioacetals has been achieved with a mixture of m-chloroperoxybenzoic and trif luoroacetic acids in dichloromethane. 156 Monothioacetals may be prepared in respectable yields by the treatment of an acetal with tributyltin thiophenoxide in the presence of boron trifluoride etherate. 157 Imine type derivatives have never been popular for the protection of carbonyl groups, probably because those groups that are sufficiently stable to be useful are not easily removed under acceptably mild conditions. However several research groups are trying to change this situation. Thus the oxidative deprotection of dimethylhydrazones with sodium perborate in acetic acid,158 of tosylhydrazones with an in situ generat-ed peroxysulphur intermediate,15' and of simple hydrazones with dinitrogen tetroxide16' have all been reported. Dinitrogen tetroxide may also be used for the deprotection of oxirnes,l6' a conversion that may alternatively be achieved by treatment with a bentonite earth although Beckmann rearrangement was a problem with some substrates.16' 4
Reactions of Aldehydes and Ketones
Aldol and Other Reactions of Enolates. - The generation of enolates of defined geometry is an important element in many modern methods of acyclic stereocontrol, and consequently a recent publication from Still's group reporting new equilibrium data for a variety of acyclic lithium enolates and the derivation of MM2 force field parameters for ketone and aldehyde lithium enolates should raise widespread interest.162 The aldol reaction has been applied to a variety of new substrate types; these include examples in which a zinc enolate derived from a 3-ketopyranose provides the nucleophilic partner, demonstrating that the elimination of O-oxygen fuctionality need not be a problem with sugar enolates [equation ( 4 2 ) I ,163 and studies on the use of fluoroketone zinc164 and aluminium165 enolates in the
General and Synthetic Methods
76
Ph
0
Reagents : i, T i C 1 4 , (Me3Si)20 I ii, P C C ; i i i , (PhCH2I2NH+CF3COZ-
S c h e m e 31
2: Aldehydes and Ketones
77
reaction. Although there are now numerous methods for achieving an aldol reaction in a diastereoselective manner, enantioselective aldol reactions are not as well documented. This year a detailed study of the effect of various chiral lithium amide bases on the stereochemical course of the aldol reaction of benzaldehyde with ethyl t-butyl ketone has been published. Although the chemical yields were always high, the enantiomeric excesses were very variable with amide ( 3 3 ) giving the best result (68% ee). 166 The reaction of boranes with a-diazocarbonyl compounds is well established for the stereo- and regiodefined synthesis of internal enol boranes, but has not been applicable to terminal enol boranes where a migration of hydrogen from boron to carbon is required. However, it has now been found that with dicyclohexylborane this migration occurs cleanly to give methyl ketone boron enolates The diastereoselective aldol reactions of the [equation ( 4 3 ) I boron enolates of ethyl ketone have been studied with the aim of 168 applying the reaction in macrolide synthesis. Perhaps the best known variant on the aldol reaction is the Lewis acid catalysed reaction between an enol silane and an acetal. Several new catslysts for this, the Mukaiyama reaction, have been reported. These include trityl salts,169 trityl chloride in the presence of tin(I1) chloride,170 electrogenerated acid,l7l and a variety of rhodium complexes,172 allowing the reaction to be performed under a variety of mild, and in the last case, neutral conditions. The synthetic value of Johnson and co-workers modificiation of the reaction using chiral acetals to effect an enantioselective aldol reaction has been somewhat reduced by the difficulty of removing the chiral auxiliary. They have now reported that the acetals derived from butane-1,3-diol not only react with silyl enol ethers under titanium tetrachloride catalysis in the presence of hexamethyldisiloxane with very high diastereoselectivity, but also that the resulting B-alkoxy ketones can easily be deprotected to the free aldol by pyridinium chlorochromate oxidation and treatment with dibenzylammonium trifluoroacetate (Scheme 31). 173 a-Bromoketones have been found to react with aldehydes in the presence of cerium salts, with the product obtained showing an interesting dependence on the particular cerium salt used. Thus when the reaction is performed with cerium(II1) chloride in the
presence of either sodium iodide or tin(I1) chloride aldols are formed, but with cerium(II1) iodide the a,B-unsaturated ketone is 174 obtained [equation (44)3 . The use of tin(I1) chloride to catalyse the reaction between silyl enol ethers and aldehydes or a ~ e t a l s ' and ~ ~ the involvement of a transient titanium enolate in the titanium(1V) chloride mediated aldol reaction of aryl alkyl ketones with aromatic aldehydes17 have been reported. The aldol-type reaction of an aldehyde with an a,@-unsaturated ketone which occurs in the presence of 1,4-diazobicyclo[2,2,2loctane (DABCO) has received further study.177 A rather different approach to these products is by the reaction of 2-lithiopropenal with aldehydes. The reagent may be prepared by treating the cyclic acetal (34) with two equivalents of sec-butyllithium, the first equivalent deprotonating the allylic position and the second adding to the acetone formed in the subsequent fragmentation. Best results were obtained when the anion was trapped with aromatic aldehydes, the reaction with ketones being very slow and low yielding (equation 178 (45)I . Interestingly simple chiral aldols have been prepared by the Baker's yeast reduction of a-methylene-8-hydroxy ketones. The preparation suffers from the disadvantage that the diastereomers require separation but, particularly when R was small, very high enantiomeric excesses were obtained [equation (46)1 .I7' Several research groups have reported non-aldol approaches to B-hydroxy aldehydes and ketones. These approaches include a non-reductive route from 4 ,5-dihydroisoxazoles (Scheme 32) ,180 the use of methallylmagnesium chloride as an acetone enolate equivalent,18' and by the boron trif luoride etherate,182 trimethylsilyl iodide183 or trimethylsilyl triflate183 catalysed rearrangement of epoxy alcohols [equation (47)l. This last reaction is particularly interesting in that it not only permits the construction of a quaternary carbon centre but, in combination with the Sharpless allylic epoxidation, should allow it to be done in an enantioselective fashion. Conjugate Addition Reactions. - Although several different copper(1) salts have been recommended as precursors in the preparation of lithium organocuprates, no side-by-side comparisons have previously been reported. However Bertz and co-workers have now measured the
2: Aldehydes and Ketones
Ph
CeI3 c-
79
+
Nal, CeC13 ___c
ph
PhCHO
(34)
Ar
q,, ArCHO
t CH*=C=CHOLi
(44)
Gcw erul mid Sy r i t h et ic Methods
80
OS03Me
are
Ph
Ph
Ph Ph
Reagents : i, McSOq, PhMe ; ii , NaNOZ
;
iii, HCOzH
Scheme 32
,Me
R OH
0
2: Aldehydes and Ketones
81
ratio of 1,4 to 1,2 addition in both THF and ether for the reaction of an alkyl (butyl) or an aryl (phenyl) cuprate with 2cyclohexenone, and find that the best results are obtained with CuCN or CuBr. Me2S.184 The goal of achieving good asymmetric induction in the conjugate addition of a chiral cuprate reagent remains elusive: however some encouraging results have been obtained in an extensive study of amido cuprates where the enantiomeric excesses,although highly variable, could reach as high as 83%. 185 The preparation and conjugate addition reactions of aalkoxycuprates (35) have also been described. 186 Alkylcopper reagents, like cuprates, are normally prepared by the reaction of an organolithium or Grignard reagent with a copper(1) salt. However it has now been found that they may also be synthesised by the reaction of an alkyl bromide with activated copper, which was prepared by the lithium naphthalide reduction of CuI.PBu3 in tetrahydrofuran. The process allows the preparation of functionalised alkylcopper reagents that would not otherwise be The conjugate addition reactions of accessible [equation (48)1. 18' alkylcopper reagents have been found to be accelerated when performed in the presence of trimethylsilyl chloride and tetramethyl -ethylenediamine (TMEDA).188 A variety of organolithium reagents haue been found to add 1,4 to aB-unsaturated ketones in the presence of the bulky Lewis acid methylaluminium bis(2,6-di-tert-butyl-4-methylphenoxide), which is readily prepared from trimethylaluminium and 2,6-di-tert-butyl-4methylphenol. The authors propose that this change in the usual regiochemistry of addition is due to the different reactivity of the enone - Lewis acid complex rather than the formation of a soft organoaluminium nucleophile.189 The conjugate introduction of an ally1 group has been studied by several research groups. Thus the reaction of allyltrimethylsilane with aB-unsaturated ketones has been found to be catalysed by trityl perchloratelgo and the diastereoselectivity of this reaction with some ester substituted enones and titanium tetrachloride catalysis has been studied [equation (49)l.191 The introduction of an a-acetoxyallyl moiety to the B- position of a ketone may be achieved by the fluoride mediated conjugate addition of 1-acyloxy-2-propenyltrimethylsilane to an enone [equation ( 5 0 1 1 . The reaction is regiospecific with respect to both reactants and shows reasonable syn-selectivity.lg2 The conjugate
General and Synthetic Methods
82
Et02C(Cl+)3Br
----c
+
Et02C(C H2l 3 C u
6
L
(48)
CO2Et
26 : 1
Q
+
& 'ViMe3 OAc
OAc
+
Q, H : OAc
4:l
Ph
+ 1 .
Pr'
Li
I .
+
Pr'
H
d'
it.
H
83
2: Aldehydes and Ketones Ph
Ph
r-iOMe
fi
iii ,iv
i,ii
__c
__c
0 Reagents : i, 8u"Li
;
i i , ZnMeZ; iii.
;iv, h y d r o l y s i s
Scheme 33
PhS,
PhSH
..
Me Et
J C0,Me
H 80 'lo
PhS
(52) Me +o
Et
General and Synthetic Methods
84
addition of chiral allylphosphonyl anions to cyclic enones has been studied and been found to proceed with rather variable, but occasionally near complete, enantiocontrol. Ozonolysis of the resulting vinyl phosphonate then leads to a chiral 1,5-keto aldehyde [equation (5111, thus achieving an overall transformation equivalent to the chiral addition of an acetaldehyde enolate. 193 A very similar transformation, the conjugate chiral addition of an acetone enolate to a cyclic enone, has been achieved by the use of chiral zinc or copper azaenolates; optical yields were in the range 71 to 92% (Scheme 33). The conjugate addition of lithiated methyl dithioacetate to a,@-disubstituted enones has been found to show moderate to high syn-diastereoselectivity. 195 The use of potassium fluoride supported on basic alumina to catalyse the Michael addition of nitroalkanes to a@-unsaturated carbonyl compounds,lg6 of phase transfer catalysis to effect the conjugate addition of N-diphenylmethylene benzylamine (36) to c h a l c ~ n e s ,and ~ ~ the ~ 1,4-addition of the alkoxylithium (37), a methanol dianion equivalent, to chiral a-sulphinyl enones,lg8 have been reported. A study of the regioselectivity of the addition of thiols and amines to conjugated allenic ketones has found that with anionic nucleophiles the 13,y -unsaturated product is formed, in distinct contrast to neutral nucleophiles which gave rise to the a,@unsaturated ketone [equation (52)] Lastly, Deslongchamps et al. have made rather neat use of the intramolecular Michael addition of a keto-ester enolate to an ynone followed by an intramolecular trapping to form tricyclic compounds [equation (53)I . 2 0 0 References
.’’’
1. 2.
3.
4. 5. 6. 7. 8. 9. 10
W.P.Griffith, S.V.Ley, G.P.Whitcombe, and A.D.White, J. Chem. SOC., Chem. Commun., 1987, 1625. K.S.Kim, S.J.Kim, Y.H.Song, and C.S.Hahn, Synthesis, 1987, 1017. P.E.Morris and D.E.Kiely, J. Org. Chem., 1987, 52, 1149. A.McKillop and L.S.Mills, Synth. Commun., 1987, 17, 647. F.P.Cossio, M.C.Lopez, and C.Palomo, TetrahedronT1987, 43, 3963. J.Muzart, Tetrahedron Lett., 1987, 28, 2131 and 4665. E.J.Parish and T.Wei, Synth. Commun., 1987, 17, 1227. S.M.Gannon and J.G.Krause, Synthesis, 1987, 915. T.Morimoto, M.Hirano, H-Ashiya, H.Egashira, and X.Zhuang, Bull. Chem. SOC. Jpn., 1987, 60, 4143. P.L.Anelli, C.Biffi, F.Montanari, and S.Quici, J. Org. Chem., 1987, 52, 2559.
2: Aldehydes and Ketones 11. 12.
13. 14.
85
R.Schobert, Synthesis, 1 9 8 7 , 7 4 1 . C.M.Amon, M.G.Banwel1, and G.L.Gravatt, J. Org. Chem., 1 9 8 7 , 52 , 4851. C.M.Afonso, M.T.Barros, and C.D.Maycock, J.Chem.Soc., Perkin Trans. 1, 1 9 8 7 , 1 2 2 1 . D.F.Taber, J.C.Amedio, and K.Jung, J. Org. Chem., 1 9 8 7 , 52, 5621.
18. 19. 20.
B.Byrne and M.Karras, - , 1 9 8 7 , 28, 7 6 9 . T.Nakano, Y.Ishii, and M-Ogawa, J. Or Chem., 1 9 8 7 , 5 2 , 4 8 5 5 . O.Bortolini, S.Campestrini, F . D i d , G.Modena, andT.Valle, J. Org. Chem., 1 9 8 7 , 52, 5 4 6 7 . Y.Lin, D.Ma, and X.Lu, Tetrahedron Lett., 1 9 8 7 , 28, 3 1 1 5 . R.J.Linderman and D.M.Graves, Tetrahedron Lett., 1 9 8 7 , 28, 4 2 5 9 . H.Chikashita, Y.Morita, and K.Itoh, Synth. Commun., 1 9 8 7 , = ,
21.
P.S.Vankar, R.Rathore, and S.Chandraseka~an,Synth. Commun.,
22. 23.
J.Lou and W.Lou, Synthesis, 1 9 8 7 , 1 7 9 . J.M.Aizpurua, M.oiarbide, and C.Palomo, Tetrahedron Lett.,
24.
J.M.Aizpurua, M.Oiarbide, and C.Palomo, Tetrahedron Lett.,
25. 26. 27.
J,Tsujiand M.Minato, Tetrahedron Lett., 1 9 8 7 , 28, 3 6 8 3 . S.Torii, T.Inokuchi, and Y-Hirata, Synthesis, 1 9 8 7 , 3 7 7 . H.C.Brown, J.S.Cha, N.M.Yoon, and B.Nazer, J. O r g . Chem., 1 9 8 7 ,
15. 16. 17.
.
677. 1987 , 17 , 195. 1987, 1987,
52 , -
2,5 3 6 1 . 28,
5365.
5400.
31.
J.S.Cha, J.E.Kim, S.Y.Oh, J.C.Lee, and K.W.Lee, Tetrahedron Lett., 1 9 8 7 , 28, 2 3 8 9 . J.S.Cha, J.E.Zm, and K.W.Lee, J. Org. Chem., 1 9 8 7 , 52, 5 0 3 0 . J.D.Cha, J.E.Kim, S.Y.Oh, and J.D.Kim, Tetrahedron Lett., 1 9 8 7 , 28, 4575. J.S.Cha, J.E.Kim, M.S.Yoon, and Y.S.Kim, Tetrahedron Lett.,
32.
R.J.P.Corriu, G.F.Lanneau, and M.Perrot, Tetrahedron Lett.,
33. 34. 35. 36.
J.S.Chaand S.S.Kwon, J. Org. Chem., 1 9 8 7 , 52, 5 4 8 6 . E.Keinan and D.Perez, J. Or . Chem., 1 9 8 7 , 52, 2 5 7 6 . C-Petrier and J.Luche, Tetrzhedron Lett., 1 9 8 7 , 28, 2 3 4 7 . T.Sakai, K.Miyata, K.Hondo, M.Utaka, and A.TakedZ Bull. Chem. SOC. Jpn., 1 9 8 7 , 60, 3 4 2 1 . T.Sakai, K.Miyata, MIUtaka, and A.Takeda, Bull. Chem. S O C .
28. 29. 30
-
1987,
37. 38. 39. 40.
28,
6231.
1987,
28,
3941.
Jpn.,
1987,
60,
1063.
C.Cardellicchio, V.Fiandanese, G.Marchese, and L.Ronzini, Tetrahedron Lett. , 1 9 8 7 , 28, 2 0 5 3 . S.Collins and Y.Hong, Tetrahedron Lett., 1 9 8 7 , 28, 4 3 9 1 . Y.Tominaga, S.Kohra, and A.Hosomi, Tetrahedron E t t . , 1 9 8 7 , 1529.
~~
41.
28,
~
C-Fehr, J.Galindo, and R.Perret, Helv. Chim. Acta, 1 9 8 7 ,
2,
1745.
42. 43. 44.
F-Weiberth and S.S.Hal1, J. Org. Chem., 1 9 8 7 , 52, 3 9 0 1 . A.R.Harris, Synth. Commun., 1 9 8 7 , 1 7 , 1 5 8 7 . D.Perez, N.Greenspoon, and E.Keina6 J. Org. Chem., 1 9 8 7 ,
52,
5570. 45. 46. 47.
A.R.Katritzky and W.Kuzmierkiewicz, J. Chem .Sot., Perkin Trans. I, 1 9 8 7 , 8 1 9 . T.Shono, S-Kashimura, Y.Yamaguchi, O.Ishige, H.Uyama, and F.Kuwata, Chemistry Letters, 1 9 8 7 , 1 5 1 1 . T.Shono, S.Kashimura, Y-Yamaguchi, and F-Kuwata, Tetrahedron Lett., 1 9 8 7 , 28, 4 4 1 1 .
48.
M-Yamamoto, K-Suzuki, S.Tanaka, and K.Yamada, Bull. Chem. S O C . Jpn., 1987, 60, 1523. 49. n A j e r a andM.Yus, Tetrahedron Lett., 1987, 28, 6709. 50. X.Gu, N.Nishida, I.Ikeda, and M-Okahara, J. Org. Chem., 1987, 52, 3192. 51. D.J.Coveney, V.F.Pate1, and G.Pattenden, Tetrahedron Lett., 1987, 28, 5949. 52. M.Matsukawa, J.Inanaga, and M.Yamaguchi, Tetrahedron Lett., 1987, 28, 5877. 53. H.C.Brown, M.Srebnik, R.K.Bakshi, and T.E.Cole, J. Amer. Chem. SOC., 1987, 109, 5420. 54. G.Parrinello and J.K.Stille, J. Amer. Chem. SOC., 1987, 109, 7122. 55. K.Kikukawa, T.Idemoto, A.Katayama, K.Kono, F.Wada, and T.Matsuda, J. Chem. S O C . , Perkin Trans. I, 1987, 1511. 56. S.L.Buchwald, A-Sayers, B.T.Watson, and J.C.Dewan, Tetrahedron Lett., 1987, 28, 3245. 57. M.Makosza andy.Owczarczyk, Tetrahedron Lett., 1987, 28, 3021. 58. T.Mukaiyama, R.S.J.Clark, and N.Iwasawa, Chemistry Lett., 1987, 479. 59. M.Ceruti, I.Degani, and R.Fochi, Synthesis, 1987, 79. 60. K.Fuji, M.Node, Y.Usami, and Y.Kiryu, J. Chem. SOC., Chem. Commun., 1987, 449. 61. A.A.Ammann, M.Rey, and A.S.Dreiding, Helv. Chim. Acta, 1987, 70, 321. 62. R.L.Danheiser and S.Savariar, Tetrahedron Lett., 1988, 28, 3299. 63. K.Hiroi, H.Nakamura, and T.Anzai, J. Amer. Chem. SOC., 1987, 109, 1249. 64. B.Corbe1, D.Hernot, J-Haelters, and G.Sturtz, Tetrahedron Lett., 1987, 28, 6605. 65. H.J.Monteiro, Tetrahedron Lett., 1987, 28, 3459. 66. K.Nakatani, Tetrahedron Lett., 1987, 28,165. 67. H.Matsuyama, Y.Miyazawa, Y.Takei, and M.Kobayashi, J. Org. Chem., 1987, 2,1703. 68. A.J.H.Klunder, W.B.Huizinga, P.J.M.Sessink, and B.Zwanenburg, Tetrahedron Lett., 1987, 28, 357. 69. M.P.Sibi, K-Shankaran, B.I.Alo, W.R.Hahn, and V.Snieckus, Tetrahedron Lett., 1987, 28, 2933. 70. V.I.Ognyanov and M.Hesse, Helv. Chim. Acta, 1987, 70,1393. 71. S.C.Welch, J.Assercq, J.Loh, and S.A.Glase, J. Org. Chem., 1987, 52, 1440. 72. A.J.Poss and R.K.Belter, J. Org. Chem., 1987, 52, 4810. 73 * E.J.Corey and A.K.Ghosh, Tetrahedron Lett., 1987, 175. 74. E.J.Corey and W.Su, Tetrahedron Lett., 1987, 28, 5241. 75. R.K.Haynes and S.C.Vonwiller, J. Chem. SOC., Chem. Commun., 1987, 92. 76. R.V.Bonnert and P.R.Jenkins, J. Chem. SOC., Chem. Commun., 1987, 6. 77. W.B.Kover, J.Jones, A.P.de Aguiar, and H.L.A.von Holleben, Tetrahedron, 1987, 43, 3199. 78. T.H.Chan and C.V.C.Prasad, J. Org. Chem., 1987, 52, 110 and 120. 79. H.Hagiwara, A.Okano, T.Akama, and H.Uda, J. ChemTSoc., Chem. Commun., 1987, 1333. 80. K.J.Shea, W.M.Fruscella, R.C.Carr, L.D.Burke, and D.K.Cooper, J. Amer. Chem. SOC., 1987, 109, 447. 81. E.Differding, O.Vandevelde, B.Roekens, T.T.Van and L-Ghosez, Tetrahedron Lett., 1987, 28, 397. 82. A.I.Meyers and B.A.Lefker, Tetrahedron Lett., 1987, 28, 1745. ~
~
2: Aldehydes and Ketones
87
88.
F.Z.Yang, M.K.Trost and W.E.Fristad, Tetrahedron Lett., 1 9 8 7 , 28 , 1 4 9 3 . T.Satoh, M.Itoh, and K.Yamakawa, Chemistry Lett., 1 9 8 7 , 1 9 4 9 . P.Dowd and S.Choi, J. Amer. Chem. SOC., 1 9 8 7 , 109, 6 5 4 8 . P.Dowd and S.Choi, J. Amer. Chem. SOC., 1 9 8 7 , 109, 3 4 9 3 . A.Krief and J.L.Laboureur, Tetrahedron Lett., 1 9 8 7 , 28, 1 5 4 5 ; A.Krief, J.L.Laboureur, and W.Dumont, Tetrahedron Lett., 1 9 8 7 , 28, 1549. B.M.Trost and G.K.Mikhai1, J. Amer. Chem. SOC., 1 9 8 7 , 109,
89.
R.C.Gadwood, 1.M.Mallick and A.J.DeWinter, J. Org. Chem., 1 9 8 7 ,
90.
ED-Abraham, M-Bhupathy, and T.Cohen, Tetrahedron Lett., 1 9 8 7 , 28 , 2 2 0 3 . S.Bienz and M.Hesse, Helv. Chim. Acta, 1 9 8 7 , 7 0 , 2 1 4 6 . H.Suginome and S.Yamada, Tetrahedron Lett., 1 9 8 7 , 28, 3 9 6 3 . I.Minami, M.Nisar, M.Yuhara, I.Shimizu, and J.Tsuji, Synthesis, 1 9 8 7 , 9 9 2 . A. de Groot, R.M.Peperzak, and J.Vader, Synth. Commun., 1 9 8 7 , 17, 1607. S.Murahashi, Y.Mitsue, and T.Tsumiyama, Bull. Chem. SOC. Jpn.,
83. 84. 85. 86. 87.
4124. 52, 774. 91. 92. 93. 94. 95.
1 9 8 7 , 60 , 3285
97.
D.LiotG, D.Brown, W.Hoekstra, and R.Monahan, Tetrahedron Lett., 1 9 8 7 , 28, 1 0 6 9 . T.Tsuda, H.Satomi, T-Hayashi, and T.Saegusa, J. Org. Chem.,
98.
T.Tsuda, T.Yoshida, T.Kawamoto, and T.Saegusa, J. Org. Chem.,
96.
1987,
52,
439.
1 9 8 7 , 52, 1 6 2 4 . 9 9 . M.Hayashi and T.Mukaiyama, Chemistry Lett., 1 9 8 7 , 1 2 8 3 . 1 0 0 . A.Padwa, D.N.Kline, and J.Perumattam, Tetrahedron Lett., 1 9 8 7 , 28, 913. 1 0 1 . T.Mitsudo, M.Kadokura, and Y-Watanabe, J. Org. Chem., 1 9 8 7 , 52, 3186. 1 0 2 . J.Nokami, A.Nishimura, M.Sunami, and S.Wakabayashi, Tetrahedron Lett., 1 9 8 7 , 2 8 , 6 4 9 . 1 0 3 . T.Satoh M.Itoh, T.Ohara, and K.Yamakawa, Bull. Chem. SOC. Jpn., 1 5 8 7 , 60, 1 8 3 9 . 1 0 4 . T.Satoh, T.Kumagawa, A.Sugimoto, and K.Yamakawa, Bull. Chem. SOC. Jpn., 1 9 8 7 , 60, 3 0 1 . 1 0 5 . T.Sakai, E.Amano, K.Miyata, M.Utaka, and A.Takeda, Bull. Chem. SOC. Jpn., 1 9 8 7 , 60, 1 9 4 5 . 1 0 6 . M.K.Tay, E.E.Aboujaoude, N.Collingnon, and P.Savignac, Tetrahedron Lett., 1 9 8 7 , 28, 1 2 6 3 . 1 0 7 . R.L.Snowden, S.M.Linder, B.L.Muller, and K.H.Shulte-Elte, Helv. Chim. Acta, 1 9 8 7 , 7 0 , 1 8 5 8 and 1 8 7 9 . 1 0 8 . M.Kosugi, H.Naka, S.Haradz H.Sano, and T.Migita, Chemistry Lett., 1 9 8 7 , 1 3 7 1 . 1 0 9 . E.Negishi and K.Akiyoshi, Chemistry Lett., 1 9 8 7 , 1 0 0 7 . 1 1 0 . 0-Achmatowicz, E . B i a l e c k a - F l o r j a f i c z y k , J.Golifiski, and J.Rozwadowski, Synthesis, 1 9 8 7 , 4 1 3 . 111. R.M.Moriarty, M.P.Duncan and O.Prakash, J. Chem. SOC., Perkin Trans. I, 1 9 8 7 , 1 7 8 1 . 1 1 2 . R.M.Moriarty, 0-Prakash, M.P.Ducan, R.K.Vaid, and H.A.Musallam, J. Org. Chem., 1 9 8 7 , 52, 1 5 0 . 1 1 3 . R.M.Moriarty, I.Prakash, and R.Penmasta, Synth. Commun., 1 9 8 7 , 1 7 fl 7Ll9, J. Org. Chem., 1 9 8 7 , 52, 9 5 4 . 1 1 4 .
[email protected]$tand, A , Tetrahedron Lett., 1 9 8 7 , 28, 115. A.R; atri zk$3 18
1 1 6 . X.Creary, J. Org. Chem., 1 9 8 7 , 52, 5 0 2 6 . 1 1 7 . H.Uno, Y.Shiraishi, K.Simokawa, and H. Suzuki, Chemistry Lett., 1987, 1153. 1 1 8 . M.Shimizu, Y.Nakahara, S.Kanemoto, and H-Yoshioka, Tetrahedron Lett. , 1 9 8 7 , 2 8 , 1 6 7 7 . 1 1 9 . S.T.Purringtox C.L.Bumgardner, N.V.Lazaridis, and P.Singh, J. Or Chem., 1 9 8 7 , 52, 4 3 0 7 . 1 2 0 . E.Zaurent, B.Marqu=, R.Tardive1, and H.Thiebault, Tetrahedron Lett., 1 9 8 7 , 28, 2 3 5 9 . 1 2 1 . N.De Kimpe, W x e Cock, and N.Schamp, Synthesis, 1 9 8 7 , 1 8 8 . 1 2 2 . S.Kajigaeshi, T.Kakinami, T.Okamoto, and S.Fujisaki, Bull. Chem. SOC. Jpn., 1 9 8 7 , 60, 1 1 5 9 . 1 2 3 . C.Sha, J.Young, and T.Jean, J. Org. Chem., 1 9 8 7 , 52, 3 9 1 9 . s . 1 2 4 . J-Youn, R.Herrmann, and I.Ugi, Synthesis, 1 9 8 7 , 1 1 2 5 . R.Davis, Synth. Commun., 1 9 8 7 , 823. 1 2 6 . R.A.Holton, D.J.Crouse, A.D.Williams and R.M.Kennedy, J. Org. Chem. , 1 9 8 7 , 52, 2 3 1 7 . 1 2 7 . T.Hiiro, N.Kambe, A.Ogawa, N.Miyoshi, S.Murai, and N.Sonoda, Synthesis, 1 9 8 7 , 1 0 9 6 . 1 2 8 . H.A.Stefani, J.V.Camasseto, and N.Petragnani, Synth. Commun., 1987, 17, 443. 1 2 9 . T.CaloSropoulou, G.B.Hammond, and D.F.Wiemer, J. Org. Chem., 1 9 8 7 , 52, 4 1 8 5 . 1 3 0 . D.EndeZ and B.B.Lohray. Angew. Chem., Int. E d . Engl., 1 9 8 7 , 26, 3 5 1 . 1 3 1 . KBernard, A.Doutheau, and J.Gor6, Synth. Commun., 1 9 8 7 , 1807. 77. 1 3 2 . J.H.Babler, Synth. Commun., 1 9 8 7 , 1 3 3 . K.Ogura, T.Uchida, T-Tsuruda, and K.Takahashi, Tetrahedron Lett., 1 9 8 7 , 28, 5 7 0 3 . 1 3 4 . m B a b l e r anrC.J.Marcuccilli, Tetrahedron Lett., 1 9 8 7 , 4657. 1 3 5 . M.Fgtizon, P.Goulaouic, and I.Hanna, Synthesis, 1 9 8 7 , 5 0 3 . 1 3 6 . L.Khamliche and A.Robert, J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 1869. 1 3 7 . Y.Hayashi, K.Wariishi, and T.Mukaiyama, Chemistry Lett., 1 9 8 7 , 1243. 1 3 8 . Y.D.Vankar, N.C.Chaudhuri, and C.T.Rao, Tetrahedron Lett., 1987 , 551. 1 3 9 . R.M.Moriarty, 0-Prakash, and M.P.Duncan, J. Chem. Soc., Perkin Trans. 1, 1 9 8 7 , 5 5 9 . 1 4 0 . R.M.Moriarty, R.Penmasta, and I.Prakash, Tetrahedron Lett., 873. 1987, 1 4 1 . E.Baciocchi, G.Civitarese, and R.Ruzziconi, Tetrahedron Lett., 1987, 28 , 5357. 1 4 2 . M.KosuZ, K.Ohashi, K.Akuzawa, T.Kawazoe, H.Sano, and T.Migita, Chemistry Lett., 1 9 8 7 , 1 2 3 7 . 1 4 3 . S.E.Thomas, J. Chem. Soc., Chem. Commun., 1 9 8 7 , 2 2 6 . on Lett., 1 9 8 8 , 1 4 4 . K.Imi, K.Imai, 3127. 1 4 5 . S.Kiyooka and T.Yamashita, Chemistry Lett., 1 9 8 7 , 1 7 7 5 .
.
17,
17,
17,
28,
28,
28,
146. D.Basavaiah, V.V.L.Gowriswari, and T.K.Bharathi, Tetrahedron Lett., 1 9 8 7 , 28, 4 5 9 1 . 1 4 7 . R.Matsuoka, Yxoriguchi, and I.Kuwajima, Tetrahedron Lett., 1987, 28, 1 2 9 9 . 1 4 8 . H.AhlbGcht and A.von Daacke, Synthesis, 1 9 8 7 , 24; H.Ahlbrecht, M.Dietz, and L.Weber, Synthesis, 1 9 8 7 , 2 5 1 ; and H.Ahlbrecht and M.Ibe, Synthesis, 1 9 8 7 , 9 2 9 . 1 4 9 . S.Torii, T.Inokuchi, and Y.Araki, Synth. Commun., 1 9 8 7 , 17,
2: Aldehydes and Ketones
89
1797. 1 5 0 . Y.Tamaru, H.Ochiai, T.Nakamura, and Z.Yoshida, Angew. Chem., Int. Ed. Engl., 1 9 8 7 , 26, 1 1 5 7 . 1 5 1 . A.R.Katritzky, W.Fan, and Q.Li, Tetrahedron Lett., 1 9 8 7 , 2, 1195. 1 5 2 . J.R.Hwu, L.Leu, J.A.Rob1, D.A.Anderson, and J.M.Wetze1, J. Org. Chem., 1 9 8 7 , 5 2 , 1 8 8 . and G-Palumbo, Synthesis, 1 9 8 7 , 3 8 6 . 1 5 3 . R.Caputo, C.F=reri, 1 5 4 . A-Fadel, R.Yefsah, and J.Salaiin, Synthesis, 1 9 8 7 , 3 7 . 1 5 5 . M.Kakimoto, T.Seri, and Y.Imai, Synthesis, 1 9 8 7 , 1 6 4 . 1 5 6 . J.Cossy, Synthesis, 1 9 8 7 , 1 1 1 3 . 1 5 7 . T.Sato, T.Kobayashi, T.GoJo, E.Yoshida, J.Otera, and H.Nozaki, Chemistry Lett., 1 9 8 7 , 1 6 6 1 . 1 5 8 . A.McKillop and J.A.Tarbin, Tetrahedron, 1 9 8 7 , 43, 1 7 5 3 . 1 5 9 . Y.H.Kim, H.K.Lee, and H.S.Chang, Tetrahedron Lett., 1 9 8 7 , 4285. 1 6 0 . S.B.Shim, K.Kim, and Y.H.Kim, Tetrahedron Lett.; 1 9 8 7 , 28, 6 4 5 . 1 6 1 . C-Alvarez, A.C.Cano, V.Rivera, and C.Mdrquez, Synth. Commun., 1987, 279. 1 6 2 . G.W.Spears, C.E.Caufield, and W.C.Stil1, J. Org. Chem., 1 9 8 7 , 52 , 1226. 1 6 3 . S.Handa, R.Tsang, A.T.McPhai1, and B.Fraser-Reid, J. Org. Chem., 1 9 8 7 , 52, 3 4 8 9 . 6481. 1 6 4 . M.Kuroboshi and T-Ishihara, Tetrahedron Lett., 1 9 8 7 , 1 6 5 . N.Kuroboshi, Y.Okada, T.Ishihara, and T.Ando, Tetrahedron Lett., 1 9 8 7 , 28, 3 5 0 1 . 1 6 6 . A.Ando and T.Shioiri, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 6 2 0 . J. Org. Chem., 1 6 7 . J.Hooz, J-Oudenes, J.L.Roberts, and A.Benderly, 1 9 8 7 , 52, 1 3 4 7 . 1229. 1 6 8 . 1.PateEon and C.K.McClure, Tetrahedron Lett. , 1 9 8 7 , 1 6 9 . M.Murakami, H-Minamikawa, and T.Mukaiyama, Chemistry Lett., 1987, 1051. 1 7 0 . T.Mukaiyama, S.Kobayashi, M.Tamura, and Y.Sagawa, Chemistry Lett., 1 9 8 7 , 4 9 1 . 1 7 1 . S.Torii, T.Inokuchi, S.Takaqishi, H.Horike, H.Kuroda, and K.Uneyama, Bull. Chem. SOC. Jpn., 1 9 8 7 , 60, 2 1 7 3 . 1 7 2 . S.Sato, I.Matsuda, and Y.Izumi, Tetrahedron Lett., 1 9 8 7 , 6657. 1 7 3 . I.R.Silverman, C.Edinqton, J.D.Elliott, and W.S.Johnson, J. Org. Chem., 1 9 8 7 , 52, 1 8 0 . 1 7 4 . S.Fukuzawa, T.Tsuruta, T.Fujinami, and S.Sakai, J. Chem. S O C . ~ Perkin Trans I, 1 9 8 7 , 1 4 7 3 . 1 7 5 . N-Iwasawa and T.Mukaiyama, Chemistry Lett., 1 9 8 7 , 4 6 3 . 1 7 6 . C.R.Harrison, Tetrahedron Lett., 1 9 8 7 , 28, 4 1 3 5 . 1 7 7 . D.Basavaiah, T.K.Bharathi, and V.V.L.Gowriswari, Synth. Commun., 1 9 8 7 , 1 7 , 1 8 9 3 . 1 7 8 . M.A.Tius, D.P.AXrab, and X.Gu, J. Org. Chem., 1 9 8 7 , 5 2 , 2 6 2 5 . 1 7 9 . M.Utaka, S.Onoue, and A.Takeda, Chemistry Lett., 1987,971. 1 8 0 . S.Kwiatkowski, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 4 9 6 . 1 8 1 . W.H.Bunnelle, M.A.Rafferty, and S.L.Hodqes, J. Org. Chem., 1 9 8 7 , 52, 1 6 0 3 . 1 8 2 . M.ShimZaki, H.Hara, K-Suzuki, and G.Tsuchihashi, Tetrahedron Lett., 1 9 8 7 , 28, 5 8 9 1 . 1 8 3 . K.Suzuki, M-Miyazawa, and G-Tsuchihashi,Tetrahedron Lett., 1 9 8 7 , 28, 3 5 1 5 . 1 8 4 . S.H..BeZz, C.P.Gibson, and G.Dabbagh, Tetrahedron Lett., 1 9 8 7 , 28 , 4251. 2040. 1 8 5 . R.K.Dieter and M.Tokles, J. Amer. Chem. S o c . , 1 9 8 7 , 1 8 6 . R.J.Linderman, A.Godfrey and K.Horne, Tetrahedron Lett., 1 9 8 7 ,
28,
17,
28,
28,
28,
109,
General und Synthetic Methods
90
28 , 3911. 1 8 7 . KM-Wehmeyer and R.D.Rieke, J. Org. Chem., 1 9 8 7 , 52, 5 0 5 6 . 27. 1 8 8 . C.R.Johnson and T.J.Marren, Tetrahedron Lett., 1 9 8 7 , 1 8 9 . K.Maruoka, K.Nonoshita, and H.Yamamoto, Tetrahedron Lett., 1 9 8 7 , 28, 5 7 2 3 . 1 9 0 . M.HayaZi and T.Mukaiyama, Chemistry Lett., 1 9 8 7 , 2 8 9 . 1 9 1 . D.Mobili and B.De Lange, Tetrahedron Lett., 1 9 8 7 , 2 8 , 1 4 8 3 . 4649. 1 9 2 . J.S.Panek and M.A.Sparks, Tetrahedron Lett,, 1987,-%, 1 9 3 . D.H.Hua, R.Chan-Yu-King, J.A.McKie, and L.Myer, J. Amer. Chem. SOC., 1 9 8 7 , 5026. 1 9 4 . m a m a m o t o , M.Kanoh, N.Yamamoto, and J.Tsuji, Tetrahedron Lett., 1 9 8 7 , 28, 6 3 4 7 . 1 9 5 . S.Berrada and?.Metzner, Tetrahedron Lett., 1 9 8 7 , 28, 4 0 9 . 1 9 6 . D.E.Bergbreiter and J.J.Lalonde, J. Org. Chem., 1 9 8 7 , 52, 1601. 1 9 7 . V.Dryanska, K.Popandova, and C.Ivanov, Synth. Commun., 1 9 8 7 , 17, 211. 1 9 8 . KH-Posner, M.Weitzberg, and S.Jew, Synth. Commun., 1 9 8 7 , 611. 1 9 9 . T.Sugita, M.Eida, H.Ito, N.Komatsu, K.Abe, and M. Suama, J. Org. Chem., 1 9 8 7 , 52, 3 7 8 9 . 2 0 0 . J.Lavall6e and P.Deslongchamps, Tetrahedron Lett., 1 9 8 7 , z , 3457.
28,
109,
17,
4
Carboxylic Acids and Derivatives BY D. W. KNIGHT 1 Carboxylic Acids
General Synthesis. - Powerful nucleophiles such as Grignard reagents and organolithiums add efficiently to the a-silyl carboxylates (1) in a Michael sense to give the saturated acids (2) These can be converted into the corresponding a-unsubstituted acids ( 3 ) simply by exposure to sodium hydroxide. Yields are generally excellent, despite the presence of a beta substituent but, as yet, interception of the intermediate enolate by alkylations or Peterson reactions is not viable except in the latter cases when the counter cation is magnesium. The proline-derived amides (4) offer an alternative to the chiral, terpene based derivatives developed by Oppolzer and Helmchen amongst others, for the elaboration of B,B-disubstituted 2 acids ( 5 ) by asymmetric Michael additions . In these examples, the nucleophiles used are DBU complexes of alkyl Grignard reagents: whereas enantiomeric enrichments of up to 82% have been achieved following acid hydrolysis [3M HCl], the chemical yields are not so impressive [ < s o % ] . Amides derived from oxazolidones of the type developed by Evans and his colleagues are one of the most useful classes of derivatives for the elaboration of chiral carboxylic acids despite the fact that problems can be encountered at the final hydrolysis stage. A significant advance in this respect is the finding that hydrolysis of the penultimate products [e.g. ( 6 ) + ( 7 ) 1 can be achieved by exposure to lithium hydroperoxide3.Chiral 2-halophenoxypropionic acids (8) can be obtained by enantioselective hydrolyses of the corresponding racemic methyl esters using the enzyme systems PLE of PPL4. In favourable cases, up to 7 0 % eels have been realised at E. 50% conversion although the yields are widely variable. A much more general method for the elaboration of chiral acids which seems destined to become a standard procedure within the obvious constraints involves asymmetric hydrogenation of di- and tri-substituted a,@-unsaturated acids [ ( 9 ) + ( 1 0 ) 1 using 5 BINAP-ruthenium(I1) complexes . Enantiomeric enrichments are in
General and Synthetic Methods
92
the order of 83-97% with chemical yields generally being quantitative. Typical conditions are to treat a solution of the substrate in methanol with 4-100 atmospheres of hydrogen at ambient temperature for 1 2 - 7 0 hours. Phenyl, hydroxy and acetoxy groups at least are tolerated and both enantiomers of the catalyst ligand are available. The presence of the free acid function is essential presumably so that an appropriate complex with the catalyst can be formed: the methods can also be applied successfully to asymmetric reductions of 6,y-unsaturated acids. Related reductions under very similar conditions have also been effected using (aminoalkyl) ferrocenylphosphine-rhodiumcomplexes: in most examples, the eels are >97% at least when a-aryl unsaturated acids are the substrates6. Two promising methods for the direct oxidation of alcohols to acids have been reported this year. Dimanganese heptoxide [Mn207], a red, explosive liquid when isolated, can be readily and apparently safely generated in solution in carbon tetrachloride and is capable of oxidising simple alcohols at temperatures as low as - 7 0 ° C . The reagent will clearly be limited in this respect however, as it will also efficiently cleave alkenes (for further examples, see under Primary alcohols can also Diacids) and oxidise ethers to esters’. be oxidised to acids using sodium hypochlorite and a catalytic amount of 4-methoxy-2,2,6,6,-tetramethyl piperidine-1-oxyl free radical under phase transfer conditions8. Yields in simple cases are essentially quantitative with a reaction time of only “ - 5 minutes, suggesting that the method could be successfully applied to more complex substrates. A classical method for the synthesis of carboxylic acids is to carboxylate an organometallic intermediate. In cases where such an intermediate is difficult to form, the principle of “reverse transmetallation” may solve the problem 9 This consists of setting up an equilibrating mixture of the starting material and its lithio derivative then carrying out a double transmetallation by sequential additions of mercuric chloride and methylmagnesium bromide. The final carboxylation step then follows and in some cases, overall yields are in excess of 8 0 % . Dry carboxylate salts can be prepared by treating an alkyl ester with the tellurium reagents NaHTe, Na2Te In spite of their rather noxious nature, the or Na2Te2 in hot DMF”. tellurium reagents are at least easy to prepare; the by-product is a sodium alkyltelluride [RTeNa].
.
93
3: Carboxylic Acids and Derivatives
Anhydrides. - Anhydrides derived from tartaric acids or malic acids could be useful synthetic intermediates were it not for the difficulties in preparing or isolating them. This limitation has been partly solved by the finding that the trihaloacetyl derivatives (11) [and the corresponding malic acid anhydrides] can be obtained from the parent diacids by heating with a trihaloacetic anhydride in A new route to the Fulgides (13) consists of a palladium dioxan". acetate-iodine catalysed carbonylation of the butyn-1,4-diols (12)12. The substituents [R1 and R2] include methyl, phenyl and fury1 examples and the yields are usually good. In a reaction which closely resembles the classical condensatioqof dimedone with aldehydes or ketones, the silyloxymaleic anhydride (14) reacts with ketones to give excellent yields of the dimers (15)13. Returns from aldehydes are somewhat lower. Diacids. - Alkenes are efficiently cleaved to the corresponding diacids by brief exposure to potassium permanganate adsorbed onto silica gel14. The reagent seems to be relatively indifferent to the type of alkene; yields are usually respectable [e.g.(16)+(17) in 62% yield] in this experimentally convenient procedure which may well cause less epimerisation than other methods. When applied to (1811, the Sharpless alkene cleavage procedure allylic alcohols 1% based on ruthenium trichloride leads to diacids (19) (60-92%1 with the l o s s of at least one carbon15. Both of these methods are also effective in the preparation of keto-esters from more highly substituted substrates. [see also ref. 7 1 . The intermediate 1,2-diols in the latter process can be independently cleaved and oxidised to the corresponding diacids using some rutheniumlead or rutheniumbismuth oxides16 The BINAP-ruthenium complexes mentioned above5 can also be used to prepare either enantiomer of methylsuccinic acid (20) in up to 90% ee by catalytic hydrogenation of itaconic acid and derivatives17 [See also ref. 1211. Another useful addition to the chiral pool is the diacid (21) which can be obtained essentially optically pure on a 50g scale by hydration of chlorofumaric acid 18 using commercial pig heart fumarase as the catalyst
.
.
Diacid Half-esters. - For a number of years, the major advances in this area have concerned various asymmetric hydrolyses of symmetrical or meso- diesters generally using either pig liver esterase [PLEI or
M, M’= Li, MgX
(2)
OCOCR,
-
R 3 g :
BINAP RU
-
RH -“ 3 2 :
H2
R2
R*
07x0 0
(11) R = CI or F
(1 0)
(9)
R’
R2
co
..
A
*
_)=o OQoSiMe30
0 0
3: Carboxylic Acids and Derivatives
95
porcine pancreatic lipase [PPL]. A full account of hydrolyses of cyclic meso-diesters ( 2 2 ) to the useful half esters (23) has been published 19 . In general, 3,4, and 6-membered ring compounds give monoesters (23) with >97% ee's [chem yields:-54-96%1 but little selectivity is found with examples of cyclopentane diesters. The method is much less effective when applied to the corresponding meso-diacetates. PLE also catalyses the hydrolysis of malonates (24) to the (El-monoesters (25); the best results are obtained when 'R' is 5-butyl [ 9 0 % chem yield with 9 6 % eel2'. Similarly, the succinates (26) can be obtained from the corresponding diesters using PPL but only at =.SO% conversion21. However, when 'R' is either methyl or benzyl, the recovered diester is essentially optically pure. The chiral monoester ( 2 7 ) has been prepared by an asymmetric Diels-Alder reaction using an unsymmetrical fumarate diester followed by selective hydrolysis22. Enantioselective hydrolyses of fi-hydroxyglutarate derivatives ( 2 8 ) using o-chymotrypsin as catalyst lead to the enantiomers ( 2 9 1 , although the optical yields are extremely dependent upon the solvent, the pH of the solution and the nature of the s ~ b s t i t u e n t24. ~ ~ Under optimum conditions however, both chemical and optical yields are >go%. PLE can also be used for this transformation as well as for selective hydrolyses of 3,4-epoxyadipates; the meso form leads to monoester (30) with 99% ee whereas the %-pair can be separated, in excellent chemical and optical yields, by using kinetic resolution conditions24 . Cyclic meso-anhydrides undergo asymmetric methanolysis in the presence of various chiral alkaloids25. Although many of the results are not impressive, the monoester (31) has been obtained with u p to 70% ee. Hydroxy-acids. - As in previous years, the main emphasis in this area has been on the preparation of chiral a-hydroxy-acids ( 3 2 ) . One of the best sources of the (&I-enantiomers of acids ( 3 2 ) is the corresponding (G)-o-amino-acids following diazotisation, intramolecular displacement and hydrolysis with overall retention of - isomers can be prepared via the configuration. The less common (D) (&I-chloro-acids followed by esterification and finally an SN2 displacement for which caesium carboxylates are especially suited2 6 . (PI-a-Hydroxy-acids are also available from asymmetric reductions of the corresponding a-keto-acids f o r which the microorganism Proteus
H
CI
C02Me C02Me
(27)
(28)
(29)
oPco2H C02Me
Me02C
C02Me C02H
C02H
H
,OH
RXCOpH
3: Carboxylic Acids and Derivatives
97
vulgaris in combination with methyl viologen is especially suitable27. A neat if somewhat longer approach to acids (32) consists of homologation of (S)-lactic acid to the dibromobutene (33) followed by regiospecific metallation and condensation with an aldehyde. The resulting diol derivatives ( 3 4 ) can, amongst other uses, be oxidatively cleaved to the hydroxy-acids (32); overall yields are excellent28 12.31-Wittig rearrangements of the chiral ester (35) derived from pulegone give, after hydrolysis, excellent yields (chemical and optical) of the a-hydroxy-acids (36)29. The rearrangements must be carried out in THF-HMPA and unfortunately are not useful when a substituent is present on the alkene function. A full account has been given of the preparation of disubstituted a-hydroxy-acids (37) by nucleophilic attack onto 2-acyl-oxazines the optical yields from this also derived from p ~ l e g o n e ~ ~Whereas .
.
procedure are excellent [80-loo%], the chemical returns leave something to be desired. A rather more specialised approach to either enantiomer of the disubstituted acids [ (37); R1=Mel has as a key step the bromolactonisation of N-acryloyl (S)-prolines31 . A qeneral approach to racemic aryl- and heteroaryl-a-hydroxyacids ( 3 8 ) consists of carbonylations of aryl iodides in the presence of lithium hydroxide and an alcohol using PdCl2(PPh3I2 as the catalyst32 . Yields vary between 61 and 72% and the sequence prFsumably proceeds the corresponding keto-acid which is su5seguently reduced by a Meerwein-Pondorf process. Acetates and benzoates of a-hydroxy-acids can be selectively hydrolysed by treatment with benzylamine or butylamine, a procedure which could be 0 2 considerable use in the manipulation of multifunctional substrates33 . The optical purity of 0-hydroxy-acids can be improved from ca.80% to 100% by crystallisation of the derived dibenzylammonium salts34. As the former level of optical purity is often achieved by reductions of the corresponding P-keto-acids by various means such as asymmetric hydrogenation or using microbial methods, this finding seems likely to have a number of significant applications. The y-keto-acid (39) is reduced stereospecifically to the syn isomer (40) in 8 3 % yield (isolated as the lactone) upon treatment begs the with Dibal-H and zinc chloride in T H F - t ~ l u e n e ~ ~This . question of whether such a procedure would be suitable €or reductions of chiral keto-acids with racemisation.
98 Keto-acids.
Generul and Synthetic Methods
-
The one-carbon nucleophile (41) behaves as an
equivalent of the acyl anion (42) [see also ref. 811 and undergoes smooth Michael additions to, for example, 2-cyclopentenone in the presence of HMPA; trapping of the intermediate enolate by primary alkyl halides leads to the intermediates (43) and thence to the y-keto-acids (44)36. Butyrolactones (45) can be directly oxidised to the y-keto-acids (46) in 71-97% yields by electrolysis using an oxide-covered nickel net electrode in 3 0 % aqueous potassium hydroxide37
.
Unsaturated Acids. - Significantly higher yields, usually double, are obtained from the classical Perkin synthesis of cinnamic acids when caesium acetate is used in place of the more conventional sodium salt3? The vinyl chloride [ (47); X = H l derived from propiolic acid undergoes smooth hydrogen-lithium exchange upon treatment with two equivalents of A-butyl lithium3'. The resulting lithio derivative [(47); x=Lil couples reasonably efficiently with a range of electrophiles [RI, RCHO, RCOR; 40-70%] leading to the o,c-unsaturated acids (48) after the usual hydrolysis steps developed by Corey. The intermediate protected derivatives vide infral prior to presumably could be further homologated [%. exposure of the carboxylic acid function. Full details have been given of the useful carbonylation procedure whereby vinyl halides (49) are converted into the unsaturated acids (50) in the presence
of Co2C08 and iodomethane under phase transfer conditions4'. Isomeric mixtures are sometimes formed and unfortunately the method cannot be applied to aryl bromides as these starting materials give rise to similar amounts of the acid and the corresponding methyl ketone. Reformatsky reactions involving y-bromosenecioic acid usually lead to mixtures of products. However, prolonged reflux of the reaction mixture in THF affords allows equilibration to the y 41 . isomer [e.g. - (51)] which eventually becomes the sole product It has long been known that low yields of B,y-unsaturated acids can be isolated from the classical Knoevenagel condensation. An optimised procedure for such condensations of aliphatic aldehydes (52) consist of refluxing in xylene with three equivalents of malonic acid and 0.001 equivalent of piperidinium acetate as the catalyst42. Yields of the P,y-unsaturated acids (53) are typically 60-85% of 95-99% (El-isomers but somewhat lower with low molecular weight, volatile, aldehydes [e.g.n-butanall. As well as possibly
3: Carboxylic Acids and Derivatives
0
99
(36)
(37)
(35)
H*HOAc
J
100
General and Synthetic Methods
constituting the current method of choice for the preparation of (El-unsaturated acids (531, the method complements the established, base-catalysed, deconjugative approach to f3,y-unsaturated acids and esters which provides largely the (Z)-isomers starting from (E)-a,e-unsaturated acids or esters. Another very old but much less studied reaction is the carboxylation of alkoxides to give carboxylic acids by a mechanism which appears to resemble a Wittig rearrangement43. The addition of 18-crown-6 has been found to improve the method which still requires high temperatures and very high pressures of carbon monoxide and produces only moderate yields, but of acids which can be rather difficult to prepare in other ways [e.g. (54)-(55) 1 . Many y,&unsaturated acids and esters have been prepared stereoselectively using the enolate Claisen rearrangement; in general, a chair-like transition state is involved as in the formation of largely the anti product (57) from the ester (56). If, however, bulky metal ions are added prior to the rearrangement then formation of the corresponding syn diastereoisomer (58) is favoured44. The cis isomer of ester (56) similary leads to different products depending on the conditions used. Largely the anti isomers (59) are produced by enolate Claisen rearrangements of esters derived 45 from 3-phenylthio allylic alcohols Direct condensation of the crotonate (60) with aromatic aldehydes gives the dienoic acids (61) in which the original double bond stereochemistry is retained46. Presumably the reaction proceeds via cyclisation of the initial alkoxide to give a pyrone which then undergoes base-induced ring opening. Iodination of the phosphorane derived from an ethyl haloacetate gives the salt (62) which condenses efficiently with aldehydes to provide the a-iodo-esters (63)47. These, in turn, can be hydrolysed with concomitant loss of the elements of hydrogen iodide to provide the acetylenic acids (64) in 52-70% overall yields. The corresponding acetylenic esters can be isolated if required simply by using milder basic conditions for the elimination step. This combination appears to be a milder and more efficient approach to acids (64) than the related processes involving the pyrolysis of acyl phosphoranes. Finally in this section is an answer to a decepetively simple problem, that of how to prepare a-chloro-unsaturated acids (65). Direct chlorination of the parent acid would probably lead to attack
.
3: Carboxylic Acids and Derivatives on the alkene function while hydrolyses or hydrogenolyses of the corresponding esters are largely precluded by the sensitivities of the two other functions. A solution, based on earlier studies of Arnold and Kulenovic, is to chlorinate the parent acid dianion using carbon tetrachloride as the halogen source48.
-
Aromatic Acids and Esters. In order to save cross referencing, both acids and esters are included in this section. A wide variety of simple cobalt salts have been examined as alternative catalysts to Co2C08 for the carbonylation of haloaromatics to aromatic acids; in many cases, similar activity was observed49 . Palladium acetate in association with dppp ligands is a very effective catalyst system for the methoxycarbonylation of aryl triflatek5’. The use of the dppp ligand is a distinct improvement relative to PPh3 and the conditions look suitable for large scale preparations as well as for the toleration of a wide range of functional groups. A related but somewhat less mild method can be used to prepare benzyl esters from In a variation of well aryl iodides in around 60% yield”. established Friedel-Crafts methodology, chloral has been shown to react efficiently with electron rich arenes to give the para-substituted homologues (66) and thence the corresponding aromatic acids following hydrolysis by basic hydrogen peroxide52. 2-Benzylbenzoic acids ( 6 8 ) have been obtained in 7 3 - 8 7 % yields by reductions of 3-arylphthalides ( 6 7 ) using triethylsilane and a (Lewis) acid [TiC14 or TFA]53. This provides a useful alternative to hydrogenolysis which is sometimes unsuccessful with such substrates. Arylacetic Acids and Esters. - The analgesic activities of a number of arylacetic acid derivatives continue to stimulate research in this area. Extrapolation of previous results has lead to a method for the direct carbonylation of benzyl bromides (69) based on the catalyst system CoCl -NaBH4-NaOH; yields of arylacetic acids ( 7 0 ) are between 68 and 8 8 %54. The cyanosulphones ( 7 1 ) can be prepared by coupling reactions between aryl iodides and the anion derived from phenylsulphonylacetonitrile using copper (I) iodide in hot HMPA55. Subsequent alkylation [RX, NaH] and degradation [Raney nickel1 then leads to moderate to excellent yields of the arylacetic acids ( 7 2 ) . A less toxic route to the precursors ( 7 1 ) would improve this approach.
I03 The L1.21-aryl shift approach to a-methyl arylacetic acids or esters (74) from aryl ketones (73) and derivatives is certainly one of the most studied reactions in this area. Rather less attractive routes in terms of reagent toxicity which presumably proceed
via
the
corresponding acetal, consist of the treatment of ketones (73) with orthoformates containing perchloric acid and either thallium trinitrateS6 or lead t e t r a a ~ e t a t e ~ ~Much . more attractive is the method whereby 2-hydroxypropiophenone acetals [ (73); X=OH, dimethyl acetall is rearranged to the esters [ (74); R=Me] by treatment with sulphuryl chloride [or SO2 and C12] in methylene chloride at -50°C containing a weak base such as triethylamine or ~ y r i d i n e ~Isolated ~. yields are usually around 85% and chiral transfer is complete with inversion in examples involving pure enantiomers. Thermal rearrangements of the sulphones (75), derived either from lactic acid or valine, are also highly selective giving excellent yields of Similarly, zinc chloride induces esters [ (5)-(74); R=MeI5'. enantioretentive rearrangements of chiral chloro acetalsi(75); C 1 in place of S02R*] derived from lactic acid or alanine; this approach has been applied specifically to Ibuprofen and Naproxen6O. Bromination of the tartrate derived acetals (76) gives largely [>9:11 the
( 2 )-bromide
(77)61.
Subsequent rearrangement, as in the foregoing
examples but using silver tetrafluoroborate,then leads to similarly excellent chemical and optical yields of the (2) enantiomers of acids (74). Ibuprofen can also be prepared in z - 8 5 % yield by oxidation of the corresponding propionaldehyde using molecular oxygen and manganous stearate as catalyst62. Carboxylic Acid Protection. - 2-Haloethyl esters can be cleaved by treatment with sodium hydrogen telluride; the acids are recovered in 84-92% yields63. Despite the noxious nature of tellurium compounds, this method looks worth considering as the only "reagent" consumed is the sodium borohydride used to prepare the tellurium reagent. Tellurium metal can be recovered at the end of the reaction sequence and reused. In contrast, 2-tosylethyl carboxylates are efficiently hydrolysed by tetra-n-butylammonium fluoride [TBAF] in THF [O"C, lh164. Most common protecting groups survive these conditions, including secondary OTBDMS functions (primary OTBDMS is removed almost completely). Ally1 esters in 6-lactams are cleanly and rapidly cleaved by a Tsuji procedure [cat.Pd(PPh3)4,pyrrolidine]; no nucleophilic displacements of other
3: Carboxylic Acids and Derivatives
103
Me0 ArCHO NaH
(59)
h3p?02Et II (62)
&C02H (65)
Me0 =
X
(73)
ArC ' 02R
4
A
OMe r
(74) (75)
y
502r*
104
Gcwrrcrl arid Synrhetic Methods
groups are observed during the brief reaction period65. l-Pyrenyl esters (78) are useful as masked acids as the ester group can be removed cleanly by photolysis [High pressure Hg lamp: MeOH]; the large fluorescent chromophore and the increase in mass when this type of derivative is prepared could also be significant features66. 2 Carboxylic Acid Esters
Esterification. - Two more esterification reagents, ( 7 9 ) " and (80)68, have been reported: both afford between 55 and 95% yields of esters from equivalents of the acid and alcohol components and both require DMAP as a catalyst. The latter is less water sensitive than DCC but neither seem to offer any obvious advantages over existing reagents. An older way to prepare esters (82) is to heat the mixed anhydrides (811, derived from an acid and 2-bromobenzoyl bromide, with an alcohol. It has now been reported that the reaction proceeds smoothly at room temperature in the presence of silver tetraf luoroborate6'. Although clearly not suitable for very large scale work, the method looks to have potential in small scale, sensitive syntheses and can also be used to prepare thioesters. Diphenyl- or dimethyltin dichloride can often be used in place of the acid catalyst in esterifications of acids using an excess of a simple alcohol to the benefit of acid sensitive substrates7'. The acylation of B-hydroxy-ketones using Ac20-DMAP and related methods often suffers from competing p-elimination. This type of side reaction can be suppressed by using cobalt (11) chloride in place of the DMAP71. The reasons behind this effect are unclear. A full account has been given of the ruthenium-catalysed preparation of enol esters ( 8 3 ) by the addition of carboxylic acids to terminal Yields using an extensive range of acids are 6 0 - 9 0 % alkyne~~~ . although the reaction sometimes fails, for example with 2-methyl-2-propenoic acid. Transesterifications of simple enol esters [ (83): R1=H] with primary and secondary alcohols are catalysed by PPL7 3 A further requirement is that the acid residue has a hydrogen at the o position. A variety of immobilized enzyme systems have also been assessed as transesterification catalysts; PPL immobilized on alumina or a similar support looks to be highly suitable74. Such materials look to be very easy to prepare using crude acetone powders or more purified enzyme samples. Particularly interesting
.
3: CarboxylicAcids and Derivatives
105
is the partial transesterification of dimethyl succinate using isopropanol which gives the @)-dimethyl ester (84) [>95%(El ; SO%] : 40%) amongst other and the mixed (S)-diester (85) I>95% (S) examples. Similar reactions can be effected using ally1 alcohol, thus allowing subsequent partial hydrolysis to the corresponding mopoesters to be carried out. The ester group in diisopropylmethylphosphonoacetates can be transesterified by treatment with a primary or secondary alcohol and DMAP in refluxing toluene75
.
General Synthesis of Esters, Thioesters, Dithioesters and Selenoesters. - Methyl esters can be obtained directly from aldehydes by oxidation using PDC in DMF containing si,x equivalents of methanol76. Presumably, oxidation of the latter in particular is relatively slow which is why the method is not useful for the direct conversion of alcohols in general to methyl esters. Yields are generally in the range 60-87% although most aromatic aldehydes are unsuitable substrates due to competing hemiacetal formation. Two equivalents of a primary alcohol (86)are oxidised to the esters (87) upon heating with catalytic amounts of RuHZ(PPh3)4; the method, now reported in full, is also useful for the conversion of appropriate the obvious diols into butyrolactones or v a l e r o l a ~ t o n e s ~ ~Within . constraints of product structure and the requirement for thermal stability, the methods looks to be a useful one. The dangers and lack of stability associated with ;-chloroperbenzoic acid make the finding that the much more stable salt, magnesium monoperphthalate is suitable for conducting Baeyer-Villiger oxidations of considerable ~ i g n i f i c a n c e ~ ~As . doubtless mentioned elsewhere in this volume, this compound will probably soon replace mCPBA although some of the yields obtained do seem to be slightly lower [see also ref. 2531. Selective decarboxylation of the mixed malonates (88) to give It the ethyl esters (89) is possible under Krapcho conditions”. has been pointed out that t-butyloxycarbonyl groups are more easily removed from r-butyl fi-keto esters under these conditions in the absence of added salts. Oxidative decarboxylations of a-keto-acids (90) can be carried out by first forming the corresponding hemiacetal with methanol followed by cleavage using N-iodosuccinimide80. The method, which is an extension of one previously applied to a-hydroxy-acids, typically provides 70-80% yields of the degradation products(91).
106
General and Synthetic Methods
O'R * :A
H
'Br
(77)
a YR \
N
\
K,B,B, (79)
0 RUH2(PPh3)4
R-OH
(86)
180 "C,24h
RAOAR (87)
RYcozEt C02Bz
R -CO2E!
(88)
(89)
3: Carboxylic Acids and Derivatives
107
The one carbon nucleophile (92) is alkylated reasonably efficiently 155-73% yields1 by primary alkyl halides; subsequent electrochemical oxidation in methanol provides the esters (93)81 The anion (92) is thus another equivalent of the one carbon acyl anion (42) 6 . An interesting rearrangement occurs when the disubstituted alkynes (94) are treated with [hydroxy(tosyloxy) iodolbenzene, [PhI(0Ts)OHl leading to esters (95)82. Yields are usually within the range 54-66% and a likely mechanism involves the intermediacy of a vinyl cation, formed by attack of the alkyne onto the iodonium reagent with loss of tosylate. A full account has been given of the generation and chemistry of the homoenolate (96)83. In general, this species is less reactive than a Grignard reagent, as expected, and behaves as a relatively soft nucleophile. As such, under appropriate conditions, it condenses efficiently with aldehydes and acyl halides, adds in a Michael fashion to enones, couples with alkyl halides and aryl halides, the latter requiring a Pd(0) catalyst and adds in an SN2' manner to allylic halides. Similar reactivity is exhibited by the chiral homoenolate ( 9 7 ) of methyl isobutyrate8'. This useful intermediate can be derived in two related ways from optically active methyl B-hydroxyisobutyrate and has been used to prepare a range of a-methyl carboxylates in good yields apparently with little or no racemisation. Yet more new reagents for the f1.41 reduction of conjugated enoates [(98)+(99)1 have been added to the ever growing list during this year. Silicon halides such as phenylsilane, PhSiH3, smoothly but slowly effect the transformation in the presence of catalytic amounts of molybdenum hexacarbonyl or Wilkinson's catalyst85. Yields are generally excellent with the simple substrates examined so far and the method also is applicable to similar reductions of unsaturated amides, acids and ketones including in the latter class, an example of a B,B-disubstituted substrate. Polymer-bound sodium borohydride is also useful f o r such reductions especially when the enone system is doubly activated to Michael additions86. The method whereby such enones are reduced using the Zn-NiC12 system in aqueous 2-methoxyethanol is much improved by the application of u l t r a ~ o u n d ~ ~It . has been pointed out that the Mg-MeOH system which has previously been used for the l1.41 reduction of acrylonitriles and acrylamides is also very suitable for effecting this transformation, especially in the presence of isolated carbon-carbon
108
General and Synthetic Methods
double bonds88. Similarly, sodium hydrogen telluride, NaTeH, will efficiently reduce enones in a [1.41 fashion and is unlikely to attack an isolated double bond8'. Cinnamates only undergo [l - 4 1 reductions when treated with either &-butyl iodide in hot acetonitrilego or with chlorotrimethylsilane, sodium iodide and an alcoholg1. Purely aliphatic substrates tend not to react. Potassium fluoride adsorbed onto basic alumina is a useful reagent for effecting the Michael addition of nitroalkanes to acrylatesg2. The method appears to be a distinct improvement on related systems as, for example, only monoadducts are formed using primary nitroalkanes in yields which are often essentially quantitative. In general, Michael additions to cyclic enoates [ C g . (10011 are not particularly efficient processes (in acyclic systems, species such as RCu.BF3 are often suitable); at least in the case of n-butyl lithium, such additions are effectively catalysed by the presence of copper trimethylsilylacetylide and chlorotrimethylsilane specifically in 4:1 ether-THF mixturesg3. The addition products 1 3 . (10111 are isolated in up to 80% yields and the reagent combination is also effective in Michael additions to often very unreactive 8,e-disubstituted enoate systems; in these cases, yields fall in the range 50-70%. The possibilities of employing other organolithium species has yet to be examined. Some useful stereoselectivities have been observed in a variety of coppermediated Michael additions to y , y-disubstituted enoatesg4. Organocuprates tend to add to (E)-enoates to give mainly the anti diastereoisomers (102) whereas additions to the corresponding (2) isomers lead, not unreasonably, to the related syn diastereoisomers. However, additions of organocoppers to such (2)-enoates give the anti isomers (102). Reasonable explanations of these phenomenon are proposed based on the modified Felkin-Ahn model. A milder and more effective phase transfer system [TEBA-DMFKHC03-60"C] has been developed for the monoalkylation of ethyl nitroacetate; yields of the homologues (103) are usually good ( ~ . 7 0 % ) , although double alkylation can still be a problem especially with reactive electrophiles such as benzyl bromideg5. 0-Silyl enolates undergo a thermal O+C migration of the silyl group when heated to 2 0 0 ° C to give the a-silyl esters (104) via an uncatalysed intramolecular processg6. When treated with N-chloro (or E-bromo) succinimide and sodium ethoxide, acetoacetates (105) undergo a "halo-deacylation" process to provide a simple and
3: Curboxylic Acids and Derivatives
109
Phl(0Ts)OH
R’
MeOH
(94) R’ = Alkyl, aryl, R2 = H, Me, Et
R2
R1AC02Me (95)
F!
phYo2Et
efficient (>80%) route to a-halo-esters ( 1 0 6 ) 9 7 . The method fails with a,o-disubstituted acetoacetates but otherwise appears to be widely applicable. An extensive range of metal halides have been examined for their suitability as reagents for the dehalogenation of a-halo-esters and ketones. Excellent yields can be obtained under a number of conditionsg8. An improved recipe for the Darzens-like preparation of epoxy-esters ( 1 0 7 ) from the corresponding aldehyde and ethyl a ,a-dichloroacetoacetate has been reported". Actual Darzens condensations can be carried out between aryl aldehydes and the thiolanium salt (108); under PTC conditions, yields of the epoxy-esters (109) are generally highloo. The reaction is unusual in that ylides derived from salt (108) do not normally react with carbonyls. However, only poor yields are obtained using higher . homologues of the salt. Diastereoselectivities of up to 92% have been observed in Michael addition of silylcuprates to esters and amides (110) derived from crotonic or cinnamic acids. The initial products (111) can be hydrolysed to the corresponding acids and furthermore, the new 0-silyl group can be exchanged for a hydroxyl function with The related Q-stannyl esters (112) retention of configuration"'. are available from alkylations of enolates of t-butyl esters, generated using lithium dicyclohexylamide, by iodomethyl(tri-nbutyl)stannanelo2. This approach appears to be an improvement on the alternative in which stannyl lithiums or cuprates are added to acrylates. The ester enolate derived from ethyl acetate adds in a Michael fashion to the sulphoxide (113) to give excellent returns of 103 . the y-sulphinyl ester (114) as essentially a single isomer Malonates add in a similarly selective manner. The chemistry of potentially useful w -azido-esters (115) has been examined' 0 4 . Homologues may be prepared by enolisation and alkylation in the usual way and by conversion to the corresponding acid chlorides, again under standard conditions, followed by condensation with Meldrum's acid. A combination of these two processes can thus lead to the B-keto-esters (116). Although it has been established previously that isocyanato acid chlorides (117) could be prepared and isolated, there was no way in which the two very reactive terminal functions of these potentially useful molecules could be distinguished. This can now be done by treatment with a trimethylsilyl ether, the isocyanato-esters (118) being isolated in 70-92% yieldsio5. By using E-trimethylsilyl amines, the corresponding isocyanato amides can be
111
3: Carboxylic Acids and Derivatives
0
t .:.
Bu3s"7C0,'Bu R
F,C-sGOl
& -
N3 (CH2)nC02Me
0
CF3 t .:* E t O 2 C A S f To1
CO,Me 0 (116) n = 1 o r 2
(115)n = 3 o r 4
ROSiMe3
similarly obtained. 0-Silyl enol ethers (1191, derived from thioesters, show excellent lk stereoselectivities in Michael additions to cyclopentenones when Ph3CSbC16 is used as the catalystlo6. Tsujitype homologation of the intermediate cyclopentyl silylenolate [e.g. (120)1 leads to the creation of a third stereocentre [G. (121)I with high selectivity. Phenyl dithioesters (124) in general are not particularly easy to prepare. Thus, a new approach proceeding by coupling of a Grignard reagent (122) with carbon disulphide followed by trapping the intermediate dithiolate (123) with 2-phenyl carbon chloridothionate should be of interest. Yields are in the range of 47-73% and, overall, the approach looks to be generally applicable given the availability of the organomagnesium specieslo7. The lithium enolate (125) of methyl dithioacetate adds in a Michael fashion to a,B-unsaturated ketones often with high SJJ (anti-Houk) stereoselectivitylo8. The selective formation of the isomers (126) can be explained by a mechanism involving intramolecular protonation of the intermediate ketone enolate by the proton o to the dithio function via a cyclic, chair-like transition state. Aryl selenoesters (127) can be prepared in high yields from aryl arylcarbonyl diselenides by tre'atment with triphenylphosphine in ether"'. The intermediates are available from couplings between aroyl selenides and arylselenenyl bromides. Diesters. - Trost and his colleagues have presented full details of their studies into the use of molybdenum complexes in place of palladium-phosphine species as catalysts for couplings between allylic acetates or carbonates and soft nuclephiles such as B-ketoIn general, the molybdenum catalysts tend esters or malonates'". to induce substitution at the more hindered site of the intermediate n-ally1 complex, although the precise nature of the catalyst and the solvent play important roles. Examples include exclusive attack at the tertiary position of linalyl acetate by sodiomalonate (129) in the presence of molybdenum hexacarbonyl; similar reactions of the allylic acetate (128) give largely regioisomer (131) with this catalyst. By contrast, use of Pd[(PPh3)I4 or other molybdenum species leads exclusively to the less hindered isomer (130). Similar homologations of allenic acetates or better, phosphates (1321, using sodiomalonate are best carried out using Pd (dba) as catalyst"' : the products (133) are isolated in up to 80% yields and the couplings are
3: Carboxylic Acids and Derivatives
113
also successful with acetoacetates and phenylsulphonylacetates; one use of these products is as precursors to cyclopentenes112. An alternative strategy for the alkylation of mono-substituted malonates is to use 1- ( E - a l k y l )quinolinium salts as the e l e ~ t r o p h i l e s ~ ~ ~ . Although the yields are not spectacular [29-62%1, the mild conditions may offer some benefits. A general problem with attempted alkylations of enolates of a-trifluoromethyl carbonyl systems is their propensity for undergoing facile $ eliminaion of fluoride. This drawback can be overcome, at least in the case of trifluoromethyl-malonates, by using an electrochemically generated base derived from pyrrolidone. Yields of the final products (134) fall in the range 31-80% with the lower yields being associated with unactivated primary iodides such as n-butyl iodide114. A variety of both malonates and succinates have been obtained from the corresponding acid chlorides by addition of two equivalents of an alcohol in the presence of a catalytic amount of potassium tetracarbonylhydridoferrate, KHFe(C0I4 115. Under these conditions, an HC1 trap is not required. Halogenation of monosubstituted malonates can be achieved using manganese (111) acetate in the presence of chloride ions116. Yields of the resulting a-chloromalonates (135) are good to excellent. A somewhat unconventional approach to a-thiomalonates (138) consists of rhodium acetate induced coupling between a dizomalonate and an allylic sulphide [-. (13611 followed by a [2.3I-sigmatropic Yields of the rearrangement of the intermediate ylide (137)'17. final products [e.g.(138)l in this and related examples are usually very high. Isopropylidene arylmalonates (139) and the corresponding diary1 derivatives can be obtained directly and in generally good to excellent yields from the parent Meldrum's acid by arylation using A range of simple substituents [p-Me, OMe, diaryliodonium salts'18. C1, Ph] can be incorporated. Both the methylthioalkylidene (140) and aminoalkylidene (141) derivatives of Meldrum's acid are available from the corresponding bis (methy1thio)methylidene analogue by displacement of one of the thiol groups using Grignard The exact nature of the final product is determined reagents'".
by the method of work-up; both product types are useful as precursors to Byketo-esters. Michael additions to arylidenemalonates involving the SAMP or RAMP derivatives (142) of cyclohexane-1,3-dione leads to the expected adducts (143) in
General and Synthetic Methods
114
C02Me
I
'@;" (128)
Na'
-
R O / .
f CozMe C02Me -
//
C02Me
//*& / COM ,e
Pd(dba),
(1 33)
(1 32)
F3C
C02Me
RXC02Me
(134)
(135)
R
O
3: Carboxylic Acids and Derivatives
115
essentialy quantitative optical yieldsl2O. Clearly, such products could be further utilised in a number of ways. A number of useful methods for the asymmetric hydrogenation of unsaturated acid derivatives have already been mentioned5' 6' 17. A further example is the successful reduction of 3-substituted itaconates (144) using chiral cationic rhodium complexes121. Good levels of kinetic resolution are observed at just above 50% conversion. Enedioates [e.g. (146)I are selectively reduced upon treatment with a mixture of LiA1H4 and TiClq in THF containing triethylamine122. This type of 11-41 reduction presumably involves a low valency titanium species; as can be seen from the example shown (1471, other alkene functions are not affected. A useful method for the elaboration of mono-2-alkyl tartrates (149) consists of treatment of the tin oxide derivatives (148) with an alkyl halide and the best part of two equivalents of caesium fluoride in DMF at ambient t e m p e r a t ~ r e l ~ ~ . 2,3-Disubstituted glutarate derivatives (150) can be prepared by Michael addition of silylketen acetals to a,B-unsaturated esters using a variety of Lewis acid catalysts which have now been extended to include the clay M o n t m ~ r i l l o n i t eand ~ ~ ~aluminium trif late125. The experimental procedure using the clay appears to be particularly simple while the triflate is capable of inducing additions to 5-substituted acceptors and to B,B-disubstituted ylidenemalonates. In general, diastereoselectivities are poor. These can be improved by a modification in which a,B-unsaturated orthoesters are used as the Michael acceptors with trityl salts as the catalysts126. The protected glutarates (151) are available using related condensations but between silylketen acetals and thioethylidene dithi~lanes'~~. A significant feature of this method is that both reactants can be disubstituted at the centres which are coupled. Condensations between glyoxalamides and a,$-unsaturated esters under typical Stetter [thiazolium salt-catalysedl conditions lead to the a-keto-monoamides (152) in 50-83% yields128. No stereochemical information is available as no examples in which both R and R1 were not hydrogen are quoted. Hydroxy-esters. - A single example suggests that an alternative method for the a-hydroxylation of esters is to heat a silylketen acetal with an N-sulphonyloxaziridine in chloroform129. The sequence presumably proceeds an a-silyloxyepoxide in an analogous way to
General and Synthetic Methods
116
NR2*
Me02C
1
D
Meo2cf. Re'* H C02Me
C02Me
R
(1 45)
(144)
-
C02Me
&
C02Me
\
C02Me
C02Me
(1 47)
(146)
Me02ChC02Me R-X
0,
o,
Sn
'Bu
B;
CsF
j\/CO,Me Me02C : OR (149)
C02Et
O
R
'
3: Curboxylic Acids and Derivatives
117
peracid oxidations of this type of substrate. The useful chiral epoxyesters (153) can be prepared in three steps from (Ll-serine and react smoothly with a variety of lithium diorganocuprates to give high yields of the a-hydroxy-esters (154)130. The same type of product can also be prepared by rearrangement of the corresponding glycidic Ia,B-epoxyl ester triggered by magnesium iodide; the reaction proceeds via the 8-iodo derivative and hence a second deiodination step using tri-n-butyltin hydride has to be included13'. [For the alternative mode of ring opening, see ref. 1641. Complete regioselectivity in favour of the a-isomer is observed and the stereochemistry at the original a-position is retained. A two step sequence has been develofled for the preparation of the more expensive (Rl-rnalic acid dimethyl ester starting from dimethyl (2R,3 R )-tartrate132. Enolate Claisen rearrangements of the ally1 a-hydroxy-esters (155) are highly stereoselective in favour of the erythro isomers (156). The origin of this selectivity appears to be associated with complexation between the lithium enolate and the a-alkoxide function which results in predominant formation of the (E)-enolate geometry133. Consistent with this is the finding that rearrangements of the corresponding (gl-allyl esters lead to the threo isomers of esters (156) and that 0- silylation results in lower stereoselectivities. Asymmetric hydrogenations of a series of pyruvates using chiral pyrrolidinebiphosphine rhodium complexes as catalysts can give up to 87% ee in the a-hydroxy-esters [(154);R1=H) so formed131. The 3-chloro derivatives (157) of these compounds have been obtained by yeast reductions of the corresponding keto-estersi3'. Ratios of the syn and anti diastereoisomers are at best 20:80 but, by way of compensation for this, both are >95% optically pure. Similarly, the a-hydroxy-esters (158) have been obtained from the corresponding As in the foregoing examples, chiral induction a,y-dioxo-e~tersl~~. is good to excellent at the a position but generally poor at the @-site. Protected a-hydroxy-esters of general type (159) have been prepared by kinetic resolution of a racemic mixture employing ester At 5 . 4 0 % chemical yield, the hydrolysis by a Coryneba~teriuml~~. optical purities of the esters are usually in excess of 99%. The acids are not recovered. A purely chemical approach to chiral a,B-dihydroxy-esters features aldol condensations of the 1,3-dioxolane-4-ones (160)
&o
7
-78 OC
-
Base
CO2Et R J Hy OH
OH
*
0 OC then CHzNz
(157)
(156)
(155)
H
H
OSiMe,
R O ,)' R2
Me"Sio~osiMe,
TMSOTf
-
OSiMe, ::>((C02SiMe3 OSi Me,
(164) (165)
3: Carbuxylic Acids and Derivatives
119
ultimately derived from (El - or (5) -p~legone'~~. Yields, both chemical and optical, of the intermediates (161) are high and the availability of both enantiomers of the starting terpene adds to the flexibility. In addition, exchange of the counter cation to zirconium leads to a preponderance of the corresponding syn isomers. The fully protected, chiral a,@-dihydroxy-esters (1631, usually as single isomers, can be accessed by a neat application of the Barton decarboxylation procedure13'. Thus, the radical intermediate (162) is obtained from the monoester of (g,R_)-tartaricacid and is trapped in situ by the usual types of Michael acceptor; subsequent elimination leads to the coresponding a,@-unsaturated derivatives. An efficient route to racemic a,@-dihydroxy-ester derivatives (165) consists of condensations between the silyl enolate (164) and carbonyls, induced by trimethylsilyl trif late14'. Unfortunately, in relevant cases, the stereoselectivity is usually poor. The butenolide (1661, derived from (&)-glutamic acid, has been used to obtain a variety of a, -dihydroxy-esters by Michael additiontrapping sequences141. For example, addition of tris (trimethylthio) methyl carbanion followed by oxidation of the intermediate enolate with MoOPH affords the lactone (167); subsequent desulphurization and hydrolysis then leads to ester (168). No doubt, many other useful schemes based on these ideas will be devised. A large number of Lewis acids are suitable for triggering condensations between silylketen acetals and aldehydes or ketones to give 8-hydroxy-esters; further additions to this list are montmorillonite clay142 and mixtures of trimethylsilyl chloride and tin (11) chloride143. As in a foregoing appli~ation'~~,the clay catalyst looks very easy to use but unfortunately, there is little stereoselectivity associated with either method. A somewhat more unconventional way to achieve this type of condensation is to treat a ketone [e.g. (169)l or an aldehyde with methyl methacrylate (170) or methyl crotonate and trimethylsilane in the presence of a catalytic quantity of rhodium (111) chloride144. Yields from these two esters, which presumably react by an initial l1.41 red~ction~~-'~, are excellent but are much lower when methyl acrylate or a,B-unsaturated lactones are the nucleophiles. A full account has been given of the preparation of chiral 8-hydroxy-esters (173) by condensations between aldehydes and the di-2-butylboron enolates of the thiazolidinethiones or oxazolidinethiones (1721, derived from cysteine or serine
respectively' 45. Typical of such condensations is predominant formation of the erythro isomer: in these examples, the selectivities are usually in excess of 97% and the reaction conditions appear to be exceptionally mild. The preparations of a variety of simple derivatives of (R)-3-hydroxybutanoic acid (174), which is readily available from the biopolymer PHB, have been de~cribed'~~. Similar starting materials and derivatives can also be obtained by asymmetric hydrogenations of the corresponding 13-keto-esters catalysed by ruthenium-BINAP complexes147. As is the case in the aforementioned reductions of a,0-unsaturated acids5 , the 100 atm.] but at reactions required high pressures of hydrogen [-. ambient temperature. Both the optical and chemical yields are essentially quantitative and both enantiomers of the catalyst ligand are available. Thus, at least for relatively simple substrates, this method would appear to be the one of choice and it should make such chiral hydroxy-esters very readily available in highly pure forms. Further developments of the yeast reduction methodology for the preparation of B-hydroxy-esters from B-keto-esters continue to be reported. In some cases, the addition of ally1 alcohol can lead to increased optical yields148 and such transformations can also be carried out under non-fermenting conditions where no sugar o r other nutrients are added other than those which are present in the tap water medium used in such reductions149. Although better optical yields are often obtained using these latter conditions relative to the more conventional methods, very substantial amounts of yeast are required [*. 250-380g per lg of keto-ester1 which will no doubt render the method rather impractical on all but relatively small scales. Yeast reductions of the potassium salts of 8-keto-acids are sometimes more effective than those of the corresponding esters as is the case with 3-0x0-heptadecanoic acid which can be converted into the optically pure hydroxy-ester (175) following esterification 150 [CH2N21, albeit in only moderate isolated yield (40%) . Subsequent a-alkylation using Frater conditions then leads to (2R,3R)-corynomycolic acid (176). Direct yeast reductions of the chiral a-fluoro-esters (177) are also highly selective leading almost exclusively to the erythro enantiomer (178)151. Similarly, the ( R ) enantiomers of esters (177) are reduced to the threo isomers with equally high selectivities. The same order of stereoselectivity in reductions of keto-esters (177) can be achieved by purely chemical means using a trialkylsilane as the reductant in the
3: Carboxylic Acids and Derivatives
121
presence of either a chelation control catalyst such as aluminium trichloride or tetra-g-butylamonium fl~oride'~~. Another useful product of this type of yeast reduction is the benzyloxy butanoate (179); in this case however, the optical yields are very dependent on the yeast:substrate:ethanol ratios, the best obtained being a 73% yield of material with 71% These authors also state that, contrary to previous reports, ethyl levulinate can be reduced by yeast to ethyl 4-hydroxypentanoate with 95% ee but only in =.15% chemical yield. A variety of esters have been examined for their suitability in the production of the higher homologues (180) of the foregoing benzyloxy keto-ester, again by "standard" yeast reductions; the 2,2-dimethylpropyl or n-hexyl esters proved to be the most suitable, giving a 98:2 ratio of enantiomers in favour of the ( 5 ) geometry154. A neat exploitation of the availability of a yeast reduction product is the conversion of B-hydroxy-ester (181) into the unsaturated derivative (182). Subsequent Michael additions and hydrolysis then lead stereoselectively [>10:11 to the homologues (183) in good chemical yields155. An alternative organism for effecting this type of reduction is the fungus Geotrichum candidum which is capable of converting the keto-esters (184) into the hydroxy-esters (185) in at least 95% optical yield in many cases156. The chemical yields are also good but a drawback could be the relatively high dilution required in the culture broth [1-8g of substrate per litrel. The useful acetylenic ester 1186) has been prepared with 91% ee from the corresponding racemic acetate by kinetic resolution at 40% conversion using lyophilised yeast as the hydrolysis ~ataylst'~~. Results with other substrates were sadly rather variable. Similar hydrolyses, but of cyclic B-acetoxy-esters, have been effected using Pseudomonas fluorescens lipase; again, optical yields are variable, but can often be 158 . essentially quantitative Another well established but older route to B-hydroxy esters is the Reformatsky reaction and, as in most previous years, there have been yet more developments of this useful methodology. Improved conditions consist of using diethyl ether as the solvent in the presence of 5-10 mol.% of trimethylsilyl chloride which serves to facilitate the initial reaction between the halo-ester and the zinc The D-trifluoro-esters (187) can be obtained in 55-79% yields but with little diastereoselection by Reformatsky reactions between an aldehyde and the appropriate a-bromo-ester using zinc and
General .and Synthetic Methods
122
HO
-.C15H31 (175)
OH Ph\/
0&C02Et (179)
Ph-0
A
H ,OH C O 2
R
3: Curboxylic Acids and Derivatives
123
.
a catalytic amount of iodine in benzene or THF 1 6 0 Def luorination114 of the intermediate zinc enolate does not appear to be a problem but the method is ineffective when applied to ketones. Effectively a Reformatsky condensation can also be carried out between a ketone and methyl chloroacetate by electrolysis using a zinc sacrificial anode and the 2,2-bipyridyl complex of nickel bromide as catalystl6'. Although the isolated yields are in the range 6 0 - 8 6 % , the method does not appear to offer any obvious advantages over the more conventional conditions. An asymmetric version of the reaction, which bears some resemblance to the aldol-type chemistry developed by Evans and colleagues, consists of condensations between the oxazolidone (188) and an aldehyde leading to very largely the syn diastereoisomers (189) following base hydrolysis with sodium methoxide162. Attempts to extend this chemistry to examples which incorporate a chiral Evans-type ligand syn/anti mixtures although, after have thus far only led to =.l:l separation, the anti isomers at least proved to be virtually optically pure. A useful addition to the chiral pool is the epoxide (1901, the one carbon homologue of epoxy-esters (153)l3O, which can be prepared from (2)-malic acid163. Couplings with lithium dialkylcuprates are reported to afford high yields of the chiral B-hydroxy-esters (191). Ring opening of glycidic ester (192) using samarium (11) iodide in THF-HMPA in the presence of dimethylaminoethanol is largely regioselective leading to the B-hydroxy ester (193) in 50-76% 164 yields, with retention of configuration at the B carbon This is complementary to an alternative method using magnesium 131 iodide which affords the corresponding a-hydroxy isomers Vinyloqous epoxy-esters also react in this way leading to the deconjugated 6-hydroxy-esters (194) in excellent yields [73-go%]. Key features of the chemistry of the 6-silyl-esters (195) are that the silyl function shows no propensity for undergoing B-elimination upon enolisation and that it can be replaced by hydroxyl with retention of configuration by treatment with fluoroboric acid (or BF3.HOAc) followed by mCPBA. This methodology has been further enhanced by the discovery of two new reagent combinations for effecting this latter transformation, namely molecular bromine and 165 mCPBA or mercury (11) acetate with peracetic acid . Unfortunately, none of these methods are compatible with the presence of an alkene function, so this limitation still remains.
.
.
124
General and Synthetic Methods
The standard method for the incorporation of benzyl protecting groups into alcohols [PhCH2Br, NaH] is often low yielding and capricious when applied to B-hydroxy-esters. Such protected derivatives (196) can be prepared in high yields using an alternative procedure wherein the parent @-hydroxy-ester is treated with benzyl 2,2,2-trichloroacetimidate and a catalytic amount of triflic acid166. Despite the requirement of an acid catalyst, even the phenyl derivative [ (196); R=Phl is formed in 71% yield along with only ~ . 8 of % the corresponding cinnamate. Essentially complete stereoselectivities have been achieved in preparations of the syn 8,6-dihydroxy-esters (197) by reductions of the corresponding B-keto-esters using sodium borohydride and methoxydiethylborane ( f o r which a new preparation is reported) as a complexing agent167. The selectivities are greater than those obtained using similar trialkylboranes. Complexing effects are also in evidence in Michael additions of organocoppers to the benzyl protected a,B-unsaturated esters (198) which lead with high selectivity to the anti isomers (199)168 . Similarly, the corresponding (2-) isomers of hydroxy-esters (198) can be converted into largely the 9isomers of esters (1991, along the same lines as related additions to y-methyl unsaturated esters94. An a-alkyl group can be introduced with excellent stereoselectivity into a 6-hydroxy-ester by direct alkylation of the corresponding enolate derived using LDA or a related base in THF-HMPA; use of this solvent mixture is essential for the production of the syn isomers (200)169. Keto-esters. - An extremely practical route to many a-keto-esters (201) consists simply of a conventional reaction between a Grignard reagent [ R M g X ] or an aryl lithium and diethyl o ~ a l a t e l ~ ~ . Presumably, the initially formed tetrahedral intermediate has an extra degree of stability, perhaps due to the presence of the remaining ester function, and is thus sufficiently long lived that most of the organometallic reagent has been consumed before it collapses. Yields are in the range of 39-85% and are often rather good. There is good literature precedence for this type of condensation such as in Corey's synthesis of aplasmomycin during which a mono-protected a,F-diketo-ester was obtained by directly coupling a 2-lithio-1,3-dithiane with dimethyl oxalate. Darzen
3: Carboxylic Acids and Derivatives
4 p C
125
0 2 E t
Ph
I
PhSiMe2
0
R/yCo2Me
e M 20C, R, )
OH
R
OH
condensations between ethyl gchloroacetate and an aldehyde lead to the B-chloro-epoxyesters (202) which on heating with either alumina or silica in xylene rearrange to the 6-chloro-keto-esters (203) in yields of 6O-98%I7l. A detailed discussion has been published of the various parameters affecting the palladium-catalysed double carbonylation of aryl halides leading to a-keto-esters [ (201); R=Arl 172. Excellent yields can be realized although the conditions are often rather harsh ( 3 . 150 atmos CO for 10h at 120°C). Aryl halides, especially the iodides, can also be coupled to a-methoxy acrylates using palladium catalysis [3-5 mol.% P ~ ( O A C ) ~DMF, , 8O"Cl to give the "protected" -a-keto-esters (204) in 2 8 - 8 0 % yields173. Vinyl triflates can also be used successfully as partners with the acrylates, but the couplings are not viable under these conditions with either vinyl iodides or aryl triflates. Another type of protected a-keto-ester (205) has been obtained from dimethyl acetylenedicarboxylate and a tertiary allylamine via a Michael addition followed by rearrangement17 An unprecedented and mechanistically obscure method for the preparation of keto-esters (206) consists simply of stirring the corresponding glutaconate with activated carbon in ethyl acetate for four days175. The procedure can also be used to oxidize other highly activated methylene groups. A variety of novel approaches to 3-formyl-esters have been reported this year. Monosubstituted derivatives (207) can be readily obtained from 0-silyl ester enolate by treatment with the Vilsmeier reagent [P0Cl3, DMF] in dichloromethane at ambient t e m p e r a t ~ r e l ~Yields ~. are within the range 51-62?,. Sequential alkylation of diethyl malate using iodomethane then ally1 bromide as the electrophiles, followed by selective hydrolysis affords the homologous half-ester (208); subsequent electrolytic degradation Although then provides the chiral B-formyl-esters (209)177. clearly limited in many respects, this route should find a number of applications as the products are reported to be enantiomerically pure. Protected forms (210) of the parent of this series, methyl 3-oxopropanoate, are available from Wacker-type oxidations of methyl acrylate in the presence of the appropriate 1,2- or 1,3-di01l~~. The methodology can also be applied successfully to other electron deficient alkenes such as a-methylenebutyrolactones. 1.3-Dioxolan-2-ylium cations (211) are generated from the corresponding aldehyde-derived dioxolanes upon treatment with a
(z)
*.
s.
3: Carboxylic Acids and Derivatives
127
t r i t y l s a l t s u c h a s Ph3C+BF4-.
Subsequent condensations w i t h
s i l y l k e t e n a c e t a l s then lead t o the protected 8-keto-esters
(212) i n
Even t h e s i m p l e s t member o f t h e series c a n b e
good y i e l d s 1 7 ' .
g e n e r a t e d from 1 , 3 - d i o x o l a n e a n d u s e d t o p r e p a r e p r o t e c t e d f3-formyl d e r i v a t i v e s [ ( 2 1 2 ) ; R'=HI. I n t h e same way as m e t h y l c y a n o f o r m a t e , t h e p - a n i s y l m e t h y l
ester
g e n e r a l l y condenses smoothly w i t h ketone e n o l a t e s t o g i v e high y i e l d s of t h e B-keto-esters
(213)l8'.
An a d d i t i o n a l f e a t u r e o f t h i s
t y p e of p r o d u c t i s t h e e a s e w i t h which t h e y can b e converted i n t o t h e d i o x o l e n o n e s ( 2 1 4 ) w h i c h may b e u s e f u l a s a " p r o t e c t e d " form o f t h e esters ( 2 1 3 ) .
Similar reactions with ester enolates afford the
unsymmetrical malonates ( 2 1 5 ) .
A number of methods h a v e b e e n
r e p o r t e d t o b e u n s u i t a b l e f o r t h e o x i d a t i o n of 9 - h y d r o x y - e s t e r s 8-keto-esters
to
[ g . S w e r n oxidations can g i v e rise t o chlorinated
p r o d u c t s ] ; a M o f f a t t t y p e r e a c t i o n u s i n g DMSO a c t i v a t e d by p h o s p h o r u s p e n t o x i d e was f o u n d t o be v i a b l e b u t v e r y s l o w .
The
a d d i t i o n of t r i e t h y l a m i n e h a s b e e n f o u n d t o d r a m a t i c a l l y a c c e l e r a t e s u c h o x i d a t i o n s a n d t h e method l o o k s a n a t t r a c t i v e o n e f o r t h e p r e p a r a t i o n of k e t o n e s i n g e n e r a l as w e l l a s B - k e t o - e s t e r s l g 1 D i b u t y l t i n o x i d e h a s been found t o c a t a l y s e a biomimetic p r o c e s s w h e r e i n a f u l l y s u b s t i t u t e d (3-hydroxy-a-keto-ester rearranges t o the isomeric 8-keto-ester
(217).
(216)
The method i s a l s o
u s e f u l f o r r i n g e x p a n s i o n s [ ( 2 1 8 ) + ( 2 1 9 ) ] l g 2 . The r e a c t i o n s c o n d i t i o n s appear t o be s u f f i c i e n t l y mild f o r t h e i n c o r p o r a t i o n of a v a r i e t y of o t h e r f u n c t i o n a l i t y e l s e w h e r e i n t h e s u b s t r a t e s . A d d u c t s ( 2 2 0 1 , formed b y [ 1 . 3 l - d i p o l a r
c y c l o a d d i t i o n s between
n i t r o n e s and a c e t y l e n i c esters, are c o n v e r t e d i n high y i e l d t o t h e The a-arylidene-8-keto-esters ( 2 2 1 ) upon o x i d a t i o n by mCPBA183. mechanism p r e s u m a b l y i n v o l v e s i n i t i a l N - o x i d a t i o n f o l l o w e d by r e a r r a n g e m e n t of t h e r e s u l t i n g N-oxide.
S i m i l a r o x i d a t i o n s of t h e
regioisomers of adducts (220) l e a d t o a-keto-esters
same pathway.
( 2 2 2 ) by t h e
F u r t h e r i n v e s t i g a t i o n s of t h e c h e m i s t r y of t h e
keto-phosphonate
(223) have r e v e a l e d t h a t t h e d i a n i o n o f t h i s
u s e f u l s t a r t i n g m a t e r i a l i s n o t formed when i t i s e x p o s e d t o two e q u i v a l e n t s of sodium o r p o t a s s i u m h y d r i d e b u t r a t h e r a n e q u i l i b r a t i n g m i x t u r e o f b o t h p o s s i b l e monoanions i s p r o d u c e d . However, much b e t t e r y i e l d s of t h e o l e f i n a t i o n p r o d u c t s ( 2 2 4 ) a r e o b t a i n e d when t w o e q u i v a l e n t s o f b a s e a r e u s e d , p o s s i b l y b e c a u s e D i a n i o n s of t h e e x t r a e q u i v a l e n t deprotonates t h e products184. phosphonate (223)
are p r o d u c e d
upon t r e a t m e n t w i t h NaH-5-BuLi
3: Carboxylic Acids and Derivatives mixtures.
129
Unsaturated B-keto-esters (224) can also be prepared by
Favorskii-type condensations between malonates and a , a ' - d i c h l o r ~ k e t o n e s ~ ~ ~Allylic . sulphides (225) have been found to behave similarly to allylic acetates in transition metal induced couplings with acetoacetate and malonate enolates which lead to variable yields of alkylated homologues 1 3 . (22611 using one equivalent of molybdenum hexacarbony1186. Potassium fluoride on celite has been found to be a good catalyst for the coupling of arene-iron complexes, carrying a suitable leaving group such as chloride, with acetoacetates to give B-aryl acetoacetates [%. (227)1 in good yields187. The useful a-diazoacetoacetate (228) and higher homologues,as well as the corresponding malonate derivatives, can be efficiently prepared from the parent compounds using diazo transfer from E-acetamidobenzenesulphonyl azide188. The reagent is reported to offer the twin advantages of lower toxicity and price relative to tosyl azide. Virtually quantitative chemical and optical yields have been obtained in the preparation of Michael adducts (229) by the addition of chiral lithioenamines [e.g.(230)1, derived from acetoacetate and This notable sequence valine, to dimethyl ethylidenemal~nate'~'. has at least a reasonable degree of generality as it can be applied to cyclic 6-keto-esters and is also effective when methyl vinyl ketone or methyl acrylate are the electrophiles. The B,y-diketo-ester derivatives (231) can be readily obtained in 73-868s yields from the corresponding B-bromo compound by treatment with sodium azide in hot aqueous acetone containing a The method apprears to be milder than trace of triethylamine'". previously reported alternatives. Simple 6'6-diketo-esters can be prepared in fair yields by condensations between silylketen acetals and diketene, catalysed by titanium tetrachl~ride''~. The parent member of this series, methyl 3,5-dioxohexanoate is regioselectively at the 4 position) alkylated between the two ketone functions upon sequential treatment with cobalt (11) acetate and a benzylic or allylic halide at 60-100°C192. Even within these constraints on the nature of the electrophile, the isolated yields are not particularly high (33-62%). Up to 65% ee of the final product (233) has been obtained from alkylations of the adduct (232) derived from 2-isopropyl norephedrine A and methyl 4-oxobutanoate followed by mild acidic hydr~lysis''~. simple approach to a,B-unsubstituted-y-keto-esters consists of
(e.
General and Synthetic Methods
130
0 MCPBA
-
0-
&
CO,Et
SPh (225)
CO2Et N2
0
Mo(C0)p
.--
3: Carboxylic Acids and Derivatives
131
sequential Michael addition of a nitroalkane to an acrylate followed by a Nef reaction. A particularly easy way to trigger this type of coupling is to treat the two components with Amberlyst-A21 resin in the absence of solventlg4. In the foregoing method, the nitroalkane can be regarded as an acyl anion equivalent; an alternative way to generate this type of intermediate for the synthesis of y-ketoesters is by electro-reduction of oxazolinium salts195. A novel method for the assembly of y-keto-esters but which can be thought of as involving an acyl anion equivalent, consists of carbonylation of an alkylmanganese pentacarbonyl followed by in situ Michael addition to acrylatelg6. Yields are quite good overall, and the Michael acceptor can carry both a- and @-methyl substituents. A particular attraction of this sequence is likely to be the mild and especially neutral conditions required. A ring expansion approach to cyclic y-keto-esters [g. (235)I consists of treating a-bromomethyl-Bketo-esters (234) with tributyltin radicalslg7. Yields are around 70% and the methodology is also applicable to acyclic examples. The precursors are prepared by alkylations of the parent $-keto-esters using dibromomethane as the electrophile and the mechanism may involve intramolecular addition of an initially formed methyl radical to the B-carbonyl function followed by cleavage of the resulting cyclopropane. The allylic chloride (236) can be used in place of chloroacetone as a synthetic equivalent of the acetone cation (237), and is especially effective in alkylations of B-ketoesters and malonates, the latter leading to the partially protected y-keto-diesters (238)l g 8 . Hydrolysis of the enol function requires 1% aqueous sulphuric acid. Details have been presented of the relatively general approach to y-keto-esters involving hydrogenation 199 of $-silyloxycyclopropane carboxylates . A system consisting of trityl chloride and tin (11) chloride is very effective in catalysing Michael reactions between silylketen acetals and enones leading to 6-keto-esters in high yield2". Where relevant, the stereoselectivities of such processes are usually high also, as in the coupling of the silyl enolate of t-butyl thiopropanoate and 1-phenylbut-2-en-1-one which, typically for these reactions, affords a 90% yield of the keto-ester (239) with and anti:syn ratio of 84:16. Enders and his colleagues have given a detailed account of their approach to chiral 6-keto-esters (240) by asymmetric Michael additions of the SAMP and RAMP 201 derivatives of methyl ketones to arylidenemalonates .
132
General and Synthetic Methods
The nitro-ketones (241) are readily available by Michael addition of the parent cyclic ketone to acrolein, catalysed by triphenylphosphine, followed by selective protection of the aldehyde function using methanol containing ammonium chloride. Ring cleavage by reaction with methoxide and finally Nef reaction of the resulting nitronate then completes this general method for the elaboration of dioxo-esters (242)202. Unsaturated Esters. - When carried out in a polar medium such as methanol, Wittig reactions between stabilized phosphoranes derived from haloacetates and aldehydes can give a preponderance of the (g)-a,B-unsaturated esters. Extreme examples of the phenomenon are to be found in various homologation reactions of carbohydrate aldehydes which give products [ g .(24311 with ~ . 2 0 : 1ratios in favour of the (2)isomers203. In contrast, such reactions of the related phosphoranes derived from a-halo-ketones with a-keto-esters lead very largely to the (El-isomers [ g .124411 when carried out in benzene204. Stobbe-like products [G. unsymmetrical arylidenesuccinates (24511 can be similarly obtained by Wittig reactions again in benzene, using a stabilized phosphorane derived from an unsymmetrical succinate diester205. A classical version of the Stobbe condensation has been used to prepare the potential phosphoenol pyruvate inhibitors (246) from an aldehyde and 3 - (diethoxyphosphinoyl)propanoate206. Ketones can also be used as the electrophiles but mixtures of stereoisomers are usually formed. The specific formation of the phosphonic acid monoesters presumably originates from an initial regiospecific deprotonation of the starting propanoate. Yet further basic conditions have been developed for effecting condensations between aldehydes and phosphonates (Wadsworth-Emmons? Wittig-Horner? - it is about time that a definitive name for this type of reaction was agreed upon!). With aromatic aldehydes, such condensations leading to a,B-unsaturated esters can be carried out at a solid-liquid interface with barium hydroxide in THF at room temperature under s~nication~'~. Only brief reaction times are required to obtain the usually excellent yields. An alternative which is perhaps of greater relevance to an industrial process is to carry out the condensation under gas-liquid phase transfer conditions over a catalyst bed containing potassium carbonate coated with poly(ethy1ene glycol)-carbowax 6 O 0 O 2 O 8 . Yields are in the
133
3: Carboxylic Acids and Derivatives
(YBr CO2Et
BuaSnH
C02Et
AlBN
(234)
(235)
YYco2E
O ,O -
C02Et
(237)
(238)
0
Ar
R, J +,CO~M~
(239) OMe
C0,Me &C02Me
(244)
C02Et
Ry ,OEt
FOH 0
C0,'Bu
(245)
region of 50-66%. Triethyl phosphonoacetate has been previously shown to undergo Knoevenagel rather than Wittig-type condensations with aldehydes when treated with titanium (IV) chloride and N-methylmorpholine
esters.
to give (El-a-phosphonato-a,$-unsaturated The corresponding (?)-isomers (247) can be obtained by a
related process but using sodiumn hydride as the base in the presence of chlorotitanium t r i i s o p r o p ~ x i d e ~ ~These ~. are apparently the kinetic products as, if triethylamine is used as the base, once again formation of the (E)-isomers is favoured. Copper-catalysed additions of Grignard reagents to the allylic acetates or the g-silylated allylic alcohols (248) afford the cyclic a,$-unsaturated esters (249), presumably by an S 2' mechanism210 . N In addition, ester enolates will also react wih the electrophiles (248) in the same manner to give the unsaturated diesters (250) which are useful as precursors to valerolactones [e.g. (251)l amongst other possibilities. Simple a,$-unsaturated esters (252) undergo largely Michael addition of lithium amide bases rather than deprotonation especially when the base (nucleophile) is lithium N-benzyl-N-(trimethylsi1yl)amide and the reactions are carried out in neat THF, without the addition o f HMPA. The resulting enolates can be efficiently alkylated using allylic bromides or primary alkyl iodides to give the 8-amino-acid derivatives (253) which upon elimination of the amine function give mainly the (E)-trisubstituted alkenes (254)211. Cyclic ketones are efficiently converted into the sulphinyl epoxides (255) by reaction with (phenysulphinyl) chloromethane212. Rearrangement induced by lithium perchlorate leads to the aldehydes (256) and thence to the corresponding unsaturated esters following oxidation, for which the sodium chlorite/hydrogen peroxide method was found to be the most suitable, and esterification. Yields overall are quite respectable but there can be uncertainty regarding the final position of the alkene function. Some new developments of the Knoevenagel approach' and related methods €or the synthesis of a,B-unsaturated esters include PTC alkylation/elimination reactions between benzylic chlorides and methyl sulphinylacetate using potassium carbonate as the base, which give 60-93% yields of (E)-cinnamates2l3 and direct condensations of aldehydes with the same nucleophile, but under normal conditions using a secondary amine as base, which lead to good yields of the (E)-sulphinyl esters (25i')214. A somewhat
3: Carboxylic Acids and Derivatives
(249) n = 1 or 2
135
(248) R’ = OAc or OSiMea (250) R2 = H or Me j n=i
i
R ~ = H
i
/
(253)
0-
F
RTco2M
R d C 0 2 M e
ON
(259)
SPh PhSH Et3N
V,*~CO,M~
PhNH2 =
PhNH A C O , M e
136
GetI em1 N I I d SvrI r het ic Methods
similar approach to the a-fluoro derivatives (258) is by reductive condensation-elimination reactions between aldehydes and methyl dichlorof luoroacetate in the presence of zinc meta1215. Yields are generally in excess of 70% but the method is ineffective when applied to ketones. A simple route to the 4-0x0 unsaturated esters (259) consists of condensations between enamines and glyoxylic acid esters or the corresponding herniacetals2l6. Unfortunately, a mixture of the (El and isomers is produced but at least these isomer in the can be readily separated by isolation of the cyclic form, the corresponding y-aminobutenolide, in which it is initially produced. A useful divergence of reactivity has been found in the reactions of allenic esters ( 2 6 0 ) with the addition of thiophenol takes h e t e r o n u ~ l e o p h i l e s ~ ~Thus, ~. place across the a-0 bond in the presence of triethylamine to give the non-conjugated ester (261). In contrast, a primary amine adds across the 0-y bond leading to the f3-amino-esters (262). 6-Silyl-esters (263) having alkyl, phenyl or ethoxy substituents on the silicon atom can be obtained by Co2(CO)8-catalysed addition of the appropriate trisubstituted silane to an excess of an acrylate218. Only 'traces of the corresponding Michael adducts are formed. A full account has been published o f the preparation of (Z)-atf3-unsaturatedesters by carbonylation of *-vinyl tellurides obtained by the addition of "PhTeH" to a terminal alkyne219. Higher homologues (264) of such esters have been prepared by a related, palladium-catalysed, addition of Bu3SnGeMe3 to a conjugated ynoate followed by tin-lithium exchange and alkylation220. Amongst other transformations the residual germanium group can be replaced by iodine. The Tsuji method for the palladium-catalysed decarboxylation of ally1 esters has been adapted to a preparation of a-methylene-esters (266) and a-methylenebutyrolactones by the incorporation of an acetyloxymethyl group into the starting mixed ester (265)221. Yields are high and the reaction can also be applied to a variety of sulphone other substrates having electron withdrawing groups (3. or nitrile) in similar positions. A full account has been given of
(z)
(z)
the highly stereoselective route to 3,4-* methylene-esters [%. (267)l by condensations of a-benzyloxyaldehydes wth a-methylthio- or a-methylthiomethyl ester enolates222. Similar reactions are also useful in the stereoselective preparation of 2,3,4-trihydroxy-ester derivatives. Esters (268) with up to 73% ee have been obtained from
3: Carboxylic Acids and Derivatives
137
condensations of aromatic aldehydes with the Michael adduct of (5)-prolinol and &-butyl a ~ r y l a t e ~ ~Unusually, ~. the optical yields are better under apparently thermodynamic conditions at ambient temperature rather than the low temperature conditions more normally associated with high asymmetric inductions. A few examples suggest that an alternative way to obtain an equivalent of the vinyl carbanion (269) is to directly generate the corresponding vinylalane by the addition of Dibal-H to methyl propiolate in THF-HMPA at 0°C224. At the least, this intermediate can be alkylated by allylic bromides to give the dienoate (270) from 2-cyclohexenyl bromide, for examp1e . In work related to the foregoing, the addition of Dibal-H to a 2,4-dienoate in the presence of 10mol% of methylcopper gives an intermediate enolate which can be efficiently alkylated with ally1 225 bromide at least, leading to the B,y-unsaturated esters (271) A perhaps more widely applicable approach to such esters is by palladium(0)-catalysed coupling of a vinyl triflate and the Reformatsky reagent derived from t-butyl bromoacetate226. Yields of 48-77% of the adducts [e.g.(27211 have been obtained but oddly, all the examples of this type of reaction reported are of triflates derived from cyclic ketones: it would seem reasonable to suppose that similar couplings could be successful with other types of triflate. The method can also be used to prepare arylacetates from aryl triflates. A clean transfer of chirality occurs in SN2' displacements involving the conversion of the mesylate (273) into B,y-unsaturated esters (274), with the incoming nucleophile approaching from the opposite face to the leaving group, as expected227. Notable features of this method which does not
.
required the use of a higher order cuprate, are its mildness and hence potential for applications to more complex substrates and the creation of a chiral quaternary centre with virtually complete asymmetric induction. Optimized procedures have been reported for the preparation of the (?)-unsaturated esters (275) by 228 deconjugation of the corresponding (El-a,B-unsaturated esters . Application of the method to (2E,4g)-dienoates leads to the (3E,55) isomers (276). Similar photo-deconjugations of a,B-unsaturated esters in the presence of a chiral proton source can give optical yields of up to 70%; however, most purity levels are lower than this at the present state of the art229. Dienolates derived from B,B-dimethylacrylates are not usually synthetically useful as, €or
Gcwerul and Synthetic Methods
138
C02R'
R2*R3Si
Me3Ge
0
OH
(265)
(267)
Arq C02Me
(274) R = n - alkyl
(273)
wco2M
R
C02Me (275)
(276)
3: Carboxylic Acids and Derivatives
139
example, condensations with aldehydes lead to gross regio- and stereo-chemical mixtures. One solution of this problem is to employ the tin derivative (277) which undergoes efficient BF3-catalysed reactions with aldehydes to give very largely the anti diastereoisomers (278)230. When the reactions are brought about by TBAF, formation of the syn isomer predominates to an extent of =.72:28. B,y-Unsaturated esters can also be obtained by reductions of conjugated dienoates using sodium dithionite under phase transfer conditions231. Yields are, however, somewhat variable [46-90%1 and mixtures of geometrical isomers are sometimes isolated A general approach to highly substituted y,b-unsaturated esters (281) consists of the palladium-catalysed coupling of ketens (279) with allylic carbonates (280)232. Yields are in the region of 60-75% and the reaction seems to be widely applicable for these two ketens at least. Related, highly substituted, y,b-unsaturated esters (282) are available from another palladium-catalysed process in which a-isocyano carboxylates are coupled with allylic acetates233. These initial products-can be hydrolysed using aqueous acid to give the corresponding a-amino-acid and the isocyano group can be reductively removed by treatment with Bu3SnH/AIBN. The attraction of this sequence is therefore that it provides an entirely neutral, two-step approach to y,b-unsaturated acids. Unexpectedly, reaction between sodium trichloroacetate and allyl bromide under phase transfer conditions leads to a good yield of the ester (283)234. The method will presumably be applicable to other allylic and benzylic systems and could be of use in cases where the allylic bromide was not particularly valuable, A rather different approach to y,b-unsaturated esters (284) is be oxidative coupling of allyl ethers with silylketen acetals, induced by DDQ235. Although mostly applied to the preparation of a-alkoxy nitriles, the method should be applicable to related ester preparations and thence presumably to 2,4-dienoatesI after elimination of the elements of methanol. A full account has been given of the highly stereoselective preparation of esters (285) by enolate Claisen rearrangements of allyl glycolates236 . A variety of unsaturated esters (287) are available from copper catalysed allylations of the three, potentially very useful, homoenolates (286)237. Both primary and secondary halides can be used to good effect, although both SN2 and SN2' processes can occur
140
General and Synthetic Methods
with equal facility, thus limiting the applications of this method [see also refs. 246 and 2861. Two very important routes ta conjugated dienoates, both based ~ 2 reactions, have been described in full. The on e 2 -coupling approach of Negishi and his colleagues utilizes Pd(0)-catalysed couplings of vinylalanes derived from terminal alkynes and 6-bromoacrylates, amongst many others, and is particularly suitable for the preparation of (2g,4g) In contrast, the approach of Stille and Groh in which vinyl iodides and vinyl stannanes 1%. 6-stannylacrylatesl are coupled, again using a palladium catalyst, can be used to prepare (2g,4E)In both methods , isolated yields are around 60%. (2Zf4Z)-Dienoates (290) are available from a sequence which features a [2.31-Wittig rearrangement of the ethers (288) followed by BF3induced elimination of the elements of trimethylsilanol from the resulting syn diastereoisomer (289)240. Formation of the iron tricarbonyl complex (291) allows the retention of the ( E , Z ) geometry of the organic ligand while the aldehyde function is reacted with methy lithium or a methyl Grignard reagent241. Subsequent removal of the ligand gives the hydroxy-dienoate (292); presumably, higher homologues could be formed in a similar fashion. Stereochemically pure (El -enynoates (293) are available in z - 5 0 % yield by coupling iodo-acetylenes with methyl acrylate in a Heck 242 reaction but using solid-liquid phase transfer conditions Traditional Heck conditions give much poorer returns. Palladium acetate-mediated oxidation of 5-substituted pyrazol-3(2H)ones (294) 243 in methanol lead to around 60% yields of the alkynoates (295) . By contrast, isomeric 5-methyl-4-substituted pyrazolones are converted to the allenic esters (296) under these conditions. Such transformations can also be effected using thallium (111) nitrate. Aryl and heteroaryl alkynoates [(295); R=Ar] can also be obtained from the parent arenes by Friedel-Crafts type coupling with trichlorocyclopropenium cations generated from tetrachlorocyclopropene in the presence of aluminium t r i ~ h l o r i d e ~ ~The ~. corresponding orthoesters (297), a protected form of this type of ester, can be obtained from this sequence by a simple modification of the final alcoholysis step. A rather different type of coupling reaction between 1,1-dimethyl-2,2,3-trichlorocyclopropane and an 0-silyl ester enolate has been used to prepare 6,y-allenic esters [e.g. (298)1245. 5-Hexynoates [e.g.(29911 may be obtained from
die no ate^^^^.
die no ate^^^'.
.
141
3: Carboxylic Acids and Derivatives
R' (279) R' = Ph or Et
OR
"r
C02Me
Ar H c ( 0 R ) 3 (297)
@*4 C02Me
142
G'wCJYCll Lltld S~vIltllc~rlCMC9ll#Li..\
the corresponding a,B-unsaturated esters by sequential addition of trimethylsilyl iodide (to give a B-iodo-silyl enolate) and the nitrosylferrate, Bu4NFe(C0)3NO; ligand exchange of the resulting n-allyliron complex by reaction with triphenylphosphite and finally alkylation by propargyl bromide delivers around a 60% yield of the ultimate product246. The intermediate iron complex can thus be regarded as another homoenolate anion equivalent237 286. The butadienyl esters (300) can be obtained from a three component, palladium catalysed, coupling reaction between a monosubstituted allene [R1CH:C;CH2], a vinyl bromide and methyl sulphonylacetate247. Malonate can equally well be used as the soft nucleophilic species; yields are usually in the regio of 70% but the stereoselectivity is often rather poor. 3 Lactones Butyrolactones. - New reagents for the direct oxidation of a,w-diols to lactones include a peroxy-molybdenum species derived from tris (cetylpyridinium) 1 2 - m o l y b d o p h o ~ p h a t,e ~a~mixture ~ of N-iodosuccinimide and silver (I) acetate249 and treatment with RuH2(PPh3I4 in the presence of methyl ally1 carbonate250. The latter two methods seem to offer the better yields; simple six- and seven-membered lactones can also be prepared in this manner. Many y,y-disubstituted butyrolactones are available from a related procedure in which butyrolactone itself is reacted with two equivalents of a Grignard and the resulting unsymmetrical diol converted back to the lactone oxidation level. Of a number of oxidants tried, one of the best found was potassium permanganate in 251 the presence of benzyltributylammonium chloride Amongst other useful observations, it has been found that PPL (porcine pancreatic lipase), either as a crude preparation or semipurified, is able to selectively hydrolyse the meso keto-diacetate (301); subsequent oxidation of the resulting monoacetate gives the useful keto-lactone (302) as well as a variety of related derivatives2 5 2 Baeyer-Villiger oxidations7* can be carried out using very cheap sodium perborate; as an example, cyclohexanone is converted into caprolactone in 79% isolated yield253. A1 though acidic conditions
.
are necessary (TFA or TFA-HOAc as solvent), it seems likely that this surprisingly previously unreported method will have many
3: Carboxylic Acids and Derivatives applications. A number of alternative methods have been developed for effecting the cyclisation of 4-pentenoic acids to the y-substituted butyrolactones ( 3 0 3 ) . The sulphenyl derivatives [ (303); R = S R l are obtained in excellent yields using mixtures of disulphides [ R S S R I and manganese (111) acetate254 and the corresponding phenylseleno analogues [ (303); R=SePHl can be prepared by a related process in which the unsaturated acid is electrolyzed are in the range 56-78% and with diphenyl d i ~ e l e n i d e ~ ~Yields ~. perhaps a better alternative is to use benzeneselenenyl triflate, PhSeOTf, which delivers yields usually in excess of 80%256. These methods are also applicable to valerolactone synthesis and the last one at least can also be used for cyclisations of the corresponding unsaturated esters and amides. Both group and face selectivities have been observed in more conventional kinetic iodolactonizations of the dienoate (304) and its two d i a s t e r e o i s ~ m e r s ~ ~Under ~. these conditions, the lactone ( 3 0 5 ) is formed almost exclusively [see also ref. 2841. A very different version of the iodolactonization protocol consists of photolysis of an appropriate acid [e.g. (30613 with iodine in aqueous acetonitrile containing various aromatic additives258. This mechanistically complex anti-Markovnikov addition is probably based on single electron transfer processes and could involve two distinct pathways; nevertheless, the final products [e.g.(307)l are formed in good yields. A related cyclisation is involved in the conversion of homoallylic alcohols (308) into lactones (309) by a palladium catalysed double carbonylation sequence259. Yields are generally greater than 70% and as little as 0.01 equivalents of the palladium catalyst will suffice for reactions carried out at ambient temperatures during a period of around six days. A similar intermediate is involved in the very efficient, palladium ( 0 ) catalysed conversion of the cyclic carbonates (310) into the vinyl butyrolactones (311)260. This Tsuji-type decarboxylation-carbonylation is tolerant of a wide variety of substituent patterns around the dioxane ring. A new catalyst for the cation-mediated cyclisation of homogeranoic acid to tetrahydroactinidiolide (312) is tin (11) trif late261; only the trans isomer is produced in 70% yield. A number of methods have been established for the cyclisation of 4-alkynoates to ylidenebutyrolactones (313); further additions to this list include silver (I) carbonate262 and a rhodium-phosphine catalyst263. The latter method appears the more attractive, at least with the simple
144
1
C02Me
(299)
'2
x?
NaHC03
0
C02H
'0 (305)
(304)
(303)
R-
I \ \
I,,
PdCIz.CUC12
-
co
0
RQ2°2Me
3: Carboxylic Acids and Derivatives
145
substrates examined, as only the (Z)-isomers are produced. Otherwise, both methods are very mild and efficient. Radical-based methods continue to make an impact in this area. A full account has been given of one of the simpler methods whereby 2,4-disubstituted butyrolactones are formed by heating together an a-bromo-acid and a terminal alkene with benzoyl peroxide264. A drawback associated with this type of cyclisation in general is that two functional groups are sacrificed during the ring forming process. One way around this is to use a catalytic quantity of a distannane as the initiator and allow the final radical in the cascade to remove a halogen from another starting molecule. This tactic is illustrated in the efficient conversion of the a-iodoester (314) into the iodo-lactone (315)265. A further example of the preparation of butyrolactones from radical-mediated cyclisations of bromomethyl acetals followed by oxidation is a preparation of the @-fluoro-lactones (316) starting from 2-fluoroallylic alcohols266 Treatment of the final product with DBU leads to formation of the corresponding butenolide. A rather different method for the preparation of ring fused butyrolactones (318) involves reductive cyclisation of an unsaturated aldehydo- or keto-ester (317) brought about by samarium (11) iodide267. The reactions, which presumably & radical anion formation by reduction of the ketone proceed y carbonyl, give variable returns [30-92%1, unfortunately with little stereoselectivity. A synthesis of the terpene 14-epiupial features an application of the manganese (111)-induced radical cyclisation of 268 malonates in the key ring forming step [(319)+(320)1 Direct a-alkylation or a-acylation of butyrolactones has been achieved by formation of the corresponding enolate using metallic potassium in the form of a mirror269. Yields are generally
.
.
excellent but, on reflection, the apparatus required does look a little complicated. Potassium enolates of thionolactones can be efficiently allylated at the a-position by treatment with an allylic bromide, provided that this is not too highly substituted270. However, the mechanism is probably not a direct 5-alkylation but rather an 5-alkylation followed by a thioclaisen rearrangement. The excellent stereoselectivities which are usually observed in Michael addition-trapping sequences using y-substituted butenolides as substrates have been further exemplified during this year. For example, a neat approach to (9g)-dihydroerythronolide features the addition of the bulky nucleophile (PhS)3CLi to the butenolide (321)
146
General and Synthetic Methods
.
271 followed by oxidation of the resulting enolate using MoOPH Desulphurization then affords the lactone (3221, the "all-+" isomer of which is available by hydrogenation of the corresponding butenolide. A second lactone ring can then be built onto this latter type of isomer to give the bicyclic system (323) and thence another butenolide (324). Repetition of these processes then leads to polypropionate chains. A somewhat more convoluted procedure, again based on an initial Michael addition but with a separate enolate homologation step, has been developed for the preparation of the butyrolactones (3251, models for a projected approach to the e r e m a n t h o l i d e ~ ~ ~Upon ~ . deprotection using trimethylsilyl bromide, these initial products are converted to the acetals (326). (+)-A Factor (327) has been prepared by asymmetric Michael addition to a chiral a-sulphinylbutenolide of the methanol carbanion equivalent (328)273. Prostaglandin mimics (329) based on an u , 8-disubstituted butyrolactone ring have also been obtained by the Michael additiontrapping sequence, using allylic sulphides as the initiating more unusual feature of sulphur n u ~ l e o p h i l e s ~ ~A~ somewhat . chemistry has been used to obtain the butyrolactones (330) from a vinyl sulphoxide upon treatment with trichloroacetyl chloride and zinc-copper couple275. The mechanism presumably involves 0-acylation by dichloroketen followed by rearrangement and cyclisation. Much the same sequence can be used to obtain the correponding phenylseleno-lactones from vinyl ~ e 1 e n o x i d e . s ~ ~A~ . very mild and simple approach to benzofuranones (331) relies on the trapping of diketen by a phenol followed by diazo group tranfer and finally Rh(OAc)2-catalysed insertion into an ortho C-H bond of the resulting a-diazo a ~ e t o a c e t a t e ~ ~ ~ . Simple y-n-alkyl butyrolactones are available in variable yields [13-79%1 but with generally excellent optical purities from yeast The reductions of the corresponding y - k e t o - a ~ i d s ~ ~ ~ . method fails in the simplest case of 4-oxopentanoic acid, but an alternative based on a selective PPL-catalysed hydrolysis can be used to obtain chiral y - v a l e r ~ l a c t o n e ~ ~The ~ . asymmetric yeast reduction method is also applicable to the preparation of the homologous 6-valerolactones from 6 - k e t 0 - a c i d s ~ ~ ~The . pheromone eldanolide (332) continues to be used as a target for the illustration of new methodology. A new approach to y-ally1 butenolides consists of the coupling of 2-trimethylsilyloxyfuran with an allylic bromide in the presence of silver trif luoroacetate280. Subsequent Michael addition of methyl
147
3: Carboxylic Acids and Derivatives
R
0 (327)
0
BtO-0-Li
= XH20H
(328) SPh
(329)
Geneml and Synthetic Methods
148
then gives the (racemic) natural material.
The same silyloxyfuran
also undergoes Lewis acid catalysed condensations with aldehydes3’’; such a coupling for which triethyl triflate proved to be the best catalyst, has been used as the key step in a synthesis
of racemic cavernosine (333)281. The related but slightly simpler structural array present in L-factor ( 3 3 4 ) and other natural products can be accessed in chiral form by reduction of chiral f3keto-sulphoxides282 or from the epoxy-alcohol (335) obtained from yeast reduction of (phenylthio)b ~ t a n - 2 , 3 - d i o n e ~ ~The ~ . two racemic diastereoisomers of lactones (334) are available from stereospecific
!z)
cyclisations of simple (E)- or -y, &-unsaturated acids using a reagent combination on mCPBA and a catalytic amount of Amberlyst-15 resin284. The (El-isomer leads to the erythro lactone and the
(z)
to the threo; none of the corresponding valerolactones were isolated. In contrast, B-trimethylsilyl homologues of the lactones (3341, formed using a similar cyclisation method, can be converted into f3 ,y-unsaturated va lerolactones
’.
A very rapid entry to y-substituted butyrolactones is the condensation of methyl 3-bromopropanoate with an aldehyde in the presence of samarium (11) iodide in THF-HMPA286. The reactions take
s.
one minute to go to completion and yields are generally excellent. Whatever the mechanism, this reaction can be reagarded as involving a homoenolate anion equivalent. Just as in some of the
only
foregoing examples of such species237’246, the methodology can be extended to include the homologous e-homoenolate equivalent, derived from ethyl 4-bromobutanoate, which can be used to prepare valerolactones. A related route to y,y-disubstituted butyrolactones as well as monosubstituted derivatives consists of condensations between aldehydes or ketones and 3,3-diethoxypropyl lithium derived 287 from 3-chloropropanal diethyl acetal and lithium naphthalenide . Yields are in the range 44-66%. A synthetic equivalent of the foregoing species is the sulphone-stabilized carbanion (336) which condenses efficiently with ketones; following desulphurization, the resulting butyrolactones are isolated in 4 6 - 7 2 % yields over the two steps288. Alternatively, base-induced elimination leads to excellent yields of the corresponding butenolides. One other asymmetric approach to a useful y-substituted butyrolactone (337) involves selective acidic hydrolysis of an hydroxy-bis lactam derived from chiral b i n a ~ h t h y l a m i n e ~ ~Although ~. the optical yields are excellent, a drawback is the inefficiency of the
3: Carboxylic Acids and Derivatives
149
preparation of the starting material. The homologous valerolactones can be similarly obtained. The regioselectivity displayed by alkyltitanium species towards ketones has been exploited in a brief synthesis of norbisabolide (339) from the diketo-ester (338)290. Palladium catalysed couplings of vinylmercurals and 3-butenoic acid afford 51-85% yields of the y-vinylbutyrolactones (3401, presumabley intramolecular nucleophilic displacement of palladium from and intermediate n-ally1 -Pd complex by ~arboxylate~’~.Although the method can be extended to include examples of valerolactones, when preparations of more highly substituted butyrolactones are attempted, the yields are distinctly lower. A novel type of catalyst fAr asymmetric reductions using borane, which seems likely to enjoy an extensive number of applications in the area of ketone reduction, is an oxazaborolidine derived from a , a - d i p h e n y l p r ~ l i n o l ~ ~One ~ . example of this reagent combination is in reductions of 6-aroylpropanoates which are very rapid and which result in the formation of nearly optically pure y-aryl-lactones (341). Racemic a,a-dimethyl homologues of this type of aryl-lactone have been obtained in moderate yields from reactions of aromatic aldehydes with 2-chloro-2-methylbutanone; the mechanism is probably a sequential aldol condensation and Favorskii rearrangement293. Total syntheses of the lactivicin derivatives (3421, rather unusual butyrolactones with 6-lactam like activities, have been achieved; the key step was based around couplings of protected cycloserine with activated derivatives of a-keto-gl~tarates~’~.Another unusual type of butyrolactone, the thio-substituted cyclopropyl derivatives (344) can be obtained from condensations of aldehydes with the 295 . bisthio-amide (343) in 55-86% yields High yields of the interesting spiro cyclohexadienone system (345) are obtained when the corresponding e-hydroxyphenylpropanoates are oxidised by phenyliodoso bis(trif1uoroacetate) [PhI(OCOCF3)2 or PIFA]296. Ene-type cyclisation of the ester (346) occurs upon thermolysis under carbon monoxide at 140°C to give a good yield of the potentially useful spirolactone (347); related substrates behave similarly297. A further use of 1,2, -dilithiated vicinal diester intermediates (348) is in the elaboration of the tricyclic systems (349) by reaction with 6-bromoethyl ~ x i r a n e ~ ’ ~ .The yields are only moderate [22-37%1 but then this is a “one-pot‘’procedure during which three bonds are formed. None of the corresponding
150
Grrirrcrl mid Sytrthrtic Mrrhocls
(330)
(332)
H &
(333)
(334)
RHN L
H
(335)
Q
0
(337)
i)MeTiCb ii) H+
0#02Me (338) (339)
0
RQ -
(340)
Phs
r;p
PhS BuLi
-
RCHO
CONHPh
(343)
H
0 1344)
3: Carboxylic Acids and Derivatives
151
valerolactone appears to be formed and so the reaction probably proceeds a 5-exo-tet cyclisation onto the more hindered end of the epoxide in the initial alkylated product. Construction of a ring fused cyclopentenone function using this type of dianionic intermediate [cf. (34811 derived from dimethyl 4-cyclohexen-1,2dicarboxylate forms a key step in a notable total syunthesis of the C15 ginkgolide bilobalide (350), reported by Corey and Su2”. Although the bis-lactone (3511, the dilaspirolactone aglycone, appears equally complex, it is prepared simply by keeping a mixture of ascorbic acid and methyl 3,4’-dihydroxydihydrocinnamate together The reaction may well involve the in water for 14 days3’’! intermediacy of a protonated quinone methide which undergoes nucleophilic attack by the ascorbic acid. a-Methylenebutyrolactones. - The enormous level of activity in this area during the past decade or so has resulted in an inevitable reduction of new developments. An unusual approach to such lactones involves attack of epoxides by the highly nucleophilic deprotonated phosphorane (352)301. Silylation of the initial alkoxides, a standard Wittig olefination with formaldehyde and finally hydrolysis gives the lactones (353). Generally, yields are good to excellent although the final hydrolysis steps will impose some constraints on the nature of the side chains which can be incorporated. Bromomethacrylate and benzaldehyde can be coupled together using a n tin (11) chloride-diethyl tartrate adduct when the hydroxy-ester (354) is produced; subsequent brief exposure to sodium hydride then gives the lactone (355) with 58% ee302. Hopefully, further developments will lead to a general and chirally efficient route to this type of lactone. In a further development of an already established approach to a-methylenebutyrolactones,complementary stereochemical results have been obtained in cyclisations of allylsilane (356)303. Whereas thermolysis with E-toluenesulphonic acid in acetone leads to a 78% yield of the =-lactone (3571, treatment with TBAF in dry THF gives largely the alternative cis-fused lactone. By contrast, acid treatment of the corresponding ( E ) isomer of silane (356) gives a trans-fused lactone. Acyclic homologues of the allylsilane (356) can also be cyclized by reaction with titanium (IV) chloride to give a variety of ring sizes, although with little stereochemical control304. Further details have been given regarding the preparation of
0
O H
0 C02Me
(349)
(348)
O
0 Y
CH,=O
(352)
OH
(353)
(351)
OH
CO,R
0
(354)
cf& HI
0
SiMe3
COZEt
(355)
p - TSA
-9 0
(356)
(357)
3: Carboxylic Acids and Derivatives
153
a-alkylidenebutyrolactones from the parent structures by first incorporating a dithiocarbonate function and then carrying out a condensation with an aldehyde305. Depending upon the conditions, either only (El or largely (2) isomers are produced. A tandem Michael/Wadsworth-Emons sequence has been developed for the elaboration of the bicyclic lactone systems (358)' 0 6 .
For
example, reaction between keto-malonate affords the six-membered rings can be been prepared in this way
an a-phosphonato butenolide and a adducts [ (358)i RL=C02Etl. Both five- and formed and other derivatives which have include dithianes [ (358);R1-R1=S (CH2)3 S ] and simpler derivatives [(358);R1=HI.
Butenolides.
-
An enzyme-based route has been developed for the
preparation of the chiral lactone (359). Dibal-H reduction to the corresponding lactol and subsequent coupling with a variety of organometallic species then affords the diols (360) usually with high levels of stereoselection at the newly created chiral centre. Finally, Jones oxidation and retro Diels-Alder fragmentation at 110°C leads to the chiral butenolides (361)307. The enantiomeric enrichments obtained are excellent, especially in the case of the
(5)-enantiomers. Another useful chiral precursor is the epoxysulphone (362) obtained from the corresponding chlorohydrin which is prepared with 85% ee (rising to 100% after two crystallizations) by at the a yeast reduction of the related k e t o - s ~ l p h o n e ~ ~Attack ~. less hindered site by copper-modified Grignard reagents followed by alkylation Q to the sulphone function using sodium iodoacetate then gives the hydroxy-acids (363). Finally lactonization and elimination gives the (2)-butenolides ( 3 6 4 ) . One weakness in this scheme is the relatively low returns ((60%) from the last two steps. The hydroxy-butenolides (365) are available by a simple condensation of 2-silyloxfuran with an aldehyde along the lines mentioned above280' 281. The stereochemistry of the final product is highly dependent on the reagent(s) used; conditions have been established for the obtention of largely the threo (shown) or the erythro 309 isomers . Disubstituted butenolides ( 3 6 6 ) can be prepared from 310 disubstituted alkynes under Water gas shift reaction conditions . However, judging from the examples quoted, this method is only generally useful when applied to cases where R1=R2 as there seems to be little regiochemical control. Higher homologues, substituted at
FR2b0eH:q Getteral and Synthetic Methods
154
R'
0
R2
0
-"-OH R
0
0
I
t
3: Carboxylic Acids and Derivatives
155
the y-position can be obtained using a related process wherein an alkyne is treated with an alkylmanganese pentacarbonyl species and carbon monoxide3l 1 . Specifica11y 3-aryl-4-methy1bu ten01 ides (367) are available from arylacetic acids by sequential esterification by chloroacetone and aldol c y c l i ~ a t i o n ~ ~The ~ . isomeric butenolides (368) have been made from vinylmalonates by bromolactonisation followed by elimination313. A specific application of this approach is in a synthesis of the natural butenolide acarenoic acid [(368); n-alk=C11H23; R=CH2CO2H1. A total synthesis of (El-neomanoalide (372) has as one of the key features a palladium (0)-mediated coupling of the stannylfuran (370) with the allylic chloride (369I3l4. The subsequent oxidation of the furan ring in the coupled product (371) is greatly assisted by the presence of the trimethylsilyl substituent. An interesting but mechanistically unclear procedure for the preparation of the amino-butenolide derivatives (374) consists of treatment of the 3(2H)-furanones (373) with an arylamine and BOP-C1 in the presence of triethylamine315. Yields are in the range 42-78% for this process which could well .have other applications. A more rational synthesis of amino-butenolides (375) proceeds by condensation of a magnesio ester enolate and a protected cyanohydrin followed by careful a~idification~'~. In an example of a radical based approach to ring-fused butenolides, the propargyl ether is first cyclised using the by now standard procedure. The initial product (377) is then easily isomerized to the more thermodynamically stable endo isomer and finally oxidised to the final product (378); all of the yields are usually very good317. A full account has been given of a total synthesis of paniculide A in which a key intermediate (381) is prepared by annulation of the vinylbutenolide (380) by a tandem Michael addition-aldol sequence using rnalonaldehyde (379) as the the initial nucleophile and final e l e ~ t r o p h i l e ~ ~Predominantly ~. (5)-ylidenebutenolides (382) are formed when 3,4-dienoic acids are treated with K13 and NaHC03 in aqueous acetonitrile319 . Surprisingly, oxidation of the borates (383) using mCPBA in ether containing sodium carbonate does not lead to the expected conjugated 3 20 butenolides but rather to the A3-isomers (384)
.
Phthalides. - A simple route to substituted phthalides (386) involves homologation of o-halobenzyl alcohols (3851 by overall
General and Synthetic Metho&
156
yoNHR ArNH
&co*H
BOP ArNH2 Et3N - Cl
R& 2!R3
KF
(380) Y - O CO,Me
0 (375)
0 (374)
NHR (373)
DMSO DMF
-
Me02C
OH
3: Carboxylic Acids arid Derivutives
157
displacement of the halogen by cyanide followed by anchiomerically assisted hydrolysis321. Both phthalides (386) and 3-substituted homologues may be obtained by @-scissions of alkoxy radicals generated from a variety of benzocyclobutanols by photolysis of their derived h y p ~ i o d i t e s ~ ~Yields ~. are within the range 41-67%. Some more useful regioselectivities have been defined in reductons of monosubstituted phthalic anhydrides to the corresponding phthalide~~~ ~ . another route to 3-cyanophthalides (388) Yet consists of treatment of the cyanohydrins (3871, derived from the corresponding aldehydes using TMSCN, KCN and 18-crown-6, with acetic acid324. Yields are generally in excess of 80%.
Some
useful stereoselectivities have been found in reactions between phthalic anhydride and substituted e - G r i g n a r d reagents leading to, for example, the spiro-phthalide (389)325.
- A full account has been given of the preparation of a-acyltetronic acids (390) by silver ion-induced
Tetronic Acids.
transesterification of r-butylthio acetoacetates by a-hydroxyesters followed by intramolecular aldol condensation326. The natural tetronic acids carlosic, carolic and carlic acids have been obtained in optically active forms from lactic acid using this approach. An alternative and also fairly general approach to acyltetronic acids (390) features hydrogenolysis of the isoxazoles (3911, derived from f1.31 dipolar cycloadditions of nitrile oxides to 4-hydroxy-2-alkynoates, followed by base-mediated ring closure of the resulting keto-imines (392)327. This route has also been used to prepare a related natural product, carolinic acid. Yields are only moderate but the methodology appears to be simple. An intramolecular aldol condensation also forms the final step in an api-_'roach to spirotetronic acids (394) starting from the a-hydroxythioesters (393)328. The intermediate is built up by esterification of the tertiary hydroxy functon in thioesters (393) using an aalkoxyacetyl chloride: yields are good throughout. Disubstituted 2,4-furandiones (396) which cannot tautomerise to the tetronic acid structure are available from diazo keto-esters (395) by treatment with BF3 etherate in methanol329. Yields are high [72-90%1 for this type of product but are poorer when the method is extended to include annulated examples. Chiral thiotetronic acids, a structural feature of a number of antibiotics, have been synthesized using a route which features [3.3] sigmatropic rearrangements of
(390)
(389)
NH
tco2R* +R
0
(397)
(398)
(399)
3: Curboxylic Acids and Derivatives dithioesters derived ultimately from
159
(2)-lactic
acid330.
Valerolactones. - The principle of steric shielding in a naphthyl camphor derivative has been used to control reductions of f3-keto-esters to give the chiral hydroxy-esters (398)331. Subsequent homologation of the ester function in the decyl derivative [ (398); R=~-C10H211,using an approach which precludes the presence of an alkene function in the side chain, then leads to the pheromone (-)-5-hexadecanolide (399). By using the appropriate reductant, either epimer of the initial hydroxy-esters (398) can be obtained. A valerolactone system with an unsaturated side chain has been obtained from stereochemically complementary Claisen rearrangements of the ally1 vinyl ether ( 4 0 0 ) ~ ~ Acid ~ . catalysed rearrangement using 2,6-dimethylphenol gives the anti diastereoisomer (401) whereas in the presence of a palladium catalyst, the corresponding syn isomer is produced, presumably via a -rr-complexwhich adopts a boat-like conformation. Subsequent Baeyer-Villiger oxidation then gives the related valerolactones [e.g.(402) from the anti isomer (40111. Further applications of these routes should be forthcoming. Yet more approaches to the Prelog-Djerassi lactone (403) have been reported333. An asymmetric synthesis relies upon Evans chiral enolate chemistry to prepare the intermediate (404); subsequently, the furan function is converted into a dihydropyranone unit by oxidation [Br2, MeOH] and acidic hydrolysis. Wittig homologation and hydrogenation then completes the synthesis. 9-Silyl enolates of the vinylogous urethane (405) undergo highly stereoselective acylations by a-methylacyl chlorides leading to the valerolactones (4061, following reduction of the initially produced keto-esters using lithium triethylborohydride [Super Hydride]334. Oxidative degradation of these compounds can then be used to prepare the hydroxy-butyrolactone (407) [when R=OBn], amongst many other possibilities. Similar reactions of the corresponding lithium enolates are less stereoselective. An extrememly simple approach to mono- and disubstituted valerolactones (409) is by condensation of the dianion (408), generated from the parent sulphonyl ester using two equivalents of 5-butyl lithium at -78°C in THF, with aldehydes or ketones followed by acidification, for which TFA proved to be the most suitable335 . Yields are in the range of 62-89%. A full description has been given of the SAMP- and RAMP-based route to nearly optically pure
$-zlkylvalerolactones by Michael additions of acetaldehyde hydrazones to unsaturated esters336. The attraction of such excellent optical yields is somewhat diminished by the relatively poor chemical returns associated with this approach. Various enantioselective aldol condensations have been exploited in syntheses of the mevinic acid analogues (410): enantiomeric enrichments of up to 94% have been realized337. An alternative approach to this type of derivative features Michael additions of Fleming's phenyldimethylsilyl cuprate reagent to a , B-unsaturated
lac tone^^^^.
These show a high degree of trans stereoselectivity as
expected and, as described above165, the silyl group can be exchanged €or hydroxyl with retention of configuration. Trapping of the intermediate enolates at least by methyl iodide leads to all-trans trisubstituted homologues.
Intramolecular Reformatsky
condensations of bromoacetates (411) using samarium ( 1 1 ) iodide are also highly stereoselective and lead to the 6-hydroxy lactones (412)339.
The probable intermediacy of a chair-like transition
state should allow predictions to be made of the likely stereochemical outcome of future examples of this reaction. Varying degrees of success have been achieved in stereoselective approaches to the valerolactones [e.g. (41311 by coupling alkoxy aldehydes with The indole alkaloid component (414) has
2-pr0penyl-1,3-dithiane~~'.
been prepared largely [4:11 with the trans stereochemistry shown by radical-mediated intramolecular Michael cyclisation of the acetal (415)341.
Similar cyclizations of the corresponding bromoacetate
were found to be much less efficient.
A
very high level of
stereochemical control at adjacent tertiary and quaternary sites has been observed in Michael additions of various 5,y-unsaturated amides to ethyl crotonate leading to the amides (416)342. reduction [LiA1H4 at - 4 O " C I
Regioselective
and acidification then affords the spiro
lactones (417). A clearly limited route to the unsaturated lactones 2 [ (418): R1,R =alkyl or cycloalkyll consists of dimerisation of an a-phenylthioketone followed by acid-catalysed rearrangement of the resulting a c y l c y ~ l o b u t a n o n e ~ ~Lithium ~. dialkylcuprates add largely to the 4 position of 2-silyloxypyrylium salts: a Mannich reaction of the resulting 2-silyl enolates (419) yields the a-methylenelactones (420) while reaction with NBS affords the bromo derivative (421)344. There would appear to be many other possibilities for the exploitation of these initial products. A three step procedure for the conversion of a butyrolactone into a valerolactone comprises
161
3: Carboxylic Acids and Derivatives
(404)
ph025
Ty
Pho2S?
coy
0
(408)
(407)
-
R R2 I
D
O
(409)
H
B
z
o
~
o
HO (413)
-*--.
,
I
R2
reduction to the lactol followed by one carbon homologation using (EtO)ZPOCH2 (CN)NMe2 and acid hydrolysis345 . Macrolides. - The useful diene synthesis based on palladium(0)catalysed couplings of vinyl triflates and vinylstannanes can be carried out intramolecularly under high dilution (103M) to give the macrolides I(422); n=5-81 in < 60% yield346. A key step in the preparation of the starting materials for this reaction is a regiospecific deprotonation of a methyl ketone function in the presence of an ester linkage. Another currently popular reaction is the Michael addition of radicals to unsaturated esters and this too has been applied to macrolide synthesis [ (423)+(424)1347 . Yields are in the region of 60% at moderate dilutions [3mMolar] in the case of formation of 16-20 membered rings and can be improved by using higher dilutions. Macrolides (424) can also be prepared from the open chain hydroxy-esters using PPL or another lipase from a pseudomonas spp348. In this simple model study, yields of up to 80% have been realized in the formation of 16- or 17-membered rings but, as is usually the case, yields are lower with smaller ring sizes. An unexpectedly difficult macrolactonization during the final stages of a total synthesis of the alkaloid monocrotaline has lead to the development of a novel procedure [ (425)+(426)] based around slow generation of a carboxylate which can then displace a mesylate group349. Unfortunately, the method does not appear to be applicable to simpler substrates and is thus perhaps only suitable for the cyclisation of similarly conformationally restricted precursors. Macrolides (427) containing a masked enone function are of obvious synthetic value especially as this feature is found in a number of natural systems. In an enormous paper, Quinkert and his many colleagues have detailed their approach to this system which is based on photolytic ring cleavage of ortho-quinol acetates to give an intermediate unsaturated keten followed by intramolecular trapping of this reactive function by a distal hydroxy group350. Excellent stereocontrol is observed in intramolecular Diels-Alder cyclizations leading to the polycyclic macrolides (428)351. The precursor enol esters were obtained from enol silyl ethers by mercury(I1) chloride-catalysed exchange with an acid chloride. An ester exchange, in this case catalysed by DMAP, has been used to prepare the intermediate (429) on the way to pyrenophorin, from the corresponding lactol and methyl
163
3: Carboxylic Acids and Derivatives
I
COX
g
(426)
(425)
0
O,Et
"C02Et
(427) 0 OyB(O'Pr),
0 SnBua
(430)
164
Geneml und Synthetic Methods
p h o s p h ~ n o a c e t a t e ~ ~This ~ . method should be applicable to the elaboratioc of a wide variety of substrates suitable for both inter- and intramolecular Wadsworth-Emmons olefinations leading to macrolides. Further extensions have been reported of the four carbon ring expansion methodology extensively studied by Hesse and his colleagues, and which generally lead to macrolides having 16 or more atoms353. Smaller rings (431) are available from related lactol fragmentations in which the key is oxidation of a strategically placed tri-n-butylstannyl group. The lactols (430) have been prepared by a tandem Michael-Michael-aldol approach from 2 - c y ~ l o h e x e n o n eor ~ ~ by ~ alkylation of enolates formed during the initial Michael addition of the tin group355.
Yields are usually
respectable, especially when compared with alternative approaches to decanolides and similar medium-sized lactones; either lead t e t r a - a ~ e t a t eor ~~~ (diacetoxyiodo)benzene are suitable oxidants. A viable, alternative, fragmentation procedure which does not require incorporation of an extra functional group is to oxidize the lactol
[e.g. (432)l by photolysis with mercury(I1) oxide and iodine356. In the example shown, @-scission of the intermediate alkoxy radical leads to the iodo-lactone (433) in 76% isolated yield. Other ring sizes can be made using this method but presumably the range of functional groups which can be incorporated is somewhat limited. Enol ethers undergo oxidative cleavage when treated with PCC; this method offers yet another alternative for the preparation of 9- and 10-membered lactones (435) in these cases also containing a ketone function, by fragmentation of a bicyclic system (434)357. Yields are generally greater than 60% and presumably a range of other functions could be accommodated. Eleven- and twelve-membered macrolides containing an acetylenic bond have been obtained by an established retro-Dieckmann procedure similar to the foregoing method of Hesse but with the acetylene functions masked as a cobalt As yet, the method fails when carbonyl complex [cf.(436)1358. applied to projected syntheses of ten-membered lactones which can be obtained in low yields ( ~ . 2 0 % )from the corresponding w-hydroxy-acids. A total synthesis of methynolide (439) features a different type of ring expansion based on [2.3]-sigmatropic rearrangement^^^'. Thus, treatment of the thiolactone (437) with the triflate derived from 1-hydroxy-2-butanone and subsequent rearrangement gives the eleven-membered lactone (438); reduction of the ketone function and acid catalysed S/O transfer establishes the
3: Carbox-vlicAcids and Derivativrs
165
rtquired twelve-membered ring which is then converted by a number of steps into the natural material. The rather unusual diyn-diolides [(440);n=0 or 11 have been prepared in ~ . 6 0 yields % simply by coupling the appropriate diols and acid chlorides or acyl imidazoles indicating that the molecules are less strained than they may appear to be at first sight360. 4 Carboxvlic Acid Amides Amide Bond Formation. - New coupling reagents for amide bond formation include an analogue of 1,l-carbonyldiimidazole based on an oxdiazolidine dione system which at least offers the advantage
of water-soluble by-products361 and chlorodimethoxy-l,3,5,-triazine derived from cyanuric chloride362. In the latter case, the reaction residues are weakly basic and can therefore be removed using dilute acids. Both reagents deliver generally good yields apparently without racemisation in examples of peptide synthesis. Formation of amides from weakly nucleophilic aromatic amines under mild conditions can pose obvious problems. A solution to these is to couple an acyl fluoride with an 3-trimethylsilylamine using a catalytic amount of TBAF to trigger the reaction363. The acyl fluorides appear to be simple to prepare from the parent acids and cyanuric fluoride. Overall, yields are excellent from this mild procedure and usually in excess of those obtained from comparable couplings using DCC-based methods or the corresponding acyl chlorides, which are also known to react with N-silylamines. An electrochemical method has been developed for the direct seems to be of conversion of esters into a m i d e ~ ~ The ~ ~ reaction . broad scope and yields are in the range 42-91% indicating that this could be the method of choice at least in some cases. Possibly a method of choice for converting esters into primary amides is amminolysis catalysed by sodium cyanide365. Excellent yields are obtained from this much milder procedure which may also be applicable to secondary and tertiary amide preparations. Little or no epimerisation occurs when N-ethyl-proline methyl ester is converted into the corresponding amide using this method.
An even simpler
method, given suitable apparatus, for the elaboration of various hydroxy-amides is to warm a lactone and an amine together at 30-65°C under 9kbar pressure366. Such reactions are usually very sluggish with all but the most nucleophilic of amines at normal pressures.
(438)
(442)
(443)
(439)
3: Carbo,uylic Acids and DerivativrJ
167
Acyl cyanides are able to selectively acylate primary amines in the presence of secondary a m i n e ~ ~ For ~ ~ example, . simply stirring benzoyl cyanide with spermidine in dichloromethane at room temperature for three hours affords an 89% yield of the bis-amide (441). It has been re-emphasized that aryl trichloromethyl ketones, ArCOCCl are excellent reagents for the aroylation of primary amines363'
.
Oxamates (442) can be built up by palladium-catalysed double carbonylations of amines in the presence of an alcohol, ROH369. The method should be especially useful in the construction of heterocyclic systems [e.g. (44311 from amino alcohols. 0-Ketoamides (444) can be prepared by coupling an amine with a t-butylthio acetoacetate in the presence of silver (I) trif l u o r ~ a c e t a t e ~ ~A~ . wide range of amines including examples which are only weakly nucleophilic have been used successfully with yields being in the range of 54-80%. A peptide bond
[cf
(47711 can be formed from an aldehyde [e.g.
(445)] by sequential imine bond formation with an a-amino-ester followed by oxidation to the oxaziridine level (446) and finally photochemically-induced rearrangement371. The latter step is not new but perhaps deserves to be.re-emphasized. N-Hydroxy-amides are available from acylations, using mixed anhydrides, of readily 372 . available 2-trimethylsilyl hydroxylamines The 4-methylphenyl analogue of Lawesson's reagent is particularly effective for the preparation of tertiary thioamides by containing a free NH the thiations of normal a m i d e ~ ~ Thioamides ~ ~ . group cannot be prepared in this way. The reverse reaction, conversion of a thioamide into an amide, can be effected in excellent yield using t-butyl thionitrate, tBuSN02374. Thiocarbamates and thiocarbonates can be similarly desulphurized. Reactions. - Asymmetric a-hydroxylation of enolates can be carried out using a chiral oxaziridine. This method delivers the best optical yields when an additional chiral auxiliary is present, the optimum so far identified being a prolinol derivative. In this way, the tertiary a-hydroxy-amides (448) are obtained with 90% enantiomeric enrichments375. An alternative approach to the related amides (449) is by reduction of the corresponding a-keto-amides, for which purpose lithium or potassium triethylborohydride are the most 376 suitable in terms of the stereoselections [up to 9:1] observed .
Hydrolyses to the parent carboxylic acids can be carried out using warm dilute aqueous hydrochloric acid with no detectable racemisation. anti stereoselection in favour of the isomers (450), the Excellent __ more unusual outcome in such reactions, has been observed in aldol-type condensations of titanium enolates derived from 377 propanamides with simple aldehydes . Oxalate diamides [e.g. (45111 are available from acyloin This method which, condensations of the corresponding perhaps surprisingly, appears to be new, affords variable yields [30-58%1 and can be used intramolecularly. f.3-Keto-amides , (452)370
car barn ate^^^^.
can be obtained in high yields from condensations of enolates of acetophenone and analogues thereof and an isocyanate, The aroyl amides (454) have been prepared in moderate yields [23-5381 by Friedel-Crafts acylations of monosubstituted benzenes using the iminium salt (453) derived from butyrolactone as the elcetrophile380 . Within the obvious constraints of symmetry, such intermediates appear to have potential in a number of other areas. A good example of the synthetic utility of Pd(0)-catalysed couplings of vinyl triflates is in the elaboration of the side chain of an anthramycin model when the triflate (455) is homologated to the dienamide (456) in relatively poor yield (35%)381. Despite this and the fact that similar couplings using B-stannylacrylates are much more efficient, the direct formation of a required amide can clearly offer advantages over proceeding 2 an intermediate ester. Tertiary 2,4-dienamides can be obtained by Wittig-type olefination reactions 382 . between and a,B-unsaturated aldehyde and an arsonium ylide Yields of all trans-isomers are excellent but the toxicity of arsenic compounds must surely mitigate against wide application of this methodology. The metallation chemistry of various phenylthiosubstituted crotonamides and methacrylamides has been investigated and has resulted in the development of routes to a number of homologues of these compounds such as the hydroxy-amides (457)383. A full discussior of the preparation of y,&-unsaturated amides using amide acetal Claisen rearrangements has been published384. By incorporation of a chiral substituent on the nitrogen, asymmetric inductions of between 1.5:l to 15.5:l can be achieved, at least in the substrates studied which were substituted only by methyl groups. Allene carboxanilides [ (458); R2 = Ph or Et] have been prepared by Wadsworth-Emmons condensations of the corresponding ketene with A1 though isolated yie Ids are relatively phosphonoacetani 1ides38
’.
3: Carboxylic Acids and Derivatives
169
zo.-
Ph
0
,OR’ OH
(450)
‘OR’
(448) (449)
R (457 1
0
(452)
170
General and Synthetic Methods
poor [20-48%1, these are reported to be better than those obtained using the related ester phosphonates. 5 Amino Acids a-Amino-acids. - Yet another equivalent of the glycine enolate can be obained by deprotonation of N,N-dibenzyl g l y ~ i n a t e s ~ ~In ~ .the presence of HMPA, reactions with activated bromides, aldehydes and ketones are particularly efficient. Similarly, enolization of the heterocyclic derivative (458) provides another such equivalent which has been used to obtain the 8-fluoro-a-amino-acids (459) following condensation with an aldehyde, reaction with (diethy1amino)sulphur ~ . relatively trif luoride [DAST] and finally h y d r o g e n ~ l y s i s ~ ~The moderate yields are compensated forbythe rapidity of the method and, unusually, although the final products are an almost equal mixture of the two possible diastereoisomers, the intermediate B-hydroxy derivatives are formed largely [E 5 : 1 ] with the allo-threonine stereochemistry [see also ref 3 9 3 1 . Phenylalanine analogues in which the phenyl ring is substituted or replaced by a heterocyclic residue are available from reductions of a-nitro-cinnamates, prepared by Henry condensations between an aromatic aldehyde and an a-nitroacetate388. A nitro group is also used in the activation of the cyclopropyl esters (460) towards attack by a variety of heteronucleophiles [x.OR, SPh, PhNH -N31 as well as by some soft carbon species [cyanide, Yields of the amino-acids (461) are generaly excellent malonate] after removal of the aryl group, designed to shield the ester function. Bromination using NBS followed by dehydrobromination of &-butyl N-BOC-glycine leads to the the imine (462) which without isolation can be coupled with Grignard reagents to give a-amino-acids (463)i thus, the sequence overall constitutes a potentially very useful Other example of the rarer glycine cation equivalent3”. nucleophiles can also be used; coupling with a cyclopentanone enamine for example gives stereospecifically, the anti derivative (464). An improved method has been reported for the preparation of N-tosyl imines [cf.(462)I from g l y o ~ y l a t e s ~ ~One ~ . use of these derivatives is as enophiles in cycloaddition reactions with alkenes leading to the unsaturated a-amino-acid esters (465). A much older approach to a-amino-acids consisting of carbonylation of a mixture 392 of an aldehyde and a primary amide has been further developed .
’”.
3: Carboxylic Acids and Derivatives
171
Yields can be very good from this simple method although the high temperatures required may preclude the presence of a number of functionalities. Many derivatives of t h r e ~ n i n eare ~ ~ available ~ from the unsaturated a-amino-ester (467) obtained by methanolysis of the oxazolidinone (466) during which the presence of a catalytic amount of caesium carbonate is Tungstate-catalysed oxidation of piperidine followed by cyanation, hydrolysis and finally reduction to remove an N-hydroxyl group has been used to prepare pipecolinic acid [2-piperidinecarboxylic acid]394. Overall, this route appears to be a very simple and cheap way for the preparation of a-amino-acids from both cyclic and acyclic secondary amines. As is to be expected however, the major emphasis in this area has once again been concerned with the development of new asymmetric approaches to a-amino-acids, both natural and non-natural. An attractive and versatile route to either enantiomer of the a-amino-acid derivatives (469) consists of regioselective attack at the B-methylene position of the B-lactones (468) by lithium dialkylcuprates or related, higher order cup rate^^'^. Yields are usually 60-70% and both enantiomers of the starting lactones can be prepared from the corresponding serine derivatives by dehydration using Mitsunobu conditions with very little racemisation [see also ref. 4071. Evans and his colleagues have provided another elegant example of the synthetic utility of chiral enolates based on the oxazolidinone ring system in a preparation of the a-bromo-amides (470)396. Subsequent nucleophilic displacement using tetramethylguanidinium azide, hydrogenation and hydrolysis then leads to a-amino-acids or esters in excellent overall yields and usually with at least 94% enantiomeric enrichments. Alternatively, the chiral enolates can be directly converted into the a-azido derivatives by treatment with trisyl a ~ i d e ~ ’ ~A. similar protocol, but starting with an a-haloacetamide derivative and using aldol condensations has been used to prepare a range of chiral 6-hydroxy-a-amino-acids (471)398, which can also be obtained by Lewis-acid mediated aldol condensations between an aldehyde and an NCS in place of Br in (470) E-a-isocyanatoacetyl oxazolidinone isomers of hydroxy-acids (471) have been and R = H I ~ ” . The 2,3-*
[e.
prepared with generally excellent enrichments by a rather different approach wherein aldehydes are condensed with methyl isocyanoacetate by using a chiral ferrocene as the base and a gold complex as the
172
Gmrral and Synthetic Methods 0
R
RMgX
BOCN-COJBu
*
BOCNH COJBu
Y R
(462)
(463) (464)
\
C02Me
O K0N B o C
(467)
R32CuLi
NR’ R2 (468)
(469)
Ph (470)
(471)
(472)
n
= 1,2
3: Curboxylic Acids und Derivatives catalyst4".
173
Various enantiomerically pure 4,5,6-trihydroxy
homologues of this type of amino-acid have also been prepared, starting with ascorbic acid401. The flexibility which is offered by these various routes together with the excellent chemical and optical yields which are usually obtained suggests that these will enjoy considerable attention in the future. The Schollkopf approach featuring homologations of chiral bis-lactim ethers has already been shown to be another powerful method for the asymmetric synthesis of both natural and non-natural a-amino-acids. Futher examples of this are syntheses of essentially optically pure a-methyl homologues of prollne and pipecolinic acid (472)402, an aldol approach to the unsaturated amino-esters(473) by selective [1.2] additions of the lactim ether titanium enolate to a , B-unsaturated aldehydes403 and syntheses of the diamino-acids (474) by Michael additions of the latter type of enolate to nitro-olefins followed by reduction and the usual hydrolysis steps404. A completely different way in which the lactim ether can be used is as Friedel-Crafts electrophiles in reactions with substituted benzenes, leading to a-aryl-glycines (475), typically of at least 95% optical purity405. Again, the impressive optical yields obtained from all of these preparations suggest that the lactim ether method will find many applications. Asymmetric Strecker syntheses of (D)-a-amino-acids have been achieved using reactions between the highly sterically congested galactose-derived imine (476) and TMSCN in the presence of zinc chloride406. Ratios of up to 13:l at the newly created chiral centre have been observed. A variety of a-amino-acid homologues (469) in which the added substituent group, R3, can be azide, phenylthio and alkynyl as well as alkyl or ary1395 are available from attack of the appropriate nucleophiles onto chiral Some useful bis-aziridines derived from (D)-1nannito1~~~. applications of enzymic chemistry in this area have also been developed. Fermenting baker's yeast is capable of distinguishing between enantiomers of N-acetyl a-amino-esters, hydrolysing the (2)-esters much more rapidly408. In many of the examples quoted, variations of the ester function have little effect on the hydrolysis and chemical yields are often 5 . 4 5 % with enantiomeric enrichments of the order of 86-100%. The presence in the important immunosuppressant cyclosporin of the unique a-amino-acid MeBMT (477) has inevitably resulted in the
development of a number of routes to this compound, which will doubtless be of use elsewhere. A reasonably stereoselective but rapid approach has as a key step the condensation of N,N,g-tristrimethylsilyl glycine with the appropriate chiral aldehyde obtained using Helmchen's camphor-derived ester enolate409. In an alternative approach, the key elements of chirality are introduced using a Sharpless epoxidation4" while the approach of Seebach and his co-workers features an application of the chirality transfer principle411 Interest in the synthesis of non-natural, a-substituted-aamino-acids has also been considerable during the period of this review. Some of the foregoing methods can and have been adapted for such preparations, notably the Schollkopf lactim ether approach. The chirality transfer principle, alluded to immediately above, is also useful in this respect. As an example, the oxazolidines (4781, obained from (&I-serine, undergo smooth deprotonation and homologation with a range of electrophiles leading to the a-substituted serines (479) in moderate to good yields after hydrolysis412. Thrronine, glycolic acid and aspartic acid h o r n o l ~ g u e scan ~ ~ ~also be prepared in this way. A slightly different type of stereocontrol has been used to obtain the alanine analogues (481) by enolate alkylations of the 6-lactam (480); under optimized conditions, at least 95% eels are obtained4I4. Somewhat lower but still respectable optical yields [75% or above] of similar a,a-dialkyl glycines have been obtained from the Stork imine alkylation method using Schiff bases derived from (D)-galactodialdehyde415. Racemic a-substituted glutamic acids are available using the original type of Stork imine which undergoes smooth Michael additions to acrylates when treated with solid potassium carbonate in methano1416. Under similar conditions, the aldol condensation products (482) can be obtained in good yields from aromatic aldehydes. The carbanion derived from cyanoacetate (483) and ethanolic sodium ethoxide is useful in the preparation of following a limited range of racemic serine analogues [-.(484)1 reactions with reactive electrophiles, reduction of the ester function [LiBHq] and acidic hydrolysis417. A "one-pot" synthesis of the N-acryloyl amino-acids (485) starting with a ketone, R1R2C0, proceeds by way of the corresponding a-amino-nitrile and delivers 40-60% yields 0verall4l8. 0-Silyl enolates can be homologated to give a,a-disubstituted amino-esters [e.g.(486) (487)I by photolysis
.
175
3: Carboxylic Acids and Derivatives
C02H
R’O (476)
R’ = pivaloyl
(477)
HO (484)
Ph
QNYH 0
R1 R2
wOMe
OSiMe3 hv NSCGEt
-
Ph
C02Me
xNHC02Et
with ethyl azidoformate; yields of around 60% are typical419
.
A method for the overall inversion of stereochemistry in the more common (g)-a-amino-acidsproceeds by way of the corresponding (S)-a-hydroxy-esters (488), available with retention of stereochemistry by the diazotisation method, followed by conversion to the trif lates and displacement using ~ - b e n ~ y l h y d r o x y l a m i n e ~ ~ ~ . Chemical and optical yields of the resulting ( R ) enantiomers (489)432 are usually very good, except when the substituent [R] is phenyl, and the final step again emphasizes the suitablility of the triflate group for such displacements. The same transformation can also be carried out using Mitsunobu conditions with N-alkoxycarbonyl 0-benzylhydroxylamines [R02CHNOCH2Ph] as the nucleophilic species421. Yields from this method are rather variable and again
-
are particularly poor with mandelic acid esters, a limitation of yet another procedure for effecting this type of inversion which features a combination of a Mitsunobu reaction using hydrazoic acid followed by Staudinger degradation of the resulting a-azido-esters, which can be isolated if required422. Overall yields are 35-61% with, in most cases, complete Walden inversion being observed. A rather different approach to a-aryl amino-esters [e.g. (490)l also involves triflate displacements but in Friedel-Crafts alkylations of aryls using threonine trif lates as the e l e ~ t r o p h i l e s ~ ~The ~ . one drawback with this simple method is that although the optical yields are excellent, the chemical returns are rather poor [ 2 0 - 4 0 % 1 . In an extension of methodology reported last year, it has now been shown that the a-azido-boronic esters (491) derived from the corresponding (S)-pinanediol boronic esters undergo an additional overall insertion of a carbon when treated with lithium dichloromethane, LiCHC12; oxidation of the resulting a-chloro-boronic esters (492) using sodium chlorite then gives the a-azido-acids (493) and thence chiral a-amino-acids generally with excellent enantiomeric enrichments424. Unoptimized yields for the whole sequence are between 32 and 63%; an additional feature is that t-butyl ester functions survive the sequence which can therefore be used to prepare glutamic acid derivatives amongst others. Both enantiomers of the useful sulphone (494) have been adjacent to prepared from the corresponding ~ e r i n e ~ Alkylation ~ ~ . the sulphone group can then be used to obtain a range on non-natural amino-acids such as homophenylalanine. The butyrolactone (495) of homoserine can be easily prepared by Dibal-H
3: Carboxylic Acids and Derivatives
177
reductions of N-trityl aspartates in 50-60% yields426. The nature of the ester groups seems relatively unimportant but rather the steric bulk of the N-trityl function plays the crucial role of screening the a-ester group from attack by the reducing agent. The same principle has been used to selectively reduce the y-ester group in monoesters of glutamic acid using lithium aluminum h ~ d r i d e ~ Such ~ ~ . mono-esters of both aspartic and glutamic acids can be obtained in often excellent yields by standard aci6-catalysed esterification but using HBF4.0Et2 as the catalyst428. An alternative and simple preparation of L-homoserine [commercially available but very expensive] from L-methionine has also been reported429. The homoserine is formed as an aqueous solution and subsequent manipulations of this lead to'the useful aldehyde (496) in 40% overall yield [see also ref. 4501. This latter intermediate undergoes a variety of Wittig homologations and just one example of the potential of this chemistry is shown by subsequent transformations of these products into trihydroxy-uamino-acids and thence into hydroxypipecolinic acids. Wittig homologations are also featured in a neat approach to the unsaturated amino-diesters (498) in which the phosphoranes (4971, derived from chiral aziridine-2-carboxylates, are key [cf.ref. 4381. Barton decarboxylation of N-BOC-phenylalanine and in situ trapping of the resulting radical species by Michael additions to activated alkenes leads to the racemic B,y-unsaturated amines (499)431. Perhaps of greater interest is the finding that the same chemistry can by used to prepare the amino-acid derivative (500) from the mono-a-benzyl ester of aspartic acid and methyl acrylate. A limited range of racemic N-benzyloxy-amino acids [cf.(489)420' 4211 can be prepared by reactions between organolithiums and the E-benzyloxime of glyoxylic acid432. An improved procedure for the preparation of 3-hydroxy-a-amino acid esters themselves from the parent amino-esters has been reported,during which little or no 433 racemisation occurs .
intermediate^^^'.
6-Amino-acids. - Good stereocontrol in favour of the anti isomers (501) has been observed in homologations of the dianion of methyl 0-benzoylaminobutanoate generated usipg two equivalents of LDA in THF at -78°C434'. Yields are usually good from a range of electrophiles including primary saturated and allylic iodides and
General and Synthetic Methods
178
CI H
/S02Ph HQ Ph BOCHN TO, , . JH
H BOCHN
TrHN
0
p C02An
(494)
R'CHO t
Et02C
NHCOR
EtOZC
(497)
NHCOR (498)
Ph"f'"" NHBOC (499)
BOCHNAC02Bz
R = C02Me, CN, NO2
(500)
NHAr
OSiMe3
c02et k N(503) H P h
3: CarboxylicAcids and Derivatives
179
aldehydes. Similar anti diastereoisomers ( 5 0 2 ) are the major products from condensations between silylketen acetals and a , 6-unsaturated imines catalysed by TMS trif late435. When silylketen acetals derived from acetoacetate are reacted in this way with E-phenylbenzaldehyde imine, a single diastereoisomer (503) is obtained suggesting further useful applications of this methodology. During a synthesis of L-daunosamine, a neat and highly stereoselective route to 6-amino acid derivatives [e.g.(505)1 has been developed based on Lewis-acid catalysed additions of silylketen (504)1436. acetals of methyl acetate to nitrones [u. Once again, the newly created centre is anti to the existing one. An asymmetric version of a previously reported route to B-amino-acids featuring condensation of tin (I11 enolates of thioesters with a-imino-esters has the chiral auxiliary attached to the imine nitrogen and leads to amino-diesters [e.g.(506)] with around 70% enantiomeric enrichment437. Ring opening of the chiral c&-aziridine-2-carboxylic acids (507), prepared from either serine or threonine, by reaction with a thiol gives largely the 6-amino-acids ( 5 0 8 ) 438. [cf.ref. (430) y-
and Other Amino-acids.
-
A new and practical route to (RI-GABOB
(511) proceeds by sequential nucleophilic attack on phenyl lithium
and azide onto (El-epichlorohydrin (509) followed by oxidative cleavage of the phenyl ring in the intermediate (510)439. An alternative and less stereoselective approach to GABOB featuring the use of an iodolactonization to introduce the hydroxyl function has been reported in full440. A new approach to fluoro-allenes has been applied to a synthesis of the potential GABA transaminase suicide inhibitor ( 5 1 2 ) 441. Many w-amino-acids can be prepared by reductive aminolysis of a cyclic anhydride for which a combination of a secondary amine, sodium borohydride and triethyloxonium tetrafluoroborate is particularly The occurence of the y-amino-acid statine (513) [shown as its 3 2 . 4 5 enantiomerl in a variety of biologically active natural products has stimulated a great deal of synthetic effort in this area: many of the methods will no doubt be applicable to the preparation of other y-amino-acids. An approach to this enantiomer and analogues thereof features first the elaboration of the chiral tetramic acids (514) from the corresponding E-BOC-a-amino-acids by condensation of a derived mixed anhydride with Meldrum's acid443. Subsequent stereocontrolled reduction to give the cis-pyrrolidones
180
-A 04-C02Me Znlp
(504)
(505)
R, H NH Ph
7 0 2 H
N H
NH,
(507)
(508)
(509)
+CO2H
OH
+ NHBOC
C02Et
0
(516)
3: Carhoxylic Acids und Derivurives
181
(515) and finally hydrolysis completes this very efficient route which must however be performed under carefully controlled conditions if high yields are to be realized. In a second approach which relies on a final reduction step, the 6-keto-ester (5161, derived from N-BOC-leucine activated as its imidazoyl derivative and ethyl lithioacetate, i s converted into 3S,4?-statine by treatment with a mixture of lithium borohydride and 2,N-dibenzoyl-D~ y s t e i n e ~ This ~ ~ . known method gave the best stereoselection [=.6:11 of a number which were examined. An alternative protocol for the homologation of leucine proceeds by way of the amino-alcohol (5171, obtained using established methodology, which is subjected to inversion at the alcohol centre by conversion into the corresponding degradation of the ally1 side chain o x a ~ o l i d i n o n e ~ ~Oxidative ~. using the Sharpless ruthenium tetroxide recipe then completes the synthesis. The 1,2- and 1,3-amino-alcohol systems in general can be prepared by cyclic carbamate formation and this too has been illustrated in an approach to S , S - ~ t a t i n e ~ The ~ ~ .key step in this methodology is cyclisation of the chloride (518) induced by treatment with silver(1) fluoride or better, in terms of stereoselection, using the latter together with a palladium(I1) catalyst. The major isomer [(518) in this case1 can be formed to an extent of 15:l. The statin synthesis is then completed by hydroboration and hydrolysis. Syntheses of both the 35,45 and 35,4E enantiomers use an extension of a previously reported method where chiral acetals undergo selective additions of a l l y l ~ i l a n e s ~ ~For ~ . the statin syntheses, N-BOC-leucinal is converted into the required chiral acetals using (g)-l13-butanediol. As another alternative, Z-leucinal can be homologated to the epoxy-alcohol (520) [without the need to use Sharpless conditions!]; this is then attacked largely regioselectively by Red-A1 to give an excellent yield of the diol (521) and thence statin following selective oxidation [Pt, air, NaHC03, H20] and h y d r o g e n ~ l y s i s ~Evans-type ~~. enolate methodology has also been used to prepare 3R,42-statin using oxazolidinones derived from methylthioacetic acid449 and statin analogues have been obtained by way of the potentially useful dithiane (522) derived from (L)-aspartic acid450 [cf.ref. 4291. Asymmetric Hydrogenation of Unsaturated Amino-acid Derivatives. - A review of this area has appeared451. Some chiral rhenium-diphosphine
analogues of the more familiar rhodium species are capable of catalysing the hydrogenation of N-acetyl-a,@-unsaturated esters to give a-amino esters with 82-988 enantiomeric enrichments452. Detailed studies of the reductions of N-acetylcinnamates using the latter type of chiral rhodium complex have provided useful kinetic data and insights into the origins of the enantioselectivities provided by these catalyses453. The potential substrates (523) for this type of asymmetric reduction have been obtained from N-protected-w-amino-aldehydes by Wadsworth-Emmons homologations using a phosphonate formally derived from g l y ~ i n e ~ The ~ ~ .( 5 ) stereochemistry has only been tentatively assigned; these authors also describe a protocol for preparing differentially protected analogues from these initial olefination products. Hydrogenations of this type using DIPAMP-Rh complexes can also be used in kinetic resolutions of the racemic a-methylene-esters (524)455. Enantiomeric enrichments of both isolates are usually impressive. Amino-acid Protection. - g-BOC-(L)-a-amino-acids can be esterified under the obligatory neutral conditions by either ethanol or benzyl alcohol using papain as the catalyst456. Only the a-carboxylic acid groups of N-BOC aspartic or glutamic acids are esterified under these mild and simple conditions. No racemisation is apparent: this would be unexpected as a further application of this method is in the kinetic resolution of racemic g-BOC-a-amino-acids as the (D)-enantiomers are not esterified. The same transformations can also be effected in good to excellent yields using mixed anhydrides prepared from isopropenyl c h l o r ~ f o r m a t e ~ ~Such ~ . reactions also appear to be free of racemisation when Na-carbamates are the substrates but this can be a problem with yQ-acyl derivatives. N'Trt-a-amino-acids can be converted into the corresponding diphenylmethyl (Dprn) esters using Mitsunobu conditions, provided that an excess of the Mitsunobu reagents is used458. Dpm esters are also formed directly from amino-acids when the latter are treated with tris (Dpm) phosphate [ (Ph2CHO)3P=Ol 459. Side chain Dpm ethers can be similarly prepared. The range of ester protecting groups which can be removed using cobalt(II1) salts has been reviewed460. A full account has been given of the mild, palladium-catalysed hydrostannolysis method for the cleavage of ally1 esters and Na-allyloxycarbonyl (Alloc)
183
3: Carboxylic Acids and Derivatives
H NHZ Pd"
n
jgs
ZHN(CH2),yC02Me NHZ
OH
BOCHN
(523)
n
= 2 or 3
(522)
NHBOC (524)
(525)
0
YNHTfl
FmocHN
(526)
C02H
A Phvo
N-(CH2),-CO~Bu(Bz) I
0
(527)
I x4 functions461. In view of this, it is perhaps predictable that a route to diallyl dicarbonate, analogous to (BOC)20 or BOC anhydride, for the introduction of groups would be developed462. Yields with this reagent are generally within the range of 81-96%.
$-allot
In view of the enormous growth of palladium chemistry, it is hardly surprising that further palladium-labile $-protecting
groups
have been developed. One example is the isopropenylallyloxycarbonyl (IPAoc) function (525) which can be removed by treatment with Pd2[dba13.CHC13 in hot d i ~ x a n ~ When ~ ~ .this is done in the presence of an activated Na-protected-a-amino-acid derivative, a peptide is formed directly in 69-80% yield. The IPAoc group survives the removal of BOC groups using TFA or 6M HC1 but the function is clearly incompatible with the hydrogenolysis of benzyl functions. A further useful feature is the observation that the sulphur group in methionine residues does not poison the palladium catalyst used to remove the IPAoc group. Two additional and highly activated acylating reagents for the introduction of a wide variety of Sa! protecting groups have been developed based on the 6-trif luorobenzotriazole nucleus464 and on the norbornene skeleton465. Both lead to excellent yields of the derivatives and the latter has the additional feature of water soluble by-products. An overview of the ~ m o and c ~other ~ ~base-labile N a protecting groups has been presented466. Another special amino protecting group is the Na-Teoc [ trimethylsi lylethyloxycarbonyl I function which is specifically removed by fluoride ions. A variety of reagents for the introduction of this functionality have been examined; the best one turned out to be the N-hydroxysuccinimide derivative T~oc-OSU~~'. A drawback associated with the standard method for the N-acylation of a-amino-acids in general using chloroformates or dicarbonates in the presence of aqueous sodium hydroxide is that traces of dipeptides can also be formed, presumably 9attack of a second amino-acid on a mixed anhydride species. This can be prevented by using Hunig's base, diisopropylethylamine as the base468. An alternative for the preparation o f N-trifluoroacetyl derivatives of amino-acids is to use a polymer-based reagent469. Many N"-amino-acid protecting groups [x. BOC, Z etc.] can be removed using a mixture of triflic acid, TFA and thioanisolc. It has now been found that the process is very much quicker [ < 10 minsl when TMS triflate is used in place of the triflic acid470. N"-2
3: Carboxylic Acids and Derivatives
185
groups can be removed extremely cleanly under electrolytic conditions, using a palladium-graphite cathode, yields of the free amino-acids being in excess of 90%~~'. The stabilities of other protecting groups to these conditions have yet to be fully defined but, at least, N-tosyl functions survive. Catalytic transfer hydrogenolysis is also a useful method for the removal of benzylic functions; ammonium formate has been suggested as another suitable source of hydrogen472. The Fmoc function is removed upon treatment with TBAF in DMF473. Presumably the mildly basic nature of the fluoride ion mimics the more conventional bases, typically ~ i p e r i d i n e ~used ~ ~ , to cleave this type of protecting group.
TBAF
has to be used with caution in some cases as it can also attack benzyl ester groups and aspartyl peptide bonds. However, its reactions with Fmoc groups are usually so rapid, indeed more rapid than piperidine, that these should not be serious drawbacks. The Na-trityl function in a,w-E-trityl diamino-acids is selectively removed upon treatment with a 1% solution of TFA in dichloromethane; subsequently, the resulting free amino group can be masked as the Fmoc derivative, thus providing an approach to the unsymmetrically 474 protected diamino-acids (526) The thiol function in (L)-cysteine can be protected as its acetamidomethyl derivative475. In such compounds the amino group
.
can then be protected as the Fmoc derivative for which purpose Fmoc azide is reported to be a superior reagent to the more conventional chloroformate, Fmoc-C1. An alternative way to protect the thiol group in this amino-acid is to form the corresponding S-t-butyl derivative; such a tactic has proven successful in a solid-state peptide synthesis476. A wide range of thiol protecting groups can be cleaved by treatment with thallium trifluoroacetate in TFA to 477 give the corresponding cystine derivatives . The trityl (Trt) function has been recommended for the protection of histidine side chains especially in combination with
Na-Fmoc groups and other protecting groups which are labile to mildly acidic conditions478. For example, and N"-Trt group can be hydrolysed selectively in the presence of an Nlm-Trt function. The
N3-(€J') the
N1-
position of histidines can be efficiently alkylated by way of
BOC479 or phenacyl derivatives, the latter method w-Aminoa1 lowing the iqtroduction of saturated alkyl groups480 ($1
I
esters can be oxidised to the N-hydroxy derivatives (527) by treatment with benzoyl peroxide and acetyl chloride in reasonable
General and Synthetic Methods
186
y i e l d s which i n c r e a s e w i t h i n c r e a s i n g c h a i n lengths481. chroman-6-sulphonyl
The groups h a s been i n t r o d u c e d as a n a c i d labile
function f o r t h e p r o t e c t i o n o f guanidine s i d e chains482.
Although
many a c i d i c r e a g e n t c o m b i n a t i o n s c a n be u s e d t o remove i t , t h e method o f c h o i c e is b r i e f
[< 5 minsl exposure
t o 45% h y d r o b r o m i c
a c i d i n acetic a c i d . References 1. 2.
M.P. Cooke, j r . , J . Org. Chem., 1 9 8 7 , 52, 5729. K . S o a i , H. M a c h i d a a n d N . Y o k o t a , J . Chem. SOC., P e r k i n T r a n s . l . , 1987, 1909. F o r a review o f t h e u s e of camphor d e r i v a t i v e s i n s i m i l a r p r e p a r a t i o n s of c h i r a l a c i d s ( 5 1 , see
43,
3. 4. 5. 6. 7. 8. 9. 10. 11.
12. 13. 14. 15. 16. 17.
18. 19. 20.
21. 22.
W. O p p o l z e r , T e t r a h e d r o n , 1 9 8 7 , 1969. D.A. E v a n s , T.C. B r i t t o n a n d J . A . E l l m a n , Tetrahedron L e t t . ,
1 9 8 7 , 28, 6141. R. D e r n o n c o u r a n d R. Azerad, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4661. F o r a m e t h o d of r e s o l v i n g a c i d s , see C.C. Duke a n d R . J . W e l l s , A u s t . J . Chem., 1 9 8 7 , 40, 1 6 4 1 . T. O h t a , H . T a k a y a , M . K i t a m u r a , K . Nagai a n d R. N o y o r i , J. Org. Chem., 1 9 8 7 , 52, 3174. T. H a y a s h i , N . Kawamura a n d Y . I t o , J . Am. Chem. SOC., 1 9 8 7 , 1 0 9 , 7876. M. T r o m e l a n d M. R u s s . Agnew. Chem. I n t . Ed. E n g l . , 1 9 8 7 , 26, 1 0 0 7 . F o r a review o f m e t h o d s of o x i d a t i o n u s i n g p o t a s s i u m p e r m a n g a n a t e , see A . J . F a t i a d i , S y n t h e s i s , 1 9 8 7 , 8 5 . P.L. A n e l l i , C . B i f f i , F. M o n t a n a r i a n d S. Q u i c i , J . O r g . Chem., 1 9 8 7 , 52, 2559. P.E. E a t o n , G.T. C u n k l e , G. M a r c h i o r o a n d R.M. M a r t i n , J. O r g . Chem., 1 9 8 7 , 52, 948. J . Chen a n d X . J . Zhou, S y n t h e s i s , 1 9 8 7 , 586. G.P. L i e s e n a n d C.N. S u k e n i k , J . O r g . Chem., 1 9 8 7 , 52, 455. F o r a m e t h o d of k i n e t i c r e s o l u t i o n o f c y c l i c a n h y d r i d e s , see M. Ohshima, N . M i y o s h i a n d T. Mukaiyama, Chem. L e t t . , 1 9 8 7 , 1233. J . K i j i , H. K o n i s h i , T. Okano, S . K o m e t a n i a n d A . Iwasa, Chem. L e t t . , 1 9 8 7 , 313. G. Maier a n d R . W i l m e s , Chem. B e r . , 1 9 8 7 , 119. J.T.B. F e r r e i r a , W.O. C r u z , P.C. V i e i r a a n d M. Y o n a s h i r o , J. Or Chem, 1 9 8 7 , 52, 3698. F.Z. Webster a n d E M . S i l v e r s t e i n , J . O r g . Chem., 1 9 8 7 , 52, 689 a n d 5 0 6 6 . 7566. T.R. F e l t h o u s e , J . Am. Chem. S o c . , 1 9 8 7 , H . Kawano, Y . I s h i i , T. I k a r i y a , M. S a b u r i , S. Y o s h i k a w a , Y. U c h i d a a n d H. Kumobayashi, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 9 0 5 . S e e a l s o T. S h i r a i w a , Y . S a d o , S . F u j i i , M. Nakamura a n d H . Kurokawa, B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 8 2 4 . M.A. F l i n d e r s a n d G . M . W h i t e s i d e s , J . O r g . Chem., 1 9 8 7 , 52, 2838. G . S a b b i o n i a n d J . B . J o n e s , J. O r g . Chem., 1 9 8 7 , 52, 4565. M, L u y t e n , S. M u l l e r , B. H e r z o g a n d R. Keese, Helv, Chim. A c t a . , 1 9 8 7 , 70, 1 2 5 0 . E . Guibe-Jampel, G . R o u s s e a u a n d J . S a l a u n , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 1 0 8 0 . S e e a l s o J . S a l a u n a n d B. K a r k o u r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4669. K . F u r a t a , S. H a y a s h i , Y.Miwa a n d H . Y a m a m o t o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5841.
120,
.
109,
3: Carboxylic Acids and Derivatives 23.
R.
Roy a n d A.W.
Rey, T e t r a h e d r o n L e t t . ,
187 1987,
28,
4935.
See
a l s o D. Terunuma, M . Motegi, M. T s u d a , T. Sawada, H. Nozawa
24. 25.
26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36.
a n d H. N o h i r a , J . O r g . Chem., 1 9 8 7 , 52, 1 6 3 0 . P . Mohr, L. R o s s l e i n a n d C . Tamm, H e l v . Chim. A c t a . , 1 9 8 7 , 142. J . H i r a t a k e , M. I n a g a k i , Y . Y a m a m o t o a n d J. Oda, J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 1 0 5 3 . For a r e l a t e d and sometimes s u p e r i o r method u s i n g c h i r a l a l c o h o l s , see M. Ohshima a n d T. Mukaiyama, Chem. L e t t . , 1 9 8 7 , 377. H. Kunz a n d H.-G. L e r c h e n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 8 7 3 . F o r o p t i m i s e d c o n d i t i o n s f o r t h e d i a z o t i s a t i o n of s e r i n e d e r i v a t i v e s , see C . M o r i n a n d G. Sawaga, S y n t h e s i s , 1 9 8 7 , 479. H . S k o p a n , H . G u n t h e r a n d H . Simon, Agnew. Chem. I n t . Ed. E n g l . , 1 9 8 7 , 26, 1 2 8 . H . M a h l e r a n d M. B r a u n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 5145. 0. T a k a h a s h i , K . Mikami a n d T. N a k a i , Chem. L e t t . , 1 9 8 7 , 6 9 . X-C. H e a n d E.L. E l i e l , T e t r a h e d r o n , 1 9 8 7 , 43, 4979. P . F . C o r e y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2801. T. K o b a y a s h i , T. S a k a k u r a a n d M. T a n a k a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2721. K . H . B e l l , A u s t . J . Chem., 1 9 8 7 , 40, 1 7 2 3 . T . Kikukawa, Y . I i z u k a , T. S u g i m u r a , T . H a r a d a a n d A. T a i , Chem. L e t t . , 1 9 8 7 , 1 2 6 7 . R . F r e n e t t e , M. Kakushima, R . Zamboni, R . N . Younq a n d T.R. V e r h o e v e n , J. O r g . Chem. I . 1987 , 52, 304. J. O t e r a . Y . N i i b o a n d H. Aikawa. T e t r a h e d r o n L e t t . . 1987. 28 , 2147 H. R u h o l l a n d H . J . S c h a f e r , S y n t h e s i s , 1 9 8 7 , 408. E . Koepp a n d F . V o g t l e , S y n t h e s i s , 1 9 8 7 , 1 7 7 . S.K. R i c h a r d s o n , A . J e g a n a t h a n a n d D . S . W a t t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2335. M. M i u r a , F. A k a s e , M. S h i n o h a r a a n d M. Nomura, J. Chem. SOC., P e r k i n T r a n s . 1 , 1 9 8 7 , 1 0 2 1 . M. B e l l a s s o u e d , F. H a b b a c h i a n d M. Gaudemar, T e t r a h e d r o n , 1 9 8 7 , 43, 1 7 8 5 . N . R a g o u s s i s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 93. V . R a u t e n s t r a u c h , H e l v . Chim. A c t a . , 1 9 8 7 , 7 0 , 5 9 3 . H . Uchiyama, M. Kawano, T . K a t s u k i a n d M . Y z a g u c h i , Chem. L e t t . , 1 9 8 7 , 351. V . K . Aggarwal a n d S. W a r r e n , T e t r a h e d r o n L e t t , 1 9 8 7 , 1925. M.T. Ayoub, M . Y . S h a n d a l a and A.W. J a f e r , S y n t h e s i s , 1 9 8 7 , 653. J. C h e n a u l t a n d J-F. E. D u p i n , S y n t h e s i s , 1 9 8 7 , 498. B . B . S n i d e r a n d Y.S. K u l k a r n i , J . Org. Chem., 1 9 8 7 , 52, 3 0 7 . F. Kudo, T. S h i b a t a , T . K a s h i m u r a , S. M o r i a n d N . S u g i t a , Chem. L e t t . , 1 9 8 7 , 577. F o r a n o p t i m i s a t i o n of P d - c a t a l y s e d c a r b o n y l a t i o n s of n a p h t h a l e n e s t o g i v e 6 - n a p h t h o i c a c i d s , see T. J i n t o k u , H. T a n i g u c h i a n d Y . F u j i w a r a , i b i d . , p . 1159. R . E . D o l l e , S.J. S c h m i d t a n d L.I. K r u s e , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 9 0 4 . A. H u t h , I . B e e t z , I . Schumann a n d K . T h i e l e r t , T e t r a h e d r o n , 1 9 8 7 , 43 1 0 7 1 . P. M e n G h e l i , M.C. R e z e n d e a n d C . Zucco, S y n t h . Commun., 457. 1987, R . R . J o s h i a n d N.S. N a r a s i m h a n , S y n t h e s i s , 1 9 8 7 , 9 4 3 . N . S a t y a n a r a y a n a a n d M. P e r i a s a m y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28 , 2633. H. S u z u k i , Q. Y i , J . I n o u e , K . Kusume and T. O g a w a , Chem. L e t t . , 1987, 887.
70,
28,
~
37. 38. 39. 40.
41. 42. 43. 44. 45. 46. 47. 48. 49.
50.
51. 52. 53. 54. 55.
1
28,
17,
Gmeral und Synthetic Methods
188 5657. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80.
81. 82. 83. 84. 85. 86.
T. Yamauchi, K. Nakao a n d K. F u j i i , J. Chem. SOC., P e r k i n T r a n s . 1, 1 9 8 7 , 1 2 5 5 . T . Y a m a u c h i , K . N a k a o a n d K . F u j i i , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 1 4 3 3 . T. Yamauchi, K. H a t t o r i , K. Nakao a n d K. Tamaki, B u l l . Chem. S O C . J p n . , 1 9 8 7 , 3, 4015. Y . H o n d a , A . O r i a n d G . T s u c h i h a s h i , B u l l . Chem. S O C . J p n . , 1987, 60, 1027. 0. P i c ~ l o ,F . S p r e a f i c o , G. V i s e n t i n a n d E. V a l o t i , J. O r g . Chem., 1 9 8 7 , 52, 1 0 . G . C a s t a l d i , S . C a v i c c h i o l i , C . G i o r d a n o a n d F. U g g e r i , J. O r g . Chem., 1 9 8 7 , 5 2 , 3 0 1 8 a n d 5 6 4 2 . D.P. R i l e y , D.P. G e t m a n , G . R . B e c k a n d R.M. H e i n t z , J . O r g . Chem., 1 9 8 7 , 5 2 , 2 8 7 . J . C h e n a n d X T Z h o u , S y n t h . Commun., 1 9 8 7 , 17, 1 6 1 . H . T s u t s u i , M . M u t o , K . M o t o y o s h i a n d 0. M i t s u n o b u , Chem. L e t t . , 1987, 1595. R . D e z i e l , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 3 7 1 . M. I w a m u r a , T . I s h i k a w a , Y . Koyama, K . S a k u m a a n d H . Iwamura, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 7 9 . D. G r e n o u i l l a t , J - P . S e n e t a n d G . S e n n y e y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5827. K. T a k e d a , K. Tsuboyama, H. T a k a y a n a g i a n d H. O g u r a , S y n t h e s i s , 1987.560. S . F u k u o k a , S . T a k i m o t o , T . K a t s u k i a n d M. Y a m a g u c h i , T e t r a h e d o n L e t t . , 1 9 8 7 , 28, 4711. A . K . Kumar a n d T.K. C h a t G p a d h y a y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 3713. S . A h m a d a n d J . I q b a l , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 114. T . M i t s u d o , Y . H o r i , Y . Yamakawa a n d Y . W a t a n a b e , J . O r g . Chem., 1 9 8 7 , 5 2 , 2 2 3 0 . M. D e g u e i l - C a s t a i n g , B . D e Jeso, S . D r o u i l l a r d a n d B. M a i l l a r d , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 9 5 3 . E . G u i b e - J a m p e l a n d G . R o u s s e a u , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3563. S. H a t a k e y a m a , K. S a t o h , K. S a k u r a i a n d S. T a k a n o , T e t r a h e d r o r L e t t . , 1 9 8 7 , 28, 2 7 1 3 . B O ' C o n n o r a n d G . J u s t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 2 3 5 . S-I. M u r a h a s h i , T . Naota, K . I t o , Y . Maeda a n d H . T a k i , J. O r g . Chem., 1 9 8 7 , 52, 4 3 1 9 . P . B r o u g h a m , M . S . Cooper, D . A . C u m m e r s o n , H . H e a n e y a n d N . Thompson, S y n t h e s i s , 1 9 8 7 , 1 0 1 5 . A . P . K r a p c h o a n d G . G a d a m a s e t t i , J . O r g . Chem., 1 9 8 7 , 52, 188( T.R. B e e b e , R . B a l d r i d g e , M . B e a r d , D . C o o k e , I . D e F a y s , V . H e n s l e y , D . Hua, J - C . L a o , D . M c M i l l e n , D. M o r r i s , R . Noe, E . O ' B r y a n , C. S p i e l b e r g e r , M . S t o l t e a n d J . W a l k e r , j r . , J . O r g , Chem., 1 9 8 7 , 52, 3 1 6 5 . J . Y o s h i d a a n d S . I s o e , Chem. L e t t . , 1 9 8 7 , 6 3 1 . R.M. M o r i a r t y , R . K . V a i d , M.P. D u n c a n a n d B . K . V a i d , Tetrahedron L e t t . , 1987, 2845. E . Nakamura, S. A o k i , K. S e k i y a , H . O s h i n o a n d I . Kuwajima, J . Am. Chem. S O C . , 1 9 8 7 , 109, 8 0 5 6 . E . Nakamura, K. S e k i y a a n d I . Kuwajima, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 3 7 . E . K e i n a n a n d D . P e r e z , J . O r g . Chem., 1 9 8 7 , E r n 2576. See a l s o N . S l o u g u i a n d G . R o u s s e a u , S y n t h . Commun, 1 9 8 7 , 17, 1 . A . N a g , A. S a r k a r , S.K. S a r k a r a n d S . K . P a l i t , S y n t h . Commun. 1 9 8 7 , 17, 1 0 0 7 .
28,
3: Carboxylic Acids and Derivutivc.s 87. 88. 89. 90. 91. 92. 93. 94.
189
C. P e t r i e r a n d J-L. Luche, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2347. S e e a l s o C . L a r p e n t , R . Dabard a n d H. P a t i n , i b i d , p.2507. T. H u d l i c k y , G . S i n a i - Z i n g o l e a n d M.G. N a t c h u s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 2 8 7 . D.H.R. B a r t o n , L. B o h e a n d X . L u s i n c h i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6609. T. S a k z , K . M i y a t a , K. H o n d o , M. U t a k a a n d A. T a k e d a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 6 0 , 3 4 2 1 . T. S a k a i , K . M i y a t a , M . U t a k a a n d A. T a k e d a , B u l l . Chem. SOC. J p n . , 1987, 60, 1063. D. B e r b r e i t e r a n d J . J . L a l o n d e , J . O r q . Chem., 1 9 8 7 , 52, 1601. H . S a k a t a a n d I . K u w a j i m a , T e t r a h e d r o m L e t t . , 1 9 8 7 , 28, 5 7 1 9 . Y . Y a m a m o t o , S . N i s h i i a n d T . I b u k a , J . Chem. SOC. Chem. Commun., 1 9 8 7 , 1 5 7 2 . S e e a l s o Y . Y a m a m o t o , J . Yamada a n d T . 5820. U y e h a r a , J . Am. Chem. S O C . , 1 9 8 7 , V . N . G o q t e , A . A . N a t u a n d V . S . P o r e , S y n t h . Commun., 1 9 8 7 , 1 7 , 1421. S . R a u c h e r a n d D . C . S c h i n d e l e , S y n t h . Commun., 1 9 8 7 , 17, 6 3 7 . G . M i q n a n i , D . Morel a n d F . G r a s s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 5505. A. Ono, T . Maruyama a n d J . K a m i m u r a , S y n t h e s i s , 1 9 8 7 , 1 0 9 3 . S . T s u b o i , H. F u r u t a n i , A. T a k e d a , K . Kawazoe a n d S . S a t o , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 2 4 7 5 . K . O . K o u a , M.E. B o r r e d o n , M. D e l m a s a n d A . G a s e t , S y n t h . Commun., 1 9 8 7 , 17, 1 5 9 3 . I . F l e m i n g a n d N . D . K i n d o n , J . O r g . Chem. SOC., Chem. Commun., 1987, 1177. M.T. G a l l a r d o , V . a n d A . Zapata, S y n t h . Commun., 1 9 8 7 , 17, 1165. T . Y a m a z a k i , N . I s h i k a w a , H . I w a t s u b o a n d T. K i t a z u m e , J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 3 4 0 . N . K h o u k h i , M . V a u l t i e r a n d R . C a r r i e , T e t r a h e d r o n , 1 9 8 7 , 43, 1811. W . Mormann a n d E . H i s s m a n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 0 8 7 . T . M u k a i y a m a , M . T a m u i r a a n d S . K o b a y a s h i , Chem. L e t t . , 1 9 8 7 , 743. P . B e s l i n , A . D l u b a l a a n d G. L e v e s q u e , S y n t h e s i s , 1 9 8 7 , 8 3 5 . S . Berrada a n d P . M e t z n e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 409. H. I s h i h a r a , N. M a t s u n a m i a n d Y . Yamada, S y n t h e s i s , 1 9 8 7 , 3 7 1 . B.M. T r o s t a n d M . L a u t e n s , T e t r a h e d r o n , 1 9 8 7 , 43, 4 8 1 7 ; J . Am. Chem. SOC., 1 9 8 7 , 1469. S e e a l s o B.M. T r o s t , G.B. T o m e t z k i a n d M-H. Hung, i b i d . , p . 2 1 7 6 . D. D j a n a n b i n i , B. C a z e s a n d J . G o r e , T e t r a h e d r o n , 1 9 8 7 , 43, 3441. M. A h m a r , B. C a z e s a n d J . Gore, T e t r a h e d r o n , 1 9 8 7 , 43, 3 4 5 3 . H . Y o n e m u r a , H . N i s h i n o a n d K . K u r o s a w a , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 342. T F u c h i g a m i a n d Y . N a k a q a w a , J. O r g . Chem., 1 9 8 7 , 52, 5 2 7 6 . S . C . C h e n , K.T. Huh a n d W . H . P a r k , S y n t h e s i s , 1 9 8 7 , 5 9 . H . Y o n e m u r a , H . N i s h i n o a n d K . K u r o s a w a , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 8 0 9 . S . T a k a n o , S . T o m i t a , M. T a k a h a s h i a n d K . O q a s a w a r a , Chem. L e t t . , 1987, 1569. Z-C. C h e n , Y-Y. J i n a n d P . J . S t a n q , J. O r q . Chem., 1 9 8 7 , 4115. X. Huanq a n d B. Chen, S y n t h e s i s , 1 9 8 7 , 480. D. E n d e r s , A.S. D e m i r , H. P u f f a n d S. F r a n k e n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 7 9 5 .
109,
95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110.
111. 112. 113. 114.
115. 116. 117.
118. 119. 120.
~
2,
109,
2,
190 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138.
139. 140. 141. 142.
143.
144. 145. 146. 147. 148. 149. 150. 151.
Gerierul arid Syrirlietic Methods J.M. Brown and A.P. James, J. Chem. SOC., Chem. Commun., 1987, 181. C.W. Hung and H.N.C. Wong, Tetrahedron Lett., 1987, 28, 2393 N. Nagashima and M. Ohno, Chem. Lett., 1987, 141. M. Kawai, M. Onaka and Y. Izumi, J. Chem. SOC., Chem. Commun 19187. 1203. N. Minowa and T. Mukaiyama, Chem. Lett., 1987, 1719. S. Kobayashi and T. Mukaiyama, Chem. Lett., 1987, 1183. Y. Hashimoto, H. Sugumi, T. Okauchi and T. Mukaiyama, Chem. Lett., 1987, 1691; 1695. H. Stetter and H. Skobel, Chem. Ber., 1987, 120, 643. F.A. Davis and A.C. Sheppard, J. Or Chem., 1987, 52, 954. M. Larcheveque and Y. Petit, Tetrahzdron Lett., 1 9 8 7 28, 1993 K. Otsubo, J. Inanaga and M. Yamaguchi, Tetrahedron Lett., 1987, 2, 4435. M. Alpegiani and S. Hanessian, Tetrahedron Lett., 1987, 28, 278. T. Sato, A. Tanaka T. Tajima and T. Fujisawa, Chem. Lett., 1987, 1979. H. Takahashi, T. Morimoto and K. Achiwa, Chem. Lett., 1987, 855. S. Tsuboi, H. Furutani, M. Utaka and A. Takeda, Tetrahedron Lett., 1987, 28, 2709; S. Tsuboi, H. Furutani and A. Takeda, Bull. Chem. SOC. J n., 1987, 60, 833. S. Tsuboi. E. Nishyvama. H. Furutani, M. Utaka and A. Takeda, J. Org. Chem., 19871 52; 1359. Y. Kato, H. Ohta and G. Tsuchihashi, Tetrahedron Lett., 1987, 28, 1303. KH. Pearson and M-C. Cheng, J. Org. Chem., 1987, 52, 3176. For new routes to 1,3-dioxolane-4-ones, see T.R. Hoye, B.H. Peterson and J.D. Miller, J. Org, Chem., 1987, 52, 1351 and W.H. Pearson and M-C. Cheng, ibid, p.1353. D.H.R. Barton, A. Gateau-Olesker, S.D. Gero, B. Lacher, C. Tachdjian and S.Z. Zard, J. Chem. SOC., Chem. Commun., 1987, 1790. T. Oesterle and G. Simchen, Liebigs Ann. Chem., 1987, 693. S. Hanessian and P.J. Murray, J. Org. Chem., 1987, 52, 1171. M. Onaka, R. Ohno, N. Kawai and Y. Izumi, Bull. Chem. SOC. Jpn., 1987, 60, 2689. For a review of this and related condensations, see M. Braun, Angew. Chem. Int. Ed. Engl., 1987, 26, 24. N. Iwasawa and T. Mukaiyama, Chem. Lett., 1987, 463; for some useful insights into these types of reactions leading to chiral products, see C. Gennari, L. Colombo, G. Bertolini and G. Schimperna, J. Org. Chem., 1987, 52, 2754. A. Revis and T.K. Hilty, Tetrahedron Lett., 1987, 28, 4809. C-N. Hsiao, L. Liu and M.J. Miller, J. Org. Chem., 1987, 52, 2201. A. Griesbeck and D. Seebach, Helv. Chim. Acta., 1987, 70, 1320. R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H. Kumobayashi and S. Akutagawa, J. Am. Chem. SOC., 1987, 109, 5856. K. Nakamura, K. Inoue, K. Ushio, S. Oka and A. Ohno, Chem. Lett., 1987, 679. D. Seebach, S. Roggo, T. Maetzke, H. Braunschweiger, J. Cercus and M. Krieger, Helv. Chim. Acta., 1987, 70,1605. M. Utaka, H. Higashi and A. Takeda, J. Chem. SOC., Chem. Commun., 1987, 1368. T. Kitazume and T. Kobayashi, Synthesis., 1987, 187.
.
3: Carboxylic Acids and Derivatives 152. 153. 154. 155. 156. 157. 158. 159. 160.
191
T , K i t a z u m e , T . K o b a s y a s h i , T. Yamamoto a n d T. Yamazaki, J. Org. Chem., 1987, 3218. A . M a n z o c c h i , R. C a s a t i , A. F i e c c h i a n d E . S a n t a n i e l l o ., J. Chem. SOC., P e r k i n T r a n s . 1,1987, 2753. D.W. B r o o k s , R.P. K e l l o g g a n d C.S. C o o p e r , J. Org. Chem., 1987,
3,
52, 192. -
D . S e e b a c h a n d B. H e r r a d o n , T e t r a h e d r o n L e t t . , 1987, 28, 3791. D. B u i s s o n , C . S a n n e r , M. L a r c h e v e q u e a n d R. A z e r a d , T e t r a h e d r o n L e t t . , 1987, 28, 3939; D. B u i s s o n , S. H e n r o t , M. L a r c h e v e q u e a n d R . A z e r a d , i b i d . , p . 5033. B . I . G l a n z e r , K . F a b e r a n d H . G r i e n g l , T e t r a h e d r o n , 1987, 43, 5791.
Z-F. X i e , H. Suemune a n d K . S a k a i , J . Chem. SOC., Chem. Commun., 1987, 838. G . P i c o t i n a n d P. M i g i n l a c , J . Org. Chem., 1987, 52, 4796. F o r a r e v i e w of m e t h o d s f o r o b t a i n i n s a c t i v a t e d z i n c , see E . E d r i k , T e t r a h e d r o n , 1987, 43, 2203. T . Yokozawa, N . I s h i k a w a a n d T . N a k a i , Chem. L e t t . , 1987,
1971. 161. 162.
S. S i b i l l e , E. d ' I n c a n , L . L e p o r t , M-C. M a s s e b i a u a n d J. P e r i c h o n , T e t r a h e d r o n L e t t . , 1987, 28, 55. Y . I t o a n d S . T e r a s h i m a , T e t r a h e d r o n L e t t . , 1987, 28, 6625 a n d
163.
M.
6629. L a r c h e v e q u e a n d S. H e n r o t , T e t r a h e d r o n L e t t . ,
1987,
28,
1781. 164.
K.
O t s u b o , J. I n a n a g a a n d M .
1987, 165.
28, 4437.
I . Fleming and P.E.J.
Yamaguchi,
Tetrahedron L e t t . ,
Sanderson, Tetrahedron L e t t . ,
1987,
28,
4229. 166. 167.
168. 169.
U . W i d m e r , S y n t h e s i s , 1987, 569. K-M. Chen, K . G . G u n d e r s o n , G . E . Hardtmann, K. P r a s a d , 0. R e p i c a n d M . J . S h a p i r o , Chem. L e t t . , 1987, 1923; K-M. Chen, G.E. Hardtmann, K . P r a s a d , 0. R e p i c a n d M . J . S h a p i r o , T e t r a h e d r o n L e t t . , 1987, 28, 155. Y . Yamamoto, S . N i s h i i a n d T . I b u k a , J . Chem. SOC., Chem. Commun., 1987, 464. K . N a r a s a k a , Y . U k a j i a n d K . W a t a n a b e , B u l l . Chem. SOC. J p n . ,
1987,
170. 171. 172. 173. 174.
60,
1457.
X . C r e a r y , J. Org. Chem., 1987, 52, 5027. S . T s u b o i , H. F u r u t a n i a n d A . T a k e d a , S y n t h e s i s , 1987, 292. T . S a k a k u r a , H. Y a m a s h i t a , T . K o b a y a s h i , T. H a y a s h i a n d M. T a n a k a , J . Org. Chem., 1987, 52, 5733. S. C a c c h i , P.G. C i a t t i n i , E. K r e r a a n d G. O r t a r , T e t r a h e d r o n
L e t t . , 1987, 28, 3039. K.A. K a n d e e l a n d J . M . Vernon,
J. Chem. SOC., P e r k i n T r a n s .
1,
1987, 2023. 175. 176. 177.
G.D.S. Ananda, P.J. C r e m i n s a n d R . J . S t o o d l e y , J . Chem. SOC., Chem. Commun., 1987, 882. C.P. Reddy a n d S . T a n i m o t o , S y n t h e s i s , 1987, 575. P. Renaud, M . H u r z e l e r a n d D . S e e b a c h , H e l v . Chim. A c t a . ,
1987,
70,292.
179.
T . Hosokawa, T. O h t a , S. Kanayama a n d S. M u r a h a s h i , J. Org. Chem., 1987, 52, 1758. F o r a d i s c u s s i o n of a v a r i e t y of s y n t h o n s of m e t h y l 3 - o x o p r o p a n o a t e , see S. Wolfe a n d R . Z . S t e r z y c k i , Can. J. Chem., 1987, 65, 26. Y. H a y a s h i , K. W a r i i s h i a n d T. M s a i y a m a , Chem. L e t t . , 1987,
180.
K.E.
178.
1243. Henegar a n d J . D .
1051.
Winkler, Tetrahedron L e t t . ,
1987,
28,
192 181. 182. 183. 184.
185. 186. 187.
188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207.
208.
D.F. T a b e r , J . C . A m e d i o , j r . , a n d K - Y . J u n g , J . O r g . C h e m . , 1 9 8 7 , 52, 5 6 2 1 . D.H.G. C r o u t a n d D.L. R a t h b o n e , J . Chem S O C . , Chem. Commun., 1987, 290. A. Padwa, D . N . K l i n e a n d J. P e r u m a t t a m , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 9 1 3 . C.M. M o o r h o f f a n d D.F. S c h n e i d e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 559. F o r s y n t h e s e s a n d c h e m i s t r y of t h e c o r r e s p o n d i n g t - b u t y l t h i o e s t e r s , see S.V. L e y a n d P.R. Woodward. i b i d , p . 345. T . S a k a i , M. I s h i k a w a , E . Amano, M. U t a k a a n d A . T a k e d a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 2 2 9 5 . Y , Masuyama, K . Yamada a n d Y . K u r u s u , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 443. R.G. S u t h e r l a n d , A.S. Abd-El-Aziz, A. P i o r k o and C.C. Lee, F o r full d e s c r i p t i o n s o f S y n t h . Commun., 1 9 8 7 , 17, 3 9 3 . r e l a t e d t r a n s f o r m a t i o n s u s i n g a r y l l e a d t r i a c e t a t e s , see D . J . A c k l a n d a n d J . T . P i n h e y , J . Chem. S O C . , P e r k i n T r a n s . 1 , 1 9 8 7 , 2689 a n d 2695. J . S . Baum. D . A . S h o o k . H . M . L . Davies a n d H . D . S m i t h . S v n t h . Commun., i 9 8 7 , 1709. K . T o m i o k a , K . Y a s u d a a n d K . K o g a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 3 4 5 ; K . T o m i o k a , W. S e o , K . Ando a n d K . K o g a , T e t r a h e d r o n L e t t . , 1987, 28, 6637. K . Van S a n t a n d M.S. S o u t h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 0 1 9 . M . O h n o , S. M a t s u o k a a n d S . E g u c h i , S y n t h e s i s . , 1 9 8 7 , 1 0 9 2 . J . C e r v i l l o . J . M a r a u e t a n d M. M o r e n o - M a n a s , J . Chem. S O C . . Chem. Commun., 1 9 8 7 , 6 4 4 . C . A g a m i , F. M e y n i e r a n d T R i z k , S y n t h . Commun., 1 9 8 7 , 17, 4 1 ; C. A g a m i a n d F . C o u t y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 5 6 5 9 . R . B a l l i n i , M. P e t r i n i a n d Synthesis., 1987, 711. T. S h o n o , S. K a s h i m u r a , Y . Yamaguchi a n d F . Kuwata, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 4 1 1 . P . De-Shong, G.A. S l o u g h a n d A.L. R h e i n g o l d , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2,2 2 2 9 . P . Dowd a n d S-C. C h o i , J . Am. Chem. S O C . , 1 9 8 7 , 109, 3 4 9 3 . X-P. Gu, N. N i s h i d a , I . I k e d a a n d M . O k a h a r a , J . O r q . Chem., 1 9 8 7 , 52, 3 1 9 2 . C . B r u c k n e r a n d H-U. R e i s s i g , Chem. B e r . , 1 9 8 7 , 120, 6 1 7 a n d 627. T . M u k a i y a m a , S. K o b a y a s h i , M . T a m u r a a n d Y. S a g a w a , Chem. L e t t . , 1 9 8 7 , 491. D . E n d e r s , A.S. D e m i r a n d B.E.M. R e n d e n b a c h , Chem. B e r . , 1 9 8 7 , 120, 1731. H . S t a c h a n d M. Hesse, H e l v . Chim. A c t a . , 1 9 8 7 , 70,3 1 5 . S. V a l v e r d e , M . M a r t i n - L o m a s , B. H e r r a d o n a n d S . G a r c i a Ochoa, T e t r a h e d r o n , 1 9 8 7 , 43, 1 8 9 5 . P.F. Schuda, C.B. Ebner a n d S . J . P o t l o c k , S y n t h e s i s , 1987, 1055. M.A. R i z z a c a s a and M.V. S a r g e n t , A u s t . J . Chem., 1 9 8 7 , 40, 1619. H . G . M c F a d d e n , R.L.N. H a r r i s a n d C.L.D. J e n k i n s , Aust. J. Chem., 1 9 8 7 , 40, 1 6 1 9 . A. F u e n t e s , J . M . Marinas a n d J . V . S i n i s t e r r a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 9 5 1 ; J . O r g . Chem, 1 9 8 7 , 52, 3 8 7 5 . For r e l a t e d a n d u s e f u l a l t e r n a t i v e , see H . M o i s o n , R . T e x i e r B o u l l e t a n d A. F o u c a u d , T e t r a h e d r o n , 1 9 8 7 , 43, 5 3 7 . E. A n a e l e t t i . P . T u n d o a n d P , . V e n t u r e l l o . J . Chem. SOC.. P e r k i n s T r a n s 1, 1 9 8 7 , 7 1 3 .
28,
17,
.
z
3: Carboxylic Acids and Derivatives 209. 210. 211. 212. 213. 214. 215. 216.
193
120,
M.T. R e e t z , R . P e t e r a n d M . v o n I t s t e i n , Chem. B e r , 1 9 8 7 , 121. H. A m r i a n d J . V i l l i e r a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 5 2 1 . T . U y e h a r a , N . A s a o a n d Y . Y a m a m o t o , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 4 1 0 . T . S a t o h , S. I t o h , T. O h a r a a n d K . Yamakawa, B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 1 8 3 9 . X . C h o n g - y i n g , L . G u a n g - j i a n a n d Z . Z h e n , S y n t h . Commun., 1839. 1987, R . T a n i k a g a , N . K o n y a , T . T a m u r a a n d A. K a j i , J. Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 8 2 5 . T . I s h i h a r a a n d M. K u r o b o s h i , Chem. L e t t . , 1 9 8 7 , 1 1 4 5 . S . L a u g r a u d , A. G u i n g a n t a n d J . d ' A n g e l o , J . O r g . Chem., 1 9 8 7 , 52, 4788. T. S u g i t a , M. E i d a , H . I t o , N. K o m a t s u , K . A b e a n d M. S u a m a , J. O r g . Chem., 1 9 8 7 , 52, 3 7 8 9 . K . T a k e s h i t a , Y . S e k i , K . K a w a m o t o , S . M u r a i a n d N . S o n o d a , J. O r g . Chem., 1 9 8 7 , 52, 4 8 6 4 . K . O h e , H. T a k a h a s h i , S. Uemura a n d N . S u g i t a , J. O r g . Chem., 1 9 8 7 , 52, 4 8 5 9 . E . P i e r s a n d R.T. S k e r l j , J . Chem. S O C . , C h e m . Commun., 1 9 8 7 , 1025. S e e a l s o T . N . M i t c h e l l , R . W i c k e n c a m p , A . A m a m r i a , R. D i c k e a n d U . S c h n e i d e r , J. O r g . Chem., 1 9 8 7 , 52, 4 8 6 8 . J . T s u j i , M. N i s a r a n d I . M i n a m i , Chem. L e t t . , 1 9 8 7 . 2 3 . A . B e r n a r d i , C . C a r d a n i , L. C o l o m b o , G . P o l i , G. S c h i m p e r n a a n d C. S c o l a s t i c o , J . O r g . Chem., 1 9 8 7 , 5 2 , 8 8 8 . M. B r a n d , S . E . D r e w e s , G . L o i z o u a n d G . H . P . ROOS, S y n t h . 795. Commun., 1 9 8 7 , T. T s u d a , T. Y o s h i d a , T. K a w a m o t o a n d T . S a e g u s a , J . O r g . Chem., 1 9 8 7 , 52, 1 6 2 4 . T. T s u d a , H . S a t o m i , T. H a y a s h i a n d T . S a e g u s a , J . O r g . C h e m . , 1 9 8 7 , 52, 439. F . O r s K i a n d F. P e l i z z o n i , S y n t h . Commun., 1 9 8 7 , 1389. T . I b u k a , N . T a n a k a , S. N i s h i i a n d Y . Y a m a m o t o , J . Chem. S O C . , C h e m . Commun., 1 9 8 7 , 1 5 9 6 . Y . I k e d a , J. U k a i , N. I k e d a a n d H. Y a m a m o t o , T e t r a h e d r o n , 1 9 8 7 , 43, 7 4 3 . 0. P i v a , F . H e n i n , J . M u z a r t a n d J - P . P e t e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 8 2 5 . Y . Y a m a m o t o , S. H a t s u y a a n d J . Yamada, J . Chem. SOC., Chem. Commun., 1 9 8 7 , 5 6 1 . F . C a m p s , J . C o l l a n d J . G u i t a r t , T e t r a h e d r o n , 1 9 8 7 , 43, 2 3 2 9 . T . M i t s u d o , M. K a d o k u r a a n d Y . W a t a n a b e , J . O r g . Chem., 1 9 8 7 , 52, 1695. Y . I t o , M. S a w a m u r a , M. M a t s u o k a , Y . M a t s u m o t o a n d T . H a y a s h i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 8 4 9 . H-C. R a t h s a n d E.V. Dehmlow, Chem. B e r . , 1 9 8 7 , 120, 6 4 7 . Y . H a y a s h i a n d T. M u k a i y a m a , Chem. L e t t . , 1 9 8 7 , 1 8 1 1 . T . J . G o u l d , M. B a l e s t r a , M . D . W i t t m a n , J . A . G a r y , L . T . R o s s a n o See also a n d J . K a l l m e r t e n , J . O r g . Chem., 1 9 8 7 , 52, 3 8 8 9 . M . D . W i t t m a n a n d J. K a l l m e r t e n , i b i d . , p. 4 3 0 3 . H. O c h i a i , Y . Tamura, K. T s u b a k i a n d 2 . Y o s h i d a , J. O r g . C h e m . , 1 9 8 7 , 52, 4 4 1 8 . E . N e g i s h i , T . T a k a h a s h i , S . B a b a , D.E. Van H o r n a n d N . O k u k a d o , J. Am. Chem. S O C . , 1 9 8 7 , 2393. J.K. S t i l l e a n d B.L. G r o h , J. Am. Chem. S O C . , 1 9 8 7 , 109, 8 1 3 . S. K u r o d a ; T. K a t s u k i a n d M. Y a m a g u c h i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 8 0 3 . J . M o r e y , D . Gree, P. Mosset, L. T r o u p e t a n d R . G o r e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 9 5 9 .
17,
~
~
217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237. 238.
17,
17,
109,
~
239. 240. 241.
~
Getteral urid Synthetic Methods
194 242. 243. 244.
T. J e f f e r y , S y n t h e s i s , 1 9 8 7 , 7 0 . R.M. M o r i a r t y , R . K . V a i d a n d P . F a r i d , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 7 1 1 . D . H . W a d s w o r t h , S.M. G e e r and M.R. D e t t y , J . Org. Chem., 1 9 8 7 , 52, 3663. N . S l o u g u i a n d G. R o u s s e a u , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 1 6 5 1 . X . I t o , S. N a k a n i s h i and Y . O t s u j i , Chem. L e t t . , 1987,2103. M . Ahmar, J-J. B a r i e u x , B. C a z e s a n d J . G o r e , T e t r a h e d r o n , 1 9 8 7 , 43, 5 1 3 . Y . I s h i i , K . Yamawaki, T . Y o s h i d a , T . U r a a n d M. Ogawa, J. O r g . Chem., 1 9 8 7 , 52, 1 8 6 8 . T.R. B e e b e , R . A d k i n s , R . B a l d r i d g e , V. Hensley, D . M c M i l l e n , D. M o r r i s , R . Noe, F.W. N g , G . P o w e l l , C. S p e i l b e r g e r and M. S t o l t e , J. O r g . Chem., 1 9 8 7 , 52, 5 4 7 2 . I . M i n a m i and J . T s u j i , T e t r a h e d r o n , 1 9 8 7 , 4 3 , 3 9 0 3 . J . Lehmann a n d N. M a r q u a r d t , S y n t h e s i s , 1 9 8 7 , 1 0 6 4 . H . Hemmerle a n d H - J . G a i s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 3471. A . M c K i l l o p a n d J . A . T a r b i n , T e t r a h e d r o n , 1 9 8 7 , 43, 1 7 5 3 . Z.K.M.A. E l S a m i i , M . I . A 1 Ashmawy a n d J . M . Mellor, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 9 4 9 . S. K o n s t a n t i n o v i c , R , . V u k i c e v i c a n d M . Lj. M i h a i l o v i c , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 5 1 1 . S. M u r a t a and T . S u z u k i , Chem. L e t t . , 1 9 8 7 , 8 4 9 . M.J. K u r t h a n d E.G. B r o w n , J . Am. Chem. S O C . , 1 9 8 7 , 6844. P.G. Gassman a n d K . J . B o t t o r f f , J . Am. Chem. S O C . , 1 9 8 7 , 7547 * Y . T a m a r u , M. H o j o a n d 2. Y o s h i d a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 325. Y . T a m a r u , T. B a n d o , M. Hojo a n d 2. Y o s h i d a , T e t r a h e d r o n 2497. L e t t . , 1987, N . G n o n l o n f o u n a n d H. Z a m a r l i k , T e t r a h e d r o n L e t t . , 1 9 8 7 , 4053. P . P a l e a n d H. C h u c h e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 4 4 7 . D.M.T. C h a n , T.B. Marder, D . M i l s t e i n a n d N . J . T a y l o r , J . Am. Chem. SOC., 1 9 8 7 , 6385. T . N a k a n o , M. Kayama a n d Y . Nagai, B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 1 0 4 9 . D.P. C u r r a n a n d C-T. C h a n g , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2477. T. M o r i k a w a , T. N i s h i w a k i , Y . I i t a k a a n d Y . K o b a y a s h i , Tetrahedron L e t t . , 1987, 671. S e e a l s o K. F u g a m i , K. O s h i m a a n d K . U t i m o t o , i b i d , p. 8 0 9 . S . F u k u s a w a , M. I i d a , A. N a k a n i s h i , T . F u j i n a m i a n d S . S a k a i , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 9 2 0 . L.A. P a q u e t t e , A . G . S c h a e f e r a n d J . P . S p r i n g e r , T e t r a h e d r o n , 1 9 8 7 , 43, 5 5 6 7 . Z . J e d l i n s k i , M. K o w a l c z u k , P . K u r c o k , M. G r z e g o r z e k a n d J . E r m e l , J . O r g . Chem., 1 9 8 7 , 52, 4 6 0 1 . S . T a k a n o , S. T o m i t a , M. T a k a h a s h i a n d K . Ogasawara, C h e m . L e t t . , 1987, 1379. G. S t o r k a n d S.D. R y c h n o v s k y , J . Am. Chem. S O C . , 1 9 8 7 , 1564 a n d 1565. R.K. B o e c k m a n , j r . , D.K. H e c k e n d o r n a n d R.L. C h i n n , T e t r a h e d r o n L e t t . , 1987, 28, 3551. G . H . P o s n e r , M. W e i t z b e r g a n d S . J e w , S y n t h . Commun., 1 9 8 7 , 1 7 , 6 1 1 , F o r a r e v i e w of asymmetric M i c h a e l a d d i t i o n s t o c h i r a l a - s u l p h i n y l b u t e n o l i d e s , see G . H . P o s n e r , A c c . Chem. R e s . , 1 9 8 7 , 20, 7 2 . R . K . H a y n e s , P.A. S c h o b e r a n d M.R. B i n n s , A u s t . J . Chem., 1 9 8 7 , 4 0 , 1 2 2 3 , R.K. H a y n e s and P.A. S c h o b e r , i b i d . , p . 1 2 4 9 . _.
245. 246. 247. 248. 249. 250. 251. 252. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 266. 267. 268. 269. 270. 271. 272. 273.
274.
28,
109,
28,
109,
28,
109,
28,
28,
109,
3: Carboxylic Acids and Derivatives 275. 276. 277. 278. 279. 280.
281. 282. 283. 284. 285. 286. 287. 288. 289. 290. 291. 292. 293. 294. 295. 296.
297. 298. 299. 300.
301.
195
J . P . M a r i n o , R . F e r n a n d e z de l a P r a d i l l a a n d E . L a b o r d e , S y n t h e s i s , 1987, 1088. J . P . Marino a n d M.W. K i m , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 9 2 5 . M . H r y t s a k a n d T . D u r s t , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1150. M . U t a k a , H . W a t a b u a n d A. T a k e d a , J. org. Chem., 1 9 8 7 , 52, 4363. A.L. G u t m a n , K . Zuobi a n d A. B o l t a n s k y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 8 6 1 . C.W. J e f f o r d , A.W. S l e d e s k i a n d J . B o u k o u v a l a s , T e t r a h e d r o n F o r s y n t h e s e s of ( + I - e l d a n o l i d e , see L e t t . , 1 9 8 7 , 28, 9 4 9 . R.M. O r t u n o , R. Merce a n d J. F o n t , T e t r a h e d r o n , 1 9 8 7 , 43, 4 4 9 7 ( f r o m g - r i b o n o l a c t o n e ) and S. B u t t , H.G. Davies, M . J . Dawson, G . C . L a w r e n c e , J . L e a v e r , S.M. R o b e r t s , M.K. T u r n e r , B.J. W a k e f i e l d , W.F. W a l l a n d J . A . W i n d e r s , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 9 0 3 ( m i c r o b i a l r e d u c t i o n method). C.W. J e f f o r d , D.Jaggi, G . B e r n a r d i n e l l i a n d H. B o u k o u v a l a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 0 4 1 . P . B r a v o , G. R e s n a t i , F . V i a n i a n d A . A r n o n e , T e t r a h e d r o n , 1 9 8 7 , 43, 4 6 3 5 , T. F u j i s a w a , E. K o j i m a a n d T . S a t o , Chem. L e t t . , 1 9 8 7 , 2 2 2 7 . C.W. J e f f o r d a n d Y. Wang, J . C h e m . S O C . , Chem. Commun., 1 9 8 7 , 1513. 2041 A.T. R u s s e l l a n d G. P r o c t e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , a n d 2045. K . O t s u b o , K . Kawamura, J . I n a n a g a and M. Y a m a g u c h i , C h e m . L e t t . , 1987, 1487. J . B a r l u e n g a , J . R . F e r n a n d e z and M. Yus, J . Chem. S O C . , Chem Commun., 1 9 8 7 , 1 5 3 4 . J . C . C a r r e t e r o , S. D e L o m b a e r t a n d L. Ghosez, T e t r a h e d r o n 2135. L e t t . , 1987, A . S a k a m o t o , Y . Yamamoto a n d J . Oda, J. Am. Chem. S o c . , 1 9 8 7 , 109, 7188. S e e a l s o F . M o r i u c h i , H. M u r o i a n d H . A i b e , Chem. L e t t . , 1987, 1141. R . Z s c h i e s c h e a n d H-U. R e i s s i g , L i e b i g s Ann. C h e m . , 1 9 8 7 , 3 8 7 . L e u c k and L.W. H a r r i s o n , T e t r a h e d r o n L e t t . , R.C. L a r o c k , D . J . 1 9 8 7 , 28, 4 9 7 7 . E . J . C o r e y , R . K . B a k s h i , S . , S h i b a t a , C-P. C h e n a n d V . K . S i n g h , J. Am. Chem. S O C . , 1 9 8 7 , 7925. T . S a k a i , A. Yamawaki, T. Katayama, H. O k a d a , M. U t a k a a n d A. T a k e d a , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 1 0 6 7 . H . N a t s u g a r i , Y . Kawano, A. M o r i m o t o , K. Y o s h i o k a a n d M. O c h i a i , J. Chem. SOC., Chem. Commun., 1 9 8 7 , 6 2 . K . T a n a k a , K . M i n a m i a n d A. K a j i , Chem. L e t t . , 1 9 8 7 , 8 0 9 . Y . T a m u r a , T. Y a k u r a , J . H a r u t a a n d Y . K i t a , J. O r g . C h e m . , 1 9 8 7 , 52, 3 9 2 7 . For an approach using electrochemical o x i d a t i o n , see M.P. C a p p a r e l l i , R.E. D e S c h e p p e r a n d J . S . S w e n t o n , i b i d . , p. 4 9 5 3 . A . J . P e a r s o n , M.W. Z e t t l e r a n d A . A . P i n k e r t o n , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 6 4 . S e e a l s o A . J . P e a r s o n a n d M.W. Zettler, i b i d . , p. 1243. P.J. G a r r a t t a n d J.R. P o r t e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 351. 7534. E . J . C o r e y a n d W. S u , J . Am. C h e m . S O C . , 1 9 8 7 , A . J . P o s s a n d R . K . B e l t e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 5 5 5 . F o r a r e l a t e d c y c l i s a t i o n s e q u e n c e , see A . J . P o s s a n d M.S. Smyth, i b i d . , p 5469. H.J. B e s t m a n n a n d M. S c h m i d t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2111.
28,
28,
109,
109,
302. 303. 304. 305. 306. 307. 308. 309. 310. 311. 312. 313. 314. 315. 316. 317. 318. 319. 320. 321. 322. 323. 324. 324. 326. 327. 328. 329. 330. 331.
G . P . V o l d r i n i , L. L o d i , E . T a g l i a v i n i , C . T a r a s c o , C . T r o m b i n i a n d A . U m a n i - R o n c h i , J . O r g . Chem., 1 9 8 7 , 52, 5 4 4 7 . C. K u r o d a , S. S h i m i z u a n d J . Y . S a t o h , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 8 6 . K . N i s h i t a n i a n d K . Yamakawa, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 655. S. M a t s u i , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 1 8 5 3 . For a route b a s e d o n k e t e n d i t h i o a c e t a l s , see A . D a t t a , H . I l a a n d H . J u n j h a p p a , T e t r a h e d r o n , 1 9 8 7 , 43, 5 3 6 7 . T . M i n a m i , K . W a t a n a b e , T. C h i k u g o a n d Y . K i t a j i m a , Chem. L e t t . , 1987, 2369. R . B l o c h ahd L. G i l b e r t , J . O r g . Chem., 1 9 8 7 , 5 2 , 4 6 0 3 ; R. B l o c h a n d M . S e c k , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2,5819. R. T a n i k a g a , K . H o s o y a a n d A . K a j i , S y n t h e s i s , 1 9 8 7 , 3 8 9 . C.W. J e f f o r d , D . Haggi a n d J . B o u k o u v a l a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 0 3 7 ; D . W . B r o w n , M.M. C a m p b e l l , A.P. T a y l o r a n d X . Zhang, i b i d . , p. 985. K . Doyama, T . J o h , K , O n i t s u k a , T. S h i o h a r a a n d S . T a k a h a s h i , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 6 4 9 . P . D e S h o n g , D . R . S i d l e r a n d G.A. S l o u g h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2233. R . D . W s h a r k a r , BV.H. D e s h p a n d e , A.B. L a n g e a n d B . K . U p a d h y e , S y n t h . Commun., 1 9 8 7 , 17, 1 5 1 3 . S . T s u b o i , H . Wada, K . M u r a n a k a a n d A . T a k e d a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 2 9 1 7 . S . K a t s u m u r a , S . F u j i w a r a a n d S . Isoe, T e t r a h e d r o n L e t t . , 1191. 1987, R . A . Mack a n d V. S t Georgiev, J . O r g . Chem., 1 9 8 7 , 52, 4 7 7 ; V . Georgiev, R . A . Mack, D . J . W a l t e r , L . A . Radov a n d J . E . B a e r , Helv. Chim. A c t a . , 1 9 8 7 , 2, 1526. T. H i y a m a , H . O i s h i , Y . S u e t s u g u , K . N i s h i d e a n d H . S a i m o t o , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 2 1 3 9 . J . P . Dulcere, J . R o d r i g u e z , M . S a n t e l l i a n d H.P. Z a h r a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2, 2 0 0 9 . F . Kido, Y . Noda a n d A . Y o s h i k o s h i , T e t r a h e d r o n , 1 9 8 7 , 43, 5 4 6 7 ; P.A. J a c o b i , C.S.R. K a c z m a r e k a n d U.E. U d o d o n g , i b i d . , p. 5457. S . T s u b o i , H . Wada, S , M i m u r a a n d A . T a k e d a , Chem. L e t t . , 1 9 8 7 , 937. A. P e l t e r a n d M. R o w l a n d s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 1 2 0 3 . M . S a r g e n t , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 2 3 1 , K . K o b a y a s h i , M. I t o h a n d H. S u g i n o m e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2,3 3 6 9 . C . S o u c y , D . F a v r e a u a n d M . M . K a y s e r , J . O r g . Chem., 1 9 8 7 , 52, 129. K . O k a z a k i , K . Nomura a n d E . Y o s h i i , S y n t h . Commun., 1 9 8 7 , 1 7 , 1021. P . Canonne, R. B o u l a n g e r a n d M. B e r n a t c h e z , T e t r a h e d r o n L e t t . , 1987, 28, 4997. P.M. B o o t h , C . M . J . Fox a n d S.V. L e y , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 1 2 1 . H . Kawakami, S. H i r o k a w a , M . A s a o k a a n d H . T a k e i , Chem. L e t t . , 1987, 85. D.T. W i t i a k a n d A . K . T e h i m , J. O r g . Chem., 1 9 8 7 , 5 2 , 2 3 2 4 . R . D . M i l l e r a n d W. T h e i s , T e t r a h e d r o n L e t t . , 1 9 8 7 7 2 8 , 1 0 3 9 . M.S. C h a m b e r s . E.J. T h o m a s a n d D . J . W i l l i a m s , J . Chem. S O C . . Chem. Commun., 1 9 8 7 , 1 2 2 8 . D . F . T a b e r , P.B. D e k e r a n d M . D . G a u l , J . Am. Chem. SOC., 1 9 8 7 , 109, 7 4 8 8 .
28,
3: Carboxylic Acids and Derivatives 332. 333.
197
M i k a m i , K. T a k a h a s h i a n d T. N a k a i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 8 7 9 . S . F . M a r t i n a n d D.E. G u i n n , J . O r g . Chem., 1 9 8 7 , 52, 5 5 8 8 . S e e a l s o R . P . S h o r t a n d S . Masamune, T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 2 8 4 1 ; C. M a l a n g a , R . M e n i c a g l i , M. D e l l ' I n n o c e n t i a n d L. L a r d i c c i , i b i d . , p . 2 3 9 ; N . Kawaauchi a n d H. H a s h i m o t o , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 1 4 4 1 . R.H. S c h l e s s i n g e r , J . R . T a t a a n d J.P. Springer, Tetrahedron L e t t . , 1 9 8 7 , 2 8 , 5 4 2 3 ; J . O r g . Chem., 1 9 8 7 , 5 2 , 7 0 8 . C.M. T h o m p s o n T T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 2 4 3 . D . E n d e r s a n d B.E.M. R e n d e n b a c h , Chem. B e r . , 1 9 8 7 , 120, 1 2 2 3 . J.E. L y n c h , R . P . V o l a n t e , R . V . W a t t l e y a n d I . S h i n k a i , S e e a l s o F. B o n a d i e s , R. T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 3 8 5 . D i F a b i o , A . G u b b i o t t i , S . M e c o z z i a n d C. B o n i n i , i b i d . , p. 703. F o r a s y n t h e s i s of t h e c o r r e s p o n d i n g B-aryl d e r i v a t i v e s , s e e G.E S t o k k e r , T e t r a h e d r o n L e t t . , 1 9 8 7 ; 2 8 , 3 1 7 9 . I . F l e m i n g , N.L. R e d d y , K . T a k a k i a n d A.C.Ware, J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 4 7 2 . G.A. M o l a n d e r a n d J.B. E t t e r , J. Am. Chem. S O C . , 1 9 8 7 , 109, 6556 J - M . F a n g a n d B-C. Hong, J. O r g . Chem., 1 9 8 7 , 52, 3 1 6 2 . M . I h a r a , N . T a n i g u c h i , K . F u k u m o t o a n d T . K a m e t a n i , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 4 3 8 . M . Y a m a g u c h i , M. Hamada, H . N a k a s h i m a a n d T . M i n a m i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 3 0 5 . Y . I t o , E . N a k a j o , K . Sho a n d K. Tamao, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 2 4 7 . T . Kume, H . I w a s a k i , Y . Y a m a m o t o a n d K . A k i b a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 3 0 5 . F . T h e i l , B. C o s t i s e l l a , H . Gross, H . S c h i c k a n d S . S c h w a r t z , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 2 4 6 9 . J.K. S t i l l e a n d M. T a n a k a , J. Am. Chem. S O C . , 1 9 8 7 , 3785. N . A . P o r t e r a n d V. H-T. C h -a Soc., 1987, 4976. A . M a k i t a , T . N i h i r a a n d Y . Yamada, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28 , 805. E . V e d e j s , S . A h m e d , S.D. L a r s e n a n d S . westwood, J . Org. Chem., 1 9 8 7 , 52, 3 9 3 7 . G . Q u i n k e r t , U-M. B i l l h a r d t , H. J a k o b , G. F i s c h e r , J. G l e n n e b e r g , P. Nagler, V. A u t z e , N . H e i m , M . W a c k e r , T. S c h w a l b e , Y . K u r t h , J . W . B a t s , G . D u r n e r , G . Zimmermann a n d H . K e s s l e r , Helv. Chim. A c t a , 1 9 8 7 , 771. F o r a n example, see G . Q u i n k e r t , N . H e i m , J . G l e n n e b e r g , U-M. B i l l h a r d t , V. A u t z e , J.W. B a t s a n d G . D u r n e r , Angew. Chem. I n t . E d . E n g l . , 1 9 8 7 , 2 6 , 3 6 2 . S e e a l s o S. B i e n z a n d M . Hesse, Helv. C h i m . A c t a , 1 9 8 7 ., 7 0 ,. 1 3 3 3 . K.J. S G a , W.M. F r u s c e l l a , R . C . C a r r , L . D . B u r k e and D . K . C o o p e r , J . Am. Chem. S O C . , 1 9 8 7 , 109, 4 4 7 . S. H a t a e y a m a , K . S a t o h , K . S a k u r a i a n d S. T a k a n o , T e t r a h e d r o n L e t t . , 1 9 8 7 ., 2 8 ,. 2 7 1 7 . F o r a -p _p l i c a t i o n of t h e i n t r a m o l e c u l a r W a d s w o r t h - E m m G s p r o c e d u r e , see K . C . N i c o l a o u , R.A. D a i n e s a n d T.K. C h a k r a b o r t y , J . Am. Chem. S O C . , 1 9 8 7 , 1 0 9 , 2 2 0 8 . ; K.C. N i c o l a o u , P . S a n i , R.A. D a i n e s , T.K. C h a k r a b o r t y a n d Y . O g a w a , i b i d . , p. 2 8 2 1 ; K . S u z u k i , T . M t s u y m o t o , K . T o m o o k a , K . M a t s u m o t o a n d G. T s u c h i h a s h i , Chem. L e t t . , 1 9 8 7 , 1 1 3 ; H - J . B e s t m a n n a n d R. S c h o b e r t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 5 8 7 . B. M i l e n k o v , A. G u g g i s b e r g a n d M. Hesse, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 1 5 ; Helv. C h i m . A c t a , 1 9 8 7 , 70,7 6 0 ; B . M i l e n k o v S e e a l s o S. S t a n c h e r a n d M. a n d M. Hesse, i b i d . , p. 3 0 8 . Hesse, i b i d . , p . 1 3 8 9 . K.
~
334. 335. 336. 337.
338. 339.
I
340. 341. 342. 343. 344. 345. 346. 347. 348. 349. 350.
109, 109,
2,
351. 352.
353.
354. 355. 356. 357. 358. 359. 360. 361. 362. 363. 364. 365. 366. 367.
G . H . P o s n e r , E . A s i r v a t h a m , K . S . Webb a n d S. J e w , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 0 7 1 . M . O c h i a i , S . I w a i , T. U k i t a a n d Y . Nagao, Chem. L e t t . , 1 9 8 7 , 133. H . S u q i m o t o a n d S . Yamada, T e t r a h e d r o n , 1 9 8 7 , 4 3 , 3 3 7 1 . S . B a s k a r a n , I . Islam, M . R a g h a v a n a n d S . C h a n d r a s e k a r a n , Chem. L e t t . , 1 9 8 7 , 1 1 7 5 . N.E. S c h o r e a n d S.D. N a j d i , J . O r g . Chem., 1 9 8 7 , 5 2 , 5 2 9 6 . E . V e d e j s , R . A . B u c h a n a n , P . C o n r a d , G . P . Meier, K J . M u l l i n s a n d Y . W a t a n a b e , J . Am. Chem. S O C . , 1 9 8 7 , 1 0 9 , 5 8 7 8 , G . J u s t a n d R . S i n q h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 9 8 1 . M. D e n a r i e , D . G r e n o u i l l a t , R . M a l f r o o t , J - P . S e n e t , G. S e n n y e y a n d P . Wolf, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 8 2 3 . Z . J . Kaminski, S y n t h e s i s , 1987, 917. S . R a j e s w a r i , R . J . J o n e s a n d M.P. Cava, T e t r a h e d r o n L e t t , 1 9 8 7 , 28, 5 0 9 9 . K . A r a i , C . S h a w , K . Nozawa, K . K a w a i a n d S . N a k a j i m a , T e t r a h e d r o n L e t t . , 1987, 28, 441. T . Hogberg, P . S t r o m , M. z n e r a n d S . R a m s b y , J . O r q . Chem., 1987, 5 2 , 2033. K . M a t s u m o t o , S . H a s h i m o t o , T. O k a m o t o , S. O t a n i a n d J . H a y a m i , Chem. L e t t . , 1 9 8 7 , 8 0 3 . S - I . M u r a h a s h i , T . Naota a n d N . N a k a j i m a , Chem. L e t t . , 1 9 8 7 , 879. R . A . R e b e l o , M.C. R e z e n d e , R . N o m e a n d C . Z u c c o , S y n t h . 1741. Commun., 1 9 8 7 , S - I . M u r a h a s h i , Y . M i t s u e a n d K . I k e , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 17, 1 7 4 1 . S . V . L e y a n d P . R . Woodward, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 0 1 9 . S e e a l s o H - 0 . K i m , R . K . O l s e n a n d 0-S. C h o i , J . O r g . Chem., 1 9 8 7 , 52, 4 5 3 1 f o r a n example o f t h e r e l a t e d Masamune m e t h o d u s i n g copper (I) s a l t s . P . D u h a m e l , B. G o u m e n t a n d J - C . P l a q u e v e n t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 5 9 5 . L. N a k o n i e c z n a a n d A . C h i m i a k , ______ S y n t h e s i s , 1987, 418. P . W i p f , C . J e n n y a n d H . H e i m g a r t n e r , Helv. C h i m . A c t a , 1 9 8 7 , 70, 1001. H . J K i m a n d Y . H . K i m , T e t r a h e d r o n L e t t , 1 9 8 7 , 28, 1 6 6 9 . F . A . D a v i s , T.G. U l a t o w s k i a n d M . S . Haque, J . O r g . Chem., 1 9 8 7 , 52, 5 2 8 9 . Y . Kawanami, I . F u j i t a , Y . T a n i g u c h i , T. K a t s u k i a n d M. Yamaguchi, Chem. L e t t . , 1 9 8 7 , 2021. P . J . M u r p h y , G . P r o c t e r a n d A.T. R u s s e l l , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 0 3 7 . D.S. C r u m r i n e , T.A. D i e s c h b o u r g , J . G . O ’ T o o l e , B.A. T a s s o n e a n d S . C . B a n d e b u r g , J . O r g . Chem., 1 9 8 7 , 52, 3 6 9 9 . S.B. H e n d i , M . S . H e n d i a n d J . F . W o l f e , S y n t h . Commun., 1 9 8 7 , 17, 13. K R . B a l a b a n , T-S. B a l a b a n a n d G.V. Boyd, S y n t h e s i s , 1 9 8 7 , 577. M.R. P e n a a n d J . K . S t i l l e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 5 7 3 . Y . Z . H u a n g , L . S h i , J . Yang a n d J . Z h a n q , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 1 5 9 . See P . B e a k a n d K . D . W i l s o n , J . O r g . Chem., 1 9 8 7 , 52, 2 1 8 . a l s o P . B e a k , J . E . H u n t e r , Y . M . J u n and A.P. W a l l i n , J . Am. C h e m . SOC., 1 9 8 7 , 5403. J . T . W e l c h a n d S . E s w a r a k r i s h n a n , J . Am. Chem. SOC., 1987, 1 0 9 , 6 7 16 . H. F i l l i o n , A. H s e i n e a n d M-H. P e r a , S y n t h . Commun., 1 9 8 7 , 17, 929.
17,
369. 370.
371. 372. 373. 374. 375. 376. 377. 378. 379. 380. 381. 382. 383.
109,
384. 385.
3: Carboxylic Acids and Derivatives 386. 387. 388. 389. 390. 391. 392. 393. 394. 395.
B . D . G r a y a n d P.W. J e f f s , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1329. S . V . P a n s a r e a n d H . C . V e d e r a s , J . O r g . C h e m , , 1 9 8 7 , 52, 4 8 0 4 . D. Dauzonne a n d R . Royer, S y n t h e s i s , 1 9 8 7 , 399. D . S e e b a c h , R . H a n e r a n d T . V e t t i g e r , Helv. Chim. A c t a , 1 9 8 7 , 70, 1507. P . M u n s t e r a n d W. S t e g l i c h , S y n t h e s i s , 1 9 8 7 , 2 2 3 . M . B a i l l a r g e a n d F . Le G o f f i c , S y n t h . Commun., 1 9 8 7 , 1 7 , 1 6 0 3 . P . Magnus a n d M. S l a t e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 2 8 2 9 . T. I s h i z u k a a n d T. K u n i e d a , T e t r a h e d r o n L e t t . , 1 9 8 x 2 8 , 4185. S . M u r a h a s h i a n d T . S h i o t a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 4 6 9 . L.D. A r n o l d , J . C . G . D r i v e r a n d J . C . V e d e r a s J . Am. Chem. SOC., 1 9 8 7 , 4649. D.A. E v a n s , J . A . E l l m a n a n d R . L . D o r o w , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 1 2 3 . D . A . E v a n s a n d T.C. B r i t t o n , J. Am. Chem. S O C . , 1 9 8 7 , 6881. D . A . E v a n s , E.B. S j o g r e n , A.E. W e b e r a n d R.E. C o n n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 9 . 7151. D.A. E v a n s a n d A.E. W e b e r , J . Am. Chem. S O C . , 1 9 8 7 , Y. I t o , M . S a w a m u r a a n d T . H a y a s h i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6215. J.A.J.M. V e k e m a n s , R.G.M. de B r u y n , R.C.H.M. C a r i s , A.J.P.M. Kokx, J . J . H . G . K o n i n g s a n d E . F . G o d e f r o i , J . O r g . Chem., 1987, 52, 1093. U . S c h z l k o p f , R . H i n r i c h s a n d R . L o n s k y , Angew. Chem. I n t . E d . E n g l . , 1 9 8 7 , 26, 1 4 3 . U . S c h o l l k o p f a n d J . B a r d e n h a g e n , L i e b i g s Ann. Chem., 1 9 8 7 , 393. F o r f u r t h e r examples o f t h e u s e o f t h e o r i g i n a l S c h o l l k o p f m e t h o d , s e e T . P . H o l l e r , A. S p a l t e n s t e i n , E. T u r n e r , R.E. K l e v i t , B.M. S h a p i r o a n d P.B. H o p k i n s , J . O r g . Chem., 1 9 8 7 , g m 4 4 2 0 ; P.K. S u b r a m a n i a n a n d R.W. Woodard, i b i d . , p. 1 5 ; H-J. Zeiss, T e t r a h e d r o n L e t t . , 1 9 8 7 , 1255. U . S c h o l l k o p f , W. K u h n l e , E. E g e r t a n d M . D y r b u s c h , Angew, 480. Chem. I n t . E d . E n g l . , 1 9 8 7 , U. S c h o l l k o p f , S . G r u t t n e r , R . A n d e r s k e w i t z , E. E g e r t a n d M. D y r b u s c h , Angew. Chem. I n t . E d . E n g l . , 1 9 8 7 , 26, 6 8 3 . H . K u n t z a n d W. S a g e r , Angew. Chem. I n t . Ed. E n g l . , 1 9 8 7 , 26, 557. A. D u r e a u l t , I . T r a n c h e p a i n , C . G r e c k a n d J - C . D e p e z a y , T e t r a h e d r o n L e t t . , 1987, 28, 3341. B . I . G l a n z e r , K. F a b e r a n d H . G r i e n g e l , T e t r a h e d r o n L e t t . , 1987, 43, 771. U. S c h z d t a n d W. S e i g e l . T e t r a h e d r o n L e t t . , 1 9 8 7 , 2849. For a s i m i l a r a p p r o a c h , see J . D . A e b i , M . K . D h a o n a n d D . H . R i c h , J. O r g . Chem., 1 9 8 7 , 5 2 , 2 8 8 1 . R . D . T u n g a n d D . H . R i c h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 1 3 9 . D. S e e b a c h , E. J u a r i s t i , D . D . M i l l e r , C. S c h i c k l i a n d T , Weber, Helv. C h i m . A c t a . , 1 9 8 7 , 237. D. S e e b a c h , J.D. A e b i , M. G a n d e r - C o q u o z a n d R . N a e f , Helv. Chim. A c t a . , 1 9 8 7 , 7 0 , 1 1 9 4 . A. F a d e 1 a n d S a l z n , T e t r a h e d r o n L e t t . , 1987, 28, 2243. I . O j i m a a n d X . Q i u , J . Am. Chem. S O C . , 1 9 8 7 , 109,6537. See a l s o I . O j i m a a n d H-J.C. C h e n , J. C h e m . S O C . , Chem. Commun., 1987, 625. U . S c h o l l k o p f , R . T o l l e , E. E g e r t a n d M . N i e g e r , L i e b i g s An. Chem., 1 9 8 7 , 3 9 9 . ~
396. 397 * 398. 399. 400. 401. 402. 403.
199
109,
109,
109,
28,
404. 405. 406. 407. 408. 409. 410. 411. 412. 413. 414. 415.
26,
28,
70,
J.
421. 422.
Changyou, C. Daimo a n d J . Yaozhong, S y n t h . Commun., 1987, F o r s i m i l a r c h e m i s t r y of t h e c o r r e s p o n d i n g n i t r i l e , see 0. T s u g e , K . Ueno, S. Kanemasa a n d K . Y o r o z u , B u l l . Chem. SOC. J p n . , 1987, 60, 3347. S . J . B . T e n d l e r , M . D . T h r e a d g i l l a n d M . J . T i s d a l e , J . Chem. S O C . , P e r k i n T r a n s . 1, 1987, 2617. S.M. H e i l m a n n , K . M . J e n s e n , L . R . K r e p s k i , D . M . Morcn, J . K . Rasmussen a n d H . K . S m i t h , 11, S y n t h . Commun., 1987, 17, 843. M . M i t a n i , 0. T a c h i z a w a , H. T a k e u c h i a n d K . Koyama, Chem. L e t t . , 1987, 1029. R.W. F e e n s t r a , E.H.M. S t o k k i n g r e e f , R.J.F. Nivard and H.J.C. O t t e n h e i j m , T e t r a h e d r o n L e t t . , 1987, 28, 1215. T . K o l a s a a n d M . J . M i l l e r , J . O r g . Chem., 1987, 52, 4978. E . F a b i a n o , B . T . G o l d i n g a n d M . M . S a d e g h i , S y n t h e s i s , 1987,
423.
F.
416.
Z.
17, 1377. 417. 418. 419. 420.
190. E f f e n b e r g e r a n d T. Weber, Angew.
Chem.
I n t . Ed. E n g l . ,
1987, 26, 142.
424. 425. 426. 427. 428. 429.
430. 431. 432. 433. 434 * 435 * 436. 437 * 438439. 440. 441.
M z t e s o n a n d E . C . B e e d l e , T e t r a h e d r o n L e t t . , 1987, 2, 4499. N.A. S a s a k i , C . H a s h i m o t o a n d P. P o t i e r , T e t r a h e d r o n L e t t . , 1987, 28, 6069. J . E . B a l d w i n , M. N o r t h a n d A . F l i n n , T e t r a h e d r o n L e t t . , 1987, 28, 3167. D.S.
K . B a r l o s , P. M a m o s , D . P a p a i o a n n o u a n d S . P a t r i a n a k o u , J. Chem. SOC., Chem. Commun., 1987, 1583. R . A l b e r t , H. D a n k l m a i e r , H. Honig a n d H . K a n d o l f , S y n t h e s i s , 1987, 635. S e e a l s o S-T. Chen a n d K-T. Wang, i b i d . , p . 581. J . E . B a l d w i n a n d A . F l i n n , T e t r a h e d r o n L e t t . , 1987, 28, 3605. S e e a l s o H . L . Sham, H . S t e i n a n d J . Cohen, J . Chem. S O C . , Chem. Commun., 1987, 1792 f o r a p r e p a r a t i o n o f t h e corresponding 1,3-dioxolane d e r i v a t i v e . J . E . B a l d w i n , R.M. A d l i n g t o n a n d N . G . R o b i n s o n , J . Chem. SOC: Chem Commun., 1987, 153. D.H.R. B a r t o n , Y . Herve, P. P o t i e r and H. T h i e r r y , T e t r a h e d r o n , 1987, 43, 4297. T . K o s a l a , S. S h a r m a a n d M . J . M i l l e r , T e t r a h e d r o n L e t t . , 1987,
28, G. D.
4973. G r u n d k e , W . Keese a n d M . R i m p l e r , S y n t h e s i s , 1987, 1115. S e e b a c h a n d H . E s t e r m a n n , T e t r a h e d r o n L e t t . , 1987, 28,
3103. G. G u a n t i , E. N a r i s a n o a n d L. B a n f i , T e t r a h e d r o n L e t t . , 1987, 28, 4331 a n d 4335. S e e a l s o A . B a t t a g l i a , G . C a i n e l l i , D . G i a c o m i n i , G . M a r t e l l i a n d M. P a n u n z i o , i b i d . , p . 4489. Y . K i t a , F . I t o h , 0. Tamura, Y . Y . K e a n d Y. Tamura, T e t r a h e d r o n L e t t . , 1987, 28, 1431. T. Yamada, H . S u z u k i a n d T. Mukaiyama, Chem. L e t t . , 1987, 293. Y . H a t a a n d M. W a t a n a b e , T e t r a h e d r o n . , 1987, 43, 3881. S. T a k a n o , M. Y a n a s e , Y . S e k i g u c h i a n d K . O g a s a w a r a , T e t r a h e d r o n L e t t . , 1987, 28, 1783. A . B o n g i n i , G. C a r d i l l o , M. O r e n a , G . P o r z i a n d S . S a n d r i , T e t r a h e d r o n , 1987, 43, 4377. A . L . C a s t e l h a n o a n d x . K r a n t z , J . Am. Chern. S O C . , 1987,
109,
3491. 442. 443. 444.
K.H.
B e l l a n d G.
F u l l i c k , S y n t h . Commun.,
1987,
P. J o u i n , B . C a s t r o a n d D . N i s a t o , J . Chem. T r a n s . 1, 1 9 8 7 , 1177. B . D . H a r r i s , K.L. B h a t a n d M.M.
28, 2837. S . Kano, T . Yokomatsu, L e t t . , 1987, 28, 6331.
17, 1965.
SOC.,
Perkin
J o u l l i e , Tetrahedron L e t t . ,
1987,
445.
H.
Iwasawa a n d S . S h i b u y a , T e t r a h e d r o n
3: Carboxylic Acids and Derivatives 446. 447. 448. 449 * 450. 451. 452. 453.
201
M. S a k a i t a n i a n d Y. O h f u n e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 9 8 7 . R . G . A n d r e w , R . E . C o n r o w , J . D . E l l i o t t , W . S . J o h n s o n a n d S. - . Ramezani, T e t r a h e d r o n L e t t . , 1987, 6535. H.Kogen a n d T . N i s h i , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 3 1 1. J . S a v r d a a n d C. Descoins, S y n t h . Commun., 1 9 8 7 , 1 7 , 1 9 0 1 . H.L. Sham, C . A . R e m p e l , H . S t e i n and J. C o h e n , J . C h e m . SOC. I Chem. Commun., 1 9 8 7 , 6 8 3 . J . M . Brown, Angew. Chem. I n t . Ed. E n g l . , 1 9 8 7 , 2 6 , 1 9 0 . B.D. Z w i c k , A.M. A r i f , A.T. P a t t o n a n d J . A . G l a d y s z , Angew. Chem. I n t . Ed. E n g l . , 1 9 8 7 , 26, 9 1 0 . C.R. L a n d i s and J. H a l p e r n , J . Am. Chem. S O C . , 1 9 8 7 , 109, 1 7 4 6 . F o r some new l i s a n d s . see C.R. J o h n s o n a n d T. I m a m o t o J . O r g . Chem., 1 9 8 7 , 2170. S e e a l s o D.E. B e r g b r e i t e r a n d R . C h a n d r a n , J . Am. Chem. S O C . , 1 9 8 7 , 109, 1 7 4 . C. S h i n , T. Obara, S. S e g a m i and Y. Y o n e z a w a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 8 2 7 . J . M . Brown, A.P. James and L.M. P r i o r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 1 7 9 . D. C a n t a c u z e n e , F . P a s c a l a n d C. G u e r r e i r o , T e t r a h e d r o n , 1 9 8 7 , 43 , 1823. P . J o u i n , B. C a s t r o , C . Zeggaf, A. P a n t a l o n i , J-P. S e n e t , S. L e c o l i e r a n d G. S e n n y e y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 6 6 5 . K. B a r l o s , J - K a l l i t s i s , P. M a m o s , S . P a t r i a n a k o u a n d G. S t a v r o p o u l o s , L e i b i g s Ann. Chem., 1 9 8 7 , 6 3 3 . C. F r o u s s i o s a n d M. Kolovos, S y n t h e s i s , 1 9 8 7 , 1 1 0 6 . P.A. S u t t o n a n d D.A. B u c k i n g h a m , A c c . Chem. R e s . , 1 9 8 7 , 20, 357 * 0. D a n g l e s , F. G u i b e , G. B a l a v o i n e , S . L a v i e l l e and A . M a r q u e t , J . O r g . Chem., 1 9 8 7 , 5 2 , 4 9 8 4 . G . S e n n y e y , G. B a r c e l o a n d J - P T S e n e t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5809. I . M i n a m i , M. Y u h a r a a n d J . T s u j i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2737. K . T a k e d a , K. T s u b o y a m a , M. H o s h i n o , M. k i s h i n o and H . ogura, S y n t h e s i s , 1 9 8 7 , 557. P . H e n k l e i n , H-U. H e y n e , W-R. H a l a t s c h a n d H . N i e d r i c h , S y n t h e s i s , 1987, 166. L.A. C a r p i n o , A c c . Chem. R e s . , 1 9 8 7 , 20, 4 0 1 . R.E. S c h u t e a n d D . H . R i c h , S y n t h e s i s , 1 9 8 7 , 3 4 6 . F.M.F. C h e n a n d N . L . B e n o i t o n , C a n . J . Chem., 1 9 8 7 , 65, 6 1 9 , 1224 and 1228. S e e a l s o F.M.F. C h e n , Y . L e e , R . S t e i n a u e r a n d N.L. B e n o i t o n , i b i d . , p. 6 1 3 . P . I . S v i r s k a y a , C.C. L a z n o f f a n d M. S t e i n m a n , J . O r g . Chem., 1 9 8 7 , 52, 1 3 6 2 . N . F u j i i , A. O t a k a , 0. I k e m u r a , K . A k a j i , S . F u n a k o s h i , Y . H a y a s h i , Y . K u r o d a a n d H . Y a j i m a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 7 4 . M.A. C a s a d e i a n d D . P l e t c h e r , S y n t h e s i s . , 1 9 8 7 , 1 1 1 8 . B.M. A d g e r , C. O ' F a r r e l l , N . J . L e w i s a n d M.B. M i t c h e l l , S y n t h e s i s , 1 9 8 7 , 5 3 ; S . Ram a n d L.D. S p i c e r , T e t r a h e d r o n L e t t , 1 9 8 7 , 28, 5 1 5 . M. U e k i a n d M . Amemiya, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 6 1 7 . K . B a r l o s , P. M a m o s , D. P a p a i o a n n o u , S. P a t r i a n a k o u , C. S a n i d a a n d W. S c h a f e r , L e i b i g s Ann. C h e m . , 1 9 8 7 , 1 0 2 5 . F . A l b e r i c i o , A . G r a n d o s , A . P o r t a , E . P e d r o s o a n d E. G i r a l t , S y n t h e s i s , 1 9 8 7 , 271. R . E r i t j a , J . P . Z i e h l e r - M a r t i n , P.A. W a l k e r , T.D L e e , K . L e g e s s e , F . A l b e r i c i o a n d B.E. K a p l a n , T e t r a h e d r o n , 1 9 8 7 , 43, 2675.
28,
2,
454. 455. 456. 457. 458. 459. 460. 461. 462. 463. 464. 465. 466. 467. 468. 469. 470. 471. 472. 473. 474. 475. 476.
~
202 477. 478. 479. 480. 481. 482.
General and Synthetic Methods N . F u j i i , A. O t a k a , S. F u n a k o s h i , K . B e s s h o a n d H. Y a j i m a , J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 6 3 . P . S i e b e r a n d B. R i n i k e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6031. J . C . Hodges, S y n t h e s i s , 1 9 8 7 , 2 0 ; J.H J o n e s , D . L . R a t h b o n e a n d P.B. W y a t t , i b i d . , p. 1 1 1 0 . C . J . C h i v i k a s a n d J . C . Hodges, J. Org. Chem., 1 9 8 7 , g . , 3 5 9 1 . M . J . M i l e w s k a a n d A . C h i m i a k , A u s t . J . Chem., 1 9 8 7 , 4 0 , 1 9 1 9 . R . Ramage a n d J . G r e e n , T e t r a h e d r o n Lett., 1 9 8 7 , 2 8 , 2 2 8 7 .
4 Alcohols, Halogeno-compounds, and Ethers BY C. J. URCH
1 Alcohols Preparation. - By addition to Alkenes. Brown has found that when methylborane, the simplest monoalkylborane, in tetrahydrofuran was treated with one equivalent of an alkene it gave the monoaddition product cleanly. Addition of another alkene then gave a dialkylmethylborane, which on carbonylation-oxidation yielded a This is a general procedure for all alkenes. In tertiary alcohol1 another paper, Brown has made trans-2-phenylcyclopentanol and trans-2-phenylcyclohexanol with very high enantiomeric purities (399% and >97% respectively) by hydroborating the cyclic alkenes with monoisopinocampheylborane, crystallisation of the product, and oxidation2. An anti-Markovnikov hydration of an olef in has been achieved using an organoborane catalytically. Thus, when the olefin was treated with dichloroaluminium hydride (prepared from lithium aluminium hydride and aluminium trichloride) and an organoborane under dry air, the corresponding alcohol was formed in good yield (Scheme 1)3. Another 'one-pot' anti-Markovnikov hydration of an olefin has been demonstrated using a rhodium (111) catalyst4 In this reaction the olefin was treated with sodium borohydride, oxygen and the catalyst to give the alcohol, though yields based on the olefin were poor. 3-Borolenate complexes (derived from isopropenylacetylene) were reacted with the electrophiles dimethyl sulphate or prenyl bromide to give homoallylic alcohols (Scheme 2)'. Tamao and Ito have prepared mono-protected 1,3-diols by intramolecular hydrosilylation of allylic and homoallylic alcohols6 Acyl and methoxymethyl protecting groups were introduced directly, whereas others were introduced by first hydrogenating the silicon-oxygen bond (Scheme 3). As the erythro- and threodiastereoisomers underwent fluoride-induced acylation at different rates, diastereomeric mixtures could be further enriched by the protection sequence. Enantioselective cis-hydroxylation of alkenes has been achieved with osmium tetroxide and a homochiral diamine
.
.
.
204
Reagen+s :
Geneml arid Synthetic Methods
i , CI,AIH, 0,, R- ' 8
(cat.)
\
Scheme 1
8 8 : 12 Reagents :
i , Me,SO,
; i i , o x i d a t ion ; iii I Me,C=CHCH,Br Scheme 2
B y &
I
8
I I, I I ~
* MOM0
OH
Reagents :
i , ( HMe,Si I,NH,
OH
H 2 P t C 1 6 ( c a t . ) ; ii, MeOCH2CI CsFor
PhCH2NMe3.BF4; iii, 30°/. H,02
Scheme 3
KHCO, ,MeOH
4: Alcohols, Hulogeno-compounds, and Ethers
205
7 with D2 symmetry . Enantiomeric excesses varied from 83-99%.
syn-a,B-Dihydroxyaldehydes have been prepared by dihydroquinidine acetate-promoted osmylation of the chiral acetals of a , @-unsaturated aldehydes8. Double stereoselection can occur, with the matched pair giving a diastereoisomeric ratio of 40:l. Fleming has investigated the osmylation of chiral allylsilanes with the
chiral centre a- to the silyl group'. With both a large group and a hydrogen atom a- to the silyl group, moderate diastereoselection was achieved. Homochiral 2-hydroxy-2-methyl carboxylic acids were prepared by an asymmetric bromolactonization with &-proline as the chiral auxiliary (Scheme 4)l o . Diastereosele,ctions of up to 95:5 were obtained. By Reduction of Carbonyl Compounds
-
The Meerwein-Ponndorf-Verley
reduction, traditionally catalyzed by aluminium triisopropoxide, can also be catalyzed by lanthanide triisopropoxides". Gadolinium triisopropoxide was the most effective catalyst for ketone reduction, whereas ytterbium triisopropoxide was best for aldehydes. Aliphatic ketones and aromatic ketones with an orthohydroxy or amino substituent were found to be reduced much more rapidly than other ketones by sodium diacetoxyborohydride in tetrahydrofuran' 2. Potassium triphenylborohydride has been shown to be a very mild reducing agent13. At -78°C it reduced 2-, 3- and 4-methylcyclohexanonewith a high degree of diastereoselection, cis-isomers repectively. Several giving the cis-,trans- and a,@-unsaturated aldehydes and ketones were reduced 1,2- with very high selectivity (up to 100%) by sodium borohydride in the presence of an organosamarium or an organoerbium complex14. Chemical yields were also good in all but very sterically crowded cases. The selective reduction of an aldehyde in the presence of a ketone was achieved in high yield using nickel boride in the presence of 15 chlorotrimethylsilane . The selective reduction of aromatic aldehydes in the presence of aromatic ketones occurred with sodium
'.
borohydride and tin (11) chloride in tetrahydrofuran' Interest in the asymmetric reduction of ketones has continued to grow. Corey has described a highly enantioselective reduction of prochiral ketones using borane and a homochiral oxazaborolidine catalyst (Scheme 5)17. Optical yields were in the range 80 - 97%. He has described several developments in the area in a subsequent paper18. In particular, by methylating the boron atom the reagent
206
Gettrrul und Syttthetic Mcthod.5
could be made much more stable and easier to handle. It was also much easier to prepare. Aromatic ketones were reduced asymmetrically with a reagent prepared from borane-dimethyl sulphide and a homochiral a m i n o a l c ~ h o l ~ ~Optical . yields, however, were only moderate. Brown has prepared several chiral dialkoxymonoalkylborohydridesand used them to reduce a series of prochiral ketones2'. The optical yields were in the range of 5 7 4 % for acetophenone. Brown has also carried out an examination of the relative effectiveness of various asymmetric reducing reagents for different classes of ketones2'. From the results obtained, preferred reagents are suggested for the asymmetric reduction of different types of ketones. Homochiral acetals have been reductively cleaved with Lewis acid-metal hydride reagents to give, after removal of the chiral auxiliary, homochiral alcohols in good optical yield in the best cases22. With homochiral alkynyl acetals, aluminium hydride reagents were found to be most effective. Asymmetric catalytic hydrogenation of ketones has been studied using a homochiral rhodium catalyst23. a-Ketoesters and a-ketoacetals gave the corresponding homochiral secondary alcohols in optical yields of up to 8 7 % . Tartaric acid-sodium bromide modified Raney nickel reduced 2-octanone in good optical yield2*. In order to prolong the optical lifetime of the catalyst for subsequent reactions it was necessary to add extra sodium salts. Optically pure allylic 6-ketosulphoxides have been reduced to give allylic 6-hydroxysulphoxides with excellent diastereoselectivities (Scheme 6)25. Subsequent asymmetric osmylation gave a trio1 in greater than 90% enantiomeric excess, which was further converted to L-penta-2-acetylarabinitol. There has been continued interest in microbial reduction of ketones to optically active secondary alcohols throughout 1987. The preferred reagent still seems to be bakers' yeast. Utaka has used this method to reduce 6-keto-octadecanoic acid, obtaining the 8-hydroxyacid in greater than 98% optical yield, though only in a moderate chemical yield ( 4 0 % )26. He has also undertaken a more general study of the reduction of y- and 6-ketocarboxylic acids27. In almost every case the corresponding y- or 6-lactone was isolated in excellent optical yield (>98%), though in variable chemical yield. The only exception was when a methyl ketone was present, when hydroxyacids (and hence lactones) were not produced. The reduction of B- and y-ketocarboxylic esters with bakers ' yeast has
207
4: Alcohols, Halogeno-compounds, and Ethers
I
+O
n=co2H
R e a g e n t s : i , NBS; i i , Bu3SnH,(PhCOOJ2 cat.,iii, 48% HBr Scheme 4
Scheme 5
Reagents : i
ZnClz
,D l 6 A L
- 7 8 OC
Scheme 6
also been investigated28. Optical yields were dependent on the conditions employed, but were excellent in the best case. Brooks
has studied the effect of ester alkoxy group modification on the yeast reduction of B-ketoesters2 9 .
In changing from methoxy to
neopentyloxy the optical yield was increased from 30% to 96%, though there was a drop in chemical yield. This study showed the value of selecting the substrate for
microbial reduction with
care.
By reducing (1,3-dithian-2-yl)acetone with a Streptomyces species (R)-l-(1,3-dithian-2-yl)propan-2-01 has been obtained in
high optical purity3'. As the (S)-isomer was obtained with baker's yeast the two microorganisms gave conveniently complementary results. The effect that the conditions under which microbial reduction was performed had on the optical outcome was demonstrated by the reduction of 4-meth~lheptan-3~5-dione( 1 )3 1 . Under anaerobic conditions the (4R_), (5S)-isomer (2) was obtained while aerobic conditions led to the diastereoisomeric (451, (SS)-product (3) (Scheme 7). Takeda has found that the reduction of 6-chloro-a-ketoesterswith bakers' yeast occurred with >95% enantiomeric excess at the alcohol-centre in most cases32-
However, there was little selectivity of reaction shown for either epimer at the chloro-centre. By Nucleophilic Alkylation - This section is in three parts. Firstly non-stereoselective additions to carbonyl groups, secondly diastereoselective reactions, and thirdly enantioselective reactions. There is obviously sometimes an overlap between these last two sections, for instance the diastereoselective addition to a single enantiomer.
Some of the reactions described are only
formally nucleophilic alkylations, though they are included in this section for completeness. Reetz has studied the addition of methyltitanium reagents to carbonyl compounds33. He found that a-alkoxy- and a-aminoketones are more reactive (by a factor of 10-30) than their non-heteroatomsubstituted analogues.
It was also shown that aldehydes were more
reactive than ketones by a factor of approximately 500. In another paper, Reetz also studied the addition of methyltitanium reagents to cyclic ketones34. In contrast to methyllithium and methylmagnesium chloride, significant differences in rates were observed with different sized rings. Seebach has published on the These chemistry of acetylenic titanium triisopropo~ides~~.
4: Alcohols, Halogeno-compounds, and Ethers
209
reagents were much more reactive towards aldehydes than ketones and hence a complete differentiation could be achieved by performing the reaction at low temperature. A Barbier-type allylation of aldehydes has been reported36.
Bismuth trichloride and metallic
aluminium effected the reaction in a water-tetrahydrofuran mixture. Yields were generally good. In another Barbier-type reaction, aldehydes have been allylated with both allylic halides and allylic phosphates using metallic antimony37. With allylic bromides and phosphates (but not iodides) it was necessary to add lithium iodide to the reaction. An electroreductive methallylation of carbonyl compounds has been achieved38. Methallyl chloride, the carbonyl compound and a catalytic amount of nickel(I1) bromide-2,2'bipyridine complex were reacted in a one-compartment cell equipped with a sacrificial zinc anode. Allylation of aromatic aldehydes and ketones by allylstannanes has been induced phot~chernically~~. Homoallylic alcohols were the major products, though pinacol and oxetane products were also observed. Allylic acetates in the presence of zinc and a catalytic amount of (tripheny1phosphine)palladium (0) acted as agents towards aldehydes4'. Regardless of the starting allylic acetate, the aldehyde
tetrakis nucleophilic allylating the regiochemistry of attacked the more
substituted end of the allylic system. Propargylic acetates have been added to carbonyl compounds using samarium diiodide and a catalytic amount of a palladium ( 0 ) complex to give either the allenic alcohol alone, or as a mixture with the propargylic alcohol4'. Reaction of secondary or tertiary acetates with terminal acetylenes gave only allenic products (Scheme 8). Acetal-protected a-hydroxy aldehydes have been prepared by the reductive cross-coupling of lI3-dioxolane with carbonyl compounds42. The reactions were carried out with samarium diiodide and iodobenzene in a mixed solvent system. 1,4-Diazabicyclo[2,2,2] octane (DABCO) has been used to catalyze the cross-coupling of a,B-unsaturated ketones with aldehydes in a general synthesis of a-methylene-8-hydroxyalk a n ~ n e s ~ ~ In. a similar reaction, acrylonitrile and methyl acrylate were coupled with a-ketoesters to give 2-[l-carboalkoxy-l-hydroxyalkyll-acrylonitriles and - a ~ r y l a t e s ~ ~a-Methylene-R-hydroxy-aldehydes . have been synthesized by reaction of a 2-lithiopropenal equivalent with aldehydes45. The reagent was prepared by treating 2 , 2-dimethyl4-methylene-lI3-dioxolane with E-butyllithium. Finally, the
210
General and Synthetic Methods
first practical use of a niobium (111) reagent has been were prepared in good yield by the d e ~ c r i b e d ~ ~2-Aminoalcohols . niobium trichloride-promoted coupling of imines with aldehydes and ketones. Moderate to high diastereoselectivity was observed, with the threo- isomer the major product with aldehydes (Scheme 9). A number of syntheses of halogenated alcohols have been published. a-Trichloromethyl carbinols have often been prepared by the condensation of chloroform with aldehydes, though with reactive aldehydes the competing Cannizzaro reaction has been a problem. This was overcome by treating the chloroform and aldehyde in dimethy1formamide wi th me thano1ic po tassium hydroxide4 . a-Trifluoromethyl carbinols have been prepared in a Barbier-type procedure48. Stirring the carbonyl compound, zinc powder and pyridine under a slight pressure of trifluoromethyl bromide gave the trifluoromethyl alcohols in moderate yield. a-Pentafluoroethyl carbinols were synthesized by treating pentafluoroethyl iodide with methyllithium in the presence of a carbonyl compound49. Iodinelithium exchange occurred rapidly to give pentafluoroethyllithium which then reacted with the aldehyde or ketone to give the fluorinated alcohol. 2,2,2-Trifluoro-l,l-dichloroethylzinc chloride has been prepared and reacted with aldehydes to give 1-substituted 3,3,3-trifluoro-2,2-dichloropropan-l-ols50. If excess zinc was used together with an aluminium trichloride catalyst 3,3-difluoro-2-chloroprop-2-en-l-ols resulted. Yamamoto has observed enhanced Cram-selectivity in carbonyl addition reactions when 'naked' anions (prepared in situ from an organometallic reagent and a tetrabutylammonium salt) were used51. On the other hand, when a 'naked' cuprate was used anti-Cram selectivity was observed, though not to a high degree. Zinc acetylides have been shown to undergo highly =-selective additions to a-alk~xyaldehydes~~. A chelation-controlled model is proposed for the reaction. Much work continues to be published on the stereoselective allylation of carbonyl compounds. Thomas has shown that a-methylcrotylstannanes react with aldehydes on heating to give anti-2-homoallylic alcohols in >98% diastereo~electivity~~. With a boron trifluoride catalyst the major product was the syn-E-homoallylic alcohol, though the reaction showed a lower degree of diastereoselection. Allyltrifluorosilanes with fluoride ion activation have been shown to be efficient aldehyde allylating reagents54. 2-Crotyltrifluorosilanes led to
'
211
4: Alcohols, Halogeno-compounds, and Ethers
Reagents : i Geotrichum candidum anaerobic aerobic
, ii
Geotrichum candidum,
Scheme 7
Scheme 8 . l
OH Reagents : i , N b C I , ( D M E ) , f H F ;
i i , R3COR4
Scheme 9
Reagent : i , M g B r i O E t
Scheme 10
212
General and Synthetic Methods
threo-homoallyl alcohols while the g-isomer gave erythro- products. Koreeda has used the Lewis acid catalyzed addition of y-alkoxyallylstannanes to aldehydes to prepare syn-vicinal diol monoalkyl ethers55. This stereochemistry was observed regardless
of the geometry of the starting y-alkoxyallylstannane. Selectively protected 1,2,3-triols have been produced by a similar reaction which involved the Lewis acid-initiated attack of y-s i1y loxya11ylstannanes on a-a1k~xyaldehydes~ 6 . Diastereofacial selectivity was governed by chelation control and a syn-relationship of substituents about the newly formed bond was highly favoured (Scheme 10). 1,2,4-Triol derivatives have been prepared in the same manner starting with 8-alkoxyaldehydes. In a variation on the methodology in the above two papers, 1,2-diols were obtained using a silyl group as a masked alcohol5’. A zinc reagent derived from allyl(diisopropylamino)dimethylsilane was reacted with aldehydes to give erythro-3-silyl-l-alken-4-ols. Hydrogen peroxide oxidation of the carbon-silicon bond then gave the 1,2-diols. Molander has published a series of papers on samarium diiodidemediated cyclisation reactions leading to cyclic alcohols. 2-Substituted cyclopentanols were prepared by cyclisation of a-substituted 6-iodo ketones5’. The diastereoselectivity of the reaction was dependent upon the steric bulk of the substituents and was found to increase with substituent size. 2-(w-Iodoalkyl)-Rketo esters and amides were cyclised by samarium diiodide to give cis-2-hydroxycycloalkane-carboxylatesand -carboxamides (Scheme 1 ~ ~ ’ .The use of allylic iodides or bromides allowed access to further functionalized cycloalkanones. The reaction has been extended to the intramolecular ketone-olefin reductive coupling of unsaturated B-ketoesters and B-ketoamides60. Again, high diastereoselectivity was oberved. Samarium diiodide was also used to achieve an intramolecular Reformatsky reaction61. High 1,3-asymmetric induction was observed in all reactions (Scheme 12). Jefford et a1 have reported that both erythro- and threo6-hydroxy-a,B-unsaturated y-lactones can be obtained with moderate selectivity by altering the conditions of the condensation of 2-trimethylsilyloxyfuran with aldehydes62. The authors have used 63 this reaction in a synthesis of cavernosine . Both 1,4- and 1,5-asymmetric induction has been observed on the addition of organotitanium reagents to y- and 6 - l a ~ t o l s ~ ~The . resulting 1,4and 1,5-diols were both produced with good --diastereoselectivity,
4:Alcohols, Halogeno-compounds, and Ethers
213
though it was higher in the case of the 1,4-diols. There has been continued interest in developing enantioselective alcohol syntheses nucleophilic addition to carbonyl compounds. Aryl Grignard reagents in the presence of homochiral diamine ligands (based on two trans-3,4-diarylpyrrolidine units) have been added to aldehydes65. The resulting benzyl alcohols were formed in 40-75% ee. The same authors added Grignard reagents to benzaldehyde with the same homochiral diamines present, using an aryloxyaluminium dichloride as a co-ordinating agent66. Optical yields were similar, being in the range 40-70%. N-Acylpyrrolidinyl methanols (derived from proline) have been used to make homochiral methyltitanium reagents67. When reacted with aldehydes these reagents gave secondary alcohols with up to 54% ee. Seebach has used homochiral 1 , Z - , 1,3- and 1,4-diols as alkoxy ligands on titanium for enantioselective nucleophilic addition to aromatic Several alkoxy ligands and carbon-centred nucleophiles were examined and alcohols with up to 96% ee were formed. During 1987 there have been many reports of the asymmetric addition of dialkylzinc reagents to aldehydes. Chaloner has used ephedrine derivatives to obtain optical yields of up to 80% in the addition of diethylzinc to ben~aldehyde~’. In another study on the asymmetric addition of diethylzinc to benzaldehyde both alkaloid and aminoalcohol ligands were used catalytically (3 mol % ) and optical yields were as high as 87%70 . In a further report on the asymmetric addition of diethylzinc to aldehydes, cinchona alkaloids were used as homochiral catalyst^'^. With benzaldehyde, quinine (2 mol % ) was found to give predominantly the ( 6 8 % ee) while quinidine gave mainly the (S)-isomer (R)-enantiomer (48% ee). A variation on the above reactions used a polymerbound asymmetric catalyst which had the advantage that it was easily recycled72 . If the reaction of diethylzinc with benzaldehyde is again used for comparison, the best catalyst (based on polymer-bound aminoisoborneol) gave the secondary alcohol in 9 2 % ee as the (2)-enantiomer. The (R)-isomer was obtained in 81% ee with an ephedrine-based catalyst. In two successive papers Corey described two different catalysts €or the asymmetric addition of diethylzinc to benzaldehydes. In the first he described the use of tridentate lithium complexes which gave optical yields in the range of 85-95%73. In addition he suggested a model which accounts for the absolute geometry of the product.
In the second paper Corey
reported a class of zinc chelates with tertiary amino phenolic alcohols which act as catalysts for the asymmetric addition of diethylzinc to aldehydes74. The model described in the previous paper was again used to rationalize the absolute geometry. During 1987 Soai published five papers on the asymmetric addition of dialkylzinc reagents to aldehydes. He used the dilithium salt of a diamino-diol derived from two ephedrine units to add diethylzinc to a series of aldehydes75. With benzaldehyde, an optical yield of 85% was obtained. Another ephedrine-based catalyst,
N,N-dibutylephedrine, was used to add dialkylzinc reagents to both aromatic and aliphatic aldehydes in excellent optical yields76. These results were particularly impressive in the case of aliphatic aldehydes (up to 93% ee with diethylzinc) where it has been more difficult to obtain high optical yields in the past. Soai has also used a homochiral piperazine-based catalyst to obtain excellent optical yields with aryl aldehydes77. Two papers from the same research group described the use of pyrrolidinylmethanolderivatives as asymmetric catalysts for the addition of dialkylzinc reagents to aldehydes78r79. Several catalysts were examined and two found which gave high, complementary enantioselectivities. Thus, with diethylzinc and benzaldehyde the pyrrolidinylmethanol ( 4 ) gave the (g)-secondary alcohol in 97% ee and the catalyst (5) was reported to give the (R)-alcohol in 100% ee (Scheme 13). These catalysts also gave reasonably good optical yields with aliphatic
aldehydes. Much work has been published on the asymmetric addition of ally1 and crotyl reagents to carbonyl compounds.
Homochiral
E- and
Z-crotyl-trans-5-dimethyl-borolanes react with aldehydes to give homoallylic alcohols with excellent diastereoselectivities and enantioselectivities80. E-Crotylborolanes gave anti-products and Z-crotylborolanes
gave syn-products with diastereoselectivities in the order of 90% for a series of aldehydes. The optical yield of the major diastereoisomer was usually 90% or better. Brown has
used optically active B-allyldiisopinocampheylborane in diastereofacial-selective allylations of a-substituted homochiral aldehydes8'.
Both enantiomers of the reagent are available [from
and (-l-a-pinenel . As the reagent showed very high diastereofacial selection, it was the reagent that controlled the (+)-
geometry of the new chiral centre (Scheme 14). With small a-substituents on the aldehyde the diastereoselection was high,
4: Alcohols, Halogeno-compounds, und Ethers
215
- R’--tfCO,R~
OH
I%OR3 Reagent
-R2
: i , SMI2 Scheme 11
0 Br 4
0 0
A
R’ JJR* Reagent
R’
#
O
H
R2
: i , SML, Scheme 12
4fH6J28-
O
Gf2Brv/ -
OH
OH
96
4
5
95
I
Scheme 14
216
though with larger groups 'matched' and 'mis-matched' pairs became evident. In a second paper, Brown has extended the reagent from a1 lyl to crotyldiisopino-campheylboranes82 - E-Crotylboranes led to anti-products about the newly formed bond and Z-crotylboranes gave syn-geometry. As with the allylborane reagent, diastereofacial selectivity was high with aldehydes with small a-substituents. Roush has used diisopropyl tartrate-modified allyl- and E- and Z-crotylboronates to achieve good diastereoselectivity in the reaction with homochiral f3-alkoxy-a-methylpropionaldehyde83. By correct choice of reagent all of the possible isomeric products were available in at least 87% ee. Homochiral a-methoxy-Ecrotylboronates have been reacted with achiral aldehydes to give the anti-Z-methoxy-homoallyl alcohols ( 6 ) in excellent optical yield (Scheme 1 5 ) 8 4 . With chiral aldehydes matched and mis-matched pairs led to excellent and fair diastereoselectivities respectively. In addition to allylboranes, allylsilanes have been used in asymmetric additions to aldehydes. In the presence of a Lewis acid a homochiral allylsilane has been reacted with both aldehydes and ketones to give homoallylic alcohols in moderate optical yields85. Mukaiyama has prepared a homochiral allylating agent based on tin (11) and a chiral diamine86. With aldehydes it gave homoallylic alcohols in up to 8 4 % ee. Asymmetric methallylation was also described. A chiral tin (IV) allylating agent has also been reported (using diethyl tartrate as the chiral auxiliary)8 7 . Enantioselectivities were moderate ( 4 0 - 6 0 % ee). The reagent could also be made with a propargyl group replacing the allyl group. This gave 1,2-dien-4-ols in similar optical yields (Scheme 16). Fleming has made an optically active heptadienylsilane (in 80% ee) (7)88. When reacted with isobutyraldehyde in the presence of a Lewis acid, a dienol ( 8 ) was formed (Scheme 17). The syn-diastereoisomer (9) was the major product, with an ee of 6 4 % . Johnson et al.have extended their use of asymmetric synthesis acetal templates to the aldol reaction8'. Acetals derived from (3S)-butan-1,3-diol undergo titanium tetrachloride-catalyzed coupling with acetone trimethylsilyl enol ether to give the aldol ether (10) as the major product (de 92 to > 9 8 % ) (Scheme 1 8 ) . The chiral auxiliary was removed by oxidation and B-elimination under conditions to which the aldol product (11) was stable. Seebach has used 3-hydroxybutanoic acid as a chiral auxiliary9'. With aldehydes it gave 6-methyl-1,3-dioxan-4-ones which, on treatment
4: Alcohols, Halogeno-compounds, and Ethers
217
S c h e m e 15
L
S c h e m e 16
(8)
17 1
OH I
(9)
Reagents : i, TiCI,, CH2C12,-780C S c h e m e 17
R
& o
+
Z M e 1.3 , R
"
..... II
O
*n R
O (10)
+ Reagents : i, TiCI,;
, Ill
i i , P C C ; iii, Bn2NH,CF,C0,
S c h e m e 18
(11)
-
218
General and Synthetic Methods
with carbon nucleophiles in the presence of a Lewis acid, yielded 3-alkoxyacids in excellent optical yields. Treatment with lithium diisopropylamide gave the corresponding secondary alcohols. Ketals have also been used to induce asymmetric addition to an a-keto group. Tamura has studied this reaction with both cyclic and acyclic a-keto ketals or acetals. With cyclic systems diastereoselectivities of up to 100% were reported when Grignard reagents were usedg1. With acyclic systems, diastereoselectivities were virtually as high ( > 9 8 % de) with a-keto ketals, but were lower with a-keto acetals (76% de was the maximum reported)92. Mukaiyama has developed an ‘in situ’ preparation of asymmetric acetals93 . Allyltrimethylsilane reacted with aldehydes and (S)-1-phenyl-1-trimethylsilyloxyethane in the presence of a diphenylboryl triflate catalyst to give homoallyl ethers in excellent optical yields (Scheme 19) Finally, Luche has shown that homochiral 2-octyl halides reacted under sonication with lithium and cyclohexanone to give alcohols in a modest enantiomeric excessg4. He suggested that two reactive intermediates exist, which follow different and opposite stereochemical paths, hence accounting €or the low overall optical yie Ids. By Opening of Epoxides. - The opening of an epoxide to give an alcohol is considered in three parts. Firstly a-deprotonation with a base followed by elimination to give an allylic alcohol, secondly nucleophilic opening with a hydride reagent, and thirdly nucleophilic opening with an organometallic reagent. By treating a prochiral epoxide (such as cyclohexene oxide) with a chiral lithium amide base asymmetric ally1 alcohols have been formed”. Two different homochiral bases have been developed that gave allylic alcohols of complementary absolute geometry. T a m has used an epoxidation to achieve 1,3-asymmetric induction96 Vanadium-catalyzed epoxidation of the homoallylic alcohol (12) gave the epoxide (13) which was opened under very mild conditions (silca gel) to give the 1,3-diol (14) (Scheme 20). 1,3-Asymmetric induction was excellent (97:3), though the chemical yield was poor. The regioselective opening of mono- and 1,2-di-substituted epoxides has been demonstrated by Soai”, using sodium borohydride in t-butanol-methanol or 1,2-dimethoxyethane-methanol. Regioselectivities were generally greater than 90:10, giving the
.
4: Alcohols, Halogeno-compounds, and Ethers more substituted alcohol.
219
Sharpless has examined the nucleophilic
opening of a series of erythro- and threo-2,3-epoxy alcoholsg8. In particular, with aluminium hydride reducing agents, the erythroisomers were reduced more selectively than their threo-counterparts. In general, the opposite was found on opening such epoxides with other nucleophiles. Increased, though not complete regioselective,C-2 opening of 2,3-epoxy alcohols with methylcuprates was achieved by using more complexing solvents and preparing the organocuprate from low-halide methyllithiumg9.
Selective opening of a 2,3-epoxy alcohol at the
C-3
position was achieved with dimethylcopper lithium and boron Again the regioselectivity of the trif luoride in ether"'.
reaction was not complete. Allylstannanes have been added to vinyl epoxides in the presence of boron trifluoride with very high regioWhen the olefinic terminus was unsubstituted or selectivities'''. had only a single small substituent, 1,2-addition occurred cleanly. When it was disubstituted or substituted with a phenyl group, 1,4-addition occurred, again cleanly, Marshall has shown that dimethylcopper lithium adds 1,4-anti to the homochiral vinyl epoxides (15) to give the E-allylic alcohols (16) (Scheme 21)Io2. The E-allylic alcohol is obtained regardless of the geometry of the double bond in the starting material. Higher order organocuprates reacted regiospecifically with 2,3-epoxy mesylates in a stepwise mannerlo3. The first equivalent of the organocuprate opened the epoxide (distal to the mesylate) and the reaction could be stopped here if required. If a second equivalent of the organocuprate was employed the epoxide that resulted from the first reaction could also be opened. Miscellaneous Methods
-
The use of dimethylboron bromide as a
reagent for the opening of cyclic ethers has been examined''*. It reacts with 2-substituted tetrahydrofurans to give the secondary alcohol as the major product (>3.5:1). 1,3-Diols have been converted into homoallylic alcohols & y their dimethylformamide acetalslo5. Quaternization of these acetals followed by thermal elimination yielded the alcohol.
Homoallylic alcohols have also
been made by nickel-catalyzed coupling of Grignard reagents with 5-alkyl-2,3-dihydrofurans. Kocienski has studied the reaction and extended it into a general stereoselective homoallylic alcohol synthesislo6 (Scheme 2 2 ) . A stereoselective synthesis of 2E,4Z-
General and Synthetic Methods
220
RCHO
+
X'' 4
Ph
S i Me,
R e a g e n t s : i , Ph,BOTf (cat.) ; i i ,
-
Scheme 19
i
Me,Si
(12) Reagents : i , VO(acac
Me,Si
sx
OH
OH
(13)
1 2 , Me,COOH ; ii, silica gel Scheme 20 ,OH
',
Reagent
OH
: i , Me,CuLi S c h e m e 21
96 '10
Scheme 22
4: Alcohols, Halogeno-compounds, and Ethers
22 1
dien-1-01s has been reportedlo7. The key steps were a zirconiummediated [2,3l-Wittig rearrangement and a Peterson olefination (Scheme 23). Another synthesis of 2,4-dien-l-ols involved the addition of organometallic reagents to 2G-pyranslo8. The reaction proceeded by ring opening to the corresponding dienones followed by addition of the organometallic reagent. A one-pot synthesis of l-substituted cyclopropanols has been described' 0 9 . Chloromethyllithium (generated in situ) was added to an acid chloride. In the same reaction lithium powder was then added to give a cyclopropanol. 1,2,2-Trisubstituted cyclopropanols have been made by the cyclopropanation of lithium enolates by diiodomethane and samarium diiodide'''. The stereo-chemistey was controlled by the geometry of the lithium enolate. 3-Alkylidenecyclohexanols have been prepared by the intramolecular ene reaction of &,€-unsaturated The diastereoselectivity of the reaction was aldehydes'". generally good, for instance in the reaction of the aldehyde (17) to give the cyclohexanol (18) (Scheme 24). Aromatic rings have been hydroxylated by lithiation followed by treatment with molecular oxygen to give phenols112. The regiochemistry of the reaction was controlled by ortho-directing substituents. Hydroxylation reactions have also been carried out by microorganisms. Fungi such as Mortierella isabellina converted . Optical yields were moderate. ethylbenzene into l-phenylethan~l"~ Some para-substituted ethylbenzenes were also hydroxylated, as were 2-ethylnaphthaleneI 2-ethylthiophene and n-propylbenzene. Ytterbium metal has been used to couple aromatic carbonyl compounds to give the corresponding p i n a ~ o l s l ~ ~Symmetrical . products were formed in good yield, as were cross-coupled products between benzophenone and other ketones when the reaction was performed in a sequential manner. A general stereocontrolled synthesis of 1 ,2-diols from diketosulphides has been reported115. Intramolecular low-valent titanium-mediated coupling of diketosulphides, for instance (19), gave the *-3,4-dihydroxythiolane (20) stereospecifically. Raney nickel desulphurisation then gave the 1,2-diol (21) (Scheme 25). A threo-selective pinacol reaction of aromatic and o,B-unsaturated aldehydes mediated by a titanium (111)syn-1 ,3-Diol magnesium (11) complex has also been described1l6. monoethers have been prepared by Schreiber by a [1,2]-Wittig rearrangement117. The diastereoselectivity of the reaction was good, though chemical yields were only moderate (Scheme 26). A
Griicml arid Sq'nr h or ic Met h ocis
222
0 I
y
o
R
, ii
/I
&
R
-
SiMe,
OH
...
T
O
H
R R e a g e n t s : i , L D A ; i i , Cp,ZrCl,
; iii
?+-OH R
SiMeg
, NaH
Scheme 23
Me2AICl
0
OH
(17)
(18) Scheme 2 4
(191
R e a g e n t s : i , TiCI4-Zn ; i i
(211
(201
,Raney, nickel Scheme 25 R'
OR '
Bu Li R
Scheme 2 6
R
H
4: Alcohols, Halogeno-compounds, and Ethers
223
route to 1,4-alkanediols from 1,2-oxaborolanes (available from ally1 alcohol) has been described118. Reaction of boron-substituted 1,2-oxaborolanes with dichloromethyllithium followed by oxidative work-up gave the 1,4-diols in good yield. An alternative route was also described. A stereoselective aldol reaction, followed by a phenylthio migration and a [2,3]-sigmatropic rearrangement of a sulphoxide were the key steps in a stereocontrolled synthesis of syn-E-2,4-dimethy1hex-3-en-lI 5 - d i 0 1 ~ ~ ~The . anti-isomer was also made, by a different route. y-Hydroxy ketones have been prepared by the reaction of 2,2-dimethyl-4-lithio-l,3-oxathiane 3,3-dioxide with methyl esters followed by treatment with silica gel'". y-Hydroxy-a,@-unsaturated ketones were made by treating aldehydes (bearing two a-hydrogen atoms) (22) with the sulphoxide (23) (Scheme 27)12'. The new double bond was produced with E-geometry. A general enantioselective synthesis of primary alcohols has been reported122. Diamides derived from a homochiral piperazine were diastereoselectively alkylated. Reduction of the product diamide then gave the primary alcohol in moderate enantiomeric excess. A microbial hydrolysis of racemic ally1 acetates has been used to produce optically active allylic alcohols123. Rhizopus nigricans was found to give moderate optical yields with most substrates, both cyclic and acyclic. Another microbially based enantioselective hydrolysis used lipase-MY (derived from Candida cyclindracea) to resolve a series of 1-substituted 2,2,2trif luoroethyl acetates124. The hydrolysis produced the (R) alcohols and the (5)-enantiomers were available from the unreacted acetates. Excellent optical yields have been obtained by the enantioselective hydrogenation of prochiral allylic and homoallylic alcohols125. A ruthenium (11) dicarboxylate complex containing BINAP (24) was shown to be an extremely efficient catalyst for this process, giving optical yields of 96% or better. Another ruthenium (11) BINAP complex (this time containing halide ligands) was found to be extremely efficient at reducing B-ketoesters to give B-hydroxyesters of very high optical purity126. In many cases enantiomeric excesses of over 9 9 % were observed. In both these ruthenium-catalyzed reactions the substrate to catalyst ratio was extremely high ( 1000 was typical) showing the great efficiency of the catalysts. Oku has published two papers on the enantioselective functionalization of prochiral 2-substituted
1,3-diols. The reaction of the bis(trimethylsily1) derivative of the diol with A-menthone selectively gave one diastereoisomeric keta1127. This was then cleaved selectively with the trimethylsilyl enol ether of acetophenone. After protection and removal of the chiral auxiliary the monoprotected diol was produced with >95% ee. In a subsequent paper Oku described an alternative ketal cleavage using triisobutylaluminium128. Stork has reported a general iterative method for the construction of polypropionate chains consisting of alternating secondary methyl and hydroxyl groups129. Starting with a 5-substituted butenolide or a 5-substituted 3-hydroxy-4-methylbutenolide ( 2 6 ) , each of the four possible diastereomeric 3-hydroxy-4-methyl-2-furanones (27-30) were synthesized. The process was then made iterative by elaborating any of the 3-hydroxy-2-furanones (27-30) to the next butenolide or 3-hydroxybutenolide (Scheme 28). Stork then utilised this methodology in a concise synthesis of (+)-(9S)-dihydroerythronolide Finally, a secondary alcohol epimerisation isourea ethers The alcohol was reacted with dicyclohexylhas been describedL3'. carbodiimide to give the isourea ether which was then reacted 2 situ with a carboxylic acid to give the inverted ester. Hydrolysis finally gave the epimeric alcohol. Protection and Deprotection - A method for the selective deprotection of either an alkyl or a phenolyl trimethylsilyl ether has been described'32. A quaternary ammonium resin (-OH form) selectively liberated a phenol whereas a carboxylate resin (H' form) selectively gave primary and secondary alcohols from a doubly protected phenolic alcohol. An oxidative method for deprotecting t-butyldimethylsilyl ethers has been reported133. A combination of t-butyl hydroperoxide and dioxobisacetylacetonate-molybdenum gave the alcohol in good yield. Denmark has described a new protecting group for alcohols, diphenylmethyl~ilyl'~~. Its stability was intermediate between trimethylsilyl and t-butyldimethylsilyl. The selective removal of a tetrahydropyranyl protecting group in the presence of a t-butyldimethylsilyl ether was achieved using magnesium bromide in ether135. The method worked well for primary and secondary alcohols, but not with tertiary or secondary benzylic alcohols. A method to deprotect benzyl ethers of sugars on a small scale has been de~cribed'~~. Anhydrous iron (111) chloride in
4: Alcohols, Halogeno-compounds, and Ethers
225
0-
0 R I T o
+ 0
H
Reagents : i ,
Et,NH
, AcOH Scheme 27
(29)
(301
Scheme 2 0
Reagents : i
,
K z R u Q h / A d o g e n 4 6 4 , K 2 S 2 0 8 , CH2Cl,,
Scheme 29
NaOH
226
G w t d and Synthetic' Methods
dichloromethane effected the reaction in greater than 70% yield. Protection of alcohols as their p-methoxybenzyloxymethyl ethers has been detailed137. The protecting group was easily added to even tertiary alcohols and, like p-methoxybenzyl ethers, could be removed oxidatively. 2-Iodobenzoyl has been shown to be an alcohol protecting group that can be removed by chlorination followed by mild basic hydrolysis138. It was particularly useful in the synthesis of 1,2-diacylglycerols. In recent years a carbon-bound silyl group has come to be regarded as a protected alcohol. Fleming has described a one-pot conversion of the phenyldimethylsilyl group into a hydroxyl group139. Treatment of the silane with either bromine or mercury (11) ions in a solution
of peracetic acid in acetic acid gave the unmasked alcohol. Oxidation - There has been continued interest in chromium oxidants in 1987, with several variations and modifications to the known reagents being published.
Potassium chlorochromate was shown to
be a useful reagent for the oxidation of saturated secondary alcohols, primary and secondary allylic alcohols and benzylic Saturated alcohols to the corresponding carbonyl compounds' primary alcohols were oxidized to the corresponding aldehydes, but only in low yields. The use of 3-carboxypyridinium dichromate (nicotinium dichromate, NDC) as an oxidant for alcohols has been It has been used in conjunction with pyridine reported in full1*'. to oxidize a wide range of alcohols. It was compared with pyridinium dichromate (PDC) and, in contrast to this reagent, was able to selectively oxidize benzylic alcohols in the presence of aliphatic alcohols. Chromic acid adsorbed on aluminium silicate has been used €or the oxidation of primary alcohols to aldehydes142. The use of chromic acid on silica gel has been extended to the oxidation of allylic alcohols143. Chromium trioxide has been used catalytically in the oxidation of alcohols to carbonyl compounds144. t-Butyl hydroperoxide was used as the co-oxidant. This oxidation system was particularly efficient for secondary benzylic alcohols. The interest in ruthenium-based oxidation systems has undoubtedly been growing in recent years. The efficiency of a ruthenium dioxide-sodium periodate oxidation system was shown to be enhanced by the addition of a phase-transfer catalyst'45. This system was particularly efficient for the oxidation of secondary
4: Alcohols, Halogeno-compounds, and Ethers carbohydrate-derived alcohols to the corresponding ketones.
227 A
phase-transfer catalyst was also found to be beneficial in the ruthenium-catalyzed oxidation of benzyl alcohols to the corresponding b e n ~ a l d e h y d e s l ~ ~In . this reaction the carbon tetrachloride functioned as a hydrogen acceptor and was converted to chloroform. Griffith and Ley have introduced two new catalytic ruthenium-based alcohol oxidants, tetra-n-butylammonium per-ru thenate (TBAP) and tetra-n-propylammonium per-ruthenate (TPAP)147.
Both use :-methyl
morpholine N-oxide as co-oxidant. The
two reagents were extremely effective in oxidizing a wide range of alcohols, including highly functionalized ones, to the corresponding carbonyl compound. A ruthenium catalyzed oxidation of primary and secondary alcohols using the most convenient co-oxidant, molecular oxygen, has also been reported148. Primary alcohols were oxidized more rapidly than secondary, while tertiary alcohols were inert under the reaction conditions. No over-oxidation of aldehydes to carboxylic acids was observed. Catalytic amounts of potassium ruthenate in the presence of a potassium peroxodisulphate co-oxidant and a phase-transfer catalyst selectively oxidized allylic and benzylic alcohols in the presence of saturated alcohols (Scheme 29)14'. Yields were excellent. Finally, in another ruthenium-catalyzed reaction, primary alcohols were converted directly into esters (Scheme 30)150. The reaction conditions also converted 1,4- and 1,5-diols to the corresponding yand &-lactones respectively. McKillop has reported a permanganate oxidation of a wide range of benzylic alcohols151. Potassium permanganate was used in conjunction with tris-2-(2-methoxyethoxy)ethylamine to give generally good yields of carbonyl compounds. A peroxo-molybdenum complex has been used to oxidize alcohols to the corresponding carbonyl compounds152. 1,2-Diols were cleaved to carboxylic acids and 1,4-, 1,5- and 1,6-diols gave the corresponding lactones. A magnesium-Oppenauer oxidation has been reported153. Halomagnesium alkoxides were converted into aldehydes and ketones in the presence of a hydride acceptor such as benzaldehyde. The advantage of this procedure is the ready availability of the halomagnesium alkoxides from Grignard reactions.
Hence, it represents an in situ oxidation
of Grignard reaction products. In another Oppenauer-type reaction, catalytic amounts of a zircocene complex have been used to oxidize allylic alcohols to 0 , @-unsaturated carbonyl compounds154. To
General and Synthetic Methods
228
avoid aldol-type reactions, hydride acceptors without a-hydrogens (such as benzaldehyde) were used. A further variant on the Moffatt (Swern) oxidation has been published155. Phosphorus pentoxide was shown to be a suitable activating agent for dimethylsulphoxide, having the advantage over the Swern procedure that chlorinated by-products were not produced. Benzylic and aliphatic secondary alcohols were oxidized by peracetic acid in the presence of sodium bromide156. Yields of the corresponding carbonyl compounds were generally good. Catalytic quantities of 4-methoxy-2,2,6,6-tetramethylpiperdine-l-oxyl (31) with sodium hypochlorite was shown to be an effective oxidizing system, the active oxidant being an oxoammonium salt (32)157. Primary alcohols could be selectively oxidized to aldehydes or, by adding a phase-transfer catalyst, to carboxylic acids. Secondary alcohols were converted into ketones. An efficient method for the oxidation of trif luoromethyl carbinols has been reported158. These usually resistant alcohols were oxidized in good yield using the Dess-Martin periodane oxidant. Finally, Tsuji has oxidized alcohols via their allyl carbonates using a phosphine-free palladium complex, or a ruthenium hydride complex as catalyst159 . The reaction worked for all alcohols except saturated primary alcohols.
2 Halogeno-compounds
Preparation. - From Alcohols. A one-pot preparation o f primary alkyl and allyl halides from the corresponding alcohols has been The alcohol was converted into the trif luoroacetate described16'. which then underwent displacement to the halide. t-Alkyl chlorides have been prepared from t-alcohols in a two-step process 161 . Firstly, the chloroglyoxylic ester was prepared which was then treated with g-hydroxy-pyridine-2-thione sodium salt to give the chlorides in good yield. t-Alkyl iodides have also been prepared from the corresponding alcohols162. The reaction was carried out by treating the alcohol with magnesium iodide in pentane to give the tertiary halides in good yield. An alternative method to convert alcohols (except tertiary alcohols) into the corresponding bromide or iodide was to use the 2-alkylisourea as an This was treated with trif lic acid and excess
4: Alcohols, Halogeno-compounds, and Ethers
229
tetrabutylammonium halide to give the alkyl halide.
It was found
that the g-alkylisourea could be used crude without loss in yield. Both alcohols and tetrahydro-2-pyranyl-protected alcohols were converted into the corresponding bromides or iodides by treatment with lf2-bis-(triphenylphosphino)ethanetetrahalide (prepared 9 situ from the bisphosphinoethane and two equivalents of the halide) t-Butyldimethylsilyl ethers, however, were inert to the reaction conditions allowing direct reaction of a differentially protected diol. Conversely, in another paper, t-butyldimethylsilyl ethers have been converted into Treatment with carbon tetrabromide, triphenylphosphine and acetone gave the halide in reasonable yield. From Alkenes. - Hydrogen iodide has been added to alkenes by using iodine on alumina (hydrogen iodide was produced in situ)166 . Moderate yields of the Markovnikov product were produced with a range of cyclic and acyclic alkenes. Halofluorination of alkenes has been accomplished using triethylamine tris-hydrofluoride (Et3N.3HF) as a fluoride ion source167. It was used in conjunction with an E-halosuccinimide to give chloro-, bromo-, and iodofluoroalkenes in generally good yield. In a related reaction, insoluble polymer-supported hydrogen fluoride was used as the fluoride source in the iodofluorination of alkenes in the presence of N-iodosuccinimide168. Under the same conditions phenyl acetylenes gave Z-iodofluoroalkenes regiospecifically (with the fluorine o- to the phenyl group). The same research group has added fluorine to an alkene by using cesium fluoroxysulphate and hydrogen fluoride to give a 1 ,2-difl u ~ r o a l k a n e ' ~ ~If hydrogen fluoride was omitted and methanol used as a solvent the reaction gave a 2-methoxyfluoroalkane. Both a ruthenium (11) and a rhenium (111) catalyst have been used to promote the addition of a tetrahalomethane to an alkenel7O. With 1,6-dienesf a ring closure occurred to give Z-lf2-disubstituted cyclopentanes as the major products (Scheme 31). A ruthenium (11) catalyst in the presence of an optically active phosphine ligand added the elements of carbon tetrachloride (from trichlormethanesulphonyl chloride with sulphur dioxide extrusion) across styrenes to give homochiral benzyl chlorides (Scheme 32)171. Only low optical yields were obtained, however. A general iodofunctionalization of alkenes used a mixture of iodine and copper (11) oxide-fluoboric acid in the presence of I
S c h e m e 30
OMe
OMe
II
I
0.
0
(311
(32I CCl,
I
Et0,C R e a g e n t s : i , CCI,
C0,Et
Et02C
C02Et
, ReC13( PPh 3 ) 2 ( M e C N 1 c a t Scheme 31
ArReagent
Ar
: i , Ru,Cl,(diop), Scheme 32
Br R e a g e n t s : i , MeS03H
Br
,
H20
S c h e m e 33
4: Alcohols, Halo~~eno-cornyounds, and Ethers
23 I
a wide variety of nucleophiles to give 1-iodo-2-substituted alkanes172. 1,3-Dienes also reacted and gave either 1,2- or lI4-products. Acetylenes gave substituted olefins. Perfluoroalkyl iodides were added to terminal olefins in the presence of a palladium catalyst173. The resulting palladium species was alkoxycarbonylated (carbon monoxide and an alcohol) to give @-perfluoroalkyl-c,e-unsaturated esters. If allyl alcohols were reacted with perfluoroalkyl iodides, also in the presence of a palladium catalyst, perfluoroalkylmethyl-substituted epoxides resulted174. Finally, Curran has used a hexabutylditin catalyst to add a-iodocarbonyl compounds across an f -olefin i n t r a m ~ l e c u l a r l y ~ ~ ~ . The major product was a 1-carbonyl 2-iodomethyl substituted cyclopentane. Interhalide Conversions. - Primary alkyl halides were converted into the corresponding alkyl fluorides by a reagent prepared from copper
(I) oxide and hydrogen fluoride, in the presence of a pyridine, in generally good yields176. Secondary alkyl fluorides were also prepared, though the yields were lower and significant amounts of alkene products were also formed. Miscellaneous. - Alkyl halides have been converted into their next higher homologues by a two-step process177. The halide was converted into its Grignard reagent and then reacted with an aminomethyl ether to give the homologated amine. This was then treated with a chloroformate to give the homologous halide. Cyclic ethers have been cleaved with acyl chlorides in the presence of a catalytic amount of cobalt (11) chloride to the corresponding w-acyloxy-l-~hloroalkanes~~~. Perfluoroalkyl groups (from perfluoroalkyl iodides) have been coupled with alkenyl, allyl and alkynyl groups (from the corresponding trialkylstannanes) in the 1-Substituted presence of a palladium (0) catalyst17'. allylstannanes reacted with allylic inversion. Monofluoromethylene (-CFH-) containing compounds have been prepared by the use of a-f luoro-a-nitro carboxylic estersl8O. Alkylation followed by decarboxylation and nitro group removal (by tributyltin hydride) gave a
general synthesis of monofluoromethylene compounds.
A mild
method for the conversion of a carbonyl group into a dif luoromethylene group (-CF2-) has been reported181. Iodine monofluoride was produced in situ and reacted with the hydrazones
of a range of carbonyl compounds to give the difluoromethylene compounds in generally good yields. 1,l-Di(trifluoromethy1)alkenes have been synthesized by the reaction of 2,2-dichlorohexafluoropropane with aldehydes and triphenylphosphinel82. Yields were variable , ranging from 4 to The organozinc species derived from bromodifluoromethyl
88%.
acetylenes have been reacted with aldehydes to give dif luorohomopropargylic alcohols183. This reaction was used to synthesize 2,2-difluoro-2-deoxy-~-ribose. 1,2-Disubstituted and lf2,3-trisubstitutedmonofluorocyclobutanes were made by the concomitant ring expansion and fluorination of cyclopropylmethyl alcohols184. The reaction was carried out with an amine-potassium
fluoride-pyridine-hydrogen fluoride complex to give good yields of the fluorocyclobutanes. Preparation of a-Halo Carbonyl Compounds. - A general two-step preparation of chloromethyl ketones has been reported'85. 6-Ketoesters were chlorinated with sulphuryl chloride and the subsequent products dealkoxycarbonylated with 50% sulphuric acid to give the chloromethyl ketones in reasonable yield. The reaction of a-fluoro-a,B-unsaturated esters with dimethylsulphoxonium methylide gave B-ketosulphoxonium ylides which, when treated with hydrogen chloride and heated, gave chloromethyl a-fluoro-a,B-unsaturated ketones186. 0-Diketones have been selectively monof luorinated by treatment of their silyl enol ethers with 5% fluorine in nitrogen to give the monof l u o r ~ d i k e t o n e l ~ ~Although . the yields were not high (26-53%) only monofluorination occurred, and the reaction is claimed to be the only general route to these compounds. Fluoromethyl ketone enol ethers have been regiospecifically produced by treating a 2-alkoxy-1,3-disilyloxy-alkane with tetrabutylammonium fluoride and mesyl fluoride18*. When the 2-alkoxy group was an allyloxy group, a [3,3]-sigmatropic rearrangement gave y,&-unsaturated fluoromethyl ketones.
1-Alkyl
substituted perfluoroalkylaluminium enolates have been made from the corresponding alkyl perfluoroalkyl ketones (via their 1-alkyl 1-perfluoroalkenyl phosphates)18'. These enolates reacted with aldehydes in an aldol reaction to give a-fluoro-aperfluoroalkyl-B-hydroxy ketones in good yield. The same research group has carried out aldol reactions with chlorodifluoromethyl ketones'". These reacted with a variety of aldehydes and ketones
4: Alcohols, Halogeno-compounds, and Ethers
233
when treated with zinc and catalytic copper (I) or silver (I) to give @,a-difluoro-B-hydroxy ketones in good yields. Finally, a-bromoalkyl aryl ketones have been prepared in enantiomerically pure formlgl. This was achieved by the hydrolysis of a mixture of the diastereomeric dimethyl tartrate ketals of the bromoalkyl aryl ketone (Scheme 33). The enantiomeric excess of the final bromoketone was higher than the diastereomeric excess of the intermediate keta1s
.
Preparation of Vinyl Halides. - 6-Styryl halides have been prepared by dehydrohalogenation of vicinal dihaloalkaneslg2. The dihalides were treated with silica gel in carbon tetrachloride in the dark to give the styryl halides in excellent yield. Functionalized vinyl iodides have been prepared by the treatment of acetylenes with iodine and mercury(I1) saltslg3. A wide range of mercury salts were used to give the E-1-iodo-2-functionalized alkenes in generally good yield. Vinylsilanes have been stereoselectively halogenated to give vinyl halideslg4. A trimethylsilyl group led to inversion of configuration (E-vinyl silanes giving Z-vinyl halides) whereas a pentafluorosilicate group led to retention of configuration. In both cases high stereoselectivity was observed. 1,l-Dichloroalkenes have been monoalkylated (and -arylated) in a stereospecific mannerlg5. The palladium catalyzed addition of a Grignard or organozinc reagent cleanly replaced the chlorine trans to the 2-substituent in high yield (Scheme 34). A second equivalent of another organometallic reagent then displaced the remaining chlorine with retention of configuration. Vinyl chlorination has been achieved using benzeneseleninyl chloride and an olefin catalyzed by aluminium trichloride or a ruthenium (11) phosphine The reaction was limited as a1 lylic chlorides were complex' also produced when the substitution allowed. A similar reaction was performed with phenylselenium trichloride which was added to an olefin and the resulting dichloroselenide then hydrolyzed to the selenoxide which then spontaneously eliminated' 9 7 . Again, a1 lyl chlorides were also produced under suitable conditions. The reaction has been extended to give 2-chloro-1-olefins selectively by the addition of phenyl selenenyl chloride to a terminal o1efinlg8. The selenide was then chlorinated and hydrolyzed to the corresponding selenoxide which eliminated to give the vinyl chloride in good yield. The coupling of carbenes,produced by
234
Grri c w 1 (ifid Syt it hctic Methods
diazirine decomposition in the presence of diazo compounds,has been used to make vinyl halides’’’. The reaction is limited by the availability of the starting materials. Methyl esters have been prepared by the reaction of methyl dichlorofluoroacetate with carbonyl compounds
Z-a-fluoro-c,B-unsaturated
Yields were good with promoted by zinc and copper (I) chloride2”. aldehydes, but only moderate with ketones. a-Fluorosulphoxides, prepared by treatment of thioacetals with mercury difluoride followed by oxidation with m_-chloroperbenzoic acid, were pyrolyzed to give vinyl fluorides2”. The olefins were formed as a mixture of E- and g-isomers. l-Fluoro-l-trifluoromethylalkenes have been prepared by a two-step process202. Trif luorovinyllithium was added to an aldehyde and the resultant alcohol treated with hydrogen fluoride in tetrahydrofuran which caused a rearrangement to the tetrafluoroalkene in moderate to good yield. B-Chloro9,y-unsaturated ketones have been prepared from p-diketones203 . The diketones were treated with carbon tetrachloride and triphenylphosphine to give the (3-chloro-Bly-unsaturatedketones as the major product. It was shown that the B,y-unsaturated ketones were thermodynamically more stable than the corresponding a,B-unsaturated isomers. 2-Chloroalk-l-en-3-ynes were synthesized by the palladium-catalyzed coupling of 1,l-dichloroethylene and If vinylalanes were used in place of acetylenes,
acetylene^^'^.
2-chloro-1,3-dienes resulted. Preparation of Other unsaturated Halides. - An improved method for the preparation of iodoacetylenes has been reported 2 0 5 . Terminal acetylenes were treated with sodium methoxide and bis(pyridine1 iodine (I) tetrafluoroborate to give good yields of the 1-iodoacetylene. Allenyl fluorides have been made by reaction of an acetylide anion with with dichlorofluoromethane to give a
l-chloro-l-fluoroalk-2-yne which was then reduced with aluminium hydride to an allenyl fluoride206. This reaction was used in the synthesis of a fluoroallenyl amino acid. Both chloro- and bromobenzenes have been converted into the corresponding iod~benzene~”. Copper (I) iodide supported on alumina or charcoal accomplished the reaction in generally good to excellent yields. Barton has described a radical decarboxylative bromination and iodination of aromatic acids208. The thiohydroxamic esters of the benzoic acids were treated with
4: Alcohols, Halogeno-compounds, and Ethers
235
bromotrichloromethane, iodoform or diiodomethane in the presence of a radical initiator to give the halobenzene in good yield.
3 Ethers
Methyl ethers have been prepared by treating the parent alcohol adsorbed onto silica gel with dia~omethane~”. Yields were excellent. Symmetrical ethers have been synthesized directly from alcohols by dehydration in the presence of zinc chloride2’’. Unsymmetrical benzyl alkyl ethers were also made in good yield by this procedure, as were cyclic ethers from the corresponding diols. The reductive coupling of carbonyl compounds, with trialkylsilanes catalyzed by trimethylsilyl iodide, has been used to make symmetrical ethers211. Unsymmetrical ethers could be made starting with a carbonyl compound and coupling it reductively with a silyl ether. E-3-Chloroallyl ethers have been synthesized by the reaction of l-chloro-2,3-epoxypropane with alkyl chlorides in the presence of solid sodium hydroxide212. Yields were only moderate. A general synthesis of t-alkoxyethynyl ethers has been reported213 . A 2-bromo-t-alkoxy ethylene was prepared and treated with sodium amide in liquid ammonia. Alkylation of the resulting anion represented a general synthesis of t-alkoxyethynyl ethers. Chiral acetylenic ethers have been prepared from chiral alcohols and trichloroethylene by known methods. They were useful precursors to stereochemically pure enol ethers, both 5- and g-isomers being available214. Direct alkoxylation of anthracene has been observed215. Treatment of anthracene with a normal alcohol and a cerium (IV) catalyst gave a 9-alkoxyanthracene. Barton has published a paper describing the 2-phenylation of alcohols with tetraphenylbismuth trif luoroacetate216. Primary alcohols gave reasonable yields of the phenyl ether, whereas secondary alcohols gave only low yields and tertiary alcohols did not react. An SN2 mechanism was proposed with attack of oxygen on the aryl carbon atom. In another paper, Barton has studied the phenylation of 0-Phenylation phenols with triphenylbismuth dichloride217. occurred with phenols with electron-withdrawing substituents and ortho-g-phenylation occurred when electron-donating substituents were present.
General and Synthetic Methods
236
Cyclic ethers have been prepared by reacting hydroxy alkenes with phenylsulphonyl chloride and Hunig's base218. Five and six membered rings were formed from acyclic precursors and four membered rings could be made with bicyclic starting materials. Harwood has prepared cyclic ethers by oxidative cyclisation of 2- (4-hydroxyalkyl) and 2- (5-hydroxyalkyl)furans with DDQ219. The reaction gave 2-(2-furanyl)tetrahydrofurans and tetrahydropyrans in reasonable yields (Scheme 35). 4 Thiols
Homochiral tertiary thiols (with the thiol group a- to a carboxylic acid or ester) have been prepared from the corresponding homochiral secondary thiols in an analogous way to Seebach's route to a-amino acids220. The secondary thiol was condensed with pivaldehyde to give predominantly the cis-1,3-oxathiolanone which was deprotonated and alkylated stereoselectively. Hydrolysis gave the tertiary thiols in > 98% ee in the best cases. Katritzky has used (benzothiazol-2-ylthio)(trimethylsily1)methane as a synthon for €$SCH2-, converting a 1ky 1 bromides into a- trimethy 1s i 1y 1thio 1s 21. By using Peterson olefination conditions, vinyl mercaptans were made. Thiols have been prepared by the reductive cleavage of the corresponding disulphides222. The reaction was performed using carbon monoxide, water and selenium. Thiol acids have been made by the Lewis acid catalyzed ene reaction of substituted propenes with carbonyl sulphide223 .
5 Thioethers
Carboxylic esters have been converted into the phenyl sulphides of the reduced carboxylic fragment by treatment with thexylphenylthioborane and zinc iodide in dichloromethane at room temperature224. Yields ranged from 70 to 90%. Thiol esters underwent decarbonylation when treated with a palladium ( 0 ) catalyst ~. at 1 0 0 ° C giving rise to aryl aryl and aryl vinyl ~ u l p h i d e s ~ ~The reaction also worked with stoichiometric amounts of a rhodium (I) compound. Diphenyldithioacetals were cleaved electroreductively to give phenylthioethers226. Under similar conditions a-carbonyldithioacetals gave methylthiovinylketones. In all cases
231
4: Alcohols, Halogeno-compounds, and Ethers
CI
CI
M = MgBr or Z n C l
Reagent
: i
PdCI2(dppb)
Scheme 34
DDQ
35 OIO
S c h e m e 35
Me
'I
(
33 1
Reagents: i
w SiMe3 ;
i i , TiCI,
S c h e m e 36
tetrabutylammonium hydrogen sulphate was used as the proton source. V o s s and co-workers showed that electroreduction of
thiopivalophenone in the presence of an alkylating agent in an alcohol as solvent gave thioethers in mixture with m o n o t h i ~ a c e t a l s ~ ~Yields ~. of each product were roughly similar. Bis(tributyltin1 sulphide has been shown to be an effective sulphur transfer reagent to a variety of alkyl and acyl halides to give the corresponding symmetrical thioethers and thioanhydrides228. The reagent has the advantage of being neutral and able to deliver the sulphur in a defined amount. In a variation of this reaction, unsymmetrical thioethers were prepared by treating trialkyltin mercaptides with alkyl halides in the presence of a fluoride or cyanide ion source229. Thioalkoxyphosphonium salts were demonstrated to give unsymmetrical thioethers when treated with a primary alcohol and, when treated with a carboxylic acid, gave thiol esters230. The best method of preparing the reagent for each type of reaction was discussed. Bartlett and Heathcock have shown that very high diastereofacial selectivity is possible on addition of nucleophiles to a chiral thionium ion231. When treated wih allyltrimethylsilane in the presence of titanium tetrachloride the dithioacetal (33) gave the two homoallylic sulphides (34) and (35) in a ratio of 97:3 (Scheme 36). To achieve this high degree of diastereofacial selectivity it is necessary to use the di- (2,4,6-trimethylphenyl) dithioacetal rather than just the diphenyldithioacetal. Reetz has shown that olefins can be regioand stereoselectively carbosulphenylated by treating 6-chlorosulphides with either dimethylzinc and titanium tetrachloride or the more reactive t r i m e t h y l a l ~ m i n i u m ~ ~The ~. reaction proceeded by neighbouring group participation via the episulphonium ion (36) to give the product of charge control which placed the methyl group at the more substituted carbon centre (Scheme 37). Very high stereocontrol was possible with cyclic olefins and allylic esters. Phenylthiomethyl ethers and esters have been prepared by anodic oxidation of phenyl trimethylsilylmethyl 233 . sulphide in the presence of alcohols and esters respectively Yields were reasonable. a-Trimethylsilylsulphoxides underwent a Pummerer-like rearrangement when treated with trifluoroacetic anhydride giving a-trif luoroacetyloxy s ~ l p h i d e s ~ When ~~. of trifluoroacetic acid are N-halosuccinimides in the presence used, a-halosulphides result. Ring-expanded a-phenylthioketones
4: Alcohols, Halogeno-compounds, and Ethers
239
(38) were produced when bis(pheny1thio)methyl alcohols (37) were treated with two equivalents of an alkyllithium & y a carbenoid-type reaction (Scheme 38)235 . Allylic and benzylic sulphides have been synthesized from the corresponding dithiocarbonates using a palladium (0)-phosphine catalyst under mild conditions236. When the allyl group was unsymmetrical, a mixture of regioisomers was formed. Phenyl allyl sulphides have also been made by acid catalyzed phenylthio migration in 9-phenylthio alcohols237. The regio- and stereochemical consequences of this reaction at the double bond were discussed. Vinyl sulphides were synthesized from dithioacetals by conversion to a-chlorosulphides with benzenesulphenyl chloride and then elimination with Hunig's base238. A mixture of E- and Z-double bonds was obtained. Aldehydes have been transformed into vinyl sulphides by treatment with dichloromethyl phenyl sulphide and chromium (11) chloride239. A mixture of E- and 5-olefins results, with the E-isomer predominant. Thiols have been added to terminal acetylenes under radical conditions using triethylborane as the radical initiator240. The thiol adds to the hydrogen terminus of the acetylene to give a mixture of E- and 5-vinyl sulphides. In a similar reaction to the above, Broka has shown that if there is a double bond suitably placed in the acetylene side-chain then a cyclisation will occur to give a five or six membered ring with an exocyclic thiophenylmethylene group (Scheme (39)241* 2-Phenylthio-lr3-butadienes have been prepared by lithium aluminium hydride or thermal induced sulphur dioxide extrusion from 3-phenylthi0-3-sulpholenes~~~.As these sulpholenes could be alkylated regiospecifically at C-5, 3,4-disubstituted 2-phenylthiobutadienes were accessible. In addition, as 2-substituted 3-sulpholenes regiospecifically added a phenylthio group at C-3 (via benzenesulphonyl chloride addition and elimination of hydrogen chloride), 1-substituted 2-phenylthiobutadienes were also available (Scheme 40). l-Phenylthio-1,3-butadienes were obtained by palladium (0)-catalyzed cross-coupling of alkenylboronates with 2-bromo-1p h e n y l t h i o - l - a l k e n e ~ ~ ~ The ~ . reaction was stereospecific, with the geometry of each double bond in the starting material being maintained in the product. A simple method for the conversion of aromatic epoxides to
240
Reagents : i , Me2Zn, T I C I , Scheme 37
n.1-L (371
(38) Scheme 38
- rs PhSH
AX BN
Scheme 39
.
..
hJ=(
R
ii i ___)
o4No
Reagents
: i,
PhSCl ; i i , E t 3 N ; i i i , heat S c h e m e LO
4: Alcohols, Halogeno-compounds, and Ethers
241
thiiranes using potassium thiocyanate has been reported244. This modification used solid potassium thiocanate and a very small amount of water. Yields were generally good, but the reaction failed with aliphatic epoxides. References 1.
2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
12. 13. 14. 15. 16. 17. 18.
19. 20. 21. 22. 23. 24. 25. 26
I
27. 28.
M. Srebnik, T.E. Cole, and H.C. Brown, Tetrahedron Lett., 1987, 28, 3771. H.C. Brown, J.V.N.V. Prasad, A.K. Gupta, and R.K. Bakshi, J. Org. Chem., 1987, 52, 310. K. Maruoka, H. Sano, KTShinoda, and H. Yamamoto, Chem. Lett., 1987, 73. Y. Aoyama,Y. Tanaka, T, Fujisawa, T. Watanabe, H. Toi, and H. Ogoshi, J. Org. Chem., 1987, 52, 2555. G. Zweifel, G.H. Hahn, and T.M. Shoup, J. Org.. Chem., 1987, 52, 5484. K. Tamao, T. Yamauchi, and Y. Ito, Chem. Lett., 1987, 171. K. Tomioka, M. Nakajima, and K. Koga, J. Am. Chem. S O C . , 1987, 109. 6213. R. Annunziata, M. Cinquini, and F. Cozzi, Tetrahedron Lett., 1987.. 28.. 3139. I. Fleming, A.K. Sarkar, and A . P . Thomas, J. Chem. SOC., Chem. Commun., 1987, 157. P.F. Corey, Tetrahedron Lett., 1987, 28, 2801. T. Okano, M. Matsuoka, H. Konishi, and J. Kiji, Chem. Lett., 1987, 181. T.E.A. Nieminen and T.A. Hase, Tetrahedron Lett., 1987, 28, 4725. N.M. Yoon and K.E. Kim, J. Org. Chem., 1987, 52, 5564. S. Komiya and 0. Tsutsumi, Bull. Chem. SOC. Jpn., 1987, 60, 3423. M. Borbaruah, N.C. Barua, and R.P. Sharma, Tetrahedron Lett., 1987, 28, 5741. A. Ono and H. Hayakawa, Chem. Lett., 1987, 853. E.J. Corey, R.K. Bakshi, and S. Shibata, J. Am. Chem. SOC., 1987, 109, 5551. E.J. Corey, R.K. Bakshi, and S. Shibata, C.-P. Chen, and V.K. Singh, J. Am. Chem. SOC., 1987, 109, 7925. A.K. Mandal, T.G. Kasar, S.W. Mahajan, and D.G. Jawalkar, Synth. Commun., 1987, 17, 563. H.C. Brown, B.T. Cho, and W.S. Park, J. Org. Chem., 1987, 52, 4020. H.C. Brown, W.S. Park, B.T. Cho, and P.V. Ramachandran, J. Org. Chem., 1987, 52, 5406. A. Mori, K. Ishihara, I. Arai, and H. Yamamoto, Tetrahedron, 1987, 43, 755. H. Takahashi, T. Moritomo, and K. Achiwa, Chem. Lett., 1987, 855. T. Osawa and T. Harda, Bull. Chem. SOC. Jpn., 1987, 60, 1277. G. Solladie, J. Hutt and C. Frechou, Tetrahedron Lett., 1987, 28, 61. M. Utaka, H. Higashi, and A. Takeda, J. Chem. SOC., Chem. Commun., 1987, 1368. M. Utaka, H. Watabu, and A. Takeda, J. Org. Chem., 1987, 52, 4363. A. Manzocchi, R. Casati, A. Fiecchi, and E. Santaniello, J. Chem. SOC., Perkin Trans. 1, 1987, 2753.
242 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53.
54. 55. 56. 57. 58. 59. 60. 61. 62.
General .and Synthetic Methods B r o o k s , R.P. Kellogg, a n d C . S . C o o p e r , J. O r g . Chem., 1 9 8 7 , 52, 1 9 2 . R . B e r n a r d i , R . C a r d i l l o , D . G h i r i n g h e l l i , a n d 0. V a j n a d e P a v a , J . Chem. S O C . , P e r k i n T r a n s . 1 , 1 9 8 7 , 1 6 0 7 . A. F a u v e and H. Veschambre, T e t r a h e d r o n L e t t . , 1 9 8 7 , 5037. S. T s u b o i , H . F u r u t a n i , M. U t a k a , a n d A . T a k e d a , T e t r a h e d r o n 2709. L e t t . , 1987, M.T. R e e t z a n d S. M a u s , T e t r a h e d r o n , 1 9 8 7 , 43, 1 0 1 . M.T. R e e t z , H. H u g e l , a n d K . D r e s e l y , T e t r a h e d r o n , 1 9 8 7 , 43, 109. N. K r a u s e a n d D. S e e b a c h , Chem. B e r . , 1 9 8 7 , 1845. M . Wada, H. O h k i , a n d K . A k i b a , J . Chem. S O C . , Chem. Commun., 1987, 708. Y . B u t s u g a n , H. I t o , a n d S. A r a k i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3707. S. S i b e l l e , E d ' I n c a n , a n d L. L e p o r t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 55. A, T a k u w a , H . T a g a w a , H . I w a m o t o , 0. S o g a , a n d K . M a r u y a m a , Chem. L e t t . , 1 9 8 7 , 1 0 9 1 . Y . Masuyama, N . K i n u g a w a , a n d Y . K u r u s u , J. O r g . Chem., 1 9 8 7 , 52, 3702. T . T a b u c h i , J . I n a n a g a , a n d M. Y a m a g u c h i , Chem. L e t t . , 1 9 8 7 , 2275. M. M a t s u k a w a , J. I n a n a g a , a n d M. Y a m a g u c h i , T e t r a h e d r o n L e t t . , 5877. 1987, D . B a s a v a i a h , T.K. B h a r a t h i , a n d V.V.L. G o w r i s w a r i , S y n t h . Commun., 1 9 8 7 , 1 7 , 1 8 9 3 . D . B a s a v a i a h , T Z . B h a r a t h i , a n d V.V.L. G o w r i s w a r i , T e t r a h e d r o n L e t t . , 1987, 28, 4351. M.A. T i u s , D . P . A s t r a b , a 2 X . G u , J . O r g . Chem., 1 9 8 7 , 52, 2625. E . J . R o s k a m p a n d S . F . P e d e r s e n , J . Am. Chem. S O C . , 1 9 8 7 , 6551. J . M . Wyvratt, G . G . H a z e n , a n d L.M. W e i n s t o c k , J . O r g . Chem., 1 9 8 7 , 52, 9 4 4 . C. F r a n c e s e , M. T o r d e u x , a n d C . W a k s e l m a n , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 6 4 2 . P.G. G a s s m a n a n d N.J. O ' R e i l l y , J. O r g . Chem., 1 9 8 7 , 52, 2 4 8 1 . M . F u j i t a a n d T. H i y a m a , B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 4377. Y . Yamamoto a n d K . M a t s u o k a , J . Chem. S O C . , Chem. Commun., 1987, 923. K.T. Mead, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 0 1 9 . C . H u l l , S.V. M o r t l o c k , a n d E . J . T h o m a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 3 4 3 . M. K i r a , M . K o b a y a s h i , a n d H . S a k u r a i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4081. M. K o r z d a a n d Y . T a n a k a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 4 3 . G.E. K e c k , D.E. A b b o t t , a n d M.R. W i l e y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 3 9 . K . Tamao, E. K a k a j o , a n d Y . I t o , J . O r g . Chem., 1 9 8 7 , 5 2 , 9 5 7 . G . A . M o l a n d e r a n d J . B . E t t e r , S y n t h . Commun., 1 9 8 7 , 17,901. G . A . M o l a n d e r , J . B . E t t e r , andJ-. Am. C h G . S O C . , 453. 1987, G . A . Molander a n d C. K e n n y , T e t r a h e d r o n L e t t . , 1 9 8 7 , 4367. G . A . M o l a n d e r a n d J . B E t t e r , J . Am. Chem. SOC., 1 9 8 7 , 109, 6556. C.W. J e f f o r d , D . J a g g i , a n d J . B o u k o u v a l a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 0 3 7 . D.W.
28,
28,
120,
28,
109
109,
2,
243
4: Alcohols, Halogeno-compounds, and Ethers 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73 74. 75. 76. 77
*
C W Jefford D. Ja G. Bernardinelli, and J. Boukouvalas, Tetiahedron Lett., 28, 4 0 4 1 . K. Tomooka, T. Okinaga, KTSuzuki, and G. Tsuchihashi, Tetrahedron Lett., 1 9 8 7 , 28, 6 3 3 5 . K. Tomioka, M. Nakajima, and K. Koga, Chem. Lett., 1 9 8 7 , 65. K. Tomioka, M. Nakajima, and K. Koga, Tetrahedron Lett., 1 9 8 7 , 28, 1 2 9 1 . H, Takahashi, A. Kawabata, and K. Higashiyama, Chem. Pharm. Bull., 1 9 8 7 , 35. 1 6 0 4 . D. Seebach, A.K. Beck, R. Imwinkelried, S. Roggo, and A. Wonnacott, Helv. Chim. Acta , 1 9 8 7 , 7 0 , 9 5 4 . P.A. Chaloner and S.A.R. Perera, Tetrahedron Lett., 1 9 8 7 , 28,
88./,
~~
3013. G . Muchow, Y . Vannoorenberghe, and G. Buono, Tetrahedron Lett.. 1 9 8 7 . 2 8 . 6 1 6 3 . Ab. A: Smaardvk and H. Wynberg, J. Org. Chem., 1 9 8 7 , 52, 1 3 5 . S . Itsuno and J.M.J. Frechet, J. Org. Chem., 1 9 8 7 , 5 2 , 4 1 4 0 . E.J. Corey and F.J. Hannon, Tetrahedron Lett., 1 9 8 7 7 2 8 , 5 2 3 3 . E.J. Corey and F.J. Hannon, Tetrahedron Lett., 1 9 8 7 , 28, 5 2 3 7 . K. Soai, M. Nishi, and Y. Ito, Chem Lett., 1 9 8 7 , 2405:
K. Soai, S . Yokoyama, K. Ebihara, and T. Hayasaka, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 6 9 0 . K. Soai, S. Niwa, Y. Yamada, and H. Inoue, Tetrahedron Lett., 1987,
3,4 8 4 1 .
79.
K. Soai, A. Ookawa, K. Ogawa, and T. Kaba, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 4 6 7 . K. Soai, A.Ookawa, T. Kaba, and K. Ogawa, J. Am. Chem. SOC.,
80.
J. Garcia, B. Kim, and
78.
1987,
109, 7 1 1 1 .
S.
Masamune, J. Org. Chem., 1 9 8 7 ,
52,
4831. 81. 82.
H.C. Brown, K.S. Bhat, and R.S. Randad, J. Org. Chem., 1 9 8 7 , 52, -
319.
H.C. Brown, K.S. Bhat, and R.S. Kandad, J. Org. Chem., 1 9 8 7 52 , 3701.
83.
K R . Roush, A.D. Palkowitz, and M.A.J. Palmer, J. Org. Chem.,
84. 85.
R.W. Hoffmann and S.Dresely, Tetrahedron Lett., 1 9 8 7 , 28, 5 3 0 3 . L. Coppi, A. Mordini, and M. Taddei, Tetrahedron Lett., 1 9 8 7 , 28 , 969. N. Minowa and T. Mukaiyama, Bull. Chem. SOC. Jpn., 1 9 8 7 , 60,
1 9 8 7 .. 52,. 3 1 6 .
86. 87. 88. 89. 90 * 9 1* 92. 93.
3697. G . P . Boldrini, L. Lodi, E. Tagliavini, C. Tarasco, C. Trombini, and A. Umani-Ronchi, J. Org. Chem., 1987,=, 5447. I. Fleming, N . D . Kindon, and A.K. Sarkar, Tetrahedron Lett., 1 9 8 7 , 28, 5 9 2 1 . I.R. Silverman, C. Edington, J . D . Elliott, and W.S. Johnson, J. Org. Chem., 1 9 8 7 , 52, 1 8 0 . D. Seebach, R. Imwinkaried, and G. Stucky, Helv. Chim. Acta, 1 9 8 7 , 70, 448.
Y. T a m E a , H. Annoura, H. Kondo, M. Fuji, T. Yoshida, and H. Fujioka, Chem. Pharm. Bull., 1 9 8 7 , 35, 2 3 0 5 . Y. Tamura, H. Annoura, M. Fuji, T. Yoshida, R. Takeuchi, and H. Fujioka, Chem. Pharm. Bull., 1 9 8 7 , 35, 4 7 3 6 . T. Mukaiyama, M. Ohshima, and N. Miyoshi, Chem. Lett., 1 9 8 7 , 1121.
94. 95. 96.
J.C. de Souza-Barboza, J.-L. Luche, and C. Petrier, Tetrahedron Lett., 1 9 8 7 , 28, 2 0 1 3 . M. Asami and H. Kirihara, Chem. Lett., 1 9 8 7 , 3 8 9 . P . Mohr and C. Tamm, Tetrahedron Lett., 1 9 8 7 , 28, 3 9 1 .
244
General and Synthetic Methods
97. 98. 99. 100. 101. 102. 103. 104.
105. 106. 107. 108. 109
Ookawa, H . H i r a t s u k a , a n d K . S o a i , B u l l . Chem. SOC. J p n . , 1987, 60, 1813. K.S. K z s h e n b a u m a n d K.B. S h a r p l e s s , Chem. L e t t . , 1 9 8 7 , 11. J . M . C h o n g , D . R . C y r , and E.K. M a r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5009. R.D. T u n g a n d D.R. R i c h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 1 3 9 . Y . N a r u t a a n d K . M a r u y a m a , Chem. L e t t . , 1 9 8 7 , 9 6 3 . J . A . Marshall a n d J . D . T r o m e t e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4985. M . J . K u r t h a n d M.A. A b r e o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 5 6 3 1 . Y . G u i n d o n , M . T h e r i e n , Y . G i r a r d , a n d C. Y o a k i m , J . O r g . Chem., 1 9 8 7 , 52, 1 6 8 0 . M . J . A c k l a n d , J . F . G o r d o n , J . R . H a n s o n , B.L. Y e o h , a n d A . H . R a t c l i f f e , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 7 5 6 . S-Wadman, R . W h i t b y , C . Yeates, P. K o c i e n s k i , and K . Cooper, J . C h e m . S O C . , Chem. Commun., 1 9 8 7 , 2 4 1 . S. K u r o d a , T. K a t s u k i , a n d M . Y a m a g u c h i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28. 8 0 3 . A . A l b z o l a , C. A n d r e s , A.G. O r t e g a , R. P e d r o s a , a n d M . V i c e n t e , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 2 1 2 5 . J . B a r l u e n g a , J . L . F e r n a n d e z - S i m o n , J . M . C o n c e l l o n a n d M. Yus, S y n t h e s i s , 1 9 8 7 , 584. T . Imamoto a n d N. T a k i y a m a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 3 0 7 . M . I . J o h n s t o n , J . A . K w a s s , R.B. B e a l a n d B.B. S n i d e r , J. O r g . Chem., 1 9 8 7 , 5419. K.A. P a r k e r a n d K . A . K o z i s k i , J . O r g . Chem., 1 9 8 7 , 52, 6 7 4 . H.L. Holland, E . J . B e r g e n , P.C. C h e n c h a i a h , S.H. K h a n , B. Munoz, R.W. N i n n i s s , a n d D . R i c h a r d s , C a n . J . C h e m . , 1 9 8 7 , 65, 502. Z . HOU, K . T a k a m i n e , Y . F u j i w a r a , a n d H. T a n i g u c h i , C h e m . L e t t . , 1 9 8 7 , 2061. J . N a k a y a m a , S. Yamaoka, a n d M. H o s h i n o , T e t r a h e d r o n L e t t . , 1987, 28, 1799. Y . H a n d a a n d J. I n a n a g a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 7 1 7 . S . L . S c h r e i b e r a n d M.T. G o u l e t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1043. D . H o n g x u n , Z. W e i k e , a n d B. J u n c h a i , T e t r a h e d r o n L e t t . , 1987, 2599. V . K . A g g a r w a l a n d S. W a r r e n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 1925. K . F u j i , M. Node, Y . U s a m i , a n d Y . K i r y u , J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 4 4 9 . J . N o k a m i , A . N i s h i m u r a , M. S u n a m i , a n d S . W a k a b a y a s h i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 4 9 . K. S o a i , H. H a y a s h i , A. S h i n o z a k i , H. U m e b a y a s h i , a n d Y . Yamada, B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 3 4 5 0 . S . I t o , M. K a s a i , H . Z i f f e r , a n d J . V . S i l v e r t o n , C a n . J . Chem., 1 9 8 7 , E., 5 7 4 . J . T . L i n , T . Y a m a z a k i , a n d T . K i t a z u m e , J. O r g . Chem., 1 9 8 7 , 52, 3211. H. T a k a y a , T . O h t a , N . S a y o , H . K u m o b a y a s h i , S . A k u t a g a w a , S . I n o u e , I . K a s a h a r a , a n d R . N o y o r i , J . Am. Chem. S O C . , 1 9 8 7 , 109, 1596. R . N o y o r i , T. Ohkuma, M. K i t a m u r a , H . T a k a y a , N . S a y o , H . K u m o b a y a s h i , a n d S . A k u t a g a w a , J . Am. Chem. SOC., 1 9 8 7 , 5856T . H a r a d a , T . H a g a s h i y a , I . Wada, N . I w a - a k e , a n d A . O k u , J. Am. Chem. S O C . , 1 9 8 7 , 109, 5 2 7 . T . Harada, I . Wada, a n d A . Oku, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4181. A.
f
110.
111. 112. 113. 114. 115. 116. 117
-
118. 119. 120. 121.
122. 123. 124. 125. 126. 127. 128.
2,
28,
28,
109,
4: Alcohols, Halogeno-compounds, and Ethers 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162.
245
109, 109,
S t o r k a n d S.D. Rychnovsky, J . Am. Chem. S O C . , 1 9 8 7 , 1564. G. S t o r k a n d S.D. Rychnovsky, J , Am. Chem. SOC., 1 9 8 7 , 1565. J . K a u l e n , Angew. Chem. I n t . Ed. E n g l . , 1 9 8 7 , 26, 7 7 3 . Y . Kawazoe, M. Nomura, Y . Kondo, a n d K . Kohda, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4307. T . Hanamoto, T . Hayama, T. K a t s u k i , a n d M. Yamaguchi, 6329. Tetrahedron L e t t . , 1987, S.E. Denmark, R.P. Hammer, E . J . Weber, a n d K.L.Habermas, J. O r g . Chem., 1 9 8 7 , 52, 1 6 5 . S. K i m a n d J . H . P a r k , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 439. M.H. P a r k , R . T a k e d a , a n d K . N a k a n i s h i , T e t r a h e d r o n L e t t . , 3823. 1987, A. P. K o z i k o w s k i a n d J . - P . Wu, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5125. R . A . M o s s , P. S c r i m i n , S. B h a t t a c h a r y a , a n d S. C h a t t e r j e e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 0 0 5 . I. F l e m i n g and P.E.J. S a n d e r s o n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4229. P.H.J. C a r l s e n , a n d J . E . B r a e n d e n , A c t a Chem. S c a n d . , S e r . B, 1987, 41, 313. F . P . C G s i o , M . C . L o p e z , a n d C. Palomo, T e t r a h e d r o n , 1 9 8 7 , 43, 3963. J.-D. Lou a n d Y . - Y . Wu, S y n t h . Commun., 1 9 8 7 , 1 7 , 1 7 1 7 . J.-D. Lou and Y . - Y . Wu, Chem. I n d . ( L o n d o n ) , 1 9 8 7 , 531. J. Muzart, T e t r a h e d r o n L e t t . , 1987, 2133. P.E. M o r r i s , J r . , a n d D . E . K i e l y , J . O r g . Chem., 1 9 8 7 , 52, 1149. Y . S a s s o n , H. Weiner, a n d S . B a s h i r , J . Chem SOC., Chem. Commun., 1 9 8 7 , 1 5 7 4 . W.P. G r i f f i t h , S.V. L e y , G.P. Whitcombe, a n d A . D . W h i t e , J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 6 2 5 . C . B i l g r i e n , S. D a v i s , a n d R.S. Drago, J. Am. Chem. SOC., 1987, 3786. K.S. K i m , S . J . K i m , Y . H . S o n g , a n d C.S. Hahn, S y n t h e s i s , 1 9 8 7 , 1017. S . - I . M u r a h a s h i , T. Naota, K . I t o , Y . Maeda, a n d H. T a k i , J. O r g . Chem., 1 9 8 7 , 52, 4319. A . M c K i l l o p a n d L.S. M i l l s , S y n t h . Commun., 1 9 8 7 , 647. Y . I s h i i , K . Yamawaki, T . Y o s h i d a , T. U r a , and M . O g a w a , J. Org. Chem., 1 9 8 7 , 52, 1 8 6 8 . B . B y r n e a n d M . K a r r a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 769. T . Nakano, Y . I s h i i , a n d M . Ogawa, J. O r g . Chem., 1 9 8 7 , 52, 4855. D.F. T a b e r , J . C . Amedio, J r . , a n d K . Y . J u n g , J. O r g . Chem., 1 9 8 7 , 52, 5621. T . Morimoto, M. H i r a n o , H. A s h i y a , H . E g a s h i r a , and X . Zhaung, B u l l . Chem. SOC. J p n . , 1 9 8 7 , 60, 4143. P.L. A n e l l i , C . B i f f i , F. M o n t a n a r i , S. Q u i c i , J. O r g . Chem., 1 9 8 7 , 52, 2559. R . J . L i n d e r m a n a n d D.M. G r a v e s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4259. I . Minami a n d J . T s u j i , T e t r a h e d r o n , 1 9 8 7 , 43, 3 9 0 3 . F . C a m p s , V . Gasol, a n d A . G u e r r e r o , S y n t h e s i s , 1 9 8 7 , 5 1 1 . D . C r i c h a n d S.M. F o r t t , S y n t h e s i s , 1 9 8 7 , 3 5 . A.G. M a r t i n e z , R.M. A l v a r e z , E.T. V i l a r , A.G. F r a i l e , J . O . B a r c i n a , M. Hanack, a n d L.R. S u b r a m a n i a n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 4 4 1 . G.
2,
28,
28,
109,
17,
163. 164. 165. 166. 167. 168. 169. 170. 171.
S . P . C o l l i n g w o o d , A.P. D a v i e s , a n d B . T . G o l d i n g , T e t r a h e d r o n Lett.,1987, 4445. S . P . S c h m i d t a n d D . W . B r o o k s , T e t r a h e d r o n L e t t . , 1987,
28,
28,
767. H. Mattes a n d C . B e n e z r a , T e t r a h e d r o n L e t t . ,
1987, 28, 1697.
L . J . S t e w a r t , D . G r a y , R.M. P a g n i , a n d G.M. Kabalka, T e t r a h e d r o n L e t t . , 1987, 4497. G . A l v e r n h e , A. L a u r e n t , a n d G . H a u f e , S y n t h e s i s , 1987, 562. A . G r e g o r c i c a n d M . Zupan, B u l l . Chem. SOC. J p n . , 1987, 60,
28,
3083. S. S t a v b e r a n d M.
Zupan, J . O r g . Chem., 1987, 52, 919. R . G r i g g , J . D e v l i n , A . Ramasubbu, R . M . S c o t t , a n d P . S t e v e n s o n , J . Chem. S O C . , P e r k i n T r a n s . 1, 1987, 1515. M . Kameyama a n d N . K a m i g a t a , B u l l . Chem. SOC. J p n . , 1987,
60,
3687. 172. 173. 174.
J . B a r l u e n g a , M.A. R o d r i g u e z , P . J . Campos, a n d G . A s e n s i o , J. Chem. S O C . , Chem. Commun., 1987, 1491. H . U r a t a , U . Y u g a r i , a n d T . F u c h i k a m i , Chem. L e t t . , 1987, 833. T . F u c h i k a m i , Y . S h i b a t a , a n d H . U r a t a , Chem. L e t t . , 1987,
521. 175. 176. 177. 178. 179. 180. 181. 182. 183.
28,
D.P. C u r a n a n d C.-T. C h a n g , T e t r a h e d r o n L e t t . , 1987, 2477. N . Yoneda, T . F u k u h a r a , K . Y a m a g i s h i , a n d A . S u z u k i , Chem. L e t t . , 1987, 1675. E . Yankep a n d G . C h a r l e s , T e t r a h e d r o n L e t t . , 1987, 427. S . Ahmad a n d J . I q b a l , Chem. L e t t . , 1987, 953. S . M a t s u b a r a , M. M i t a n i , a n d K . U t i m o t o , T e t r a h e d r o n L e t t . ,
28,
1987, 28, 5857. Y. T a k z c h i , K . N a g a t a , a n d T . K o i z u m i , J . Org. Chem., 1987, 52, 5061. __ S. R o z e n , M. B r a n d , D. Z a m i r a n d D . Hebel, J. Am. Chem. S O C . , 1987, 109, 896. M. Hanack a n d C . Korhummel, S y n t h e s i s , 1987, 944.
184.
Y . Hanzawa, K . I n a z a w a , A . Kon, H . A o k i , a n d Y . K o b a y a s h i , T e t r a h e d r o n L e t t . , 1987, 659. S. Kanemoto, M . S h i m i z u , a n d H . Y o s h i o k a , T e t r a h e d r o n L e t t . ,
185. 186.
N. E.
28,
1987, 28, 6313. D e S m p e , W. E l k i k a n d M.
D e Cock, a n d N . Schamp, S y n t h e s i s , 1987, 188. I m b e a u x - O u d o t t e , B u l l . SOC. Chim. F r . , 1987,
861. 187. 188. 189. 190.
S . T . P u r r i n g t o n , C.L. B u m g a r d n e r , N . V . L a z a r i d i s , a n d P. S i n g h , J . O r g . Chem., 1987, 52, 4307. M. S h i m i z u , Y . N a k a h a r a , S . Kanemoto, a n d H . Y o s h i o k a , T e t r a h e d r o n L e t t . , 1987, 52, 1677. M. K o r u b o s h i , Y . Okada, T. I s h i h a r a , a n d T. Ando, T e t r a h e d r o n L e t t . , 1987, 3501. M. K o r u b o s h i a n d T. I s h i h a r a , T e t r a h e d r o n L e t t . , 1987,
28,
28,
6481. 191. 192. 193. 194. 195. 196. 197. 198. 199.
G . C a s t a l d i a n d C. G i o r d a n o , S y n t h e s i s , 1987, 1039. A . R . S u a r e z a n d M . R . M a z z i e r i , J . O r g . Chem., 1987, J . B a r l u e n g a , J . M . M a r t i n e z - G a l l o , C . Najera, a n d M. Chem. SOC., P e r k i n T r a n s . 1, 1987, 1017. K. Tamao, M. A k i t a , K . Maeda, a n d M . Kumada, J. O r g .
22, 1145. Yus, J. Chem.,
1987, 52, 1 1 0 0 . A . M i n z o , K . S u z u k i , and K . Tamao, J . Am. Chem. S O C . , 1987, 109, 1257. N . K a m i g a t a , T. S a t o h , a n d M. Y o s h i d a , Chem. L e t t . , 1987, 345. L . Engman, J. O r g . Chem., 1987, 52, 4086. L. Engman, T e t r a h e d r o n L e t t . , 1987, 2, 1463. M.P. D o y l e , A . H . D e v i a , K . E . B a s s e t t , J . W . M a h a p a t r o , J . Org. Chem., 1987, 52, 1619.
Terpstra, and S.N.
4: Alcohols, Halogeno-compounds, and Ethers 200. 201. 202. 203. 204. 205. 206. 207. 208. 209. 210. 211. 212.
213. 214. 215. 216. 217. 218. 219. 220. 221
. )
222. 223. 224. 225. 226. 227. 228. 229. 230. 231.
247
T . I s h i h a r a a n d M. K u r o b o s h i , Chem. L e t t . , 1 9 8 7 , 1 1 4 5 . S . T . P u r r i n g t o n a n d J . H . P i t t m a n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3901. W.R. D o l b i e r , J r . , T.A. G r a y , a n d K . O h n i s h i , S y n t h e s i s , 1 9 8 7 , 956. T . S u g i t a , H . I t o , A. N a k a j i m a , M. S u n a m i , A. K a w a k a t s u , M. S u a m a , a n d K . I c h i k a w a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 7 2 1 . V . R a t o v e l o m a n a n a , A. Hammoud, a n d G . L i n s t r u m e l l e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 6 4 9 . J . B a r l u e n g a , J . M . G o n z a l e z , M.A. R o d r i g u e z , P . J . Campos, a n d G. A s e n s i o , S y n t h e s i s , 1987, 661. A . L . C a s t e l h a n o a n d A. K r a n t z , J. Am. C h e m . S O C . , 1 9 8 7 , 109, 3491. J . H . C l a r k a n d C.W. J o n e s , J. Chem. S O C . , Chem. Commun. 1 9 8 7 , 1409D . H . R . B a r t o n , B . L a c h e r , a n d S . Z . Z a r d , T e t r a h e d r o n , 1 9 8 7 , 43, 4321. H . O g a w a , T . Hagiwara, T. C h i h a r a , S . T e r a t a n i , a n d K . T a y a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 6 0 , 6 2 7 . S. K i m , K . N . C h u n g , a n d S . YaG, J . O r g . Chem., 1 9 8 7 , 52, 3917. M.B. S a s s a m a n , K.P. K o t i a n , G.K.S. P r a k a s h , a n d G . A . O l a h , J. O r g . Chem., 1 9 8 7 , 52, 4 3 1 4 . X.-P. Gu, I . I k e d a , a n d M. O k a h a r a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 6 6 7 . M.A. P e r i c a s , F. S e r r a t o s a , a n d E. V a l e n t i , T e t r a h e d r o n , 1 9 8 7 , 43, 2311. A, Moyano, F . C h a r b o n n i e r , a n d A.E. G r e e n e , J . O r g . Chem., 1 9 8 7 , 52, 2 9 1 9 . T . S u g i y a m a , Chem. L e t t . , 1 9 8 7 , 1 0 1 3 . D.H.R. B a r t o n , J . - P . F i n e t , W.B. M o t h e r w e l l , a n d C. P i c h o n , JChem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 2 5 1 . D.H.R. B a r t o n , N . Yadav-Bhatnagar, J . - P . F i n e t , J. Khamsi, W.B. M o t h e r w e l l , a n d S . P . S t a n f o r t h , T e t r a h e d r o n , 1 9 8 7 , 43, 323. S . M . T u l a d h a r a n d A . G . F a l l i s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 523. L.M. Harwood a n d J . R o b e r t s o n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 5175. B. S t r i j t v e e n a n d R.M. Kellogg, T e t r a h e d r o n , 1 9 8 7 , 43, 5 0 3 9 . A . R . K a t r i t z k y , W. K u z m i e r k i e w i c z , a n d J . M . A u r r e c o e c h e a , 17_1 O r g . Chem., 1 9 8 7 , 52, 8 4 4 . A . O g a w a , Y . N i s h i y a m a , N . K a m b e , S. Murai, a n d N . S o n o d a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 2 7 1 . L . V . D u n k e r t o n a n d M . S a s a , S y n t h . Commun., 1 9 8 7 , 1217. S. K i m a n d S . S . K i m , T e t r a h e d r o n L e t t . , 1 9 8 7 , 1913. K . O s a k a d a , T. Y a m a m o t o , a n d A . Y a m a m o t o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 3 2 1 . N . S c h u l t z - v o n I t t e r a n d E . S t e c k h a n , T e t r a h e d r o n , 1 9 8 7 , 43, 2475. K . L a n g e r , S. T e s c h - S c h m i d t k e , a n d J . V o s s , Chem. B e r . , 1 9 8 7 , 120, 67. __ D.N. Harpp, M. G i n g r a s , T. A i d a , a n d T.H. C h a n , S y n t h e s i s , 1987, 1122. D . N . Harpp a n d M. G i n g r a s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 3 7 3 . H . O h m o r i , H. Maeda, K . K o n o m o t o , K . S a k a i , a n d M. M a s u i , Chem. P h a r m . B u l l . , 1 9 8 7 , 35, 4 4 7 3 . I . M o r i , P.A. B a r t l e t t , a n d C . H . H e a t h c o c k , J . Am. C h e m . S O C . , 1987. 109. 7199.
28,
17, 3,
232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 242. 243. 244.
M.T.
R e e t z and T . S e i t z , Angew. Chem.,
26 , 1 0 2 8 . -
I n t . Ed. E n g l . ,
1987,
T . K o i z u m i , T . F u c h i g a m i , a n d T . N o n a k a , Chem. L e t t . , 1 9 8 7 , 1095. H . I s h i b a s h i , H. N a k a t a n i , K . M a r u y a m a , K . M i n a m i , and M. I k e d a , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 1 4 4 3 . W.D. Abraham, M. B h u p a t h y , a n d T . Cohen, T e t r a h e d r o n L e t t . , 2203. 1987, X . Lu a n d Z . N i , S y n t h e s i s , 1 9 8 7 , 6 6 . V . K . Aggarwal a n d S . W a r r e n , J . Chem. SOC., P e r k i n T r a n s . 1 , 1 9 8 7 , 2579. D. B a r t e l s , R . H u n t e r , C . D . S i m o n , a n d G . D . T o m l i n s o n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 9 8 5 . K. T a k a i , Y . K a t a o k a , T. O k a z o e , a n d K . U t i m o t o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 4 4 3 . Y. I c h i n o s e , K. W a k a m a t s u , K . N o z a k i , J . - L - B i r b a u m , K . O s h i m a , a n d K . U t i m o t o , Chem. L e t t . , 1 9 8 7 , 1 6 4 7 . C.A. B r o k a and D.E.C. R e i c h e r t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1503. S.-S.P. C h o u , S.-Y. L i o u , C . - Y . T s a i , a n d A . - I . Wang, J. O r g . Chem., 1 9 8 7 , 52, 4 4 6 8 . T . Ishiyama, N. M i y a u r a , a n d A. S u z u k i , Chem. L e t t . , 1 9 8 7 , 2 5 . H . B o u d a , M.E. B o r r e d o n , M. D e l m a s , a n d A . G a s e t , S y n t h . 943. Commun., 1 9 8 7 ,
28,
17,
5
Amines, Nitriles, and Other Nitrogencontaining Functional Groups BY G. M. ROBERTSON 1
Amines
Acyclic Amines. - Owing to the ready synthesis of appropriate precursors, reductive routes to amines continue to be a productive area. The tin(I1) complex (l), derived from condensation of bis(thiophenyl)tin, thiophenol, and triethylamine, is soluble in organic solvents and is a highly effective reducing agent for the conversion of azides to primary amines. The related dibutyltindihydride is, however, not as reactive. An efficient synthesis of secondary amines in a chemoselective manner has been developed2 utilizing the reduction of azides with dichloroorganoboranes (Scheme 1). A one-pot procedure for the transformation of tert-alkyl chlorides into tert-alkyl azides has been reported3 via conversion to an intermediate trimethylsilyl azide and in situ reduction with triethyl phosphite (Scheme 2 ) . Unfortunately, highly sterically hindered chlorides fail to react under these conditions. A simple conversion of alcohols into amines or amino acid esters also utilizes the reduction of azido-intermediates. Thus, in a one-pot sequence, reaction of the alcohol with hydrazine, diisopropyl azodicarboxylate, and an excess of triphenylphosphine followed by acid hydrolysis furnishes amines in moderate to good yields (Scheme 3). 4 The reduction of both aliphatic and aromatic nitro compounds to amines by sodium borohydride is facilitated by the use of 10% palladium on carbon as ~ a t a l y s t . ~Under these conditions ester groups are unaffected. A new method for the reductive alkylation of primary and secondary amines with either aldehydes or ketones employs hydrogen telluride as reductant for the intermediate imine (Scheme 4) . 6 A general method for the preparation of N-alkyl-N-trimethylsilylalkoxymethylamines has been reported. These reagents are efficient intermediates for monoalkylaminomethylation of organo-
Generul and Synthetic Methods
250
Reagents: i.
R'BCI,,
-
i, ii
R'-N~ CH ,.,
25'C;
ii, MeOH
Scheme
-
R R-+Cl
R'NHR'
1
-
R+N3
R
R
Reagents: i. Me3SiN,,
SnC14, CH ,,
R *HCL
1 5 - 20 'C;
HC1(g), 25'C
ii, (EtO),P,
Scheme 2
-
ii
I
ROH Reagents: i, HN,.
Ph3P.
ii. HCI.
RN=P(Ph),
C6H6; ' P r 0 2 C N = N C 0 2 ' P r .
RNH, . H C l
THF. 50'C;
50'C
Scheme
RNH, Reagents: i. Al,Te3,
+
E1,N.
3
R'CHO - R N H C H ~ R '
A;
H20 Scheme 4
R'NHZ
-
R'NHSiMe3
ii
Me3Si N'
R'
I
iii
OR2
Reagents: i, TMSCI, Et20, -2O'C t o 35'C; 2 i i , BuLi. hexane, THF, -1O.C; ClCH,OR , 0 t o 20.C; 3
iii, R M , Desilylation Scheme 5
R'NHCH2R3
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
25 1
metallic reagents, and hence for the synthesis of unsymmetrical secondary amines (Scheme 5 ) . Primary and secondary amines can be N-methylated to dimethyl and monomethyl tertiary amines, respectively, with a combination of paraformaldehyde, sodium borohydride and trifluoroacetic acid (Scheme 6) .8 The synthesis of 5-phenyliodoniocarboxamide tosylates from carboxamides and their degradative hydrolysis in acetonitrile, allows the facile conversion of carboxamides to alkyl ammonium tosylates in The reaction of methoxy-E,g-bis(trimethylhigh yields (Scheme 7). sily1)aminomethane (2) with Grignard reagents (Scheme 8) provides a versatile new method for the conversion of alkyl halides to primary amines in high yield. 10 (S)-a-Methylphenylethylamines are obtained in 56 to 62% enantiomeric excess, from the N-alkylation of the chiral synthon, (-)-N-cyanomethyl-4-phenyl-l,3-oxazolidine ( 3 1 , followed by reductive cleavage of the chiral auxiliary (Scheme 9) .ll Two methods for the stereoselective reduction of oxime or imine derivatives have been reported this year. anti-Selectivity in the chelation controlled reduction of acyclic a-alkoxy and a,B-dialkoxyketone oximes with lithium aluminium hydride provides a stereoselective route to chiral amines (Scheme 10) .12 The reduction of N-diphenylphosphinyl imines of substituted cycloalkanones with L-Selectride provides, after deprotection, a highly diastereoselective route to axial amines (Scheme 11) .13 The preparation of B-amino esters by the condensation of silyl ketene acetals with imines (Scheme 12) is catalyzed by trimethylsilyltrif late to give high anti-diastereoselectivity;l4 the product anti-B-amino esters can then be cyclised to trans-a-lactams. The efficient zinc iodide catalyzed 1,3-addition of the ketene silyl acetal (4) with the chiral nitrone ( 5 ) proceeds with 100% anti-diastereoselectivity and forms the key step in a synthesis of Ebenzoyl-L-daunosamine (6) (Scheme 1 3 ) . 15 Complimenting the original direct reduction of ketone-derived SAMP hydrazones to the corresponding amines, the addition of organocerium reagents to aldehyde-derived SAMP hydrazones, followed by hydrogenolysis provides a general synthesis of chiral a-branched primary amines from the corresponding aldehydes (Scheme 14) .16 An improved preparation of a range of related proline derived chiral
General and Synthetic Methods
252 1
Ph CH2NH2
PhCH2NMe2
w
Ph a N H M c Reagents: i. (HCHO),,
Ph W N M e 2
Na6H4, CF3C0,H.
THF
Scheme
RCONH2
+
I
6
-
-
ii
RCONHIPh.OTs
a
Reagents: i. PhI(0Me)OTs; MeCN, 25'C;
ii, H 2 0 . MeCN Scheme 7
I
M e OCH,CI
MeOCH2N(SiMe3)2
(2)
R CH2NH2
. HCI Reagents:
i, NaHMDS, T H F .
-
-1O'C
ii. RMgX. E t 2 0 , O'C
li
iii
R CH2N(Si Me l2
to 2 5 ' C ;
to r e f l u x ;
iii. HCl. H 2 0 Scheme 8
R N H J . OTs-
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
A :
Ph
Ph I
Nc-NC;)
253
D
"c';s
NC
(3) ii
I
...
qJyNMe Ill
P
liv NHMe XQJy
Reagents: i. LDA. MeI, THF; ii, LDA, HMPA, THF, -78'C: iii. NaBH4, EtOH; iv, Hp. 10% Pd/C, MeOH Scheme 9
anti : syn 7 : 3 Reagent:
i . LiAlH4. 25'C
Scheme 10
ArCHZBr, -78'C:
0
II
0
II ii i 4
Reagents: i . ClPPh,.
Et,N,
Petrol ether, -LO 'C
CH,CL,.
i i . LiBH ( s - B u I ~ . 25 'C;
iii, HCL. THF ( o r C6H6) Scheme 11
k' Reagent: i . TMSOTf
,
CH,Cl,.
-65°C Scheme 12
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
Reagents: i. ZnI,, CH,Cl,.
MeCN. - 7 8 ' C ;
ii.
255
H,, Pd/C, AcOH. 25'C
Scheme 13
Reagents: i.
1
R L i . CeCl,.
THF; MeOH; ii. H,, Raney N i , 375 psi, 6 0 ' C
Scheme 1 4
Reagents: i. TsCl. Et,N, iii, L i , NH,,
CH,CI,.
A;
ii. R,NH.
THF. EtOH, - 7 8 'C
to
A
Scheme 15
DBU, Toluene,
A;
256
Getierul arid Sjvitheric Methods
amine bases features amination of the N-tosyl-9-tosylproline (7) (Scheme 15) .17 The product amines thus prepared are formed with higher enantiomeric purities than via previous methods. The nucleophilic addition of even bulky Grignard reagents to hindered alkyl and aryl nitriles is efficiently catalyzed by copper(1) salts. This method has been used to prepare a range of hindered primary amines a tandem addition-reduction sequence (Scheme 16). l8 The development of chemoselective niobium based reducing agents permits the pinacol-type coupling of nitriles to vicinal diamines with good diastereoselectivity and moderate to good yields (Scheme 17). 19 Aromatic Amines. - An improved procedure for the ammonolysis of both aryl and alkyl halides has been reported utilizing quaternary ammonium salts as phase transfer catalysts to improve the solubility and reactivity of ammonia in organic media. 20 Nucleophilic substitution of aromatic halides by a range of primary and secondary amines has also been achieved by reaction under high pressure, 6-12 Kbar, in yield is dependent on the steric bulk of the amine employed. Samarium diiodide has been reported as a mild reagent for the efficient reduction of aromatic nitro compounds to the corresponding amines (Scheme 18) .22 This reagent is also highly effective for the deoxygenation of :-oxides to amines. The chemoselective phenylation of both aromatic and aliphatic amines is made possible by the copper(I1) catalyzed reaction with phenyllead triacetate (Scheme 19).23 In contrast to analogous reactions using five-valent bismuth derivatives, neither phenols nor indoles are phenylated. Aromatic amines can be N-cyclopropylated in excellent yield through a two step sequence of 1-ethoxycyclopropylation followed by reduction with sodium borohydride in the presence of boron trifluoride etherate (Scheme 20) .24 A convenient route to secondary Mannich bases under mild and essentially neutral conditions involves the trimethylsilyl triflate catalyzed addition 25 of silyl enol ethers to aryl Schiff bases (Scheme 21).
5: Amines,Nitriles, and Other Nitrogen-containing Functional Groups
Reagents: i. 'BuMgCl. THF. CuBr.
A;
257
ii. Li. NH3, PhC0,Na
Scheme 16
NH2 Reagents: i.
NbCI,
(THF),.
tctrahydrothiophene.
Bu3SnH; KF; KOH
Scheme 17
A r NO,
Reagents: i . SmI,.
ArNH,
MeOH, 2 5 'C: ii. SmI,, THF,
A
Scheme 18
RqJNHz I
*
Reagents:i. PhPb(OAcI3. Cu(OAc12. CH,Cl,. Scheme 19
25 'C
R
aNH
Gerieral and Synthetic Methods
258
Reagents:
ii. NaBH4, BF$OEt,.
i. CH,Cl,.
THF
Scheme 20
R
A
Ar
Me3Si0 Reagents: i
, TMSOTF, CH,CL,.
O'C
R Scheme 2 1
-
II
I
R
R
R xNHBOC
(8) Reagents: i . DIBAL. toluene. - 7 8 . C ;
ii. A l M e 3
Scheme
Reagents: i . PbBr,.
Al,
BF,.OEt,.
22
Et,O
Scheme
23
Z n . CH,I,,
THF
NHBOC
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
259
Allylic, Homoallylic and Allenic Amines. - The chemistry and biological importance of allylamines as a new class of antifungal agents has been reviewed.26 A straightforward synthesis of chiral allylamines from a-amino acids features a non-racemizing olefination of the intermediate aldehyde ( 8 ) with a mixture of triethylaluminium and diiodomethane (Scheme 22). 27 Reaction of imines with in-situ generated ally1 lead reagents in the presence of boron trifluoride etherate provides an efficient route to primary homoallylic amines (Scheme 23) . 2 8 Copper(1) or nickel(I1) catalyzed addition of Grignard reagents to a-aminoacetylenes is the key step in a facile route to B-substituted-aallenyl primary amines (Scheme 24). 29 Cyclic Amines. - Quaternary azetidinium compounds can be formed 2 cyclization of 3-aminopropanols by capitalizing on the small size and good leaving group ability of triflates (Scheme 25). 30 A number of new methods for the preparation of pyrrolidines, ranging from N-radical cyclization to chiral cycloadditions of azomethine ylides were reported this year. Thus, Newcomb et a131 have utilized g-hydroxypyridine-2-thione carbamates (9) as aminyl and aminium radical sources for the elaboration of @-substituted pyrrolidines in moderate to good yields (Scheme 26), whilst Schlesssinger et a1 have reported an efficient route to either optical antipode of trans-2,5-dimethylpyrrolidine,starting from either p- or &-alanine and featuring cyclization of the alkene (10) (Scheme 27) .32 An improved aminoselenation procedure and the addition of the boron trifluoride complexes of dihomoallylcuprates to aldimines are the key features of a new route to a-methylene substituted pyrrolidine derivatives (Scheme 28).33 The intramolecular trapping of in situ generated primary amines by electrophilic olefins enables the cyclization of w-olefinic azides to pyrrolidines and piperidines (Scheme 29) .34 Cyclization occurs under very mild conditions, with good diastereoselectivity, which is independent of the geometry of the starting olefin. 3-substituted pyrrolidine carboxylic acids can be prepared enantioselectively using 1,3-dipolar cycloaddition of azomethine ylides with enones, followed by pig liver esterase hydrolysis (Scheme 3 0 ) .35
General and Synthetic Methods
260
Reagents:
i . E t M g B r . THF. 1O'C
ii
to 25'C;
Scheme
24
I
*
r7
YN
R N -OH
K,CO,.
CH,CI,.
A;
Et20, -25'C
RMgBr. CuBr. Me$.
Reagents: i . Tf,O.
MeOnN(SiMe3)2.
-78'C
Tf-
t o 25'C
Scheme
25
BU
I
h
0-
S
(9) t
Reagents: i . BUSH, T F A . C,H,.
2 5 'C.
hv
Scheme
Reagents: i . Hg(OAc12. THF. 2 5 'C;
26
NaBH4. 2 . 5 M NaOH. 2 5 ' C
ii. HCL. MeCN. 0%. N a I , T M S C I O'C t o 25'C. H 2 0 Scheme
27
26 1
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
Reagents; i. 5 0 2 , TFA, CH2C12. -70 "C; PhSeCI, CHzClz, -70°C to 25°C i i . Ph3SnH, PhMe. A. Scheme 20
FE R'
y-R2
J
L
n = lor2 Reagents: i . Ph3P. T H F : H 2 0 .
25'C
Scheme
29
i
Me3S iANAOMe
I
Bn
H
0"
CO E t Reagents: i. CF3C02H,
, CH2CL2.
O'C
Scheme 30
-
Si Me
(11)
Reagents:
i . T M S I , CH2C12. - 5 0 % Scheme 31
C02Et I
Hudlicky and co-workers have reported a new route to pyrrolizidine alkaloids using a [4 + 11 annulation approach.36 The synthesis of the supinidins ethyl ether forms an example of this method,
2 the
alkylative ring opening of the vinyl aziridine ( 1 1 )
with trimethylsilyl iodide and ensuing cycloaddition (Scheme 31). Chemoselective reduction of N-heteroaromatic rings in the presence of benzene rings has been achieved using a nickelaluminium alloy in aqueous potassium hydroxide. 37 Similarly the heteroaromatic ring of quinolines and isoquinolines can be hydrogenated selectively to the corresponding benzopiperidines by reaction with carbon monoxide and water in the presence of a rhodium carbonyl catalyst (Scheme 32) .38 Quinolines are reduced directly, whilst isoquinolines require further reduction of the initially formed 3-formyl compounds. Intramolecular Mannich reaction of the amine ( 1 2 ) provides an interesting route to the spirocyclic ring system of the nitramine 39 alkaloids (Scheme 33). The acid catalyzed cyclization of the N-tosylenamine (13) to form an azepinyl ring is a key step in a new organometal controlled 40 synthesis of the ergot alkaloid (t)-aurantioclavine (Scheme 34). A novel application of the modifed Polonovski reaction using trifluoroacetic anhydride as the acylating agent has been reported
in a new route to Wenkert's enamine (14), a key intermediate in the synthesis of eburnane alkaloids (Scheme 3 5 ) . The cyclisation of iminium ions, generated in the presence of a sulphonic acid or silver salt catalyst, proceeds regiospecifically to give 1,2,5,6-tetrahydropyridines containing substituents at 41 positions 1,2,3 or 4 (Scheme 36).
The synthetic potential of the acyliminium-vinyl silane cyclization has continued to be exploited and has been utilized €or the regiocontrolled synthesis of indolizidinones and quinol41 izidinones, such as the elaeokanine intermediate (15) (Scheme 37). Similarly an enantioselective synthesis of the antibiotic ( + I streptazolin features the stereoselective vinyl silane terminated cyclization of the tartrate derived N-acyliminium ( 1 6 ) , followed by intramolecular acylation (Scheme 3 8 ) .42 Cyclizations of acyclic 5acyliminium ions are also the key step in the silicon assisted cyclocondensation of glyoxylic estes to proline and pipecolic acid derivatives. Cyclization can be initiated under thermal or Lewis
263
5: Amines, Nitriles, und Other Nitrog~~i-cotitaining Functional Groups
Reagents: i. Rh6(C0),6.
CO ( 5 6 k g / c r n 2 ) . H20, MeO-
OH ,
150°C
Iiii Reagents:
i. Rh6(C0Il6.
ii. LiALH,:
CO ( 5 6 k g / c m 2 ) ,
H20, MeOwoH.
150°C
iii. oq. NoOH. E t O H Scheme 32
+ OH
H
I
Bn Reagents: i . HCHO
MeOH. HCl
Scheme 33
264
Genera1 atid Sy r i th etic. Methods
c
OEt
Ts
TS
(13) Reagents: i. p-TsNH2, MeCN. p - TSA. 9O'C
Scheme 34
I
I BOC
BOC
(14) Reagents: i . MCPBA
CH,CI,.
O'C:
Tf,O. -13'C to 25'C: KCN, H,O. Scheme 35
HOAc. p H 5
265
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
eR3 R4
&R3
Si Me3
1,
RZ '1
R
R' Reagents: i. R'CHO. C S A . MeCN. 8 0 - 1 2 0 'C
Scheme 36
-----Reagents: i . CF3C0,H.
O ? P B r
A; Scheme 37
1 Me
i, ii
OMe
ve
--OH
C0,Et
OMe
Reagents: i. NaBH4. MeOH, O'C.
i i . TFA. Scheme 38
A:
Grnctrd avid Svri th rtic Methods acid conditions (Scheme 39) .43
For propargyl silane terminated
cyclizations the Lewis acid method is more efficient, whilst for ally1 silane cyclizations thermal initiation is operationally simpler and is therefore preferred. A novel route to the erythrane alkaloids features the photochemically initiated, allylsilane terminated iminium ion 44 cyclization of the perchlorate salt (17) (Scheme 40). Protecting Groups. - The selective deacylation of tert-butoxycarbonyl-acylamides is possible using a range of mild reagents, especially diethylaminoethylamine (DEAEA), the method constitutes a novel approach for the deacylation of carboxamides (Scheme 41). 45 Activated carbonates derived from 5-hydroxy-5-norbornene-2, 3-dicarboximido carbonochloridate (18) provide excellent reagents for the introduction of all the currently used carbamate protecting groups (Scheme 42) .46 Aliphatic amines (and alcohols) can be efficiently acetylated by ethyl acetate through the use of A1P04-A1203 as a solid acetyl carrier,47 and the selective acylation of amines is possible using S - a c y l - S e - p h e n y l s e l e n o s u l p h i d e s in the presence of mercuric acetate (Scheme 43). 48 The reductive trialkylsilylation of azo compounds by lithium metal in the presence of transition metal halides as catalysts leads to monosilylated lithio species such as (19). Alkylation of such lithio-compounds then completes a novel route to protected secondary amines (Scheme 4 4 ) .49 A new method for the rapid deprotection of N-benzyl protected amines and amino acids uses catalytic transfer hydrogenation with ammonium formate to give high yields of the debenzylated product (Scheme 45) 2
Enamines
An efficient new route to N-acyl enamines via the palladium catalyzed isomerization of allylic amides has been reported, (Scheme 46) .52
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
-
#-SiMej
i or ii
n t d N C0,Me I ACOzR
n(
C0,Me I i. ( X = H I
Reagents:
Et,N.
A
MsCl. MeCN , 2 5 ‘C:
ii. ( X = A c ) Et,AICI.
CH,CI,.
0 to 20’C
Si Me, i or ii
“
~ C0,Me IC 0
,
R
-
Reagents: i, ( X = H I . Et,N. MsCl. MeCN. 25’C:
ii. ( X = Ac) Et,AlC[.
CH,Cl,.
n( G C 0 , R
CO, I Me
A:
0 to 2O’C
Scheme 39
Si Me, (17) Reagent: i .
h v , MeOH Scheme 4 0
Reagents: i. (BOC),O.
DMAP. MeCN. ii.
Scheme
Et,NwNEtz 41
267
General and Synthetic Method5
268
0
R’
H,N
A
R’
COP
Reagents: i . Et,N.
Dioxane. H,O:
&O!OR2,
Dioxane
0 ( 18)
Scheme b 2
RNHZ
0 Reagents: i .
P h S e S b N o z ,
HgIOAc),.
CH,CL,,
25 ‘C
Scheme 4 3
-
PhN=NPh
Reagents: i.
t
BuMe,SiCI.
t
PhN<
Si Me, Bu Li (19)
L i . FeCI,.
ii
T H F ; RX
Scheme 44
R’
Reagents: i .
R’\ ,/NH R
I
-e
RZ>NBn
HCO,NH,.
1O0/o Pd/C.
MeOH.
Scheme b5
A:
SiMeiBu PhN’ R ‘
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
Reagents: i. 10% P d / C .
Et,N,
269
THF. 1 2 0 ' C Scheme 4 6
t4eN-O" H
Me I
"'YY"' NH,
-
Reagent:
i . Ni A1 alloy. aq.
OH
KOH Scheme 1 7
OSiMe: Bu
I P
HO
I Ts
Reogent:
i . Red- A t .
THF, -78.C Sc heme 4 8
270 3
Amino Alcohols
Chemoselective reduction of oxazoles and isoxazoles using a nickelaluminium alloy in aqueous potassium hydroxide provides an efficient route to 47).
0-
and P,-aminoalcohols respectively (Scheme
The regioselective reduction of homochiral aziridines to R amino alcohols using Red-A1 at -78°C is the key step in a new enantiospecific route to 6-lactams (Scheme 48).53 The facile preparation of hydantoins derived from phenyl or
(I-
methylphenylalanine forms the basis of a new route to chiral 6-amino alcohols, through their N-3 alkylation with epoxides followed by enantiomeric resolution and hydrolysis of the chiral auxiliary (Scheme 4 9 ) . 5 4 The asymmetric ring opening of symmetrical epoxides with either aniline or trimethylsilyl azide is catalyzed by zinc or copper (2R, 3R)-tartrate to give, after reduction, trans-P-amino alcohols in high yield with modest to poor enantiomeric excess (Scheme 50) . 5 5 Pedersen and Roskamp have reported a very useful new route to R-amino alcohols via a crossed pinacol-type coupling reaction of imines with ketones using a chemoselective niobium(II1) reagent (Scheme 51) . 5 6 A novel method equivalent to cis-hydroxyamination has been developed by Trost and Sudhaker.5TThus, treatment of epoxides with tosyl isocyanate catalyzed by palladium dibenzylideneacetone yields cyclic carbamates of the type (201, suitable €or conversion to a range of amino alcohol derivatives (Scheme 52). The N-0 bond of dihydrooxazines can be cleaved by microbial reductive splitting to give %-1,4-amino alcohols. The yields obtained are generally better than with chemical reductions (Scheme 5 3 ) .58
The synthesis of secondary aminoethylthiols is possible & y either condensation of primary amines with a-carbethoxyethanethiol or through the ring cleavage of thiazolidines with Grignard reagents (Scheme 54) .59
4
Azo Compounds
The azo-hydrazone tautomerism reaction has been reviewed. 6 o
Azo
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
27 1
0
Reagents: i .
/o ,
L i C I . DMF; i i . Recrystatlization. resolution:
B a ( O H I Z . H,O.
A Scheme 4 9
Reagents:
i. Me3SiN,.
C u ( 2 R . 3R1
- tartarate;
i i MeOH. H C I .
A;
iii. Hz. 10% Pd/C. MeOH Scheme 50 NHBn /
At
I
)1
OH
0 Reagents:
i . NbCI,. ( D M E ) , THF:
R ' A R 2 . THF
Scheme
51
RIT;R+q 9 4
i
_____)
------)
eR H?
R
R3 Reagents:
i,
TsNCO.
Pd2(dbal,.
CHCI,.
P ( 0 ' P r l 3 . THF. 25'C
Scheme 52
NAc
Grrieral arid Syrithetic. Method5
272 HC 1
I
m
OMe
OH
t r i s / HCI .
Reagents: i. M. thermoantolrophicum, H2, met hylviologen. buffer pH 8 - 5 . 36'C Scheme 53
I
ArN02 Reagent:
i.
ArN=NAr
c
NaTe. DMF. THF,
70'C Scheme 5 4
R
0-9-
R
T
T
+
s
CN
R CN major : minor 76
0 Reagents: i.
TSCN. AIBN.
I D
10%
/'o
0 CN
CGH6.
A
Scheme 55
RC02Et Reagents:
I
i. HONH,.HCl.
-
0
ii
R
KOH. MeOH. 25'C:
Scheme
56
ii. P B r 3 . C&.
RCN
A
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups compounds can be prepared under aprotic conditions
273
via
the reduction
of aromatic nitro compounds with sodium telluride (Scheme 54) .61 5
Nitriles and Isocvanides
The synthetic potential of nitriles in heterocyclic synthesis has been reviewed.6 2 The radical addition of tosyl cyanide to unsaturated hydrocarbons is catalyzed by AIBN to give a range of branched aliphatic nitriles (Scheme 55). 6 3 A new method for the conversion of esters to nitriles, in excellent yield, involves the treatment of intermediate hydroxamic acids with two equivalents of phosphorus tribromide in benzene (Scheme 56). 64 The lanthanide trichlorides (Ln = La, Ce, Sm) and E ~ ( f o d ) ~but , especially samarium trichloride, catalyze the addition of trimethylsilyl cyanide to both aldehydes and ketones to yield cyanohydrins in high yield (Scheme 5 7 ) . 6 5 Corresponding treatment of epoxides yields R-silyloxynitriles. A new procedure for the facile transformation of aldehydes into one carbon homologated nitriles proceeds __ via the electrochemical reduction of the readily prepared nitroalkenes in the presence of titanium tetrachloride (Scheme 58).66 In the presence of catalytic amounts of trityl perchlorate, secondary and tertiary ally1 ethers are efficiently converted into the corresponding B,y-unsaturated nitriles by reaction with silyl cyanides (Scheme 5 9 ) . 6 7 A convenient method for the conversion of silyl chlorides into the synthetically useful silyl cyanides under mild conditions involves their treatment with sodium cyanide impregnated XAD-resin. 68 The asymmetric hydrocyanation of aldehydes with trimethylsilyl cyanide promoted by the chiral titaniurn(IV1 reagent ( 2 0 ) gives the corresponding cyanohydrins with good to moderate yields and enantiomeric purities (Scheme 6 0 ) . 6 9 A s an alternative to the Sandmeyer reaction, treatment of aromatic diazosulphides with tetrabutylammonium cyanide under photolytic conditions provides the corresponding nitrile the 70 intermediate diazonium salt (Scheme 61). The synthetic potential of the isocyanide to cyanide conversion
274
General and Synthetic.Methods
i
RZ
R’ Reagents: i .
TMSCN, SrnCl,.
25’C
CH,Cl,.
A0
I
8 8 *I.
OTMS
-
Scheme 57
-
I
R Reagents:
w
N
i . TiCI,.
O
z
R -CN
DMF. Et4NOTs. electrolysis.
25 . C
Scheme 58
I
R’ Reagents: i.
R’
Me3SiCN, MeOTrC104, CH,Cl,.
- 23’C
Scheme 59
I
RCHO
Reagents: i.
Ph Ph Me3SiCN, P h x O p o H
*
R
0
,
. T ~ C L ~P( rOl t ~
Me 0 K O H Ph Ph (20) Scheme 60
4 molecular sieves. toluene
275
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
I
N=NSPh
CN
Reagents: i , B y N C N . MezSO. h v . 300W, 25'C Scheme 61 CN
R'CHO
+
KCN
+
R'NH~.HCL
R'
3
NHR'
Reagents: i . Al,O,,
M e C N . 50'C.
ultrasound
Scheme 62
Reagents:
i, Bu,SnH,
CH,Cl,,
25'C:
i i . HF, MeOH
Scheme 63
Reagent:
i . dry yeast. HZO, glucose. 25'C Scheme 6 4
Reagents:
i . Et,N,
MeCN, 2 5 ' C .
d i l aq. H C l Scheme 6 5
276
General and Synthetic Methods
has been demonstrated through the vapour phase thermolysis of isocyanides to provide excellent chemical and optical yields. 7 1 A three component condensation of carbonyl compounds, potassium cyanide, and amine salts is catalyzed by the combined use of alumina and ultrasound to give a-amino nitriles in excellent yields (Scheme 6 2 ) .72 6
Nitro and Nitroso Compounds, and Nitramines
An improved procedure for the preparation of trimethylnitropyrrole involves nitration with a mixture of sulphuric acid and potassium nitrate.73 This is a procedure which is applicable to large scale preparations and should be useful for general aromatic nitration. Reduction of nitroalkenes upon treatment with tributyltin hydride, in the absence of catalyst provides a new method for the reduction of a,B-unsaturated nitro compounds to the corresponding 74 nitro alkanes (Scheme 63). Asymmetric hydrogenations of 2-aryl-1-nitropropenes by fermenting Bakers yeast yield B-methylarylnitroethanes in high yields and optical purities (Scheme 64) .75 Iron(II1) and manganese(II1) porphyrins have been reported as highly effective catalysts for the oxidation of nitroso to nitro compounds even at 76 -78°C. Reactions of carbanions derived from a,B-unsaturated nitro compounds with electrophiles provide a simple method for the preparation of a-subs tituted a 1lylic nitro compounds (Scheme 65) A convenient procedure for the isomerization of E- to Z-nitroalkenes utilizes the erythro-selective conjugate addition of benzeneselenol to the E-isomer, followed by syn-elimination of benzeneselenenic acid (Scheme 66) .78 Recent synthetic applications of g-nitrosoamines and related compounds have been reviewed. A new route for the conversion of secondary amines to nitrosamines has been reported which utilizes the solvolysis of the ionic nitrate, bis(tripheny1phosphine)nitrogen nitrate (21) to provide the nitrosating agent (Scheme 67) . 8 0 Non acidic nitration of secondary amines to nitramines without the formation of nitrosamine by-products is straightforwardly achieved with 2(trifluoromethyl)-2-propylnitrate (Scheme 68) .81
.
5: Amines, Nitriles, and Other Nitrogen -containing Functional Groups
277
PhSe Reagents: i. PhSeNa. EtOH,
i i . AcOH, -78'C: iii, HzO,, CH,Cl,.
-78'C;
Scheme 66
I
H
NO Reagent:
i . (N(PPh,),)(NO,)
( 2 1 ) . CH,Cl,,
25'C
Scheme 67
R'
Rz
i
N ''
_____)
i. CF3C(ONO),MeZ.
,RZ N
I
H
Reagent:
,'R
SO'C Scheme 68
Reagents:
i. R B t . NaOH, K2C03' C6H6. 8un4NHS04. 80.C:
i i . pTSA, E t O H , 78'C Scheme 69
0%
378 7
Hydrazines and Hydrazides
Monoalkylhydrazones are conveniently synthesized by the phase transfer catalyzed N-alkylation of acetone E- (diethoxyphosphonoyl) hydrazone, followed by acidic deprotection (Scheme 6 9 ) .8 2 The amino group of amino acids can be converted to the corresponding hydrazine, with retention of configuration, by using potassium hypochlorite instead of sodium hypochlorite to invoke rearrangement of the intermediate hydantoic acids (Scheme 70) .83 A new preparation of arylhydrazones has been achieved by the addition of aryllithium or Grignard reagents to di-tert-butyl azodicarboxylate and subsequent acid hydrolysis (Scheme 71).84 Two variations for the preparation of acyl hydrazines by amination of the corresponding hydroxamic acids have been reported utilizing either tosylate or hydropyridinium leaving groups (Scheme 72) . 8 5 A convenient new synthesis of a-halohydrazides involves hydrazine opening of a,a-dicyanoepoxides (Scheme 73) ; 8 6 a-halohydrazides are an important source of heterocyclic intermediates. 8
Hvdroxvlamines
An efficient general method for the chemoselective preparation of opposed to g-alkylated) hydroxylamines from alkyl halides has been reported using 5-alkylation of the sodium salt of ethyl 3-methyl-5-hydroxy-4-isoxazolecarboxylate (22) (Scheme 74) 87 Hydroxylamine can be selectively 0- and mono-E-alkylated to give N,g-dimethylhydroxylamine by utilizing transient carbamate formation with ethyl chloroformate (Scheme 75) . 8 8
N-alkylated ( a s
.
9
Imines
Recent advances in the chemistry of imines and in particular their cycloaddition reactions have been reviewed,8 9 with an emphasis on l-aza-1,3-butadienes. Sterically hindered ketimines can be prepared by copper catalyzed nucleophilic addition of bulky Grignard reagents to either alkyl or aryl nitriles (Scheme 7 6 ) . 18
5: Am ines, Nitriles. and Other Nitrogen-containing Function a1 Groups
-
279
-
H
I
II
R+co2H
Y O z H
R+co2H NHZ
HNYNH2 0
Reagents: i .
KOCN. H,O,
6 0 % conc. HCI, ii KOH,
NHNH2
KOCL, 25 'C
Scheme 70
H
I
ii
ArNHNH2 Reagents: i ,
THF, -lO'C;
AcOH, -1O'C
t o 25'C;
ii, HCI, dioxane, Pr'OH,
A
Scheme 71
I
H R'
C H,
iii. pTsCI. p y r i d i n c , CH2C12.
A;
Scheme 72
iv, R'NH,.
h
i , MeCN, 25'C
Reagent:
Scheme 73
RBr
i
CO,E t R - N 3 0
ii
RNHOH.HCL
CO,E t
(221,DMF. 1 1 0 - i z o ' c ;
i i , ACOH. H,O,
HCI.
A
Scheme 72
0 EtO
A
c
t
-
II
A N / M e
EtO
Reagents: i , HONH,. H C I , 50%
I
OMe
NaOH ( t o pH 11). 25'C;
( t o pH 11 - 1 2 ) . 3 5 ' C ;
MeNHOMe.HC1
ii, conc. HCI,
Me,SO,,
50% NoOH
A
Scheme 75
I
RCN
Reagents: i. Bu'MgCl. THF, CuBr,
A;
ii, anhydrous N H 3 . 0 to 5'C t o 25'C
Scheme
76
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
28 1
Palladium(0) catalyzed addition of disilanes to isocyanides is a convenient method for the preparation of !-substituted bis (silyl) imines (Scheme 77),” which act as precursors to the corresponding ketones. 1,2- and 1,3-Diamines can be prepared directly from the corresponding dicarbonyl compounds via titanium tetrachloride catalyzed condensation with the appropriate amine (Scheme 7 8 ) 91 Cyclic imines ranging from A’-pyrrolines to 1-aza-1-cycloheptenes are formed in good yields from the boric acid mediated decarboxylation of the corresponding exocyclic 6-enaminoesters (Scheme 7 9 ) . 92 The key feature in a new synthesis of the antitumoral compound prothracaroin (231, is the elaboration of the pyrrolo[l,4l-benzodiazepine ring system. Thus cyclization of the thioacetal (24) is catalyzed by mercuric dichloride to give the carbinol amine intermediate (25): subsequent elimination then gives the prothracaroin ring skeleton (Scheme 801 .93 A new synthesis of C-unsubstituted and C-mono- alkylated ketene imines has been reported using the potassium tert-butoxide promoted vacuum gas/solid dehydrocyanation of appropriately substituted imidoyl 94 chlorides (Scheme 81).
.
10
Amidines
In a new route to unsubstituted amidines, reaction of nitriles with lithium hexamethyldisilazide etherate first gives the lithioamidine species (26). Hydrolysis of (26) then gives N-unsubstituted amidines in high yield. Alternatively, heating the intermediates (26) with trimethylsilyl chloride in toluene gives the corresponding fully silylated amidines (27) (Scheme 82). 9 5 The reaction of amines with nitriles to give a range of cyclic and acyclic disubstituted amidines can be catalyzed efficiently by lanthanide(II1) triflates, especially by lanthanum triflate (Scheme 83) .96 11 Oximes A new synthesis of oximes from carbonyl compounds a Peterson-type reaction with the e - s i l y l derivative (28) has been described. The intermediate adduct can be quenched directly to the
282
General and Synthetic Methods
R3SiSiRj
+
I
R'NC
D
r35i
r35i Reagent:
i, Pd(PPh3I4, toluene,
R' >N'
b,
Scheme 77
NR3
R'
0
R' U
Reagents: i.
R
-
2
R3NH2.
C,H,,
TiCL,.
25'C
Scheme 78
C0,Et Reagent
i,
NR3 NR3
I
H3B03. 180 ' C
Scheme 79
R
283
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups OH
EtS
Prot hracaroin R
c
q-q 0
(23)
( € 1 - CH=CH2Me
Reagents: i,
HgCl,.
CaCO,,
R MeCN, H 2 0 , 25'C
Scheme 8 0
CN
CN
Reagents: i ,
t e t r a g l y m e . N C S , - 3 0 to 15'C;
i i . K O B ~ I ~A O. ' C ,
torr
Scheme 81
KOH, -30 t o 25'C;
General and Synthetic Methods
284
-
N Li
I
RCN
R
KN(SiMe31
ii
2
R NHZ
- HCL
(26)
1
iii
Reagents: i,
(TMS1,NLi.
OEt,,
iii, TMSCL, toluene,
E t 2 0 ; i i , 6 M tthanolic HCL. O'C;
A Scheme 8 2
2dNH2
Reagent:
i.
+
R2CN
D
Ln(CF3SO3I3, MeCN.
A
Scheme 83
R' >=O RZ
Reagents: i.
Me,SiN-OSiMe, K+
R' . RZ RgN/o ( 2 8 ) . THF, - 7 8 ' C t o 25'C; Scheme 8 4
OE
R'
ECI, -78'C
285
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups
parent oxime or trapped with a range of electrophiles to give O-substituted oxime derivatives (Scheme 8 4 ) ” O-Ally1 ethers have been developed as an acid and base stable protecting group for oximes. 9 8 O-Oxime alkylation is selective in the presence of hydroxyl and amino groups, whilst palladium catalysed deprotection using triethylammonium formate as the reductant is straightforward even in the presence of acid or base sensitive functional groups (Scheme 8 5 ) .
.
12
Carbodiimides
A new method for the preparation of carbodiimides, especially unsymmetrically substituted variants, has been reported the dehydration of ureas with arenesulphonyl chlorides under conditions of solid-liquid phase transfer catalysis (Scheme 86) 99
.
13
Azides and Diazonium Compounds
Asymmetric halogenation of chiral amide enolates derived from chiral N-acyloxazolidines ( 2 9 ) provides the basis for the preparation of chiral azides ( 3 0 ) by halide displacement with tetramethylguanidinium azide (Scheme 8 7 ) . l o o The chiral azides so formed are then of use for the synthesis of enantiomerically pure a-amino acids. Alternatively, chiral azides, of the opposite antipode to (301, can be prepared directly by electrophilic azidation of the chiral gacyloxazolidines with trisyl azide (Scheme 8 8 ) . lo’ This method constitutes a generally applicable approach for the introduction of azides in an electrophilic manner. A method for the direct conversion of allyl silanes to allyl azides has been developed utilizing a reagent mixture of iodosylbenzene, trimethylsilyl azide, and boron trifluoride etherate 102 (Scheme 8 9 ) . The controlled reduction of g-allyl-N-nitrosoamides to hydrazides with zinc in acetic acid, followed by nitrosation with iso-amylnitrite and subsequent fragmentation affords a new method for the conversion of aliphatic amines and amides to azides under 103 mild conditions (Scheme 90). The first example of simultaneous introduction of both selenoand azido-functions into organic molecules has been reported this
Reagents: i ,
wBr, KOH.
ii,
Pd(OAc12, PPh,,
DMF, 0 to 4O'C;
Et3NH02CH, aq. Et O H ,
A
S c h e m e 85
H H R1/Ny\R2
I P
2
R' N =c =N R
0 Reagents: i.
TsCI, C6H6, K,CO,,
Et,kCH,PhCL-.
A
S c h e m e 86
Reagents: i, Bu2BOTf, CH2C12, -78'C;
NBS. CH2CI,,
ii. tetramethyiguanidiniumazide. CH,Cl,,
( R ) : 1s) ratios S c h e m e 87
-75'C;
O'C,
7 8 : 2 2 to 95: 5
5: Amines, Nitriles, and Other Nitrogen-containing Functionul Groups
Reagents: i, (PhIO),,
Me,SiN,,
BF,. OEt , CH,CI,.
287
-78'C
Scheme 89 Ac
I
RNHAc Reagents: i ,
ii
NO+HS04-,
Zn.
Ac,O,
iAmyIONO, CCl,,
AcOH. NaOAc,
A Scheme 9 0
Reagents: i ,
PhSeCI. NaN,.
DMSO. 25'C Scheme 91
Reagent:
II
RN-NHAc
i , N a H , THF. 109'C. 10-6mrn Scheme 9 2
RN,
Geriercrl arid Synthetic Methods
288 I
RX
Reagents: i,
RNCO
D
Ag(0,N-NCN).
toluene,
MgS04, -2O'C
Scheme 93
R'
R' I
>NH R2
Reagents: i,
Se02. 30%
\+
*
2 /N-
R H,O,.
MeOH. O'C
Scheme 94
O
5: Amines, Nitriles, and Other Nitrogen -containing Functional Groups
289
year. Thus, stereospecific reaction of olefins with phenylselenyl chloride and sodium azide in DMSO gives the corresponding a-seleno azides in high yields. The reaction proceeds in a non-regiospecific manner via azide ion attack on an intermediate selenium ion compound (31) (Scheme 91). Treatment of enone tosyl hydrazones with sodium hydride at high temperature and low pressure in THF provides a potentially general route to exocyclic a, 8-unsaturated diazocompounds (Scheme 92)
.
14
Isocyanates and Isothiocyanates
The synthesis and reactions of six-membered heterocyclic isocyanates and isothiocyanates has been reviewed. The treatment of alkyl or aralkylhalides with the silver salt of nitrocyanamide provides the first efficient conversion of organic halides to isocyanates (Scheme 93). 107
15
Nitrones
The oxidation of secondary amines with hydrogen peroxide in the presence of selenium dioxide as catalyst is a highly efficient new method for the preparation of nitrones in the presence of olefins (Scheme 94) .Io8 References 1. 2.
M.Barta, F.Urpi, and J.Vilarrasa, Tetrahedron Lett., 1987, 28, 5941. B.Carboni, M-Vaultier, and R.Carrie, Tetrahedron, 1987, 43, 1799.
3. 4. 5. 6. 7. 8. 9. 10. 11.
A.Koziara, K.Osowaska-Pacewicka, S.Zawadzki, and A.Zwierzak, Synthesis, 1987, 487. E-Fabiano, B.T.Golding, and M.M.Sadeghi, Synthesis, 1987, 190. M.Petrini, R-Ballini, and G.Rosini, Synthesis, 1987, 713. N.Kanabe, 1-Inagaki, N.Miyoshi, A.Ogawa, and N.Sonoda, Chem.Lett., 1987, 1275. G.Courtois and L-Miginiac, Tetrahedron Lett., 1987, 28, 1659. G.W.Gribble and C.F.Nutaitis, Synthesis, 1987, 709. 1.M.Lazbin and G.F.Koser, J.Org.Chem., 1987, 52, 476. H.J.Bestmann, G.Wolfe1, and K.Moderer, Synthesis, 1987, 848. J.L.Marco, J.Royer, and H.P.Husson, Synth.Comun., 1987, 17, 669.
12. 13.
H.Iida, N.Yamazaki, and C-Kibayashi. J.Chem.Soc., Chem. Commun., 1987, 746. R.O.Hutchink and M.C.Rutledge, Tetrahedron Lett., 1987,
28,
5619. 14.
G-Guanti, E.Narisano, and C.Banti, Tetrahedron Lett., 1987,
28 , 4331. -
290 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34 * 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51.
52. 53.
54.
GrrieruI u ri d Sy ri t h d c Mrth ods Y.Kita, F.Itoh, O.Tamura, Y.Y.Ke, and Y.Tamura, Tetrahedron Lett., 1987, 28, 1431. S.E.Denmark, T.Weber, and D.W.Piotrowski, J.Am.Chem.Soc., 1987, 109, 2224. S.K.Hendrie and J.Leonard, Tetrahedron, 1987, 43, 3289. F.J.Weiberth and S.S.Hal1, J.Org.Chem., 1987, 52, 3901. E.J.Roskamp and S.F.Pedersen, J.Am.Chem.Soc., 1987, 109, 3152. G.Barak and Y.Sasson, J.Chem.Soc., Chem.Commun., 1987,1267. T.Ibata, Y.Isogami, and J.Toyoda, Chem-Lett., 1987, 1187. Y.Zhang and R.Lin, Synth.Commun., 1987, 17, 329. D.H.R.Barton, N.Yadavbhatnagar, J.P.Firet, and J.Khamsi, Tetrahedron Lett., 1987, 23, 3111. J.Kang and K.S.Kim, J-CheESoc., Chem.Commun., 1987, 897. R.A.Pilli and D.Russowsky, J.Chem.Soc., Chem.Commun., 1987, 1053. A.Stutz, Angew.Chem.Int.Ed.Engl., 1987, 26, 320. T.Moriwake, S.Hamono, S-Saito, and S.Tor=, Chem-Lett., 1987, 2085. H.Tanaka, S.Yarnashita. Y.Ikemoto, and S.Torii, Chem.Lett., 1987, 673. J.R.McCarthy, C.L.Barney, D.P.Matthews, and T.M.Barger, Tetrahedron Lett., 1987, 28, 2207. P.W.Erhardt and A.H.Owens, Synth.Commun., 1987, 17, 469. M.Newcomb and T.M.Deeb, J.Am.Chem.Soc., 1987, 109,3163. R.H.Schlessinqer and B.J.Ivandwicz, Tetrahedron Lett., 1987, 28, 2083. M.Wada, A.Aiura, and K.Akiba, Heterocycl., 1987, 26, 929. N.Knouzi, M-Vaultier, L.Toupet, and R. Carrie, Tetrahedron Lett., 1987, 28, 1757. Y.Morimoto and K.Achiwa, Chem.Pharm.Bull., 1987, 35, 3845. T.Hudlicky, G-Sinaizingde, and G.Seoane, Synth.Commun., 1987, 17, 1155. G.Tunn, J.Org.Chem., 1987, 52, 1043. S.I.Murahashi, Y.Imada, andT.Hirai, Tetrahedron Lett., 1987, 28, 77. W.CarrXhers and R.C.Moses, J.Chem.Soc., Chem.Commun., 1987, 509. L.S.Hegedus, J.L.Toro, W.H.Miles, and P.J.Harrington, J.Org.Chem ., 1987, 52, 3319. C.J.Flann, T.C.Malone, and L.E.Overman, J.Am.Chem.Soc., 1987, 109. 6097. C.J.Flann and L.E.Overman, J.Am.Chem.Soc., 1987, 109, 6115. H.H.Mooiweer, H-Hiemstra, H.P.Fortgens, and W.N.Speckamp, Tetrahedron Lett., 1987, 2 , 3285. R.A.Schofield and P.S.Mariano, J.Org.Chem., 1987, 52, 1478. L.Grehm, K.Gunnarsson, and U.Ra-Acta Chemxcand., Ser. B., 1987, 41, 18. P-Henklein, H.U.Heyne, W.R.Halatsch, and H.Niedrich, Synthesis, 1987, 166. A.Costa and J.M.Rieqo, Canad.J.Chem., 1987, 65, 2327. T.Torii, Y.Yamada, T.Oshima, S.Imao, and E.Eekawa, Nippon Kagaku Kaishi, 1987, 1442. M.Kira, S.Nagai, M.Nishimura, and H.Sakurai, Chem-Lett., 1987, 153. S.Ram and L.D.Spicer, Synth.Commun., 1987, 17, 415. S.Ram and L.D.Spicer, Tetrahedron Lett., 1987, 28, 515. K.T.Wanner and A.Kartner, Heterocycl., 1987, 26, 917. D.Tanner and P.Somfai, Tetrahedron Lett., 1 9 8 7 28, 1211. M.J.O.Anteunis, L-Spiessens, M.Dewitte, R.Callens, and F.Reiniers, Bull.Soc.Chim.Belg., 1987, 96, 459.
5: Amines, Nitriles, and Other Nitrogen-containing Functional Groups 55. 56. 57. 58. 59 * 60. 61. 62. 63. 64.
29 1
H.Yamashita, Chem.Lett., 1 9 8 7 , 5 2 5 . E.J.Roskamp and S.F.Pedersen, J.Am.Chem.Soc., 1 9 8 7 , 109, 6 5 5 1 . B.M.Trost and A.R.Sudhaker, J.Am.Chem.Soc., 1 9 8 7 , 109, 3 7 9 2 . K.Klier, G.Kresze, O.Werbitzky, and H.Simon, Tetrahedron Lett., 1 9 8 7 , 28, 2 6 7 7 . J.Laduranty, F.Barbot, and L.Miginiac, Canad.J.Chem., 1 9 8 7 , 65, 859. H.Mustroph, Z.Chem., 1 9 8 7 , 27, 2 7 3 . H.Suzuki, H.Manabe, T.Kawagughi, and M.Inquye, Bull.Chem.Soc. Jpn., 1 9 8 7 , 60, 7 7 1 . M.H.Elnagili, S.M,Sherif, and R.M.Mohareb, Heterocycl., 1 9 8 7 , 26, -
497.
J.M.Fang and M.Y.Chen, Tetrahedron Lett., 1 9 8 7 , 2 8 , 2 8 5 3 . A.Liguori, G.Sindona, G.Romeo, and N.Uccella, Syzhesis, 1 9 8 7 , 168.
65.
A.E.Vougioukas and H.B.Kagan, Tetrahedron Lett., 1 9 8 7 , 28,
66.
A-Sera, H.Tarii, I.Nishiguchi, and T-Hirashima, Synthesis,
67. 68. 69.
M.Murakami, T.Kato, and T.Mukaiyama, Chem.Lett., 1 9 8 7 , 1 1 6 7 . K.Sukata, Bull.Chem.Soc.Jpn., 1 9 8 7 , 60, 2 2 5 7 . K-Narasaka, T.Yamada, and H.Minamikawa, Chem.Lett., 1 9 8 7 ,
70.
G.Petrillo, M.Novi, G.Garbarino, and C-Dellerba, Tetrahedron, 1 9 8 7 , 4 3 , 4 6 2 5 . M-Meier and T.C.Ruchard, Chem.Ber., 1 9 8 7 , 120, 1. T.Hanafusa, J.Ichihara, and T.Ashida, Chem.Lett., 1 9 8 7 , 6 8 7 . M.R.Favia, Org.Prep.Proced.Int., 1 9 8 7 , 19, 4 8 . J.M.Aizpurua, M.Oiarbide, and C.Palomo, Tetrahedron Lett.,
5513. 1987, 631.
2073. 71. 72. 73. 74.
1987,
28,
5365.
79. 80.
H.Ohta, K.Ozaki, and G.Tsuchihashi, Chem.Lett., 1 9 8 7 , 1 9 1 . K.A.Jorgensen, J.Chem.Soc., Chem.Commun., 1 9 8 7 , 1 4 0 5 . N.Ono, I.Hamamoto, A-Kamimura, A.Kaji, and R.Tamura, Synthesis., 1 9 8 7 , 2 5 8 . N.Ono, A-Kamimura, T.Kawai, and A.Kaji, J.Chem.Soc., Chem.Commun., 1 9 8 7 , 1 5 5 0 . J.E.Saavedra, Org.Prep.Proced.Int., 1 9 8 7 , 1 9 , 8 3 . J.C.Fanning a n d m . S o c . , Chem.Commun., 1 9 8 7 ,
81.
J.C.Bottard, R.J.Schmitt, and C.D.Bedford, J.Org.Chem., 1 9 8 7 ,
75. 76. 77. 78.
955. 52,
2292.
82.
S.Zawczki, K.Osowska-Pacewicka, and A-Zwierzck, Synthesis,
83. 84.
J.Viret, J.Gabard, and A.Collet, Tetrahedron, 1 9 8 7 , 4 3 , 8 9 1 . J.P.Demers and D.H.Klaubert, Tetrahedron Lett., 1 9 8 7 7 2 8 ,
85.
T-Okawara, Y.Kamazawa, T.Yamasuki, and M-Furukawa, Synthesis,
86. 87. 88. 89. 90.
P.Leyrel, M.Baudyfloch, and A.Robert, Synthesis, 1 9 8 7 , 3 0 6 . G-Doleshall, Tetrahedron Lett., 1 9 8 7 , 28, 2 9 9 3 . O.P.Goe1 and U.Krolls, Org.Prep.Proced.Int., 1 9 8 7 , 19, 7 5 . J.S.Sandhu and E.Sain, Heterocycl., 1 9 8 7 , 26, 7 7 7 . Y.Ito, S.Nishimura, and M-Ishikawa, Tetrahedron Lett., 1 9 8 7 , 28, 1293. D.Armesto, P.Bosch, M.G.Gallego, J.F.Martin, M.J.Ortiz, R.Perezossorio, and A.Ramos, Org.Prep.Proced.Int., 1 9 8 7 , 2,
1987, 485. 4933. 1987, 183.
91.
181. 92.
D.Bacos, J.P.Celerier, and G.Lhommet, Tetrahedron Lett., 1 9 8 7 , 28,
-
93.
2353.
D.R.Langley and D.E.Thurston, J.Org.Chem., 1 9 8 7 ,
52,
91.
292 94.
General and Synthetic Methods B.Decorte, J.M.Denis, and N.Dekimpe, J.Org.Chem.,
1987,
52,
1147. 95.
R.T.Boere, R.T.Oakley, and R.W.Reed, J.Organomet.Chem., 1 9 8 7 ,
96.
3 3 1 - 1~-~ 61. J.H.Forsberg, - - - r
97. 98.
V.T.Spaziamo, T.M.Balasubramanian, G.K.Liu, S.A.Kingsley, C.A.Duckworth, J.J.Poternca, P.S.Brown, and J.L.Miller, J.Org.Chem., 1 9 8 7 , 52, 1 0 1 7 . R.V.Hoffman and G.A.Buntain, Synthesis, 1 9 8 7 , 831. T.Yamada, K.Goto, Y.Mitsuda, and J.TsuJi, Tetrahedron Lett.,
99.
Z.M.Jaszay, I.Petnehazy, L-Toke, and B.Szajam, Synthesis,
100.
D.A.Evans, J.A.Ellman, and R.L.Dorow, Tetrahedron Lett., 1 9 8 7 ,
1987, 1987, 101. 102. 103. 104.
28, -
108.
4557.
520.
1123.
~.A.Evansand T.C.Britton, ~.Am.Chem.Soc., 1 9 8 7 , 109, 6 8 8 1 . M.Arimoto, H.Yamaguchi, E.Fujita, M.Ochiai, and Y.Nagao, Tetrahedron Lett., 1 9 8 7 , 28, 6 2 8 9 . J.Garcia and J.Vilarrasa, Tetrahedron Lett., 1 9 8 7 , 2 8 , 341. A.Hassner and A.S.Amarasekara, Tetrahedron Lett., 1 9 8 7 , 28, 5185.
105. 106. 107.
28,
0.L.Chapman and C.J.Abelt, J.Org.Chem., 1 9 8 7 , 52, 1 2 1 8 . G-Labbe, Synthesis, 1 9 8 7 , 5 2 5 . J.H.Boyer and T-Manimaran, Synthesis, 1 9 8 7 , 9 0 7 . S.Murahashi and T.Shiota, Tetrahedron Lett., 1 9 8 7 , 28, 2 3 8 3 .
Organometallics in Synthesis BY T. N. DANKS, S. E. THOMAS, AND T. GALLAGHER Part I:
The Transition Elements
Introduction
1
The annual number of publications dealing with the use of organotransition metal complexes in synthesis continues to increase. As in previous years, therefore, space limitations have resulted in a selective report. A revised and extended edition of the standard text 'Principles and Applications of Organotransition Metal Chemistry' by J P Collman and L S Hegedus has been published.' Subjects of review articles include applications of higher-order mixed organocuprates to organic synthesis, new applications of tetracyanoethylene in organometallic chemistry, controlled carbometalation as a new tool for carbon-carbon bond formation and its application to cyclisation, synthesis and stereoselective reactions of a,O-unsaturated acyl ligands bound to the chiral auxiliary [ (r15-C5H5) Fe (CO)(PPh3)] , chemistry and synthetic utility of cobalt-complexed propargyl cations, the use of metal reagents in stereo- and regioselective functionalisation of conjugated dienes,7 new synthetic reactions of allyl alkyl carbonates, allyl O-keto carboxylates, and allyl vinylic carbonates catalysed by palladium complexes, cyclopropanes from reactions of transition-metalcarbene complexes with olefins, and directed homogeneous hydrogenation.
*
2
Reduction
The use of ruthenium(I1) complexes of either the (El- 6r (5)-2,2'(binap) ligand as asymmetric hydrogenation catalysts has produced several outstanding results. For example, prochiral B-keto esters are hydrogenated to optically acive B-hydroxy esters in nearly quantitative yields and with extremely high enantioselectivities (Scheme 1) High-yielding and highly enantioselective hydrogenations of allylic and homoallylic alcohols,l2 a,6- or B,v-unsaturated carboxylic acids,l3 and itaconic bis(dipheny1phosphino)-1,l'-binaphthyl
.
Yield 93 - 99'1, e.e. 98 - 100%
R = Me.Et. P r ' . B u " . P h R' = Me. Et. Pri , But Reagent
I,
cat R u X 2 [ ( R ) - or ( S ) - b i n a p ] ( X z I . Br, CI). 50-100 a t m H2. MeOH. r t , 1-4 days
Scheme 1
R = H, Me, NH,. OMe. CI
a5
- 97"/0
I
W
R =
N 'CHO
65 - 69"Io
H, OMe. OCH2Ph
Reagent : i. cat. R h 6 KO),,.
excess H,O.
56kg cm-2C0.
2 - rnethoxyethanol. 150 'C. 2Lh
Scheme 2
I
R
H. COMe. COzMe
55
- 78%
Reagent : i. cat. R h C 1 3 . 3H20. cat. Aliquat 336. H2, H 2 0 . CHC13 or M e N 0 2 . 30'C, L - 7 h
295
6: Organometallics in Synthesis
acid and related dicarboxylic acids,l4 have also been achieved using catalytic amounts of ruthenium(I1)-binap complexes. A further asymmetric hydrogenation of note is an enantioselective reduction of trisubstituted acrylic acids G. tetrasubstituted alkenes, using a 15 chiral (aminoalky1)ferrocenylphosphinerhodium complex. An efficient system f o r reducing the nitrogen-containing ring of quinolines and isoquinolines has been reported. Carbon monoxide and water in the presence of catalytic amounts of Rh6(C0Il6 convert a range of quinolines and isoquinolines into lf2,3,4-tetrahydroquinolines and ~-formyl-1,2,3,4-tetrahydroisoquinolinesrespectively (Scheme 2 ) .16 Addition of HMPA to a Sm12 - THF system used for the reduction of organic halides to alkanes renders the system remarkably mild, rapid, and efficient. Typically, yields of >95% were achieved at room temperature within one hour for a range of alkyl and aryl iodides, bromides and chlorides.l 7 Methods for converting alkenes to alkanes in the presence of a nitro group are rare as a result of the susceptibility of nitro groups to reduction. Selective alkene hydrogenation in the presence of aromatic nitro groups has been achieved however using a RhC13 18 Aliquat 336 catalyst system (Scheme 3). 3
-
Oxidation
The Sharpless asymmetric epoxidation reaction has been employed as the key step in numerous syntheses.
Use of the reaction as a method
for kinetic resolution has also received much attention this year. y-Iodo allylic alcohols,l 9 Y -tributylstannyl allylic alcohols,2o and Y-trimethylsilyl allylic alcohols21 are cleanly resolved thus providing a convenient source of a number of optically active chiral building blocks. Oxygen may be used to oxidise dyclohexadiene to trans-1 ,4diacetoxy-2-cyclohexene via a three component catalyst relay (Scheme 4) .22 This represents the first example of a selective oxidation using triple catalysis with oxygen as the ultimate oxidant. Alkane C-H bond activation continues to be a challenge. Of note in this area are reports of an iridium-catalysed conversion of pinane to B-pinene (Scheme 5) ,23 and a rhodium-catalysed transformation of pentane to but-1-ene (Scheme 6 ) .24 A chiral diamine consisting of two trans-3,4-diphenyl-
296
Gtwc.vcrl und Syrithetic Methods OH
I
X=O.N
Scheme 4
Reagent : i. cat.
I r H 5 (PPri3)2.100'C. lh (12 turnovers)
Scheme 5
eo
MeCHO
Reagent : i , cat. R h C l (CO)(PMe&, hv. r.t.. 16.5h (92 turnovers)
Scheme 6
6: Organometallics in Synthesis
297
pyrrolidine units with C2 symmetry linked by a two-carbon chain has been shown to impart high enantioselectivity to the dihydroxylation of alkenes by osmium tetroxide (Scheme 7) .25 Both enantiomers of the diamine are readily accessible and the absolute stereochemistry of the product diol can be predicted. 4
Isomerisations and Rearrangements
The rate of isomerisation of (~)-4-hydroxy-2-cyclopentenone to 1,3cyclopentanedione is greater than the rate of isomerisation of the (E)-enantiomerwhen the reaction is catalysed by a rhodium(1)- R) binap complex. Thus, kinetic resolution provides a convenient method for the isolation of (R)-4-hydroxy-2-cyclopentenone, an important building block in prostaglandin synthesis, from read available (+)-4-hydroxy-2-cyclopentenone (Scheme 8 ) . 26 It has been reported that during the isomerisation of 2-methylprop-2-en-1-01 to 2-methylpropanal under rhodium(1) catalysis, stabilisation of the intermediate 2-methylprop-1-en-1-01 occurs as a result of its complexation to the rhodium(1). This facilitates observation of the disfavoured enol tautomer by 'H n.m.r. spectroscopy (Scheme 9). 27 The stereochemical outcome of the Claisen rearrangement of enol ethers of several cyclic ketones can be controlled by the choice of catalyst employed (Scheme 10) .2a The E 4 anti selectivity observed when 2,6-dimethylphenol is used as the catalyst is altered to E + syn selectivity when PdCl2(RCNI2 (R=Me,Ph) is used to catalyse the reaction. 5
Carbon-Carbon Bond-Formina Reactions
via Organometallic Electrophiles - Nucleophilic attack on unsaturated organic molecules n-bound to transition metals continues to receive much attention. Of note is a novel method of functionalising the indole skeleton via nucleophilic displacement of a halogen. Thus, complexation of 4 - or 5-chloroindoles to ruthenium(II1, followed by nucleophilic attack on the complex by a range of reagents and subsequent decomplexation, provides a variety of 4- or 5-substituted indoles (Scheme 11) .29 The first para-tele substitution reaction of halogenobenzenetricarbonylchromium(0) complexes has been reported (Scheme 12) . 3 0
298
G mc'rd mid Sy ti thrt ic Meth odLy
Yield 70 - 85%
e e 90 - 99% R
a l k y l . a r y l . C02Me
Scheme 7
H0'
HO (i1
Yield 27% e. e. 91 %
H
Reagent
I.
/OMe
cat. 1. THF. O'C.14 days.
'OMe
H
(I) Scheme 8
ClOl
6: Organometallics in Synthesis
Reagent
299
: i. cat.
[ Rh KO)(PPh3)3]CIO,
Scheme 9 R
II
I
-
OMe anti
I R = H,
iii
Bu’
Reagents : i,
+
syn
‘ 7
Yield 95°/0 d.e. 76 -96%
Yield 95%
d.e.74-!36%
; i i . cat. 2, 6 -dimethylphenol, toluene, 100-12O’C. 10-17h;
iii. cat. PdCl2 (RCN)* (R
OH
Scheme 10
Me, Ph). toluene, r.t
,
1 - 1Oh
300
General and Synthetic Methods
0-
‘yu
...
Me N u = O M e , OCHZPh. SCHzCOzH, CH(C02Me)Z. CH(C02Et)Z , N H M e Reagents :
i, 1. 2 -dichloroethane or DMF. 50-6O’C. 16h (70-90°10); ii. Nu-. THF, 50-60’C, 10-12h. ( 7 0 - 8 5 % ; iii, hv or A (80-90%)
Scheme 11
U
n
NU
=
’y’
,CMezCN
Ph Reagent : i. L i N u ;
ii.
Scheme 12
CF,CO,H
6: Organometallics in Synthesis
30 1
The reactivity of n-bound ligands containing heteroatoms has started to attract more interest. Thus, the action of organolithium and Grignard reagents on tricarbonyliron(0) complexes of a,@-unsaturated ketones has been studied and shown to produce 1,4-diketones cleanly (Scheme 13) .31 It has been demonstrated that nucleophilic attack on thiophene ligands rc-bound to a ruthenium(I1) centre occurs at a carbon atom adjacent to the sulphur and results in cleavage of the carbon-sulphur bond to give products with butadienethiolate ligands co-ordinated through sulphur (Scheme 14) .32'33 High asymmetric induction has been observed on addition of nitromethane,34 trimethylsilyl cyanide, and Reformatsky reagents3 to the aldehyde functionality in tricarbonylchromium(0) complexes of ortho-substituted benzaldehydes. This effect is exploited in an asymmetric Darzens reaction (Scheme 15) .37 The reactivity of (propargy1)hexacarbonyldicobalt cations has been the subject of a number of investigations. A double stereodifferentiating reaction occurs when a homochiral boron enolate adds to a racemic methoxyethyl-substituted cobalt complex (Scheme 16) .38 It is of note that the racemic complex is converted into a 12:l mixture of diastereoisomers in a yield (80%) that eliminates the possibility of a simple kinetic resolution. Intermediacy of cations that (1) racemise at a rate that is fast relative to alkylation and (2) react at different rates with the chiral nucleophile has been advanced as an explanation for this observation. A 6-oestradiol with a (propargy1)hexacarbonyldicobalt substituent at 16a, required for assessment of its potential as a substrate €or hormone receptor assays using i.r. spectroscopy, has been synthesised. The synthesis required development of conditions that favoured nucleophilic attack on the (propargy1)hexacarbonyldicobalt cation by an enol in the presence of an activated aromatic ring (Scheme 17) .39 Transient transoid (pentadieny1)tricarbonyliron cations have been invoked to explain the stereocontrolled carbon-carbon bond formation that occurs when nucleophiles are added to the acetates of substituted (pentadienol)tricarbonyliron ( 0 ) complexes (Scheme 18) .40 Allylation via nucleophilic attack on allylpalladium cations continues to find numerous applications. Nucleophilic addition to a substrate bearing both primary and secondary carbonate groups resulted in displacement of the primary carbonate when the reaction
59-79'10
KO), R' = Me, Bun. Bu' .But R2 = Me, Bun , Reagents.
I.
11.
R2Li or R2MgBr. Et,O. But Br
-78'C.
7h.
Scheme 13
Nu
Nu = OMe, SMe. SEt. SPr', CH(C0,Me)2 Reagent : i , THF. rt., 2h
Scheme 14
303
6: Organometallics in Synthesis
I
I
Cr KO) 3
Cr
Yield 61°/0 e.e. (after decmplexation)88% Reagent : i .
NaH. THF : HMPA
(10: 1 ) . -78‘C.
10h
Scheme 15
A I
+ OMe
I
B Yield 80% A:B. 12:l Reagent
: i,
Bu2BOTf. CH2CI,.
Scheme 16
-1o.c
304
c
+
I 1
HO Reagent : i . (Me3SiI2NH. CH2CIZ, -1o'C
(80%)
Scheme 17 OAc
Nu
I
I
KO), R't: R 2 = H. Me, Et Nu = Me, Et, CH2CH=CH2, CH2COPh Reagent : i. NuSiMe,/BF,.
69-89%
OEtz or Nu3AI. CH2CI,, -78.C. 2h
Scheme 18
6: Organometallics in Synthesis
305
was carried out under palladium catalysis, and displacement of the secondary carbonate when the reaction was carried out under tungsten catalysis (Scheme 19) .41 The sensitivity of the palladium catalysed reaction to steric effects and the greater dependence of the tungsten catalysts on electronic effects is advanced as an explanation for this change in selectivity. It has been demonstrated that addition of isocyanates to vinyl epoxides under palladium catalysis produces oxazolidin-2-ones. Alkenes can thus be converted to amino alcohol derivatives of defined stereochemistry; this conversion has been utilised in a synthesis of (-)-acosamine (Scheme 20) 42 Asymmetric epoxidation followed by palladiumcatalysed opening of the epoxide with carbon dioxide proceeds with retention of configuration and may be equated to an enantioselective cis hydroxylation. This procedure forms the basis of a synthesis of a key precursor of (+) -citreoviral (Scheme 21) .43 Ethyl a-isocyanopropionate and other a-isocyanocarboxylates undergo palladium catalysed allylation (Scheme 22) . 4 4 Allylation in the presence of an optically active ferrocenylphosphine ligand resulted in moderate asymmetric induction (e.e. 39%). A new method for generating chiral methyl groups has been reported. The method uses the rhenium fragment (n5-C5H5)Re( N O ) (PPh3) as a template (Scheme 23). 4 5
.
via Organometallic Nucleophiles - The nucleophilicity of anions generated via deprotonation of (arene)tricarbonylchromium(O) complexes has been studied further. Deprotonation of complexes derived from 3-methoxyoestra-1,3,5(lO)-trienes followed by addition of MoOPH to the anion and decomplexation leads to 2-hydroxy-3methoxy derivatives (Scheme 24) .46 The reaction sequence provides a route to catechol oestrogens which are of interest due to their importance as oestrogen metabolites. Reaction of (rl 6-naphthalene) tricarbonylchromium(0) with (tetramethylpiperidyl)-lithium followed by addition of electrophiles to the anion generated yields 2 substituted naphthalene complexes bearing a substituent in the coSimilarly, deprotonation o€ ordinated ring (Scheme 25) 4 7 ' 4 8 (acenaphthylene)tricarbonylchromium(O) and subsequent addition of electrophiles provides 3-substituted acenaphthylene complexes (Scheme 26) . 4 9 Aromatic hydrocarbons complexed to tricarbonylchromium(0) units are readily nitrosated at the benzylic position by ButONO to
.
General and Syntlirtic Methods
306
Reagents : i I NaCH(C02Me)2,cat Pd(0). THF. 50'C; i i . NaCH ( C 0 2 M e ) 2 . cat W (0). THF. 5 0 ' C
Scheme 19
+ 4
HO
T BDMSO
AcNH (-)
-acosamine Reagents
I.
11,
III
I
IV.
5"' OOH. cat TI (OPr')4, cat ( + ) - diethyltartrate (93°/0), (COCI),, Me,SO. Et,N and then Ph3PCH3Br. BU'OK (80"/.). TsNCO. cat (dibenzyl i d e n e a ~ e t o n ePdZCHCi3. )~ cat p ( 0 P 1 - l )(lOOo/.J, ~ HCI. MeOH (62%)
Scheme 20
6: Organometallics in Synthesis
307
liii HC02 H'
iv
I----
(+)-citreoviral Reagents : i, But OOH. cat. T i
cat. (-)-diethyltartrate;
i i . (COCI 12, MezSO, Et,N and then Ph3PC(Me)C02Et; iii. COz, cat. (dibenzylideneacetoneI3Pd2CHCI3, cat. dppp (55%); iv. DIBAL-H (72%)
Scheme 21
Y
flAc I
NC C02Et
CN
Scheme 22
C02Et
General and Synthetic Methods
308
-
s”: Re_+
iv
Me0 Me0
OMe
Scheme 23
OMe
OMe
6: Organometallics in Synthesis
309
4
OTBDMS
BDMS
Meo
1.
ii. iii
H
. )
O
G
Me0
Cr(CO),
65 'lo Reagents : i. 6uLi ii. MoOPH i i i . hv
Scheme 24
-
i , ii
Cr KO),
Cr(CO)3
62 - 97 '10 R = Me, Et. C02Me, SiMe3 Reagents : i , TMPLi ; i i . MeI. EtOS02CF3, CI. C02Me. or MejSiCl
Scheme 25
-&
i.ii
CdCO),
Cr(C0I3 R = Me, SiMe3, CH(OH)Ph, CH(0H)Me
Reagents : i. LDA ;
-
10 20%
ii, Mel. MejSiCl, PhCHO or MeCHO
Scheme 26
give
(g)-and
(E)-oximes (Scheme 2 7 ) . 5 0
In the absence of the
tricarbonylchromium(0) unit, ortho or para nitro groups are required to activate benzylic hydrogens towards nitrosation. It has been reported that (c4-isoprene)tricarbonyliron ( 0 ) can be deprotonated with lithium diisopropylamide and that the resulting co-ordinated isoprene anion reacts with electrophiles at low temperature (Scheme 28) .51 This represents the first example of anion generation adjacent to a simple (diene)tricarbonyliron(o) unit . (-)-Captopril has been synthesised using the chiral auxiliary [ ( n -C H )Fe (CO)(PPh3)] (Scheme 29) .52 Stereoselective alkylation of (51) [ :5-C5H5) Fe (CO)(PPh3)COEtl with bromomethyl-t-butyl sulphide, followed by oxidative decomplexation in the presence of L-proline t5
2
butyl ester gave, after deprotection, enantiomerically and diastereomerically pure (-)-Captopril in 59% overall yield. Experimental results which demonstrate good agreement with a previously proposed theoretically-based conformational analysis of CH2R ligands attached to the pseudooctahedral chiral auxiliary [n5-C5W5) Fe (CO)(PPh3)I have 53 been presented and discussed. The benzophenanthridine alkaloids, ( + ) - and (-)-corynoline, have been synthesised by a route that utilises the 1-ferrocenyl-2-methylpropyl group as a chiral auxiliary. The key step in the asymmetric synthesis of (+)-corynoline involves condensation of a Schiff base with a racemic homophthalic anhydride. During the course of this condensation, the chiral auxiliary influences the absolute and relative configurations of two asymmetric centres (Scheme 30). 54 Complexation of an alkyne to the C O ~ ( C O ) unit ~ results in 140” C-C-H bond angles about the “alkyne” carbon atoms. An intramolecular retro-Dieckmann reaction, which had previously failed to proceed due to geometric constraints imposed by an alkyne linkage, has been shown to proceed smoothly after complexation of the alkyne (Scheme 31) . 5 5 The reaction of primary allylic acetates with Grignard reagents in the presence of catalytic amounts of Li2CuC14 can be controlled to give either a- or v-substitution of the allylic acetoxy group (Scheme 32) .56 Low catalyst concentrations and rapid addition of the Grignard reagent favour a-substitution whilst higher catalyst concentration and slow addition of the Grignard reagent favour Ysubstitution.
311
6: Orgunometullics in Synthesis
R
Total yield 45-80%
H. Me, Et, OMe Reagents : i, B d O N O . ButOK. DMSO. O'C;
i i : H20
Scheme 27
7O-79% R = Me. CHZPh, CH(OH)Ph, or C(0H)PhZ Reagents : i . LDA. THF. -78'C. l h : ii. MeI. PhCH2Br, PhCHO. or PhCOPh
Scheme 28
3 12
Grtirrul mid Syritlwiic Mrthvds
i. ii
I
iii. i v
(-1 - Captopril Reagents : i. BuLi : ii. Bu'SCHzBr; iii. B5: vi. V. ' CF,
COzH I Hg (OAC)z
Scheme 29
6: Organometallicsin Synthesis
313
J$f
+
0
-Ld
L o
0
; 'H
L o
ii
0
\
Fe
\\
( + ) - corynoline Reagents : i. Toluene, llO'C.
84h (81%):
ii. CF, CO,H. HSCH,CO,H. ct. 72h (90%)
Scheme 30
Geneml arid Synthetic. Methods
3 14
R = Me, CH,CH=CH,
Reagent
SO-71"Io
;
i. NaH. 1.2-dimethoxyethane, r.t.. 14h
Scheme 31
I
Bun 9 6 : 4 conditions A 14 : 86 conditions B Conditions A :
Bu"Mg6r added over 15 min, 2 mol 'lo LizCuC14. THE -3O'C Conditions 6 : BunMgBr added over 150 min. 5 mol O l 0 Li2CuC1h. THE O'C
Scheme 32
Ho2cA Ho2cfzH I,
Ph
ii
*
Ph
Me
Me
e.e. 27% Reagents : i. CuC1. cinchonidine, MeCN. 60'C. i i . CHN ,,
Scheme 33
8h;
6: Organornetallics in Synthesis
315
Decarboxylation of malonic acids has been shown to occur asymmetrically when the reaction is performed in the presence of copper (11) chloride and certain chiral alkaloids (Scheme 33) .57 Charge reversal of cationic n-ally1 palladium complexes, which can be achieved by their reduction with zinc or samarium diiodide, has been exploited in synthetically interesting reactions. Thus, allylic acetates are reduced by zinc in the presence of a catalytic amount of Pd(PPh3)4 to give nucleophilic reagents which add to aldehydes to produce homoallylic alcohols (Scheme 34) .58 Similarly, palladium-catalysed reduction of allylic acetates with samarium iodide in the presence of Bu3SnC1 results in the production of allylstannanes (Scheme 35).59
3-Iodo-l-trimethylsiloxypropenes, derived from the reaction between a , 6-unsaturated ketones and trimethylsilyl iodide, give Q 3ally1 complexes on treatment with tetrabutylammonium tricarbonylnitrosylferrate. After addition of triphenylphosphite to the reaction mixture the resultant phosphite-substituted complexes react cleanly with 2-propynyl bromide to gLve 4-pentynyl ketones. These complexes may thus be regarded as synthetic equivalents of 6-acylcarbanions (Scheme 36) . 6 0 via Coupling and Cycloaddition Reactions - It has been demonstrated that NbC13(dimethoxyethane), prepared by the addition of NbC15 to a solution of tributyltin hydride in dimethoxyethane, can be used to couple imines with aldehydes and ketones to give 2-amino alcohols (Scheme 37).61 The stereoselectivity of the coupling of vinyl bromide and the Grignard reagent derived from 1-phenethyl chloride, which is catalysed by nickel or palladium complexed to ligands derived from amino acids, can be inverted by addition of anhydrous zinc bromide (Scheme 38) .62 To date, the direct coupling of two alkynes to give enynes has failed to be synthetically useful because of problems with sidereactions such as trimerisation. A method for controlling this attractive coupling has been developed and homo-coupling and crosscoupling of alkynes can now be achieved in high yield (Scheme 63 39).
1,l-Dichloro derivatives of terminal alkenes are stereoselectivity monoalkylated or monoarylated by Griqnard or orqanozinc reagents in the presence of a palladium catalyst.
A s the monohalo-
Generul und Synthetic Methods
316
Ph
70'10 Reagent : i . Zn. c a t . Pd(PPh,),,
dioxane. rt.. 5 days
Scheme 34
+
Bu3SnCI ~ B u , 71 'lo
Reagent : i . %I,,
cat. Pd(PPh3)&.THF. r.t.. 6h
Scheme 35
OSiMe3 I _____)
iv
f---
Reagents : i. Me3SiI;
i i . Bu4NFe(C0)3NO; iii. P(OPh)3 ; iv,
Scheme 36
" 7 Br
OH3,'d 'OH3 'OH3CLH93 '13'0303W
'
'OH3 IH3'H34d Jd03aW '03'13 =
0
(3Wa )'139N
+
2R0,C
L
81'10
C02Me
-
= -
C02Me + Ph
Ph
Reagents
I,
cat Pd(OAc),. cat tris(2,6-dirnethoxyphenyl)phosphine
C 6 H 6 , r t , 19h,
Cat Pd(OAc),
11.
. cat
tris(2.6-dimethoxypheny1)phosphtne
C 6 H 6 . r t , 30min
Scheme 39
p
Ph
ir. i
OMe 65 "lo
66 "lo
Reagents :
I ,
[ PhZP(CH214 PPhz]
PhMgBr, cat. PdCl
cat
PdCI,(PPh,),
,
Et,O.
35'C,
,
EtzO, 35 'C, 2h ;
3h
Scheme 40
11,
p - CIC6H4MgBr.
6: Organornetallics in Synthesis
3 19
alkenes thus obtained can be converted into trisubstituted alkenes stereoselectively, geometrical isomers may be obtained from the same dihalide by reversing the order of addition of the Grignard reagents (Scheme 40) .64 Large-ring lactones have been synthesised by coupling vinyl triflate and vinylstannane groups placed at the ends of esters (Scheme 41) .6 5 The palladium-catalysed coupling proceeds smoothly to form 12 - 1 5 membered lactones in good yield. The viability of catalysing aldol additions with chiral rhodium catalysts and generating optically active products has been demonstrated. Thus, reaction of an enolsilane and benzaldehyde in the presence of a rhodium(1)-norphos catalyst gave an optically active aldol product (Scheme 42) .66 It has been reported that rhodium complexes catalyse aldol-type reactions between enolsilanes and acetals.6 7 New ligands have been designed for the gold catalyst of an asymmetric aldol-type reaction between methyl isocyanoacetate and aldehydes. Ferrocenylphosphine ligands containing morpholino or piperidino groups at the end of the ferrocene side chain increase the stereoselectivity of the reaction generating oxazolines in up to 96% e.e. (Scheme 43) .68 Asymmetric hydrocyanation of aldehydes has been reported using cyanotrimethylsilane and a chiral alkoxy titanium(1V)-molecular sieve system (Scheme 44). 69 The first example of a [6+31 cycloaddition has been reported. Thus, trimethylenemethane equivalents react with tropones under palladium catalysis to give nine-membered carbocycles in good yield (Scheme 45) . 7 0 In a related f4+3] cycloaddition reaction, trimethylenemethane equivalents and dienes combine to give octahydroazulenes (Scheme 46) .71 A novel catalytic intramolecular palladium-ene reaction has been used to cyclise 6,~-unsaturatedallylic acetates (Scheme 47) 72 The reaction, which tolerates various functional groups and is applicable to mono-, di-, and trisubstituted alkenes, complements a previo1Jsly reported magnesium-ene process. Nickel catalysed intramolecular [4+41 cycloadditions have been used to generate the AB and BC ring systems of the taxane diterpenes (Scheme 48) .73 This methodology thus provides a general and efficient route to angularly substituted bicyclo[6.4.0ldodecanes and bicyclo[5.3.l]undecanes. The effect of allylic substituents on the
Reagent
:
I,
cat. Pd(PPh&, L i C l
,
THF. 65 'C
Scheme 41
OSiMe3
I ,
PhCHO + +OMe
Ho, H
ii
Phq
O
M
e
Yield 75% e.e. 12"10
Reagents : i , c a t .
CIO, Ph,P'
CH,CI,.
cat.
'PPh*
U
r.t., 2h;
ii, HF. H 2 0 . THF
Scheme 42
q:y
321
6: Organometallics in Synthesis
+
I ___)
CNfiCOzMe
I
(32Me
95:5 Overall yield 86% e.e.of trans product 96%
P Reagent : i. cat. LAu(c-C6H,,NC)2] CHzCI,.
O
BF4, cat. PPh2
25'C. 10-40h
Scheme 4 3
0 RAH
+
Me3SiCN
-
R
Yield 66-89% e.e. 68- 96
Reagent : i .
TiCI2(OPr'
molecular sieves (&A),
,
toluene, -65%
12-48h
Scheme 44
Me
322
4 1 -84 '10
R = H. Me, OMe R 1 = H, Me, COEt R 2 = Me, OMe
Reagent
I ,
cat
Pd(0Ac)z
I
cat
3-12h
P(OPr ' 1 3 , toluene, 80-85'C,
Scheme 45
R
d
+
Fe3 _____) I
R&l
R
\
OCOMe
65- @"lo R = C02Me. COzCHzCH2Ph. SOzPh R 1 = Me, OTBDMS Reagent
I,
cat
Pd(OAc)*, c a t
P(OPr')3. c a t B u L i , THF. r t
Scheme 46
,
4-22h
6: Organometallics in Synthesis
323
71-91 ' l o AcO
R
Y = (SO2 - p -MePh), H. Me
, (CO,Me)*
R =
Reagent :
I,
cat
Pd(dibenzylideneacetone)2,cat PPhJ, THF or MeC02H,
70-80'C.
15-40h
Scheme 47
'"""YE
TBDMSO
I
I
52 ' l o
-
CO, Me
R'O
Taxol Reagents
'
I,
cat Ni(COD),, toluene,
cat
PPh,,
toluene. 110°C. 2 5 h ,
60"C,3h qrheme
48
11.
cat NI (COD),. cat PPh,
324
General and Synthetic Methods
stereochemical outcome of nickel catalysed [4+41 cycloadditions has been studied. Stereoselective synthesis of (Z)-alkenyl ethers has been achieved via alkylidenation of ester carbonyl groups using a reagent derived from 1,l-dibromoalkanes, zinc and titanium tetrachloride (Scheme 49). 75 via Carbonylation Reactions - Generation of cyclopentenones dicobalt octacarbonyl mediated coupling of carbon monoxide with a alkene and an alkyne (the Pauson-Khand reaction) has been employed as a key step in syntheses of quadrone, a compound with anti-tumour properties (Scheme 50) , 7 6 Japanese hop ether, an iridoid terpene which appears to affect the aroma and taste of beer (Scheme 51) ,77 a 6a-carbocycline analogue (Scheme 5 2 ) , 7 8 and potential precursors to the guaianolide and pseudoguaianolide families (Scheme 53). 79 Several simple aromatic and aliphatic compounds have been functionalised via carbonylation reactions. Benzaldehyde is the major product of a photo-assisted carbonylation of benzene catalysed by RhCl(C0) (PMe3)2 under mild conditions (1 atm. pressure of CO, 3 7 "C)8 o f 81 and n-pentane is regioselectively carbonylated to n-hexenal under similar conditions (Scheme 54) .82 B-Naphthoic acid has been prepared by carboxylation of naphthalene using carbon monoxide and a pa 1 1adium/phenanthro1ine cata1yst systern. It has been reported that tetrakis(tripheny1phosphine)palladium(0) catalyses a regiospecific carbonylation of methyleneaziridines to a-rnethylene-B-lactams under mild conditions (Scheme 55) .a4 Co-ordination of the alkene and the nitrogen atom to the metal accounts €or the regiospecificity of this ring expansion. Annelation of a chromium carbene ligand, an alkyne and a carbonyl ligand has been used to construct the C ring of the anthracyclinone skeleton in a formal total synthesis of 11-deoxydaunomycinone (Scheme 56). 85 Although asymmetric hydroformylation is currently an important challenge and has received considerable attention, enantiomeric excesses achieved to date have been moderate. It has now been reported, however, that hydroformylation of styrene, 2-ethenyl-6methoxynaphthalene, and vinyl acetate using an optically active platinum catalyst in the presence of triethyl orthoformate leads to acetals in high enantiomeric excess (Scheme 57) .86
325
6: Organometallics in Synthesis
70 - 96% I?' = Me, Pr. P r ' ,Bu, Bu' , Ph
- 1OO:O
2 :E, 78:22
R2= Me, Et, Pr'. But &I H. Me, Bui Reagent : i, Zn, TiCI,.
TMEDA, THF, 25'c, 2-3h
Scheme 49
OMOM Reagent
: i, Co2(CO),,
45 O1.a CO,cat.
2.6-di-t-butyl-4-methylpyridine,
quadrone
heptane, 8 6 % , 30h
Scheme 50
+ Japanese hop ether
HC =CH
I
Reagent : i , CO. C2H2. C6H,.60'C
Scheme 51
326
0 Me,Si
I
6a-car bocycline anal og ue
45 " l o
Reagent
I,
COZ(CO)e,CO, Ph3 PO, heptane, 8 5 " C , 3 days
Scheme 52
Q OSi Ph,'Bu H?
?H
HCOMe
CH
Me0 H
o
75%
Reagent . i , CO,(CO)~, CO, dimethoxyethane , 65'C . 3 days
Scheme 53
327
6: Organometallics in Synrhesis
+
CO(latm)
Reagent :
I
,
CHo 2725'10 (based on Rh)
A T
60°10 (based on Rh)
T CHO
not detected
cat. RhCL(CO)(PMe3)2, h v . r.t , , 16 5 h
Scheme 54
/
I
R
R
a o
53 - 03 ' l o R = Bun , Hex". I-adamantyl. CH2CH2CH20Me,CH2CH(OMe)2 Reagent :
I,
cat. Pd(PPh,),
or Pd(OAc),/PPh3,
CH,CI,,
r t., 2 0 - 9 0 h
Scheme 55
Reagents : i , Bu'OMe. 40°C. l h ;
i i , CO. CH,CI,
Scheme 56
,70"C, 7 2 h
328
Ph
-
4
I
Ph
100% conversion e.e. > 96*f0
Reagent : i , cat
rQ
,
H2
,
CO. CH(OEt),. 60'C, 150h
Ph2P
Scheme 57
70'1.
iiil
X
z
OH, NH,, SPh. SePh. C I . Br, I
75 - awO
R = COMe. C02E t. CN, Ph
50-75%
Reagents : i .
I
1"/0 NalHg, THF. 25.C. dark ;
ii, hv in the presence of tetramethylpiperidino oxide (followed by reduction), NO (followed by reduction), PhSSPh , PhSeSePh. MeS02CI. BrCCI, , or I 2 ; IiI, CHz%HR.
hv. CHzC12, 40°C
36h
Scheme 58
6: Organometallics in Synthesis
329
i.ii. iii
Reagents : i ,
NaiHg ;
ii, Et COX;
iii, pyridine ; Iv. CH2=CHC02Et.
hv. CHzClz. 40'C, 18-24h
Scheme 59
-C02Ph
-
' BnO
-QPh
___)
+
P - C O P h
LOTBDMS
OTBDMS
'-0TBDMS
8n3
50"lo
(-1- a- kainic
Reagent :
30%
acid
(+)-a-allokainic a c i d
i , ChlorocobaIoxime(III), NaBH4, NaOH. MeOH. O'C
Scheme 6 0
330 6
Miscellaneous Reactions
Methodology providing direct access to a wide range of functionalised radical cyclisation products has been reported. Thus, photolytic homolysis of an alkyl-cobalt bond (generated by an intramolecular radical cyclisation) in the presence of radical trapping reagents leads to oxygen, nitrogen, sulphur, selenium, halogen, and carbon functionalised products (Scheme 58) .87'88 Homolytic cleavage of acyl-cobalt bonds produces acyl radicals which undergo oxidative addition to activated carbon-carbon double bonds (Scheme 59) .89 Enantiospecific syntheses of (-)-a-kainic acid and (+)-a-allokainic acid based on a cobalt-mediated intramolecular cyclisation process have been reported (Scheme 60) .90 References 1. 2. 3.
4. 5. 6.
7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21.
J.P.Collman, L.S.Hegedus, J.R.Norton, and R.G.Finke, 'Principles and Applications of Organotransition Metal Chemistry', University Science Books, Mill Valley, California, 1987. B.H.Lipshutz, Synthesis, 1987, 3 2 5 . A.J.Fatiadi, Synthesis, 1987, 959. E-I Negishi, Acc. Chem. Res., 1987, 20, 65. S.G.Davies, 1.M.Dordor-Hedgecock, R.J.C.Easton, S.C.Preston, K.H.Sutton, and J.C.Walker, Bull. SOC. Chim. Fr., 1987, 608. K.M.Nicholas, Acc. Chem. Res., 1987, 2 0 , 207. J.E.Backval1, Bull. SOC. Chim. Fr., 1987, 665. J.Tsuji and I.Minami, Acc. Chem. Res. 1987, 2,140. M-Brookhart and W.B.Studabaker, Chem. Rev., 1987, 87, 411. J.M.Brown, Angew. Chem., Int. Ed. Engl., 1987, 26, 190. R.Noyori, T.Ohkuma, M.Kitamura, H.Takaya, N.Sayo, H.Kumobayashi, and S.Akutagawa, J. Am. Chem. SOC., 1987, 109, 5856. H.Takaya, T.Ohta, N.Sayo, H.Kumobayashi, S.Akutagawa, S.Inoue, I.Kasahara, and R.Noyori, J. Am. Chem. SOC., 1987, 109, 1596. T.Ohta, H.Takaya, M.Kitamura, K.Nagai, and R.Noyori, J. Org. Chem., 1987, 52, 3174. H.Kawano, Y.Ishii, T.Ikariya, M.Saburi, S.Yoshikawa, Y.Uchida, and H.Kumobayashi, Tetrahedron Let-c., 1987, 28, 1905. T.Hayashi, N.Kawamura, and Y.Ito, J. Am, Chem. SOC., 1987, 109, 7876. S-I Murahashi, Y.Imada, and Y.Hirai, Tetrahedron Lett., 1987, 28, 77. J-Inanaga, M-Ishikawa, and M.Yamaguchi, Chem. Lett., 1987, 1485. I.Amer, T.Bravdo, J.Blum, and K.P.C.Vollhardt, Tetrahedron Lett., 1987, 2 8 , 1321. Y.Kitano, T.M=sumoto, T.Wakasa, S-Okamoto, T-Shimazaki, Y.Kobayashi, F.Sato, K.Miyaji, and K.Arai, Tetrahedron Lett., 1987, 28, 6351. Y.Kitano, T.Matsumot0, S.Okamoto, T.Shimazaki, Y.Kobayashi, and F.Sato, Chem. Lett., 1987, 1523. M.Kusakabe, H.Kato, and F.Sato, Chem. Lett., 1987, 2163.
6: Organometallics in Synthesis
33 1
2 2 . J.E.Backval1, A.K.Awasthi, and Z.D.Renko, J. Am. Chem. S O C . , 1 9 8 7 , 109, 4 7 5 0 . 2 3 . Y.Lin, D.Ma, and X.Lu, J. Organomet. Chem., 1 9 8 7 , 323, 4 0 7 . 2 4 . T-Sakakura. T.Havashi, and M.Tanaka. Chem. Lett.. 1 9 8 7 . 8 5 9 . 2 5 . K.Tomioka, 'M.Nakajima; and K.Koga, J . Am. Chem. SOC. , i 9 8 7 , 109, 6213. 2 6 . M.Kitamura, K.Manabe, R.Noyori, and H.Takaya, Tetrahedron Lett., 1 9 8 7 , 28, 4 7 1 9 . 2 7 . J.Park and C.S.Chin, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 2 1 3 . 2 8 . K.Mikami, K.Takahashi, and T-Nakai, Tetrahedron Lett., 1 9 8 7 , 28, 5879. 2 9 . R.M.Moriarty, Y-Y.Ku, and U.S.Gil1, J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 4 9 3 . 3 0 . F.Rose-Munch, E-Rose, and A.Semra, J. Chem. SOC., Chem. Commun., 1987, 942. 3 1 . S.E.Thomas, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 2 2 6 . 3 2 . G.H.Spies and R.J.Angelici, Organometallics, 1 9 8 7 , 5 , 1 8 9 7 . 3 3 . J.W.Hachgenei and R.J.Angelici, Ang. Chem., Int. Ed. Engl., 1 9 8 7 , 26, 9 0 9 . 3 4 . A.Sol1adi.e-Cavallo, G.LapitaJs, P.Buchert, A.Klein, S.Colonna, and A.Manfredi, J. Organomet. Chem., 1 9 8 7 , 330, 3 5 7 . 3 5 . A.Solladie-Cavallo, A-C.Dreyfus, F.Sanch, and A-Klein, Chem. Lett., 1 9 8 7 , 1 5 8 3 . 3 6 . J.Brocard, L.Pelinski, and J.Lebibi, J. Organomet. Chem., 1 9 8 7 , 3 3 7 , c47. 3 7 . C.Baldoli, P.Del Buttero, E-Licandro, S.Maiorana, and A.Papagni, J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 7 6 2 . 3 8 . S.L.Schreiber, M.T.Klimas, and T.Sammakia, J. Am. Chem. S O C . , 1 9 8 7 , 109, 5 7 4 9 . 3 9 . M.Gruselle, S.Greenfield, and G.Jaouen, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1 3 5 3 . 4 0 . M.Uemura, T.Minami, Y.Yamashita, K.Hiyoshi, and Y-Hayashi, Tetrahedron Lett., 1 9 8 7 , 28, 6 4 1 . 4 1 . B.M.Trost, G.B.Tometzki, and M-H.Hung, J. Am. Chem. S O C . , 1 9 8 7 , 109, 2176. 4 2 . -:Trost and A.R.Sudhakar, J. Am. Chem. SOC., 1 9 8 7 , 109, 3 7 9 2 . 4 3 . B.M.Trost, J.K.Lynch, and S.R.Angle, Tetrahedron Lett., 1 9 8 7 , 28, 375. 4 4 . Y.Ito, M.Sawamura, M.Matsuoka, Y.Matsumot0, and T.Hayashi, Tetrahedron Lett., 1 9 8 7 , 28, 4 8 4 9 . 4 5 . E.J.O'Connor M-Kobayashi, H.G.Floss, and J.A.Gladysz, J. Am. Chem. SOC., 1 9 8 7 , 109, 4 8 3 7 . 4 6 . J.C.Gil1, B.A.Marples, J.R.Traynor, Tetrahedron Lett., 1 9 8 7 , 28, 2643. 4 7 . E.P.Kundig, V.Desobry, C.Grivet, B.Rudolph, and S.Spichiger, Organometalics, 1 9 8 7 , 5 , 1 1 7 3 . 4 8 . E.P.Kundig, C.Grivet, and S.Spichiger, J. Organomet. Chem., 1 9 8 7 , 322, C 1 3 . 4 9 . R.U.Kirss, P.M.Treiche1, and K.J.Haller, Organometallics, 1 9 8 7 , 6, 242. 5 0 . D.Senecha1, M-C.Senecha1-Tocquer, D.Gentric, J-Y.Le Bihan,
B.Caro, M.Gruselle, and G.Jaouen, J. Chem. 1987, 632.
SOC.,
Chem. Commun.,
5 1 . M.F.Semmelhack and E.J.Fewkes, Tetrahedron Lett., 1 9 8 7 , 28, 1497. 5 2 . G-Bashiardes and S.G.Davies, Tetrahedron Lett., 1 9 8 7 , 28, 5 5 6 3 . 5 3 . S.G.Davies, 1.M.Dordor-Hedgecock, K.H.Sutton, and M-Whittaker, J. Am. Chem. SOC., 1 9 8 7 , 109, 5 7 1 1 . 5 4 . M.Cushman and J.Chen, J. Org. Chem., 1 9 8 7 , 52, 1 5 1 7 .
332
General and Synthetic Methods
5 5 . N.E.Schore and S.D.NaJdi, J. Org. Chem., 1 9 8 7 , 52, 5 2 9 6 . 5 6 . J.E.Backval1 and M.Sellen, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 827. 5 7 . O.Toussaint, P.Capdevielle, and M.Maumy, Tetrahedron Lett., 1987, 28, 539. 5 8 . Y.MasuEma, N.Kinugawa, and Y.Kurusu, J. Org. Chem., 1 9 8 7 , 52, 3702. 5 9 . T.Tabuchi, J.Inanaga, and M-Yamaguchi, Tetrahedron Lett., 1 9 8 7 , 28, 215. 6 0 . K I t o , S.Nakanishi, and Y.Otsuji, Chem. Lett., 1 9 8 7 , 2 1 0 3 . 6 1 . E.J.Roskamp and S.F.Pedersen, J. Am. Chem. SOC., 1 9 8 7 , 109, 6551. 6 2 . G.A.Cross and R.M.Kellogg, J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 1746. 6 3 . B.M.Trost, C-Chan, and G.Ruhter, J. Am. Chem. SOC., 1 9 8 7 , 109, 3486. 6 4 . A.Minato, K.Suzuki, and K.Tamao, J. Am. Chem. SOC., 1 9 8 7 , 109, 1257. 6 5 . J.K.Stille and M.Tanaka, J. Am. Chem. SOC., 1 9 8 7 , 109, 3 7 8 5 . 6 6 . M.T.Reetz and A.E.Vougioukas, Tetrahedron Lett., 1 9 8 7 , 2 8 , 7 9 3 . 6 7 . S.Sato, I.Matsuda, and Y.Izumi, Tetrahedron Lett., 1 9 8 7 y 2 8 , 6657. 6 8 . Y.Ito, M. Sawamura, and T.Hayashi, Tetrahedron Lett. 1 9 8 7 , 28, 6215. 6 9 . K.Narasaka, T.Yamada, and H.Minamikawa, Chem. Lett., 1 9 8 7 , 2 0 7 3 . 7 0 . B.M.Trost and P.R.Seoane, J. Am. Chem. SOC., 1 9 8 7 , 109, 6 1 5 . 7 1 . B.M.Trost and D.T.MacPherson, J. Am. Chem. SOC., 1 9 8 7 , 109, 3483. 7 2 . W.Oppolzer and J-M.Gaudin, Helv. Chim. Acta, 1 9 8 7 , 7 0 , 1 4 7 7 . 7 3 . P.A.Wender and M.L.Snapper, Tetrahedron Lett., 1 9 8 7 r 2 8 , 2 2 2 1 . 7 4 . P.A.Wender and N.C.Ihle, Tetrahedron Lett., 1 9 8 7 , 2 8 , 2 4 5 1 . 7 5 . T-Okazoe, K.Takai, K.Oshima, and K.Utimoto, J. OrgFChem., 1 9 8 7 , 52, 4410. 7 6 . TMagnus, L.M.Principe, and M.J.Slater, J. Org. Chem., 1 9 8 7 , 52, 1483. 7 7 . KC.Billington, W.J.Kerr, and P.L.Pauson, J. Organomet. Chem., 1 9 8 7 , 328, 2 2 3 . 7 8 . P.Magnus and D.P.Becker, J. Am. Chem. SOC., 1 9 8 7 , 109, 7 4 9 5 . 7 9 . V.Sampath, E.C.Lund, M.J.Knudsen, M.M.Olmstead, and N.E.Schore, J. Org. Chem., 1 9 8 7 , 52, 3 5 9 5 . 8 0 . T.Sakakura and M.Tanaka, Chem. Lett., 1 9 8 7 , 2 4 9 . 81. T.Sakakura and M.Tanaka, Chem. Lett., 1 9 8 7 , 1 1 1 3 . 8 2 . T.Sakakura and M.Tanaka, J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 758. 8 3 . T-Jintoku, H.Taniguchi, and Y.Fujiwara, Chem. Lett., 1 9 8 7 , 1 1 5 9 . 8 4 . H.Alper and N.Hame1, Tetrahedron Lett., 1 9 8 7 , 28, 3 2 3 7 . 8 5 . K.H.Dotz and M-Popall, Angew. Chem., Int. Ed. E g l . , 1 9 8 7 , 26, 1158. 8 6 . G.Parrinello and J.K.Stille, J. Am. Chem. S O C . , 1 9 8 7 , 1 0 9 , 7 1 2 2 . 8 7 . V.F.Pate1 and G.Pattenden, Tetrahedron Lett., 1 9 8 7 , 2 8 , 1 4 5 1 . 8 8 . V.F.Pate1 and G-Pattenden, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 871. 8 9 . D.J.Coveney, V.F.Pate1, and G.Pattenden, Tetrahedron Lett., 1 9 8 7 , 3,5 9 4 9 . 90. J.E.Baldwin and C-S.Li, J. Chem. Soc., Chem. Commun., 1 9 8 7 , 1 6 6 .
6: Organometallics in Synthesis
PART 11:
333
Main Group Elements
1 Group I General Aspects.- The reductive cleavage of thiothers is an important synthetic entry into organolithiums derivatives and this area, as well as the more general aspects of ether and thioether cleavage by organoalkali metal compounds, has been reviewed. 2 ,4 , 6-Tri-t-butylphenylithium ( 1 ) is a valuable base for the highly selective kinetic deprotonation of unsymmetrically substituted ketones. For example, reaction of benzyl methyl ketone with ( 1 ) in the presence of Me3SiC1 gives good selectivity for methyl group deprotonation.2 The use of silanes as bases, rather than as 3 nucleophiles, within this context has also been examined. Trost and co-workers have studied the axial selectivity available in the addition of a variety of organometallic nucleophiles to cyclic ketones and enones. Non-bonding interactions are generally thought to be responsible for the low axial selectivity usually observed, but if sufficiently nonsterically demanding nucleophiles such as LiCH2CN or NaCH2CN are used, good selectivity results. Perfluoroalkyl ketones are obtained from esters in good yields using perfluoroalkyl lithiums. The success of this methodology relies on the generation of these normally unstable nucleophiles using Gassman's procedures, in the presence of the ester component.5 This year has seen a number of developments in the area of lithium amide bases. The preparation of a series of hindered bases, eg (2) and (3), together with an evaluation of their stabilities in ether solvents has appeared. Optically active amide bases have found new applications in asymmetric synthesis. The enantioselective dehydrohalegenation of prochiral B-chloroacids gives the corresponding a,B-unsaturated acids in up to 82% enantiomeric excess (e.e.) (Scheme 1) .8 Chiral bases may also be used as "chiral auxiliaries" in the enantioselective alkylation of carboxylic acid dianions, and also in aldol processes." The equilibration of a series of (El- and (2)-lithium enolates using catalytic phenylmercuric chloride has been examined, and using the resulting thermodynamic data valuable MI42 force field parameters were obtained. 1 1
334 Li
R
Li
Y
NR’ t
HO,C
C02H
3
up t o 82”/0 e.e.
Scheme 1
m = l , n = 2
(4) Reagents
I,
m = 2, n =1
Li, Na(Me0CH CH 0) ALH ( c a t a l y t i c ) , pentane; 2 2 2 2
Scheme 2 R’-
X
R’TeLi
_____)
R’T~R, (5)
R e a g e n t : i, B u n L i
Scheme 3
R e a g e n t s : i , L D A , HMPA, t h e n Me1
Scheme 4
ii, CL,,,SiMe,H
6: Organometallicsin Synthesis
335
Selective 1ithiations.- Further details regarding the in situ generation and use of BunLi, BuSLi and ButLi using ultrasound have appeared.12 Amide bases, ylids and a number of other anions have also been prepared under these conditions. 2-Bornyl lithium (4) has been prepared from the corresponding chloride and, in contrast to the organomagnesium derivative, the lithiospecies is somewhat more stable. This anion has been used to prepare chiral silane derivatives (Scheme 2). l 3 A new entry to organolithiums based on lithium-tellurium exchange has been reported (Scheme 3 ) . Procedures have been developed that avoid the need to isolate the intermediate t 14 tellurides (5; R 2 = Ph, Bun, Bus, Bu 1 . The regioselective lithiation of 4,6-dialkyl-2H-pyran-2-ones depends on the nature of the alkyl substituents. In general, lithiation (LDA, HMPA, -78°C) occurs adjacent to C-4 unless this position is more highly branched than the residue C-6 (Scheme 4) .15 Barluenga and co-workers have described the generation of 3,3-diethoxypropyl lithium ( 6 ) and the application of this species as a propanal homoenolate equivalent (Scheme 5). l 6 The use of lithium naphthalide was necessary for the success of this methodology, as attempted metallation using lithium metal failed. The same research group has also described the generation of the E-functionalised organolithiums (7),17 and a related in situ halogen-lithium exchange has been used to prepare a variety of 18 l-substituted cyclopropanols (Scheme 6 ) . Cyclisation reactions of organometallic reagents are important synthetic processes. Bailey has reported the results of a study on the regiospecific cyclisation of alkenyl-substituted organolithiums ( 8 ) . The scope of the process in terms of ring size and A related study stereocontrol available has also been examined.” involving cyclisation of benzyllithiums to pendant alkenyl residues has been published.2 o Intramolecular conjugate additions of aryl, alkenyl and alkyl lithiums to a,B-unsaturated acyl 20 phosphoranes also proceed efficiently. Substituted ally1 lithiums are a class of important ambident nucleophiles that can react with electrophiles at either the a- or y - site. The effect of heterocyclic substituents on the a/y selectivity of anions ( 9 ) in their reactions with aldehydes has been studied. The kinetic product has been shown to be the a-adduct (10) but these rearrange on longer reaction times to the more stable
Reagents: i , Li+C,0H87, THF, - 7 8 ° C
Scheme 5
cl-co.c,
C
l
T
O
M
g
R
B
R
Ll
Reagents:
i,
Lie,
ii, H30+
Scheme 6
R e a g e n t s : i, LDA, THF, - 7 8 ° C ; ii, R C H O , t h e n H +
Scheme 7
r -Li
R
R
6: Organometallicsin Synthesis
337
y-adduct (11) (Scheme 7 ) . 22 Deprotonation (LDA) of ( a4-isoprene)Fe (CO) gives the corresponding dienyl lithium (12). This species is unstable above -3O"C, undergoing conversion to the isomeric '14-trimethylenemethane complex, but may be trapped at low temperatures with a variety of e l e ~ t r o p h i l e s . ~Additions ~ of ZnBr2 to (12) gives an organozinc species that shows an improved reactivity towards enolizable ketones. Amides have evolved as important directing groups for the lithiation of various types of nucleii. Full details on the remote lithiaton of carboxamides (13-15) have appeared24. The complex-induced proximity effect dominates over both resonance and inductive effects, so that loss of the thermodynamically more acidic protons a- to the carboxamide residue is not observed. The role of complexation of the amide with the lithiating species (usually BuSLi) has been demonstrated. Although remote lithiation of the sulphide (15) occurred, metallation of the homologous derivative (16) took place a- to the amide (Scheme 8). Eaton has studied the use of amides as activating groups for the lithiation of the cubane nucleus. One of the difficulties associated with this chemistry is that the equilibrium [[17)=(18)] for lithiation using an amide base lies to the left hand side. However, if this deprotonation is carried out in the presence of a Hg(I1) salt, the organomercury derivative (19) is formed in high yield. Treatment of (19) with MeLi effects mercury-lithium exchange to give the organolithium species (18) cleanly (Scheme 9 ) .24 This process, coined "reverse transmetallation", therefore provides an indirect, but efficient means of generating otherwise inaccessible organometallic reagents. The corresponding Grignard derivative may be produced by mercury-magnesium exchange using MeMgBr . Reverse transmetallation has also been applied to other systems with high C-H acidity. For example, the cyclopropylcarboxamide (20)26 undergoes much the same process leading to the organomercury species (21) from which both the lithio and Grignard derivatives, (22) and (23),may be produced. In this particular case transmetallation of (21) with MeLi does lead to some attack at the amide residue. The dilithiated cubane (24) and the 2,6-dilithiobenzamide (25) have been obtained in a similar fashion.
General and Synthetic Methods
338
C0.N P r i
I
C0.N Pr i2 I
*
R / y P h
Li
mN&P2ph
Pri2NC0
I
+
R
Li
R uSPh
(15)n = 1 (16)n = 2 R e a g e n t s : i, BusLi, TMEDA
Scheme 8 II
0
0
It
II NPr l2
ii
C0.N Pr;
iii or i v
C IHg
C0.N P r l 2
CO.NPrI2
(22) M = L i (23) M = M g B r
(21) Reagents
I,
Lithium 2 , 2 , 6 , 6 - t e t r a m e t h y L p i p e r i d i d e ( L T M P ) ,
iv, MeMgBr
Scheme 9
0
11,
LTMP, HgCLZ,
111,
MeLi,
6: Organornetallies in Synthesis
339
Full details concerning the use of a-aminoalkoxides as directing/protecting groups for the lithiation of heterocycles such as furans, pyrroles, indoles, and thiophenes have appeared.27 This extends a process that was first investigated on aryl derivatives and is based on the reversible addition of an amide nucleophile (LiNR2) to an aldehyde. The precise nature of the amide nucleophile is important to the outcome of the reaction. For instance, N-methyl-2-fomylpyrrole undergoes either ring metallation (at C - 5 ) or lithiation of the N-methyl group depending on the amide used (Scheme 10). Similar observations were recorded for N-methyl-2-fomylindole. Bromine-lithium exchange has been used successfully to generate the N-t-butoxycarbonyl (N-Boc) lithio and dilithiopyrroles ( 2 6 ) and (27)28. Previously, problems had been encounted with the formation of these anions by direct deprotonation of N-Boc (or N-tosyl) pyrrole. Carboxamide-directed metallations have been employed for the direct hydroxylation (by 0 2 ) of aryl lithuims to provide access to a range of poly(a1koxy) ben~amides.~’ Di- and Trianions and Alkenyl and Alkynyl Anions.Chloro-methyllithium (generated in situ) reacts at low temperature with RRIC=O to give, after lithiation with lithium naphthalide, the is dianion (28) which can be trapped with an e l e ~ t r o p h i l e . ~This ~ related to work already discussed.18 Katritsky has extended the use of lithiocarbonates as an anion-stabilizing function to (hydroxymethy1)trimethylsilane. Dianion ( 2 8 ) may be formed under standard conditions and reacts with esters to give a-hydroxyketones, thus acting as a methanol dianion equivalent (Scheme 11)31. Secondary allylic alcohols isomerise under basic conditions to give the homoenolate (29) which is trapped efficiently with alkyl halides (Scheme 1 2 ) .32 New synthetic applications of the bis(ester enolates) (30) have been described.33 Dianions (31) and ( 3 2 ) have been prepared by regiospecific lithiations of the parent oxazole or thiazole carboxylic acids and the factors that control the site of lithiation in related derivatives have been probed.34 Trilithiation of 3-acetyltetramic acids and reactions of the resulting anion ( 3 3 ) with aldehydes provided a useful entry to the corresponding 3-dienoyl or trienoyl derivatives.3 5
General and Synthetic Methods
340
-
I
c---
MeO MeW
0
W MeC
H
O
W
C
H
O
I
74 .I.
88 ' l o
Reagents: i, lithium N-methylpiperazide, 6u"Li ( 3 equiv), TMEDA, then Me1 ; ii, Lithium N, N', N ' - t r i m e t h y l e t h y t e n e d i a m i d e , Bu"Li ( 3 equiv.),TMEDA then Me1
Scheme 10
Q
Li
Boc
B oc
(27)
(26)
n OH Me3Si
i
R e a g e n t s : i, Bu"Li,
Li
2 Me3Si
Me3Si-OC0,Li
CO,;
ii, Bu'Li;
H+
iii, RCOZEt, t h e n
Scheme 11
R
Y
-
OH
R
m LiO
0
Li
(29) R e a g e n t s : i, KOBut, Bu"Li, Et,O,
-6 " C to r o o m temp;
S c h e m e 12
OLi
OLi
11,
R ' X , -20°C
6: Organometallics in Synthesis
Li
34 1
C0,L i (3.11) X =
Li
O
(33)
(32) X = S
R3snl/SnR3 - c'HbHgc' - 1=/ Li
Reagents:
i, HgCl,;
Li
ii, B u * L i , - 7 5 "C
S c h e m e 13
LiIC
Li
R e a g e n t s : i , BunLi
I K0But(2
Ph
equiv.), t h e n
LiBr;
S c h e m e 14
ii, E l e c t r o p h i l e (E+), then
H+
Mercury-lithium exchange has been used to prepared ( E l - and (Z)-1,2-dilithioethenein a stereospecific manner (Scheme 13). Attempts to generate these dianions from the bis(stanny1)ethenes by direct tin-lithium exchange failed: only one stannyl residue could 36 be displaced using BunLi. The dilithiation of cinnamonitrile leads to dianion (34) which can be trapped with a range of e l e c t r o p h i l e ~ . ~The ~ type and structure of the products obtained depend on the factors affecting the reactivity and configurational stability of (34). This paper includes a useful overview of the current state of related di- and polyanion chemistry. 2-Isopropenylacetylene undergoes dilithiation to give (35) which has been used as an equivalent of an isoprenyl anion in 38 pheromone synthesis (Scheme 14). Lithiation of the orthoester (36) gives an anion (37) that is synthetically equivalent to either (38) or (39).39 The anion (37) reacts well with alkyl halides and aldehydes and the chloro substituent in the final product can be cleaved using HSnBu3. In a related area, the sulphonyl-substituted alkenyl anion (40) has been obtained once again by direct deprotonation.4 0 This species can be trapped and should therefore function as an equivalent of a 6-acylvinyl anion (411, although the authors did not actually expose this equivalence so the full synthetic value of anion ( 4 0 ) has yet to be realised. A simple procedure for the preparation of the anion (43), a 2-lithiopropenal equivalent that has been previously described by both Evans and Still, involves fragmentation of (421, a precursor that is readily available from epichlorohydrin and acetone (Scheme 16) .41 Two equivalents of BuSLi are required to remove the acetone that is released on fragmentation. Anion (43) was trapped with various aldehydes and modest diastereoselectivity was observed with a-alkoxy aldehydes. There has been much interest in nucleophilic carbohydrates over recent years. This year has seen an advance in this area by Schmidt who has reported the lithiation of 2-substituted glucal.4 2 Anions (44) and (45) allow the introduction of a substituent at C - 1 , while maintaining a heteratom at C-2. There are problems associated with (44), namely competitive benzylic deprotonation, and the sulphur-stabilized alkenyl anion (45) is better behaved.
6: Orgariometallics in Synthesis
343
(36)
(37)
(38)X = C l (39)X = H R e a g e n t s : i, B u t L i ( 2 equiv.), THF, - 7 8 "C
S c h e m e 15
L m Me o
Li
Me
R e a g e n t s : i, B u s L i ( 2 e q u i v . ) , THF, - 7 8 ° C ;
ii, R C H O ; iii, R3SiCL
S c h e m e 16
B n O**
OBn (44)
OBn (45)
0
A series of dienyl- and trienyllithium derivatives eg ( 4 6 ) and (47) have been prepared by bromine-lithium exchange. These anions are useful homologating agents and this value has been illustrated, in the case of (461, by the facile conversion of B-ionone to retinal (Scheme 17) .43 The synthesis and lithiation of 1-methoxymethyl (MOM) dienes (and trienes) has been reported (Scheme 18)44, and the intramolecular alkylation of lithioalkenes has been used by Negishi to control exocyclic alkene geometry in an extension of earlier work (Scheme 19) .45 The preparation of alkenyl lithium ( 4 8 ) bearing a triorganostannyl group together with their reactions with aldehydes and ketones have been reported.4 6 The related trimethyl lead derivatives (49) have also been prepared. These anions, which are not only more stable but also less basic than the stannyl derivative (481, react with electrophiles to give the corresponding 47 (E)-alkenylleads in a highly selective fashion. Allenyl lithiums possess useful reactivity and this year has seen some activity.in this area. The 3-(t-butyldimethylsilyloxy) allenyl lithium (50) has been used as an equivalent of the anion (51) [see (41) above]. The use of the t-butyldimethylsilyl rather than trimethylsilyl residue is important in this process, since the Me3Si- group was prone to premature cleavage. Anion (51) reacted as an allenyl anion, with a range of alkyl halides, but gave, as anticipated, the acetylenic products when trapped with aldehydes4* (Scheme 20). The configurational stability of the carbamoyl derivatives ( 5 2 ) has been ~ t u d i e d . ~ ’The relatively high degree of stability observed has been exploited in the stereoselective synthesis of tetra- and pentasubstituted 1,3-butadienes via the allene-Claisen rearrangement(Scheme 21).
Sulphur-Stabilized Anions.- As in previous years, this important aspect of organosulphur chemistry has been included in this section of the report. The reaction of sulphur-stabilized anions to enones can proceed via 1,2- or 1,4 addition. The factors that control this regioselectivity have been discussed together with some more general comments on the reaction.50
6: Organometallics in Synthesis
R e a g e n t s : i, (461, then
345
H30+
Scheme 17
R e a g e n t s : i, L D A ; ii, B u s L i , T M E D A , d i m e t h o x y e t h a n e ( D M E ) , - 7 8
'C
Scheme 18
OR Br
Br R e a g e n t : i, B u t L i
Scheme 19
R3sn1Li R'
R"
H
Generul und Synthetic Methods
346
+/ - - -M e
'9
A OR
), Li
Me Me I
0
Me
/
Me M
e
q
:
C
'R OH Reagents:
I,
LDA,
M e 3 S i C L , t h e n H30t
0.NPr i2
347
6: Organometallics in Synthesis
The lithio-derivative of methoxy(pheny1thio)methane (53) is a useful reagent and its scope has been increased further by the observations that adducts (54) undergo nucleophilic allylation (or propargylation) the course of which is determined by the nature of the Lewis acid used(Scheme 22) .51 Mercaptomethylation of alkyl halides has been achieved using the sulphur-stabilized anion (55) as an equivalent of LiCH 2SH. Facile displacement of the thiol product from adducts (56) is This affected using B u " L ~ . ~ ~ chemistry has been extended to incorporate the trimethylsilyl derivative(57) which undergoes facile fluoride-induced cleavage to provide an anion closely related to (55) which was trapped with aldehydes to give ultimately 2-hydroxythiols. Deprotonation of the pyranose derivative (58) gives an anion that reacts with various electrophiles to give (60) as the major The stereochemical outcome of this reaction has been explained in terms of the boat conformer (59)(Scheme 24).54
product.
Normally, allylic anions ( 6 1 ) derived from ketene-S,S-acetals react with 'hard' electrophiles, such as H20, at the a-site (adjacent to the sulphur substituents).
This reactivity can,
however, be controlled depending on the nature of the proton source used. 55 The diastereoselectivity available by the reaction of aldehydes with anion ( 6 1 , R = Me) has been examined. The major products are the anti y-adducts ( 6 2 ) , but this selectivity was lost with most ketones.5 6 a-Aminoketene-S,S-acetals (63) are an unexploited group of reagents, but undergo smooth deprotonation and alkylation. The adducts ( 6 4 ) may be reduced to give protected aminoketones (Scheme 25) .57 The configuration of sulphoxide-stabilized anions remains an area of controversy. One of the difficulties in this area is the configurational assignment of products. This has been discussed and, in addition, the stereospecificity of deuteration and methylation of a chiral a-sulphinyl phenyl methyl carbanion has been reported.58 The reaction of chiral sulphinylallyl anions (65) with enones leads to 1,4-adducts in 70-96"a.e. 59 Alkylations of dianions derived from
B-hydroxysulphoxides and
a-hydroxysulphones lead to diastereomeric products. The stereochemical outcome of these processes involves chelation of Li'
348
General and Synthetic Methods
1 PhS
PhS
<
OMe (53)
Me0
(54)
Reagents: i, R X ; ii, TiCI,,,
CH2=CH-SnBun3
, CH2C12, -20
iii, BF3, CH2=CH-SnBU"3
'C;
CH2C12, - 20 "C
Scheme 2 2
R e a g e n t s : i, L D A ;
ii, R X ;
iii, B u n L i , t h e n
H30+;
iv, F - , then
RR'C=O
Scheme 2 3
0-Ph
-
PhS
Reagents : I , BunLi,
Li--0Li
then E +
Scheme 24
PhS
E
6: Organometallics in Synthesis
(61, R = 3, 5-C12C,H,)
349
w i t h HO , w i t h MeCH(COzEt),
R’CHO
D
1
90
: 99 : 10
Rl&3 Me
(61, R = M e 1
s
(62)
(64)
(63)
R e a g e n t s : i, B u n L i , THF, - 4 0 ° C ; ii, B2H6, T H F
S c h e m e 25
L
Reagents:
i,
Bun L i (2.2 e a u i v . ) . then
F+
major
product
major
product
major
product
to the sulphinyl group, but chelation is not thought to be important in the case of sulphone-stabilized anions (Scheme 26). 6o Significant asymmetric induction has been observed in the reaction of the optically active lithiated vinyl sulphoxide (66) with aldehydes leading to adducts (67).61 The diastereoselectivity of lithiated sulphoximines (68) with aldehydes leading to (B-hydroxyalkyl)sulphoximines has been studied.62 Methyl esters react with the lithiooxathianes dioxide (69) to give, after treatment with silica gel, y-hydroxy ketones. 63 Terminal epoxy bis(su1phones) undergo cyclisation on treatment with base. The distribution of products,(70) versus (71),has been looked at and the selective formation of the 7-membered ring (71, 64 n=4) is worthy of note (Scheme 28). The sulphone-stabilized anion (72)65 and dianion (73)66 have found applications in the synthesis of y- and 6-lactones (Scheme 291, and the rearrangement of allylic sulphones has been exploited to allow a double alkylation of the (2-pheny1thio)allylic sulphone (74) (Scheme 30).67 The presence of an -S02Ar residue at C - 3 of a furan directs metallation to C-2 of the furan ring, but attempts to generate dianions led to ring metallation of the aryl (Ar) 68 residue. The addition of BunLi to the sulphonyl acetal (75) leads to elimination of methanol, followed by situ metallation of the resulting vinyl sulphone. The resulting anion was trapped and various aspects of the chemistry of the subsequent adducts have been described (Scheme 31) .69 Use of the known peracid arrangement of the vinyl sulphones allows the lithiated alkenylsulphone (76) to be used as an acyl anion equivalent (77).70 Further aspects of the chemistry of 2,5-dihydrothiophene-1, 1-dioxides have appeared this year. These heterocycles have been used extensively to synthesise 1,3-dienes by SO2 extrusion. Sulphone-stabilized anions play an important role in this area, allGwing access to substituted heterocycles and thereby, more highly functionalised lI3-dienes. The aldehyde/ketone adducts ( 7 8 ) may be obtained in improved yields by careful control of the In other work, the trimethylsilyl residue reaction
condition^.'^
offers a useful way to control the regioselectivity in a double alkylation requence. 72 In the absence of the Me3Si group, 2,5-dialkylated adducts are usually obtained(Scheme 32).
6: Organornetallies in Synthesis
35 1
(66)
0
N Si Me3 (68)
Reagents: i, LDA, THF;
ii, RCO,Me,
S i O z , CHzCIZ
Scheme 27
,rn
NaOEt
PhSOz
Ph SO, so
PhSO, n n n n
= 1 = 2 = 3 = 4
(70) only product
major -
S c h e m e 28
OH
(71)
-
only product minor
o n l y product
352
PhSO,
u k
PhSO,
0 " R'
0
I
R' '**Me OH
R'
Li I
Leo,
Li
PhSOz
I\
(73) R e a g e n t s : i, R'RC=O,
S0,Ph
t h e n H30+
29
Scheme
R
(74)
/ PhSOz&R
R' R e a g e n t s : i, B u n L i ,
RX;
ii, S i 0 2 o r h v ; i i i , B u n L i , R ' X
S c h e m e 30
PhSOzJbye
i
~
(75) Reagents
1
i, BunLi ( 2 e q u i v . ) ;
PhSO, Y
O
M
e
-
F
O
M
E
Li ii, E + ( R X , R C H O , R R ' C = O ,
Scheme
PhSO,
31
CICO2Me,
Me3SiCL)
e
6: Organometallics in Synthesis
353
pYi SOzPh
S0,Ph
(76)
(77)
R e a g e n t s : i, l i t h i u m h e x a m e t h y l d i s i l a z i d e (LHMDS), THF, -78'C, HMPA;
ii, B u n L i , THF, -105'C,
t h e n R ' X ; iv, I-,
t h e n R'R"C=O,
t h e n M g S i l ; iii, Bu"Li,
THF, -105'C,
R"I
Scheme
32
BrMg*cN
(80) A r ' = P h or 3 , 5
(79)
Me,Si
-
Me,CsH,
l--& MgCl
S c h e m e 33
Grnrrd urid Synthetic M(Jthods
354 2 Group I1
Magnesium.- The chemistry of di(Grignard) reagents has been reviewed this year.73 The nature of the magnesium metal used is often critical to the successful generation of organomagnesium reagents. Rieke has described a new procedure for producing highly reactive magnesium and makes comparisons of this material with that produced by pre-existing methods. This is based on the use of lithium as a reducing agent and a variety of multifunctional Grignard reagents e.g. ( 7 9 ) have been prepared.74 The same research group has also described methods for activating copper.7 5 Chiral diamines, such as ( 8 0 ) , have been used as ligands for the asymmetric addition of ArMgBr to aldehydes to give benzylic alcohols in 40-75% e.e. This reaction may also be carried out in the presence of 2,4,6-trimethylphenoxyaluminium dichloride which extends the scope of the reaction.76 Grignard reagents derived from furfuryl halides are notoriously unstable but the presence of a trimethylsilyl residue on the furan ring dramatically stabilizes reagents such as (81). It is not clear how this arises but the suggestion is made that the anion-stabilizing influence of silicon 77
is transmitted through the heterocyclic ring. In contrast to many alkyl and alkenyl metal derivatives, ally1 metals do not usually cause problems with competitive enolization in their reactions with ketones. A good illustration of this is the use of (82) as an acetone enolate equivalent where the alkenyl residue serves as a masked carbonyl €unction. This reagent reacts smoothly with easily enolized or severely hindered ketones (Scheme 33) .78 The reaction of Grignard reagents with enol ethers, using a low valent nickel, as a stereoselective entry to trisubstituted alkenes has been developed in terms of a broader range of substrates and catalysts. Kocienski et al.have applied these developments towards the synthesis of a key intermediate in the synthesis of zoapatanol . 7 9 Dithioacetals also undergo a Ni (11)-catalysed coupling with Grignard reagents to give alkenyl products (Scheme 34) . 8 0 The cross-coupling of pyridyl Grignard reagents with phenyl sulphinyl pyridines provides access to a range of bi(pyridines1. 8 1 Zinc and Mercury.-
Methods for the activation of zinc and the
355
6: Organometallics in Synthesis
n
R
Reagents : i, RMgBr, N i C I Z ( P P h 3 ) z ( c a t a l y s t )
Scheme 3 1
M
F,
,hCO,
Me
(83, M = Z n 8 r )
R
&
RU
Y ...
R'
R
Ill
____)
I
0 R
S c h e m e 35
OZnEt
3 56
Generul and Synthetic Methods
synthesis of organozinc reagents have been reviewed.8 2 Trimethylsilyl chloride in catalytic quantities has been used to activate zinc for the synthesis of Reformatsky reagents.83 The use of zinc-based chemistry allows access to the trifluromethylsubstituted enolate (83, M = ZnBr). The corresponding organolithium (83, M = Li) undergoes fragmentation and the corresponding ketene silyl acetal has limited reactivity.84 Full details on the chemistry of zinc homoenolates, derived from alkyl propionates, and their use in C-C bond formation have been p~blished.~’A series of organozincs ( 8 4 ) have been prepared and these reagents undergo a range of useful transition metal-catalysed reactions with carbon electrophiles (Scheme 35) .86 The preparation and characterisation of an ethylzinc enolate ( 8 5 ) has been described. This species, which is thought to be dimeric in nature, does many of the same reactions as the corresponding lithium enolate, but is somewhat less reactive.87 The asymmetric additions of zinc azaenolates (86) to prochiral cycloalkenones has been achieved in up to 92% e.e. (Scheme 36)88 and the asymmetric addition of R2Zn to aldehydes has attracted a great deal of attention again this year. The most common approach has involved the use of optically active amine ligands to control/induce asymmetry in the product. A wide range of amines,their corresponding lithium salts and even polymer-bound derivatives have been used and 89 e.e.‘s of up to 96% have often been obtained. The reaction of phenyl-substituted cyclopropanes with various mercury (11) salts and iodine affords 1,3-bifunctionalised phenylpropanes in a regiospecific manner (Scheme 37) . Proporgylic amines react with Hg(II)C12 in the presence of HC1 to give ammonium trichloromercurates ( 8 7 ) via a trans addition of Hg-Cl, controlled by the amine residue.’l Vinyl mercuric chlorides (88) react with w-alkenyl carboxylic acids in the presence of Pd(I1) to alkenyl-substituted lactones (89).92
3 Group I11
Boron.- New and improved methods €or the synthesis of organoboranes have appeared this year. Dialkylalkoxyboranes,eg Et2BOMe may be generated by reaction of Et3B with methanol in THF at low
357
6: Organometallics in Synthesis
0
phHph OMe
(86) Reagents : i, BunLi,
then Z n M e 2 ;
ii,
d
Scheme 36
Reagents : i, HgXZ ( X
= CL,
B r , OAc, C O C F 3 , O N 0 2 1, 1 2
Scheme 3'1
%*
R'
R'
wR 'HgCI
(87)
(89) n = 1,2
(88)
0
m
R R e a g e n t s : i, d i c y c l o h e x y l borane, THF,
5
Dl A B
I
O C
S c h e m e 38
358 temperature.9 3
One of the main problems with preparing diborane from NaBH4/BF3Et20 is that the product is contaminated with BF3 and Et20 which may on occasion be problematic. This can be avoided by a modification of a procedure first described by Freeguard and Lon (1965) based on the reaction of NaBH4 with 12. The present modifications are operationally simple and a variety of Lewis base-borane complexes have been prepared.94 The use of dimethylboron bromide in the reqiocontrolled cleavage of cyclic ethers, including oxiranes, has been explored. 95 Brown has published full details on a number of important aspects of organoboron chemistry. This includes synthesis of secondary amines by the reaction of azides with alkyldichloroboranes , 96 the autoxidation of organoboranes as a route to alkyl hydroperoxides,9 7 and an improved synthesis of primary amines via hydroboration of alkenes using dimethylborane. 98 A useful mechanistic study correlating the relative rates of
hydroboration and oxymercuration of a series of alkenes has appeared and concludes that the transition states of both reactions have The reactivity of MeBH2 as a very similar steric requirements.” hydroborating agent has been examined and this reagent shows a reactivity that is highly solvent dependent. l o o Enamines undergo facile hydroboration on treatment with BH3Me2S and the resulting [2-(dialkylamino)alkyll boranes can be oxidized to give aminoalcohols. The best reagent for this sensitive step is trimethylamine N-oxide. l o ’
Improved procedures for the synthesis of
trans-(2-phenylcyclo~entyl- and cyclohexy1)boronates in high enantiomeric excess have been described. These are important intermediates in the synthesis of optically active trans-2-phenyl cyclopent- and -cyclohex-1-01, which are valuable chiral auxiliaries. 102 The regiospecific synthesis of boron enolates by the reaction of dialkylboranes and diazoketones has been reported (Scheme 38) l o 3 and Masamune has explored the use of the chiral boron enolate (90) in the aldol reaction.
New reducing agents based on boron continue to attract attention, particularly within the sphere of asymmetric synthesis, l o 5 and procedures f o r the large-scale preparation of lithium dialkylborohydrides (LiBR2H2) and the use of these reagents to gain access to some unusual dialkylboranes (91)-(93) have been
6: Organometallics in Synthesis
359
c;i '0
R
24
Me,BH
S
ktl+BH 2
(92)
(93)
Me (94)
(95)
(96)
w.',", HN,
8-0 H
(97)
/o
B H
(98)
(99, x
(99, X =N3)
Ii R e a g e n t s : i, LiCHCLZ;
ii, N a N 3 ; iii, N a C 1 O Z , t h e n
Scheme 39
HZ/Pd/C
reported. Potassium triphenylborohydride (from Ph3B and KH) has been shown to be a mild and selective reducing agent for a variety of functional groups. 1 0 7 Asymmetric hydroborations and reductions have seen some impressive contributions this year. A series of new cyclic boronic esters e.g. (94)-(96) with chirality on the alkyl and/or the diol moieties have been prepared. These esters react with KH to give chiral borohydrides which reduce ketones with variable levels of 108 asymmetric induction. Chiral aminoalcohols are useful chiral auxiliaries to place on boron log and Corey has used the proline-derived complex (97) as a catalyst in the BH3 THF-mediated asymmetric reduction of ketones. This highly efficient reducing system and the mechanism of the reaction, in terms of the sense of induction observed, has been discussed. The valine-derived complex (98) has been used in a similar way by Itsuno in the latest of a series of publications in this area.logc This year has seen further developments in the homologation of alkylboronates using (dichloromethy1)lithium. The chloroboronates (99, X=C1) have been converted to the corresponding azides (99, X=N3) which undergo a second homologation to give ultimately the (L)-a-aminoacids ( 1 0 0 ) in 92-96% e.e. (Scheme 39) . l o o Full details have also appeared from Brown's group on the use of optically pure borinic esters (101) in the synthesis of a-chiral acyclic ketones in >99% e-e. An example of the process is shown in Scheme 4O.l1l Alkyl/aryl-1-alkynylalkoxyboranes RB(OR')C=CR" have been prepared in high yield by the reaction of a lithioalkyne (LiC=CR") with a borinic ester, followed by reaction with HC1 at low temperature. 1 1 2 Boranes are important components of a range of coupling processes and (E)- (2-bromoethenyl)dibromoboranes (192) are useful reagents for the synthesis of 1,2-disubstituted alkenes (Scheme 41) The synthesis of a variety of l-phenylthio-1,3-dienes have been described by cross coupling of the benzodioxaboroles (103) with (El-or (Z)-2-bromo-l-phenylthioethene in the presence of Pd(Ph3P)4. The use of isomerically pure allylborons is a useful way of controlling both relative and absolute stereochemistry. Aldoximes react with (E)- and ( Z ) -crotylboronates under pressure to give, after reduction, primary amines with high levels of diastereoselectivity (Scheme 42) .l15 The reaction of a-alkoxy aldehydes with
6: Organometallics in Synthesis
361
(101) R e a g e n t s : i, 3 - L i t h i o f u r a n ,
+
ii, CIZCHOMe, LiOBut then H202 or Me3N -0
Me,SiCL;
-
Scheme LO
R e a g e n t s : i, H-C=C-H;
ii, R'ZnCI, PdCL2(PPh3)z
;
iii, R " X , LiOH
Scheme It
Reagents
, ii,
i, Me*$o)
0
M?&*)
; i i i, dihydrotipoic
acid, Fe(l1)
'0
Scheme 42
m
m
9,,0
1 (1051
-
maleic
RCHO
anhyU r i d e
O&
0 (106)
Scheme 4 3
R---
OH
0
General and S'n t her ic Methods
362
y-alkoxyboronates, (E)- (104) and ( Z ) - (104), has been studied in terms of the diastereocontrol available. Allylboronates (106), available via Diels-Alder cycloaddition, react with aldehydes to set a total of four stereocentres (Scheme 43) . l 1 7 Rousch has discussed the value of variously substituted allylborons in setting multiple stereocentres and makes some useful comparisons with allyl- and crotylstannanes. Masamune has examined the potential of
-
-
homochiral borolanes, (E) (107) and ( Z ) ( 1 0 7 ) , in the diastereo and enantioselective synthesis of homoallylic alcohols. Organoboranes have been prepared by nucleophilic addition of alkyl lithiums and other organometallics (cuprates, enolates and 2-lithio-lI3-dithiane) to hindered alkenylboranes (108). The use of the mesityl residues suppresses competitive 'ate' formation. The dienyl derivatives (109) have also been studied (Scheme 44) .144 A controllable boron-Wittig reaction is based on dimesitylboryl-stabilized carbanions (100). Selectivity, which is efficient, depends very much on the conditions used (Scheme 45). The major erythro adduct (111) has to be trapped by Me3SiC1 to prevent reversion and loss of stereochemistry.1 2 1 Aluminium and Thallium.- The very bulky aluminium Lewis acid complexes MAD (112) and MAT (113) force alkyl lithiums to add in a conjugate sense to cyclic enones.1 2 2 Bu3 A1 promoted the reductive rearrangement of 1-alkenylacetals in a highly selective fashion (Scheme 46) .123 Full details of earlier work on the cross coupling reactions of alkenylaluminiums with aryl and vinyl halides have appeared 124 and the reactivity of these vinylalanes towards nitroalkenes has been 125 studied. Hydroalumination of a wide range of enones, dienones and ynones gives the synthetically useful aluminium enolates which have been trapped by a variety of electrophiles.126 This methodolgy is useful for the synthesis of aldehyde-derived silyl enol ethers, which are difficult compounds to prepare in other ways. 126a Thallium (111) trifluoracetate is useful for the cleavage of sulphur-protecting groups in cysteine derivatives. 1 2 7
363
6: Organometallics in Synthesis
A r = 2, 4, 6 -Me3C,H, R e a g e n t s : i, R ' L i
;
ii, Bun4NF,
HZO; iii, R ' L i t h e n R " X
S c h e m e 44
Ar'
R
w
Ar,BCHR'
7
R e a g e n t s : i, Ar'CHO,
(CF3C0),O;
ii, Ar'CHO,
t h e n M e 3 S i C ( ; i i i , HF, MeCN
Scheme 4 5
% (112, R = M e ) (113, R = Bu')
General and Synthetic Methods
364
Me,S i
R
Reagents:
I ,
(1171, L e w i s
a c i d ; ii, M e S O 2 C ( , E t 3 N
S c h e m e 47
q
,SiMe,
,SiMe3
X
SiMe3
0+OH
H**
major ( X = NMe, 1
major (X = OEt, OH)
(119) Reagents
1,
rn- CICgH4C03H,
CH2CL2,
-20 "C, t h e n
S c h e m e 48
H20
6: Organometallics in Synthesis
365
4 Group IV Silicon.- General aspects. The silicon 6-effect underpins much of modern silicon-based synthetic methodology. 128 The trimethylsilyl-accelerated retro-Diels-Alder reaction has been used to determine a quantitative measure of the 6-effect, which has been estimated as 4.2 kcal mol-l. 128a
Allyl and Vinyl Si1anes.- The ammonium salt (114) reacts with a series of RMgX (R= Bun,-Ph-,PhCH2- and Me3SiCH2-) in the presence 129 of Cu(I1) to give the isoprenylsilanes (115) in good yield. The stereospecific silylation of optically active n-allylpalladium complexes with e.g. Me3SiSiC13 followed by an ethanol quench gives the optically active allyl silanes (116), which are formed with net retention of configuration.130 A synthesis of terminally substituted (El-ally1 silanes based on the Krief-Reich elimination of O-seleno-y-silyl alcohols has been reported. The allylsilane precursor, aldehyde ( 1 1 7 ) may be regarded as a synthetic equivalent of the vinyl cation (118)(Scheme 47) .I3' The use of an allylsilane as a directing group in the stereoselective hydroxylactonisation of unsaturated carboxylic acid derivatives has been described (Scheme 48), and the importance of the carboxylate derivative (119, X=NMe2,0Et,0H) on the stereochemical outcome of the cyclisation has been analysed. 132 (1R)-(El-Myrtenal has been used as starting material for the synthesis of C-centred optically active allyl silanes (120). This reagent reacts with prochiral ketones to give tertiary homoallylic alcohols in 21-50%e.e. 1 3 3 The dialkylboron-substituted allyl silanes (121) have been prepared and these reagents undergo a series of useful synthetic transformations leading to a variety of functionalised allyl silanes.134 l-Trimethylsilyl-2,3-dienes (123) have been prepared in 40-92% yield by acid-catalysed elimination of the stannyl alcohols (122).135 Allyl silanes continue to be useful synthetic reagents. Thus, the stereochemical outcome of the osymylation, epoxidation and methylenation (Me3Al,CH212) of allyl silanes has been reported.136 1-Acyloxyallyl silanes (124) undergo fluoride-mediated conjugate addition to e n ~ n e s land ~ ~ similar conjugate additions of allyl silanes can also be promoted by the use of trityl perch10rate.l~~~
Gerwrcrl arid Synthetic Mtdiods
366
S n Bun3
C Me,Si
A
R
Me,Si OH (122)
(123)
Ry
0Y
5
F
3
R'
0
(125) R IR' = Me or H
(124)
(126) R / R ' = M e o r H
OSiMeg Reagents:
i, P h 2 B O S 0 2 C F 3 ,
PhA(1271
t h e n RCHO
Scheme 4 9
;
ii, Me3SiI
6: Organometallics in Synthesis
367
This same Lewis acid, which has been applied by Mukayama in a range of areas that are beyond the scope of this report, also promotes the addition of allyltrimethylsilane and cyanotrimethylsilane to secondary and tertiary allylic alcohols to give 1,5-dienes and ply-unsaturated nitriles respectively.138b Pentaco-ordination of silicon provides a mild mechanism of activation. The allyltrifluorosilanes (125) undergo highly selective allylation of aldehydes on treatment with CsF13’ and this allylation reaction has also been achieved using the allylsilicates (126) Mukaiyama has also investigated the asymmetric synthesis of homoallylic alcohols (Scheme 4 9 ) - Good diastereoselectivity has been observed using (S)-l-phenyl-l-trimethylsilyoxyethane (127) as the sacrificial directing group. The intramolecular Lewis acid or fluorideion-catalysed addition of allyl silanes (128) to aldehydes leads to polycyclic a-methylene lactones and new examples of this reaction have appeared, with an emphasis on stereochemical control.142 The addition of the optically active dienylsilane (129) reacts with isobutyraldehyde in an antiselective fashion (89% e.e.1. 143 New applications of the use of iminium ions as initiators for allyl and propargyl silane cyclisation have appeared from several groups. 144 The bifunctional derivative (130) reacts with ketone enolates to give annulated products, and serves as a useful equivalent to the zwitterionic species (131)(Scheme 50) .14’ New annulation methodology based on the iodoallylsilane (132) and the acetoxy derivative (133) has been described by M01ander’~~ Ally1 silanes react with iodosylbenzene and T r ~ s t lrespectively. ~ ~ [(PhIO) I and azidotrimethylsilane and BF3.Et20 to give allylic f 48 azides. Silicon-stabilized anions continue to attract attention. The reactivity of the (triphenylsily1)allylanions (134), and also the corresponding (triphenylgermyl) derivative, with electrophiles has been described.14’ The diastereoselective addition of anion (135) to aldehydes provides, after oxidative silyl cleavage, an entry to syn-1,2-diols. This anion, which reacts with electrophiles a- to the silyl moiety, may therefore be regarded as an equivalent of anion (136).150 The regioselectivity observed in the reaction of (137) with electrophiles has been shown to depend o n the ‘size’ of the electrophile used - larger residues reacting preferentially at the
368 S i Me3 I
4--,
Me2Si Ph
\
R e a g e n t s : i, (130),Pd(PPh3)4, then
Bun4 NF
Scheme 50
A,
Me3Si
eS i P h ,
X
M+
(134) M = L i , M g I , Z n E t
(132) X = I (133) x = O A c Me,(Pr',Nl
Si
M+ (135) M = ZnCl
A
Ar
Me3Si0
Li+
R &SiMe3
Ar
(137)Ar = 4 - B u t -
(138) R = al k y l , O R
C,H4
R%
"Si"
(139) " S i " = Me,Si,
F3Si, F,Si-
6: Organornetallics in Synthesis
369
y-site. 15' New synthetic routes to alkenylsilanes have been reported.152 One particularly interesting example involves the reaction of alkenyl chlorides with lithium diisopropylamide, in the presence of Me3SiC1, which has been applied to silylenol ethers of a-haloketones and esters to give (138).152a The stereosectivity observed in the halogenation of alkenylsilanes (139) depends markedly on the nature of the silyl leaving group and provides a useful synthesis of either ( E ) - or ( Z ) a A 1keny1si1anes undergo ary 1ation, with a 1keny 1ha 1ides. inversion of configuration, with PhPdOAc, a reagent that is generated in situ.153b The intramolecular electrophilic addition of iminium ions to bromoalkenylsilanes has been elegantly used by Overman to prepare a variety of piperidine derivatives. 154 This reaction has been used as the key step in the total synthesis of e.g. (5)-elaeakanine A and (+)-streptazolin (Scheme 51). The synthesis of (+)-streptazolin involves an interesting intramolecular acylation of an alkenyl lithium. Cycloalkenylsilanes have been prepared in moderate to good yields via the carbometallation of 1-silylalkynes followed by Pd(0)-catalysed cyclisation (Scheme 52) 155 Allenylsilanes have been prepared by displacement of secondary propargyl carbonates with (Me2PhSi)2CuLi.156 This extends earlier work on the displacement of
.
tertiary propargyl acetates. Other Silicon-containing Reagents.- Dichlorosilanes have been utilized by Chan as useful reagents to determine the enantiomeric purity of alcohols. 157 In an area that has seen a number of developments over recent years, a combination of Me3SiC1 and N,N,N',N' - tetramethylethylenediamine (TMEDA) has been shown to promote the conjugate addition of RCu to enones. 58 Diiodosi1ane , ( H Si12) prepared by iodination of phenylsilane, effectively 2 deoxygenates alcohols and ethers, showing a high selectivity for A range of cyanosilanes [R3SiCN and secondary oxygen functions.15' R2Si(CN)2] may be prepared from the corresponding chlorosilane using KCN impregnated on Amberite XAD resin and the useful synthetic intermediate, bis(trimethylsilyl)carbodiimide, has been prepared from cyanotrimethylsilane and cyanamide.161
370
General and Synthetic Methods
Si Meg
(L) -tartaric
( 5 ) -elacakanine A
CF3C 02H
acid
m
N&-OMe
--OMe
x(
0
--
OMe
OMe
@--OMe
Eto2C
Et02C H
OMe
OMe
I+)-streptazolin
Scheme 51 Me3Si
-E-R
Me3Si
Me3Si I
6rZn
R e a g e n t s : i, l O O " C , s e a l e d t u b e ; i i , Pd(Ph3PI4
Scheme 52
II
R
7
6: Organometallicsin Synthesis
371
Pd(0)-Catalysed reactions of disilanes (R3SiSiRV3)with isocyanides (RI'NC) give the unusual bis(sily1) imines (140).162 The 'stabase' protected ally1 amine (141) undergoes facile Ni(I1)-catalysed crosscoupling with Grignard reagents. The 'stabase' group, first introduced by Magnus, is readily cleaved leading to substituted allylic amines. 163 Cerium(II1) moderates the reactivity of a-silylanions to allow the methylenation (Peterson reaction) 164 and the synthesis of allylsilanes from esters165 (Scheme 53) . The slylated pyridone (142) undergoes F--induced cleavage to provide an equivalent of the 166 highly reactive organolithium derivative (143). Hydrosilylation 167 of aldehydes/ketones can be carried out in 168 the absence of a catalyst using the silicate complex (144). and mechanistic 169b aspects of the Stereochemical hydrosilylation of alkenes have been described. Optically active alcohols have been shown to be useful chiral auxiliaries for the asymmetric conjugate addition of various The influence of the silylcuprates to a,$-unsaturated esters. 17' trimethylsilyl moiety on the Wagner-Meerwein rearrangement of bicyclic alcohols has been explored 17' and the same research group has continued to develop the directing effect of the trimethylsilyl group in (145). The versatility of this substrate, which can be prepared in optically pure form has been illustrated in a synthesis of (+) - a - c ~ r c u m e n e ' ~(Scheme ~ 54) . The trimethylsilyl group has also been used as a control element in the synthesis of 2-substituted-1,3-dienes (Scheme 55). 173 The presence of this residue in the a,@-unsaturated carboxylate (147) activates this system towards conjugate addition by RLi and RMgX.174 The oxidative cleavage of the C-Si, bond is effectively achieved electrochemically, and this reaction has been applied to a variety of organosilicon derivatives. 175 a-Silylated ketones and aldehydes (148) have been prepared by Enders in > 9 6 % e.e. using his metallated SAMP/RAMP methodology. 176 A series of B-functionalised acylsilanes have been obtained using trimethylsilyl-activated nucleophiles (Scheme 56).177 Acylsilanes undergo fluoride-ion cleavage and, in some cases, this process has been shown to lead to migration of either alkyl or aryl groups from silicon (Scheme 57). 178
General and Synthetic Methods
312
. ..
Me,Si
R e a g e n t s : i, CeC13;
A
I , I1
Li
ii, T M E D A , R’RC=O;
iii, R C 0 2 M e ( 0 . 5 equiv.), t h e n SiOz
Scheme 5 3
(142, M = M e 3 S i ) (143, M = L i )
(144)
(+)-a-curcumene R e a g e n t s : i, 4-MeC6H4Mg6r, CuBr, Me2S, Me3SiCI, HMPA; ii, 3-CLC H CO H, then MeO-, M e O H 6 4 3
Scheme 5 4 OH
(146) R e a g e n t s : i, R C H O ; i i , C r 0 3 , p y . , t h e n
CH2=CHMgBr;
Scheme 55
i i i , CH3C02H, Na02CCH3
6: Organometallics in Synthesis
373
SiMe, I
R ' 4 C o ;
0
R/H
jc,. Xd S i M e 3
OSi Me3
4
Me,
4Si
S i Me3
Br Reagents: i, Me3SiX ( X
=
NEtZ, SPh, Br, N 3 ) a n d also Ph3P/Me3SiCI; ii, H';
iii, Br,
Scheme 56
i
- XR
0 RASi R e a g e n t s : i, Bun4NF, HO ,,
I
R
R'R'; THF
Scheme 5 7
R
0 Ph3Ge& Ge Ph,
GePh3
Bun,Sn H,
(152)
R e a g e n t s : i, Ph3SnH, E t j B (0.1 equiv.), 2 5 ° C
Scheme 5 8
374
Guierli 1 utid Sy t I thetic Mi&
ods
Germanium,Tin and Lead.- The emphasis here is on the chemistry of organotins but germanium and lead derivatives have not been completely absent from the literature. The halogenation of arylgermanes has been investigated 17' and both (El-and ( Z ) -alkenyltriphenylgermanes (149 have been prepared in a regio and stereoselective fashion by the addition of Ph3GeH to terminal alkynes. 180 The stereochemistry [ ( E l / ( 2 ) 1 of the product depends on the temperature at which addition is carried out. The acyl germane (150) has been used, under acidic conditions, as an acetate equivalent in an aldol-type process. 181 A comprehensive account 182 of the organic chemistry of tin has been published this year and the use of tri-n-butyltin hydride as a reagent in synthesis has also been reviewed. 183 The reducing properties of the two tin complexes (151) and (152) have been examined.184 The amine complex (151) is soluble in organic solvents and is a good reducing agent for azides. The Et3B-induced addition of Ph3SnH to a l k y n e ~ ' is ~ ~ an efficient way to prepare alkenylstannanes and this chemistry has now been applied to a tandem addition-cyclisation reaction (Scheme 58) 185a Full details of the Pd(0)-catalysed addition of Me3SiSnR3 ( R = Me,Bun) to alkynes have appeared together with some of the chemistry of the resulting adducts. 18' In a related process, germylstannylation of acetylenic esters has been achieved using Me3GeSnBun3 giving, as the major product, (153) (48-56%) and (154)(14-16%). Once again, some of the chemistry of these adducts has been examined. 187 The homoallylic stannanes (155) have been prepared in a highly regioselective fashion by the electrophilic cleavage of (trimethylsily1)methylcyclopropanes (Scheme 59). 188 Alkenyl- and alkynylaluminium reagents react with (Et0)2CHSnBun3 to give good yields of the alkoxystannanes (156, R=alkenyl, alkynyl).189 A new approach to 2-(trialkylstannyl)-l,3-dienes is based on the hydrostannylation and subsequent 1,4-elimination of 1-trimethylsilyl-4-hydroxy-2-alkynes (157) (Scheme 60). A significant advantage of this chemistry has been the accessibility of (157) from a range of aldehydes, ketones and eonones. 190 Allenylstannanes have attracted some interestl'land the synthesis of a range of allenylstannanes (158) has been reported. lg2 The Diels-Alder reaction of P-stannylenones (159) provides adducts that may be readily manipulated to give bicyclo [4.1.O1heptanes, as
.
6: Orgunometullics in Synthesis
375
Me3Gkc02Et R
SnBun3
I
SiMe3
*
C13Sn
R (155) Reagents: i , SnCL4,
CH2CL2, 15 " C
Scheme 5 9
6un3sn
--
t
(156)
1
(157) ii
Sn Bun,
SnBun3 ...
+Rf
Ill 4
R
Me3Si
R
R e a g e n t s : i, BunLi, then RR'C=O;
R'
i i , HSnBun3, A I B N ; iii, (CH3CO)20, Et3N, then Bun4NF-
Scheme 6 0
Bun3Sn
R' +
(158, X
c 4 x
R
OEt or SPh)
B un3Sn ?Me
(159)
316
Gmeml mid Synthetic.Methods
illustrated by a synthesis of A3-carene (Scheme 61) .lg3 Normally aryl or alkenyl groups on tin will be cleaved by electrophiles such as I2 in preference to alkyl residues. This may, however, be reversed, depending on the environment of the tin atom, if a mechanism involving intramolecular assistance (by an adjacent heteroatom) is available (Scheme 62). This is an important process, although a finely balanced one [(160) vs (161)l since it makes available a range of unusual stannanes. Stannanes have also been shown to be useful directing substituents on pyridyl derivatives for both nucleophilic and electrophilic substitution. l g 5 New procedures for the preparations of allyl stannanes have appeared and the reactivity of these derivatives towards iminium ions lg7 and enones lg8 has been evaluated. The diastereoselectivity available in the addition of allyl stannanes, including the more highly substituted variants (162-164), to 199 aldehydes and ketones has attracted some attention. Our appreciation of the value of organotins in cross-coupling reactions is largely due to the efforts of Stille and his group and this year has seen further strides and the publication of a series of highly informative full papers. 2 o o The key components are alkenyl stannanes (165) and alkynyl stannanes (166) and (165, R1=H); the latter undergoes smooth Pd(0)-catalysed reaction with substituted aryl bromides to give a range of functionalised styrenes.200a Stereospecific coupling of alkenylhalides and (165,R1=C02Et, alkyl) gives dienes with full retention of alkene geometry of both components. The conditions required are very mild and the pheromone of the forest tent caterpillar (167) has been prepared without the need of hydroxyl protection (Scheme 63) .200b Alkenyl halides also couple with (166, R 1=alkyl) with retention of configuration 2ooc and vinyl triflates (168, n=5-8) cyclise to the remote alkenyl tin residue with Pd(0) to give macrocyclic lactones (169, n=5-8) in nearly 60% yield. 200d, 200e A range of aryl, alkenyl, allyl and acyl halides couple with the masked acetylating agent (170) using PdC12(PPh3)2. After coupling, hydrolysis of the resulting enol ether liberates the corresponding methyl ketone.201 Alkenyltins (165, R1 = alkyl) undergo a facile dimerisation, with t-butyl hydroperoxide and Pd(0Ac) to give 1,4-disubstituted-l,3-dienes. Cross coupling of (165,R12' =alkyl) with allylstannanes gives 1, 4-dienesf202
6: Organometallics in Synthesis
377
A3 - c arene
1 . 2 ~ 1m i x t u r e of regioisomers Reagents: i , (159); ii, MeLi, then SOC12, py.
Scheme 61
R
R
Reagent
;
i,
I2
Scheme 6 2
378
&
Bu;Sn
B un3Sn Sn Bun3
(162)
w
-
General and Synthetic Methods
S
n
(€1 -and (Z) - (164)
(163)
M
e
OMe
3 Pd( Me C N)* C l2 m
I
OH
OH
(167)
Scheme 6 3
(175, M = Si ) (176, M = S n )
(174)
R
hSi
ii
R e a g e n t s : i, PPh,, s u n l i g h t , THF, - 7 8 ° C ; tetrafluoroborate
m
t i , [PPh,]:,
Scheme 6 4
R
-bPh,
BF4
3,5-dimethyIpyrid1nium
6: Organometallics in Synthesis
379
Tetraalkylleads (R14Pb) also undergo Pd ( 0 ) -catalysed coupling with acyl halides (RCO.Cl) to give the corresponding ketones (RCO.R1).203 Tetraalkylleads also function as stable, storable alkylating agents, reacting with aldehydes in the presence of Lewis acids such as TiC14. Where applicable, these reactions proceed with a higher degree of 1,2- and 1,3-asymmetric induction than is observed with the corresponding organozincs. 2 0 4 Allyllead, generated in situ from allylbromide, aluminium Al(0) and PbBr2, undergoes a reductive addition to N-benzylimines giving N-benzylhomoallylic amines in good yield.205 Barton and co-workers have demonstrated that PhPb(OAc)3 is a good reagent for the phenylation of aromatic and aliphatic amines when the reaction is carried out in the presence of a catalytic quantity of e.g. Cu(OAcI2. 206 5
Group U
Phosphorus.- A series of bicyclic phosphoramides e.g. (171) have been prepared from (L)-glutamic acid a,s chiral, nonracemic analogues of HMPA.207 The electrochemical coupling of diphenylchlorophosphine, Ph2PC1 (172), and alkyl or benzyl halides provides access to a range of tertiary mono- and diphosphines. For example, (172) and 1,2-dichloroethane give the diphosphine (173) and with benzyl chloride, (172) gives the benzylic derivative (174).208 Palladium(0)-catalysed coupling of arylhalides (ArX) with the silyl-and stannylsubstituted phosphines (175) and (176) provides a mild route to aryldiphenylphosphines (ArPPh2) under conditions that will tolerate the presence of a range of other functional groups.2 0 9 Nitroformyl, hydroxyl and amino groups, however, are not compatible. New approaches to the synthesis of phosphonium salts have been developed. Triphenylphosphine reacts with the alkynyliodonium salts (177) (prepared from 1-trimethylsilyl-1-alkynes), in sunlight, to give the alkynylphosphonium species (178)210 and ally1 silanes (179) with the triphenylphosphine radical cation, generated electrochemically, to give good yields of the corresponding allylphosphonium salts (180)211 (Scheme 64). The synthetic importance of the Wittig reaction and its variants is reflected again this year. The effect of high pressure
380
Geneml and Synthetic Methods
on the Wittig reaction of non-stabilized ylides and hindered ketones has been examined by Dauben.2 2 2 Successsful reactions have been carried out at 7kbar and 15kbar, but even under these conditions ketones such as finchone and 2,2,6,6-tetramethylcyclohexanone remain inert. Ring-opening of aziridines, derived from amino acids, with stabilized ylides is facile and has been effectively used to prepare optically pure unsaturated a-amino acids (Scheme 6 5 ) . 213 Cyclic and acyclic hydroxyketones undergo an accelerated Wittig reaction with stabilized ylides to give the corresponding (El-trisubstituted 214 alkenes with a high level of stereoselectivity. (Ethoxycarbonyliodomethy1)triphenylphosphonium iodide (182) reacts with aldehydes (RCHO) in the presence of K2C03 to give 8-substituted propiolic acids (RC:CC02H); the initally formed alkenyl iodide undergoes elimination of HI under these reaction conditions.215 Iodide (182) is prepared simply by treating the parent salt (181) with K2C03 and iodine in methanol. Phosphorus ylides based on the dibenzophosphole ring system react with aldehydes to give trans-disubstituted oxaphosphetanes which decompose at 70-110°C to give alkenes with good to excellent (E)-selectivity.216 A full paper has appeared on the base-induced rearrangement of vinyl phosphonates that initially appeared last year. This is a particularly useful method for obtaining cyclic ketophosphonates (183). A new synthesis of 2-formylalkyl phosphonates (184) has been described.218 Phosphonoacetate (185) undergoes facile ester exchange using N,N-(dimethylaminolpyridine (DMAP) and the corresponding acetamides may also be obtained using an amine nucleophile. 219a The value of this methodology has been illustrated in a synthesis of (-)-prenophorinwhere the key ester exchange provides (186) which is then set up to form the macrocycle by a double Horner-Wittig reaction 219b (Scheme 66). Phosphonates (187), bearing electron withdrawing substituents have been prepared by base-induced phosphonylation. The cyanoacetal (187) is a good example of the level of functionality that may be incorporated 220 (Scheme 67). Allylic phosphonates (188) react with a series of 'soft' nucleophiles (Nu), such as malonate anion, in the presence of Pd(0) to give the alkenyl phosphonates (189).221 Trialkylphosphates [(R0)3P=Ol can be directly converted to the a-lithiophosphonates (190) by treatment with two equivalents of RCH2Li.222 An earlier
6: Organometallics in Synthesis
38 1
A r = 4 -NO,C,H, Reagents: i , Ph36-
?HCOzEt,
PhMe, h e a t ; ii, (HCHO),
Scheme 6 5
+ y-
ph3pY CozEt
X
(181, Y = B r , X = H) (182, Y = I, X = I )
0
It
(P r O),P-
C02Me
R' ( 184)
(185)
I
m
U J
0
( - 1 - pyreophorin Reagents : i , (1851, DMAP ( c a t a l y t i c )
S c h e m e 66
382
Getirral arid Synthetic Method3
0
0
II
-(Eto)”pYR
R-X
X
X = CN, CO,Et,
NO,
II (E
to’2pYYo NC OMe
(187)
R e a g e n t s : i, LDA, t h e n CLPO(OEt1,
Scheme 6 7
0
0
II
II
(Eto)2pFo’2pY (R
OAc
Li
(188)
(193)
(195) R e a g e n t s ; i, N a H , ( 2 e q u i v . ) ;
ii,
FCHO~ r i i , N a H , then B u n L i Scheme 6 8
6: Organornetallies in Synthesis
383
claim that the dianion (191) can be generated by treatment of the parent phosphonate (192) with two equivalents of KH or NaH has been rejected.223 It is suggested that monodeprotonation of (192) occurs to give an equilibrating mixture of (193) and (194). Anion (193) reacts with e.g. 3-methylbutenal to give ketoester (195). The high yields previously observed for this step have been attributed to the use of the second equivalent of base to deprotonate (195) thus preventing quenching of (193). The use of NaH followed BunLi did, however, provide a source of the elusive dianion (191)(Scheme 6 8 ) . Modifications to the Wittig-Horner reaction have included the use of MgO or ZnO as a catalyst 224 and the fluoride-induced reactions of 225 a-(trialkylsily1)alkylphosphonates have also attracted attention. Chiral 1,3,2-oxazaphosphorinanes have been shown by Denmark et al.to be effective chiral auxiliaries and their application tothe -carbanion-accelerated Claisen rearrangement has been reported this year.226 Base-induced rearrangement of (196) proceeds with a high level of asymmetric induction. The conjugate addition reactions of phosphorus-stabilised anions continue to find synthetic application. The phosphonyl derivative ( 1 9 7 ) has been obtained in optically pure form, and has been used as a chiral acetaldyde enolate (Scheme 69) ; gr&- (197) is also available.227 The reactivity of (198) and 228 related species towards enones has also been investigated. Arbuzov reaction of (199) with an alkyl halide (RX) followed by reaction of the resulting phosphinate with a Grignard reagent (RlWgX) provides optically active phosphine oxides (200) in 2-45%e.e.229 Reaction of 2-butyn-1,4-diol with C1PPh2 gives, by a double 2,3-sigmatropic rearrangement, the bis (phosphineoxide)-1,3-diene (201).230 An earlier report had suggested (202) as the product of this reaction. Full details of the use of the Horner-Wittig reagents (203) and (204) in the synthesis of N-allylamines/amides have appeared231 together with a general approach to the synthesis of l-phenythio-1,3-butadienes, based on a variety of (phenylthio) substituted phosphine oxides.2 3 2 The Horner-Wittig reaction of 233 (205)has been applied to the synthesis of alkylidenecyclopropanes and barium (11) hydroxide has been shown to be an effective 234 catalyst for the sonochemical Horner-Wittig. Arsenic, Antimony and Bismuth.-
Applications of the arsenic ylides
384
I
m
H
28
Reagents. i , B u " L i ,
then
- 9 5 "loe.e.
ano
; .1 1', 03, MeZS
Scheme 69 0
R
II
Me
ph2p*
Li
+
.
r o \ 'P0 P h R0
(199)
(198)
0
II
PhP
--PPh,
II
0
0
0
II h2P-
NC 0. Ph
H (204)
p ! P h z
6: Organometallics in Synthesis
385
(206) and (207) to natural product synthesis have been reported.235 Antimony metal and allylic halides or phosphates provide reagents that allylate aldehydes in a Barbier-type process. With a , @-unsaturated aldehydes, only l12-adducts were isolated.236 Allylic halides also react with aldehydes in the presence of Bi (111)C13 and aluminium, to give homoallylic alcohols.237 Bismuth reagents have proven value as arylating agents for alcohols and mines, and Barton has published details of a series of studies that define the scope of these reagents.238
6
Grouw VI
Sulphur.- Interest in the chemistry of the Group VI elements continues unabated. Some effort has been made to divide this section on organosulphur chemistry into groups based on functional group, but some overlap has been inevitable given the multiplicity of different oxidation levels and substitution patterns that are frequently encountered. Carboxylic acids react with thexyl(pheny1thio)borane to give directly bis(pheny1thio)ketals by a reductive process. Esters react further to give the corresponding phenylsulphide. 239 Bis(phenylthio)acetals(208) are known to behave as precursors to carbenoids under appropriate conditions, and Cohen has illustrated the application of this chemistry to ring expansion leading to a- (phenylthio)ketones.240 A similar expansion of the related sulphone adducts ( 2 0 9 ) has also been described.241 The methoxy derivative (210) undergoes an analogous reaction leading to a-methoxyketones (Scheme 70). Full details of the oxidative cleavage of the (phenylthiolmethyl cycloalkanols (211) reported last year, have appeared.242 Bis (phenylthio)acetals react with Hg (11)F2 to give a-fluorosulphides that are useful precursors of the corresponding sulphoxides and vinyl fluorides.243 Alkenyl sulphides react, presumably again via a sulphonium ion, with silyl derivatives to give adducts shown in good yields (Scheme 71). a-Trimethylsilylsulphoxides and sulphides undergo a desilyative Pummerer-like reaction to give a-acetoyl o r c-halo sulphides 245 and the first examples of a sila-Pummerer reaction involving cyclopropylsulphoxides ( 2 1 1 a ) have been used to prepare
386
General and Synthetic Methods
b,.
OH S P h
ii
W
S
P
h
bS 0
- bX
... Ill
*
iv
SO2P h X
X = SPh,OMe
(209, X = S P h ) (210, X = O M e ) R e a g e n t s : i, ( P h S ) 2 C H L i ; Et2AlCI
;
i ; i , XCH SO Ph, B u n L i ( X = S P h ) , B u t L i ( X = O M e ) , 2 2
ii, B u n L i ;
iv, Et2AICl
S c h e m e 70
SPh
SPh R
R
hR'
Nu NU
Reagents:
I,
= SPh, CN, C H 2 C H = C H 2
T i c [ & , M e 3 S i N u , CH2C12
S c h e m e 71
387
6: Organometallics in Synthesis X
HSi
RYph
S-Ph Me3
II
0 (212, x = H ) (213, X = OMe)
(211a)
PhS-NnO
R' Reagents: i , h
C
l
, ZnC12;
W
i i , ( 2 1 6 , R ' = C H 2 0 M e ) , ZnCL2
Scheme 7 2
0
PPh "'rf 0 1218)
(219)
Ph'
388
General and Synthetic Methods
cyclopropanone-0,s-ketals. 245
Cyanomethylsuphides (212) undergo electrochemical oxidative methoxylation to give the methoxy adducts (213) in good yields,247 and the C-S bond of a variety of bis(pheny1thio) acetals, and other organosulphur groups, may be cleaved cathodically. 2 4 8 a-Nitrosulphides (214) serve as sulphonium ion precursors (using SnC14) and may be trapped efficiently by silyl enol ethers and allylsilanes.249 N-(Phenyl thio) morpholine (2151, in the presence of CF3S03H, functions as @SPh, and has been used to affect sulphenoethenification of w-unsaturated alcohols.250 Other aspects of this important cyclisation process involving both 0- and N-nucleophiles have been discussed.251 New syntheses of alkenylsulphides have been developed. 252 The cyclopentenyl sulphides are prepared by a (3+2) annulation process involving 1-alkynylsulphides (216)253 (Scheme 7 2 ) . This chemistry has been illustrated by a synthesis of (+)-4-epihelminthasporal (217).254 6-(Phenylsulphiny1)nitroalkenes (218) are readily available, and have found applications as alkyne equivalents in Diels-Alder processes. 255 The amidosulphoxides (219) undergo an intramolecular Pummerer-type rearrangement using ketene acetals to give 0- (phenylthio)pyrrolidines (220),255 and the asymmetric induction available in this type of conversion as applied to 6-lactams has been studied, using a chiral sulphoxide as the controlling stereocentre.2 5 7 This year has also seen new methods €or the asymmetric oxidation of ~ u l p h i d e s . ~ ~The * reagent (221) is particularly effective for the oxidation of nonfunctionalised sulphides with selectivities of up to 91% e.e. being observed;258c (S)-(221) is also available. A modification of the classical Andersen synthesis has been developed for the preparation of optically pure ( E ) - and ( Z ) alkenylsulphoxides,259 and an asymmetric synthesis of a,a-disubstituted cyclobutanones has been based on a 1,2-rearrangement of an optically active cyclopropylsulphoxide. Separation of the diastereomers (222) is not necessary, both isomers undergoing rearrangement to (223) (Scheme 73) . 2 6 0 The Horner-Wittig reaction has been applied to the synthesis of
389
6: Organometallics in Synthesis
0-
?-
I
I
D+-
I
Ar
rn
I
I **
3 : 2 mixture of isomers
I
(222) ii
Me
94 "I. e.e. R e a g e n t s : i, BunLi, t h e n PhCO.Me; i i , r e f l u x , PhH, H S
Scheme 73
0 R
h
C02Me
S03H
(226)
- RYozph - R-P S0,Ph
I
R-+
)I
PhSe
1
PhSe
iv
... Ill
R4 Reagents :
PhSe
R'
iii
d"2ph
R\//C
I, P h S 0 2 S e P h , AIBN, h e a t ; i i , Et3N; i;i, 3-CIC6H4C03H, h e a t ; iv,LDA, R'X
Scheme 7 4
I
alkenylsulphonates (224)261 and also allenylsulphones. 262
The
enolpivalate (225) undergoes an addition/elimination reaction with organocuprates to give @ ,@-substituted a l k e n y l s ~ l p h o n e s . ~ ~ ~ Stereochemical aspects of the iodosulphonization or sulfonylmercuration of alkenes and dienes have been investigated.264 This chemistry is useful for the synthesis of alkenyl-, allyl- and dienylsulphones. Isomerically pure (E)- and (Z)- ( 2 2 6 ) have been prepared. In the Diels-Alder reaction (Z)-(226) exhibits opposite regiochemistry to that observed with ( E ) - (226), thus providing a useful way of reversing the normal directing influence of an ester moiety. 226 Selenosulphonation of terminal alkynes provides the basis of a general synthesis of allenylsulphones(Scheme 74).265 The stereochemical consequences of the addition of organometallics to cyclooctenyl and cyclooctodienyl sulphones have been examined. These results are significant within the context of manipulating 8-membered rings.267 The chemistry of 2,5-dihydrothiophene-S,S-dioxides has already been mentioned (see Scheme 32). A number of other manupulations have been reported.2 6 8 These have been summarised (Scheme 75). The conversion of (227) to (228) is carried out using ultrasonically dispersed potassium. 268e Selenium and Tellurium.- The synthesis and reactivity of the crystalline aryl selenylazide ( 2 2 9 ) has been reported.269 The corresponding phenyl derivative is unstable. The application of benzeneselenyl triflate to a selenium-Polonovski reaction has been successful,270 and this reagent has also been used in the selenolactionisation of unsaturated carboxylic acids and related cyclizations of unsaturated alcohols.271 8-Hydroxyselenides (230) undergo a facile Ag(1)-promoted ring expansion with migration of the more highly substituted group being preferred. 27 Di chlorocarbene, another 'soft' electrophile will also promote this process. Alkenylselenides have been prepared from bis(methylse1eno) ketals using SnC14. The regiochemistry of the addition of benzeneselenyl chloride to electron deficientalkenes depends largely on the nature of the electron-withdrawing group274 and the addition of benzene selenol to allenes, in the presence of oxygen, gives alkenylseleni'des in good yield.275 Cyanamidoselenenylation of
6: Organometallics in Synthesis
391
dR s02
\
ref. 268c
and
n= 0,2
r e f 268d
c
b
r e f . 269f
(228)
Scheme 75
phsH
Getierul arid Synthetic Methods
392
.GR HNCN
or :CC12
/
/
R
R
(230)
A
R W R '
R OAc
L O R I #
___) 11
A/=b
Ar
R'' = Me or Ac Reagents: i, (PhTeO)20, AcOH; ii, Ph Te ( c a t a l y t i c ) , Bu'OOH, MeOH, or AcOH 2 2
S c h e m e 76
Ph
R
5
R'
- RxeHo I
NH
R'
CO, Et
R e a g e n t s : i , P h T e ( 0 ) O C O C F 3 , NH2C02Et, BF3.Et20; i i , h e a t
S c h e m e 77
R e a g e n t s : i , PhTeCL3; i i , ( P h T e 0 ) 2 0
S c h e m e 78
R
R'
H
HNKo 0
393
6: Organometallics in Synthesis
alkenes using N-phenylselenophthalimide and cyanimide leads directly to adducts (231) which have been used to prepare a variety of amine derivatives.276 Optically active selenoxides have been prepared in up to 40% e.e. by oxidation of prochiral selenides under "Sharpless" conditions. 277 Enantiomeric diary1 selenoxides may be separated by chromatographic techniques.278 Addition of phenylselenium trichloride (PhSeC13) to alkenes occurs in a stereospecific fashion. The resulting adducts may be used to prepare allylic or vinylic halides.279 New procedures have been described for the generation of NaTe, Na2Te2 and NaHTe, and the use of these powerful nucleophiles in the dealkylative cleavage of esters has been investigated.280 Benzenetellurinic anhydride, (PhTeO)ZO, reacts with alkenes in acetic acid to give 1,2-diacetates,281 and diarylditellurides can be used in a catalytic fashion to achieve a similar transformation Benzenetel lurium iodide (PhTeI) with styrenes 2 8 2 (Scheme 76 ) reacts efficiently with the lithium enolates of ketones and esters to give the corresponding a-phenyltelluryl derivatives.283 The dialkyl telluronium ylides (232) and is readily generated from dibutyl telluride and an a-haloester,nitrile, or ketone, and react with aldehydes to give the corresponding a,@-unsaturated derivatives. 284 Phenyltel lurinyl trifluroracetate reacts with alkenes in the presence of H NCO2Et leading to cyclic carbanates in high yield via adducts (233)385(Scheme 77) . Phenyltellurium
.
trichloride (PhTeC13) triggers the cyclisation of unsaturated alcohols286 and a related transformation can be achieved using (PhTeO) 2 8 7 (Scheme 78).
394
Grwerul arid Synthetic Methods References
1 2 3 4 5
6 7
8 9
10 11 12 13 14 15 16
17 18 19 20 21 22 23 24 25 26 27
26,
M a e r c k e r , Angew. Chem., I n t . E d . E n g l . , 1 9 8 7 , 973. Y o s h i f u j i , T. Nakamura, a n d N . I n a m o t o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 3 2 5 . H . O e h m e a n d H . Weiss, J . O r g a n o m e t a l , Chem., 1 9 8 7 , (216. B.M. T r o s t , J . F l o r e z , a n d D . J . J e b o r a t n a m , J . Am. Chem. SOC., 1987, 613. H . Uno, Y . S h i r a i s h i , K . S i m o k a w a , a n d H . S u z u k i , C h e m i s t r y L e t t . , 1987, 1153. I . E . K o p k a , S.A. F a t a f t a h , a n d M . W . R a t h k e , J . O r g . Chem., 1 9 8 7 , 52, 4 4 8 . C.M. C a i n a n d N.S. S i m p k i n s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 3, 3723. L . D u h a m e l , A. R a v a r d , J . C . P l a q u e v e n t , a n d D . D a v o u s t , 5517. Tetrahedron L e t t . , 1987, ( a ) A . A n d o a n d T . S h i o i r i , J . Chem. S O C . , Chem. Commun., 1987, 656. ( b ) A.C. Regan a n d J. S t a u n t o n , i b i d , 1 9 8 7 , 5 2 0 . A . Ando a n d T . S h i o i r i , J . Chem. S O C . , Chem. C o r n . , 1 9 8 7 , 1620. G.W. S p e a r s , G.E. C a u f i e l d , a n d W.C. S t i l l , J . O r g . Chem., 1987, 52, 1226. E . E i n h o r n a n d J . L . L u c h e , J . O r g . C h e m . , 1 9 8 7 , 52, 4 1 2 4 . G.E. E r i c k s o n a n d J . L . F r y , J . O r g . C h e m . , 1 9 8 7 , 52, 4 6 2 . T . H i i r o , N . K a m b e , A . O g a w a , N . M i y o s h i , S . M u r a i a n d N. S o n o d a , Angew. C h e m . , I n t . E d . E n g l . , 1 9 8 7 26, 1 1 8 7 . R . K . D i e t e r a n d J . R . F i s h p a u g h , J . O r g . Chem., 1 9 8 7 , 52, 923. ( a ) J . B a r l u e n g a , C. R u b i e r a , J . R . F e r n a n d e z , a n d M . Y u s , J. Chem. SOC., Chem. Commun., 1 9 8 7 , 4 2 5 . ( b ) J. B a r l u e n g a , J . R . F e r n a n d e z , a n d M. Yus, i b i d , 1 9 8 7 , 1534. J . B a r l u e n g a , C. R u b i e r a , J . R . F e r n a n d e z , J . F l o r e z a n d M . Yus, S y n t h e s i s , 1 9 8 7 , 8 1 9 . J. Barluenga, J . L . Fernandez-Simon, J . M . C o n c e l l o n , a n d M. Yus, S y n t h e s i s , 1 9 8 7 . 5 8 4 . W.F. B a i l e y , T . T . N u r m i , J . J . P a t r i c i a , a n d W . Wang, J . Am. Chem. S O C . , 1 9 8 7 , 2442. A . K r i e f a n d P . B a r b e a u x , , J . C h e m . S O C . , Chem. Commun., 1987, 1214. M.P. C o o k e J r . , a n d R . K . W i d e n e r , J . O r g . Chem., 1 9 8 7 , 5 2 , 1 3 8 1 . E. E p i f a n i , S. F l o r i o , a n d G . I n g r o s s o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 3 8 5 . M.F. S e m m e l h a c k a n d E . J . F e w k e s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1497. ( a ) P . B e a k , J . E . H u n t e r , Y . M . J u s , a n d A . P . W a l l i n , J . Am. Chem. S O C . , 1 9 8 7 , 109, 5 4 0 3 . ( b ) P . B e a k a n d K . D . W i l s o n , J . O r g . C h e m . , 1 9 8 7 , 52, 2 1 8 . P . E . E a t o n , G.T. C u n k l e , G . M a r c h i o r o , a n d R . M . M a r t i n , J . A m . Chem. S O C . , 1 9 8 7 , 948. F o r d i r e c t d e p r o t o n a t i o n of c y c l o p r o p y l amides see: P . E . E a t o n , R . G . D a n i e l s , D . C a s u c c i , a n d G.T. C u n k l e , J . O r g . Chem., 1 9 8 7 , 5 2 , 2 1 0 0 . D.L. C o m i n s a% M . O . K i l l p a c k , J . O r g . Chem., 1 9 8 7 , 52, 1 0 4 . A. M.
2,
109,
28,
109,
109,
6: Organometallics in Synthesis 28 29 30 31 32 33
34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49
50 51 52 53 54 55
395
C h e m and M . P . C a v a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 6 0 2 4 . K . A . P a r k e r a n d K.A. K o z i s k i , J . O r g . C h e m . , 1 9 8 7 5 2 , 6 7 4 . J. B a r l u e n g a , J.L. F e r n a n d e z - S i m o n , J . M . C o n c e l l o n , a n d M. Y u s , J . C h e m . SOC., C h e m . C o m m u n . , 1 9 8 7 , 9 1 5 . A . R . K a t r i t s k y a n d S . S e n g u p t a , T e t r a h e d r a n L e t t . , 1 9 8 7 , 28, 1847. T . C u v i g n y , M. J u l i a , L . J u l l e n , a n d C . R o l a n d o , T e t r a h e d r o n L e t t . , 1987, 2587. ( a ) P . J . G a r r a t t and J . P . P o r t e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 351; ( b ) P . J . G a r r a t t , M. P i e l k e , and J . P . P o r t e r , i b i d , 1 9 8 7 , 28, 589. P . C o r n w a l l , C . P . D e l l , a n d D.W. K n i g h t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 5 8 5 . R.C.F. Jones a n d A . D . B a t e s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1565. A . M a e r c k e r , T . G r a u l e , a n d W. D e m u t h , A n g e w . C h e m . , I n t . E d . E n g l . , 1 9 8 7 , 26, 1 0 3 2 . B.-A. F e i t , B. H a a g , and R . R . S c h m i d t , J. O r g . C h e m . , 1 9 8 7 , 52, 3825. P.A.A. K l u s e n e r , W . K u l i k , and L . B r a n d s m a , J . O r g . C h e m . , 1987, 52, 5261. S . K . R i c h a r d s o n , A . J e g a n a t h i a n , and D . S . W a t t , T e t r a h e d r o n L e t t . , 1987 2335. C . N a j e r a and M. Y u s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 6709. M.A. T i u s , D . P . A s t r a b , and X . G u , J . O r g . C h e m . , 1 9 8 7 , 52, 2625. R . R . S c h m i d t , R . P r e u s s , and R . B e t z , Tetrahedron L e t t . , 1 9 8 7 , 28, 6591. L . D u h a m e l , P . D u h a m e l , a n d J . P . Lecouve, T e t r a h e d r o n 1 9 8 7 , 4 3 , 4 3 3 9 and 4 3 4 9 . P . G . M c D o u g a l a n d J . G . R i c o , ________ J . O r g . C h e m . , 1 9 8 7 , 52, 4 8 1 7 . E . N e g i s h i , Y. Z h a n g , and V . B a g h e r i , Tetrahedron L e t t . , 1 9 8 7 , 28, 5 7 9 3 . T . N . M i t c h e l l and W . R e i m a n , J . O r g a n o m e t a l . C h e m . , 1 9 8 7 , 322, 141. T . N . M i t c h e l l and W. R e i m a n , J. O r g a n o m e t a l . C h e m . , 1 9 8 7 , 322, 151. R . M a t s u o k a , Y . H o r i g u c h i , and I . K u w a j i m a T e t r a h e d r o n L e t t . , 1987, 28, 1299. ( a ) D T H o p p e and C. G o n s c h o r r e k , Tetrahedron L e t t . , 1 9 8 7 , 28, 785. ( b ) E . E g e r t , H B e c k , D S c h m i d t , C . G o n s c h o r r e k , and D. H o p p e , I b i d , 1 9 8 7 , 28, 7 8 9 . T . C o h e n , W.D. A b r a h a m , and M. M y e r s , J . Am. C h e m . S O C . , 1987, 7923. T. Sato, S. O k u r a , J . O t e r a , and H . N o z a k i , Tetrahedron L e t t . , 1 9 8 7 , 28, 6 2 9 9 . A . R . K a t r i t s k y , J . M . A u r r e c o e c h e a , a n d L.M. V a z q u e z de M i g e l , J . C h e m . S O C . , P e r k i n T r a n s . l., 1 9 8 7 , 7 6 9 . A . R . K a t r i t s k y , W . K u z m i e r k i e w i c z , a n d J.M. A u r r e c o e c h e a , J. O r g . C h e m . , 1 9 8 7 , 52, 8 4 4 . S . V a l v e r d e , S. G a r c i a - O c h o a , M. M a r t i n - L o m a s , J . C h e m . SOC., C h e m . C o m m u n . , 1 9 8 7 , 3 8 3 . S . H u n i g , N. K l a u n z e r , and R . S c h l u n d , A n g e w . C h e m . , I n t . E d . E n g l . , 1 9 8 7 , 26, 1 2 8 1 . W.
28,
28,
109,
28,
Generul und Synthetic Methods
396 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75
76
77 78 79
80 81
J.-M.
F a n g , B.-C.Hong,
a n d L.-F.
L i a o , J. O r g . C h e m . ,
52, 855. -
1987,
( a ) P.C.B. P a g e , M.B. van N i e l , a n d D . W e s t w o o d , J. Chem. S O C . , Chem. Commun., 1 9 8 7 , 7 7 5 ; (b) P.C.B. P a g e , a n d M.B. v a n N i e l , i b i d , 1 9 8 7 , 4 3 . K . N a k a m u r a , M . H i g a k i , S . Adachi, S . O k a , a n d A . O h n o , J. O r g . C h e m . , 1 9 8 7 52, 1 4 1 4 . D . H . Hua, S. V e n k a t a r a m a n , M . J . C o u l t e r , a n d G . S i n a i - Z i n g d e , J . Org. Chem., 1 9 8 7 , 52, 7 1 9 . ( a ) R . T a n i k a g a , K . Hosoya, K . Hamamura, a n d A . K a j i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 7 0 5 . (b) T . S a t o , T . Hoh, a n d T . F u j i s a w a , I b i d , 1 9 8 7 , 2 8 , 5 6 7 7 . S. H o u s e , P.R. J e n k i n s , J . F a w c e t t a n d D . R . Russell,& Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 8 4 4 . K . J . Hwanq, E.W. L o q u s c h , L.H. B a n n i g a n , a n d M.R. T h o m p s o n , J . O r g . Chem., 1 9 8 7 , 52, 3 4 3 5 . K . F u j i , M . Node, Y . U s a m i , a n d Y . K i r y n , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 4 4 9 . F . B e n e d e t t i , S. F a b r i s s i n , J . G i a n f e r r a r a , a n d A . R i s a l i t i , J . Chem. S O C . , C h e m . Commun., 1 9 8 7 , 4 0 6 . J . C . Carretero, S. Dehombaert, a n d L. G h o s e z , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2 1 3 5 . C.M. T h o m p s o n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 4243. A . P a d w a , W.H. B u l l o c k a n d A . D . D y s z l e w s k i T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 1 9 3 . G . D . H a r t m a n a n d W . H a l c z e n k o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3241. N.S. Simpkins, T e t r a h e d r o n L e t t . , 1987, 28, 989. M. Y a m a m o t o , K . S u z u k i , S. T a n a k a , a n d K T Y a m a d a , B u l l . Chem. S O C . J p n . , 1 9 8 7 . 60, 1 5 2 3 . S . Yamada, H . S u z u k i , H . N a i t o , T . N o m o t o , a n d H . T a k a y a m a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 3 3 2 . H.-H. TSO, T . C h o u , a n d W.C. L e e , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 9 3 5 . F . B i c k e l h a u p t , Angew. Chem., I n t . E d . E n g l . , 1 9 8 7 , 2 6 , 9 9 0 . T . P . B u r n s a n d R . D . R i e k e , J . O r g . C h e m . , 1 9 8 7 , 52 3 6 7 4 . ( a ) R.M. Wehmeyer a n d R . D . R i e k e , J . O r q . Chem., 1 9 8 7 , 52, 5056. ( b ) T.-C. Wu, R.M. Wehmeyer, a n d R . D . R i e k e , I b i d , 1 9 8 7 , 52, 5057. ( a ) K . T o m i o k a , M . N a k a j i m a a n d K . Koga, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 2 9 1 . ( b ) K . T o m i o k a , M . N a k a j i m a , a n d K . Koga, C h e m i s t r y L e t t . , 1987, 65. K . T a k a n i s h i , H . Urabe, and I . K u w a j i m a , T e t r a h e d r o n L e t t . , 1987, 28, 2281. W.H. B u n n e l l e , M . A . R a f f e r t y , a n d S . L . Hodges, J . O r g . Chem., 1 9 8 7 , 52, 1 6 0 3 . ( a ) S. Wadman, R . W h i t b y , C. Yeates, P . K o c i e n s k i , a n d K . Cooper, J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 4 1 . ( b ) R . W h i t b y , C. Yeates, P . K o c i e n s k i , a n d G . C o s t e l l o , i b i d , 1987, 429. Z . J . N i a n d T.Y. L u h , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 1515. N. Furukawa, T. S h i b u t a n i , a n d H. F u j i h a r a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28 5 8 4 5 .
28,
397
6: Organometallics in Synthesis 82 83 84 85 86 87 88 89
E. E r d i k , T e t r a h e d r o n , 1 9 8 7 , 43, 2 2 0 3 . P i c o t i n a n d P . M i g i n i a c , J. O r g . Chem, 1 9 8 7 , 5 2 , 4 7 9 6 . Yokozawa, N . I s h i k a w a a n d T. N a k a i , C h e m i s t r y x e t t . , 1 9 8 7 , 1970. E. N a k a m u r a , S . A o k i , K . S e k i y a , H. O s h i n o , a n d I . K u w a j i m a , J . Am. Chem. S O C . , 1 9 8 7 , 109, 8 0 5 6 . Y . Tamaru, H. O c h i a i , T. Nakamura, a n d Z . Y o s h i d a , Angew. Chem. I n t . E d . E n g l . , 1 9 8 7 26, 1 1 5 7 . M . M . H a n s e n , P.A. B a r t l e t t a n d C.H. H e a t h c o c k , O r g a n o m e t a l l i c s , 1987, 6 , 2069. K . Y a m a m o t o , M. K a n o h , i. Yamamoto, a n d J . T s u j i , T e t r a h e d r o n L e t t . . 1 9 8 7 ,. 2 8 ., 6 3 4 7 . ( a ) K . S o a i , A Ookawa, K . O g a w a , a n d T . Kaba, J . C h e m . S O C . , Chem. Commun., 1 9 8 7 , 4 6 7 ; ( b ) K . S o a i , S . Yokayama, K . E b i h a r a , a n d T . H a y a s a k a , i b i d , 1987, 1690; (c) S . I t s u n o a n d J . M . J . F r e c h e t , J . Org. Chem., 1 9 8 7 , 52, 4140; (d) K . S o a i a n d A . Ookawa, T . Kaba a n d K . O g a w a , J . Am. Chem. S O C . , 1 9 8 7 , 109, 7 1 1 1 ; (el P.A. C h a l o n e r a n d S.A.P. P e r e r a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 0 1 3 ; (f) K . S o a i , S . N i w a , Y . Yamada, a n d H . I n o u e , i b i d , 1 9 8 7 , 28, 4841; ( g ) E . J . C o r e y a n d F . J . Hannon, i b i d , 1 9 8 7 , 5233, and 5237; ( h ) G . Muchow, Y . V a n n o o r e n b e r g h e , a n d G . B u o n o , i b i d , 1 9 8 7 , 28, 6 1 6 3 ; (i) K. S o a i , M. N i s h i , a n d Y. I t o , C h e m i s t r y L e t t . , 1987, 2405; (j) A . A . S m a a r d i j k a n d H . W y b e r g , J . O r g . Chem., 1 9 8 7 , 52, 135. J . B a r l u e n g a , J . M . M a r t i n e z - G a l l o , C. Najera, a n d M. Y u s , S y n t h e s i s , 1987, 582. R . C . L a r o c k , L.D. B u r n s , S . V a r a p a t h , C . E . R u s s e l l , J.W. R i c h a r d s o n J r . , M.N. J a n a k i r a m a n , a n d R.A. J a c o b s o n , Organometallics, 1987, 5 , 1780. R . C . L a r o c k , D . J . L e n c k , a n d L.W. H a r r i s o n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 9 7 7 . K.-M. C h e n , K . G . G u n d e r s o n , G.E. H a r d t m a n n , K . P r a s a d , 0. R e p i c , a n d M.J. S h a p i r o , C h e m i s t r y L e t t . , 1 9 8 7 , 1 9 2 3 . C. N a r a y a n a a n d M . P e r i a s a m y , J . O r g a n o m e t a l . Chem., 1 9 8 7 , 323, 145. Y . G u i n d o n , M. T h e r i e n , Y . G i r a n d , a n d C. Y o a k i m , J . Org. Chem., 1 9 8 7 , 52, 1 6 8 0 . ( a ) H.C. B r o w n , M.M. M i d l a n d , A.B. L e v y , A. S u z u k i , S . Sono, a n d M. I t o h , T e t r a h e d r o n , 1987, 43, 4079; ( b ) R . C a r b o n i , M . V a u l t i e r , a n d R . C a r r i e , i b i d , 1 9 8 7 , 43, 1799. H.C. Brown a n d M . M . M i d l a n d , T e t r a h e d r o n , 1 9 8 7 , 4 3 , 4 0 5 9 . K i m , M . S r e b n i k , a n d B. S i n g a r a m , H.C. B r o w n , K.-W. T e t r a h e d r o n , 1 9 8 7 , 43, 4 0 7 1 . D.J. N e l s o n , P . J . Cooper, a n d J . M . Coerver, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 9 4 3 . M . S r e b n i k , T.E. C o l e , and H-C Brown, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 7 7 1 . G. T.
28,
90 91 92 33 94 95 96
97 98 99 100
101 102 103 104 105 106 107 108 109
110 111 112 113
114 115 116 117
119 120
C.T. G o r a l s k i , B . S i n g a r a m , a n d H . C . B r o w n , J . O r g . Chem., 1987, 52, 4014. H.C. Brawn, J . V . N . V . P r a s a d , A . K . G u p t a , a n d R . K . B a k s h i , J. O r g . Chem., 1 9 8 7 , 5 2 , 3 1 0 . J. HOOZ, J . O u d e n e z J . L . Roberts, a n d A. B e n d e r s l y , J. O r g . Chem., 1 9 8 7 , 5 2 , 1 3 4 7 . R.P. S h o r t a n d S. E s a m u n e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2841. F o r a g e n e r a l d i s c u s s i o n see: H.C. B r o w n , W.S. P a r k , B.T. C h o , a n d R . V . R a m a c h a n d r a n , J . O r g . Chem., 1 9 8 7 , 52, 5 4 0 6 . H . C . Brown, M.V. R a n g a i s h e n v i , a n d A . S . R a c h e r l a , J . O r g . Chem.. 1 9 8 7 .. 5 2 ., 7 2 8 . N . M . Yoon a n d K . E . K i m , J . O r g . C h e m . , 1 9 8 7 , 52, 5 5 6 4 . H . C . B r o w n , B.T. C h o , a n d W.S. P a r k , J . O r g . Chem., 1 9 8 7 , 52, 4020. ( a ) E . J . C o r e y , R . K . R a k s h i , a n d S . S h i b a t a , J . Am, Chem. S O C . , 1 9 8 7 , 109, 5 5 5 1 ; ( b ) E . J . C o r e y , C.-P. C h e n , a n d V . K . S i n g h , i b i d , 1 9 8 7 , 109, 7925; ( c ) S . I t s u n o , Y . S a k u r a i , K . I t o , A . Hirao, a n d S . N a k a h a m a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60. 3 9 5 . D . S . M a t t e s o n a n d E.C. B e e d l e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4499. H . C . Brown, M . S r e b n i k , R . K . B a k s h i , a n d T . E . C o l e , J . Am. Chem. S O C . , 1 9 8 7 , 5420. H . C . Brown a n d M. S r e b n i k , O r g a n o m e t a l l i c s , 1 9 8 7 , 5, 6 2 9 . S . H y u g a , Y . C h i b a , N . Y a m a s h i n a , S . Hara, a n d A . S u z u k i , Chemistrv L e t t . . 1987. 1757. T. Ishiyama, N. Miyaura, and A. Suzuki, Chemistry L e t t . , 1987, 25. R.W. H o f f m a n n a n d A . E n d e s f e l d e r , L i e b i g s Ann. C h e m . , 1 9 8 7 , 215. R.W. H o f f m a n n , R M e t t e r n i c h , a n d J . W . L a n z , L i e b i g s Ann. Chem., 1 9 8 7 , 8 8 1 . M . V a u l t i e r , F . T r u c h e t , B . C a r b o n i , R.W. H o f f m a n n , a n d I . D e n n e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 1 6 9 . ( a ) W.R. R o u s c h , A . D . P a l k o w i t z , a n d M . A . J . P a l m e r , J . O r g . Chem., 1 9 8 7 , 52, 3 1 6 ; ( b ) H.C. Brown, K . S . B h a t , a n d R . S R a n d a d , i b i d , 1 9 8 7 , 52, 319. ( c ) H . C . B r o w n , K . S . B h a t , a n d R . S . R a n d a d , i b i d , 1 9 8 7 , 52, 3701. J . G a r c i a , B.M. K i m , a n d S . M a s a m u n e , J . O r g . Chem., 1 9 8 7 , 52, 4831. K P . C o o k e J r . , a n d R . K . W i d e n e r , J . Am. Chem. S O C . , 1 9 8 7 , 1 0 9 ,. 9 3 1 . ~~. A . P e l t e r , D . BUSS, a n d E . C o l c l o u g h , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 9 7 . K . Maruoka, K . N o n o s h i t a , a n d H. Y a m a m o t o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 7 2 3 . ( a ) R. M e n i c a g l i , C . M a l a n g a , M . G u i d i , a n d L . L a r d i c c i , Tetrahedron, 1987, 43, 171; (b) R. M e n i c a g l i , M a l a n g a , M. D e l l ' I n n o c e n t i , a n d L. L a r d i c c i , J . O r g . Chem., 1 9 8 7 , 5 2 , 5 7 0 0 . E . N e g i s h i , T . T a k a h a s h i , S . B a b i , D.E. v a n H o r n e , a n d N . O k u k a d o , J . Am. C h e m . S O C . , 1 9 8 7 , 109, 2 3 9 3 .
28,
~
2,
~~~~
121 122 123
c.
124
6: Organometallics in Synthesis 125 126
127 128
129 130 131 132 133 134
135 136 137 138
139 140
141 142
143 144
145 146
399
Pecunioso a n d R. M e n i c a g l i , T e t r a h e d r o n , 1987, 43, 5411. ( a ) T . T s u d a , H . S a t o m i , T . H a y a s h i , a n d T . S a e g u s a , J. O r g . Chem., 1 9 8 7 , 52, 4 3 9 ; ( b ) T. T s u d a , T. Y o s h i d a , T. K a w a m o t o , a n d T. S a e g u s a , J. O r g . Chem., 1 9 8 7 , 52, 1 6 2 4 . N. F u j i i , A. O t a k a , S. Funakoski, K . Bessho, a n d H . Y a j i m a , J . Chem. S o c . , Chem. Commun., 1 9 8 7 , 1 6 3 . ( a ) P . M a g n u s , P.M. C a i r n s , a n d J . M o u r s o u n i d i s , J . A m e r . Chem. S O C . , 1 9 8 7 , 109, 2 4 6 9 ; ( b ) J . B . L a m b e r t , G . Wang, R . B . F i n z e l , a n d D . H . T e r a m u r a , i b i d , 1 9 8 7 , 109, 7 8 3 8 . A . Hosomi, K . H o a s k i , Y . T o m i n a q a , K . O t a k a , a n d H . S a k u r a i , J . O r g . Chem., 1 9 8 7 52, 2 9 4 7 . a n d Y . I t o , J . Chem. S O C . , T . H a y a s h i , A . Y a m a n o t o , T . Iwata, Chem. Commun., 1 9 8 7 , 3 9 8 . T.K. S a r k a r a n d S.K. G h o s h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2061. A.T. R u s s e l a n d G . P r o c t o r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 2041. L. Coppi, A. R i c c i , a n d M. T a d d e i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28 , 9 6 5 . ( a ) K . K . Wang a n d K.E. Y a n g , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1003: ( b ) K . K . Wang a n d S . D h u m r a n g u a r a p o r i n , i b i d , 1 9 8 7 , 28, 1007. C. N a t i v i , A . R i c c i , a n d M. T a d d e i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28 , 2751. I . F l e m i n g , A . K . S a r k a r , a n d A . P . T h o m a s , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 5 7 . J . S . P a n e k a n d M.A. S p a r k s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4649. ( a ) M. H a y a s h i a n d T. M u k a i y a m a , C h e m i s t r y L e t t . , 1 9 8 7 , 289: ( b ) M. M u r a k a m i , T . Kato, a n d T. M u k a i y a m a , i b i d , 1 9 8 7 , 1167. M. K i r a , M. K o b a y a s h i , a n d H . S a k u r a i , , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4 0 8 1 . A . H o s o m i , S . K o h r a , a n d Y . T o r n i n a g a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 5 1 7 . T. Mukaiyama, M. Ohshima, a n d N . M i y o s h i , C h e m i s t r y L e t t . , 1987, 1121. ( a ) C . K u r o d a , S . S h i m i z u , a n d J . Y . S a t o h , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 8 6 ; ( b ) K . N i s h i t a n i a n d K . Yamakawa, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 655. I . F l e m i n g , N . D . K i n d o n , and A . K . S a r k a r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 9 2 1 . ( a ) P.A. Grieco a n d W . F . F o b a r e , J . Chern. S O C . , Chem. Commun., 1 9 8 7 , 1 8 5 ; ( b ) H . H . M o o i w e e r , H . H i e m s k r a , H.P. F o r t q e n s , and W.N. S p e c k a m p , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 2 8 5 . ( c ) D.Damour, J . P o r n e t , a n d L . M i g i n i a c , i b i d , 1 9 8 7 , 28, 4689. A . H o s o m i , J . H o a s h i , S. K o h r a , Y . T o m i n a g a , K . O t a k a , a n d H . S a t u r a i , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 5 7 0 . ( a ) G . A . M o l a n d e r a n d D.C. S c h u b e r t , J . Amer. Chem. S O C . , A.
1987, 109, 576; 147
109,
G X M o l a n d e r a n d D . C . S c h u b e r t , i b i d , 1987, 6877. B . M . T r o s t a n d P.R S e o a n e , J . A m e r . Chem. S O C . , 1987,
(b) (a)
109, 615; 148 149 150 151 152
109,
( b ) B.M. T r o s t a n d D . T . M a c P h e r s o n , i b i d , 1987, 3483. M . A r i m o t o , H. Yamaguchi, a n d E . F u g i t a , T e t r a h e d r o n L e t t . ,
1987, 28, 6289. K. Wakamatsu, K. Oshima a n d K . U t i m o t o , C h e m i s t r y L e t t . , 1987, 2029. K . Tamao, E . N a k a j o , a n d Y . I t o J . O r g . Chem., 1987, 52, 957. R.F. H o r v a t h a n d T.H. C h a n , J . O r g . Chem., 1987, 28, 4489. (a)
N.
Shimizu,
F.
S h i b a t a , and Y .
Tsuno, B u l l .
Chem. SOC.
1987, 60, 777; ( b ) K. T a k a i , Y . K a t a o k a , T O k a z o e , a n d K . U t i m o t o , T e t r a h e d r o n L e t t . , 1987, 28, 1443; ( c ) Y . H a t a n a k a a n d T. Hiyama, i b i d , 1987, 28, 4715; Jpn.,
153
154
155 156 157 158
( d ) J . B a r l u e n g a , J . M . M a r t i n e z - G a l l a , G. N a j e r a , and M. Yus, J . Chem. S O C . , P e r k i n T r a n s l., 1987, 1017. ( a ) K. Tamao, M . A k i t a , K Maeda, a n d M . Kumada, J . O r g . Chem., 1987, 12, 1100; ( b ) K . I k e n a g a , K . Kikukawa, a n d T. M a t s u d a , i b i d , 1987,
52, -
1276.
( a ) C . J . F l a n , T . C . M a l o n e , a n d L . E . Overman, J . A m e r . Chem. S O C . , 1987, 6097; ( b ) S . F . McCann a n d L . E . Overman, i b i d , 1987, 109, 6107; ( c ) C . J . F l a n a n d L . E . Overman, i b r 1 9 8 7 , 109,6115. J . v a n d e r Louw, J . L . v a n d e r B a a n , F . B i c k e l h a u p t , a n d G.W. Klumpp, T e t r a h e d r o n L e t t . , 1987, 2889. I . F l e m i n g , K . T a k a k i , a n d A.P. Thomas, J . Chem. S O C . , P e r k i n Trans’. 1.. 1987. 2269. T . H . Chan, Q . - J . P e n g , D . Wang, a n d J . A . Guo, J . Chem. SOC., Chem. Commun., 1987, 325. C . R . J o h n s o n a n d T . J . M a r r e n , T e t r a h e d r o n L e t t . , 1987,
109,
28,
28,
17
L I .
159 160 161 162
E . K e i n a n a n d D . P e r e z , J . O r g . Chem., 1987, 52, 4846. K. S u k a t a , B u l l . Chem. S O C . J p n . , 1987, 60, 2 x 7 . K. Mai a n d G . P a t i l , J . O r g . Chem., 1987752, 275. Y . I t o , S. N i s h i m u r a , a n d M . I s h i k a w a , T e t r a h e d r o n L e t t . , 1987, 28, 1293.
163
T.M. B a r g a r , J . R . McCowan, J . R . M c C a r t h y , a n d E . R . Wagner, J . O r g . Chem., 1987, 52, 678. C . R . J o h n s o n a n d B . D . T a i t , J . O r g . Chem., 1987, 52, 281. B . A . Narayanam a n d W . H . B u n n e l l e , T e t r a h e d r o n L e t t . , 1987,
164 165 166
28, 6261. A.R.
K a t r i t z k y and S. Sengupta,
Tetrahedron L e t t . ,
1987,
28,
5419. 167 168
M. M.
F u j i t a a n d T . Hiyama, T e t r a h e d r o n L e t t . , 1987, 28, 2263. K . S a t o , a n d H . S a k u r a i , J . O r g . Chem., 1987, 52,
Kira,
948. 169
170
(a)
K.
Tamao, T .
Yamauchi,
and Y.
I t o , Chemistry
Lett.,1987, 171; ( b ) V.J. Eddy a n d J . E . H a l l g r e n , J . O r g . Chem., 1987, 52, 1903. I. F l e m i n g a n d N . D . K i n d o n , J . Chem. S o c . , Chem. Commun., 1987, 1177. See a l s o : I. F l e m i n g , N . L . Reddy, K . T a k a k i , a n d A . C . Ware, i b i d , 1987, 1472.
6: Organometallics in Synthesis 171 172 173 174 175
401
28,
M . A s a o k a a n d €3. T a k e i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 6343. M. Asoaka, K . Shima, a n d H . T a k e i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5669. P.A. B r o w n , R.V. B o n n e r t , P . R . J e n k i n s , a n d M . R . S e l i m , 693. Tetrahedron L e t t . , 1987, 5729. M.P. C o o k e J r . , J. O r g . C h e m . , 1 9 8 7 , ( a ) J . Yoshida a n d S . I s o e , C h e m i s t r y L e t t . , 1 9 8 7 , 6 3 1 ; ( b ) J . Y o s h i d a , T . Mirata, a n d S . Isoe, T e t r a h e d r o n L e t t . , 1987, 28, 211; ( c ) J T Y o s h i d a and S . I s o e , i b i d , 1 9 8 7 , 6621; (d) I. Fleming and P.E.J. Sanderson, Tetrahedron L e t t . , 1 9 8 7 , 28, 4 2 2 9 ; D . E n d e r s a n d B.B. L o h r a y , Angew. C h e m . I n t . E d . E n g l . , 351. 1987, A. R i c c i , A. D e g l ' I n n o c e n t i , G. B o r s e l l i , a n d G. R e g i n a t o , T e t r a h e d r o n L e t t . , 1987, 28, 4093. P.C.B. P a s e . S . R o s e n t h a l T a n d R . V . W i l l i a m s . T e t r a h e d r o n L e t t . , 1 9 8 7 ; 28, 4 4 5 5 . . S.M. M o e r l e i n , J. O r g . Chem., 1 9 8 7 , 52, 6 6 4 . ( a ) Y . I c h i n o s e , K . N o z a k i , K . Wakamatsu, K . O s h i m a , and K. U t i m o t o , Tetrahedron L e t t . , . 1987, 3709; ( b ) Y . I c h i n o s e , H . Oda, K . O s h i m a , a n d K . U t i m o t o , B u l l . Chem. SOC. J p n , 1 9 8 7 , 60, 3 4 6 8 . S . K i y o o k a , F . S h i o t a , a n d T . S h i b u y a , C h e m i s t r y Lett., 1987, 495. " T i n i n O r g a n i c s y n t h e s i s " , by M , P e r e y n e , J . - P . Q u i n t a r d a n d A. Rahm, B u t t e r w o r t h s , London, 1 9 8 7 . W.P. Neuman; S y n t h e s i s , 1 9 8 7 , 6 6 5 : M. B a r t r a , F. U r p i , a n d J. Vilarrasa, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 9 4 1 . ( a ) K . N o z a k i , K . O s h i m a , a n d K . U t i m o t o , J . Amer. Chem. SOC., 1987, 2547. (b) G . S t o r k a n d R . Mook, i b i d , 1 9 8 7 , 2829; F o r o t h e r r o u t e s t o a l k e n y l s t a n n a n e s see r e € 1 8 0 b a n d J . G . D u b o u i n , M R a t i e r , a n d B . T r o u v e , J . O r g a n o m e t a l . Chem., 181. 1987, T.N. M i t c h e l l , R . W i c k e n k a m p , A . A m a m r i a , R . D i c k e , a n d U . S c h n e i d e r , J . O r g . Chem., 1 9 8 7 , 52, 4 8 4 6 . E . P i e r s a n d R . T . S k e r l j , J . Chem. S O C . , C h e m . Commun., 1987, 1025. I. Ryn, H . S u z u k i , S . M u r a i , a n d N. S o n o d a , O r g a n o m e t a l l i c s , 1987, 6 , 212. A . D u c E e n e a n d J . - P . Q u i n t a r t , J . Chem. S o c . , Chem. Commun., 1987, 29. C . N a t i v i , M . T a d d e i , a n d A . Mann, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 347. R. Y a m a g u c h i , M . M o r i y a s u , I . T a k a s e , M. K a w a n i s i , a n d S . K o s i m a , Chemistry L e t t . , 1987, 1519. T . T a k e d a , H . O s h i m a , M . I n o u e , A . T o g o , a n d T. F u j i w a r a , Chemistry L e t t . , 1987, 1345. C.R. J o h n s o n a n d J . F . K a d o w , J . O r g . Chem., 1 9 8 7 , 52, 1 4 9 3 . B . J o u s s e a u m e a n d P . V i l l e n e u s e , J . Chem. S o c . , C h e m . Commun., 1 9 8 7 , 5 1 3 . D.L. C o m i n s a n d N . B . M a n t l o , T e t r a h e d r o n L e t t . , 1 9 8 7 , 759. ( a ) T. T a b u c h i , J. I n a n a g a , a n d M. Yamaguchi, T e t r a h e d r o n
28,
2,
28,
176 177 178 179 180
181 182 183 184 185
26,
28,
109,
109,
331,
186 187 188 189 190 191 192 193 194 195 196
28,
General and Synthetic Methods
402
197 198 199
L e t t . , 1987, 28, 215; (b) T. T a k e d z S . O g a w a , N . O h t a , a n d T. F u j i w a r a , Chemistry L e t t . , 1987, 1967; (c) I . F l e m i n g a n d M . R o w l e y , J . Chem. S O C . , P e r k i n T r a n s . l . , 1987, 2259. P.A. Grieco a n d A . B a h s a s , J . O r g . Chem., 1 9 8 7 , 5 2 , 1 3 7 8 . D . Mobilio a n d B . D e L a n g e , T e t r a h e d r o n L e t t . , 1 9 8 7 , 1483. ( a ) Y . Yamamoto, S . H a t s u y a , a n d J . Yamada, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 5 6 1 . ( b ) A . T a k u w a , 0 . Soga, T . M i s h i m a , a n d K . M a r u y a m a , J O r g . Chem., 1 9 8 7 , 52, 1 2 6 1 ; (c) G.E. K e c k , D.E. A b b o t t , a n d M . R . W i l e y , T e t r a h e d r o n 139; L e t t . , 1987, ( d ) M . Koreeda a n d Y . T a n a k a , i b i d , 1 9 8 7 , 28, 1 4 3 . ( a ) D . R . McKean, G . P o r r i n e l l o , A . F . R e n a l d o , a n d J . K . S t i l l e , J . O r g . Chem., 1 9 8 7 , 52, 4 2 2 ; ( b ) J . K . S t i l l e a n d B.L. G r o h , J . A m e r . Chem. S O C . , 1 9 8 7 , 109, 813; (c) J . K . S t i l l e a n d J . H . S i m p s o n , i b i d , 1 9 8 7 , 1 0 9 , 2138; ( d ) J . K . S t i l l e a n d M. T a n a k a , ibi-987, 109,3785. (el A.M. E c h a v a r r e n a n d J . K . S t i l l e , i b i d , 1 9 8 7 , 5478. M . K o s u g i , T . S u m i y a , Y . Obara, M . S u z u k i , H . S a n o , a n d T . M i g i t a , B u l l . Chem. S O C . J p n . , 1 9 8 7 , 60, 7 6 7 . S . Kanemoto, S . M a t s u b a r a , K . Oshima, K . U t i m o t o , a n d H . Nosaki, Chemistry L e t t . , 1987, 5. J . Yamada a n d Y . Y a m a m o t o , J . Chem. SOC., Chem. Commun., 1987, 1302. Y . Y a m a m o t o a n d J . Yamada, J . A m e r . Chem. S O C . , 1 9 8 7 , 109, 4395. H. T a n a k a , S . Y a m a s h i t a , Y . I k e m o t o , a n d S . T o r i i , C h e m i s t r y L e t t . , 1987, 673. D.H.R. B a r t o n , N . Y a d a v - B h a t n a g e r , J.-P. F i n e t , a n d J. Khamsi, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 3 1 1 1 . J . O r g . Chem., J . F . P e y r o n e l , 0. S a m u e l , a n d J.C.Fiaud, 1 9 8 7 ., 5 2 ,. 5 3 2 0 . J.C. F z e s t , J . Y . Nedelec, a n d J. P e r i c h o n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 8 8 5 . S.E. Tunney a n d J . K . S t i l l e , J . O r g . Chem., 1 9 8 7 , 52, 7 4 8 . M . O c h i a i , M . K u n i s h i m a , Y . Nagoa, K . F u j i , a n d E . F u j i t a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 7 0 8 . T. Takanami, K . Suda, H. O h m o r i , a n d M. Masui, C h e m i s t r y L e t t . , 1987, 1335. W.G. D a u b e n a n d J . J . T a k a s u g i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4377. J . E . B a l d w i n , R . M . A d l i n g t o n , a n d N . G . R o b i n s o n J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 5 3 . P . G a r n e r a n d S . R a m a k a n t h , J . O r g . Chem., 1 9 8 7 5 2 , 2 6 2 9 . J . C h e n a u l t a n d J.-F.E. Dupin, S y n t h e s i s , 1987, 498. E . V e d e j s a n d C. M a r t h , T e t r a h e d r o n L e t t . , 1987 28, 3445. T . C a l o g e r o p o u l o u , G . B Hammond, a n d D.F. W i e m e r J. O r g . Chem., 1 9 8 7 , 52, 4 1 8 5 . M.-P. T e u l a d e a n d P . S a v i g n a c , S y n t h e s i s 1 9 8 7 , 10 3 7 . ( a ) S. Hakakeyama, K . S a t o h , K . S a k u r a i , a n d S T a k a n o , T e t r a h e d r o n L e t t . , 1987 , 2 8 , 2 7 1 3 ; (b) S. Hakakeyama, K. S a t o h , K . S a k u r a i , a n d S T a k a n o ,
3,
2,
200
109,
20 1 202 203 204 205 206 207 208 209 210 211 212 213 214 215 216 217 218 219
6: Organometallics in Synthesis
403
28,
220 221
2717. i b i d , 1987, A.A. K a n d i l , T.M. P o r t e r , a n d K . N . S l e s s e r , S y n t h e s i s , 1 9 8 7 , 411. ( a ) J. Zhu a n d X . Lu, J. Chem. SOC., Chem. Commun., 1 9 8 7 , 1318; ( b ) J . Zhu a n d X. Lu, T e t r a h e d r o n L e t t . , 1 9 8 7 , 1897. M.-P. T e u l a d e a n d P . S a v i g n a c , T e t r a h e d r o n L e t t . , 1 9 8 7 , 405. C.M. Moorhoff a n d D.F. S c h n e i d e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 559. H . Moison, F. T e x i e r - B o u l l e t , a n d A . F o u c a u d , T e t r a h e d r o n 1 9 8 7 , 43, 537. T. Kawashima, T. I s h i i , a n d N . I n a m o t o , B u l l . Chem. S O C . ~pn., 1 9 8 7 , 60, mi. S.E. Denmark a n d J.E. M a r l i n , J . Org. Chem., 1 9 8 7 , 52. 5 7 4 2 . D . H . Hua, R . Chan-Yu-King, J . A . M c K i e , a n d L. Myer, J . A m e r . Chem. SOC., 1 9 8 7 , 5026. ( a ) R . K . Haynes a n d S.C. V o n w i l l e r , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 9 2 . (b) R.K. Haynes a n d A. K a t s i f i s , i b i d , 1987, 340. T . Kato, K . K o b a y a s h i , S. Masuda, M. S e g i , T . N a k a j i m a , a n d S . Suga, Chemistry L e t t . , 1987, 1915. T. B o l l o k and H. Schmidbaur, T e t r a h e d r o n L e t t . , 1987, 1085. D. C a v a l l a , W.B. C r u s e , a n d S . W a r r e n , J . Chem. SOC., P e r k i n T r a n s . l . , 1987, 1883. J . I . G r a y s o n , S. W a r r e n , a n d A.T. Z o s l o n a , J. Chem. S O C . , P e r k i n T r a n s . l., 1 9 8 7 , 9 6 7 . G . M . M e i j s a n d P.C.H E i c h i n g e r , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 5558. J.J. S i n i s t e r r a , A. F u e n t e s , a n d J.M. M a r i n a s , J . Org. Chem., 1 9 8 7 , 52, 3 8 7 5 . ( a ) Y . Z . Huang, L. S h i , J . Yang, a n d J . Zhang, T e t r a h e d r o n 2159. L e t t . , 1987, (b) L. S h i , W . X i a , J . Yang, X . Wen, a n d Y . Z . Huang, i b i d , 7 9 8 7 , 28, 2 1 5 5 . Y. B u t s u g a n , H . I t o , a n d S . A r a k i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 3707. M. Wada, H. O h k i , a n d K . A k i b a , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 7 0 8 . ( a ) D.H.R. B a r t o n , J . - P . F i n e t , C . G i a n n o t i , a n d F . H a l l e y , J . Chem. SOC., P e r k i n T r a n s . l., 1 9 8 , 2 4 1 ; ( b ) D.H.R. B a r t o n , J . - P . F i n e t , W.B. M o t h e r w e l l , a n d C. Pichon, i b i d , 1987, 251; ( c ) D.H.R. B a r t o n , N. Yadaw-Bhatnager, J . - P . F i n e t , J. Khamsi, W.B M o t h e r w e l l , a n d S . P . S a n f o r t h , T e t r a h e d r o n , 1 9 8 7 , 43, 3 2 3 . B a r t o n , J.-P. F i n e t , a n d J . Khamsi, T e t r a h e d r o n ( d ) D.H.R. L e t t . , 1 9 8 7 , 28, 8 8 7 . S. K i m a n d S . S . K i m , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2 8 , 1 9 1 3 . W.D. Abraham, M . B h u p a t h y , a n d T . Cohen, T e t r a G d r o n L e t t . , 1 9 8 7 , 2 8 , 2203. B . M . T z s t a n d G . K . M i k h a i l , J. A m e r . Chem. S O C . , 1 9 8 7 , 4124. K. T a k a k i , M . Yasumura, T. Tamura, a n d K . Negoro, J . O r g . Chem., 1 9 8 7 , 52, 1 2 5 6 .
28,
22 2 223 224 225 226 227 228 229 230 231 232 233 234 235
236 237 238
239 240 241 242
28,
109,
28,
28,
109,
Gmerul und Synthetic Methods
404 243 244 245 246 247 248 249 250 25 1
252
253 254 255 256 257 258
S.T.
P u r r i n g t o n a n d J.H.
Pittman, Tetrahedron Lett.,
28, 3901. -
T . T a k e d a , Y. K a n e k o , H . Nagagawa, a n d T . F u j i w a r a , Chemistry L e t t . , 1987, 1963. H. I s h i b a s h i , H. N a k a t o n i , K . Maruyama, K. Minami, a n d M. I k e d a , J . C h e m . S O C . , Chem. Commun., 1 9 8 7 , 1 4 4 3 . ( a ) M. B h u p a t h y a n d T . C o h e n , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4793; ( b ) M. B h u p a t h y a n d T . C o h e n , i b i d , 1 9 8 7 , 28, 4 7 9 7 . M. K i m u r a , K . Koie, S . M a t s u b a r a , Y . S a w a k i , a n d H . I w a m u r a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 2 2 . N. Schultz-von Itter and E. Streckham, Tetrahedron, 1987, 43, 2475. N . Ono. T.X. J u n , T , H a s h i m o t o , a n d A . K a j i , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 9 4 7 . P . B r o w n b r i d g e , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 2 8 0 . ( a ) S.M. T u l a d h e r a n d A . G . F a l l i s , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 523; Abd E l S a m i l , M . I . A 1 Ashmawy, a n d J . M . M e l l o r , ( b ) Z.K.M. T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 9 4 9 . ( a ) H . I s h i b a s i , H . N a k a t a n i , H . S a k a s h i t a , a n d M. I k e d a , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 3 3 8 ; ( b ) B. B a r t e l s , R . H u n t e r , C . D . S i m o n , a n d G . D T o m l i n s o n , Tetrahedron L e t t . , 1987, 28, 2985; (c) K. T a k a i , Y. K a t a o k a T T . Okazoe, a n d K. U t i m o t o . B . D . G r a y , C . M . M c M i l l a n , J . A M i l l e r , a n d G.M. U l l a h , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 8 9 . B . D . G r a y a n d J . A . M i l l e r , J . Chem. S O C . , Chem. Commun., 1987, 1136; M.E. J u n g a n d D . D . Grove, J . Chem. S O C . , C h e m . Commun., 1987, 753. Y . K i t a , 0. T a m u r a , T . M i k i , a n d Y . T a m u r a , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 6 4 7 9 . T . K a n e k o , Y . O k a m o t o , a n d K . H a t e d a , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 1 5 1 1 . ( a ) S. Colonna, A. M a n f r e d i , M . S p a d o n i , L. Casella, a n d M. G u l l a t t i , J . Chem. S O C . , P e r k i n T r a n s . l . , 1 9 8 7 , 7 1 ; ( b ) S.H. Z h a o , 0 . S a m u e l , a n d H . B . K a g a n , T e t r a h e d r o n , 1 9 8 7 , 43, 5135; ( c ) F.A. D a v i s , J . P . M c C a u l e y , S . C h a t t o p a d h y a y , M.E. H a r a k a l , J . C . T o w s o n , W . H . W a t s o n , a n d I . T a v a n i e p o u r , JAmer. Chem. S O C . , 1 9 8 7 , 3370. H . K o s u g i , M . K i t a o k a , K . T a g a m i , A . T a k a h a s h i , a n d H . Uda, J . O r g . Chem., 1 9 8 7 , 52. 1 0 7 8 . K . H i r o i , H . N a k a m u r a , a n d T . A n z a i , J. A m e r . Chem. S O C . , 1 9 8 7 , 109, 1 2 4 9 . ( a ) J . C . C a r r e t e r o a n d L. G h o s e z , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1101; ( b ) J . C Carretero, H. Demillequand, a n d L Ghosez, T e t r a h e d r o n , 1 9 8 7 , 43, 5 1 2 5 . H. F i l l i o n , A. H s e i n e , M.-H. P e r a , V. Dufaud, a n d B. Refouvelet, S y n t h e s i s , 1987, 708. G.M.P. G i b l i n a n d N . S . S i m p k i n s , J . Chem. S O C . , Chem. Commun., 1 9 8 7 , 2 0 7 . ( a ) K . Inomata, S. S a s a o k a , T. Kobayashi, Y . Tanaka, S. I g a r a s h i , T . O h t o n i , H . K i n o s h i t a , a n d H. Kotake, B u l l ,
109,
259 260 261
262 263 264
1987,
6: Organometailics in Synthesis
265
266 267 268
Chem. SOC. J p n . , 1 9 8 7 , 60, 1 7 6 7 ; ( b ) J . B a r l u e n g a , J . M . M a r t i n e z - G a l l o , C . Najera, F . J . F a n a n a s , a n d M . Y u s , J . Chem. S O C . , P e r k i n T r a n s . 1, 1 9 8 7 , 2605; ( c ) F o r a u s e f u l s u m m a r y of m e t h o d s u s e d t o prepare a l l y l i c s u l p h o n e s see D . J . K n i g h t , P . L i n , S . J . R u s s e l l , a n d G . H . W h i t h a m , J . Chem. SOC., P e r k i n T r a n s 1, 1 9 8 7 , 2 7 0 1 ; D . J . K n i g h t , P . L i n , a n d G.H. Witham, i b i d , 1 9 8 7 , 2707. ( a ) T.G. B a c k , M . V i j a y a , a n d K . R . M u r a l i d h a r a n , T e t r a h e d r o n L e t t . , 1987, 28, 1737; ( b ) T.G. B a c k , S . C o l l i n s , M . V . K r i s h n a , a n d K . - W . Law, J. O r g . Chem., 1 9 8 7 , 52, 4 2 5 8 . ( c ) T.G. B a c k a n d M.V. K r i s h n a , i b i d , 1 9 8 7 , 52, 4 2 6 4 . A.D. B u s s , G.C. H i r s t , a n d P . J . P a r s o n s , J . Chem. S O C . , Chem. Commun.. 1 9 8 7 . 1 8 3 6 . S.A. H a r d i n g e r a n d P . L . F u c h s , J . O r g . Chem., 1 9 8 7 , 52, 2739. ( a ) P.J. H a r r i n g t o n a n d K.A. D i F o r e , T e t r a h e d r o n L e t t . , 1987, 495; ( b ) H.-H. TSO, T. C h o u , a n d S.-C. H u n g , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 1 5 5 2 ; ( c ) T . C h o u , S.-C. Hung, a n d H . - H . TSO, J . O r g . Chem., 1987, 52, 3394; T s a i , and A.-J. Wanq, ( d ) S . S . P . C h o u , S.-Y. L i o u , C.-Y. 4468; i b i d , 1987, ( e ) T . C h o u a n d M.-Li You, i b i d , 1 9 8 7 , 52, 2 2 4 . (f) T . C h o u , S . J . L e e , H . - H . TSO, a n d C . F . Yu, i b i d , 1 9 8 7 , 52, 5082. T G . B l a c k a n d R . G . K e r r , J . Chem. SOC., Chem. Commun., 1987, 134. R. Okazaki and Y. I t o h , Chemistry L e t t . , 1987, 1575. ( a ) S. M u r a t a , a n d T . S u z u k i , C h e m i s t r y L e t t . , 1 9 8 7 , 8 4 9 ; ( b ) S. M u r a t a , a n d T. S u z u k i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 4297: ( c ) S. M u r a t a a n d T . S u z u k i , i b i d , 1 9 8 7 , 2 8 , 4 4 1 5 ; (d) M. M i h a i l o v i c , S . K o n s t a n t i n o v i c , a n d x . V u k i c e v i c , ibid, 1 9 8 7 , 28, 4 3 4 3 ; ( e ) M.T. C r i m m i n s , W . G . H o l l i s , a n d J . G . L e v e r , i b i d , 1 9 8 7 , 28, 3647; (f) G . M e h t a , H . S . P . Rao, a n d K . R . R e d d y , J . Chem. SOC., C h e m . Comun., 1 9 8 7 , 7 8 . A . K r i e f a n d J . L . L a b o u r e r u , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1545. K.M. N s u n d a a n d L . Hevesi, J . Chem. S O C . , Chem. Comrnun., 1987, 1518. ( a ) A . T o s h i m i t s u , K . T e r a o , a n d S . U e m u r a , J . Chem. SOC., Chem. Commun., 1 9 8 1 , 1 0 5 9 . ( b ) N . Ono, A . K a m i m u r a , T . K a w a i , a n d A . K a j i , J. Chem. SOC., Chem. Commun., 1 9 8 1 , 1 5 5 0 . T. M a s a w a k i , A. Oqawa, N . K a m b e , I . R y n , and N . S o n o d a , C h e m i s t r y L e t t . , 1987, 2407. R . H e r n a n d e z , E.I. L e o n , J . A . S a l a z a r , a n d E . S u a r e z , J. Chem. S O C . , Chem. Comrnun., 1 9 8 7 , 3 1 2 . T . S h i m i z u a n d M . K o b a y a s h i , J . O r q . Chem., 1 9 8 7 , 52, 3 3 9 9 . M. T i e c c o , M. T i n g o l i , L. T e s t a f e r r i , a n d D. B a r t o l i , T e t r a h e d r o n L e t t . , 1 9 8 7 , 2,3 8 4 9 .
2,
269 27 0 27 1
272 273 27 4
275 276 277 278
405
279
Engman, J . O r q . Chem., 1 9 8 7 , 5 2 , 4 0 8 6 ; Enqman, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 1 4 6 3 . (a) Chen a n d X . - J . Zhou, x n t h e s i s , 1 9 8 7 , 5 8 9 ; (b) S u z u k i , H . Manabe, T . K a v a g u c h i , a n d M . I n o u y e , B u l l . Chem. S O C . , J n . , 1 9 8 7 , 6 0 , 7 7 1 ; ( c ) D.H.R. B:rton, L . B o h e , a n d X. L u s i n c h i , T e t r a h e d r o n L e t t . , 1987, 6609. N . Kambe, T . T s u k a m o t o , N . M i y o s h i , J . M u r a i , a n d N . S o n o d a , Chemistry L e t t . , 1987, 269. N . Kambe, T . F u j i o k a , A . Ogawa, N . M i y a s h i , a n d N . S o n o d a , Chemistry L e t t . , 1987, 2077. T . H i i r o , N . Kambe, A . Oqawa, N . M i y o s h i , S . M u r a i , a n d N . Sonoda, S y n t h e s i s , . 1987, - 1 0 9 6 . X . Huang, L . X i e , a n d H . Wu, T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 801. N . X . Hu, Y. Aso, T . O t s u b o , a n d F . O g u r a , J . Chem. SOC., Chem. Commun., 1 9 8 7 , 1 4 4 7 . J.V. C o m a s s e t o , H . M . C . F e r r a z , N . P e t r a g r a n i , a n d C . A . B r a n d t , T e t r a h e d r o n L e t t . , 1 9 8 7 , 28, 5 6 1 1 . N . X . Hu, Y. Aso, Y. O t s u b o , a n d F T O g u r a , T e t r a h e d r o n L e t t . , 1987, 1281. (a)
(b)
280
L. L. J. H.
28,
28 1 282 283 284 285 286 287
28,
7 Saturated Carbocyclic Ring Synthesis BY T. V. LEE 1
Three-membered Rings
Cyclopropanes are readily prepared from transition metal carbene complexes reacting with alkenes, and this area has been reviewed'. The chemistry of samarium metal and its derivatives is currently highly topical, and one use of the metal is in the cyclopropanation of allylic alcohols': which efficiently gives cyclopropanes such as (1). The reaction proceeds with excellent diastereoselectivity and good chemoselectivity, since simple alkenes are apparently inert. Further studies on the cyclopropanation of unsaturated chiral acetals have been as has more work upon the stereoselective synthesis of doubly activated vinylcyclopropanes5. As part of a synthesis of racemic prezizanol and prezizaene, vinylcyclopropanes were obtained by reaction of vinyl iodides and cyclopropylzincs, under palladium catalysis6.
2
Four-membered Rincrs
report of an improved procedure for cyclobutene formation from the cycloaddition of dichloroketene to acetylenes will be of value7. [2+2] Cyc1oa:ditions of this type are still highly topical with interest being mainly focused upon the intermolecular variant. Thus, a relatively unusually substituted [3.2.01 heptanone can be obtained by cycloaddition of the ketene iminium salt generated from the amide (2) whilst photolysis of the diene (3) or of the 1 ,3-dione derivative (4) also gives the intramolecular [2+21 adduct. A more comprehensive account of a variation of this last example involving cyclooctenone derivatives has also appeared12
A
',
.
3
Five-membered Rings
Generated Methods. The use of carbometalation reactions in cyclizations is still very topical and has recently been reviewed13 as has the use of radical cycli~ations'~. Also popular in cyclopentane formation is the use of metal catalysed ene reactions as exemplified by the palladium catalysed cyclization of the diene (5)l5 and the iron (0) induced reaction of the triene ( 6 ) .16 This
(3) ,To s
Tos
PPh,
7: Saturated Carbocyclic Ring Synthesis
409
last example is highly diastereoselective, allowing the formation of the trans-trans cyclopentane by use of the allylic ether alkene of opposite configuration. A further use of samarium chemistry, beyond that previously discussed, involves the chemoselective intramolecular reaction of the allyl iodide (7) with the ketoamide function to give 8 0 % of the *-substituted cyclopentane'" 18. Metalation at an allyl position is also involved in the reaction of the alkyne ( 8 ) with the zinc species ( 9 ) leading to methylenecyclopentanes, as shown in Scheme ll'. Methylenecyclopentanes are of course also the product of the reactions of trimethylenemethane undergoing [3+21 additions, and further work in this area has appeared on the use of chromium, molybdenum and tungsten complexes of this species2'. Furthermore the atom transfer cycloaddition of the iodide (10) in Scheme 2 also 1eads to me thy1enecyc1opentanes . a,@-Unsaturated iron acyl complexes such as ( 1 1 ) can be converted to their cyclic counterparts by reaction with allylstannanes22 and further studies on rhodium catalysed insertion processes have allowed the conversion of suitably substituted furans (12) to useful substituted c y c l ~ p e n t e n o n e s ~ ~Additionally, . a report upon the preparation of functionalised cyclopentane carboxylic acids by Ni(0) catalysed reaction of carbon dioxide and 1,3-butadiene has appeared24 whilst further examples of the synthetic utility of bis-Grignard reagents have been described, including their use in cyclopentane 26. Benzyllithiums can be generated from selenides such as (13) to give after cyclization diastereoisomeric mixtures of c y ~ l o p e n t a n e s ~ ~ . Another cyclization process involves an interesting radical chain process by reaction of the unsaturated ester (14); however the process is non stereospecific28 . A new route to useful disubstituted cyclopentanes involves anodic Grob type fragmentation of readily available bicyclic carboxylic acids such as (15)29 whereas the reaction of ( 1 6 ) gives equally useful five-membered rings by combining the Lewis acid induced cyclization of acid chlorides and alkynes with reductive d e c h l ~ r i n a t i o n ~ ~A. further new synthesis of cyclopentanes utilises Lewis acid treatment of some diketones of the type (17) in a pathway involving ring opening followed by ring closure3' and a hetero intramolecular Diels-Alder reaction has been used as a key step in 32 a new synthesis of deoxyloganin .
410
General and Synthetic Methods Me3SivR
Me3si2
-R
Me3Si-
+
J0 R' l i ! n B r
-
BrZn
(9)
(8) Reagents
i
R'O
i, 100OC; ii,Pd (PPh3),,650C
Scheme 1 Si Me3
(10) Reagents : i, Bu3Sn Sn Bu3,hx 70*C.C6H6
Scheme 2
SnBu, A S n B u , AICI,
0-
Rh (OAc), 2
C HO
eMe
Ph
Me
i. Hg ( 0 A c ) ~ i i, N aBH4
Ph, Me &CHI
7: Saturated Carbocyclic Ring Synthesis
41 1
LiOHlMeOH
anode
0
,&
0
0
+
0
h7.t
i,ii
. )
C02Et Reagents : i, T M S - I ; ii, base
Scheme 3
OH
heat
General and Synthetic Methods Fused Five-membered Rings.
Vinylcyclopropane rearrangements
can be most valuable but are limited by their requiring high temperatures, so that the mimicking of the rearrangement by using iodotrimethylsilane, followed by ring closure, is a most useful o b ~ e r v a t i o n(Scheme ~~ 3). Thermal conditions were the only ones of use in achieving the rearrangement of the diene (18) as part of a hydroazulene synthesis34. Synthetically useful enzymic transformations are highly topical and have been used to prepare the synthetically useful fused cyclopentane precursors (19)35 and (20)36. The use of the bis-enolate anions of diesters in annulations has been extended to the synthesis of the enone (21)37 which was a key precursor in the first synthesis of racemic b i l ~ b a l i d e ~ ~Two . full accounts o f the use of v-0x0-a-ester enolate anions3’ and of the de Mayo reaction4’ in synthesising naturally occurring fused cyclopentanes will be of interest, as is the phase transfer catalysed Michael addition of the enolate anion of (22) to the enol ether (23) (Scheme 4 ) to give, after ring closure, a usefully substituted fused cyc1opentane4l. The Pauson-Khand cyclization continues to be synthetically useful as detailed in a full account of its use in the synthesis of q ~ a d r o n ewith ~ ~ the same group describing its use in an enantiospecific synthesis of 6a-carbocycline (24)43. A manganese (111) mediated reaction of enol ethers has also been reported to give access to fused cyclopentanes44 . Allylsilanes continue to be of great use for the synthesis of carbocyclic rings, especially when utilised in palladium induced cyclizations. Thus by varying the palladium species one can obtain either the saturated45 or ~ n s a t u r a t e dfused ~~ system (25) or ( 2 6 ) (Scheme 5 ) . A further excellent way of preparing fused cyclopentanes is to use an intramolecular carbenoid insertion process, which are now commonly induced by rhodium catalysts. This has now been extended to phosphorus47r48 and to sulphur4’ containing compounds as shown in Scheme 6 . Finally, cyclization reactions of alkyl, alkenyl and aryl organolithium reagents are known to lead to both fused five and six-membered rings and further reports of this strategy will be 4
Six-membered Rinus
Diels-Alder Reactions. The Diels-Alder reaction continues to be the mainstay of six-membered rinu svntheses. However there h a s
7: Saturated Carbocyclic Ring Synthesis
413
0
#
.
. \
Hd
\C02Et
(20)
(1 9)
But
OL i
I 111C I
6 Li
--a Me%c
C
But
Me02C
C02Ph
(21)
Et02$
C0,E t
koMe I
+ (22)
(@ CN
CN
(23)
i-
Reagents: ,i NaOH, P T C ; ii, CF,CO,H;
iii, Bu,NOH
Scheme 4 Me3Si I
I
'2-p.
Si Meg [CO,(CO)J
H0"
6H
(2 4)
&I
or ii
ButMe2Si0
BU'M e,SiO
OSi Me,J Reagents : i,(dba),P%CHCl,,HOAc,PMHS
-
(25) 6,7 CH2CHZ (26) 6.7 HC = C H
( 2 5 ) ; ii, Pd(OAc1, -(26) Scheme 5
Genemi (it id S v t it h rtic Met Ii ods
414
67 ' l o
m & S 0 2 P h
L
0
Qo S02Ph
75 'lo
Reagent: i, Rh(OAc),
Scheme 6
145OC
____)
Me0 Me0
OMe
OBn
(31)
Scheme 7
7: Saturated Carbocyclic Ring Synthesis
415
been a very noticeable drop in activity in this specific area when compared with the plethora of reports which appeared over the last few years, notably in papers addressing the intramolecular variant. Despite this a timely review on the Diels-Alder reaction of ortho-quinodimethanes is worthy of note52 as is a review on the use of radical cations to catalyse c y c l ~ a d d i t i o n s ~ ~ . A large amount of effort is being expended towards obtaining efficient asymmetric induction in Diels-Alder reactions. Recent reports aimed at achieving this include the use of chiral Lewis acids54 but more typically involve the incorporation of a chiral auxiliary into the diene or dienophile. Good selectivity is shown by the use of methoxymethyl pyrrolidines in this way55 as it is with menthyl acrylates such as (27)56. Further examples involve using optically active f ~ m a r a t e splus ~ ~ attempts via arabinose based a ~ x i l l a r i e s ~ ~The . selectivities in this last report were however disappointing. Amongst the new dienophiles reported are the E- and phenylsulphonyl substituted acrylates (28) and (29) which display complementary regio~hernistry~~ and a nitroacetylene equivalent (30I6O. The first use of dienylboronates as dienes is also of interest6'. Although currently less popular than in recent years the intramolecular variant of this important reaction has still produced some notable papers, including the most useful and critically comprehensive review of them to date62. Thus the first preparation of the phorbol skeleton utilised the cyclization of the triene (31)63 and a series of papers on the first transannular intramolecular Diels-Alder r e a ~ t i o n ,~ demonstrated ~-~~ in Scheme 7 , have appeared. Additionally it has been reported that performing the reaction in a solution of calcium chloride enhances the IMDA of furan whilst a sequence of furan cleavage and IMDA have been combined into an efficient one-pot process 6 8 . Other Syntheses of Six-membered Rings. Tandem reactions are very much in vogue, especially when a Michael reaction is involved. A number of examples of the double Michael reaction have been described and amongst these are the closure of (321, the key step in a new synthesis of pentalenic acid6', the highly efficient preparation of the tricycle (33)70, and the formation of the
z-
derivative^^^
416
(33) 80% 0 -CH2 NO2
+ Ph
,R
R*: R"
C HO
+
i'l
I
'-Ph
"VHH R" OH
1 .____)
SiMe,
(36) Reagent : i, SnF2,THF
Scheme 8
H
Me SOMe
4
0
yj
iv
(37) Reagents : i, PhCOCI; ii, P Br3 Br2; iii, MeSCH2SOMe, KH; iv, H,O+
Scheme 9
@,b
7: Saturated Carbocyclic Ring Synthesis
417
decalins (34) and (35) in a ratio of 4:l and a combined yield of 45%71. Additionally one example of a tandem Michael-Claisen process has now been discovered72 . As mentioned above allylsilanes continue to be useful in synthesis with the intermolecular closure onto an epoxide cf the allylsilane (36) being the key step in a synthesis of the A-ring of the ta~anes’~.Surprisingly until this year there had been no report upon the use of a Robinson annulation of a sugar, but this has now been achieved using 2-trimethylsilyl MVK74. The chiral synthesis of cyclohexanes has attracted the attention
of a number of groups. These include an extension of a previous annulation strategy to a reaction with chiral epoxy aldehydes (Scheme 8)75, a full account of using anthranilic acid derivatives to induce a ~ y m m e t r y ~the ~ , use of a chiral amide base77, and finally, by starting with the chiral piperidine derivative (37) as shown in Scheme 978. 5
Seven-membered, Medium and Large Rings
The synthesis of a number of notable fused seven and eight-membered ring compounds has b’een achieved such as the total synthesis of the guaianolide gnididione7’, of grosshemin80, and the skeleton ophiobolanes81 . Seven and eight-membered rings have also been prepared by reaction of the 1,4-diketone (38) or the ketoaldehyde (39) with an allylsilane, in a clever extension of an annulation described above82 (Scheme 10). Additionally, more use has been made of the nickel catalysed [4+41 cycloaddition reported last year83, including the introduction of a photolytic modification of the reaction84.
A series of full papers which describe the direct synthesis of ten to fourteen-membered rings under conditions which remove the need for high dilution has a ~ p e a r e d ~ ’ - ~ The ~ . reaction requires the presence of at least two centres of unsaturation to be successful as seen for the reaction of (40). Another series of papers describes the utility of a Wittig rearrangement of cyclic ethers to prepare larger r i n g ~ ~ ~ - ’ lwhilst , a new synthesis of muscone uses a silyloxy-Cope rearrangementg2. 6
Rincr Expansion Methods
Sulphur stabilised ring expansion methods have proven to be most
Gmeral and Synthetic. Methods
418
wtMe (38)
&Me
100 Y o
h--&.
Ph
(39)
6 3 '10
Scheme 10
n
C02Me
II
K2C03
111
,I
LfC02Me
n
C0,Me
II
i(
M e 02C C02Me C02Me
(40 1 S02Ph &.Me
(41)
111
H (42 1
419
7: Saturated Carbocyclic Ring Synthesis
Reagent : i, SnCI,
Scheme ll
420
Gmrrul und Synthetic Methods
reaction of the sulphone (41) with Lewis acid to form the fused ketone (42)9 3 , whilst base treatment of the alcohol (43) gave the ring expanded cyclopentanoneg4. A full account of the closely related reaction of (44) will also be usefulg5 as are details of related selenium stabilised reactionsg6‘ 97. Some very interesting radical induced ring expansions have also been reported this yearg8
”.
A particularly ingenious reaction is
the Sn(1V) mediated conversion of acetals such as (45) to give fused cyclic ethers as shown in Scheme 11lo0.
REFERENCES 1. 2. 3.
4. 5. 6. 7. 8. 9.
10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.
M.Brookhart and W.B.Studabaker, Chem-Revs., 1987, 87, 411. G.A.Molander and J.B.Etter, J.Org.Chem., 1987, 52, 3942. E.A.Mash, K.A.Nelson, and P.C.Heidt, Tetrahedron Letters, 1987, 28, 1865. KA.Mash and K.A.Nelson, Tetrahedron, 1987, 43,679. J.E.Backval1, J.O.Vagberg, C.Zercher, J.P.Genet, and A.Denis, J.Org.Chem., 1987, 52, 5430. E.Piers, M.Jean, and P.S.Marrs, Tetrahedron Letters, 1987, 28, 5075. A.A.Ammann, M.Rey, and A.S.Dreiding, Helv.Chim.Acta, 1987, 3, 321. W.T.Brady, Y.-S.Giang, L.Weng, and M.M.Dad, J.Org.Chem., 1987, 52, 2216. S.Ghosh, S.R.Raychaudhuri, and R.G.Salomon, J.Org.Chem., 1987, 52, 83. K R - M a t l i n and D.J.McGarvey, Tetrahedron Letters, 1987, 28, 5087. A.R.Matlin, T.C.Leckta, D.J.McGarvey, P.W.Jacob, and H.A.Picken, Tetrahedron Letters, 1987, 28, 5083. M.C.Pirrung and N.J.G.Webster, J.Org.Chem., 1987, 52, 3603. E-I.Negishi, Acc.Chem.Res., 1987, 20, 65. M-Ramaiah, Tetrahedron, 1987, 43, 3541. W.Oppolzer and J-M-Gaudin, HelxChim.Acta, 1987, 70, 1477. J.M.Takacs and L.G.Anderson, J.Amer.Chem.Soc., 1987, 109, 2200. G.A.Molander, J.B.Etter, and P.W. Zinke, J.Amer.Chem.Soc., 1987, 109, 453. G.A.Molander and C.Kenny, Tetrahedron Letters, 1987, 28, 4367. J.van der Louw, J.L.van der Baan, F.Bickelhaupt, and G.W.Klumpp, Tetrahedron Letters, 1987, 28, 2889. R.Aumann and J.Uphoff, Angew.Chemie, Int.Ed.Engl., 1987, 5, 357. D.P.Curran and M-H.Chen, J.Amer.Chem.Soc., 1987, 109, 6558. J.W.Herndon, J.Amer.Chem.Soc., 1987 109, 3165. E.Wenkert, M.Guo, F.Pizzo, and K.Ramachandran, Helv.Chim.Acta, 1987, 70, 1429. H.HobeE, S.Gross, and A.Milchereit, Angew-Chemie, Int.Ed.Engl., 1987, 26, 571.
7: Saturated Carbocyclic Ring Synthesis
42 1
25. P.Canonne, R.Boulanger, and M.Bernatchez, Tetrahedron Letters, 1987, 28, 4997. 26. P.Canonne and M.Bernatchez, J.Org.Chem., 1987, 52, 4025. 27. A.Krief and P.Barbeaux, J.Chem.Soc., Chem.Commun., 1987, 1214. 28. K.Weinges and W.Sipos, Angew.Chemie, Int.Ed.Engl., 1987, 26, 1152. 29. R.Michaelis, U-Miller, and H.J.Schafer, Angew.Chemie, Int.Ed.Engl., 1987, 26, 1026. 30. C.J.Rizzo, N.K.DunlaK and A.B.Smith 111, J.Org.Chem., 1987, 52, 5280. 31. H.Suemune, K.Oda, and K.Sakai, Tetrahedron Letters, 1987, 2, 3373 * 32. L.F.Tietze, H-Denzer, X.HoldgrUn, and M.Neumann, Angew-Chemie, Int.Ed.Engl., 1987, 26, 1295. 33. AsFleming, G-Sinai-Zingde, M.Natchus, and T.Hudlicky, Tetrahedron Letters, 1987, 2, 167. 34. M.Sworin and K.C.Lin, J.Org.Chem., 1987, 52, 5640. 35. Z.F.Xie, H.Suemune, a.nd K.Sakai, J.Chem.Soc., Chem.Commun., 1987, 838. 36. D.W.Brooks and P.Barbeaux, J.Org.Chem, 1987, 52, 2036. 37. E.J.Corey and W.Su, Tetrahedron Letters, 1987, 28, 5241. 38. E.J.Corey and W.Su, J.Amer.Chem.Soc., 1987, 10977534. 39. J.P.Marino and E-Laborde, J.Org.Chem., 1987, 52, 1. 40. B.W.Disanayaka and A.C.Weedon, J.Org.Chem., 1987, 52, 2905. 41. V.I.Ognyanov and M.Hesse, Helv.Chim.Acta, 1987, 70, 1393. 42. P.Magnus, L.M.Principe, and M.J.Slater, J.Org.Chem., 1987, 52, 1483. 43. P.Magnus and D.P.Becker, J.Amer.Chem.Soc., 1987, 109, 7495. 44. E.J.Corey and A.K.Gosh, Tetrahedron Letters, 1 9 8 7 , 1 2 8 , 175. 45. B.M.Trost and F.Rise, J.Amer.Chem.Soc., 1987, 109, 3161. 46. B.M.Trost and D.J.Jebaratnam, Tetrahedron Letters, 1987, 28, 1611. 47. H.M.L.Davies and L.V.T.Crisco, Tetrahedron Letters, 1987, 28, 371. 48. B.Corbe1, D.Hernot, J.-P.Haelters, and G.Sturtz, Tetrahedron Letters, 1987, 28, 6605. 49. H.J.Monteiro, Tetrahedron Letters, 1987, 28, 3459. 50. M.P.Cooke Jr. and R.K.Widener, J.Org.Chem., 1987, 52, 1381. 51. W.F.Bailey, T.T.Nurmi, J.J.Patricia, and W.Wang, J.Amer.Chem.Soc., 1987, 109, 2442. 52. J.L.Charlton and M.M.Alauddin, Tetrahedron, 1987, 43, 2873. 53. N.L.Bauld, D.J.Bellville, B.Harirchian, K.T.Lorenz, R.A.Pabon Jr., D.W.Reynolds, D.D.Wirth, H-S.Chiou, and B.K.Marsh, Acc.Chem.Res., 1987, 20, 371. 54. H.Takemura, N-Komeshima, I.Takahashi, S.Hashimoto, N.Ikota, K.Tomioka, and N.Koga, Tetrahedron Letters, 1987, 28, 5687. 55. D.Dopp and M.Pies, J.Chem.Soc., Chem.Commun., 1987, 1734. 56. Y.Arai, Y.Hayashi, M.Yamamoto, H.Takayama, and T.Koizumi, Chem.Letters, 1987, 185. 57. K.Furuta, S.Hayashi, Y.Miwa, and H.Yamamoto, Tetrahedron Letters, 1987, 28, 5841. J.Chem.Soc., Chem.Commun., 58. T.K.M.Shing and?.Lloyd-Williams, 1987, 423. 59. A.D.Buss, G.C.Hirst, and P.J.Parsons, J.Chem.Soc., Chem.Commun., 1987, 1836. 60. M.E.Jung and D.D.Grove, J.Chem.Soc., Chem.Commun., 1987, 753. M.Vaultier, F-Truchet, B.Carboni, R.W.Hoffmann, and I.Denne, 61. Tetrahedron Letters, 1987, 28, 4169, 62. D.Craig, Chem.Soc.Revs., 1987, 16, 187. 63. P.A.Wender, R.M.Keenan, and H.Y.Lee, J.Amer.Chem.Soc., 1987, 109, 4390. -
64.
K.Baettig, C.Dallaiere, R.Pitteloud, and P.Deslongchamps, Tetrahedron Letters, 1987, 2,5249. 65. K.Baettig, A-Marinier, R.Pittleloud, and P.Deslongchamps, Tetrahedron Letters, 1987, 28, 5253. 66. G.Berube and P.Deslonqchamps, Tetrahedron Letters, 1987, 28, 5255. 67. B.A.Keay, J.Chem.Soc., Chem.Commun., 1987, 419. 68. H-J.Wu and K.Pan, J.Chem.Soc., Chem.Commun., 1987, 898. 69. M.Ihara, M.Katogi, K.Fukumoto, and T.Kametani, J.Chem.Soc., Chern.Commun., 1987, 721. 70. J-F.Lavelle and P.Deslongchamps, Tetrahedron Letters, 1987, 28, 3457. 71. F.Richter and H.H.Otto, Tetrahedron Letters, 1987, 2 , 2945. 72. T.H.Chan and C.V.C.Prassad, J.Org.Chem., 1987, 52, 110. 73. L.Patterson, T.Frejd, and G.Magnusson, Tetrahedron Letters, 1987, 28, 2753. 74. R.V.BoGert and P.R.Jenkins, J.Chem.Soc.; Chem Commun., 1987, 6. 75. G.A.Molander and D.C.Schubert, J.Amer.Chem.Soc., 1987, 109, 576. 76. A.G.Shultz, P.J.McCloskey, and J.J.Court, J.Amer.Chem.Soc., 1987, 109, 6493. 77. C-Duharnel, A.Ravard, J.C.Plaquevent, and D-Davoust, Tetrahedron Letters, 1987, 28, 5517. 78. A.Thurkauf, P-Hillery, A.E.Jacobson, and K.C.Rice, J.Org.Chem., 1987, 5466. 79. C.P.Del1 and D.W.Knight, J.Chem.Soc., Chem.Commun, 1987, 349. 80. J.H.Riqby and C.Senanayake, J.Amer.Chem.Soc., 1987, 109, 3147. 81. J.H.Riqby and C.Senanayake, ______ J.Org.Chem., 1987, 52, 4634. 82. G.A.Molander and D.C.Schubert, J.Arner.Chem.Soc, 1987, 109, 6877. 83. P.A.Wender and M.L.Snapper, Tetrahedron Letters, 1987, 28, 2221. 84. P.A.Wender and C.R.Correia, J.Amer.Chem.Soc., 1987, 109, 2523. 85. D.Brillon and P.Deslongchamps, Can.J.Chem., 1987, 6 5 , 4 3 . 86. D.Brillon and P.Deslongchamps, _______ Can.J.Chem., 1987, 65, 56. 87. P.Deslongchamps, S.Lamothe, and H-S.Lin, Can.J.Chern., 1987, 65, 1298. 88. J.A.Marshal1, J-Lebreton, B.S.DeHoff, and T.M.Jenson, Tetrahedron Letters, 1987, 2,723. 89. J.A.Marshal1 and J-Lebreton, Tetrahedron Letters, 1987, 28, 3323. 90. J.A.Marshal1, T.M.Jenson, and B.S.DeHoff, J.Org.Chem., 1987, 52, 3860. 91 * J.A.Marshal1, J.Lebreton, B.S.DeHoff, and T.M.Jenson, J.Org.Chem. , 1987, 52, 3883. 92. R.W.Thies and K.P.Daruwala, J.Org.Chem., 1987, 52, 3798. 93. B.M.Trost and G.K.Mikhai1, J.Amer.Chem.Soc., 1987, 109, 4124. 94. W.D.Abraham, M.Bhupathy, and T.Cohen, Tetrahedron Letters, 1987, 28, 2203. 95. R.C.Gadwood, I.M.Mallick, and A.J.DeWinter, J.Org.Chem., 1987, 52, 774. 96. A.Krief and J.L.Labourer, Tetrahedron Letters, 1987, 28, 1545. 97. A.Krief, J.L.Labourer, and W.Dumont, Tetrahedron Letters, 1987, 28, 1549. 98. P.Dowd and S.C.Choi, J.Amer.Chem.Soc., 1987, 109, 3493. 99. P-Dowd and S.C.Choi, J.Amer.Chem.Soc., 1987, 109, 6548. 100. P-M-Herrington,M.H.Hopkins, P.Mishra, M.J.Brown, and L.E.Overman, J.Org.Chem., 1987, 52, 3711.
z,
Saturated Heterocyclic Ring Synthesis BY
1
K. COOPER AND P. J. WHllTLE
Oxygen-containing Heterocycles
Three-membered Rings.- The Sharpless epoxidation continues to be the most popular method €or synthesis of homochiral epoxides and full details of the catalytic Sharpless epoxidation have now been published',
as have details of the modification of the Sharpless
reaction which reduces reaction times by using either catalytic calcium hydride or silica gel2. The biogenetically patterned epoxidation using bovine serum albumen as the chiral catalyst has received further attention with a study on the epoxidation of naphthoquinones ( 1 ) 3 . Enantiomeric excesses are variable (14-77%) and dependent on pH, the nature of the oxidising agent and the structure of the starting materials. Epoxidation of a,B-unsaturated carbonyl compounds is usually conducted under basic conditions and unless the pH is carefully controlled, base sensitive substrates are incompatible with the reaction.
However, by using tetrabutyl ammonium fluoride and
hydrogen peroxide or t-butyl hydroperoxide, base sensitive substrates can be epoxidised in good yield (60-96%), e.g. cinnamaldehyde gives the epoxide ( 2 ) in 80% yield4. Regioselective epoxidation of polyenes is a difficult problem and one interesting solution published this year utilises intramolecular delivery of the peracid. Thus, the peroxy esters (4) and (6) prepared from the triene ( 3 ) are converted into the epoxides (5) and ( 7 ) respectively on treatment with copper triflu~roacetate~. Four-membered Rings.- The Paterno-Bilchi reaction is a well known method for the synthesis of oxetanes, but until now vinyl sulphides have not been reported as one of the components. Photoaddition of vinyl sulphides to benzophenone leads to variable yields (12-79%) of the oxetanes (8) and (9) with the 3-thiomethyl regioisomers (9) predominating6. I n contrast, 2-iminooxetanes (10) are generated in high yield (85%) in the [2+21 cycloaddition of ketenimines to
Ph But OOH
''
__F
BSA
0
0
(2
OH
OH
1
8: Saturated Heterocyclic Ring Synthesis
425
aldehydes under Lewis acid catalysis with lanthanide shift reagents7 . Five-membered Rings.- Tetrahydrofurans. tetrahydrofurans have been reviewed8.
Synthetic routes to Radical mediated ring closure
has continued to flourish as a method of five membered ring synthesis and two research groups have demonstrated the use of acetylenic bonds to generate methylene substituted tetrahydrofurans. Thus, Srikrisha and Sunderbabu showed that the propargyl bromoethers (111, prepared from the corresponding propargyl alcohols and ethyl vinyl ether in the presence of NBS, afford the tetrahydrofurans (12) in high yields (65-89%) on treatment with in situ generated tri-n-butyl tin hydride'. Similarly Dulcere et al. synthesised the tetrahydrofurans (15) in high yield (88-92%) from the propargyl bromoethers (14) using tri-n-butyl tin hydride in the presence of AIBN".
The propargyl bromoethers (14) were readily prepared from
propargyl alcohol and the unsaturated carbonyl compounds (13). Kobayashi's group has extended the range of functional groups which are tolerated in radical mediated ring closures with the use
of fluorine substituted double bonds as the radical acceptors. Thus, the fluoroalkenyl ethers (16), on treatment with tri-n-butyl tin hydride and catalytic AIBN, afford the fluoroalkyl substituted 11 tetrahydrofurans (17) in good yield (67-100%)
.
As demonstrated in the previous examples the majority of radical mediated reactions have used organostannanes as initiators. Pattenden's group has continued to explore cobalt(1) as an alternative, and has recently observed a divergence in stereochemical outcome dependant on the initiator used. The bromoether (19), as a mixture of diastereoisomers, produced the equatorial side chain isomer (18) on treatment with tri-n-butyl tin hydride, whereas cobalt(1) initiation afforded the axial side chain isomer (20); an explanation for the divergence of stereochemical outcome was proposed' 2. Overman's group has now adapted their highly useful and intriguing pyrrolidine synthesis to the synthesis of substituted tetrahydrofurans. The method is based on the Lewis acid catalysed rearrangement of the acetals (21) to give, formally via an oxa-Cope rearrangement followed by Prins type cyclisation and pinacol rearrangement, the tetrahydrofurans ( 2 2 ) in a stereo- and enantioselective fashion13. Yields are high (70-94%), and the all cis-stereochemistry
is generated by quenching at low temperature.
General and Synthetic Methods
426
.. h3 __c
Ph
Ph
MeS
d 2 Ph
63
J c
R’
R2
R’
Bun3SnH ___c
Bu0
BuO (16 1
X . X ’ = F o r H ; R 2 = a l k y l or
(17
F
1
R2
Ph
427
8: Saturated Heterocyclic Ring Synthesis
?L
B
r
Bu5S n H c-------------
AI BN
R3
R3
Scheme 1
428
General und Synthetic Methods
The method has been extended, in an analogous manner to the pyrrolidine methodology, to bicyclic systems whereby a ring enlarging furan annulation takes place (see Scheme 1) .14 Lewis acid catalysed rearrangement of 4,5-dihydro-1,3-oxepines has previously been shown to give 2,3-%-substituted tetrahydrofurans. Frauenrath and Runsink have now shown that the appropriately substituted dihydrooxepines (23) undergo similar rearrangement to give the 2,3,5-substituted tetrahydrofurans (24) and (25) where the 2,3-%-2,5-trans stereochemistry, which is present in several polyether antibiotics, predominate^'^. Polyether antibiotics have also provided the stimulus €or the work of Harwood and Robertson who have shown that the hydroxyalkyl furans (26) undergo an oxidative cyclisation in the presence of DDQ to give the furanyl tetrahydroiurans (27) 5 . Two research groups have focussed on the biomimetic polyepoxide cyclisation cascade reaction as an approach to polyether antibiotics. Robinson's group constructed the enantiomerically pure diepoxides (28) and (30) by stepwise Sharpless epoxidations and then submitted them to a pig liver esterase preparationl7- Ester hydrolysis € 0 1 lowed by the cascade cyclisation led to the bicycle (29) and the tricycle (31) respectively in good yield (77 and 70%) and contrasts with the poor results obtained with chemical hydrolysis. Paterson's group also synthesised their polyepoxide starting materials by sequential Sharpless epoxidations but they utilised an acid catalysed cascade reaction to generate their polyethers. From several examples reported perhaps the most interesting is the cyclisation of the triepoxide (32) to give, in 58% yield, the tricycle (331, a fragment of the antibiotic etheromycin". Nucleophilic addition to a,@-epoxysulphides is known to give a-substituted carbonyl compounds. The reaction has now been applied in an intramolecular sense and can give either 2-acyl cyclic ethers or 3-keto cyclic ethers". Thus the epoxysulphoxides (34) cyclise in the presence of pyridinium p-toluenesulphonate to give tetrahydrofurans (35,n=1) or tetrahydropyrans (35,n=2), whereas the epoxysulphoxides (36) give the larger ring keto ethers (37). The latter reaction fails when n=O. Intramolecular cyclisation of the acetylenic alcohols (38) proceeds cleanly and in high yield (80-98%) to give the a-methylene tetrahydrofurans (39) under silver catalysis2', being an extension of the known silver assisted cyclisation of allenic alcohols.
8: Saturated Heterocyclic Ring Synthesis
: o
10 M
e
0
429
2
__c
OH e
C
OH
(28)
(29)
: o M
e
O
: o 2
c
e
CHO
OH
OH
(34)
(35)
Gem s430
Grriem1 NII d Sv ri t hetic. Methods
0
(36)
(37)
c02 Rz
*= R' + *R1
COzR2
8: Saturated Heterocyclic Ring Synthesis
43 1
Walkup and Park have now shown that allenic alcohols also cyclise in the presence of palladium (11). The palladium intermediates (40) so generated can then be carbonylated to give 2-tetrahydrofuranyl acrylates (41) and (42) in variable yield (44-92%) as 1:l mixtures21. However use of mercury(I1) trifluoroacetate to promote ring closure and subsequent addition of palladium (11) followed by carbonylation usually gives predominantly cis stereochemistry. Palladium (11) catalysis also features in the synthesis of the tetrahydrofuran derivatives (44), whereby allylic alcohols and vinyl ethers are converted to the organopalladium compounds (43). These compounds then undergo intramolecular insertion followed by @-elimination to give the vinyl tetrahydrofurans in variable yield (47-94%)22 . Dihydrofurans and Benzofurans.- A simple and direct synthesis of 3(2H)-furanones, a structural feature of several biologically active natural products, has been accomplished via oxidative fission of the are keto furans (45) followed by in situ c y ~ l i s a t i o n ~ ~Yields . moderate (55-82%) with the over oxidation products (46) accounting for the lower yields in some cases. The versatility of cobalt(1) initiated radical cyclisations has been amply demonstrated in the synthesis of a range of substituted benzofurans. Thus, treatment of the iodoaryl ally1 ether (47) with cobalt(1) to give the organocobalt intermediate (48), followed by photolysis in the presence of 02, NO, SOz, (PhSeI2, (PhSI2, MeS02C1 or BrCC13 led to the oxygen, nitrogen, selenium and halogen 24 substituted benzofurans in high yield (75-85%) . Addition of 2-trimethylsilyloxyfuran (50) to the quinones (49) leads directly to the substituted furo[2,3-blbenzofurans (51), the ring system present in the marine natural product panacene, in good yields (51-91%)25. Furo[2,3-b]pyridines on the other hand are generated by the intramolecular Diels-Alder reaction of the triazine ethers (52,n=1) followed by elimination of nitrogen26. The reaction is also applicable to 2,3-dihydropyrano[2,3-blpyridines. Five-membered Rings with More than One Oxygen.- The reaction of 2,3-epoxyalcohols (53) with paraformaldehyde and caesium carbonate in acetonitrile affords l13-dioxolanes (55), generally in high yield (88-95%), and is thought to proceed via the intermediate (54)27. Alternatively epoxides can be converted to 1,3-dioxolanes (56) in
OH
8: Saturated Heterocyclic Ring Synthesis
433
(53)
R'
+ h7 R2 0
(55)
(54)
Bun3 S n I I B u ' ~PI
*
c02
R2R&
0k0 0 R'
0 (57)
( 58)
X
r n SiMe3 + (59)
I m s i - O R
I
i, RCHO. AIX3 ii,RIC HO. AIX3
R
(64)
(63)
434
General and Synthetic Methods
excellent yield (80-100%) by treatment with carbon dioxide in the presence of tri-n-butyl tin hydride/tetra-n-butyl phosphonium iodide as catalyst2*, whereas propargyl alcohols ( 5 7 ) react with carbon dioxide under cobaltocene catalysis to give a-methylene substituted 1,3-dioxolanones (58)29 . Six-membered Rings.- Tetrahydr0pyrans.- Two research groups have independently published a similar new method for the synthesis of 2,6-disubstituted 4-halogenotetrahydropyrans with all cis configuration. Thus Taddei's group demonstrated that the addition of allyl silane ( 5 9 ) to two equivalents of the aldehydes (60) in the presence of Lewis acid leads to the tetrahydropyrans (62) in moderate yield (43-86%)30. Consideration of the expected mechanism, initial formation of the allyl silyl ether (611, led them to propose that unsymmetrical products should be obtainable by quenching the intermediate with a different aldehyde and such products (63) are readily obtained (41-62% yields). Chan's group used the alkoxyallylsilanes (64) as starting materials and Vere also able to produce unsymmetrical products (63) by the addition of aldehydes or cyclohexanone in the presence of Lewis acid31 . Lewis acid cyclisation of the dioxenium cations 65), generated from trialkyl orthoformates, to homoallylic alcohols ( 6 6 ) leads to The use of the 2-alkyl-4-halogenotetrahydropyrans (67) and (68) tetrahalogeno tin compounds gives the highest yields and also affords (68) as the predominant The Darzens reaction has been used predominantly as a method for the synthesis of epoxides, but this year has seen its application to the synthesis of epoxide fused tetrahydropyrans. Thus, base treatment of the bromo esters (69) leads to an intramolecular addition to the ester carbonyl followed by epoxide ring formation giving the 2,7-dioxabicycloI4.1.Olheptanes (701, generally in excellent yield (>go%)33 . As an extension to the synthesis of cyclopentanes by iron(0) catalysed carbocyclisation, Takaes et al. have treated the diene allyl ethers (71) with iron(0) to give the substituted tetrahydropyrans (72)34. The reaction proceeds through a formal iron catalysed ene reaction and yields are good (57-84%). Dihydropyrans.- Hetero Diels-Alder reactions remain the most popular method of entry into dihydropyrans to be published this year.
8: Saturated Heterocyclic Ring Synthesis
435
B ~ O K
R3 = CN,C02EtI COMe, SOPh
OMe
Scheme 2
Grweral and Synthetic Mrthods Bulman Page's group has successfully applied the Lewis acid catalysed Diels-Alder reaction of dienes to ketones, a hitherto poorly described reaction35. The best results (yields 69-80%) are given with electron deficient ketones such as lf2-diketones, pyruvates, acyl nitriles and oxomalonates (see Scheme 2). The other two reports of new hetero Diels-Alder reactions are of the inverse type where the carbonyl compound forms part of the 4 n component. Thus, 8-acyloxy-a-phenylthio unsaturated carbonyl compounds (73) react with ethyl vinyl ether at high temperature to give a mixture of the endo (74) and (75) products. In all
exo
cases the endo products predominate and yields are good (57-96%)36. Benzylidene 2-oxocarboxylic acid esters (77), prepared by condensation of the aldehydes (76) with 2-oxocarboxylic acids and subsequent esterification, cyclise to give the benzopyran annulated dihydropyrans (78) in excellent yield (96-99%) as mixtures of
'
d ia stereoisomers . The C- or 0-alkylation of 8-ketoesters with allylic compounds under palladium catalysis has been well studied, but simultaneous Cand 0-alkylation is unusual. Huang and Lu have shown that by using the bifunctional allylic acetate (79) 8-diketones and a-ketoesters undergo C- and 0- alkylation in the presence of palladium and DBU to give dihydropyrans (80) in moderate yield (51-84%)38 . y-Allenic cyanohydrins (81) cyclise in the presence of BF-Et 0 3 2 to give the dihydropyrans (82)39, Yields are good (65-74%) and the presence of two alkyl substituents on the allene terminus is essential to the success of the reaction. On the other hand the allene sulphoxides (83) undergo base catalysed cyclisation to the dihydropyrans (84)40.
The monocyclic allene (86) has been generated
for the first time by n-butyl lithium treatment of (85). The allene ( 8 6 ) was not isolated but was characterised by the range of cycloadditions it undergoes41. The reported synthesis of 4H-pyrans (87) by Ibrahim42 has been reinvestigated by Martin et al. and revised structures for many of the products are given43. Six-membered Rings with More than One Oxygen.- A formal [2+2+2] cycloaddition is proposed for the reaction between 1,3-diketones (88), olefins and molecular oxygen to give the cyclic peroxides (89)44. Catalytic electrical activation is required to initiate the reaction and yields are variable (11-79%). One electron transfer oxidation of ( 9 0 ) in the presence of ethylene glycol affords the
437
8: Saturated Heterocyclic Ring Synthesis
0
phsd +< OAR2
OEt
R’
(73)
Q J?
CHo
+
LR
0
C02H
i, KOH,MeOH
R’=OMe,a l k y l , a r y l
1
ii, CLCQMe.Et3N.DMAP.CH2CI2
; R2 = a l k y l , a r y l
438 R' BF30Et20
R2
__l___t
MeOH
R'
a R2
phs5fI? j
CN
NaH .THF
LOH
(83)
BunL i __c
0
R'YR2 +
(88)
(89)
8: Saturated Heterocyclic Ring Synthesis
439
bicyclic ethers (91) exclusively in high yield (77-90%)45. Medium- and Large-ring Ethers.- Cycloaddition of dimethyl acetylenedicarboxylate to the dihydropyrans (92) leads to the bicycles (93) which are readily converted, either thermally or using Lewis acid catalysis, to the eight ring ethers (94)46. Yields are moderate (55-81%) and the reaction can also be applied to dihydrofurans leading to the seven ring ethers (95). The Paterno-Bdchi reaction has also been applied to large ring ether synthesis and involves the photocycloaddition of the keto vinyl ethers (96) followed by methanolic oxetane ring opening to give the 47 ethers (97) The intramolecular zinc ene reaction of the allylic ethers (98) proceeds at 8 0 ° C to give the large ring ethers (99) after quenching with either trimethyl tin chloride (99,X=SnMe3) or ammonium chloride
.
(99,X=H)4 8 . 2
Sulphur-containing Heterocycles
During the course of investigations into the synthesis of polyether antibiotics Nicolaou et al. have isolated the first example of a stable 1,2-dithietane. Irradiation of the dithionolactone (100) lec directly to the dithietane (101) in 65% yield. The chemical and physical properties of (101) are discussed and include the expected sulphur extrusion product (102) and the unexpected rearrangement product (103)49. The regioselectivity of the [ 2 + 2 1 cycloaddition of thioketones to ketene dimethyl acetals to give thietanes (104) In general the and (105) has been studied by Ooms and Hartman5'. monoalkyl substituted ketene acetals give 3,3-dimethoxy isomers (104) whereas monoaryl substituted ketene acetals afford the 2,2-dimethoxy isomers (105) exclusively. Dialkylketene acetals, however, give mixtures of regioisomers. The hetero Diels-Alder reaction of suitably substituted triazines followed by nitrogen extrusion to give substituted pyridines is well known. Taylor's group has now applied the reaction in an intramolecular sense to furnish dihydrothienopyridines. Thus, cycloaddition of the 3-thioalkynyl- or 3sulphonoalkynyl-1,2,4-triazines (106, n = 0 , 2 ) affords the dihydrothienopyridines (107) on heating, whereas the sulphoxidotriazines (106, n=l) cyclise at room temperature.51 5-Thioalkynyl-l,2,4-
C@ Me
I
A
I
C02 Me
COZMe
R
Y
Lewis acid
COz Me G C OR z M e
(95)
8: Saturated Heterocyclic Ring Synthesis
441
&* hJ
__jc
0 H
S
H
H
H
MeoxoMe hJ
+
qo
R3
R4
R'f;
Me0
M e 0 R4
+
R3
R2fl R3
OMe R4 OMe
442
General and Synthetic MethodJ
triazines (108, X=S) on the other hand afford the dihydrothienopyrimidines (110, X = S ) via the adduct (109, X=S) which eliminates R2CN rather than RICN, since the bridgehead N-N bond is weak.52 Expulsion of HCN occurs in the similar hetero Diels-Alder reaction of 2-thienoalkynyl pyrimidines (111, X = S ) to give dihydrothienopyridines ( 1 1 2 , X = S ) .53 Both the latter reactions can be applied to the oxygen containing systems (X=O). The dicyclohexylammonium salts of the monothio-B-dicarbonyl compounds (113) add to unsaturated carbonyl compounds to afford the 3-acyl-2H-thiopyrans (114). The reaction gives good yields (55-86%) and is thought to proceed via a Michael addition followed by aldol condensation.5 4 Michael addition of thiophenol to a,B-unsaturated carbonyl compounds ( 1 1 5 ) followed by Lewis acid catalysed electrophilic cyclisation leads to thiochromans (116) in variable yield (35-95%), where tin tetrachloride is the preferred Lewis acid.55 3 Heterocycles Containing More than One Heteroatom Nitrogen- and Oxygen-containing Rings Five-membered Rings. Grigg's group has continued their studies into the use of oximes in cycloaddition reactions to furnish isoxazolidines. The reactions proceed via an initial Michael addition and subsequent dipolar cycloaddition of the generated nitrone and therefore afford the possibility of four variants made up from either inter- or intramolecular Michael addition and cycloaddition. An example of each type is outlined in Scheme 3. 5 6 t 5 7 The usefulness of dipolar cyclo-additions of nitrile oxides would be considerably extended if the reactions could be induced to proceed with enantiocontrol. Curran and Houk's groups have reported on just such an approach using chiral acrylates. A range of chiral auxilliaries were used including menthol and Oppolzer's camphor sulphonamides under both thermal and Lewis acid catalysed conditions, but enantioselectivity was generally poor. 58 The best results were obtained with the dicyclohexyl sulphonamide (117) and the nitrile oxides (118) where diastereomeric excesses were of the order of 55%. Two research groups have demonstrated independently that the intramolecular delivery of nitrogen by a neighbouring hydroxyl group is most effectively achieved by the cyclisation of N-benzoyl carbamates. Thus Knapp's group converted the alkenes (119) to the
8: Saturated Heterocyclic Ring Synthesis
443
A
A
I
R9 R2
__t
R’nT
R2
N
-
R’
X
R
W
(110)
N
(114) R 4 = CHO, COCH3, or COPh
QJSH
R’ J?R2
5 R’
444
Generul and Synthetic Methocls
Inter molec ul ar. int ramolecutar
u
C02Me
+
+ 0
Intramolecular , inter molecular
0' H
Scheme 3
8: Saturated Heterocyclic Ring Synthesis
445
benzoyl carbamate derivatives (120) via bromohydrin formation and subsequent capture of the alcohol function with benzoyl isocyanate and showed that base treatment affords the oxazolidinones (121) in good yield (61-88%).59 On the other hand McCombie and Nagabhushan converted the epoxy alchohols (122) to the epoxy carbamates (123) which also underwent base mediated ring formation with concomitant benzoyl migration leading to (124) in high yield (79-87%).60 4-Vinyloxazolidinones (126) have been synthesised via palladium catalysed ring closure of the ally1 dicarbamates (125) where yields are generally good (58-98%),61 whereas 4-methyleneoxazolidinones can be prepared by ruthenium catalysed treatment of propargylamines (127) with carbon dioxide (yields 63-80%) .62 Six-membered Rings Yamamoto et al. have developed the single observation made by Kato's group into a general synthesis of lI3-oxazines from acyl Meldrum's acids. Thus, heating the Schiff bases (128) with the acyl Meldrum's acids (129) affords the oxazines (130) which undergo thermal conversion to the oxazines (131).63 Yields of the initial adducts are good (54-83%), although the thermal conversion proceeds in more variable yield (24-75%). Alternatively, reaction of the Schiff bases (128) and Meldrum's acids (129) in the presence of trimethylsilyl chloride and triethylamine leads to the oxazine carboxylic acids (132) in high yield (70-go%), after aqueous hydrolysis of the intermediate silyl 64 esters. Denmark's group has continued their investigations into cycloadditions involving N=O heterodienes. They have now shown that vinylnitrosium cations (133) add intramolecularly to olefins giving polycyclic products (134) after trapping the intermediate cycloadducts with cyanide. 65 The yields and stereochemical outcome are dependent on the stereochemistry of the starting materials. a-Acylketenimines (135) have been used as the starting material for a range of heterocyclic products as outlined in Scheme 4,66 and the use of chlorosulphonyl isocyanate in heterocycle synthesis has been reviewed.67 Nitrogen- and Sulphur, and Sulphur- and Oxygen-containing Rings Nitrogen containing aromatic heterocycles react with trimethylsilyl methyl sulphide in the presence of fluoride ion to give polycyclic 1 ,3-thiazolidines (136), usually in high yield (43-96%),68 and the lI3-diazabutadienes (137) react with sulphene to give 1,2,4thiadiazene-1,l-dioxides in good yield (64-90%).69
N SO2 (117)
v (127)
major diastereoisomer
NHR
+
C02
Ru, Ph3P
O K N R
0
8: Saturated Heterocyclic Ring Synthesis
R2
J
447
50°C
Ph
Me3S iC I,E tgN
R’ N L f o * s i M e 3 Ph*O
H20
R2
R 3S iOTf T
(134)
NAr
NEt
NAr
(135)
Scheme 4
448 R3
R3
R3
F-
R' R
2
I
~
S
Ar
Ar
I /
Rl
N\
asH R2go
R2
+
ii. A c 2 0
N"2
H
O
0
MeoO-S-NH2R' COCl
Me0 \
R'
(140)
8: Saturated Heterocyclic Ring Synthais
449
1,5-Benzothiazepinonones (139) can be synthesised in variable yield (17-90%) from 2-aminobenzene thiols by heating with the lactones (138) in the presence of pyridine, followed by acetic anhydride mediated cyclisation.70 1,4-Benzothiazepines on the other hand have been synthesised via phosphorus oxychloride mediated cyclisation of the thioether amides (140), although the yields are poor (8-37%).71 Several methods have been published during previous years for the preparation of thiocarbonyl ylids such that the ylids are now readily accessible. Hosomi et al.have now discovered that thioformylium methylide (141) reacts with carbonyl compounds to afford 1,3-oxathiolanes (142) in variable yield (35-86%),72 and the synthesis and reactions of sultones has been reviewed.73 4
Nitrogen-containing Heterocycles
Three- and Four-membered Rings. - The azomethine ylides (144) are formed by gas phase thermal cycloreversion of the oxazolidines (143) and undergo ring closure to give the substituted aziridines (145) in moderate to good yields.74 The reaction fails when carried out in the solution phase; cycloaddition of the intermediate azomethine ylides with formaldehyde, to reform starting material, is now the dominant reaction mode. The N-difluoromethylaziridine (149) has been prepared by a similar ylide cyclization route.75 Addition of difluorocarbene to the imine ester (146) produces the azomethine ylide (147) which undergoes prototropic rearrangement to give the ylide (148). Cyclization then affords the product (149) in moderate yield. The palladium-catalysed addition of the perfluoroalkyl iodides (150) to the allylic amines (151) furnishes the aziridines (152) in moderate yields.76 [2+21 Cycloaddition of an imine to an electron-rich alkene is a potentially simple route to the azetidine system but the reaction is seldom successful in practice because conditions which allow efficient formation of the dipolar intermediate generally promote reactions other than ring closure. Aben et al.have now shown that the azetidines (155) are formed in excellent yields, from the imines (153) and the enamine (154), by carrying out the reaction at high pressure.77 The products are unstable at room temperature under normal pressure and decompose to give a range of ring-opened products. Reaction of epi-chlorohydrin with primary amines is a well established method for the synthesis of azetidine-3-01s but the
Genrml und Synthetic Methods
450
i I
R4
R4
Ph Ph
w C O z E t N
I
CF2 H
Ih21 ‘C02
Et
8: Saturated Heterocyclic Ring Synthesis
45 I
reaction usually only works well for bulky N-substituents. Conversion of the intermediate l-(akylamino)-3-chloro-2-propanols to their trimethylsilyl derivatives (156) allows formation of the azetidinyl trimethylsilyl ethers (157) to be achieved with a wide range of N-substituents, although yields are still only moderate. 78 Five-membered Rings. - Syntheses of the indolizidine7' and pyrrolizine" ring systems have been reviewed and a report on radical reactions in organic synthesis includes the preparation of five- and six-membered nitrogen heterocycles.81 Interest in the formation of five-membered nitrogen rings by [ 3 + 2 1 dipolar cycloaddition of azomethine ylides, and related species, has waned considerably this year, no doubt because the major synthetic challenges associated with the general use of these intermediates have now largely been met, as is well illustrated by the work described in full papers from the groups of Tsuge82-84 and Z~chiwa.~~ One ' ~ new ~ route to azomethine ylides has been reported, which is based upon pyrolytic cycloreversion of 1,3-oxazolidines. Thus, FVP of the oxazolidines (159), which are readily available from the a-amino esters (1581, followed by intramolecular [3+21 cycloaddition affords the pyrrolidines (160) in excellent yields.87 Interestingly, this reaction completely fails when carried out in solution where, as was the case with the azomethine ylides (144) discussed earlier, cycloaddition of the intermediate azomethine ylide with formaldehyde to reform starting material competes effectively with the intramolecular cyclization. Formation of hydroisoindoles by use of the intramolecular Diels-Alder reaction holds great potential as a general route but sluggish reactivity and low stereoselectivity can still present problems. Guy et al.have now shown that introduction of a bulky substituent into the allylic unit of the azatrienes (161) substantially increases both reactivity and stereoselectivity: the cisproducts (162), for example, are formed in quantititative yield.88 In a related study, Mellor et al.have shown that a wide range of functionalised hydroisoindoles (165) can be prepared by acylation of the aminodienes (163) with the acid chlorides (164) (or 89 corresponding anhydrides) and subsequent cyclisation. Stereoselectivity can be high, generally in favour of trans products, but the cis adducts (166) are also available in some cases by reductive dehalogenation of the initially formed trans adducts of diene with halogen-substituted dienophile.
General and Synthetic Methods
452
12 Kbar
PhCH= N- R
____t
/-
But OMc
\H
Me
Me
I
U
(153) (155)
(154) OSiMe3 I
Me3Si0
NEt3 __l_t
MeCN
R-NH
R
CI (157 1
(156)
R'-NH-CH-C-o
II
2 (CHZO)
-0
toluene retlux
I R2
I. R'
R' ( 159)
R
toluene
170 'C
(16
8: Saturated Heterocyclic Ring Synthesis
453
Two publications from Carrie and co-workers describe further applications of the general methods of nitrogen ring synthesis pioneered by this group which utilizes nulceophilic cyclization of an amine, generated in situ by reduction of the corresponding azide with Ph3P/H20. Thus, the indolizidines (168) and (169) are formed in moderate yields from the azido-diene (167) by reduction, followed by lI6-Michae1-type addition and acylation. In the second report, the functionalised nitrogen heterocycles (171) are prepared in good yields and under mild conditions by reduction of the azides (170) and subsequent intramolecular 1,4-addition.91
The
products (171) are formed as mixtures of diastereomers. Knight and co-workers have described an elegant synthesis of the optically active substituted pyrrolidines (174) by IrelandClaisen rearrangement of the azalactones (1731, which are readily available from the corresponding amino acid derivatives (172).9 2 The relative stereochemistry of the products (174) is consistent with the intermediacy of a boat-like transition state in which the R group occupies an equatorial position. Remarkably, complete chiral induction occurs to give only one isomer even when R=methyl. An enantiospecific total synthesis of (-)-a-kainic acid has been 93 achieved by the same group using this methodology. Intramolecular ene-type reaction of the diene-Fe(C0I3 complexes (175), in the presence of a suitable ligand, affords the spirolactam derivatives (176) as mixtures of epimers, in generally good yields.94 The mechanism of the reaction is under investigation but the stereochemistry of the products suggests a step involving co-ordination of the alkene unit to iron. FVP of the Meldrum's derivatives (177) and subsequent trapping of the reaction intermediates with MeOH/NEt3 affords the bicyclic enaminoesters (180) in moderate yields. 9 5 By analogy with earlier work, the aminomethyleneketenes (178) are probable reaction intermediates which then undergo a novel cyclization to form the acid chlorides (179). Two extensions of known ring-forming procedures have provided useful routes to unsaturated five-membered nitrogen heterocycles. Livinghouse and his group have described the preparation of 2acylpyrrolines in good yields by intramolecular acylation of silyloxyalkenes with a-keto imidoyl chlorides (Scheme 5) .96 The intermediate imidoyl chlorides are not purified but cyclized directly, under high dilution at low temperature. Intramolecular
COzEt
HNC0 7 Et
CO2Et
I
Reagents : i , ( P r i I Z N - L i
ii, HF-HzO
1
( 3 equiv.), ButMe2SiCl ( 3 e q u i v . ) , THF, -100 + - 2 O o C
-THF;
iii, CHzN2, E t 2 O
6iJR2-
Fe (CO ) 2 L
BU"ZO.L reflux
R3
0 R' (175 1
L = CO.Ph,P
R'
(176 1
;
8: Saturated Heterocyclic Ring Synthesis
455
rn=lor2 n =lor2
(177)
COzMe MeOH
NEt 3
i. LiCH2NC
-
ii, But MeZSiCL
R4COCI
J
py.
OSi I
L Scheme 5
0
reaction of an allylsilane with an iminium ion is a well characterised route to nitrogen heterocycles and Damour et al.have now shown that the analogous reaction can be carried out using propargyltrimethylsilanes, to produce a range of 3-allenyl nitrogen heterocycles. Thus, reaction of the alkylaminopropargylsilanes (181) with formaldehyde, under Mannich-type conditions, forms the intermediate iminium salts (182) which cyclize, in variable yields, to give the products (183).97 Several new examples of the preparation of five-membered nitrogen heterocycles by radical cyclization have appeared this year. Newcomb et al.have shown that the N-hydroxypyridine-2-thione carbarnates (184) are a convenient source of aminyl radicals which undergo efficient cyclization in the presence of a hydrogen atom donor and a weak organic acid to give the substituted pyrrolidines (185), with moderate stereoselectivity.98 The improvement in yields seen in the presence of the acid suggests the involvement of aminyl cation radicals in the cyclization step. In a similar, C-C bond forming, reaction the perhydroindole-2-carboxylic acids (187) and (188) have been prepared by a route which involves cyclization of the carbon radical formed by photolysis of the N-hydroxy-2-thiopyridone derivative (186).99 Treatment of the allyl-2,2,2-trichloroethylamines (189) with tributylstannane under standard radical forming conditions affords cis-2,4-disubstituted-3,3-dichloropyrrolidines (190) in the excellent yields.l o o Advantages of this procedure, compared with
cyclization of the corresponding 2-monohaloethylamines, are much greater stereoselectivity and the compatibility of the free N-H with the reaction conditions.
In a similar procedure, the a-chloro
amides (191) cyclize efficiently to the substituted y-butyrolactams (193), via the intermediate methylthio-substituted carbon radicals (192). l o ' Cyclization of the analogous a-chloroamides lacking the methylthio group is very much less efficient. The pyrrolidines. (196) are formed in moderate yields by homolytic ' S E T ' ring expansion of the N-acryloyl aziridines (194). I o 2 The ketyl species (195) are likely intermediates. Two natural product syntheses which utilize radical cyclizations have been reported. Formation of the tetracyclic enol acetate (198) by cyclization of the radical derived from the tributylstannane (197) is the key step in the synthesis of (+)-3-demethoxyerythratidinone reported by Danishefsky and his grouplo3 and Baldwin et al. have described a synthesis of
457
8: Saturated Heterocyclic Ring Synthesis
C E C -(C H2),,-
Me3Si-CH2-
NHR
n = 2-4
/
CF3COZH l C H Z O
THF,H20
CF3C0, R
1 Bu
I h 3, CF3COZH But SH
*
'"R- 2
'-R2
(184)
o"q2Buti
COR
0- N S
COR @--c*2*"t
2-py
-s
2-py-s
; H
Generul and Synthetic Methods
458
-
R2
Bu"SnH
CI3C R' A
A1 BN
NI
cu R2
R'
I
I
H
0
R-N
GsMe
-
0
T Bun3SnH
A[ BN
R - N Y C
L
(191)
M+
(194)
c
(195)
H
8: Saturated Heterocyclic Ring Synthesis
459
(-1-a-kainic and (+)-a-allokainic acids which is based upon cobalt-mediated cyclization of the N-alken-2-yl iodide (199) to give the intermediate substituted pyrrolidines (200) and (201). l o g Two new halolactamization procedures have been reported, both based upon the use of thioimidates to achieve N- rather than 0cyclization. Treatment of the y,b-unsaturated thioimidates (202) with iodinelo5 or bis (collidine)bromonium perchloratelo6 affords the functionalised y-lactams (203) in moderate to good yields and with high regio- and diastereoselectivity. In a related cycloamination procedure, Mellor and co-workers have shown that sulphenylation of the unsaturated amides (204) in the presence of manganese acetate leads directly to the pyrrolidine derivatives (205) in moderate yields. Attempted cyclization of a higher homologue, to form a piperidine derivative, was not successful. Two useful palladium-mediated cyclization procedures have been described this year. Conditions for the cyclization of a range of 2-iodoaryl alkenes to form nitrogen heterocycles have been optimized, with the result that several ring systems are now available in high yields using this methodolgy. Cyclization of N-methallyl-2-iodoaniline (206), for example, fails under standard conditions but addition of one equivalent of sodium formate, to reduce the initial organopalladium cyclization product (2071, enables a good yield of the indoline (208) to be obtained.108 The pyrrolidine derivatives (213) are produced in high yield by reaction of the allylic tosylamides (209) with ethyl vinyl ether (210) in the presence of palladium acetate.'" The organopalladium complexes (211) and (212) are probable intermediates. An interesting variant of the standard alkylation procedures for formation of nitrogen heterocycles has been described by Bulman Page and his group.'" Generation of the anion (215) by deprotonation of the primary aminoketene dithioacetal (214) followed by reaction with a bis-electrophile (216) and subsequent base-induced cyclization gives, in a one-pot operation, the five- and sixmembered nitrogen heterocycles (217). Only two examples have been described so far [(216)=1,2-dichloroethane, epichlorohydrinl but the ready availability of the precursor (214), together with the simplicity and potential generality of the route, could make this a very useful procedure for the preparation of a wide range of functionalised nitrogen heterocycles. Condensation of the conjugated enones (218) with diethyl aminomalonate (219) in the
General arid Synthetic Methods
460
N-CO, Ph
-'
0 Si Me 2 8u
BnO
t + -0SiMez
B nO
R2
R4
But
OSi Me2 But
BnO
1 2 1 THF
R'*sMe H
R3
R5 I
Br (colt )2CL04
CH2Cl2
(202)
I , PhS S P h,Mn (OAc 13, C F3C 02 H
c
ii, Na2C03
(204)
PhS
dR I
COAr (205)
8: Saturated Heterocyclic Ring Synthesis
46 1
H
H
I
I
2’1.
Pd(OAc)2, BU”4N+Cl-
NEt3, N a 0 2 C H ( 1 equiv.) , DMF
t-
-co2
\pd
H
I
HC02
-
L
Pd
H
QJ3Jdo
YNHTS R Pd (OAC) 2
t o I uene
(209)
r R&oEt I Ts
462
n
XS
Ph
R' andlor R 2 = a l k y l
BU"L i __.t
n
NH2
(220)
8: Saturated Heterocyclic Ring Synthesis
463
presence of zinc chloride affords the novel 2,2-diethoxycarbonyl-3, 3-dialkyl-3,4-dihydro-2H-pyrroles (220) in generally good yields.'" The reaction is general for R1 or R2=alkyl but fails with aryl substitution here. Six-membered Rings. - A review of the chemistry of imines has appeared which includes several examples of the use of azadienes in In the same vein, six-membered nitrogen ring synthesis.'12 Barluenga and his group have reported an efficient synthesis of the electron-deficient 2-azadiene (221) and its reaction with the cyclic enamines (222) to give the fused tetrahydropyridine derivatives (223) Reaction of the vinylketene silyl acetals (225) with the imine-TiC14 complex (2241, at low temperature, affords the 5,6dihydro-2-pyridones (226) in variable yield, together with the 5The ratio of products can be amino-2-alkanoates (227).'I4 controlled to a certain extent by varying the reaction conditions but the substitution pattern has the greatest effect: formation of cyclized products is favoured when the 3-position of (225) is, and the 2-position is not, substituted. Grigg and co-workers have reported a high yielding one-pot procedure for the formation of the cyclic nitrones (230) from the unsaturated keto-esters (228) by a two-step process involving initial formation of the oxime (229) followed by 6 - a - t r i g cyclization.57 Inter- or intramolecular 1,3-dipolar cycloaddition
of the nitrones (230) with alkenes can be carried out in high yield, making them extremely versatile synthetic intermediates. Three related cationic cyclization procedures for the construction of six-membered nitrogen rings have been described. Lewis acid-mediated cyclization of the a-amino aldehydes, or acetals, (231) affords the substituted piperidines (232) and (233) in moderate yields. Although the diastereoselectivity of the cyclization is low when X=CHO, the corresponding ethylene acetals cyclize to give exclusively the =-products (232). In their continuing studies of the use of in situ-generated iminium ions in synthesis, Grieco and his group have described a total synthesis of (+)-yohimbone which utilises, as the key step, a novel polyolefin cyclization in which an unstabilised iminium ion is the initiator and Thus, the trans- isoquinoline an allylsilane the terminator. '16 derivative (235) is formed in good yield by treatment of the trifluoroacetate salt of (234) with aqueous formaldehyde. Pyrroles have been little exploited as terminators in cationic cyclizations
464
/ R 4
+
TiCI,
RI
OSiMe3
/
- 100°C
+ NHR4
COzMe
-
C02Me
H2NOH
H 2 0 , r.t.
R1
R2
R’
J
R2
8: Saturated Heterocyclic Ring Synthesis
465
despite the obvious potential for easy access to bicyclic nitrogen ring systems. The main problem is the tendency of the pyrrole starting materials to polymerise under the acid-catalysed reaction conditions, but Tanis and Raggon have now found that when an epoxide is used as the initiator cyclization can be effected with relatively weak Lewis Acids to give products in moderate to good yields (Scheme The route is useful for the formation of six- and seven6 ) . '17 membered rings, and cyclization usually occurs onto the most substituted carbon of the epoxide, although 6-endo, antiMarkovnikov, cyclization is preferred over the corresponding 5 - e ~ ~ mode. In a preliminary report, van der Louw et al. have shown that the substituted piperidine (238) is formed in good yield and under mild conditions by an intramolecular metallo-ene reaction of the 2(allylmethylaminomethyl)-2-propenylzinc,or magnesium, halides (236), followed by trapping of the cyclized intermediate (237) with chlorotrimethylstannane.48 Quenching with NH4C1 to give directly the product (237, met=H) is much less efficient. Palladium-catalysed cyclization of 5-alkynlyamines is a well documented route to tetrahydropyridines but yields can sometimes be low. Au(II1) has now been shown to be an effective catalyst for this procedure: the alkynylamines (239) are converted to the tetrahydropyridines (240) under mild and neutral conditions and, for the examples given, in much higher yields compared with the palladium-catalysed reactions. 118 Base-catalysed cyclization of the unsaturated amine derivatives (241) leads to mixtures of the diastereomeric 2,3-disubstituted piperidines (242) and (243) in good yields.'" The ratio of products varies, depending upon the geometry of the double bond in (241) and excellent diastereoselectivity f o r either product can be achieved. These stereochemical results can be rationalised by assuming chair-like transition states where steric effects between the unsaturated ester unit and the N- and 0- substituents are minimised. The mono- and bicyclic piperidine derivatives (245) are formed, in moderate yields, by a photochemical reductive cyclization of the N- unsaturated B-ketoamides (244).120 Cyclization occurs only in the 6-=-trig(-dig) mode and, although diastereoselectivity is low €or cyclization of N- ally1 derivatives, use of the corresponding N- propargylamines efficiently yields a single 5-methylene-substituted product where the double bond is available for further modification at a later stage.
466
General and Synthetic Methods
major : minor Y=H o d
X = CH0,CH(OR2), ( 231 1
(233)
(232)
i, CF3CO2H ii,CH20,HzO.THF
I
I
40 ' C
e . g . BF,-OEt2, Et2AIC12 n=2
[4 1 4 Scheme 6
<")
Me
Me
I
met met
\ /
= MgCI.ZnBr
-
Me
ClSnMe3
___c
met
SnMe3
8: Saturated Heterocyclic Ring Synthesis
467
Two useful carbanion-mediated routes to six-membered nitrogen rings have been reported this year. Enders and co-workers have utilised their SAMP-/RAMP- hydrazone methodology in a general enantioselective synthesis of the substituted tetrahydro-2,5(lH,3H)quinolinediones (249).12' The key step is the asymmetric Michael addition of the anions derived from the enhydrazinones (246) to the arylidene malonates (2471, to furnish the 1,4-adducts (248). Lactamization, followed by reductive removal of the chiral auxiliary and loss of the ester group, then gives the products (249) in good overall yield and in very high enantiomeric purity. The 4-aryl-1,2,3,4-tetrahydroisoquinolines (252) are formed in moderate overall yields by a general procedure which involves formylation of the anion derived from the N-methyl benzamides (250) followed by cyclization and reduction. 22 The corresponding 3,4-tetrahydroisoquinol-l-ones are also available from the cyclized products (251) by a dehydration - catalytic reduction sequence. A useful synthesis of the 4-aryl-1,4-dihydro-3(2H)isoquinolinones (256) has been reported by Petrov et al. 123 Reaction of the N-benzyliminies (253) with dichlorocarbene gives the intermediate 2,2-dichloroaziridines (254) which are converted to the products (256) by hydrolytic rearrangement to the a-chloroarylacetamides (255) followed by Friedel-Crafts cyclization. Although the route comprises three steps, the starting materials are readily available and yields are generally good. The use of iminium salts in nitrogen ring synthesis is very well documented when substituents are standard alkyl or aryl groups but formation of these species adjacent to an electron-withdrawing trifluoromethyl group is much more difficult. Fuchigami et al.have now shown that the a-trifluoromethyl iminium cation (258) can be generated easily, from the a-methoxy N-alkyl-N-(2,2,2-trifluoroethy1)aniline (257) and can be trapped with the silyl enol ether (259) to give the product (2601, in moderate yield. 124 The 4,4-disubstituted 1,4-dihydropyridines (262) are available from the 125 a-pyrone derivatives (261) by the route shown in Scheme 7. Although yieds are only moderate at best, the route is straightforward and may have more general application. Two similar approaches to the nortropane ring system have been reported this year, both of which start from 1,3-cycloheptadiene and use as the key step an intramolecular nucleophilic displacement reaction (Scheme 8). Bdckvall et al.prepared the intermediate (266)
Getterul und Synthetic Methods
468
R' -C=C-(CH2),
- CHR' I
R' CH2
McCN
NH2
NEt3
\
C 0 2R 2
*
R'
iii, . 6unLi.TMEDA,THt A r CH=C(C02R2)2 - 7 8 "C
R'
NH
I
-NR,*
R' f i 2 R 2
I
R'
(247)
=
-"J
NR 2)c
(248)
i, A ,toluene ii,
Z n ,AcOH
J5b0
R' R'
I
H e . e.3 97
469
8: Saturated Heterocyclic Ring Synthesis
R
R
":&:I
R
pR3 R2 R
'
a
N
R3
ZnCL2
+---
470 Et
Ti C14
I
phNY cF3 OMe (257)
1
-H+
- MejSiOH Et
x:
(26 0 1
Et 02C
H N 3
R = electron - withdrawing group
(261)
1
/!eCOZEt
Scheme 7
8: Saturated Heterocyclic Ring Synthesis
47 1
by palladium-catalysed chloroacetoxylation of 1,3-cycioheptadiene (2631, to give the chloroacetate (2641, followed by nucleophiiic displacement with inversion to form the N-toluenesulphonyl derivative (265). Hydrogenation of the double bond, followed by conversion of the acetate to mesylate then gives (266) which undergoes efficient base-catalysed cyclization to produce the nortropane derivative (270).126 Starting with 6-benzyloxy-l,3cycloheptadiene, exo- and endo-tropanol derivatives can be prepared by an analogous reaction sequence. In the second approach, nitroso cycloaddition to 1,3-cycloheptadiene, followed by N-0 reductive cleavage gives the intermediate (268) in excellent yield. Conversion to the chloride (269) followed by base-catalysed cyclization and debenzylation then affords nortropane (271).127 The unsaturated intermediate (268) can also be converted by a similar procedure to N-benzylnortrop-6-ene (272) in good yield. Six-Membered Rings Containing Two Nitrogens. - A new synthesis of 5 ,6-dihydropyrimidines has been reported by Garratt et a1 . 128 Reaction of the N-cyano-imine derivatives (273) with the amines (274) to give the intermediates (2751, followed by reaction with a second amine (276) and cyclization,affords the products (278) in good yields, presumably via the intermediates (277). The method is potentially general for the synthesis of 5,6-dihydropyrimidines and preliminary experiments suggest that it may be useful in five-membered hetercyclic synthesis also. In another base-catalysed > cyclization procedure to the same ring system, the unsaturated thioureas (279) have been shown to cyclize in high yields to give the 2-thioxo-5,6-dihydro-pyrimidine derivatives (280). Medina et al.have utilised a novel intramolecular oxidative cycloaddition to prepare the tricyclic tetrahydropyridazines (282) from the 1,2-dihydro-3H-pyrazol-3-ones (281).130 The mildness of the reaction conditions, together with the generally high yields obtained and the stereospecific nature of the cyclization make this a potentially very useful method for the synthesis of a range of fused six-membered nitrogen heterocycles. Cyclization of an 2-aryl radical onto an azo nitrogen has been investigated by Beckwith and co-workers as a potential route to The results show five- and six-membered nitrogen heterocycles.13' that treatment of the halides (283) with tri-n-butylstannane does indeed lead to formation of cyclized products (284) and (285) but yields are only moderate at best. Nevertheless, the tetrahydro-
472
-0-0 NHTs
YHTs
CI
iii, iv, v
ii
OMS
OAc
(266)
(265)
vilR=Ts R
I
0
R
= Bn
__f
ix
(2 6 3)
(270) vii
I
xii
4
,COPh
NHCOPh
-0
ix, x , x i ___t
or x ,xi
CI
OH
(267)
(269)
(268) h i i i
Bn I
4 (272)
Reagents : i , Pd(OAc12, L i CI, LiOAc ,p
-
benroquinone, HOAc; ii. NaNHTS;
iil. H2/ RhCl (PPh3)z; i v , N a O H , M c O H - h O ; v,MsCl/NEt3; vi ,KzC03/MeOH; vii, PhCONHOH/MeqNtIO~-; v i i i , A l / H g ; i x , H Z / P d / C ; x.LiAlH4; x i , SOCl2; xii, pyridine; xiii, K2C09 ultrasound
Scheme 8
473
8: Saturated Heterocyclic Ring Synthesis
1
R2-NH 2 (276)
N
NCN
N
f:HR2i
.R3
S PhCH=CH CONHCSNHR
NaOEt
\NKN/H
_c_c
(279)
Ph
(280)
yJ
cc-0
R’
Pb(OAc) 4 . )
CH2C12, 23 “C,5-15 rnin
R2
474
Get1em1 ati d Syti thet ic Methods
cinnolines are formed as major products and optimization of reaction conditions could make this a useful route to this ring system. Reaction of 2-phenylenediamine with the 2,3-epoxy-aldehydes or -esters (287) leads to formation of the 2 - hydroxyalkyl-1,2dihydroquinoxalines (288) in good yields. 132 The aldehyde reaction proceeds via formation of an intermediate imine and subsequent ring opening of the epoxide, but for the epoxy esters the sequence is reversed. The reaction is therefore only successful in this latter case when nucleophilic ring opening at C2, rather than at C 3 , of (287) is favoured. Seven- and Eight-Membered Rings. - A review covering the synthesis of aza modified adamantane derivatives has appeared. 133 The azabicyclo t4.2.1.1 nonane derivative (292) is formed in good yield by Lewis acid-catalysed reaction of 2,5-dimethoxy-l-methoxycarbonylpyrrolidine (289) with l-ethoxy-l-trimethylsilyloxy-1,4-pentadiene (290), probably via the intermediacy of the a-methoxylated pyrrolidine (291).1 3 4 Irradiation of benzonitrile in the presence of the enol ethers (293) leads to formation of the seven- and eightmembered nitrogen heterocycles (295) in moderate yields, based upon starting materials consumed.135 The azetidines (294) are likely intermediates. Reaction of the 2-phenylenediamines (296) with 2hydroxy-6-methyl-4-pyrone (297) produces the diazepines (298) and (299) in good combined yield.136 The requirement for a chromatographic purification step is a disadvantage but the experimental procedure is 2imple and may have general application. The 5,5-disubstituted 5,6-dihydro-4H-1,2-diazepines (303) can be prepared in excellent yields by reaction of the dihydroxyazines (302) with aluminium chloride. 137 The latter compounds are readily available by reaction of the azines (300) with lithium di-isopropylamide, followed by addition of the ketones ( 3 0 1 ) . The method gives easy access to the 5,5-substitution pattern, making this a useful addition to the methods currently available for synthesis of this ring system. Intramolecular base-catalysed cyclization of the
bis(2-isocyano-2-tosylethyl)benzenes (3041, in the presence of the alcohols (3051, affords the 1,6-dihydro-3-benzazocines (306) in good yields via a multistep addition-prototropic rearrangement sequence.138 Finally, the synthesis and stereochemistry of benzodiazocines has been reviewed. 139 B-Lactams, Penicillins, Cephalosporins and Related Compounds.Reviews have appeared on enantioselective syntheses of carbapenem
8: Saturated Heterocyclic Ring Svnthesis
475
X=H,OH
X = H, OEt
(2861
(288)
(287)
C02Me
COzMe
1
N
COzEt
C“
(290)
Gcverul and Syrrthrtic Methods
416
n=1,2
(294)
(293)
OMe
Ry-JNH2+
R
NH2
Me&OH
Bu"0H
.. Ar 'I,
Ph
>co
(301)
I
A
8: SLIt u rated Heterocyclic Ring Synthesis
477
antibiotics140 and the use of chlorosulphonyl isocyanate in heterocyclic , including a-lactam, synthesis. 6 7 An asymmetric synthesis of the important intermediate, azetidinone (308), has been achieved by Pummerer reaction of the enantiomerically pure sulphoxide (307).141 Resolution of (307) is easily effected by HPLC on a chiral support and the product (308) is formed in good yield and with high optical purity. The mechanism of the reaction is The achiral 0x0 amide N,N-di-isopropylphenylglyoxylamide (309) forms chiral cystals which can be separated
under investigation.
easily by standard seeding techniques upon recrysallisation from benzene. When these crystals are irradiated in the solid state the Norrish Type I1 photocyclization product, 3 - h y d r o x y - l - i s o p r o p y 1 - 4 , 4 dimethyl-3-phenylazetidin-2-one (310) is formed in high optical and chemical ~ i e 1 d s . l ~Purification ~ to 100% e.e. can be achieved b y recrystallisation from benzene and the process is capable of bulk scale-up, making it a potentially very useful example of a phatochemically mediated conversion of achiral to chiral material in the absence of a chiral source. The reaction of an enolate anion with an imine is a well characterised method for the formation of (3-lactams but the use of enolizable imines in the reaction has been reported to be unsuccessful. Two research groups have now shown that, under appropriate conditions, this is not a limitation to the method. Wada et al.report that good yields of the substituted azetidinones (313) can be obtained, generally as mixtures of cis and trans isomers, by reaction of the lithium enolates (311) with the enolizable aldimines (312), in the presence of dimethylaluminium chloride, 143 while Cainelli and co-workers show that moderate yields of the N-unsubstituted azetidinones (315) can be obtained simply by reaction of the lithium enolates (311) with the N-trimethylsilylimines (314) at low temperature under standard ~ 0 n d i t i o n s . l ~The ~ same group has also reported two useful routes to 4-unsaturated azetidine derivatives based upon enolate-imine procedures. Reaction of the enolates (316) with the ketenimines (317) at low temperature gives, after hydrolytic work-up, the corresponding 145 4-alkylidineazetidin-2-ones (318) in moderate to good yields. The products are usually obtained as exclusively Z-isomers, corresponding to attack of the enolate from the less hindered face of the ketenimine. In a similar type of reaction, the 4-0x0- and 4-thioxo-azetidin-2-ones (321) are formed, in variable yields, by
478
I
N=C
Tos
0
TMSOTf
( P r ' l 2 NEt
0
O*C,CHCl3
0 67
h3 (Hg)
PhCO-CON( Pr )2
_____jc
solid state
O L
e.e.
ph-Eie 0
(309)
Pr i
93% e.e. (310)
R5
RxoLi OR^ ~2
(311)
8: Saturated Heterocyclic Ring Synthesis
479
ALEt3
A
toluene
x = s,o Ar
=
OOM~
-
=+\
EtO
KM no4
0
Ph
I
R
(325)
R
Gtwral and Synthetic. Method
480
0
II
n
V
Y
0
Scheme 9
Ar-NHNH,
MeO-C
,
Me C / \
Me
II 0
(327)
Co.2 Me
(328)
C02Me
(330) R' = M e . R 2 = H (331) R' = H . R 2 = M e
8: Saturated Heterocyclic Ring Synthesis
48 1
reaction of the lithium (or sodium) enolates (316) with the heterocumulenes (319) to give the intermediates (320), followed by
triethylaluminium-mediated cyclization. 14' The products (321, x=S) are easily converted to 4-thioacetoxyazetidinones (322), important intermediates for the synthesis of a wide range of 6-lactams. The iron carbonyl complex (323) reacts smoothly with two equivalents of the isocyanides (324) to give the 3-iminoazetidinylidene complexes (325) in excellent yields Oxidative removal of the iron carbonyl moiety then affords the 6-lactams (3261, again in excellent yields. Two reports dealing with new routes to 1,2diazetidin-3-ones have appeared. Taylor and Hinkle have investigated conditions for efficient intramolecular alkylation or acylation of hydrazine intermediates to form the ring system and two successful procedures are illustrated in Scheme 9.148 Yields are still only moderate but the routes have general application. In the second report the lI2-diazetidin-3-ones (328) are prepared in high yields by treatment of the readily available 2-arylhydrazino isobutyric esters (327) with 2-propylmagnesium iodide. Attack at the ester function is a competing reaction when methylmagnesium iodide is used and, interestingly, no cyclization occurs when sodium (NaH) is used as the counterion. Finally, Baldwin and his group have described a radical-mediated ring expansion of a penam (329) to the cephams (330) and (331) which may mimic the biosynthetic ring expansion of penicillins to cephalosporins. 150 Treatment of (329) with triphenylstannane, under radical chain conditions, gives the products (330) and (331) in good, combined yield. References
1. 2. 3. 4. 5. 6. 7.
Y.Gao, R.M.Hanson, J.M.Klunder, S.Y.Ko, H.Masamune and K.B.Sharpless, J. Am. Chem. SOC., 1987, 109, 5765. 2.-M.Wang and W.-S.Zhou, Te'trahedron, 1987, 43, 2935. S.Colonr,a, A.Manfredi, R.Annunziata and M.Spadoni, Tetrahedron, 1987, 43, 2157. M-Miyashita, T.Suzuki and A.Yoshikoshi, Chem. Lett., 1987, 285. I.Saito, T.Mano, R.Nagata and T-Matsuura, Tetrahedron Lett., 1987, 28, 1909. T.H.Mo=is, E.H.Smith and R.Walsh, J. Chem. SOC., Chem. Commun., 1987, 964. G.Barbaro, A.Battaglia and P-Giorgianni, Tetrahedron Lett., 1987, 28, 2995. T.L.B.=ivin, Tetrahedron, 1987, 43, 3309. A-Srikrishna and G-Sunderbabu, Tetrahedron Lett., 1987, 28, 6393. J.P.Dulcere, J-Rodriquez, M.Santelli and J.P.Zahra, Tetrahedron Lett., 1987, 28, 2009. I
8. 9. 10
.
T-Morikawa, T.Nishiwaki, Y.Iitaka and Y.Kobayashi, Tetrahedron Lett., 1987, 28, 671. 12. M.J.Begley, H z h a n d a l , J.H.Hutchinson and G.Pattenden, Tetrahedron Lett., 1987, 28, 1317. 13. M.H.Hopkins and L.E.Overman, J. Am. Chem. Soc., 1987, 109, 4748. 14. P.M.Herrinton, M.H.Hopkins, P-Mishra, M.J.Brown and L.E.Overman, J. Org. Chem., 1987, 52, 3711. 15. H-Frauenrath and J.Runsink, J. Org. Chem., 1987, 52, 2707. 16. L.M.Harwood and J. Robertson, Tetrahedron Lett., 1987, 28, 5175. 17. S.T.Russe1, J.A.Robinson and D.J.Williams, J. Chem. S O C . , Chem. Commun., 1987, 351. 18. I.Paterson, 1.Boddy and I.Mason, Tetrahedron Lett., 1987, 28, 5205. 19. T.Satoh, K.Iwamoto and K-Yamakawa, Tetrahedron Lett., 1987, 28, 2603. 20 - P.Pale and J.Chuche, Tetrahedron Lett., 1987, 28, 6447. 21. R.D.Walkup and G-Park, Tetrahedron Lett., 1 9 8 7 7 2 8 , 1023. 22. K.Fugami, K.Oshima and K.Utimoto, Tetrahedron Lett., 1987, 2, 809. 23. R.Antonioletti, F.Bonadies and A.Scettri, Tetrahedron Lett., 1987, 28, 2297. 24. V.F.PaG1 and G-Pattenden, Tetrahedron Lett., 1987, 28, 1451. 25. M.A.Brimble and J.J.Gibson, Tetrahedron Lett., 1987, 28, 4891. 26. E.C.Taylor, J.E.Macor and J.L.Pont, Tetrahedron, 1987, 43, 5145. 27. S.W.McCombic and W.A.Metz, Tetrahedron Lett., 1987, 28, 383. 28. A.Baba, T.Nozaki and H-Matsuda, Bull. Chem. SOC. Jpn., 1987, 60, 1552. 29. Y.Inoue, J-Ishikawa, M.Taniguchi and H.Hashimoto, Bull. Chem. SOC. Jpn., 1987, 60, 1204. 30. L.Coppi, A.Ricci and M.Taddei, Tetrahedron Lett., 1987, 2 , 9 7 3 . 31. Z.Y.Wei, J.S.Li, D.Wang and T.H.Chan, Tetrahedron Lett., 1987, 28, 3441. 32. F.Perron and K.F.Albizati, J. Org. Chem., 1987, 52, 4128. 33. M-Mitani, H.Hirayama, H-Takeuchi and K.Koyama, Tetrahedron Lett., 1987, 28, 4573. 34 * J.M.Takacs, L.G.Anderson, M.W.Creswel1 and B.E.Takacs, Tetrahedron Lett., 1987, 2,5627. 35. P.C.B.Page, P.H.Williams, E.W.Collington and H.Finch, J. Chem. S O C . , Chem. Commun., 1987, 756. 36. S.Aparao, M.E.Maier and R.R.Schmidt, Synthesis, 1987, 900. 37. L.-F.Tietze, T.Brumby and M.Pretor, Synthesis, 1987, 700. 38. Y.Huang and X.Lu, Tetrahedron Lett., 1987, 28, 6219. 39. J.Grimaldi and A.Cormons, Tetrahedron Lett., 1987, 28, 3487. 40. G-Pairaudeau, P.J.Parsons and J.M.Underwood, J. Chem. S O C . , Chem. Commun., 1987, 1718. 41. M.Schreck and M-Christl, Angew. Chem., Int. Ed., 1987, 26, 690. 42. N.S.Ibrahim, Heterocycles, 1986, 24, 935. 43. N.Martin, C.Pascua1, C.Seoane andJ.L.Soto, Heterocycles, 1987, 26, 2811. 44. J.Yoshida, K.Sakaguchi, S.Isoe and K.Hirotsu, Tetrahedron Lett., 1987, 28, 667. 45. L.Lopez, V.Calo and F.Stasi, Synthesis, 1987, 947. 46. K.C.Nicolaou, C.-K-Hwang, M.E.Duggan and K.B.Reddy, Tetrahedron Lett., 198’7, 28, 1501. 47. H.A.J.Carless, J-Beanland and S.Mwesiqye-Kibende, Tetrahedron Lett., 1987, 28, 5933. 11.
~
8: Saturated Heterocyclic Ring Synthesis 48. 49. 50. 51. 52. 53. 54. 55. 56. 57.
J.van der Louw, J.L.van der Baan, H.StieltJes, F.Bickehaupt and G.W.Klumpp, Tetrahedron Lett., 1987, 2 , 5929. K.C.Nicolaou, C.-K-Hwang, M.E.Duggan and P.J.Carrol1, J. m . Chem. SOC., 1987, 109, 3801. P.Ooms and PI-Hartman,Tetrahedron Lett., 1987, 28, 2701. E.C.Taylor and J.E.Macor, J. Orq. Chem., 1987, 52, 4280. E.C.Taylor and J.L.Pont, J. Org. Chem., 1987, 5 2 4 2 8 7 . A.E.Frissen, A.T.M.Marcelis and H.C.van der Plas, Tetrahedron Lett., 1987, 28, 1589. D-Grief, M.Pufit and M.Weissenfels, Synthesis, 1987, 456. J.Cossy, F.Henin and C-Leblanc, Tetrahedron Lett., 1987, 2, 1417. P.Armstrong, R.Grigq and W.J.Warnock, J. Chem. SOC., Chem. Commun., 1987, 1325. P-Armstrong, R.Grigg, S.Surendrakumar and W.J.Warnock, J. Chem. SOC., Chem. Commun., 1987, 1327. D.P.Curran, B.H.Kim, H.P.Piyasena, R.J.Loncharich and K.N.Houk, J. Org. Chem., 1987, 52, 2137. S.Knapp, P.J.Kukkola, S.Sharma and S-Pietranico, Tetrahedron Lett., 1987, 28, 5399. S.W.McCombie and T.L.Nagabhushan, Tetrahedron Lett., 1987, 28, 5395. T.Hayashi, A.Yamamoto and Y-Ito, Tetrahedron Lett., 1987, 28, 4837. T-Mitsudo, Y.Hori, Y.Yamakawa and Y.Watanabe, Tetrahedron Lett., 1987, 28, 4417. Y.Yamamoto, Y.Watanabe and S-Ohnishi, Chem. Pharm. Bull., 1987, 35, 1860. Y.Yamamoto and Y.Watanabe, Chem. Pharm. Bull., 1987, 35, 1871. S.E.Denmark, C.J.Cramer and M.S.Dappen, J. Org. Chem., 1987, 52, 877. L.Capuano, K.Djokar, N-Schneider and C.Wamprecht, Liebigs Ann. Chem., 1987, 183. A.Kama.1 and P.B.Sattur, Heterocycles, 1987, 26, 1051. A.Hosomi, S.Hayashi, K.Hoashi, S.Kohra and Y.Tominaqa, J. Org. Chem., 1987, 52, 4423. S.N.Mazumdar, M.Sharma and M.P.Mahajan, Tetrahedron Lett., 1987, 28, 2641. V.Ambroqi and G-Grandolini, Synthesis, 1987, 724. J.Szab6, G.Bernhth, A.Kat6csI L.Fodor and P.Soh'ar, Can. J. Chem., 1987, 65, 175. A.Hosomi, S.H%ashi, K . Hoashi, S.Kohra and Y.Tominaga, J. Chem. SOC., Chem. Commun., 1987, 1442. D.W.Roberts and D.L.Williams, Tetrahedron, 1987, 43, 1027. M.Joucla, J.Mortier and R-Bureau, Tetrahedron Lett., 1987, 2, 2975. J.R.McCarthy, C.L.Barney, M.J.O'Donnel1 and J.C.Huffman, J. Chem. SOC., Chem. Commun., 1987, 469. T-Fuchikami, Y.Shibata and H.Urata, Chem. Lett., 1987, 521. R.W.M.Aben, R.Smit and J.W.Scheeren, J. Org. Chem., 1987, 52, 365. R.H.Higgins, Q.L.Eaton, L.Worth,Jr. and M.V.Peterson, J. Heterocyclic Chem., 1987, 24, 255. S.RaJeswari, S.ChandrasekhGan and T.R.Govindachari, Heterocycles, 1987, 25, 659. G.Hall, J.K.Sugden and M.B.Waghela, Synthesis, 1987, 10. M-Ramaiah, Tetrahedron, 1987, 43, 3541. O.Tsuge, S-Kanemasa, M.Ohe and S-Takenaka, Bull. Chem. SOC. Jpn., 1987, 60, 4079. O.Tsuge, S.Kanemasa, M.Ohe, K.Yorozu, S.Takenaka and K.Ueno, Bull Chem. S O C . Jpn., 1987, 60, 4067. ~
58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83.
483
484 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95 * 96. 97. 98. 99. 100 .
101. 102. 103.
104. 105, 106. 107. 108. 109. 110. 111. 112. 113.
114. 115. 116. 117. 118.
O.Tsuge, S.Kanemasa, T.Yamada and K.Matsuda, J. Org. Chem., 1987, 52, 2523. N.Imai>nd K.Achiwa, Chem. Pharm. Bull., 1987, 35, 593. N.Imai, Y.Terao and K.Achiwa, Chem. Pharm. Bull., 1987, 35, 2085. M.Joucla and J.Mortier, Tetrahedron Lett., 1987, 28, 2973. A.Guy, M.Lemaire, Y.Graillot, M.Negre and J.A.GueEe, Tetrahedron Lett., 1987, 28, 2969. J.M.Mellor and A.M.Wagland, Tetrahedron Lett., 1987, 28, 5339. S.Boulaajaj, T.Le Gall, M-Vaultier, R.Gr&e, L.Toupet and R-Carri’e, Tetrahedron Lett. 1987, 28, 1761. N.Knouzi, M-Vaultier, L.Toupet andR.CarriG, Tetrahedron Lett., 1987, 28, 1757. J.Coop= and D.W.Knight, Tetrahedron Lett., 1987, 28, 3031. J.Cooper, D.W.Knight and P.T.Gallagher, J. Chem. S O C . , Chem. Commun., 1987, 1220. A.J.Pearson, M.Zettler and A.A.Pinkerton, J. Chem. SOC., Chem. Commun., 1987, 264. H-Dhimane, J-C.Pommelet, J.Chuche, G.Lhommet and M-Haddad, Tetrahedron Lett., 1987, 28, 885. M.Westling and T.LivinghoGe, J. Am. Chem. S O C . , 1987, 109, 590. D.Damour, J.Pomet and L-Miginiac, Tetrahedron Lett., 1987, 28, 4689. M.Newcomb and T.M.Deeb, J. Am. Chem. S O C . , 1987, 109, 3163. D.H.R.Barton, J.Guilhem, Y.HervE, P.Potier and J-Thierry, Tetrahedron Lett.. 1987. , 28. - , 1413. Y-Watanabe, Y.Ueno, C.Tanaka, M.Okawara and T.Endo, Tetrahedron Lett., 1987, 28, 3953. H-Ishibashi, T.Sato, M.Irie, S.Harada and M.Ikeda, Chem. Lett., 1987, 795. G.Bentz, N.Besbes, A.Laurent and H.Stamm, Tetrahedron Lett., 1987, 28, 2511. S.J.Danishefsky and J.S.Panek, J. A m . Chem. SOC., 1987, 109, 917. J.E.Baldwin and C.-S.Li, J. Chem. SOC., Chem. Commun., 1987, 166. H.Takahata, T.Takamatsu, M.Mozumi, Y.-S.Chen, T-Yamazaki and K.Aoe, J. Chem. SOC., Chem. Commun., 1987, 1627. S.Kano, T.Yokomatsu, H.Iwasawa and S.Shibuya, Heterocycles, 1987, 26, 359. Z.K.M.Abd El Samii, M.I.Al Ashmawy and J.M.Mellor, Tetrahedron Lett., 1987, 28, 1949. R.C.Larock andS.Babu, Tetrahedron Lett., 1987, 28, 5291. K-Fugami, K.Oshima and K-Utimoto, Tetrahedron Lett., 1987, 28, 809. P.C.Bulman Page, M.N.van Niel, and D.Westwood, J. Chem. SOC., Chem. Commun., 1987, 775. G.B.Itoua and J.-Y.Laronze, Synthesis, 1987, 353. J.S.Sandhu and B.S?in, Heterocycles, 1987, 26, 777. J-Barluenga, M-Tomas, A.Ballesteros and V.Gotor, J. Chem. SOC., Chem. Commun., 1987, 1195. S.M.Brandstadter, I.OJima and K.Hirai, Tetrahedron Lett., 1987, 28, 613. S.Kano, T.Yokomatsu, H.Iwasawa and S.Shibuya, Heterocycles, 1987, 26, 2805. P.A.Grieco and W.F.Fobare, J. Chem. SOC., Chem. Commun., 1987, 185. S.P.Tanis and J.W.Raggon, J. Org. Chem., 1987, 52, 819. Y-Fukuda, K.Utimoto and H.Nozaki, Heterocycles, 1987, 25, 297.
8: Saturated Heterocyclic Ring Synthesis
485
119. M.Hirama, T.Iwakuma and S.It$;, J. Chem. SOC., Chem. Commun., 1987, 1523. 120. J.Cossy, D.Belotti and J.P.Pete, Tetrahedron Lett., 1987, 28, 4545. 121. D-Enders, A.S.Demir, H.Puff and S-Franken, Tetrahedron Lett., 1987, 28, 3795. 122. N.S.NaEsimhan and P.A.Pati1, J. Chem. SOC., Chem. Commun., 1987, 191. 123. O.S.Petrov, V.I.Oqnyanov and N.M.Mollov, Synthesis, 1987, 637. 124. T.Fuchiqami, Y.Nakaqawa and T.Nonaka, J. Org. Chem., 1987, 52, 5489. 125. V.Kvita and H.-P.Sauter, Angew. Chem. Int. Ed. Enql., 1987, 26, 790. 126. J.E.B3cIcvall, Z.D.Renko and S.E.Bystrbm, Tetrahedron Lett., 1987, 28, 4199. 127. A.Bathgate and J.R.Malpass, Tetrahedron Lett., 1987, 28, 5937. 128. P.J.Garratt, C.J.Hobbs, C.S.J.Walpole and R.Wriqglesworth, J. Chem. SOC., Chem. Commun., 1987, 568. 129. E.A.A.Hafez, M.R.H.E?moqhayar and M.M.M.Ramiz, Liebiqs Ann. Chem., 1987, 65. 130. J.C.Medina, R.Cadilla and K.S.Kyler, Tetrahedron Lett., 1987, 28, 1059. 131. cL.J.Beckwith, S.Wanq and J-Warkentin, J. Am. Chem. SOC., 1987, 109, 5289. 132. S.Murata, T.Suqimoto and S.Matsuura, Heterocycles, 1987, 26, 883. 133. S.Equchi, T.Okano and H.Takeuchi, Heterocycles, 1987, 26, 3265. 134. T.Shono, Y.Matsumura, K.Uchida and K.Tagami, Chem. Lett., 1987, 919. 135. J.Mattay, J-Runsink, R.Heckendorn and T.Winkler, Tetrahedron, 1987, 43, 5781. 136. M.E1 Abbassi, E.M.Essassi and J.Fifani, Tetrahedron Lett., 1987, 28, 1389. 137. J-BarlGnqa, M.J.Iqlesias and V.Gotor, J. Chem. Soc., Chem. Commun., 1987, 582. 138. H.Sasaki and T-Kitagawa, Chem. Pharm. Bull., 1987, 35, 3475. 139. S.Grasso, M.Zappala and A-Chimirri, Heterocycles, 1987, 26, 2477. 140. T.Nagahara and T.Kametani, Heterocycles, 1987, 25, 729. 141. T.Kaneko, Y-Okamoto and K.Hatada, J. Chem. SOC., Chem. Commun., 1987, 1511. 142. F.Toda, M.Yagi and S.-i.Soda, J. Chem. SOC., Chem. Commun., 1987, 1413. 143. M.Wada, H.Aiura and K.-y.Akiba, Tetrahedron Lett., 1987, 2, 3377. 144. G.Cainelli, D.Giacomini, M.Panunzio, G-Martelli and G.Spunta, Tetrahedron Lett., 1987, 28, 5369. 145. A.Battaglia, G-Cainelli, D.Giacomini, G.Martelli and M.Panunzio, Tetrahedron Lett., 1987, 28, 4347. 146. G.Cainelli, D.Giacomini, M-Panunzio, G-Martelli and G.Spunta, Tetrahedron Lett., 1987, 28, 3593. 147. R-Aumann and H.Heinen, Chem. Ber., 1987, 120, 1297. 148. E.C.Taylor and J.S.Hinkle, J. Orq. Chem., 1987, 52, 4107. 149. J.G.Schant1 and M.Decristoforo, Tetrahedron Lett, 1987, 28, 6577. 150. J.E.Baldwin, R.M.Adlington, T.W.Kang, E.Lee and C.J.Schofield, J . Chem. SOC., Chem. Commun., 1987, 104.
9
Highlights in Total Synthesis of Natural Products ~
~~
____
BY C. W. ELLWOOD, D. C. HARROWVEN, AND G. PATFENDEN Terpenes
1
A number of research groups have described. new synthetic approaches towards members of the angular triquinane class of sesquiterpenes. Thus, Curran and Kuo,'
for example, have applied their tandem
radical cyclisation strategy ( 1 ) (2) to silpbperfolene ( 3 ) , and Crimmins et alL have described a modification to their earlier route to silphenene (7), whereby the key intermediate (5) produced by intramolecular [ 2 + 21 cyclodaddition from ( 4 1 ,
is converted to
( 7 ) ,via cleavage of the precursor (6) in the presence of Bu3SnH.
The related 3-oxosilphenene ( 1 0 ) has been elaborated through intramolecular Diels-Alder cycloaddition of the cyclopentenone (8) followed by ring contraction of the resulting cycloadduct (9) as key steps.
3
The first synthesis of the intriguing diterpene laurenene (14) containing the [5,5,5,71 fenestrane ring system has now been d e ~ c r i b e d . ~The synthesis builds on earlier work, and starts with the intermediate (11) used in a recent synthesis of silphenene (7). Elaboration of (11) to the keto-aldehyde (12), followed by aldolisation, led to the tetracyclic alkene (13) which was then converted to laurenene in five steps. Specionin (15) is a novel iridoid terpene which has been found to be an effective insect antifeedant.
Three syntheses of specionin
have now been described, and they feature nitrile oxide cycloaddition, k.(17)-(16), use of the ubiquitous bicyclooctenol ( 1 8 ) 6 and starting from the available (-)-catalp01 ( 1 9 ) .7 A novel electrochemical oxidative cyclisation from the phenol
(20) to the tricyclic intermediate (21) features in a synthetic approach towards cedranoxide (22) which is a constituent of the Equally elegant is the plant Juniperus foetisdissima.' intramolecular [ 4 + 21 tropone olefin cycloaddition (23)-(24) which provides the basis of a new strategy to the cedrane ring system of the pipitzols (25).
Cope rearrangement of the divinylcyclopropane
intermediate (26) to the bicyclic diene ( 2 7 ) is at the focal point
of a new synthesis of prezizaene (28). l o
9: Highlights in Total Synthesis of Natural Products
487
Steps
Bu3SnH
wo / &,
@ hv
(4)
0
Steps
BuaSnH
____)
fi SPh
A ____)
Steps ____)
@? 0
488
J
Steps t -
s;:l.
1 RO
RO
OEt AcO
HO
OP-D-GIU
9: Highlights in Total Synthesis of Natural Products
'8
Me0 145 "C ___)
xylene
489
Me0
Steps tC
OBn
H
O0, e
OBn
TMSO
H
Steps
OH
Z
OH
The diterpene phorbol (32) is amongst the most challenging contemporary synthetic targets. During 1987, Wender et all' described the first synthesis of the phorbol carbon skeleton the phorboid (31) which had as a key feature the synthesis of
e.
intermediate ( 3 0 ) through an intramolecular Diels Alder reaction of the triene (29). Another diterpene, amphidicolin (33) is no trivial target, and an enantioselective total synthesis of this molecule from the advanced intermediate (34) is shown retrosynthetically in Scheme 1.12 Using the tricyclic ketone (35) as starting point, White and Somers,13 have shown that elaboration to (36) followed by an hydroxy-assisted ene reaction leads to the stemodane carbon framework (37), precursor to 2-desoxystemodinone (38). Forskolin (391, which is isolated from the Indian plant Coleus forskohlii has been the subject of intense interest owing to it's antihypertensive and other biological properties. During 1987, several synthetic approaches to forskolin were published; these routes featured the Diels Alder reaction,l4 a tandem radical cyclisation-intramolecular Mukaiyama aldolisation approach, l 5 and an oxy-Cope rearrangement strategy16 (Scheme 2) . The elegant approach to cembranoids discovered by Marshall all7
and based on a Wittig rearrangement ring contraction of macrocyclic propargylic ethers, has now been extended with the use
of chiral bases leading to >60% In addition, Marshall and co-workers have shown that this remarkably efficient rearrangement can also be used to synthesise cyclodecenyne precursors of the germacranolides from 13-ring ethers ( 4 0 ) + (41)+ (42). I 9 A related route involving [2,3] rearrangement of diallyl ethers has been highlighted by Takaheshi et a1 .2 o McMurry and Bosch21 have demonstrated that a wide range of natural bicyclic vinylcyclopropanes e.g. casbene (431, bicyclogermacrene (44) and lipidozene (45) can be synthesised by intramolecular titanium induced coupling reactions involving cycloprane aldehydes (Scheme 3) - In a similar manner, humulene
e.
(46) and flexibilane (47) have been synthesised from intramolecular 22 reductive coupling of appropriate keto-aldehyde precursors. 2
Alkaloids
The synthesis of a variety of indole alkaloids has featured strongly this year. Thus, Jones et alL5 for example completed a formal total
9: Highlights in Total Synthesis of Natural R-oducts
49 1
RO"
:
HO/
(33)
'
(35)
(34)
Scheme 1
8-. (37)
(36)
HO
492
&='\
OH
II
OAc
OH (39)
Gevieml mid Synthetic Methods
9: Highlights in Total Synthesis of Natuml Products
493
synthesis of geneserine (51) by preparing the compound (50). The key reaction in their sequence was a radical cyclisation which converted the amide (48) to the indole derivative (49). Stork and c o - ~ o r k e r sreported ~~ an elegant approach to gelsamine (52) which also utilised a radical cyclisation in a key step.
Thus ( 5 3 ) was
first treated with Bu3SnH and AIBN to afford (54). A short sequence of steps then led to the tricyclic compound (55). A Claisen rearrangement of the silyl enol ether corresponding to (55) finally gave the product (56) of this model study. A sigmatropic rearrangement also featured in the synthesis of hippadine (58) reported by Prabhakar et al.25 The hydroxamic ester (57) underwent a sigmatropic rearrangement and in situ dehydration to give the natural product in "one pot". The same target molecule was also synthesised by Kanematsu and co-workers.2 6 Their key intermediate (60) was prepared allene-diene ( 5 9 ) .
an intramolecular Diels-Alder reaction of the
A cycloaddition reaction of a different nature featured in the enantioselective synthesis of ( + ) , ( - ) and ( ? ) -vindoline (64)
reported by Kuehne et al.27 In the key step the intermediate (61) was first subjected to N-alkylation; this induced a fragmentation reaction and generated the transient intermediate ( 6 2 ) .
The
intramolecular cyclisation of this material then gave ( 6 3 1 , a compound with the basic carbocyclic framework of vindoline (64). Rapoport and Feldman2' also reported a synthesis of ( - 1 vindoline (64). Their route featured an interesting rearrangement. The intermediate (65) was treated with tbutylhypochlorite then DBU to give the product ( 6 6 ) of an alkylation-rearrangement reaction. Also in the field of indole alkaloid synthesis, Winterfeld et a12' reported an enantioselective synthesis of either ( + ) or ( - ) vincamine (68). Their pivotal intermediate was the lactam (67). By careful choice of reaction sequence, this was elaborated to give either natural or unnatural vincamine (68). A rapid synthesis of (2)-elaeocarpidine (70) has been reported by Gribble and Switzer.30 The key step involved DIBAL-H reduction of the amide (69) to give the product directly. Indole alkaloids have also succumbed to advances in palladium chemistry. Thus, Hegedus et a13' have developed a racemic synthesis of both the clavicipitic acids (73) whereby the bromoiodoindole (71) was first subjected to two successive Heck reactions giving intermediate (72). Elaboration of this
I
Me
Me (48)
(49)
Me
Me
(50)
(511
OEt
(53)
(54)
(55)
(56)
___L)
0 (57)
n0 0
n
0 0
(58) Steps
L
O
(58)
E = C02CH2CH2CI
495
9: Highlights in Total Synthesis of Natural Products
H
Me0
9&
CH30
-
CH~O
'\
CH302C
0
\
0
/
H
C02CH3
(64)
Ts (72)
Ts (71)
CO Me
+
H
H
H (74)
NH2
OH
OMe OMe
CC-1065 (75)
9: Highlights in Total Synthrsis of Natural Products
497
intermediate then led to the target molecules protected as their N-acetyl methyl esters. The same research group also reported that similar methodology could be used to synthesise (+I-auranticlavin (74).32 A major target for synthesis in 1987, was the antitumourantibiotic CC 1065 (75). The first total synthesis of this compound was reported by Kelly et a133 in this year. Synthetic studies of this compound fall into two groups, G. those concerned with the CPI unit (76) and those concerned with the synthesis of PDE-I (77) and the PDE-I "dimer" (78). Magnus et a134 reported a synthesis of the CPI portion of the molecule from the 3,3'-bipyrrole (79) using a route which involved constructing the acid (80) and subjecting it to a Friedel-Crafts style ring closure. A similar bipyrrole (81) was used by the same research group to prepare PDE-I (77) and thence the PDE-I "dimer" (78).35 In this case a double Friedel-Crafts style acylation with oxalyl chloride was used to generate the third ring from the bipyrrole unit and give the compound (821 . A completely different approach to PDE-I was reported by Bolton, Moody, Rees and T o J o . ~These ~ authors used vinyl nitrene chemistry in their key steps, G. conversion of the vinyl azide (83) to the pyrrole (84) was followed by a similar protocol to convert (85) to (86). Vinyl nitrene chemistry also featured as a key step in the total synthesis of lennoxamine (89) reported by Moody and W a r r e l l ~ w .In ~ ~this case, the vinyl nitrene was used to form a seven- rather than a five-membered ring in the conversion of (87) to (88). Ryckmann and Stevens38 have reported an elegant synthesis of ( 2 1 porantherine (93). Their approach involved the generation of the tricyclic structure (91) from the symmetrically substituted 6-lactam (90). Elaboration of this intermediate then gave the tetracycle (92). An aprotic Bamford-Stevens reaction was used to introduce
the requisite alkene functionality.
Elsewhere, Schultz et a13'
prepared unnatural (+)-pumiliotoxin (97) in a sequence which began with a Birch reduction of the L-proline anthranilic acid derivative (94); this reduction gave the key intermediate (95). Catalytic hydrogenation using a soluble catalyst next gave (96). Removal of the chiral auxiliary and elaboration of the product finally led to (+)-pumiliotoxin (97). The use of chiral auxiliary also featured in the total synthesis of acivicin (101) reported by Mzengesa, Yang
General arid Synthetic Methods
498
4
HO
T
0
N
H
H
k
0
' / OH
H
2
H
OMe PDE-I
O
d +>NH2
' / OH
OMe
OMe PDE-I dimer
(78)
(77) EtO,C,
Et02C. M#H
Steps ____)
N R
M@H R (79) R = S02Ph
(80) X = CH2C02H
C02Me
B
r
d
N
3
C02Me
OBzl
OMe
(83)
Steps_Me02C*
___c
Br$
/
OBzl
OMe
(84)
N3
' OMe
(85)
OBzl
(76)
499
9: Highlights in Total Synthesis of Natural Products
OMe
OMe
OMe
Me
500
General and Synthetic Methods
(94)
(951
H
OMe
OMe
(99)
c'\
'OBn
Ho2cq (103)
0
C02H
N
(104)
COPH
9: Highlights in Total Synthesis of Natural Products
50 1
and Whitne~.~' They took the nitrone (98) and the protected vinyl glycine (99) and obtained (100) after a [3 + 21 cycloaddition reaction and hydrolysis of the sugar residue. Chlorination, followed by removal of the protection on the amino acid functionality then gave the natural product. Takano et a141 have reported a synthesis of acromelic acid A (104) utilising a 1,3dipolar cycloaddition. The dipole was generated by thermolysis of azidridine (102). An intramolecular dipolar cycloaddition then gave the product (103); this was followed by a series of relatively trivial conversions which resulted in a formal total synthesis of acromelic acid A (104). 3
SDiroacetals
The experimental details of two syntheses of milbermycin 0, (1051, the simplest member of the metabolites isolated from Streptomyces
, have been reported.42r43 Kociegski and his collaborators have additionally reported a more efficient route to the advanced
sp.
precursor (106) involving the nucleophilic addition of the organocuprate (108) to the epoxide ( 1 0 7 ) .44 A similar fragment (109) was identified by Crimmins as a useful intermediate €or the construction of milbermycin D (110).45 In addition to this synthesis, these workers have reported an attractive entry towards the hexahydrobenzofuran moeity, common in many of the higher members of this class. The highlight of their approach was the sequential selenium-induced electrophilic cyclisation and [2,3]-sigmatropic selenoxide rearrangement (111)+(112).46
A
second entry to this hexahydrobenzofuran portion, via diazoketone 47 cyclisation of (113) to (114), is similarly noteworthy. Danishefski et a148,49 have reported the first total synthesis of a higher metabolite, avermectin Ala (124). The spiroacetal (116) was established via an intramolecular oxidative cyclisation
of the alcohol (115) by the action of HgO-12.
After elaboration to
(117), the second key fragment (118) was attached by a classical crossed aldol condensation-elimination process. Deprotection and oxidation next led to the aldehyde (119). This aldehyde then underwent the critical intramolecular Nozaki ring closure to the hexahydrobenzofuran (120) upon sequential treatment with trimethylaluminium and lithium thiophenoxide, mcpba, and syn-elimination of ~
the intermediate sulphoxide.
Oxidation, and depivaloylation then
502
General and Synthetic Methods
0
OSiMe2But
-*=ko OSiMe2But
+
OBzl
OBz
I
+-*
H OH
OSi-Bu'Ph, (1 09)
me'*
/Steps
g - O BR :u Ht M e 2 PhSeCl ___)
HO
\
(OSi- Bu'Me2
H202
___)
H (1 11) R = SiMe3
/OSi-ButMe2
R = SiMe3
70% 2 steps
OH (1 12) R = SiMe3,
503
9: Highlight5 in Total Synthosi.\ of Natural Products
C02H
0 : ’ H
OAc
I Steps TBSO...
Me
Me’..
+
Me
Aldol _____)
-H20
OMe
OMe
(1 9)
ER = CH20TBS R = CHO
504
Grnrml und Synthetic Methods
afforded the hydroxy acid (121) which was lactonised through the action of 2-chloro-N-methylpyridinium iodide and triethylamine. Finally, the double bond was deconjugated, by kinetic protonation of the enolate derived from (122), and the synthesis completed by attachment of the synthetic disaccharide unit. The novel bisabolane sesquiterpene (+)-phyllanthocin (129), a potentially useful antitumour agent, has continued to attract the attentions of synthetic chemists. Martin et a1 have outlined a novel strategy featuring a stereo- and regioselective intermolecular dipolar cycloaddition of the nitrile oxide (126) to the alkene (125). 5 0 The resulting isoxazoline was later unmasked, by the action of Raney nickel revealing the latent B-hydroxy ketone (127), which then underwent acid-catalysed intramolecular transacetalation to the Williams intermediate (128).51
In an alternative approach to phyllanthocin, Smith and his co-workers52 utilised nucleophilic addition of the lithiodihydropyran (130) to the aldehyde (131) as a key step. Further manipulations, including the acid-catalysed spiroacetalisation of (132) to (133), and the union of the synthetic glycoside and phyllanthocin precursors (134) and (135) respectively accomplished the first synthesis of phyllanthoside (136).53
4
Macrolides
In a concise synthesis of the macrolide ( + ) - (9s)-dihydroerythronolide (143), Stork et a1 have demonstrated the utility of butenolide sequences.
in the construction of the appropriate polypropionate Thus, the Grignard reagent (139) and the ketone (1401, 56
derived from the butenolide (137)5 5 and the cyclopentene (138) respectively, were coupled to afford the linear unit (141). This unit was then further elaborated to the secoacid (142) which underwent smooth macrolactonisation upon treatment of its trifluoroacetate salt with dicyclohexylcarbodiimide and DMAP. Removal of the acetal moieties by treatment with acid completed the sequence, which also constituted a formal total synthesis of erythromycin A (144). 5 7 An interesting and unusual "photolactonisation" procedure has been explored in the synthesis of the lichen macrolide (+)-aspicilin (148). Thus, the o-quinol acetate (145) was transformed, & y the intermediate ketene sulphone (146) into macrolactone (147) simply
9: Highlights in Total Synthesis of' Natural Products
505
506
General and Synthetic Methods
H
O *H
\ OMe
Me02C
IVlWJpb
H
Bno%H
H
MEMO (131)
.
o ,
x\
&o, Me02C'
-1
A 10
(129)
1
Ph
Steps
(130)
B
n
H O
11 T
l\7 n R
$-'
0
9: Highlights in Total Synthesis of Natural Products
1
Steps
507
General and Synthetic Methods
508
(1 45)
..OH “‘OH
RS
-
Steps
509
9: Highlights in Total Synthesis of Natural Products
58 by the action of light. Vedejs et a1 have also demonstrated the utility of organosulphur chemistry in connection with the total synthesis of methynolide (155).59 Treatment of the sulphide (149) with the triflate (150) first effected ring expansion to the medium ring sulphide (152) 2 ylid (151). Further manipulations, including isomerisation of the thiolactone (153) to the macrolactone (154) eventually secured the natural product. Suzuki et a1 similarly chose the synthesis of a macrolide to demonstrate the utility of a novel epoxy alcohol rearrangerment, (156) to (1571, recently developed within their research group. The first synthesis of mycinolide IV (158) followed, in a straightforward fashion, utilising the intramolecular Wadsworth-Emmons protocol to effect macrocyclisation.6o The construction of the long sought after amphotericin B (165) has recently been accomplished in the laboratories of Nicolaou. 61’62r63 The formulation and combination of the key fragments (159) to (164) have been extensively reported in previous articles of this series, but a less cursory inspection of this work is highly recommended. 5
Ionophores
The ionophore antibiotic A-23187 (calciomycin) (1691, which is known to selectively transport divalent cations, has been the subject of two new syntheses this year. In the first synthesis, Kishi and his collaborators chose to couple the key fragments (1661, (167) and (168) by Wadsworth-Emmons and aldol protocols. They then effected a base catalysed spiro-ketalisation of the resulting hydroxy ketone.64 In an alternative approach, the spiroacetal (171) was generated from the cyclopropane (170) by treatment with tosic acid. In sequence, with suitable functional group manipulations, the pyrrole and benzoxazole were then introduced via pyrrole magnesium 65 chloride and the amino phenol (172) respectively. 6
Other Natural Products
The cyclic peptide didemnin B (173) isolated from the tunicate Tridemnum solidum is the first marine natural product to enter clinical trials as an anticancer agent.
The same molecule is also
510
&
C;enrr.d and Synthetic. Merhods
L i p O S E M
&
OSEM
SiMe, F
0
0
THF,-78 "C
SiMe,
\
(' 56)
BF3.OEt2
CH$12,-78
SEMO
\
K2C03, 18-C-6
Toluene, 70 "C
35%
s; -_-__
---0MPM
0
MPMO
0
DDQ
CHzCI2-H20
"C
ccH + 51 1
9: Highlights in Total Synthesis of Natural Products
F!;Q
(Et 0 1 20
0
0
0
NMe
(166)
Me02C Me
Me H
Me
(167)
/f
'
0
0
I Me02C
wMe
NMe I C02CH2CCI,
I
-bl
I
C02CH2CCI,
Bu'OJQ-0
NHMe (R = Me)
RO,C
E
(R= H) (169)
Reagents: a. i, (167), NaH then (166); ii, HS(CH2)3SH, BF3.OEt2;iii, Cu0,CuC12, 88% b. (168), C6HI1NMgBr, 61% c. i, NaOMe; ii, Zn, AcOH,THF,cat.cHCI d. LiSPr, HMPA
512
General and Synlhetic Method\
p-TSOH-H20
-
OTBDPS
HO
OTBDPS
(171)
OH
9
3S, 4R, 5S-lst
I
-
CH20 O=C/ H37 II I R-N -C-C -N H C -H
I
2S, 4S-Hip
\
C= 0
L-THr L-Leu
H '
0
L-Pro
5 13
9: Highlights in Total Synthesis r,f Natural Products
cyclo[~-Val-~-Pro-~-Leu-~-(gln)Thz-(gly)Thz] (174)
0 8
11
9
OMe
AcO
General and Synthetic Methods
514
OH -C02H
OH
R (183) O
H
9: Highlights in Total Synthesis of Natural Products
515
exceedingly active as an immunosuppressive agent in vivo and vitro. Several man-year’s effort by Rinehart and his collaborators66 have now resulted in the total synthesis of didemnin B and related co-metabolites. A second cyclic peptide, dolastatin 3 (174), which shows useful anti-leukemic properties, has also been the subject of total synthesis by Pettit et a1.67 Bilobalide (175) is a member of the ginkgolide family of unusual polycyclic structures isolated from the ginkgo tree, Ginkgo biloba. In a sequence which features a one step synthesis of the enone (176), containing all the carbon atoms needed for the synthesis, Corey and Su68 have now completed a neat synthesis of ( ? ) bilobalide. A synthesis of the 2,6-dioxabicyclo[3.2.l]octane
ring system
(181b) found in the natural aurovertins e.g. (177) has been de~cribed.~’The work was based on a biogenetic model, and utilised two key epoxide cyclisation steps &y (178)+(179) and (180)+(1812) has been described. A similar protocol has been used
.
to approach the related c i t r e o v i r i d i n ~ l sand ~ ~ citreoviridins 71 Other target orientated synthetic work which is worth more than a cursory inspection includes studies towards azadirachtin (182),72 pseudomonic acid C (183)73 and ikarugamycin (184).74 References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.
12. 13. 14. 15.
D.P.Curran and S.-C.Kuo, Tetrahedron, 1987, 43, 5653. M.T.Crimmins and S.W.Mascarella,rahedronxett., 1987, 28, 5063. M.Ihara, A-Kawaguchi, H.Ueda, M.Chihiro, K.Fukumoto and T.Kametani, J.Chem.Soc., Perkin Trans. 1, 1987, 1331. T.Tsunoda, M.Amaike, U.S.F.Tambunan, Y.Fujise, S.Ito and M.Kodama, Tetrahedron Lett., 1987, 28., 2537. D.P.Curran, P.B.Jacobs, R.L.ElliottTnd B.H.Kim, J.Am.Chem.Soc., 1987, 109. 5280. N.Huss= and J.Leonard, Tetrahedron Lett., 1987, 28, 4871. E.Van der Eycken, A.Janssens and M.Vandewalle, Tetrahedron Lett., 1987, 28, 3519. Y.Shizuri, Y.Okuno, H.Shigemori and S.Yamamura, Tetrahedron Lett., 1987, 28, 6661. R.L.Funk and KL.Bolton, J.Org.Chem., 1987, 52, 3173. E.Piers, M.Jean and P.S.Marrs, Tetrahedron Lett., 1987, 28, 5075. P.A.Wender, R.M.Keenan and H.Y.Lee, J.Am.Chem.Soc., 1987, 109, 4390. R.A.Holton, R.M.Kennedy, H.-B.Kim and M.E.Krai€t, J.Am.Chem.Soc., 1987, 109, 1597. J.D.White and T.C.Somers, J.Am.Chem.Soc., 1987, 109, 4424. F.E.Ziegler, B.H.Jaynes and M.T.Saindane, J.Am.Chem.Soc., 1987, 109, 8115. J.H.Hutchinson, G-Pattenden and P.L.Myers, Tetrahedron Lett., 1987, 28, 1313 ~
General and Synthetic Methods
516
16. J.A.Oplinger and L.A.Paquette, Tetrahedron Lett., 1987, 2, 5441. 17. J.A.Marshal1, T.M.Jenson and B.S.DeHoff, J.Org.Chem., 1987, 52, 3860. 18. J.A.Marshal1 and J.Lebreton, Tetrahedron Lett., 1987, 28, 3323. 19. J.A.Marshal1, J-Lebreton, B.S.DeHoff and T.M.Jenson, Tetrahedron Lett., 1987, 28, 723; J.Org.Chem., 1987, 52, 3883. 20 T-Takahashi, H-Nemoto, Y - E n d a , J.Tsuji, Y.Fukazawa, Txkajima and Y.Fujise, Tetrahedron, 1987, 43, 5499. J.Org.Chem., 1987, 52, 4885. 21. J.E.McMurry,-na 22. J.E.McMurry, J.R.Matz and K.L.Kees, Tetrahedron, 1987, 43, 5489. 23. C.Wright, M.Shulkind, K.Jones and M.Thompson, Tetrahedron Lett., 1987, 28, 6389. 24. G.StorE M.E.Krafft and S.A.Biller, Tetrahedron Lett., 1987, 2, 1035. 25 - S.Prabhakar, A.M.Lobo and M.M.Marques, J.Chem.Res. ( S ) , 1987, 167. 26. K.Hayakawa, T.Yasukouchi and K.Kanematsu, Tetrahedron Lett., 1987, 28. 5895. 27. M.E.Kuehne, D.E.Podhorez, T.Mulamba and W.G.Bornmann, J.Org. Chem., 1987, 52, 347. 28. P.L.Feldman and H-Rapoport, J.Am.Chem.Soc., 1987, 109, 1603. 29. K.Hakam, M-Thielmann, T.Thielmann and E.Winterfeldt, Tetrahedron, 1987, 43, 2035. 30. G.W.Gribble and F.L.Switzer, Synth.Comm., 1987, 17, 377. 31. P.J.Harrington, L.S.Hegedus and K.F.McDanie1, J.Am.Chem.Soc., 1987, 109, 4335. 32. L . S Hedgus, J.L.Toro, W.H.Miles and P.J-Harrington, J.Org.Chem. , 1987, 52, 3319. 33. R.C.Kelly, I.Gebhard, N.Wicnienski, P.A.Aristoff, P.D.Johnson and D.G.Martin, J.Am.Chem.Soc., 1987, 109, 6837. 34. P.Magnus, T-Gallagher, J.Schultz, Y.-S.Or and T.P.Ananthanarayan, J.Am.Chem.Soc., 1987, 109, 2706. 35. P-Carter, S.FitzJohn, S.Halazy and P.Magnus, J.Am.Chem.Soc., 1987, 2, 2711. 36. R.E.Bolton, C.J.Moody, C.W.Rees and G.Tojo, J.Chem.Soc., Perkin Trans. 1, 1987, 931. 37. C.J.Moody and G.J.Warrellow, Tetrahedron Lett., 1987, 28, 6089. 38. D.M.Ryckman and R.V.Stevens, J.Am.Chem.Soc., 1987, 109,4940. 39. A.G.Schultz, P.J.McCloskey and J.J.Court, J.Am.Chem.Soc., 1987, 109, 6493. 40. S.Mzengeza, C.M.Yang and R.A.Whitney, J.Am.Chem.Soc., 1987, 109, 276. 41. S.Takano, Y.Iwabuchi and K-Ogasawara, J.Am.Chem.Soc., 1987, 109, 5523. 42. R.Baker, M.J.O'Mahony and C.J.Swain, J.Chem.Soc., Perkin Trans. I, 1987, 1623. 43. P.J.Kociefiski, S.D.A.Street, C.Yeates, and S.F.Campbel1, J.Chem. SOC., Perkin Trans. 1, 1987, 2171. 44. P.J.KocieAski, S.D.A.Street, C.Yeates, and S.F.Cambel1, J.Chem.Soc., Perkin Trans. 1, 1987, 2189. 45. M.T.Crimmins, W.G.Hollis, Jr., and D.M.Bankaitis-Davis, Tetrahedron Lett., 1987. 28, 3651. ~.46. M.T.Crimmins, W.G.Hollis, Jr., and J.G.Lever, Tetrahedron Lett., 1987. 3647. , 28. , 47. J.D.WhSe and A.P.Dantanarayana, Tetrahedron Lett., 1987, 28, 6417. 48 S.J.Danishefsky, D.M.Armistead, F.E.Wincott, H.G.Selnick and R.Hungate, J.Am.Chem.Soc., 1987, 109, 8117. f
____I
I
~
-
_
9: Highlights in Total Synthesis of Natural Products
517
49. S.J.Danishefsky, H.G.Selnick, D.M.Armistead and F.E.Wincott, J.Am.Chem.Soc., 1987, 109, 8119. 50. S.F.Martin, M.S.Dappen, B.Dupre and C.J.Murphy, J.Org.Chem., 1987, 52, 3706. 1984, 106, 2949. 5 1 . D.R.Williams and S.-Y.Sit, J.Am.Chem.Soc., 9 8 7 , 1 0 9 , 1269. 52. A.B.Smith, 111, and M.Fukui, J.Am.Chem.Soc., 1 _______ 1987,109, 1272. 53. A.B.Smith, 111, and R.A.River-Soc., 54. G.Stork and S.D.Rychnovsky, J.Am.Chem.Soc., 1987, 109, 1565. 55. G.Stork and S.D.Rychnovsky, J.Am.Chem.Soc., 1987, 109, 1564. 56- G.Stork, 1.Paterson and F.K.C.Lee, J.Am.Chem.Soc., 1982, 104, 4686. 57. R.B.Woodward et al, J.Am.Chem.Soc., 1981, 103, 3213. 58. G-Quinkert, N.Heim, J.Glenneberg, U.-M-Billhardt, V.Autze, J.W.Bats and G.Ddrner, Angew.Chem.Int.Ed.Engl., 1987, 26, 362. 59. E.Vedejs, R.A.Buchanan, P.Conrad, G.P.Meier, M.J.Mullins and Y-Watanabe, J.Am.Chem.Soc., 1987, 109, 5878. 60. K.Suzuki, T.Matsumoto, K.Tomooka, K.Matsumoto and G-Tsuchihashi, Chem.Lett., 1987, 113. 61. K.C.Nicolaou, R.A.Daines, J.Uenishi, W.S.Li, D.P.Papahatjis and T.K.Chakraborty, J.Am.Chem.Soc., 1987, 109, 2205. 62. K.C.Nicolaou, R.A.Daines and T.K.Chakraborty, J.Am.Chem.Soc., 1987, 109, 2208. 63. K.C.Nicolaou, R.A.Daines, T.K.Chakraborty and Y.Ogawa, J.Am.Chem.Soc., 1987, 109, 2821. 64. D.P.Negri and Y.Kishi, Tetrahedron Lett., 1987, 28, 1063. 65. R.K.Boeckman, Jr., A.B.Charette, T.Asberom and B.H.Johnston, J.Am.Chem.Soc., 1987, 109, 7553: 66. K.L.Rinehart, V.Kishore, S-Nagarajan, R.J.Lake, J.B.Gloer, F.A.Bozich, K.-M.Li, R.E.Maleczka, Jr., W.L.Todsen, M.H.G.Munro, D.W.Sullins and R.Sakai, J.Am.Chem.Soc., 1987, 109, 6846. 67. G.R.Pettit, Y.Kamano, C.W.Holzapfe1, W.J.van Zyl, A.A.Tuinman, C.L.Herald, L-Baczynskyj and J.M.Schmidt, J.Am.Chem.Soc., 1987, 109, 7581. 68. E.J.Corey and W.Su, J.Am.Chem.Soc., 1987, 109, 7534. 69. J.E.Forbes and G-Pattenden, Tetrahedron Lett., 1987, 28, 2771. 70. S.Nishiyama, Y-Shizuri, H.Toshima, M.Ozaki, S.Yamamura, K.Kawai, N.Kawai and H.Furukawa, Chem.Lett., 1987, 515. 71. D.R.Williams and F.H.White, J.Org.Chem., 1987, 52, 5067. 72. S.V.Ley, D-Santafianos,W.M.Blaney and M.S.J.Simmonds, Tetrahedron Lett., 1987, 28, 221. 73. J.C.Barrish, H.L.Lee, E.G.Baggiolini and M.R.Uskokovic, J.Org.Chem., 1987, 52, 1372. 74. J.K.Whitesel1 and M.A.Minton, J.Am.Chem.Soc., 1987, 109, 6403.
Reviews on General and Synthetic Methods COMPILED BY K. CARR, D. J. COVENEY, AND G. PAlTENDEN
1
Fluoroorsanic ComDounds
J.Mann,'Modern Methods €or the Introduction of Fluorine into Orqanic Molecules:
An Approach to Compounds with Altered Chemical and
Biological Activities', Chem.Soc.Rev., 1987, 2
s,381.
Carbonvl Comwounds
D.J.R.Massy, 'a-Thioalkylation
2 Aldehydes
and Thiols', Svnthesis,
1987, 589. G.A.Artamkina and I.P.Beletskaya, 'The Cleavage of the Carbon-Carbon Bond in Carbonyl Compounds and Alcohols Under the Influence of B a s e s ' , Russ.Chem.Rev.,
1987,
56,
983.
T.Mukaiyama and M.Murakami, 'Cross-Couplinq Reactions Based on Acetals', Synthesis, 1987, 1043. 3
Peptides
S.M.Andreev, N.A.Samoilova, Y.A.Davidovich and S.V.Roqozhin, 'Polymeric Reagents in the Synthesis of Peptides, Russ.Chem.Rev., 1987, 56, 366. P.A.Sutton and D.A.Buckinqham, 'Cobalt(II1)-Promoted Hydrolvsis of Amino Acid Esters and Peptides and the Synthesis of Small Peptides, Acc.Chem.Res., 4
1987,
2,357.
Orqanometallics
Genera 1 'The Chemistry of the Metal-Carbon Bond:
The Use of Orqanometallic
Compounds in Organic Synthesis', Vo1.4, Ed. F.R.Hartley, John Wiley & Sons, Chichester, 1987. E.-1-Negishi, 'Controlled Carbometallation as a New Tool for Carbon-Carbon Bond Formation and its Application to Cyclisation', Acc.Chem.Res.,
1987,
2,
65.
Revitws on General and Synthetic Methods
519
J.Dubac and A.Laporterie, 'Ene and Retro-Ene Reactions in Group 14 Organometallic Chemistry', Chem.Rev., 1987, 87, 319. 'Organometallic Compounds; Chemistry Sourcebooks', Chapman and Hall, London, 1987, (Series covers a wide range of organometallics and reagents). Main Group Elements N.S.Narasimham and R.S.Mali, 'Heteroatom Directed Aromatic Lithiation Reactions for the Synthesis of Condensed Heterocyclic Compounds', Top.Curr.Chem.,l987, 138, 63. E.Bickelhaupt,'Di-Grignard Reagents and Metallacycles', Angew.Chem., Int.Eng.Edn., 1987, 26, 990. Y.Yamamoto, 'Allylic Tin Compounds in Organic Synthesis', Aldrichimica Acta, 1987, 2, 45. 'Tin in Organic Synthesis', M.Pereyre, J.Quintard and A-Rahm, Butterworths, Sevenoaks, 1987. 'Perspectives in the Organic Chemistry of Sulfur-Studies in Organic Chemistry', Vo1.28, Eds. B.Zwanenburg and A.J.H.Klunder, Elsevier Science Publishers, Amsterdam, 1987. 'Organoselenium Chemistry', D.Liotta, John Wiley & Sons, Chichester, 1987. A.Krief, 'Synthesis and Synthetic Applications of 1-Metallo-1Selenocyclopropanes and -Cyclobutanes and Related 1-Metallo-1Silylcyclopropanes', Top.Curr.Chem., 1987, 135, 1. I.D.Sadekov, B.B.Rivkin and V.I.Minkin, 'Organotellurium Compounds in Organic Synthesis', Russ.Chem.Rev., 1987, 56, 343. 'The Chemistry of Organic Selenium and Tellurium Compounds', Vo1.2, Ed.S.Patai, John Wiley & Sons, Chichester, 1987. Transition Elements 'Principles and Applications of Organotransition Metal Chemistry', 2nd Edn. J.P.Collman, L.S.Hegedus. J.R.Norton and R.G.Finke, Oxford University Press/University Science Books, Oxford, 1987. P.Binger and H.M.Bkh, 'Cyclopropenes and Methylenecyclopropanes as Multifunctional Reagents in Transition Metal Catalysed Reactions', Top.Curr.Chem., 1987, 135, 77. 'Organometallic Chemistry Reviews; Annual Surveys: Transition Metals in Organic Synthesis, Organic Reactions of Selected n-Complexes', Eds. R.B.King and J.P.Oliver, Elsevier Science Publishers: Amsterdam and New York, 1987. H.Yasuda and A.Nakamura, 'Diene, Alkyne, Alkene and Alkyl Complexes of Early Transition Metals: Structures and Synthetic Applications in
Geneml and Synthetic Methods
520
Organic and Polymer Chemistry' Angew.Chem.Int.Enq.Edn., 723.
1987,
26,
K.M.Nicholas, 'Chemistry and Synthetic Utllltv of Cobalt-Complexed Propargyl Cations', Acc.Chem.Res., 1987, 20, 207. V.N.Kalinin, 'Arenechromium Tricarbonyls in Orqanic Synthesis', Russ.Chem.Rev., 1987, 56, 682. J.Tsuji and I.Minami, 'New Synthetic Reactions of Allyl Alkyl Carbonates, Allyl 8-Keto Carboxylates, and Allyl Vinylic Carbonates Catalysed by Palladium Complexes', Acc.Chem.Res., 1987, 2,140. R.H.Lioshutz, 'Applications of Hiqh-Order Mixed Organocuprates to Organic Synthesis', Synthesis, 1987, 325. 5
Cycloaddition and other Pericycle Processes
D.Craiq, 'Stereochemical Aspects of the Intramolecular Diels-Alder Reaction', Chem.Soc.Rev., 1987, 16, 187. 'Hetero-Diels Alder Methodology in Organic Synthesis', D.L.Boger and S.M.Weinreb, Academic Press, San Diego, 1987. A.Ichihara, 'Retro-Diels-Alder Strategy in Natural Product Synthesis', Synthesis, 1987, 207. M.L.Petrov and A.A.Petrov, 'The 1,3-Anionic Cycloaddition Reactions of a , B - Unsaturated Thiolates and their Analogues', Russ.Chem.Rev., 1987, 56, 152. A.J.Fatiadi, 'Addition and Cycloaddition Reactions of Tetracyanoethylene (TCNE) in Organic Chemistry', Synthesis, 1987, 749. M-Brookhart and W.B.Studabaker, 'Cyclopropanes from Reactions of Transition- Metal-Carbene Complexes with Olefins', Chem.Rev., 1987, 87, 411. N.M.Przhevalskii andI.I.Grandberg, 'The Cope Aza-Rearrangement in Organic Synthesis', Russ.Chem.Rev., 1987, 56, 477. N.J.Bauld, D.J.Bellville, B.Harirchian, K.T.Lorenz, R.A.Pabon, Jr., D.W.Reynolds, D.D.Wirth, H.-S.Chiou, and B.K.Marsh, 'Cation Radical Pericyclic Reactions', Acc.Chem.Res., 1987, 20, 371. C.J.Moody, 'Claisen Rearranqements in Heteroaromatic Systems', Adv. Heterocycl.Chem., 1987, 42, 203. 6
Macrocycles
'Synthesis of Macrocycles', Eds. R.M.Izatt and J.Christensen, John
Reviews on General and Synthetic Methods
52 1
Wiley & Sons, Chichester, 1 9 8 7 . H.W.Wasserman, 'New Methods in the Formation of Macrocyclic Lactams and Lactones of Biological Interest', Adrichimica Acta, 1 9 8 7 , 20, 63.
7
Heterocvcles
E.N.Karanlova, 'The Synthesis of Saturated Cyclic Sulphides', Russ.Chem.Rev., 1 9 8 7 , 56, 546. D.S.Donald and O.W.Webster, 'Synthesis of Heterocycles from Hydrogen Cyanide Derivatives', g.Heterocycl.Chem., 1 9 8 7 , 41, 2 . 'Synthesis of Fused Heterocycles', Ed. G.P.Ellis, John Wiley Chichester, 1 9 8 7 .
&
Sons,
'Chemistry of Diazirines', Ed. M.T.H.Liu, Wolfe Medical Pulications Limited, London 1 9 8 7 . R.Grigg, 'Prototropic Routes to 1,3-
and 1,5-Dipolesf and lf2-Ylides:
Applications to the Synthesis of Heterocyclic Compounds', Chem.Soc.Rev., 1 9 8 7 , 16, 8 9 . M.H.Elnagdi, G.E.H.Elgemeie and M.R.H.Elmoghayar, 'Chemistry of Pyrazolopyrimidines', Adv.Heterocyl.Chem., 1 9 8 7 , 41, 3 2 0 . G.Hall, J.K.Sugden and M.B.Waghela, 'Pyrollizine Chemistry', Synthesis, 1 9 8 7 , 10. 'Thiophene and its Derivatives', Part 3 , Ed. S.Gronowitz, WileyInterscience, Chichester, 1 9 8 7 . T.L.Gilchrist, 'Ring-Opening of Five-Membered Heteroaromatic Anions', Adv.Heterocycl.Chem., 1 9 8 7 , 41, 4 2 . I.Hermercz, 'Chemistry of Diazabicycloundecene (DBU) and Other Pyrimidoazepines', Adv.Heterocycl.Chem., 1 9 8 7 , 42, 2 . G.L'abbe, 'Six-Membered Heterocyclic Isocyanates and Isothiocynates: Synthesis and Reactions', 8
Synthesis, 1 9 8 7 , 5 2 5 .
Natural Products
P.G.Baraldi, A.Barco, S.Benetti, G.P.Pollini and D.Simoni, 'Synthesis of Natural Products via Isoxazoles', Synthesis, 1 9 8 7 , 857.
Ae. de Groot and T.A. van Beck, 'Terpenoid Antifeedants (Part 11). The Synthesis of Drimane and Clerodane Insect Antifeedants', Recl.Trav.Chim. Pay-Bas, 1 9 8 7 , 106, 1. J.W.Huffman (Ed.), 'Current Topics in Sesquiterpene Synthesis', Tetrahedron, (Symposium in Print), 1 9 8 7 ,
43,
5467.
522
Geneml and Synthetic Methods 9
Asymmetric and Selective Synthesis
M.Srebrik and P.V.Ramachandrau, 'The Utility of Chiral Organoboranes in the Preparation of Optically Active Compounds', Aldrichimica Acta, 1987, 2,9. 'Asymmetric Synthesis', E d s . G.M.Coppola and H.F.Schuster, John Wiley & Sons, 1987. G.H.Posner, 'Asymmetric Synthesis of Carbon-Carbon Bonds Using Sulfinyl Cycloalkenones, Alkenolides, and Pyrones', Acc.Chem.Res., 1987,2, 72. K.A.Kochetov and V.M.Belikov, 'Modern Asymmetric Synthesis of a-Amino acids', Russ.Chem.Rev., 1987, 56, 1 0 4 5 . 'Asymmetric Synthesis: Construction of Chiral Molecules Using Amino Acids', G-Coppola and H.F.Schuster, John Wiley and Sons: New York, 1987. 'Stereoselective Synthesis', M-Nogradi, VCH Verlagsgesellschaft, Weinheim, 1987. R.W.Hoffmann, 'Stereoselective Synthesis of Building Blocks with Three Consecutive Stereoqenic Centers: Important Precursors of Polyketide Natural Products', Angew.Chem.Int.Eng.Edn., 1987, 26, 489. M.Braun, 'Stereoselective Aldol Reactions with a-Unsubstituted Chiral Enolates', Angew.Chem.Int.Eng.Edn., 1987, 26, 2 4 . Y.Yamamoto, 'Acyclic Stereocontrol via Allylic Organometallic Compounds', Acc.Chem.Res., 1987, 20, 243. 10
Sugars
S.J.Danishefsky and M.P.DeNinn0, 'Totally Synthetic Routes to the Higher Monosaccharides', Angew.Chem.Int.Eng.Edn., 1987, 26, 1 5 . G.O.Aspinal1, 'Chemical Modification and Selective Fragmentation of Polysaccharides', Acc.Chem.Res., 1987, 20, 114. 11
Photochemistry, Electrochemistry and Radicals
W.J.Leigh and R-Srinivasan, 'Organic Photochemistry with Far-Ultraviolet Photons. The Photochemistry of Allyl-, Vinyl-, and Alklylidenecyclopropanes', Acc.Chem.Res., 1987, 20, 107. J.J.McCullough, 'Photoaddition of Aromatic Compounds', Chem.Rev., 1987, 87, 811.
Reviews on General and Synthetic Methods
523
B.L.Feringa, 'Photo-Oxidation of Furans', Recl.Trav.Chim.Pays-bas, 1987, 106, 469. M.A.Fox, 'Selective Formation of Organic Compounds by Photoelectrosynthesis at Semiconductor Particles', Top.Curr.Chem., 1987, 142, 71. 'Recent Advances in Electroorganic Synthesis', Ed. S.Torii, Elsevier Science Publishers: Amsterdam, 1987. J.H.P.Utley, 'Electrogenerated Bases', Top.Curr.Chem., 1987, 142, 131. E-Steckham, 'Organic Synthesis with Electrochemically Regenerable Redox Systems', Top.Curr.Chem., 1987, 142, 1. H.-J.Schafer, 'Oxidation of Organic Compounds at the Nickel Hydroxide Electrode, Top.Curr.Chem., 1987, 142, 101. K.Uneyama, 'The Chemistry of Electrogenerated Acids (EGA); How to Generate EGA and How to Use it', Top.Curr.Chem., 1987, 142, 167. M.Ramaiah, 'Radical Reactions in Organic Synthesis', Tetrahedron, 1987, 43, 3541. D.Crich, 'O-Acyl Thiohydroxamates: New and Versatile Sources of Alkyl Radicals for Use in Organic Synthesis', Aldrichimica Acta, 1987, 20, 35. 12
Reagents
W.P.Neumann, 'Tri-2-butyltin Hydride as a Reagent in Organic Synthesis, Synthesis, 1987, 665. 'Preparative Chemistry Using Supported Reagents', Ed. P.Laszlo, Academic Press, California, 1987. M.D.Mizhiritskii and Y.A.Yuzhelevskii, 'New Silylating Agents. Methods of Synthesis and Properties', Russ.Chem.Rev., 1987, 56, 355. G.A.Olah, L.Ohannesian and M-Arvanaghi, 'Formylating Agents', Chem.Rev., 1987, 87, 671. 13 Oxidation and Reduction
A.J.Fatiadi, 'The Classical Permanganate Ion: Still a Novel Oxidant in Organic Chemistry', Synthesis, 1987, 85. 'New Developments in Selective Oxidation', B.Delmon and P.Ruiz, Elsevier, Amsterdam, 1987. J.M.Brown, 'Directed Homogenous Hydrogenation', Angew.Chem.Int.Eng. Edn. , 1987, 26, 190.
524
General and Synthetic Methods
K.Mullen, 'New Reductive Transformations of Unsaturated Cyclic Hydrocarbons', Angew Chem.Int.Eng.Edn., 1 9 8 7 , 26, 2 0 4 . 14
Resolution Methods
F.Toda, 'Isolation and Optical Resolution of Materials Utilizing Inclusion Crystallisation', Top.Curr.Chem., 1 9 8 7 , 140, 4 3 . D.Worsch and F.Vogtle, 'Separation of Enantiomers by Clathrate Formation', Top.Curr.Chem., 1 9 8 7 , 140, 2 1 . 15
General
V.T.D'Souza and M.L.Bender, 'Miniature Organic Models of Enzymes', Acc.Chem.Res., 1 9 8 7 , 20, 1 4 6 . A.J.Kresge, 'Unusual Reactivity of Prostacyclin: Rational Drug Design through Physical Organic Chemistry', Acc.Chem.Res., 1 9 8 7 , 20, 364.
J-Lindley and T.J.Mason, 'Sonochemistry Part 2 - Synthetic Applications', Chem.Soc.Rev., 1 9 8 7 , %,* 2 7 5 . A-Maercker, 'Ether Cleavage with Orqano-Alkali-Metal Compounds and Alkali Metals', Angew.Chem.Int.Eng.Edn., 1 9 8 7 , 26, 9 7 2 . L.A.Carpino, 'The 9-Fluorenylmethyloxycarbonyl Family of Base-Sensitive Amino-Protecting Groups', Acc.Chem.Res., 1 9 8 7 , 20, 401.
D.L.Lloyd, 1.Gosney and R.A.Ormiston, Arsonium Ylides (with some mention also of Arsimimines, Stibonium and Bismuthonium Ylides), Chem.Soc.Rev., 1 9 8 7 , 16, 45. 16 Miscellaneous
E.B.Merkushev, 'Organic Compounds of Polyvalent Iodine - Derivatives of Iodosobenzene', Russ.Chem.Rev., 1 9 8 7 , 56, 8 2 6 . B.Halton and P.J.Stang, 'Alkylidenecycloproparenes and Related Compounds', Acc.Chem.Res., 1 9 8 7 , 20, 4 2 9 . U.Pindur, J-Muller, C.Flo and H.Witze1, 'Ortho Esters and Dialkoxycarbonium Ions: Reactivity, Stablility, Structure, and New Synthetic Applications', Chem.Soc.Rev., 1 9 8 7 , 16, 75. T.D.Petrova and V.E.Platonov, 'Methods of Synthesis of Compounds with Halogenoimidolyl Groups', Russ.Chem.Rev., 1 9 8 7 , 56, 1125.
Reviews on General and Synthetic Methods
525
E.Breitmaier, F.W.Ullrich, B.Potthoff, R.Bfihme and H-Bastian, ' 3 Alkoxyacroleins in Organic Synthesis', Synthesis, 1987, 1. C.K.Bradsher, 'Formation of Six-membered Aromatic Rings by Cycloalkylation of some Aldehydes and Ketones', Chem.Rev., 1987,=, 1277.
G.P.Ellis and T.M.Romney-Alexander, 'Cyanation of Aromatic Halides', Chem-Rev., 1987, 87, 7 7 9 . 0.Meth-Cohn, 'New Synthetic Applications of Oxycarbonylnitrenes', Acc.Chem,Res., 1987, 20, 18. A.J.Fatiadi, 'New Applications of Tetracyanoethylene in Organometallic Chemistry', Synthesis, 1987, 959. G.Maas, 'Transition-Metal Catalysed Decomposition of Aliphatic Diazo Compounds - New Results and Applications in Organic Synthesis', Top. Curr.Chem., 1987, 137, 75.
Author Index
I n t h i s i n d e x t h e number g i v e n i n p a r e n t h e s i s i s t h e C h a p t e r number o f t h e c i t a t i o n and t h i s i s f o l l o w e d b y t h e r e f e r e n c e number o r numbers o f t h e r e l e v a n t c i t a t i o n s wi t h i n t h a t C h a p t e r
Abbott, D.E. (4) 56; (6ii) 199 Abd-El-Aziz, A.S. (3) 187 Abd El Samii, Z.K.M. (3) 254; (6ii) 251; (8) 107 Abe, K. (2) 199; (3) 217 Abelt, C.J. (5) 105 Aben, R.W.M. (8) 77 Aboujaoude, E.E. (2) 106 Abraham, W.D. (2) 90; (4) 235; (6ii) 50, 240; (7) 94 Abreo, M.A. (4) 103 Achiwa, K. (3) 134; (4) 23; (5) 35; (8) 85, 86 Achmatowicz, 0. (2) 110 Ackland, D.J. (3) 187 Ackland, M.J. (4) 105 Adachi, S. (6ii) 58 Adger, B.M. (3) 472 Adkins, R. (3) 249 Adlington, R.M. (3) 430; (6ii) 213; (8) 1.50 Aebi, J.D. (3) 409, 412 Afonso, C.M. (2) 13 Agami, C. (3) 193 Aggarwal, V.K. (3) 45; (4) 119, 237 Ahlbrecht, H. (2) 148 Ahmad, S. (3) 71; (4) 178 Ahmar, M. (3) 112, 247 Abed, S. (3) 349 Aibe, H. (3) 289 Aida, T. (4) 228 Aikawa, H. (3) 36 Aiura, A. (5) 33 Aiura, H. (8) 143 Aizpurua, J.M. (2) 23, 24; (5) 74 Akaji, K. (3) 470 Akama, T. (2) 79 Akase, F. (3) 40
Akiba, K. (1) 50; (3) 344; (4) 36; (5) 33; (6ii) 237; (8) 143 Akita, M. (4) 194; (6ii) 153 Akiyoshi, K. (2) 109 Akutagawa, S. (3) 147; (4) 125, 126; (6i) 11, 12 Akuzawa, K. (2) 142 A1 Ashmawy, M.I. (3) 254; (6ii) 251; (8) 107 Alauddin, M.M. (7) 52 Albericio, F. (3) 475, 476 Alberola, A. (4) 108 Albert, R. (3) 428 Albizati, K.F. (8) 32 Al-Hassan, M.I. (1) 14 Al-Nuri, M. (1) 75 Alo, B.I. (2) 69 Alpegiani, M. (3) 132 Alper, H. (6i) 84 Alvarez, C. (2) 161 Alvarez, R.M. (4) 162 Alvernhe, G. (4) 167 Amaike, M. (9) 4 Amamria, A. (1) 32; (3) 220; (6ii) 186 Amano, E. (2) 105; (3) 185 Amarasekara, A.S. (5) 104 Ambrogi, V. (8) 70 Amedio, J.C., jun. (2) 14; (3) 181; (4) 155 Amemiya, M. (3) 473 her, I. (6i) 18 Ammann, A.A. (2) 61; (7) 7 Amon, C.M. (2) 12 Amri, H. (3) 210 Ananda, G.D.S. (3) 175
Ananthanarayan, T.P. (9) 34 Anderskewitz, R. (3) 405 Anderson, A.G. (1) 93 Anderson, D.A. (2) 152 Anderson, L.G. (7) 16; (8) 34 Anderson, M.B. (1) 41 Andersson, C.-M. (1) 21 Ando, A. (2) 166; (6ii) 9, 10 Ando, K. (3) 189 Ando, T. (1) 36; (2) 165; (4) 189 Andres, C. (4) 108 Andrew, R.G. (3) 447 Anelli, P.L. (2) 10; (3) 8; (4) 157 Angeletti, E. (3) 208 Angelici, R.J. (6i) 32, 33 Angle, S.R. (6i) 43 Annoura, H. (4) 91, 92 Annunziata, R. (4) 8; (8) 3 Anteunis, M.J.O. ( 5 ) 54 Antonioletti, R. (8) 23 Anzai, T. (2) 63; (6ii) 260 Aoe, K. (8) 105 Aoki, H. (4) 183 Aoki, S. (3) 83; (6ii) 85 Aoyama, Y. (4) 4 Aparao, S. (8) 36 Arai, I. (4) 22 Arai, K. (3) 364; (6i) 19 Arai, Y. (7) 56 Araki, S. (4) 37; (6ii) 236 Araki, Y. (2) 149 Arase, A. (1) 64 Arif, A.M. (3) 452
General and Synthetic Methods
528
Arimoto, M. (1) 39; (5) 102; (6ii) 148 Aristoff, P.A. (9) 33 Armesto, D. (5) 91 Armistead, D.M. (9) 48, 49 Armstrong, P. (8) 56, 57 Armstrong, R.W. (1) 71 Arnold, L.D. (3) 395 Arnone, A. (3) 282 Asami, M. (4) 95 Asao, N. (3) 211 Asaoka, M. (3) 327; (6ii) 171, 172 Asberom, T. (9) 65 Asensio, G. (1) 100; (4) 172, 205 Ashida, T. (5) 72 Ashiya, H. (2) 9; (4) 156 Asirvatham, E. (3) 354 Ago, Y. (6ii) 285, 287 Assercq, J. (2) 71 Astrab, D.P. (2) 178; (4) 45; (6ii) 41 Aumann, R. (7) 20; (8) 147 Aurrecoechea, J . M . (4) 221; (6ii) 52, 53 Autze, V. (3) 350; (9) 58 Awasthi, A.K. (6i) 22 Ayoub, M.T. (3) 46 Azerad, R. (3) 4, 156 Baba, A. (8) 28 Baba, S. (1) 70; (3) 238; (6ii) 124 Babler, J.H. (2) 132, 134 Babu, S. (8) 108 Baciocchi, E. (2) 141 Back, T.G. (1) 30, 89; (6ii) 265 Bacos, D. (5) 92 Baczynskyj, L. (9) 67 Biickvall, J.E. (6i) 7, 22, 56; (7) 5; (8) 125 Baer, J.E. (3) 315 Baettig, K. (7) 64, 65 Baggiolini, E.G. (9) 73 Bagheri, V. (1) 19; (611) 45 Bahsas, A. (1) 53; (6ii) 197 Bailey, W.F. (1) 1 ; (6ii) 19; (7) 51 Baillarge, M. (3) 391 Baker, R. (9) 42 Bakshi, R.K. (2) 53; (3) 292; (4) 2, 17, 18; (6ii) 102, 109, 111 Balaban, A.R. (3) 380 Balaban, T.-S. (3) 380
Balasubramanian,T.M. (5) 96 Balavoine, G. (3) 461 Baldoli, C. (6i) 37 Baldridge, R. (3) 80, 249 Baldwin, J . E . (1) 60, 102; (3) 426, 429, 430; (6i) 90; (6ii) 213; (8) 104, 150 Balestra, M. (3) 236 Ballesteros, A. (8) 113 Ballini, R. (3) 194; (5) 5
Bandeburg, S.C. (3) 378 Bando, T. (3) 260 Banfi, L. (3) 435 Bankaitis-Davis, D.M. (9) 45 Bannigan, L.H. (6ii) 62 Banti, C. (5) 14 Banwell, M.G. (2) 12 Barak, G. (5) 20 Barbaro, G. (8) 7 Barbeaux, P. (6ii) 20; (7) 27, 36 Barbot, F. ( 5 ) 59 Barcelo, G. (3) 462 Barcina, J.O. (4) 162 Bardenhagen, J. (3) 403 Barger, T.M. (5) 29; (6ii) 163 Barieux, J.-J. (3) 247 Barlos, K. (3) 427, 458, 474 Barluenga, J. (1) 100; (3) 287; (4) 109, 172, 193, 205; (6ii) 16-18, 30, 90, 152, 264; (8) 113, 137 Barney, C.L. (5) 29; (8) 75 Barrish, J.C. (9) 73 Barros, M.T. (2) 13 Barta, M. (5) 1 Bartela, B. (1) 25; (6ii) 252 Bartels, D. (4) 238 Bartlett, P.A. (4) 231; (6ii) 87 Bartoli, D. (6ii) 278 Barton, D.H.R. (3) 89, 139, 431; (4) 208, 216, 217; (5) 23; (6ii) 206, 238, 280; (8) 99 Bartra, M. (6ii) 184 Barua, N.C. (4) 15 Basavaiah, D. (2) 146, 177; (4) 43, 44 Bashiardes, G. (61) 52 Bashir, S. (4) 146 Baskaran, S. (3) 357 Bassett, K.E. (4) 199
Bates, A.D. (6ii) 35 Bates, G.S. (1) 66 Bathgate, A. (8) 127 Bats, J.W. ( 3 ) 350; (9) 58 Battaglia, A. (3) 435; (8) 7, 145 Baudyfloch, M. (5) 86 Bauld, N.L. (7) 53 Baum, J.S. ( 3 ) 188 Beak, P. (3) 383; (6ii) 24 Beal, R.B. (4) 111 Beanland, J. (8) 47 Beard, M. (3) 80 Beau, J.-M. (1) 71 Beck, A.K. (4) 68 Beck, G.R. (3) 62 Beck, H. (6ii) 49 Becker, D.P. (6i) 78; (7) 43 Beckwith, A.L.J. (8) 131 Bedford, C.D. (1) 99; (5) 81 Beebe, T.R. (3) 249 Beedle, E.C. (3) 424; (6ii) 110 Beetz, I. (3) 51 Begley, M.J. (8) 12 Bell, K.H. (3) 33, 442 Bellassoued, M. (3) 41 Bellville, D.J. (7) 53 Belotti, D. (8) 120 Belter, R.K. (2) 72; (3) 300 Benderly, A. (2) 167; (6ii) 103 Benedetti, F. (6ii) 64 Benezra, C. (4) 165 Bennett, P.A.R. (1) 60 Benoiton, N.L. (3) 468 Bentz, G. (8) 102 Bergbreiter, D.E. (1) 4; (2) 196; (3) 92, 453 Bergen, E.J. (4) 113 Bernard, D. (2) 131 Bernardi, A. (3) 222 Bernardi, R. (4) 30 Bernardinelli, G. (3) 281; (4) 63 Bernatchez, M. (3) 324; (7) 25, 26 Bernath, G. (8) 71 Berrada, S. (2) 195; (3) 108 Bertolini, G . (3) 143 Bertz, S.H. (2) 184 Berube, G. (7) 66 Besbes, N. (8) 102 Beslin, P. (3) 107 Bessho, K. (3) 477; (611) 127
Author Index Bestmann, H.-J. (3) 301, 352; (5) 10 Betz, R. (6ii) 42 Bhandal, H. (8) 12 Bharathi, T.K. (2) 146, 177; (4) 43, 44 Bhat, K.L. (3) 444 Bhat, K.S. (4) 81, 82; (6ii) 118 Bhattacharya, S. (4) 138 Bhupathy, M. (2) 90; (4) 235; (6ii) 240, 246; (7) 94 Bialecka-Florjanczyk, E. (2) 110 Bickelhaupt, F. (6ii) 73, 155; (7) 19; (8) 48 Bienz, S. (2) 91; (3) 350 Biffi, C. (2) 10; (3) 8; (4) 157 Bilgrien, C. (4) 148 Biller, S.A. (9) 24 Billhardt, U.-M. (3) 350; (9) 58 Billington, D.C. (6i) 77 Binns, M.R. (3) 274 Birbaum, J.-L. (1) 25; (4) 240 Black, T.G. (6ii) 269 Blade, R.J. (1) 114 Blaney, W.M. (9) 72 Block, R. (3) 307 Blum, J. (6i) 18 Boddy, I. (8) 18 Boeckman, R.K., jun. (3) 272; (9) 65 Boere, R.T. (5) 95 Bohe, L. (3) 89; (6ii) 280 Boivin, T.L.B. (8) 8 Boldrini, G.P. (4) 87 Bollok, T. (6ii) 230 Boltansky, A. (3) 279 Bolton, G.L. (9) 9 Bolton, R.E. (9) 36 Bonadies, F. (3) 337; (8) 23 Bongini, A. (3) 440 Bonini, C. (3) 337 Bonnert, R.V. (1) 57; (2) 76; (6ii) 173; (7) 74 Booth, P.M. (3) 326 Borbaruak, N.C. (4) 15 Bornmann, W.G. (9) 27 Borredon, M.E. (3) 100; (4) 244 Borselli, G. (6ii) 177 Bortolini, 0 . (2) 17 Bosch, G.K. (9) 21 Bosch, P. (5) 91 Botta, M. (1) 113 Bottard, J.C. (5) 81
529
Bottaro, J.C. (1) 99 Bottorff, K.J. (3) 258 Bouda, H. (4) 244 Boukouvalas, J (3) 280, 281, 309; (4) 62, 63 Boulaajaj, S. (8) 90 Boulanger, R. (3) 324; (7) 25 Boyd, G.V. (3) 380 Boyer, J.H. (5) 107 Bozich, F.A. (9) 66 Brady, W.T. (7) 8 Braenden, J.E. (4) 140 Brand, M. (3) 223; (4) 181 Brandsma, L. (6ii) 38 Brandstadter, S.M. (8) 114 Brandt, C.A. (1) 65; (6ii) 286 Braun, M. (3) 28, 142 Braunschweiger, H. (3) 149 Bravdo, T. (6i) 18 Bravo, P. (3) 282 Brillon, D. (7) 85, 86 Brimble, M.A. (8) 25 Britton, T.C. (3) 3, 397; (5) 101 Brocard, J. (6i) 36 Broka, C.A. (4) 241 Brookhart, M. (6i) 9; (7) 1 Brooks, D.W. (3) 154; (4) 29, 164; (7) 36 Brougham, P. (3) 78 Brown, D. (1) 103; (2) 96 Brown, D.W. (3) 309 Brown, E.G. (3) 257 Brown, H.C. (2) 27, 53; (4) 1, 2, 20, 21, 81, 82; (dii) 96-98, 100-102, 105, 106, 108, 111, 112, 118 Brown, J.M. (3) 121, 451, 455; (6i) 10 Brown, M.J. (7) 100; (8) 14 Brown, P.A. (1) 57; (6ii) 173 Brown, P.S. (5) 96 Brownbridge, P. (611) 250 Bruckner, C. (3) 199 Brumby, T. ( 8 ) 37 Buchanan, R.A. (3) 359; (9) 59 Buchert, P . (6i) 34 Buchwald, S.L. (1) 40; (2) 56 Buckingham, D.A. (3) 460 Buisson, D. (3) 156 Bullock, W.H. (6ii) 67
.
Bumgardner, C.L. (2) 119; (4) 187 Bunnelle, W.H. (1) 42; (2) 181; (6ii) 78, 165 Buntain, G.A. (5) 97 Buono, G. (4) 70; (6ii) 89 Bureau, R. (8) 74 Burke, L.D. (2) 80; (3) 351 Burns, L.D. (6ii) 91 Burns, T.P. (6ii) 74 BUSS, A.D. (6ii) 266; (7) 59 BUSS, D. (1) 12; (6ii) 121 Butsugan, Y. (4) 37; (6ii) 236 Butt, S. (3) 280 Byrne, B. (2) 15; (4) 153 Bystrom, S.E. (8) 126 Cacchi, S. (3) 173 Cadilla, R . (8) 130 Cain, C.M. (6ii) 7 Cainelli, G. (3) 435; (8) 144-146 Cairns, P.M. (6ii) 128 Callens, R. (5) 54 Calo, V. (8) 45 Calogeropoulou, T. (2) 129; (6ii) 217 Camasseto, J.V. (2) 128 Campbell, M.M. (3) 309 Campbell, S.F. (9) 43, 44 Campestrini, S. (2) 17 Campos, P.J. (1) 100; ( 4 ) 172, 205 Camps, F. (3) 231; (4) 160 Cannone, P. (3) 324; (7) 25, 26 Cano, A.C. (2) 161 Cantacuzene, D. (3) 456 Capdevielle, P. (6i) 57 Capet, M. (1) 111 Caporusso, A.M. (1) 97 Capparelli, M.P. (3) 296 Capuano, L. (8) 66 Caputo, R. (2) 153 Carboni, B. (5) 2; (6ii) 117; (7) 61 Carboni, R. (6ii) 96 Cardani, C. (3) 222 Cardellicchio, C. (2) 38 Cardillo, G. ( 3 ) 440 Cardillo, R. (4) 30 Caris, R.C.H.M. (3) 401 Carless, H.A.J. (8) 47 Carlsen, P.H.J. (4) 140 Caro, B. (6i) 50
530
Carpino, L.A. (3) 466 Carr, R.C. (2) 80; (3) 351 Carretero, J.C. (3) 288; (6ii) 65, 261 Carrie, R. (3) 104; (5) 2, 34; (6ii) 96; (8) 90, 91 Carroll, P.J. (8) 49 Carruthers, W. (5) 39 Carter, P. (9) 35 Casadei, M.A. (3) 471 Casati, R. (3) 153; (4) 28 Casella, L. (6ii) 258 Castaldi, G. (3) 61; (4) 191 Castelhano, A.L. (1) 91; (3) 441; (4) 206 Castro, B. (3) 443, 457 Casucci, D. (6ii) 26 Caufield, C.E. (2) 162; (6ii) 11 Cava, M.P. (3) 363; (6ii) 28 Cavalla, D. (6ii) 231 Cavicchioli, S . (3) 61 Cazes, B. (3) 111, 112, 247 Celerier, J.P. (5) 92 Cen, W. (1) 94 Cercus, J. (3) 149 Ceruti, M. (2) 59 Cervillo, J. (3) 192 Cha, J.S. (2) 27-31, 33 Chakraborty, T.K. (3) 352; (9) 61-63 Chaloner, P.A. (4) 69; (6ii) 89 Chambers, M.S. (3) 330 Chan, C. (1) 106; (6i) 63 Chan, D.M.T. (3) 263 Chan, T.H. (2) 78; (4) 228; (6ii) 151, 157; (7) 72; (8) 31 Chandran, R. (1) 4; (3) 453 Chandrasekaran, S . (2) 21; (3) 357; (8) 79 Chang, C.-T. (3) 265; (4) 175 Chang, H.S. (2) 159 Chang, V.H.-T. (3) 347 Changyou, 2. (3) 416 Chan-Yu-King, R. (2) 193; (6ii) 227 Chapman, O.L. (5) 105 Charbonnier, F. (1) 95, 96; (4) 214 Charette, A.B. (9) 65 Charles, G. ( 4 ) 177 Charlton, J.L. (7) 52
General and Synthetic Methods
Chatterjee, S . (4) 138 Chattopadhyay, S . (6ii) 258 Chattopadhyay, T.K. (3) 70 Chaudhuri, N.C. (2) 138 Chem, M. (6ii) 28 Chen, B. (3) 119 Chen, C.-P. ( 3 ) 292; (4) 18; (6ii) 109 Chen, F.M.F. (3) 468 Chen, H.-J.C. (3) 414 Chen, J. (3) 10, 63; (6i) 54; (6ii) 280 Chen, K.-M. ( 3 ) 167; (6ii) 93 Chen, M.-H. (7) 21 Chen, M.Y. (5) 63 Chen, S.-T. (3) 428 Chen, S.C. (3) 115 Chen, Y.-S. (8) 105 Chen, 2.-C. (1) 93; (3) 118 Chenault, J. (1) 101; (3) 47; (6ii) 215 Chenchaiah, P.C. (4) 113 Cheng, M.4. (3) 138 Chiba, Y. (1) 16; (6ii) 113 Chihara, T. (4) 209 Chihiro, M. (9) 3 Chikashita, H. (2) 20 Chikugo, T. (3) 306 Chimiak, A. (3) 372, 481 Chimirri, A. (8) 139 Chin, C.S. (6i) 27 Chinn, R.L. (3) 272 Chiou, H.4. (7) 53 Chivikas, C.J. (3) 480 Cho, B.T. (4) 20, 21; (6ii) 105, 108 Choi, 0.-S. (3) 370 Choi, S . (2) 85, 86 Choi, S.-C. (3) 197; (7) 98, 99 Chong, J.M. (4) 99 Chong-ying, X. (3) 213 Chou, S.S.-P. (4) 242; (6ii) 268 Chou, T. (611) 72, 268 Christl, M. (8) 41 Chuche, H. (3) 262 Chuche, J. (8) 20, 95 Chung, K.N. (4) 210 Ciattini, P.G. (3) 173 Cinquini, M. ( 4 ) 8 Civitarese, G. (2) 141 Clark, J.H. (4) 207 Clark, R.S.J. (2) 58 Coche, L. (1) 6 Coerver, J.M. (611) 99 Cohen, J. (3) 429, 450
Cohen, T. (1) 110; (2) 90; (4) 235; (6ii) 50, 240, 246; (7) 94 Colclough, E. (1) 12; (6ii) 121 Cole, T.E. (2) 53; (4) 1; (6ii) 100, 111 Coll, J. (3) 231 Collet, A. ( 5 ) 83 Collingnon, N. (2) 106 Collington, E.W. (8) 35 Collingwood, S.P. (4) 163 Collins, S . (1) 30; (2) 39; (6ii) 265 Collman, J.P. (6i) 1 Colombo, L. (3) 143, 222 Colonna, S. (61) 34; (6ii) 258; (8) 3 Comasseto, J.V. (1) 65; (6ii) 286 Comins, D.L. (6ii) 27, 195 Concellon, J.M. (4) 109; (6ii) 18, 30 Conn, R.E. (3) 398 Conrad, P. (3) 359; (9) 59 Conrow, R.E. (3) 447 Cooke, D. (3) 80 Cooke, M.P., jun. (3) 1; (6ii) 21, 120, 174; (7) 50 Cooper, C.S. (3) 154; (4) 29 Cooper, D.K. (2) 80; (3) 351 Cooper, J. (8) 92, 93 Cooper, K. (1) 51; (4) 106; (6ii) 79 Cooper, M.S. (3) 78 Cooper, P.J. (6ii) 99 Coppi, L. (4) 85; (6ii) 133; (8) 30 Corbel, B. (2) 64; (7) 48 Corey, E.J. (2) 73, 74; (3) 292, 299; (4) 17, 18, 73, 74; (611) 89, 109; (7) 37, 38, 44; (9) 68 Corey, P.F. (3) 31; (4) 10 Cormons, A. (8) 39 Cornwall, P. (6ii) 34 Correia, C.R. (7) 84 Corriu, R.J.P. (2) 32 Cossio, F.P. (2) 5 ; (4) 141 Cossy, J. (2) 156; (8) 55, 120 Costa, A. ( 5 ) 47 Coetello, G . (611) 79 Costisella, B. (3) 345
53 1
Author Index
Coulter, M.J. (6ii) 59 Court, J.J. (7) 76; (9) 39 Courtois, G. (5) 7 Couty, F. (3) 193 Coveney, D.J. (2) 51; (6i) 89 Cozzi, F. (4) 8 Craig, D. (7) 62 Cramer, C.J. (8) 65 Creary, X. (2) 116; (3) 170 Cremins, P.J. (3) 175 Creswell, M.W. (8) 34 Crich, D. (4) 161 Crimmins, M.T. (6ii) 271; (9) 2, 45, 46 Crisco, L.V.T. (7) 47 Cross, G.A. (61) 62 Crouse, D.J. (2) 126 Crout, D.H.G. (3) 182 Crumrine, D.S. (3) 378 Cruse, W.B. (6ii) 231 Cruz, W.O. (3) 14 Cummerson, D.A. (3) 78 Cunkle, G.T. (3) 9; (611) 25, 26 Curran, D.P. (3) 265; (4) 175; (7) 21; (8) 58; (9) 1, 5 Cushman, M. (61) 54 Cuvigny, T. (1) 111; (6ii) 32 Cyr, D.R. (4) 99 Dabard, R. (1) 5; (3) 87 Dabbagh, G. (2) 184 Dad, M.M. (7) 8 Daimo, C. (3) 416 Daines, R.A. (3) 352; (9) 61-63 Dallaiere, C. (7) 64 Damour, D. (6ii) 144; (8) 97 d'Angelo, J. (3) 216 Dangles, 0. (3) 461 Danheiser, R.L. (2) 62 Daniels, R.G. (6ii) 26 Danishefsky, S J. (8) 103; (9) 48, 49 Danklmaier, H. (3) 428 Dantanarayana, A.P. (9) 47 Dappen, M.S. (8) 65; (9) 50 Daruwala, K.P. (7) 92 Datta, A. (3) 305 Dauben, W.G. (6ii) 212 Dauzonne, D. (3) 388 Daves, G.D., jun. (1) 21 Davies, A.P. (4) 163
.
Davies, H.G. (3) 280 Davies, H.M.L. (3) 188; (7) 47 Davies, S.G. (61) 5, 52, 53 Davis, F.A. (2) 114; (3) 129, 375; (6ii) 258 Davis, R. (2) 125 Davis, S. (4) 148 Davoust, D. (6ii) 8; (7) 77 Dawson, M. J. (3) 280 de Aguiar, A.P. (2) 77 de Bruyn, R.G.M. (3) 401 De Cock, W. (2) 121; (4) 185 Decorte, B. (5) 94 Decristoforo, M. (8) 149 Deeb, T.M. (5) 31; (8) 98 DeFays, I. (3) 80 Degani, I. (2) 59 de Groot, A. (2) 94 Degueil-Castaing, M. (3) 73 Dehmlow, E.V. (3) 234 DeHoff, B.S. (7) 88, 90, 91; (9) 17, 19 Dehombaert, S. (6ii) 65 De Jeso, B. (3) 73 Deker;P.B. (3) 331 De Kimpe, N. (2) 121; (4) 185; (5) 94 De Lange, B. (2) 191; (6ii) 198 Del Buttero, P. (6i) 37 Dell, C.P. (611) 34; (7) 79 Dellerba, C. (5) 70 Dell'Innocenti, M. (3) 333; (6ii) 123, 177 Delmas, M. (3) 100; (4) 244 De Lombaert, S. (3) 288 Demers, J.P. (5) 84 Demillequand, H. (6ii) 261 Demir, A.S. (3) 120, 201; ( 8 ) 121 Demuth, W. (611) 36 Denarie, M. (3) 361 Denis, J.M. (5) 94 Denmark, S.E. (1) 90; (4) 134; (5) 16; (6ii) 226; (8) 65 Denne, I. (6ii) 117; (7) 61 Denzer, H. (7) 32 Depezay, J.-C. (3) 407 Dernoncour, R. (3) 4 DeSchepper, R.E. (3) 296 Descoins, C. (3) 449 De-Shong, P. (3) 196, 311
Deshpande, B.V.H. (3) 312 Deslongchamps, P. (2) 200; (7) 64-66, 70, 85-87 Desobry, V. (61) 47 de Souza-Barboza, J.C. (4) 94 Detty, M.R. (3) 244 Devia, A.H. (4) 199 Devlin, J. (4) 170 Dewan, J.C. (2) 56 Dewinter, A.J. (2) 89; (7) 95 Dewitte, M. (5) 54 Deziel, R. (3) 65 Dhaon, M.K. (3) 409 Dhimane, H. (8) 95 Dhumranguaraporin, S. (6ii) 134 Dhumrongvaraporn, S. (1) 43 Dicke, R. (1) 32; (3) 220; (6ii) 186 Dieschbourg, T.A. (3) 378 Dieter, R.K. (2) 185; (611) 15 Dietz, M. (2) 148 Di Fabio, R. (3) 337 Differding, E. (2) 81 DiFore, K.A. (6ii) 268 Di Furia, F. (2) 17 d'Incan, E. (3) 161; (4) 38 Disanayaka, B.W. (7) 40 Djananbini, D. (3) 111 Djokar, K. (8) 66 Dlubala, A. (3) 107 Dolbier, W.R., jun. (4) 202 Doleshall, G. (5) 87 Dolle, R.E. (3) 50 Dopp, D. (7) 55 Dordor-Hedgecock, I.M. (61) 5, 53 Dorow, R.L. (3) 396; (5) 100 Dotz, K.H. (6i) 85 Doubleday, W. (1) 110 Doutheau, A. (2) 131 Dowd, P. (2) 85, 86; (3) 197; (7) 98, 99 Doyama, K. (3) 310 Doyle, M.P. (4) 199 Drago, R.S. (4) 148 Dreiding, A.S. (2) 61; (7) 7 Dresely, K. (4) 34 Dresely, S . (4) 84 Drewes, S.E. (3) 223 Dreyfus, A.-C. (6i) 35 Driver, J.C.G. (3) 395 Drouillard, S. (3) 73
532 Dryanska, V. (2) 197 Dubouin, J . G . (6ii) 185 Duchene, A. (611) 189 Duckworth, C.A. (5) 96 Diirner, G. (9) 58 Dufaud, V. (1) 88; (6ii) 262 Duggan, M.E. (8) 46, 49 Duhamel, C. (7) 77 Duhamel, L. (6ii) 8, 43 Duhamel, P. (3) 371; (6ii) 43 Duke, C.C. (3) 4 Dulcere, J.P. (3) 317; (8) 10 Dumont, W. (2) 87; (7) 97 Duncan, M.P. (2) 111, 112, 139; (3) 82 Dunkerton, L.V. (4) 223 Dunlap, N.K. (7) 30 du Penhoat, C.H. (1) 111 Dupin, J.-F.E. (1) 101; (3) 47; (6ii) 215 Dupre, B. (9) 50 Dureault, A. (3) 407 Durner, G. (3) 350 Durst, T. (3) 277 Dyrbusch, M. (3) 404, 405 Dyszlewski, A.D. (6ii) 67
General and Synthetic Methods Ellman, J.A. (3) 3, 396; (5) 100 Elmoghayar, M.R.H. (8) 129 Elnagili, M.H. (5) 62 Emebayashi, H. (4) 122 Enders, D. (2) 130; (3) 120, 201, 336; (6ii) 176; (8) 121 Endesfelder, A . (6ii) 115 Endo, T. ( 8 ) 100 Engman, L. (1) 22; (4) 197, 198; (6ii) 279 Epifani, E. (611) 22 Erdik, E. (6ii) 82 Erhardt, P.W. (5) 30 Erickson, G.E. (6ii) 13 Eritja, R. (3) 476 Ermel, J. (3) 269 Essassi, E.M. ( 8 ) 136 Estermann, H. (3) 434 Eswarakrishnan, S (3) 384 Etter, J.B. (3) 339; (4) 58, 59, 61; (7) 2, 17 Evans, D.A. (3) 3 , 396-399; (5) 100, 101
.
Faber, K. (3) 157, 408 Fabiano, E. (3) 422; (5) Easton, R.J.C. (6i) 5 Eaton, P.E. (3) 9; (6ii) 25, 26 Eaton, Q.L. (8) 78 Ebihara, K. (4) 76; (6ii) 89
Ebner, C.B. (3) 204 Ebner, M. (3) 365 Echavarren, A.M. (6ii) 200 Eddy, V.J. (6ii) 169 Edington,.C. (2) 173; (4) 89 Edrik, E. (3) 159 Effenberger, F. (3) 423 Egashira, H. (2) 9; (4) 156 Egert, E. (3) 404, 405, 415; (6ii) 49 Eguchi, S. (3) 191; (8) 133 Eichinger, P.C.H. (6ii) 233 Eida, M. (2) 199; (3) 217 Einhorn, E. (6ii) 12 El Abbassi, M. (8) 136 Eliel, E.L. (3) 30 Elkik, E. ( 4 ) 186 Elliott, J.D. (2) 173; (3) 447; ( 4 ) 89 Elliott, R.L. (9) 5
4 Fabrissin, S. (6ii) 64 Fadel, A. (2) 154; (3) 413 Fallis, A.G. (4) 218; (6ii) 251 Fan, W. (2) 151 Fananas, F.J. (6ii) 264 Fang, J.-M. (3) 340; (5) 63; (6ii) 56 Fanning, J.C. (5) 80 Farid, P. (1) 80; (3) 243 Fataftah, S . A . (6ii) 6 Fatiadi, A . J . (3) 7; (6i) 3 Fauve, A. ( 4 ) 31 Favia, M.R. (5) 73 Favreau, D. (3) 323 Fawcett, J. (6ii) 61 Feenstra, R.W. (3) 420 Fehr, C. (2) 41 Feit, B.-A. (6ii) 37 Feldman, P.L. (9) 28 Felthouse, T.R. (3) 16 Fernandez, J.R. (3) 287; (6ii) 16, 17 Fernandez de la Pradilla, R. (3) 275 Fernandez-Simon, J . L. (4) 109; (6ii) 18, 30 Ferraz, H.M.C. (6ii) 286
Ferre, E. (1) 79 Ferreira, J.T.B. (3) 14 Ferreri, C. (2) 153 Fetizon, M. (2) 135 Fewkes, E.J. (6i) 51; (611) 23 Fiandanese, V. (1) 17; (2) 38 Fiaud, J.C. (6ii) 207 Fiecchi, A . ( 3 ) 153; (4) 28 Fifani, J. ( 8 ) 136 Fillion, H. (1) 82, 88; (3) 385; (6ii) 262 Finch, H. (8) 35 Finet, J.-P. (4) 216, 217; (6ii) 206, 238 Finke, R.G. (6i) 1 Finzel, R.B. (6ii) 128 Firet, J.P. (5) 23 Fischer, G . (3) 350 Fishpaugh, J.R. (6ii) 15 Fitzjohn, S. (9) 35 Flann, C.J. (5) 41, 42; (6ii) 154 Fleck, T. (1) 10 Fleming, A. (7) 33 Fleming, I. (3) 101, 165, 338; (4) 9, 88, 139; (6ii) 136, 143, 156, 170, 175, 196 Flinders, M.A. (3) 18 Flinn, A. (3) 426, 429 Florez, J. (6ii) 4, 17 Florio, S. (6ii) 22 Floss, H.G. (61) 45 Fobare, W.F. (6ii) 144; (8) 116 Fochi, R. (2) 59 Fodor, L. ( 8 ) 71 Folest, J.C. (6ii) 208 Font, J. (3) 280 Forbes, J.E. (9) 69 Forrest, A.K. (1) 60 Forsberg, J.H. (5) 96 Fortgens, H.P. (5) 43; (6ii) 144 Fortt, S.M. (4) 161 Foucaud, A. (3) 207; (6ii) 224 Fox, C.M.J. (3) 326 Fraile, A.G. (4) 162 Francese, C. (4) 48 Franken, S. (3) 120; ( 8 ) 121 Fraser-Reid, B. (2) 163 Frauenrath, H. (8) 15 Frechet, J . M . J . (4) 72; (6ii) 89 Frechou, C. (4) 25 Frejd, T. (7) 73 Frenette, R. (3) 35
533
Author I n d a Frissen, A.E. (8) 53 Fristad, W.E. (2) 83 Froussios, C. (3) 459 Fruscella, W.M. (2) 80; (3) 351 Fry, J.L. (6ii) 13 Fryzuk, M.D. (1) 66 Fuchigami, T. (3) 114; (4) 233; (8) 124 Fuchikami, T. (4) 173, 174; (8) 76 Fuchs, P.L. (1) 41; (6ii) 267 Fuentes, A . (3) 207; (6ii) 233 Fugami, K. (1) 13; (3) 266; (8) 22, 109 Fugita, E. (6ii) 148 Fuji, K. (2) 60; (4) 120; (6ii) 63, 210 Fuji, M. (4) 91, @ ? Fujihara, H. (6ii) 81 Fujii, K . (3) 56, 57 Fujii, N. (3) 470, 477; (6ii) 127 Fujii, S. (3) 17 Fujinami, T. (2) 174; (3) 267 Fujioka, H. (4) 91, 92 Fujioka, T. (6ii) 282 Fujisaki, S. (2) 122 Fujisawa, T. (3) 133, 283; (4) 4; (6ii) 60 Fujise, Y. (9) 4, 20 Fujita, E. (1) 39; (5) 102; (6ii) 210 Fujita, I. (3) 376 Fujita, M. (4) 50; (6ii) 167 Fujiwara, S. (3) 314 Fujiwara, T. (1) 46; (6ii) 192, 196, 244 Fujiwara, Y. (3) 49; (4) 114; (6i) 83 Fukazawa, Y. (9) 20 Fukuda, Y. (8) 118 Fukuhara, T. (4) 176 Fukui, M. (9) 52 Fukumoto, K . (3) 341; (7) 69; (9) 3 Fukuoka, S. (3) 69 Fukusawa, S. (3) 267 Fukuzawa, S. (2) 174 Fullick, G. (3) 442 Funakoshi, S. (3) 470, 477; (611) 127 Funk, R.L. (9) 9 Furata, K. (3) 22 Furstner, A. (1) 8 Furukawa, H. (9) 70 Furukawa, M. (5) 85 Furukawa, N. (6ii) 81
Furuta, K. (7) 57 Furutani, H. (3) 99, 135, 136, 171; (4) 32 Gabard, J. (5) 83 Gadwood, R.C. (2) 89; (7) 95 Gais, H.-J. (3) 252 Galindo, J. (2) 41 Gallagher, P.T. (8) 93 Gallagher, T. (9) 34 Gallardo, M.T. (3) 102 Gallego, M.G. (5) 91 Gander-Coquoz, M. (3) 412 Gannon, S.M. (2) 8 Gao, Y. (8) 1 Garbarino, G. (5) 70 Garcia, J. (4) 80; (5) 103; (6ii) 119 Garcia-Ochoa, S. (3) 203; (6ii) 54 Garner, P. (1) 11; (6ii) 214 Garratt, P.J. (3) 298; (6ii) 33; (8) 128 Gary, J.A. (3) 236 Gaset, A . (3) 100; (4) 244 Gasol, V. (4) 160 Gassman, P.G. (3) 258; (4) 49 Gateau-Olesker, A . (3) 139 Gaudemar, M. (3) 41 Gaudin, J.-M. (6i) 72; (7) 15 Gaul, M.D. (3) 331 Gebhard, I. (9) 33 Geer, S.M. (3) 244 Gennari, C. (3) 143 Gentric, D. (6i) 50 Georgiev, V.St. (3) 315 Gero, S.D. (3) 139 Getman, D.P. (3) 62 Ghiringhelli, D. (4) 30 Ghosez, L. (2) 81; (3) 288; (6ii) 65, 261 Ghosh, A.K. (2) 73 Ghosh, S. (7) 9 Ghosh, S.K. (1) 44; (6ii) 131 Giacomini, D. (3) 435; (8) 144-146 Gianferrara, J. (6ii) 64 Giang, Y.-S. (7) 8 Giannoti, C. (6ii) 238 Giblin, G.M.P. (6ii) 263 Gibson, C.P. (2) 184 Gibson, J.J. (8) 25 Gil, G. (1) 79 Gilbert, L. (3) 307
Gilchrist, T.L. (1) 116 Gill, J.C. (61) 46 Gill, U.S. (61) 29 Gingras, M. ( 4 ) 228, 229 Giordano, C. (3) 61; (4) 191 Giorgianni, P. (8) 7 Giralt, E. (3) 475 Girard, Y. (4) 104; (611) 95 Gladysz, J . A . (3) 452; (6i) 45 Glanzer, B.I. (3) 157, 408 Glase, S.A. (2) 71 Glenneberg, J. (3) 350; (9) 58 Gloer, J.B. (9) 66 Gnonlonfoun, N. (3) 261 Godefroi, E.F. (3) 401 Godfrey, A. (2) 186 Goel, O.P. (5) 88 Gogte, V.N. (3) 95 Gojo, T. (2) 157 Goldback, M. (1) 109 Golding, B.T. (3) 422; (4) 163; (5) 4 Goldstein, S. (1) 75 Golinski, J. (2) 110 Gonschorrek, C. (1) 84; (6ii) 49 Gonzalez, J.M. (1) 100; (4) 205 Goralski, C.T. (6ii) 101 Gordon, J.F. (4) 105 Gore, J . (2) 131; (3) 111, 112, 247 Gore, R. (3) 241 Gosh, A.K. (7) 44 Goto, K. (5) 98 Gotor, V. (8) 113, 137 Goulaouic, P. (2) 135 Gould, T.J. ( 3 ) 236 Goulet, M.T. (4) 117 Goument, B. (3) 371 Govindachari, T.R. (8) 79 Gowriswari, V.V.L. (2) 146, 177; (4) 43, 44 Graillot, Y. (8) 88 Grandolini, G. (8) 70 Grandos, A. (3) 475 Grass, F. (3) 97 Grasso, S. (8) 139 Graule, T. (6ii) 36 Gravatt, G.L. (2) 12 Graves, D.M. (2) 19; (4) 158 Gray, B.D. (3) 386; (6ii) 253, 254 Gray, D. (4) 166 Gray, T.A. (4) 202 Grayson, J.I. (6ii) 232
534 Greck, C. (3) 407 Gree, D. (3) 241 Gree, R . (8) 90 Green, J. (3) 482 Greene, A . E . (1) 95, 96; (4) 214 Greenfield, S. (6i) 39 Greenspoon, N. (2) 44 Gregorcic, A. (4) 168 Grehm, L. (5) 45 Grenouillat, D. (3) 67, 361 Gribble, G.W. (5) 8; (9) 30 Grieco, P . A . (1) 53; (6ii) 144, 197; (8) 116 Grief, D. (8) 54 Griengl, H. (3) 157, 408 Griesbeck, A. (3) 146 Griffith, W.P. (2) 1; (4) 147 Grigg, R. (4) 170; (8) 56, 57 Grimaldi, J. (8) 39 Grivet, C. (61) 47, 48 Groh, B.L. (1) 69; (3) 239; (6ii) 200 Gross, H. (3) 345 Gross, S. (7) 24 Grove, D.D. (6ii) 255; (7) 60 Grundke, G. (3) 433 Gruselle, M. (61) 39, 50 Gruttner, S. (3) 405 Grzegorzek, M. (3) 269 Gus X. (2) 50, 178; (4) 45; (6ii) 41 Gu, X.-P. (3) 198; (4) 212 Guang-jian, L . (3) 213 Guanti, G. (3) 435; (5) 14 Gubbiotti, A. (3) 337 Guerreiro, C. (3) 456 Guerrero, A. (4) 160 Guette, J.A. (8) 88 Guggisberg, A. (3) 353 Guibe, F. (3) 461 Guibe-Jampel, E. (3) 21, 74 Guidi, M. (6ii) 123 Guignant, A . (3) 216 Guilhem, J . (8) 99 Guindon, Y. (4) 104; (6ii) 95 Guinn, D . E . (3) 333 Guitart, J . (3) 231 Gullatti, M. (6ii) 258 Gunderson, K.G. (3) 167; (6ii) 93 Gunnarsson, K. (5) 45 Gunther, H. (3) 27
General and Synthetic Methods GUO, B.4. (1) 110 Guo, J . A . (611) 157 Guo, M. (7) 23 Gupta, A.K. (4) 2; (6ii) 102 Gutman, A . L . (3) 279 Guy, A. (8) 88 bag, B. (6ii) 37 Habbachi, F. (3) 41 Habermas, K . L . (4) 134 Hachgenei, J . W . (6i) 33 Haddad, M. (8) 95 Haelters, J.-P. (2) 64; (7) 48 Hafez, E . A . A . (8) 129 Hagashiya, T. (4) 127 Haggi, D. (3) 309 Hagiwara, H. (2) 79 Hagiwara, T. (4) 209 Hahn, C.S. (2) 2; (4) 149 Hahn, G.H. (4) 5 Hahn, W.R. (2) 69 Hakakeyama, S. (6ii) 219 Hakam, K. (9) 29 Halatsch, W.-R. (3) 465; (5) 46 Halazy, S. (9) 35 Halczenko, W. (6ii) 68 Hall, G. (8) 80 Hall, S.S. (2) 42; (5) 18 Hallberg, A . (1) 21 Haller, K . J . (6i) 49 Halley, F. (6ii) 238 Hallgren, J.E. (6ii) 169 Halpern, J. (3) 453 Hamada, M. (3) 342 Hamamoto, I. (5) 77 Hamamura, K. (6ii) 60 Hamel, N. (6i) 84 Hammer, R.P. (4) 134 Hammond, G.B. (2) 129; (6ii) 217 Hammoud, A . (4) 204 Hamono, S. (5) 27 Hanack, M. (4) 162, 182 Hanafusa, T. (5) 72 Hanamoto, T. (4) 133 Handa, S. (2) 163 Handa, Y. (4) 116 Haner, R . (3) 389 Hanessian, S. (1) 113; (3) 132, 141 Hanna, I. (2) 135 Hannon, F.J. (4) 73, 74; (6ii) 89 Hansen, M.M. (6ii) 87 Hanson, J . R . (4) 105 Hanson, R.M. (8) 1 Hanzawa, Y. (4) 183 Haque, M.S. (3) 375
Hara, H. (2) 182 Hara, S. (1) 10, 16; (6ii) 113 Harada, S. (2) 108; (8) 101 Harada, T. (3) 34; ( 4 ) 24, 127, 128 Harakal, M.E. (6ii) 258 Hardinger, S . A . (6ii) 267 Hardtmann, G.E. (3) 167; (6ii) 93 Harirchian, B. (7) 53 Harlow, R . L . (1) 73 Harmata, M.A. (1) 90 Harpp, D.N. (4) 228, 229 Harrington, P.J. (5) 40; (6ii) 268; (9) 31, 32 Harris, A.R. (2) 43 Harris, B.D. (3) 444 Harris, R . L . N . (3) 206 Harris, S.M. (1) 102 Harrison, C.R. (2) 176 Harrison, L.W. (3) 291; (6ii) 92 Hartman, G.D. (6ii) 68 Hartman, W. (8) 50 Haruta, J. (3) 296 Harwood, L.M. (4) 219; (8) 16 Hase, T . A . (4) 12 Hashimoto, C. (3) 425 Hashimoto, H. (3) 333; (8) 29 Hashimoto, S. (3) 366; (7) 54 Hashimoto, T. (6ii) 249 Hashimoto, Y. (3) 127 Hassner, A . (5) 104 Hata, Y. (3) 438 Hatada, K. (8) 141 Hatakeyama, S. (3) 75, 352 Hatanaka, Y. (1) 33; (6ii) 152 Hateda, K. (6ii) 257 Hatsuya, S. (3) 230; (6ii) 199 Hattori, K. (3) 58 Haufe, G. (4) 167 Hayakawa, H. ( 4 ) 16 Hayakawa, K. (9) 26 Hayama, T. (4) 133 Hayami, J. (3) 366 Hayasaka, T. (4) 76; (6ii) 89 Hayashi, H. (4) 122 Hayashi, M. (1) 98; (2) 99, 190; (6ii) 138 Hayashi, S. ( 3 ) 22; (7) 57; (8) 68, 72 Hayashi, T. (2) 97; ( 3 ) 6, 172, 225, 233, 400;
535
Author Index (61) 15, 24, 44, 68; ( 6 i i ) 126, 130; (8) 61 Hayashi, Y. (2) 137; (3) 179, 235, 470; ( 6 i ) 40; (7) 56 Haynes, R.K. (2) 75; (3) 274; ( 6 i i ) 228 Hazen, G.G. (4) 47 H e , X.-C. (3) 30 Heaney, H. ( 3 ) 78 Heathcock, C.H. (4) 231; ( 6 i i ) 87 Hebel, D. (4) 181 Heckendorn, D.K. (3) 272 Heckendorn, R. (8) 135 Hegedus, L.S. (5) 40; ( 6 i ) 1; (9) 31, 32 Heidt, P.C. (7) 3 Heilmann, S.M. (3) 418 H e i m , N. (3) 350; (9) 58 Heimgartner, H. ( 3 ) 373 Heinen, H. (8) 147 Heintz, R.M. (3) 62 Helhnerle, H. (3) 252 Hendi, M.S. (3) 379 Headi, S.B. (3) 379 Hendrie, S.K. (5) 17 Henegar, K . E . (3) 180 Henin, F. (3) 229; ( 8 ) 55 Henklein, P. (3) 465; (5) 46 Henrot, S. (3) 156, 163 Hensley, V. (3) 80, 249 Hekald, C.L. (9) 67 Hernandez, R. ( 6 i i ) 276 Herndon, J.W. (7) 22 Hernot, D. (2) 64; (7) 4 8 Herradon, B. (3) 155, 203 Herrington, P.M. (7) 100; ( 8 ) 14 Herimann, R . (2) 124 Herve, Y. (3) 431; (8) 99 Herzog, B. (3) 20 Hesse, M. (2) 70, 91; ( 3 ) 202, 350, 353; (7) 41 Hevesi, L. ( 6 i i ) 273 Heyne, H.-U. (3) 465; (5) 46 Hiemstra, H. (1) 92; (5) 43; ( 6 i i ) 144 Higaki, M. ( 6 i i ) 58 Higashi, H. (3) 150; (4) 26 Higashiyama, K. (4) 67 Higgins, R.H. (8) 78 H i i r o , T. (2) 127; ( 6 i i ) 14, 283 H i l l e r y , P. (7) 78 H i l t y , T.K. (3) 144 Hinkle, J.S. (8) 148 Hinrichs, R. (3) 402 Hirai, K. (8) 114
Hirai, Y. (5) 38; ( 6 i ) 16 Hirama, M. (8) 119 Hirano, M. (2) 9; (4) 156 Hirao, A. ( 6 i i ) 109 Hirashima, T. (5) 66 Hirata, Y. (2) 26 Hiratake, J. (3) 25 Hiratsuka, H. (4) 97 Hirayama, H. (8) 33 H i r o i , K. ( 2 ) 63; ( 6 i i ) 260 Hirokawa, S. (3) 327 H i r o t s u , K. (8) 44 Hirst, G.C. ( 6 i i ) 266; (7) 59 Hissman, E. (3) 105 Hitomi, T. ( 1 ) 59 Hiyama, T. (1) 33; (3) 316; (4) 50; ( 6 i i ) 152, 167 Hiyoshi, K . ( 6 i ) 40 Hoashi, K . (1) 63; ( 6 i i ) 129, 145; (8) 68, 72 Hobbs, C.J. (8) 128 Hoberg, H. ( 7 ) 24 Hodges, J.C. (3) 479, 480 Hodges, S.L. (2) 181; ( 6 i i ) 78 Hoekstra, W. (1) 103; (2) 96 Hoffman, R.V. (5) 97 Hoffmann, R.W. (4) 84; ( 6 i i ) 115-117; (7) 61 Hogberg, T. (3) 365 Hoh, T. ( 6 i i ) 60 Hojo, M. (3) 259, 260 Holdgriin, X. (7) 32 Holland, H.L. ( 4 ) 113 H o l l e r , T.P. (3) 403 H o l l i s , W.G., jun. ( 6 i i ) 271; (9) 45, 46 Holton, R.A. (2) 126; (9) 12 Holzapfel, C.W. (9) 67 Honda, Y. (3) 59 Hondo, K. (2) 36; (3) 90 Hong, B.-C. (3) 340; ( 6 i i ) 56 Hong, Y. (2) 39 Hongxun, D. (4) 118 Honig, H. (3) 428 HOOZ, J. ( 2 ) 167; ( 6 i i ) 103 Hopkins, M.H. (7) 100; ( 8 ) 13, 1 4 Hopkins, P.B. (3) 403 Hoppe, D. (1) 84; ( 6 i i ) 49 Hori, Y. (3) 72; (8) 62 Horiguchi, Y. (1) 85; (2) 147; ( 6 i i ) 4 8 Horike, H. (2) 171
Horne, K . (2) 186 Horvath, R.F. ( 6 i i ) 151 Hoshi, M. (1) 64 Hoshino, M. (3) 464; (4) 115 Hosoda, A. (1) 112 Hosokawa, T. (3) 178 Hosomi, A. (1) 63; (2) 40; ( 6 i i ) 129, 140, 145; (8) 68, 72 Hosoya, K. (3) 308; ( 6 i i ) 60 Hou, Z. (4) 114 Houk, K . N . (8) 58 House, S. ( 6 i i ) 61 Hoye, T.R. (3) 138 Hrytsak, M. (3) 277 Hse'ine, A. (1) 8 2 , 88; (3) 385; ( 6 i i ) 262 Hsiao, C.-N. (3) 145 Hu, N . X . (611) 285, 287 Hua, D. (3) 80 H u a , D.H. (2) 193; ( 6 i i ) 59, 227 Huang, X. (3) 119; ( 6 i i ) 284 Huang, Y. (1) 94; ( 8 ) 38 Huang, Y.Z. (3) 382; ( 6 i i ) 235 Hudlicky, T. (3) 88; (5) 36; (7) 33 Huffman, J.C. ( 8 ) 75 Hugel, H. (4) 34 Huh, K.T. (3) 115 Huizinga, W.B. (2) 68 H u l l , C. (4) 53 Hung, C.W. (3) 122 (3) 110; ( 6 i ) Hung, M.-H. 41 Hung, S . 4 . ( 6 i i ) 268 Hungate, R. (9) 4 8 Hunig, S. ( 6 i i ) 55 Hunter, J.E. (3) 383; ( 6 i i ) 24 Hunter, R. (1) 25; (4) 238; (611) 252 Hurzeler, M. (3) 177 Hussain, N. (9) 6 Husson, H.P. (5) 11 Hutchins, R.O. (5) 13 Hutchinson, J.H. (8) 12; (9) 15 Huth, A. (3) 51 H u t t , J. (4) 25 Hwang, C . 4 . (8) 46, 49 Hwang, K.-J. (1) 28; ( 6 i i ) 62 Hwu, J.R. (2) 152 Hyuga, S. (1) 16; (611) 113
536 Ibata, T. (5) 21 Ibe, M. (2) 148 Ibrahim, N.S. (8) 42 Ibuka, T. (3) 94, 168, 227 Ichihara, J. (5) 72 Ichikawa, K. (4) 203 Ichinose, Y. (1) 25, 26; (4) 240; (6ii) 180 Idemoto, T. (2) 55 Igarashi, S . (6ii) 264 Iglesias, M.J. (8) 137 Ihara, M. (3) 341; (7) 69; (9) 3 Ihle, N.C. (61) 74 Iida, H. (5) 12 Iida, M. (3) 267 Iitaka, Y. (3) 266; (8) 11 Iizuka, Y. (3) 34 Ikariya, T. (3) 17; (61) 14 Ike, K. (3) 369 Ikeda, I. (2) 50; (3) 198; (4) 212 Ikeda, M. (4) 234; (6ii) 245, 252; (8) 101 Ikeda, N. (3) 228 Ikeda, Y. (3) 228 Ikemoto, Y. (5) 28; (6ii) 205 Ikemura, 0 . (3) 470 Ikenaga, K. (1) 15; (6ii) 153 Ikota, N. (7) 54 Ila, H. (3) 305 Imada, Y. (61) 16 Imai, K. (2) 144 Imai, N. (8) 85, 86 Imai, Y. (2) 155 Imamoto, T. (3) 453; (4) 110 Imao, S. (5) 48 Imbeaux-Oudotte, M. (4) 186 Imi, K. (2) 144 Imwinkelried, R. (4) 68, 90 Inagaki, I. (5) 6 Inagaki, M. (3) 25 Inamoto, N. (611) 2, 225 Inanaga, J. (1) 7, 45, 78; (2) 52; (3) 131, 164, 286; (4) 41, 42, 116; (6i) 17, 59; (6ii) 196 Inazawa, K. (4) 183 Ingrosso, G. (611) 22 Inokuchi, T. (2) 26, 149, 171 Inomata, K. (1) 31; (6ii)
264
General and Synthetic Methods Inoue, H. (4) 77; (6ii) 89 Inoue, J. (3) 55 Inoue, K. (3) 148 Inoue, M. (6ii) 192 Inoue, S . (4) 125; (6i) 12 Inoue, Y. (8) 29 Inouye, M ( 5 ) 61; (6ii) 280 Inubushi, A. (1) 98 Iqbal, J. (3) 71; (4) 178 Irie. M. 8) 101 Ishibashi, H. (4) 234; (6ii) 245, 252; (8) 101 Ishige, 0. (2) 46 Ishihara, H. (3) 109 Ishihara, K. (4) 22 Ishihara, T. (1) 36, 55; (2) 164, 165; (3) 215; (4) 189, 190, 200 Ishii, T. (1) 59; (6ii) 225 Ishii, Y. (2) 16; (3) 17, 248; (4) 152, 154; (6i) 14 Ishikawa, J. (8) 29 Ishikawa, M. (3) 185; (5) 90; (6i) 17; (6ii) 162 Ishikawa, N. (3) 103, 160; (6ii) 84 Ishikawa, T. (3) 66 Ishiyama, T. (1) 116; (4) 243; (6ii) 114 Ishizuka, T. (3) 393 Islam, I. (3) 357 Isoe, S. (1) 38; (3) 81, 314; (6ii) 175; (8) 44 Isogami, Y. (5) 21 Ito, H. (2) 199; ( 3 ) 217; (4) 37, 203; (6ii) 236 Ito, K. (3) 77, 246; (4) 150; (61) 60; (6ii) 109 Ito, S. (4) 123; (8) 119; (9) 4 Ito, Y. (3) 6 , 162, 233, 343, 400; (4) 6, 57, 75; (5) 90; (61) 15, 44, 68; (6ii) 89, 130, 150, 162, 169; (8) 61 Itoh, F. (3) 436; (5) 15 Itoh, K. (2) 20 Itoh, M. (2) 84, 103; (3) 322; (6ii) 96 Itoh, S. (3) 212 Itoh, Y. (611) 270 Itoua, G.B. (8) 111 Itsuno, S. (4) 72; (6ii) 89, 109 Ivandwicz, B.J. (5) 32 Ivanov, C. (2) 197 Iwa-ake, N . (4) 127
Iwabuchi, Y. (9) 41 Iwai, S. (3) 355 Iwakuma, T. (8) 119 Iwamoto, H. (4) 39 Iwamoto, K. (8) 19 Iwamura, H. (3) 66; (6ii) 247 Iwamura, M. (3) 66 Iwasa, A. (3) 12 Iwasaki, H. (3) 344 Iwasawa, H. ( 3 ) 445; (8) 106, 115 Iwasawa, N. (2) 58, 175; (3) 143 Iwata, T. (6ii) 130 Iwatsubo, H. (3) 103 Izumi, Y. (2) 172; (3) 124, 142; (6i) 67 Jacob, P.W. (7) 11 Jacobi, P.A. (3) 318 Jacobs, P.B. (9) 5 Jacobson, A.E. (7) 78 Jacobson, R.A. (6ii) 91 Jafer, A.W. (3) 46 Jaggi, D. (3) 281; (4) 62, 63 Jakel, E. (1) 109 Jakob, H. (3) 350 James, A.P. (3) 121, 455 Janakiraman, M.N. (6ii) 91 Janssens, A . (9) 7 Jaouen, G. (6i) 39, 50 Jaszay, Z.M. (5) 99 Jawalkar, D.G. (4) 19 Jaynes, B.H. (9) 14 Jean, M. (7) 6; (9) 10 Jean, T. (2) 123 Jebaratnam, D.J. (6ii) 4; (7) 46 Jedlinski, Z. (3) 269 Jeffery, T. (1) 107; (3) 242 Jefford, C.W. (3) 280, 281, 284, 309; (4) 62, 63 Jeffs, P.W. (3) 386 Jeganathan, A . (3) 39; (6ii) 39 Jenkins, C.L.D. (3) 206 Jenkins, P.R. (1) 57; (2) 76; (6ii) 61, 173; (7) 74 Jenny, C. (3) 373 Jensen, K.M. (3) 418 Jenson, T.M. (7) 88, 90, 91; (9) 17, 19 Jew, S. (2) 198; ( 3 ) 273, 354 Jin, Y.-Y. (3) 118
Author Index Jintoku, T. (3) 49; (6i) 83 Joh, T. (3) 310 Johnson, C.R. (1) 9; (2) 188; (3) 453; (6ii) 158, 164, 193 Johnson, P.D. (9) 33 Johnson, W.S. (2) 173; (3) 447; (4) 89 Johnston, B.H. (9) 65 Johnston, M.I. (4) 111 Jones, C.W. (4) 207 Jones, J. (2) 77 Jones, J.B. (3) 19 Jones, J.H. (3) 479 Jones, K. (9) 23 Jones, R.C.F. (6ii) 35 Jones, R.J. (3) 363 Jordan, A.D., jun. (1) 62 Jorgensen, K.A. (5) 76 Joshi, R.R. (3) 53 Joucla, M. (8) 74, 87 Jouin, P. (3) 443, 457 Joullie, M.M. (3) 444 Jousseaume, B. (6ii) 194 Juaristi, E. (3) 411 Julia, M. (1) 111; (6ii) 32 Jullen, L. (6ii) 32 Jun, T.X. (6ii) 249 Jun, Y.M. (3) 383 Junchai, B. (4) 118 Jung, K. (2) 14 Jung, K.-Y. (3) 181; (4) 155 Jung, M.E. (6ii) 255; (7) 60 Junjhappa, H. (3) 305 Jus, Y.M. (6ii) 24 Just, G. (3) 76, 360 Kaba, T. (4) 78; (6ii) 89 Kabalka, G.M. (4) 166 Kaczmarek, C.S.R. (3) 318 Kadokura, M. (1) 68; (2) 101; (3) 232 Kadow, J.F. (611) 193 Kagan, H.B. (5) 65; (6ii) 258 Kaji, A. (3) 214, 295, 308; (5) 77, 78; (6ii) 60, 249, 274 Kajigaeshi, S. (2) 122 Kakajo, E. (4) 57 Kakimoto, M. (2) 155 Kakinami, T. (2) 122 Kakushima, M. (3) 35 Kallitsis, J. (3) 458 Kallmerten, J. (3) 236 Kamal, A. (8) 67 Kamano, Y. (9) 67
537
Kamazawa, Y. (5) 85 Kambe, N. (1) 24; (2) 127; (4) 222; (6ii) 14, 275, 281-283 Kametani, T. (3) 341; (7) 69; (8) 140; (9) 3 Kameyama, M. (4) 171 Kamigata, N. (4) 171, 196 Kamimura, A. (5) 77, 78; (6ii) 274 Kamimura, J. (3) 98 Kaminski, Z.J. (3) 362 Kanabe, N. (5) 6 Kanayama, S . (3) 178 Kanda, Y. (9) 20 Kandeel, K.A. (3) 174 Kandil, A.A. (6ii) 220 Kandolf, H. (3) 428 Kaneko, T. (6ii) 257; (8) 141 Kaneko, Y. (6ii) 244 Kanemasa, S . (3) 416; (8) 82-84 Kanematsu, K. (9) 26 Kanemoto, S . (1) 52, 74; (2) 118; (4) 184, 188; (6ii) 202 Kang, J. (5) 24 Kano, S. (3) 445; (8) 106, 115 Kanoh, M. (2) 194; (6ii) 88 Kaplan, B.E. (3) 476 Karkour, B. (3) 21 Karras, M. (2) 15; (4) 153 Kartner, A. (5) 52 Kasahara, I. (4) 125; (6i) 12 Kasai, M. (4) 123 Kasar, T.G. (4) 19 Kashimura, S. (2) 46, 47 Kashimura, T. (3) 49 Kataoka, Y. (1) 34; (4) 239; (6ii) 152, 252 Katayama, A. (2) 55 Katayama, T. (3) 293 Kato, H. (6i) 21 Kato, T. (5) 67; (6ii) 138, 229 Kato, Y. (3) 137 Katocs, A. (8) 71 Katogi, M. (7) 69 Katritzky, A.R. (2) 45, 115, 151; (4) 221; (611) 31, 52, 53, 166 Katsifis, A. (6ii) 228 Katsuki, T. (1) 58; (3) 44, 69, 240, 376; (4) 107, 133 Katsumura, S. (3) 314 Kaulen, J. (4) 131
Kavaguchi, T. (6ii) 280 Kawabata, A. (4) 67 Kawaguchi, A. (9) 3 Kawaguchi, T. (5) 61 Kawai, K. (3) 364; (9) 70 Kawai, M. (3) 124 Kawai, N. (3) 142; (9) 70 Kawai, T. (5) 78; (6ii) 274 Kawakami, H. (3) 327 Kawakatsu, A. (4) 203 Kawamoto, K. (3) 218 Kawamoto, T. (2) 98; (3) 224; (611) 126 Kawamura, K. (3) 286 Kawamura, N. (1) 59; (3) 6; (6i) 15 Kawanami, Y. (3) 376 Kawanisi, M. (6ii) 191 Kawano, H. (3) 17; (6i) 14 Kawano, M. (3) 44 Kawano, Y. (3) 294 Kawashima, T. (6ii) 225 Kawauchi, N. (3) 333 Kawazoe, K. (3) 99 Kawazoe, T. (2) 142 Kawazoe, Y. (4) 132 Kayama, M. (3) 264 Kayser, M.M. (3) 323 Ke, Y.Y. (3) 436; (5) 15 Keay, B.A. (7) 67 Keck, G.E. (4) 56; (6ii) 199 Keefer, L.K. (5) 80 Keenan, R.M. (7) 63; (9) 11 Kees, K.L. (9) 22 Keese, R. (3) 20 Keese, W. (3) 433 Keinan, E. (1) 3; (2) 34, 44; (3) 85; (6ii) 159 Kellogg, R.M. (4) 220; (6i) 62 Kellogg, R.P. (3) 154; (4) 29 Kelly, R.C. (9) 33 Kennedy, R.M. (2) 126; (9) 12 Kenny, C. (4) 60; (7) 18 Kerr, R.G. (6ii) 269 Kerr, W.J. (6i) 77 Kessler, K. (3) 350 Khamliche, L. (2) 136 Khamsi, J. (4) 217; ( 5 ) 23; (611) 206, 239 Khan, S.H. (4) 113 Khoukhi, N. (3) 104 Kibayashi, C. (5) 12 Kido, F. (3) 318 Kiely, D.E. (2) 3: (4) 145
538 K i j i , J. (3) 12; (4) 11
Kikukawa, K. (1) 15; (2) 55; ( 6 i i ) 153 Kikukawa, T. (3) 34 Killpack, M.O. ( 6 i i ) 27 K i m , B. (4) 80 K i m , B.H. (8) 58; ( 9 ) 5 K i m , B.M. ( 6 i i ) 119 K i m , H.-B. (9) 12 K i m , H.-0. (3) 370 K i m , H . J . (3) 374 K i m , J.D. (2) 30 K i m , J.E. (2) 28-31 K i m , K. ( 2 ) 160 K i m , K.-W. ( 6 i i ) 98 K i m , K.E. (4) 13; ( 6 i i ) 107 K i m , K.S. (2) 2; (4) 149; (5) 24 K i m , M.W. (3) 276 K i m , S. (4) 135, 210, 224; ( 6 i i ) 239 K i m , S.J. (2) 2; (4) 149 K i m , S.S. (4) 224; ( 6 i i ) 239 K i m , Y.H. (2) 159, 160; (3) 374 K i m , Y . S . (2) 31 Kimura, M. ( 6 i i ) 247 Kindon, N.D. (3) 101; ( 4 ) 88; ( 6 i i ) 143, 170 Kingsley, S.A. ( 5 ) 96 Kinoshita, H. (1) 31; ( 6 i i ) 264 Kinugawa, N. (4) 40; ( 6 i ) 58 Kira, M. (4) 54; (5) 49; ( 6 i i ) 139, 168 Kirihara, H. (4) 95 Kirshenbaum, K.S. (4) 98 Kirss, R.U. ( 6 i ) 49 Kiryu, Y . (2) 60; (4) 120; ( 6 i i ) 63 Kishi, Y. (1) 71; (9) 64 Kishimura, S. (3) 195 Kishino, M. (3) 464 Kishore, V. (9) 66 Kita, Y. (3) 296, 436; (5) 15; ( 6 i i ) 256 Kitagawa, T. (8) 138 Kitajima, Y. (3) 306 Kitamura, M. (3) 5 , 147; (4) 126; (61) 11, 13, 26 Kitamura, T. (1) 105 Kitano, Y. ( 6 i ) 1 9 , 20 Kitaoka, M. (1) 29; (6ii) 259 Kitazume, T. (3) 103, 151, 152; (4) 124 Kiyooka, S. (2) 145; ( 6 i i ) 181
General and Synthetic Methods Klaubert, D.H. (5) 84 Klaunzer, N. ( 6 i i ) 55 Klaver, W.J. (1) 92 Klein, A. ( 6 i ) 34, 35 K l e v i t , R.E. (3) 403 Klier, K. ( 5 ) 58 K l i m a s , M.T. ( 6 i ) 38 Kline, D.N. (2) 100; (3) 183 Klumpp, G.W. ( 6 i i ) 155; (7) 19; (8) 48 Klunder, A . J . H . (2) 68 Klunder, J . M . (8) 1 Klusener, P . A . A . ( 6 i i ) 38 Knapp, S. (8) 59 Knight, D.J. ( 6 i i ) 264 Knight, D.W. ( 6 i i ) 34; ( 7 ) 79; ( 8 ) 92, 9 3 Knouzi, N. (5) 34; ( 8 ) 9 1 Knudsen, M.J. ( 6 i ) 79 KO, S.Y. (8) 1 Kobayashi, K. (3) 322; ( 6 i i ) 229 Kobayashi, M. (2) 67; (4) 54; ( 6 i ) 45; ( 6 i i ) 139, 277 Kobayashi, S. (2) 170; (3) 106, 126, 200 R'obayashi, T. (1) 31; (2) 157; (3) 32, 151, 152, 172; ( 6 i i ) 266 Kobayashi, Y. ( 1 ) 112; ( 3 ) 266; (4) 183; ( 6 i ) 1 9 , 20; ( 8 ) 11 Kocienski, P. (1) 51, 86; (4) 106; ( 6 i i ) 79; (9) 43, 44 Kodama, M. (9) 4 Koepp, E. (3) 38 Koga, K. ( 3 ) 189; (4) 7, 65, 66; ( 6 i ) 25; ( 6 i i ) 76 Koga, N. (7) 54 Kogen, H . (3) 448 Kohda, K. (4) 132 Kohra, S. (2) 40; ( 6 i i ) 140, 145; (8) 68, 72 Koie, K. ( 6 i i ) 247 Koizumi, T. (4) 180, 233; (7) 56 Kojima, E. (3) 283 Kokx, A.J.P.M. (3) 401 Kolasa, T. (3) 421 Kolovos, M. (3) 459 Komatsu, N. (2) 199; (3) 217 Komeshima, N. (7) 54 Kometani, S . (3) 1 2 Komiya, S . (4) 14 Kon, A. (4) 183 Kondo, H. (4) 91 Kondo, Y. (4) 132
Konings, J.J.H.G. (3) 401 Konishi, H. (3) 12; ( 4 ) 11 Kono, K. (2) 55 Konomoto, K. (4) 230 Konstantinovic , S. ( 3 ) 255; ( 6 i i ) 271 Konya, N. ( 3 ) 214 Kopka, I.E. ( 6 i i ) 6 Koreeda, M. ( 4 ) 55; ( 6 i i ) 190 Korhummel, C. (4) 182 Koruboshi, M. (4) 189, 190 Kosala, T. (3) 432 Koser, G.F. (5) 9 Kosima, S. ( 6 i i ) 191 Kosugi, H. ( 1 ) 29; ( 6 i i ) 259 Kosugi, M. ( 2 ) 108, 142; ( 6 i i ) 201 Kotake, H. ( 1 ) 31; ( 6 i i ) 264 Kotian, K.P. ( 4 ) 211 Koua, K.O. ( 3 ) 100 Kover, W.B. (2) 77 Kowalczuk, M. (3) 269 Koyama, K. (3) 419; (8) 33 Koyama, Y . ( 3 ) 66 Koziara, A. (5) 3 Kozikowski, A.P. (4) 137 Kozima, S. (1) 59 Koziski, K.A. (4) 112; ( 6 i i ) 29 K r a f f t , M.E. (9) 1 2 , 24 Krantz, A. (1) 91; (3) 441; (4) 206 Krapcho, T.R. (3) 80 Krause, J . G . (2) 8 Krause, N. (4) 35 Krepski, L.R. ( 3 ) 418 Kresze, G. (5) 58 K r i e f , A. (2) 87; ( 6 i i ) 20, 272; (7) 27, 96, 97 Krieger, M. ( 3 ) 149 Krishna, M.V. (1) 30, 89; ( 6 i i ) 265 K r o l l s , U. (5) 88 Kruse, L.I. (3) 50 Ku, Y.-Y. ( 6 i ) 29 Kudo, F. (3) 49 Kuehne, M.E. (9) 27 Kuhnle, W. (3) 404 Kukkola, P. J. (8) 59 Kulik, W. ( 6 i i ) 38 Kulkarni, Y.S. (3) 48 Kumada, M. ( 4 ) 194; (611) 153 Kumagawa, T. (2) 104 Kumar, A.K. (3) 70 Kume, T. (3) 344
Author Index Kumobayashi, H. (3) 17, 147; (4) 125, 126; (61) 11, 12, 14 Kundig, E.P. (6i) 47, 48 Kunieda, T. (3) 393 Kunishima, M. (611) 210 Kuntz, H. (3) 406 Kunz, H. (3) 26 KUO, S.-C. (9) 1 Kurcok, P. (3) 269 Kuroboshi, M. (1) 55; (2) 164, 165; (3) 215; (4) 200 Kuroda, C. (3) 303; (6ii) 142 Kuroda, H. (2) 171; (3) 470 Kuroda, S. (1) 58; (3) 240; (4) 107 Kurokawa, H. (3) 17 Kurosawa, K. (3) 113, 116 Kurth, M.J. (3) 257; (4) 103 Kurth, Y. (3) 350 Kurusu, Y. (1) 47; (3) 186; (4) 40; (61) 58 Kusakabe, M. (61) 21 Kusume, K. (3) 55 Kuwajima, I. (1) 85; (2) 147; (3) 83, 84, 93; (6ii) 48, 77, 85 Kuwata, F. (2) 46, 47; (3) 195 Kuzmierkiewicz, W. (2) 45; (4) 221; (611) 53 Kvita, V. (8) 125 Kwang, T.W. (8) 150 Kwass, J.A. (4) 111 Kwiatkowski, S. (2) 180 Kwon, S.S. (2) 33 Kyler, K.S. ( 8 ) 130 Labbe, G. (5) 106 Laborde, E. (3) 275; (7) 39 Laboureur, J.L. (2) 87; (6ii) 272; (7) 96, 97 Lacher, B. (3) 139; (4) 208 Laduranty, J. ( 5 ) 59 Lake, R.J. (9) 66 Lalonde, J.J. (2) 196; (3) 92 LaMaire, S.J. (1) 40 Lambert, J.B. (6ii) 128 Lamothe, S. (7) 87 Landis, C.R. (3) 453 Lange, A.B. (3) 312 Langer, K. (4) 227 Langley, D.R. (5) 93 Lanneau, G.F. (2) 32
539 Lanz, J.W. (611) 116 Lao, J.4. (3) 80 Lapitajs, G. (61) 34 Larcheveque, M. (3) 130, 156, 163 Lardicci, L. (1) 97; (3) 333; (611) 123 Larock, R.C. (3) 291; (611) 91, 92; (8) 108 Laronze, J.-Y. (8) 111 Larpent, C. (1) 5; (3) 87 Larsen, S.D. (3) 349 Laugraud, S. (3) 216 Laurent, A. (4) 167; (8) 102 Laurent, E. (2) 120 Lautens, M. (3) 110 Lavallee, J. (2) 200 Lavelle, J.-F. (7) 70 Lavielle, S. (3) 461 Lavy, A.B. (6ii) 96 L a w , K.-W. (1) 30; (6ii) 265 Lawrence, G.C. (3) 280 Lazaridis, C.L. (4) 187 Lazaridis, N.V. (2) 119 Lazbin, I.M. (5) 9 Laznoff, C.C. (3) 469 Leaver, J. (3) 280 Lebibi, J. (6i) 36 Le Bihan, J.-Y. (61) 50 Leblanc, C. (8) 55 Lebreton, J. (7) 88, 89, 91; (9) 18, 19 Leckta, T.C. (7) 11 Lecolier, S. (3) 457 Lecouve, J.P. (6ii) 43 Lee, C.C. (3) 187 Lee, E. (8) 150 Lee, F.K.C. (9) 56 Lee, H.K. (2) 159 Lee, H.L. (9) 73 Lee, H.Y. (7) 63; (9) 11 Lee, J.C. (2) 28 Lee, K.W. (2) 28, 29 Lee, S.J. (6ii) 268 Lee, T.D. (3) 476 Lee, W.C. (611) 72 Lee, Y. (3) 468 Lefker, B.A. (2) 82 Le Gall, T. (8) 90 Legesse, K. (3) 476 Le Goffic, F. (3) 391 Lehmann, J. (3) 251 Lemaire, M. (8) 88 Lenck, D.J. (6ii) 92 Leon, E.I. (6ii) 276 Leonard, J. (5) 17; (9) 6 Leong, W. (1) 104 Le Petit, J. (1) 79 Leport, L. ( 3 ) 161; (4) 38
Lerchen, H.-G. (3) 26 Leu, L. (2) 152 Leuck, D.J. (3) 291 Lever, J.G. (6ii) 271; ( 9 ) 46 Levesque, G. (3) 107 Lewis, N.J. (3) 472 Ley, S.V. (2) 1; (3) 184, 326, 370; (4) 147; (9) 72 Leyrel, P. (5) 86 Lhommet, G. (5) 92; (8) 95 Li, C.-S. (61) 90; (8) 104 Li, J.S. (8) 31 Li, K.-M. (9) 66 Li, Q. (2) 151 Li, W.S. (9) 61 Liao, L.-F. (6ii) 56 Licandro, E. (61) 37 Liesen, G.P. (3) 11 Lietze, L.-F. (8) 37 Liguori, A. (5) 64 Lin, H.-S. (7) 87 Lin, J.T. (4) 124 Lin, K.C. (7) 34 Lin, P. (611) 264 Lin, R. (5) 22 Lin, Y. (2) 18; (61) 23 Linder, S.M. (2) 107 Linderman, R.J. (2) 19, 186; (4) 158 Linstrumelle, G. (4) 204 Liotta, D. (1) 103; (2) 96 Liou, S.-Y. (4) 242; (611) 268 Lipshutz, B.H. (61) 2 Liu, G.K. ( 5 ) 96 Liu, L. (3) 145 Livinghouse, T. (8) 96 Lloyd-Williams, P. (7) 58 Lobo, A.M. (9) 25 Lodi, L. (3) 302; (4) 87 Logusch, E.W. (1) 28; (6ii) 62 Loh, J. (2) 71 Lohray, B.B. (2) 130; (611) 176 Loizou, G. (3) 223 Loncharich, R.J. (8) 58 Lonsky, R. (3) 402 Loomis, G. (1) 111 Lopez, L. (8) 45 Lopez, M.C. (2) 5; (4) 141 Lorenz, K.T. (7) 53 LOU, J.-D. (2) 22; (4) 142, 143 Lou, w. (2) 22 Lu, X. (1) 48, 49; (2)
540
General and Synthetic Methods
Maiorana, S. (61) 37 Makita, A. (3) 348 Makosza, M. (2) 57 Malanga, C. (3) 333; (6ii) 123 Maleczka, R.E., jun. (9) 66 Malfroot , R. (3) 361 Malhotra, R. (1) 99 Mallick, I.M. (2) 89; (7) 95 Malone, T.C. (5) 41; (6ii) 154 Malpass, J.R. (8) 127 Ma, D. (2) 18; (61) 23 Mamos, P. (3) 427, 458, McCann, S.F. (6ii) 154 474 McCarthy, J.R. (5) 29; (6ii) 163; (8) 75 Manabae, K. (61) 26 Manabe, H. (5) 61; (611) McCauley, J.P. (6ii) 258 McCloskey, P.J. (7) 76; 280 Mandal, A.K. (4) 19 (9) 39 McClure, C.K. (2) 168 Manfredi, A. (6i) 34; McCombie, S.W. (8) 27, 60 (611) 258; (8) 3 McCowan, J.R. (6ii) 163 Manimaran, T. (5) 107 McDaniel, K.F. (9) 31 Mann, A. (1) 67; (611) McDougal, P.G. (1) 61; 190 Mano, T. (8) 5 (6ii) 44 McFadden, H.G. (3) 206 Mantlo, N.B. (611) 195 McGarvey, D.J. (7) 10, 11 Manzocchi, A. (3) 153; Machida, H. (3) 2 (4) 28 Mack, R.A. (3) 315 Mar, E.K. (4) 99 McKean, D.R. (6ii) 200 Marcelis, A.T.M. ( 8 ) 53 McKie, J.A. (2) 193; Marchese, G. (1) 17; (2) (6ii) 227 38 McKillop, A. (2) 4, 158; Marchioro, G. (3) 9; (3) 253; (4) 151 (611) 25 McMillan, C.M. (6ii) 253 Marco, J.L. (5) 11 McMillen, D. (3) 80, 249 Marcuccilli, C.J. (2) 134 Marder, T.B. (3) 263 McMurry, J.E. (9) 21, 22 Macor, J.E. (8) 26, 51 Mariano, P.S. (5) 44 McPhail, A.T. (2) 163 Marinas, J.M. ( 3 ) 207; (6ii) 234 MacPherson, D.T. (61) 71; (611) 147 Marinier, A. (7) 65 Maeda, H . (4) 230 Marino, J.P. (3) 275, Maeda, K. (4) 194; (611) 276; (7) 39 Marlin, J.E. (611) 226 153 Maeda, Y. (3) 77; (4) 150 Marples, B.A. (6i) 46 Maekawa, E. (5) 48 Marquardt, N. (3) 251 Maekawa, T. (1) 36 Marques, M.M. (9) 25 Maercker, A. (6ii) 1, 36 Marquet, A. (3) 461 Maetzke, T. (3) 149 Marquet, B. (2) 120 Magnus, P. (3) 392; (6i) Marquet, J. (3) 192 76, 78; (6ii) 128; (7) Marquez, C. (2) 161 Marren, T.J. (2) 188; 42, 43; (9) 34, 35 Magnusson, G. (7) 73 (6ii) 158 Marrs, P.S. (7) 6 ; ( 9 ) 10 Mahajan, M.P. ( 8 ) 69 Mahajan, S.W. (4) 19 Marsh, B.K. ( 7 ) 53 Mahapatro, S.N. (4) 199 Marshall, J.A. (4) 102; Mahler , H. (3) 28 (7) 88-91; (9) 17-19 Mai, K. (6ii) 161 Martelli, G. (3) 435; (8) Maier, G. ( 3 ) 13 144-146 Maier, M.E. ( 8 ) 36 Marth. C. (611) 216 Maillard, B. (3) 73 Martin, D.G. (9) 33
18; (4) 236; (61) 23; (611) 221; ( 8 ) 38 Luche, J.-L. (2) 35; (3) 87; (4) 94; (611) 12 Luh, T.Y. (6ii) 80 Lund, E.C. (61) 79 Lusinchi, X. (3) 89; (6ii) 280 Luyten, M. (3) 20 Lynch, J.E. (3) 337 Lynch, J.K. (6i) 43
Martin, J.F. (5) 91 Martin, N. (8) 43 Martin, R.M. (3) 9; (dii) 25 Martin, S.F. (3) 333; (9) 50 Martinez, A.G. (4) 162 Martinez-Gallo, J.M. (4) 193; (611) 90, 152, 264 Martin-Lomas, M. (3) 203; (6ii) 54 Maruoka, K. (2) 189; (4) 3; (611) 122 Maruyama, K. (1) 76; (4) 39, 101, 234; (611) 199, 245 Maruyama, T. (3) 98 Maryanoff, B.E. (1) 62 Masamune, H. (8) 1 Masamune, S. (3) 333; (4) 80; (6ii) 104, 119 Masawaki, T. (1) 24; (611) 275 Mascarella, S.W. (9) 2 Mash, E.A. (7) 3, 4 Mason, I. (8) 18 Massebiau, M.-C. (3) 161 Masuda, S. (611) 229 Masuda, Y. (1) 64 Masui, M. (4) 230; (6ii) 211 Masuyama, Y. (1) 47; ( 3 ) 186; (4) 40; (6i) 58 Matlin, A.R. (7) 10, 11 Matsubara, S. (1) 59, 74; (4) 179; (611) 202, 247 Matsuda, H. ( 8 ) 28 Matsuda, I. (2) 172; (61) 67 Matsuda, K. ( 8 ) 84 Matsuda, T. (1) 15; (2) 55; (6ii) 153 Matsui, S. (3) 305 Matsukawa, M. (1) 7; (2) 52; (4) 42 Matsumoto, K. (3) 352, 366; (9) 60 Matsumoto, T. (61) 19, 20; (9) 60 Matsumoto, Y. (3) 233 Matsumura, Y. (8) 134 Matsunami, N. (3) 109 Matsuoka, K. (4) 51 Matsuoka, M. (3) 233; (4) 11 Matsuoka, R. (1) 85; (2) 147; (611) 48 Matsuoka, s. (3) 191 Matsuoka, Y. (61) 44 Matsuura, S. (8) 132 Matsuura. T. (8) 5 Matsuyk, H.'(2) 67
Author Index Mattay, J. (8) 135 Mattes, H. (4) 165 Matteson, D.S. (3) 424; (6ii) 110 Matthews, D.P. (5) 29 Matz, J.R. (9) 22 Maumy, M. (6i) 57 Maus, s. (4) 33 Maycock, C.D. (2) 13 Maynier, F. (3) 193 Mazumdar, S.N. (8) 69 Mazzieri, M.R. (4) 192 Mead, K.T. (4) 52 Mecozzi, S. (3) 337 Medina, J.C. (8) 130 Mehta, G. (611) 271 Meier, G.P. (3) 359; (9) 59 Meier, M. (5) 71 Meijs, G.M. (6ii) 233 Mellor, J.M. (3) 254; (611) 251; (8) 89, 107 Menegheli, P. (3) 52 Menicagli, R. (3) 333; (611) 123, 125 Meou, A. (1) 79 Merce, R. (3) 280 Metternich, R. (6ii) 116 Metz, W.A. (8) 27 Metzner, P. (2) 195; (3) 108 Meyers, A . I . (2) 82 Michaelis, R. (7) 29 Midland, M.M. (6ii) 96, 97 Mieminen, T.E.A. (4) 12 Miginiac, L. (5) 7, 59; (6ii) 144; (8) 97 Miginiac, P. (3) 159; (6ii) 83 Migita, T. (2) 108, 142; (611) 201 Mignani, G. (3) 97 Mihailovic, M. (3) 255; (6ii) 271 Mikami, K . (3) 29, 332; (6i) 28 Mikhail, G.K. (2) 88; (6ii) 241; (7) 93 Miki, T. (6ii) 256 Milchereit, A. (7) 24 Milenkov, B. (3) 353 Miles, W.H. (5) 40; (9) 32 Milewska, M.J. (3) 481 Miller, D.D. (3) 411 Miller, J.A. (6ii) 253, 254 Miller, J.D. (3) 138 Miller, J.L. (5) 96 Miller, M.J. (3) 145, 421, 432
541
Miller, R.D. (3) 329 Miller, U. (7) 29 Mills, L.S. ( 2 ) 4; (4) 151 Milowsky, A.S. (1) 75 Milstein, D. (3) 263 Mimura, S. (3) 319 Minami, I . (1) 56, 77; (2) 93; (3) 221, 250, 463; (4) 159; (61) 8 Minami, K. (3) 295; (4) 234; (6ii) 245 Minami, T. (3) 306, 342; (61) 40 Minamikawa, H. (2) 169; (5) 69; (6i) 69 Minato, A. (1) 23; (4) 195; (61) 64 Minato, M. (2) 25 Minowa, N. (3) 125; (4) 86 Minton, M.A. (9) 74 Mirata, T. (6ii) 175 Mishima, T. (611) 199 Mishra, P. (7) 100; (8) 14 Mitani, M. (3) 419; (4) 179; (8) 33 Mitchell, M.B. (31 472 Mitchell, T.N. (1) 32; (3) 220; (6ii) 46, 47, 186 Mitsuda, Y. ( 5 ) 98 Mitsudo, T. (1) 68; (2) 101; (3) 72, 232; (8) 62 Mitsue, Y. (2) 95; (3) 369 Mitsunobu, 0. (3) 64 Mitsuymoto, T. (3) 352 Miura, M. (3) 40 Miwa, Y. (3) 22; (7) 57 Miyaji, K . (6i) 19 Miyashi, N. (611) 282 Miyashita, M. (8) 4 Miyata, K. (1) 2; (2) 36, 37, 105; (3) 90, 91 Miyaura, N. (1) 116; (4) 243; (6ii) 114 Miyazawa, M. (2) 183 Miyazawa, Y. (2) 67 Miyoahi, N. (5) 6 Miyoshi, N. (2) 127; (3) 11; (4) 93; (6ii) 14, 141, 281, 283 Mobili, D. (2) 191; (6ii) 198 Modena, G. (2) 17 Moderer, K. (5) 10 Moerlein, S.M. (6ii) 179 Mohareb, R.M. (5) 62 Mohr, P. (3) 24; (4) 96
Moison, H. (3) 207; (611) 224 Molander, G.A. (3) 339; (4) 58-61: (6ii) 146; (7) 2, 17, 18, 75, 82 Mollov, N.M. (8) 123 Monahan, R., I11 (1) 103; (2) 96 Montanari, F. (2) 10; (3) 8; (4) 157 Monteiro, H.J. (2) 65; (7) 49 Moody, C.J. (9) 36, 37 Mooiweer, H.H. (5) 43; (611) 144 Mook, R. (6ii) 185 Moorhoff, C.M. (3) 184; (6ii) 223 Mordini, A. (4) 85 Morel, D. (3) 97 Moren, D.M. (3) 418 Moreno-Manas, M. (3) 192 Morera, E. (3) 173 Morey, J. (3) 241 Mori, A. (4) 22 Mori, I. (4) 231 Mori, S. (3) 49 Moriarty, R.M. (1) 80; (2) 111-113, 139, 140; (3) 82, 243; (61) 29 Morikawa, T. (3) 266; (8) 11 Morimoto, A. (3) 294 Morimoto, T. (2) 9; (3) 134; (4) 23, 156 Morimoto, Y. (5) 35 Morin, C. (3) 26 Morita, Y. (2) 20 Moriuchi, F. (3) 289 Moriwake, T. (5) 27 Moriyasu, M. (611) 191 Mormann, W. (3) 105 Morris, D. (3) 80, 249 Morris, P.E., jun. (2) 3; (4) 145 Morris, T.H. (8) 6 Mortier, J. (8) 74, 87 Mortlock, S.V. (4) 53 Moses, R.C. (5) 39 Moss, R.A. (4) 138 Mosset, P. (3) 241 Motegi, M. (3) 23 Motherwell, W.B. (4) 216, 217; (6ii) 238 Motoyoshi, K. (3) 64 Moursounidis, J. (6ii) 128 Moutet, J.-C. (1) 6 Moyano, A. (1) 95, 96; (4) 214 Mozumi, M. (8) 105 Muchow, G. (4) 70; (6ii)
542
89 Mukaiyama, T. (1) 98; (2) 58, 99, 137, 169, 170, 175, 190; (3) 11, 25, 106, 125, 126, 127, 143, 179, 200, 235, 437; (4) 86, 93; (5) 67; (6ii) 138, 141 Mulamba, T. (9) 27 Muller, B.L. (2) 107 Muller, S. (3) 20 Mullins, M.J. (3) 359; (9) 59 Munoz, B. (4) 113 Munro, M.H.G. (9) 66 Munster, P. (3) 390 Murahashi, S. (2) 95; (3) 77, 178, 367, 369, 394; (4) 150; (5) 38, 108; (6i) 16 Murai, J. (6ii) 281 Murai, S. (2) 127; (3) 218; (4) 222; (6ii) 14, 188, 283 Murakami, M. (2) 169; (5) 67; (6ii) 138 Muralidharan, K.R. (1) 89; (6ii) 265 Muranaka, K. (3) 313 Murata, S. (3) 256; (6ii) 271; (8) 132 Murata, T. (1) 38 Muroi, H. (3) 289 Murphy, C.J. (9) 50 Murphy, P.J. (3) 377 Murray, P.J. (3) 141 Musallam, H.A. (2) 112 Mustroph, H. (5) 60 Muto, M. (3) 64 Muzart, J. (2) 6; (3) 229; (4) 144 Mwesigye-Kibende, S, (8) 47 Myer, L. (2) 193; (6ii) 227 Myers, M. (6ii) 50 Myers, P.L. (9) 15 Mzengeza, S. (9) 40 Naef, R. (3) 412 Nag, A . (3) 86 Nagabhushan, T.L. (8) 60 Nagagawa, H. (6ii) 244 Nagahara, T. (8) 140 Nagai, K. (3) 5; (6i) 13 Nagai, S. (5) 49 Nagai, Y. (3) 264 Nagao, Y. (1) 39; (3) 355; (5) 102 Nagarajan, S . (9) 66 Nagashima, N. (3) 123
General and Synthetic Methods Nagata, K. (4) 180 Nagata, R. (8) 5 Nagler, P. (3) 350 Nagoa, Y. (6ii) 210 Naito, H. (611) 71 Najdi, S.D. (3) 358; (6i) 55 Najera, C. (2) 49; (4) 193; (611) 40, 90, 152, 264 Naka, H. (2) 108 Nakagawa, Y. (3) 114; (8) 124 Nakahama, S. (6ii) 109 Nakahara, Y. (2) 118; (4) 188 Nakai, T. (3) 29, 160, 332; (6i) 28; (6ii) 84 Nakajima, A. (4) 203 Nakajima, M. (4) 7, 65, 66; (61) 25; (611) 76 Nakajima, N. (3) 367 Nakajima, S. (3) 364 Nakajima, T. (6ii) 229 Nakajo, E. (3) 343; (6ii) 150 Nakamura, E. (3) 83, 84; (611) 85 Nakamura, H. (2) 63; (6ii) 260 Nakamura, K. (3) 148; (6ii) 58 Nakamura, M. (3) 17 Nakamura, T. (2) 150; (6ii) 2, 86 Nakanishi, A . (3) 267 Nakanishi, K. (4) 136 Nakanishi, S. (3) 246; (61) 60 Nakano, T. (2) 16; (3) 264; (4) 154 Nakao, K. (3) 56, 57, 58 Nakashima, H. (3) 342 Nakatani, H. (4) 234; (6ii) 245, 252 Nakatani, K. (2) 66 Nakayama, J. (4) 115 Nakonieczna, L. (3) 372 Naota, T. (3) 77, 367; (4) 150 Narasaka, K. (3) 169; (5) 69; (6i) 69 Narasimhan, N.S. (3) 53; (8) 122 Narayana, C. (6ii) 94 Narayanan, B.A. (1) 42; (6ii) 165 Narisano, E. (3) 435; (5) 14 Naruta, Y. (1) 76; (4) 101 Naso, F. (1) 17
Natchus, M.G. (3) 88; (7) 33 Nativi, C. (1) 67, 83; (6ii) 135, 190 Natsugari, H. (3) 294 Natu, A.A. (3) 95 Nazer, B. (2) 27 Nedelec, J.Y. (611) 208 Negishi, E. (1) 19, 70; (2) 109; (3) 238; (61) 4; (6ii) 45, 124; (7) 13 Negoro, K. (6ii) 242 Negre, M. (8) 88 Negri, D.P. (9) 64 Nelson, D.J. (6ii) 99 Nelson, K.A. (7) 3, 4 Nemoto, H. (9) 20 Neuman, W.P. (6ii) 183 Neumann, M. (7) 32 Newcomb, M. (5) 31; (8) 98 Ng, F.W. (3) 249 Ni, Z. (4) 236 Ni, Z.J. (611) 80 Nicholas, K.M. (6i) 6 Nicolaou, K.C. (3) 352; (8) 46, 49; (9) 61-63 Niedrich, H. (3) 465; (5)
46 Nieger, M. (3) 415 Nihira, T. (3) 348 Niibo, Y. (3) 36 Ninniss, R.W. (4) 113 Nisar, M. (1) 56; (2) 93; (3) 221 Nisato, D. (3) 443 Nishi, M. (4) 75; (6ii) 89 Nishi, T. (3) 448 Nishida, N. (2) 50; (3) 198 Nishide, K. (3) 316 Nishiguchi, I. (5) 66 Nishii, S. (3) 94, 168, 227 Nishimura, A. (2) 102; (4) 121 Nishimura, M. (5) 49 Nishimura, S. (5) 90; (6ii) 162 Nishino, H. (3) 113, 116 Nishitani, K. (3) 304; (6ii) 142 Nishiwaki, T. (3) 266; (8) 11 Nishiyama, E. (3) 136 Nishiyama, S. (9) 70 Nishiyama, Y. (4) 222 Nivard, R.J.F. (3) 420 Niwa, S. (4) 77; (6ii) 89 Noda, Y. (3) 318
Author Index
543
Node, M. (2) 60; (4) 120; (6ii) 63 Noe, R. (3) 80, 249 Nohira, H. (3) 23 Nokami, J. (2) 102; (4) 121 Nome, R. (3) 368 Nomoto, T. (611) 71 Nomura, K. (3) 324 Nomura, M. (3) 40; (4) 132 Nonaka, T. (4) 233; (8) 124 Nonoshita, K. (2) 189; (6ii) 122 North, M. (3) 426 Norton, J . R . (61) 1 Novi, M. (5) 70 Noyori, R. (3) 5, 147; (4) 125, 126; (6i) 11-13, 26 Nozaki, H. (1) 74; (2) 157; (6ii) 51, 202; (8) 118 Nozaki, K. (1) 25-27; (4) 240; (6ii) 180, 185 Nozaki, T. (8) 28 Nozawa, H. (3) 23 Nozawa, K. (3) 364 Nsunda, K.M. (6ii) 273 Nugent, W.A. (1) 73 Nurmi, T.T. (1) 1; (6ii) 19; (7) 51 Nutaitis, C.F. (5) 8 I
Oakley, R.T. (5) 95 Obara, T. (3) 454 Obara, Y. (6ii) 201 O'gryan, E. (3) 80 Ochiai, H. (2) 150; (3) 237; (6ii) 86 Ochiai, M. (1) 39; (3) 294, 355; (5) 102; (6ii) 210 O'Connor, B. (3) 76 O'Connor, E.J. (6i) 45 Oda, H. (6ii) 180 Oda, J. (3) 25, 289 Oda, K. (7) 31 O'Donnell, M.J. (8) 75 Oehme, H. (6ii) 3 Oesterle, T. (3) 140 O'Farrell, C. (3) 472 Ogasawara, K. (3) 117, 270, 439; (9) 41 Ogawa, A. (1) 24; (2) 127; (4) 222; (5) 6; (6ii) 14, 275, 282, 283 Ogawa, H. (4) 209 Ogawa, K. (4) 78; (611) 89
Ogawa, M. (2) 16; (3) 248; (4) 152, 154 Ogawa, S. (1) 46; (6ii) 196 Ogawa, T. (3) 55 Ogawa, Y. (3) 352; (9) 63 Ognyanov, V.I. (2) 70; (7) 41; (8) 123 Ogoshi, H. (4) 4 Ogura, F. (6ii) 285, 287 Ogura, H. (3) 68, 464 Ogura, K. (2) 133 Oh, S.Y. (2) 28, 30 Ohara, T. (2) 103; (3) 212 Ohashi, K. (2) 142 Ohe, K. (3) 219 Ohe, M. (8) 82, 83 Ohfune, Y. (3) 446 Ohki, H. (1) 50; (4) 36; (6ii) 237 Ohkuma, T. (1) 54; (3) 147; (4) 126; (6i) 11 Ohmori, H. (4) 230; (6ii) 211 Ohnishi, K. (4) 202 Ohnishi, S. (8) 63 Ohno, A. (3) 148; (6ii) 58 Ohno, M. (3) 123, 191 Ohno, R. (3) 142 Ohshima, M. (3) 11, 25; (6ii) 141 Ohta, H. (3) 137; (5) 75 Ohta, N. (1) 46; (6ii) 196 Ohta, T. (3) 5, 178; (4) 125; (6-1)12, 13 Ohtani, T. (1) 31; (611) 264 Oiarbide, M. (2) 23, 24; (5) 74 Oishi, H. (3) 316 Ojima, I. (3) 414; (8) 114 Oka, S. (3) 148; (6ii) 58 Okada, H. (3) 293 Okada, Y. (2) 165; (4) 189 Okahara, M. (2) 50; (3) 198; (4) 212 Okajima, T. (9) 20 Okamoto, S. (61) 19, 20 Okamoto, T. (2) 122; (3) 366 Okamoto, Y. (6ii) 257; (8) 141 Okano, A. (2) 79 Okano, T. (3) 12; (4) 11; (8) 133 Okauchi, T. (3) 127 Okawara, M. (8) 100
Okawara, T. (5) 85 Okazaki, K. (3) 324 Okazaki, R. (6ii) 270 Okazoe, T. (1) 20, 34; (4) 239; (6i) 75; (6ii) 152, 252 Okinaga, T. (4) 64 Oku, A. (4) 127, 128 Okukado, N. (1) 70; (3) 238; (6ii) 124 Okuno, Y. (9) 8 Okura, S. (6ii) 51 Olah, G.A. (4) 211 Olmstead, M.M. (6i) 79 Olsen, R.K. (3) 370 O'Mahony, M.J. (9) 42 Onaka, M. (3) 124, 142 Onitsuka, K. (3) 310 Ono, A. (3) 98; (4) 16 Ono, N. (5) 77, 78; (6ii) 249, 274 Onoue, S. (2) 179 Ookawa, A. (4) 78, 97; (7) 89 Ooms, P. (8) 50 Oplinger, J . A . (9) 16 Oppolzer, W. (3) 2; (6i) 72; (7) 15 Or, Y.-S. (9) 34 O'Reilly, N.J. (4) 49 Orena, M. (3) 440 Ori, A. (3) 59 Orsini, F. (3) 226 Ortar, G. (3) 173 Ortega, A.G. (4) 108 Ortiz, M . J . (5) 91 Ortuno, R.M. (3) 280 Osakada, K. (4) 225 Osawa, T. (4) 24 Oshima, H. (6ii) 192 Oshima, K. (1) 13, 20, 25-27, 74; (3) 266; (4) 240; (61) 75; (6ii) 149, 180, 185, 202; (8) 22, 109 Oshima, M. (4) 93 Oshima, T. (5) 48 Oshino, H. (3) 83; (6ii) 85 Osowska-Pacewicka, K. (5) 3, 82 Otaka, A. (3) 470, 477; (6ii) 127 Otaka, K. (1) 63; (611) 129, 145 Otani, S. (3) 366 Otera, J. (2) 157; (3) 36; (611) 51 O'Toole, J . G . (3) 378 Otsubo, K. (3) 131, 164, 286 Otsubo, T. (611) 285, 287
544 Otsuji, Y. (3) 246; (6i) 60 Ottenheijm, H.J.C. (3) 420 Otto, H.H. (7) 71 Oudenes, J. (2) 167; (6ii) 103 Overman, L.E. (5) 41, 42; (6ii) 154; (7) 100; (8) 13, 14 Owczarczyk, Z. (2) 57 Owens, A.H. (5) 30 Ozaki, K. (5) 75 Ozaki, M. (9) 70
General and Synthetic Methods
Pascual, C. (8) 43 Patel, V.F. (2) 51; (6i) 87-89; (8) 24 Paterson, I. (2) 168; (8) 18; (9) 56 Patil, G. (6ii) 161 Patil, P.A. (8) 122 Patin, H. (1) 5; (3) 87 Patrianakou, S. (3) 427, 458, 474 Patricia, J . J . (1) 1; (611) 19; (7) 51 Pattenden, G. (1) 115; (2) 51; (6i) 87-89; (8) 12, 24; (9) 15, 69 Patterson, L. (7) 73 Pabon, R.A., jun. (7) 53 Patton, A.T. (3) 452 Padwa, A . (2) 100; (3) Pauson, P.L. (6i) 77 183; (6ii) 67 Pearson, A.J. (3) 297; Page, P.C.B. (6ii) 57, (8) 94 Pearson, W.H. (3) 138 178; (8) 35, 110 Pagni, R.M. (4) 166 Pecunioso, A. (611) 125 Pedersen, S.F. (4) 46; Pairaudeau, G. (1) 87; (5) 19, 56; (6i) 61 (8) 40 Pale, P. (3) 262; (8) 20 Pedrosa, R . (4) 108 Palit, S.K. (3) 86 Pedroso, E. (3) 475 Palkowitz, A.D. (4) 83; Peek, R.J. (1) 114 Pelinski, L. (61) 36 (6ii) 118 Palmer, M.A.J. (4) 83; Pelizzoni, F. (3) 226 (6ii) 118 Pelter, A. (1) 12; (3) 320; (6ii) 121 Palomo, C. (2) 5, 23, 24; (4) 141; (5) 74 Pena, M.R. (3) 381 Palumbo, G. (2) 153 Peng, Q.-J. (6ii) 157 Penmasta, R . (2) 113, 140 Pan, K. (7) 68 Panek, J.S. (2) 192; Peperzak, R.M. (2) 94 Pera, M.-H. (1) 82, 88; (6ii) 137; (8) 103 Pansare, S.V. (3) 387 (3) 385; (6ii) 262 Pantaloni, A. (3) 457 Perera, S.A.R. (4) 69; (6ii) 89 Panunzio, M. (3) 435; (8) 144-146 Pereyne, M. (6ii) 182 Perez, D. (1) 3; (2) 34, Papagni, A. (61) 37 Papahatjis, D.P. (9) 61 44; (3) 85; (6ii) 159 Perezossorio, R . (5) 91 Papaioannou, D. (3) 427, 474 Periasamy, M. (3) 54; Paquette, L.A. (3) 268; (611) 94 Pericas, M.A. (4) 213 (9) 16 Perichon, J. (3) 161; Parish, E.J. (2) 7 Park, G. (8) 21 (611) 208 Park, J. (6i) 27 Perret, R . (2) 41 Park, J.H. (4) 135 Perron, F. (8) 32 Park, M.H. (4) 136 Perrot, M. (2) 32 Perumattam, J. (2) 100; Park, W.H. (3) 115 Park, W.S. (4) 20, 21; (3) 183 Pete, J.-P. (3) 229; ( 8 ) (6ii) 105, 108 120 Parker, K.A. (4) 112; Peter, R. (3) 209 (6ii) 29 Peterson, B.H. (3) 138 Parrinello, G. (2) 54; Peterson, M.V. (8) 78 (6i) 86 Petit, Y. (3) 130 Parsons, P.J. (1) 87; Petnehazy, I. (5) 99 (611) 266; (7) 59; (8) 40 Petragnani, N. (2) 128; Pascal, F. (3) 456 (611) 286
Petrier, C. (2) 35; (3) 87; (4) 94 Petrillo, G. (5) 70 Petrini, M. (3) 194; (5) 5
Petrov, O.S. (8) 123 Pettit, G.R. (9) 67 Peyronel, J.F. (6ii) 207 Piccolo, 0. (3) 60 Pichon, C. (4) 216; (6ii) 238 Picken, H . A . (7) 11 Picotin, G. (3) 159; (6ii) 83 Pielke, M. (6ii) 33 Piers, E. (1) 18; (3) 220; (6ii) 187; (7) 6; (9) 10 Pies, M. (7) 55 Pietranico, S. (8) 59 Pilli, R.A. (5) 25 Pinhey, J.T. (3) 187 Pinkerton, A . A . (3) 297; (8) 94 Piorko, A. (3) 187 Piotrowski, D.W. (5) 16 Pirrung, M.C. (7) 12 Pitteloud, R . (7) 64, 65 Pittman, J.H. (1) 37; (4) 201; (6ii) 243 Piva, 0. (3) 229 Piyasena, H.P. (8) 58 Pizzo, F. (7) 23 Plaquevent, J.-C. (3) 371; (6ii) 8; (7) 77 Pletcher, D. (3) 471 Podhorez, D.E. (9) 27 Poli, G. (3) 222 Polizzi, C. (1) 97 Pomet, J. (8) 97 Pommelet, J.-C. (8) 95 Pont, J.L. (8) 26, 52 Popall, M. (6i) 85 Popandova, K. (2) 197 Pore, V.S. (3) 95 Pornet, J. (6ii) 144 Porrinello, G. (611) 200 Porta, A. (3) 475 Porter, J . R . (3) 298; (6ii) 33 Porter, N.A. (3) 347 Porter, T.M. (611) 220 Porzi, G. (3) 440 Posner, G.H. (2) 198; (3) 273, 354 Poss, A.J. (2) 72; (3) 300 Poternca, J.J. (5) 96 Potier, P. (3) 425, 431; (8) 99 Potlock, S.J. (3) 204 Powell, G. (3) 249
Author Index
Prabhakar, S. (9) 25 Prakash, G.K.S. (4) 211 Prakash, 0. (2) 111-113, 139, 140 Prasad, C.V.C. (2) 78; (7) 72 Prasad, J.V.N.V. (4) 2; (6ii) 102 Prasad, K. (3) 167; (6ii) 93 Preston, S.C. (6i) 5 Pretor, M. (8) 37 Preuss, R. (6ii) 42 Principe, L.M. (6i) 76; (7) 42 Prior, L.M. (3) 455 Procter, G. (3) 285, 377; (611) 132 Puff, H. (3) 120; (8) 121 Pulst, M. (8) 54 Purrington, S.T. (1) 37; (2) 119; (4) 187, 201; (6ii) 243 Qiu, W. (1) 35 Qui, X. (3) 414 Quici, S. (2) 10; (3) 8; (4) 157 Quinkert, G. (3) 350; (9) 58 Quintard, J.-P. (6ii) 182, 189 Racherla, A.S. (6ii) 106 Radov, L.A. (3) 315 Rafferty, M.A. (2) 181; (6ii) 78 Raggon, J.W. (8) 117 Raghavan, M. (3) 357 Ragoussis, N. (3) 42 Rahm, A. (6ii) 182 Rajeswari, S. (3) 363; (8) 79 Ram, S. (3) 472; (5) 50, 51 Rarnachandran, K. (7) 23 Ramachandran, P.V. (4) 21; (6ii) 105 Ramage, R. (3) 482 Ramaiah, M. (7) 14; (8) 81 Ramakanth, S. (1) 11; (6ii) 214 Ramasubbu, A. (4) 170 Ramezani, S. (3) 447 Ramiz, M.M.M. (8) 129 Ramos, A. (5) 91 Ramsby, S. (3) 365 Randad, R.S. (4) 81, 82; (611) 118
545 Rangaishenvi, M.V. (6ii) 106 Rao, C.T. (2) 138 Rao, H.S.P. (6ii) 271 Rapoport, H. (9) 28 Rasmussen, J.K. (3) 418 Ratcliffe, A.H. (4) 105 Rathbone, D.L. (3) 182, 479 Rathke, M.W. (6ii) 6 Rathore, R. (2) 21 Raths, H.-C. (3) 234 Ratier, M. (6ii) 185 Ratovelomanana, V. (4) 204 Raucher, S. (3) 96 Rautenstrauch, V. (3) 43 Ravard, A. (6ii) 8; (7) 77 Raychaudhuri, S.R. (7) 9 Reates, C. (4) 106 Rebelo, R.A. (3) 368 Reddy, C.P. (3) 176 Reddy, K.B. (6ii) 271; (8) 46 Reddy, N.L. (3) 338; (611) 170 Reed, R.W. ( 5 ) 95 Rees, C.W. (9) 36 Reetz, M.T. (3) 209; (4) 33, 34, 232; (61) 66 Refouvelet, B. (1) 88; (6ii) 262 Regan, A.C. (6ii) 9 Reginato, G. (6ii) 177 Regnarsson, U. (5) 45 Reichert, D.E.C. (4) 241 Reiman, W. (6ii) 46, 47 Reiniers, F. (5) 54 Reissig, H.-U. (3) 199, 290 Reitz, A.B. (1) 62 Rempel, C.A. (3) 450 Renaldo, A.F. (6ii) 200 Renaud, P. (3) 177 Rendenbach, B.E.M. (3) 201, 336 Renko, Z.D. (61) 22; (8) 126 Repic, 0. (3) 167; (611) 93 Resnati, G. (3) 282 Revis, A. (3) 144 Rey, A.W. (3) 23 Rey, M. (2) 61; (7) 7 Reynolds, D.W. (7) 53 Rezende, M.C. (3) 52, 368 Rheingold, A.L. (3) 196 Ricci, A. (1) 83; (611) 133, 135, 177; (8) 30 Rice, K.C. (7) 78 Rich, D.H. (3) 409, 410,
467 Rich, D.R. (4) 100 Richards, D. (4) 113 Richardson, J.W., jun. (6ii) 91 Richardson, S.K. (3) 39; (6ii) 39 Richter, F. (7) 71 Rico, J.G. (1) 61; (6ii)
44 Riego, J.M. (5) 47 Rieke, R.D. (2) 187; (6ii) 74, 75 Rigby, J.H. (7) 80, 81 Riley, D.P. (3) 62 Rimpler, M. (3) 433 Rinehart, K.L. (9) 66 Riniker, B. (3) 478 Risaliti, A. (6ii) 64 Rise, F. (7) 45 Rivera, V. (2) 161 Rivero, R.A. (9) 53 Rizk, T. (3) 193 Rizzacasa, M.A. (3) 205 Rizzo, C.J. (7) 30 Robert, A. (2) 136; (5) 86 Roberts, D.W. ( 8 ) 73 Roberts, J.L. (2) 167; (6ii) 103 Roberts, K.A. (1) 93 Roberts, S.M. (3) 280 Robertson, J. (4) 219; (8) 16 Robinson, J.A. (8) 17 Robinson, J.E. (1) 114 Robinson, N.G. (3) 430; (611) 213 Robl, J.A. (2) 152 Robson, D.C. (1) 115 Rodriguez, J. (3) 317; (8) 10 Rodriguez, M.A. (1) 100; (4) 172, 205 Roekens, B. (2) 81 Roggo, S. (3) 149; (4) 68 Rolando, C. (611) 32 Romeo, G. (5) 64 Ronzini, L. (1) 17; (2) 38 Roos, G.H.P. (3) 223 Rose, E. (61) 30 Rose-Munch, F. (61) 30 Rosenthal, S. (611) 178 Rosini, G. (3) 194; ( 5 ) 5 Roskamp, E.J. (4) 46; ( 5 ) 19, 56; (6i) 61 Rossano, L.T. (3) 236 Rosslein, L. (3) 24 Rousch, W.R. (4) 83; (6ii) 118 Rousseau, G. (1) 81; (3)
546
General and Synthetic Methods
(6i) 24, 80-82 Sakamoto, A. (3) 289 Sakashita, H. (6ii) 252 Sakata, H. ( 3 ) 93 Sakuma, K. (3) 66 Sakurai, H. (1) 63; (4) 54; (5) 49; (6ii) 129, 139, 145, 168 Sakurai, K. (3) 75, 352; (6ii) 219 Sakurai, Y. (6ii) 109 Salaun, J. (2) 154; (3) 21, 413 Salazar, J.A. (611) 276 Salomon, R.G. (7) 9 Sammakia, T. (61) 38 Sampath, V. (6i) 79 Samuel, 0. (6ii) 207, 258 Sanch, F. (6i) 35 Sanderson, P.E.J. (3) 165; (4) 139; (6ii) 175 Sandhu, J.S. (5) 89; (8) 112 Sandri, S. (3) 440 Sanforth, S.P. (6ii) 238 Sani, P. (3) 352 Sanida, C. (3) 474 Sanner, C. (3) 156 Sano, H. (2) 108, 142; (4) 3; (6ii) 201 Santafianos, D. (9) 72 Santaniello, E. (3) 153; (4) 28 Santelli, M. (3) 317; (8) Saavedra, J.E. (5) 79 Sabbioni, G. (3) 19 10 Saburi, M. (3) 17; (61) Sargent, M.V. (3) 205, 14 321 Sadeghi, M.M. (3) 422; Sarkar, A. (3) 86 Sarkar, A.K. (4) 9, 88; (5) 4 Sado, Y. (3) 17 (611) 136, 143 Saegusa, T. (2) 97, 98; Sarkar, S.K. (3) 86 (3) 224, 225; (611) 126 Sarkar, T.K. (1) 44; Sagawa, Y. (2) 170; (3) (611) 131 200 Sasa, M. ( 4 ) 223 Sager, W. (3) 406 Sasaki, H. (8) 138 Saimoto, H. (3) 316 Sasaki, N.A. (3) 425 Sain, B. (8) 112 Sasaoka, S. (611) 264 Sain, E. (5) 89 Sassaman, M.B. (4) 211 Saindane, M.T. (9) 14 Sasson, Y. (4) 146; (5) Saito, I. (8) 5 20 Saito, S. (5) 27 Sato, F. (61) 19, 20, 21 Sakaguchi, K. (8) 44 Sato, K. (611) 168 Sakai, K. (3) 158; (4) Sato, S. (2) 172; (3) 99; 230; (7) 31, 35 (61) 67 Sakai, R. (9) 66 Sato, T. (2) 157; (3) 133, 283; (611) 51, 60; Sakai, S. (2) 174; (3) 267 (8) 101 Sakai, T. (1) 2; (2) 36, Satoh, J.Y. (3) 303; (611) 142 37, 105; (3) 90, 91, 185, 293 Satoh, K. (3) 75, 352; Sakaitani, M. (3) 446 (6ii) 219 Sakakura, T. (3) 32, 172; Satoh, T. (2) 84, 103,
21, 74, 85, 245 Rowlands, M. (3) 320 Rowley, M. (6ii) 196 Roy, R. (3) 23 Royer, J. (5) 11 Royer, R. (3) 388 Rozen, S. (4) 181 Rozwadowski, J. (2) 110 Rubiera, C. (6ii) 16, 17 Ruchard, T.C. (5) 71 Rudolph, B. (6i) 47 Ruholl, H. (3) 37 Ruhter, G. (1) 106; (6i) 63 Runsink, J. (8) 15, 135 RUSS, M. (3) 7 Russel, S.T. ( 8 ) 17 Russell, A.T. (3) 285, 377; (6ii) 132 Russell, C.E. (6ii) 91 Russell, D.R. (611) 61 Russell, S.J. (6ii) 264 Russowsky, D. (5) 25 Rutledge, M.C. (5) 13 Ruzziconi, R. (2) 141 Rychnovsky, S.D. (3) 271; (4) 129, 130; (9) 54, 55 Ryckman, D.M. (9) 38 Ryu, I. (1) 24; (611) 188, 275
104; (3) 212; (4) 196; ( 8 ) 19 Satomi, H. (2) 97; (3) 225; (6ii) 126 Sattur, P.B. (8) 67 Satyanarayana, N. (3) 54 Sauter, H.-P. ( 8 ) 125 Savariar, S. (2) 62 Savignac, P. (2) 106; (6ii) 218, 222 Savrda, J. (3) 449 Sawada, T. (3) 23 Sawaga, G. (3) 26 Sawaki, Y. (6ii) 247 Sawamura, M. (3) 233, 400; (6i) 44, 68 Sayers, A. (2) 56 Sayo, N. (3) 147; (4) 125, 126; (6i) 11, 12 Scettri, A. (8) 23 Schaefer, A.G. (3) 268 Schafer, H . J . (3) 37; ( 7 ) 29 Schafer, W. (3) 474 Schamp, N. (2) 121; (4) 185 Schantl, J.G. (8) 149 Scheeren, J.W. ( 8 ) 77 Schick, H. (3) 345 Schickli, C. (3) 411 Schimperna, G . (3) 143, 222 Schindele, D.C. (3) 96 Schlessinger, R.H. (3) 334; (5) 32 Schlund, R. (6ii) 55 Schmidbaur, H. (6ii) 230 Schmidt, D. (6ii) 49 Schmidt, J.M. (9) 67 Schmidt, M. (3) 301 Schmidt, R.R. (6ii) 37, 42; (8) 36 Schmidt, S.J. (3) 50 Schmidt, S.P. (4) 164 Schmidt, U. (3) 409 Schmitt, R.J. (1) 99; (5) 81
Schneider, D.F. (3) 184; (6ii) 223 Schneider, M.P. (1) 109 Schneider, N. (8) 66 Schneider, U. (1) 32; (3) 220; (611) 186 Schober, P.A. (3) 274 Schobert, R. (2) 11; (3) 352 Schofield, C.J. (8) 150 Schofield, R.A. (5) 44 Schollkopf, U. (3) 402-405, 415 Schore, N.E. (3) 358; (6i) 55, 79
Author Index Schreck, M. (8) 41 Schreiber, S.L. (4) 117: (61) 38 Schubert, D.C. (611) 146; (7) 75, 82 Schuda, P.F. (3) 204 Schultz, A.G. (9) 39 Schultz, J. (9) 34 Schultz-von Itter, N. (4) 226: (611) 248 Schumann, I. (3) 51 Schute, R.E. (3) 467 Schwalbe, T. (3) 350 Schwartz, S. (3) 345 Scolastico, C. (3) 222 S c o t t , R.M. (4) 170 Scrimin, P. (4) 138 Seck, M. (3) 307 Seebach, D. (3) 146, 149, 155, 177, 389, 411, 412, 434: (4) 35, 68, 90 Segami, S. (3) 454 Segi, M. ( 6 i i ) 229 Seigel, W. (3) 409 S e i t z , T. (4) 232 Seki, Y. (3) 218 Sekiguchi, Y. (3) 439 Sekiya, K. (3) 83, 84; (611) 85 Selim, M.R. (1) 57: ( 6 i i ) 173 Sellen, M. (61) 56 Selnick, H.G. (9) 48, 49 Semelhack, M.F. (61) 51: (611) 23 Semra, A. (61) 30 Senanayake, C. (7) 80, 81 Senechal, D. (61) 50 Senechal-Tocquer, M.-C. (61) 50 Senet, J.-P. (3) 67, 361, 457, 462 Sengupta, S. (2) 115; (611) 31, 166 Sennyey, G. (3) 67, 361, 457, 462 Seo, W. (3) 189 Seoane, G. (5) 36: (8) 43 Seoane, P.R. (61) 70: (611) 147 Sera, A. (5) 66 S e r i , T. (2) 155 Serratosa. F. (4) 213 Sessink, P.J.M. (2) 68 Sha, C. (2) 123 Sham, H.L. (3) 429,,450 Shandala, M.Y. (3) 46 Shankaran, K. (2) 69 Shapiro, B.M. (3) 403 Shapiro, M.J. (3) 167: (611) 93
547 Sharma, M. (8) 69 Sharma, R.P. (4) 15 Sharma, S. (3) 432; (8) 59 Sharpless, K.B. (4) 98; (8) 1 Shaw, C. (3) 364 Shea, K.J. (2) 80: (3) 351 Shen, Y. (1) 35, 94 Sheppard, A.C. (2) 114; (3) 129 S h e r i f , S.M. (5) 62 Shi, L. (3) 382: (611) 235 Shibata, F. (611) 152 Shibata, S. (3) 292; (4) 17, 18; (611) 109 Shibata, T. (3) 49 Shibata, Y. (4) 174: (8) 76 Shibutani, T. ( 6 i i ) 81 Shibuya, S. (3) 445; (8) 106, 115 Shibuya, T. (611) 181 Shigemori, H. (9) 8 Shim, S.B. (2) 160 S h i m , K. (611) 172 Shimazaki, M. (2) 182 Shimazaki, T. (61) 19, 20 Shimizu, I. (1) 56: (2) 93 Shimizu, M. (1) 52; (2) 118; (4) 184, 188 Shimizu, N. (611) 152 Shimizu, S. (3) 303: (611) 142 Shimizu, T. (611) 277 Shin, C. (3) 454 Shing, T.K.M. (7) 58 Shinkai, I. (3) 337 Shinoda, K. (4) 3 Shinohara, M. (3) 40 Shinozaki, A. (4) 122 Shiohara, T. (3) 310 S h i o i r i , T. (2) 166; ( 6 i i ) 9, 10 Shiota, F. ( 6 i i ) 181 Shiota, T. (3) 394: (5) 108 S h i r a i s h i , Y. (2) 117; (611) 5 Shiraiwa, T. (3) 17 Shizuri, Y. (9) 8, 70 Sho, K. (3) 343 Shono, T. (2) 46, 47: (3) 195; (8) 134 Shook, D.A. (3) 188 Short, R.P. (3) 333: (611) 104 Shoup, T.M. (4) 5 Shulkind, M. (9) 23
Shulte-Elte, K.H. (2) 107 Shultz, A.G. (7) 76 S i b e l l e , S. (4) 38 S i b i , M.P. (2) 69 S i b i l l e , S. (3) 161 S i d l e r , D.R. (3) 311 Sieber, P. (3) 478 Silverman, I.R. (2) 173: (4) 89 S i l v e r s t e i n , R.M. (3) 1 5 S i l v e r t o n , J.V. (4) 123 Simchen, G. (3) 140 Sinmonds, M.S.J. (9) 72 Simokawa, K. (2) 117: (611) 5 Simon, C.D. (1) 25; (4) 238: (611) 252 Simon, H. (3) 27; (5) 58 Simpkins, N.S. (611) 7, 69, 263 Simpson, J.H. (1) 108; ( 6 i i ) 200 Sinaizingde, G. (5) 36 Sinai-Zingde, G. (611) 59; (7) 33 Sinai-Zingole, G. (3) 88 Sindona, G. (5) 64 Singaram, B. (611) 98, 101 Singh, P. (2) 119: (4) 187 Singh, R. (3) 360 Singh, V.K. (3) 292; (4) 18: (611) 109 S i n i s t e r r a , J.V. (3) 207: ( 6 i i ) 234 Sipos, W. (7) 28 S i t , S.-Y. (9) 51 Sjogren, E.B. (3) 398 S k e r l j , R.T. (1) 18: (3) 220; (611) 187 Skobel, H. (3) 128 Skopan, H. (3) 27 S l a t e r , M.J. (3) 392; (61) 76; (7) 42 Sledeski, A.W. (3) 280 S l e s s e r , K.N. (611) 220 Slough, G.A. (3) 196, 311 Slougui, N. (1) 81: (3) 85, 245 Smaardijk, A.A. (4) 71; (611) 89 Smit, R. (8) 77 Smith, A.B., I11 (7) 30: (9) 52, 53 Smith, E.H. (8) 6 Smith, H.D. (3) 188 Smith, H.K., I1 (3) 418 Smyth, M.S. (3) 300 Snapper, M.L. (61) 73; (7) 83 Snider, B.B. (3) 48; (4)
548 111 Snieckus, V. (2) 69 Snowden, R.L. (2) 107 Soai, K. (3) 2; (4) 75-78, 97, 122; (611) 89 Soda, S.-i. (8) 142 Soga, 0. (4) 39; (611) 199 Sohar, P. (8) 71 Solladie, G . (4) 25 Solladie-Cavallo, A. (61) 34, 35 Somers, T.C. (9) 13 Somfai, P. (5) 53 Song, Y.H. (2) 2; (4) 149 Sono, S. (611) 96 Sonoda, N . (1) 24; (2) 127; (3) 218; (4) 222; (5) 6; (6ii) 14, 188, 275, 281-283 Soto, J.L. (8) 43 Soucy, C . (3) 323 South, M.S. (3) 190 Spadoni, M. (611) 258; (8) 3 Spaltenstein, A. (3) 403 Sparks, M.A. (2) 192; (611) 137 Spaziamo, V.T. (5) 96 Spears, G.W. (2) 162; (611) 11 Speckamp, W.N. (1) 92; (5) 43; (611) 144 Spicer, L . D . (3) 472; (5) 50, 51 Spichiger, S. (6i) 47, 48 Spielberger, C. (3) 80, 249 Spies, G.H. (61) 32 Spiessens, L. (5) 54 Spreafico, F. (3) 60 Springer, J.P. (3) 268, 334 Spunta, G . (8) 144, 146 Srebnik, M. (2) 53; (4) 1; (6ii) 98, 100, 111, 112 Srikrishna, A. (8) 9 Stach, H. (3) 202 Stamm, H. (8) 102 Stancher, S. (3) 353 Stanforth, S.P. (4) 217 Stang, P.J. (1) 93, 105; (3) 118 Stasi, F. (8) 45 Staunton, J. (611) 9 Stavber, S. (4) 169 Stavropoulos, G . (3) 458 Steckhan, E. (4) 226 Stefani, H.A. (2) 128 Steglich, W. (3) 390
General and Synthetic Methods Stein, H. (3) 429, 450 Steinauer, R. (3) 468 Steinman, M. (3) 469 Sterzycki, R.Z. (3) 178 Stetter, H. (3) 128 Stevens, R.V. (9) 38 Stevenson, P. (4) 170 Stewart, L.H. (4) 166 Stieltjes, H. (8) 48 Still, W.C. (2) 162; (611) 11 Stille, J.K. (1) 69, 108; (2) 54; (3) 239, 346, 381; (61) 65, 86; (611) 200, 209 Stokker, G . E . (3) 337 Stokkingreef, E.H.M. (3) 420 Stolte, M. (3) 80, 249 Stone, C . (1) 66 Stoodley, R.J. (3) 175 Stork, G . (3) 271; (4) 129, 130; (611) 185; (9) 24, 54-56 Streckham, E. (611) 248 Street, S.D.A. (9) 43, 44 Strijtveen, B. (4) 220 Strom, P. (3) 365 Stucky, G. (4) 90 Studabaker, W.B. (61) 9; (7) 1 Sturtz, G. (2) 64; (7) 48 Stutz, A. (5) 26 Su, W. (2) 74; (3) 299; (7) 37, 38; (9) 68 Suama, M. (2) 199; (3) 217; (4) 203 Suarez, A.R. (4) 192 Suarez, E. (611) 276 Subramanian, L.R. (4) 162 Subramanian, P.K. (3) 403 Suda, K. (611) 211 Sudhakar, A.R. (5) 57; (6i) 42 Suemune, H. (3) 158; (7) 31 Suetsugu, Y. (3) 316 Suga, S. (611) 229 Sugden, J.K. (8) 80 Sugimoto, A. (2) 104 Sugimoto, H. (3) 356 Sugimoto, T. (8) 132 Sugimura, T. (3) 34 Suginome, H. (2) 92; (3) 322 Sugita, N. (3) 49, 219 Sugita, T. (2) 199; (3) 217; (4) 203 Sugiura, T. (1) 77 Sugiyama, T. (4) 215 Sugumi, H. (3) 127 Sukata, K. (5) 68; (6ii)
160 Sukenic, C . N . (3) 11 Sullins, D.W. (9) 66 Sumiya, T. (611) 201 Summersell, R . J . (1) 116 Sunami, M. (2) 102; (4) 121, 203 Sunderbabu, G. (8) 9 Surber, B.W. (1) 93 Surendrakumar, S. (8) 57 Sutherland, R . G . (3) 187 Sutton, K.H. (6i) 5, 53 Sutton, P . A . (3) 460 Suzuki, A. (1) 16, 116; (4) 176, 243; (611) 96, 113, 114 Suzuki, H. (2) 117; (3) 55, 437; (5) 61; (611) 5, 71, 188, 280 Suzuki, K . (1) 23, 54; (2) 48, 182, 183; (3) 352; (4) 64, 195; (6i) 64; (611) 70; (9) 60 Suzuki, M. (611) 201 Suzuki, T. (3) 256; (611) 271; (8) 4 Svirskaya, P.I. (3) 469 Swain, C.J. (9) 42 Swenton, J.S. (3) 296 Switzer, F.L. (9) 30 Sworin, M. (7) 34 Szabo, J. (8) 71 Szajam, B. (5) 99 Taber, D.F. (2) 14; (3) 181, 331; (4) 155 Tabuchi, T. (1) 7, 45, 78; (4) 41; (61) 59; (611) 196 Tachdjian, C. (3) 139 Tachizawa, 0. (3) 419 Taddei, M. (1) 67, 83; (4) 85; (611) 133, 135, 190; (8) 30 Tagami, K. (1) 29; (611) 259; (8) 134 Tagawa, H. (4) 39 Tagliavini, E. (3) 302; (4) 87 Taguchi, T. (1) 112 Tai, A. (3) 34 Tait, B . D . (1) 9; (611) 164 Tajima, T. (3) 133 Takacs, B.E. (8) 34 Takacs, J.M. (7) 16; (8) 34 Takagishi, S. (2) 171 Takahashi, A. (1) 29; (611) 259 Takahashi, H. (3) 134,
Author Index 219; (4) 23, 67 Takahashi, I. (7) 54 Takahashi, K. (2) 133; (3) 332; (6i) 28 Takahashi, M. (3) 117, 270 Takahashi, 0. (3) 29 Takahashi, S. (3) 310 Takahashi, T. (1) 70; (3) 238; (611) 124; (9) 20 Takahata, H. (8) 105 Takai, K. (1) 20, 34; (4) 239; (61) 75; (611) 152, 252 Takaki, K. (3) 338; (611) 156, 170, 242 Takamatsu, T. (8) 105 Takamine, K. (4) 114 Takanami, T. (611) 211 Takanishi, K. (611) 77 Takano, S. (3) 75, 117, 270, 352, 439; (6ii) 219; (9) 41 Takase, I. (611) 191 Takasugi, J.J. (6ii) 212 Takaya, H. (3) 5, 147; (4) 125, 126; (61) 11-13, 26 Takayama, H. (611) 71; (7) 56 Takayanagi, H. (3) 68 Takeda, A. (1) 2; (2) 36, 37, 105, 179; (3) 90, 91, 99, 135, 136, 150, 171, 185, 278, 293, 313, 319; (4) 26, 27, 32 Takeda, K. (3) 68, 464 Takeda, R. (4) 136 Takeda, T. (1) 46; (611) 192, 196, 244 Takei, H. (3) 327; (6ii) 171, 172 Takei, Y. (2) 67 Takemura, H. (7) 54 Takenaka, S. (8) 82, 83 Takeshita, K. (3) 218 Takeuchi, H. (3) 419; (8) 33, 133 Takeuchi, R. (4) 92 Takeuchi, Y. (4) 180 Taki, H. (3) 77; (4) 150 Takimoto, S. (3) 69 Takiyama, N. (4) 110 Takuwa, A. (4) 39; (6ii) 199 Tamaki, K. (3) 58 Tamao, K. (1) 23; (3) 343; (4) 6, 57, 194, 195; (6i) 64; (6ii) 150, 153, 169 Tamaru, Y. (2) 150; (3)
549
259, 260; (611) 86 Tambunan, U.S.F. (9) 4 T a m , C. (3) 24; (4) 96 Tamura, M. (2) 170; (3) 106, 200 Tamura, 0. (3) 436; (5) 15; (611) 256 Tamura, R. (5) 77 Tamura, T. (3) 214; (6ii) 242 Tamura, Y. (3) 237, 296, 436; (4) 91, 92; (5) 15; (611) 256 Tanaka, A. (3) 133 Tanaka, C. (8) 100 Tanaka, H. (5) 28; (611) 205 Tanaka, K. (3) 295 Tanaka, M. (3) 32, 172, 346; (61) 24, 65, 80-82; (6ii) 200 Tanaka, N. (3) 227 Tanaka, S. (2) 48; (611) 70 Tanaka, Y. (1) 31; (4) 4, 55; (611) 199, 264 Taniguchi, H. (3) 49; (4) 114; (61) 83 Taniguchi, M. (8) 29 Taniguchi, N. (3) 341 Taniguchi, Y. (3) 376 Tanikaga, R. (3) 214, 308; (611) 60 Tanimoto, S. (3) 176 Tanis, S.P. (8) 117 Tanner, D. (5) 53 Tarasco, C. (3) 302; (4) 87 Tarbin, J.A. (2) 158; (3) 253 Tardivel, R. (2) 120 Tarii, H. (5) 66 Tassone, B.A. (3) 378 Tata, J.R. (3) 334 Tavaniepour, I. (611) 258 Tay, M.K. (2) 106 Taya, K. (4) 209 Taylor, A.P. (3) 309 Taylor, E.C. (8) 26, 51, 52, 148 Taylor, N.J. (3) 263 Tehfm, A.K. (3) 328 Tendler, S.J.B. (3) 417 Teramura, D.H. (611) 128 Terao, K. (6ii) 274 Terao, Y. (8) 86 Terashima, S. (3) 162 Teratani, S. (4) 209 Terpstra, J.W. (4) 199 Terunuma, D. (3) 23 Tesch-Schmidtke, S. (4) 227
Testaferri, L. (6ii) 278 Teulade, M.-P. (611) 218, 222 Texier-Boullet, R. (3) 207; (611) 224 Theil, F. (3) 345 Theis, W. (3) 329 Therien, M. (4) 104; (611) 95 Thiebault, H. (2) 120 Thielert, K. (3) 51 Thielmann, M. (9) 29 Thielmann, T. (9) 29 Thierrp, H. (3) 431 Thierrp, J. (8) 99 Thies, R.W. (7) 92 Thomas, A.P. (4) 9; (611) 136, 156 Thomas, E.J. (3) 330; (4) 53 Thomas, S.E. (2) 143; (61) 31 Thompson, C.M. (3) 335; (611) 66 Thompson, M. (9) 23 Thompson, M.R. (611) 62 Thompson, N. (3) 78 Thorn, D.L. (1) 73 Threadgill, M.D. (3) 417 Thurkauf, A. (7) 78 Thurston, D.E. (5) 93 Tiecco, M. (6ii) 278 Tietze, L.F. (7) 32 Tingoli, M. (611) 278 Tisdale, M.J. (3) 417 Tius, M.A. (2) 178; (4) 45; (611) 41 Toda, F. (8) 142 Todsen, W.L. (9) 66 Togo, A. (611) 192 Toi, H. (4) 4 Tojo, G. (9) 36 Toke, L. (5) 99 Tokles, M. (2) 185 Tolle, R. (3) 415 Toms, M. (8) 113 Tometzki, G . B . (3) 110; (61) 41 Tominaga, Y. (1) 63; (2) 40; (611) 129, 140, 145; (8) 68, 72 Tomioka, K. (3) 189; (4) 7, 64-66; (61) 25; (6ii) 76; (7) 54 Tomita, S. (3) 117, 270 Tomlinson, G.D. (1) 25; (4) 238; (6ii) 252 Tomooka, K. (3) 352; (9) 60 Tordeux, M. (4) 48 Torii, S. (2) 26, 149, 171; (5) 27, 28; (6ii)
550
205 Torii, T. (5) 48 Toro, J.L. (5) 40; (9) 32 Toshima, H. (9) 70 Toshimltsu, A. (611) 274 Toupet, L. ( 5 ) 34; (8) 90, 91 Tour, J.M. (1) 72 Toussaint, 0. (61) 57 Towson, J.C. (611) 258 Toyoda, J. ( 5 ) 21 Tranchepain, I. (3) 407 Traynor, J.R. (61) 46 Treichel, P.M. (61) 49 Trombini, C. (3) 302; (4) 87 Tromel, M. (3) 7 Trometer, J.D. (4) 102 Trost, B.M. (1) 72, 106; (2) 88; (3) 110; (5) 57; (61) 41-43, 63, 70, 71; (611) 4, 147, 241; (7) 45, 46, 93 Trost, M.K. (2) 83 Troupet, L. (3) 241 Trouve, B. (6ii) 185 Truchet, F. (611) 117; (7) 61 Tsai, C.-Y. (4) 242; (6ii) 268 Tsang, R. (2) 163 TSO, H.-H. (611) 72, 268 Tsubaki, K. (3) 237 Tsuboi, S . (3) 99, 135, 136, 171, 313, 319; (4) 32 Tsuboyama, K. (3) 68, 464 Tsuchihashi, G. (1) 54; (2) 182, 183; (3) 59, 137, 352; (4) 64; (5) 75; (9) 60 Tsuda, M. (3) 23 Tsuda, T. (2) 97, 98; (3) 224, 225; (611) 126 Tsuge, 0. (3) 416; ( 8 ) 82, 83, 84 Tsuji, J . (1) 56, 77; (2) 25, 93, 194; (3) 221, 250, 463; (4) 159; (5) 98; (61) 8; (6ii) 88; (9) 20 Tsukamoto, T. (6ii) 281 Tsumiyama, T. (2) 95 Tsuno, Y. (6ii) 152 Taunoda, T. (9) 4 Tsuruda, T. (2) 133 Tsuruta, T. (2) 174 Tsutsui, H. (3) 64 Tsutsumi, 0. (4) 14 Tufariello, J.J. (1) 75 Tuinman, A.A. (9) 67 Tuladhar, S.M. (4) 218;
General and Synthetic Methods
(611) 251 Tundo, P. (3) 208 Tung, R.D. (3) 410; (4) 100 Tunn, G. (5) 37 Tunney, S.E. (611) 209 Turner, E. (3) 403 Turner, M.K. (3) 280
109, 118 Uyama, H. (2) 46 Uyehara, T. (3) 94, 211
Vader, J. (2) 94 Vagberg, J.O. (7) 5 Vaid, B.K. (3) 82 Vaid, R.K. (1) 80; (2) 112; (3) 82, 243 Uccella, N. (5) 64 Vajna de Pava, 0. (4) 30 Valenti, E. (4) 213 Uchida, K. (8) 134 Valle, G. (2) 17 Uchida, T. (2) 133 Valoti, E. (3) 60 Uchida, Y. (3) 17; (61) Valverde, S. (3) 203; 14 (611) 54 Uchiyama, H. (3) 44 Van, T.T. (2) 81 Uda, H. (1) 29; (2) 79; (611) 259 van der Baan, J.L. (611) 155; (7) 19; (8) 48 Udodong, U.E. (3) 318 Ueda, H. (9) 3 Van der Eycken, E. (9) 7 van der Louw, J. (6ii) Ueki, M. (3) 473 155; (7) 19; (8) 48 Uemura, M. (61) 40 Uemura, S. (3) 219; (611) van der Plas, H.C. (8) 53 274 Vandevelde, 0. (2) 81 Uenishi, J. (1) 71; (9) Vandewalle, M. (9) 7 61 Van Horn, D.E. (1) 70; Ueno, K. (3) 416; (8) 83 (3) 238; (6ii) 124 Vankar, P.S. (2) 21 Ueno, Y. (8) 100 Vankar, Y.D. (2) 138 Uggeri, F. ( 3 ) 61 van Niel, M.N. (611) 57; Ugi, I. (2) 124 Ukai, J. (3) 228 (8) 110 Ukaji, Y. (3) 169 Vannoorenberghe, Y. (4) Ukita, T. (3) 355 70; (611) 89 Van Sant, K. (3) 190 Ulatowski, T.G. (3) 375 Ullah, G.M. (611) 253 van Zyl, W.J. (9) 67 Umani-Ronchi, A . (3) 302; Varapath, S . (6ii) 91 Vaultier, M. (3) 104; (5) (4) 87 Underwood, J.M. (1) 87; 2, 34; (6ii) 96, 117; (7) 61; (8) 90, 91 (8) 40 Uneyama, K. (2) 171 Vazquez de Migel, L.M. Uno, H. (2) 117; (611) 5 (611) 52 Upadhye, B.K. (3) 312 Vedejs, E. (1) 10; (3) Uphoff, J. (7) 20 349, 359; (611) 216; Ura, T. (3) 248; (4) 152 (9) 59 Urabe, H. (6ii) 77 Vederas, H.C. (3) 387 Urata, H. (4) 173, 174; Vederas, J.C. (3) 395 Vekemans, J.A.J.M. (3) (8) 76 Urpi, F. (5) 1; (6ii) 184 401 Usami, Y. (2) 60; (4) Venkataraman, S. (6111) 59 120; (611) 63 Venturello, P. (3) 208 Ushio, K. (3) 148 Verhoeven, T.R. (3) 35 Uskokovic, M.R. (9) 73 Vernon, J.M. (3) 174 Utaka, M. (1) 2; (2) 36, Veschambre, H. (4) 31 37, 105, 179; (3) 90, Vettiger, T. (3) 389 91, 135, 136, 150, 185, Viani, F. (3) 282 278; (4) 26, 27, 32 Vicente, M. (4) 108 Utimoto, K . (1) 13, 20, Vieira, P.C. (3) 14 25-27, 34, 59, 74; (2) Vijaya, M. (6ii) 265 144; (3) 266; (4) 179, Vilar, E.T. (4) 162 239, 240; (61) 75; Vilarrasa, J. (5) 1, 103; (6ii) 149, 152, 180, (6ii) 184 185, 202, 252; (8) 22, Villeneuse, P. (6ii) 194
Author Index
Villieras, J. (3) 210 Viret, J. (5) 83 Visentin, G. (3) 60 Vogtle, F. (3) 38 Volante, R.P. (3) 337 Voldrini, G.P. (3) 302 Vollhardt, K.P.C. (6i) 18 von Daacke, A. (2) 148 von Holleben, H.L.A. (2) 77 von Itstein, M. (3) 209 Vonwiller, S.C. (2) 75; (6ii) 228 Voss, J. (4) 227 Vougioukas, A.E. (5) 65; (61) 66 Vukicevic, R. (3) 255; (611) 271 Wacker, M. (3) 350 Wada, F. (2) 55 Wada, H. (3) 313, 319 Wada, I. (4) 127, 128 Wada, M. (1) 50; (4) 36; (5) 33; (6ii) 237; (8) 143 Wadman, S. (1) 51; (4) 106; (611) 79 Wadsworth, D.H. (3) 244 Waghela, M.B. (8) 80 Wagland, A.M. (8) 89 Wagner, E.R. (6ii) 163 Wakabayashi, S. (2) 102; (4) 121 Wakamatsu, K. (1) 25, 26; (4) 240; (6ii) 149, 180 Wakasa, T. (6i) 19 Wakefield, B.J. (3) 280 Wakharkar, R.D. (3) 312 Wakselman, C. (4) 48 Walker, J., jun. (3) 80 Walker, J.C. (61) 5 Walker, P.A. (3) 476 Walkup, R.D. (8) 21 Wall, W.F. (3) 280 Wallin, A.P. (3) 383; (611) 24 Walpole, C.S.J. (8) 128 Walsh, R. (8) 6 Walter, D.J. (3) 315 Wamprecht, C. (8) 66 Wang, A.-I. (4) 242; (6ii) 268 Wag, D. (611) 157; (8) 31 Wang, G. (611) 128 Wang, J. (3) 284 Wang, K.-T. (3) 428 Wang, K.K. (1) 43; (611) 134 Wang, S. (8) 131
551
Wang, W. ( 1 ) 1; (6ii) 19; (7) 51 Wang, 2.-M. (8) 2 Wanner, K.T. (5) 52 Ware, A.C. (3) 338; (6ii) 170 Wariishi, K. (2) 137; (3) 179 Warkentin, J. (8) 131 Warnock, W.J. (8) 56, 57 Warrellow, G.J. (9) 37 Warren, S. (3) 45; (4) 119, 237; (6ii) 231, 232 Watabu, H. (3) 278; (4) 27 Watanabe, K. (3) 169, 306 Watanabe, M. (3) 438 Watanabe, T. (4) 4 Watanabe, Y. (1) 68; (2) 101; (3) 72, 232, 359; (8) 62-64, 100; (9) 59 Watson, B.T. (2) 56 Watson, W.H. (6ii) 258 Watt, D.S. (3) 39; (611) 39 Wattley, R.V. (3) 337 Webb, K.S. (3) 354 Weber, A.E. (3) 398, 399 Weber, E.J. (4) 134 Weber, L. (2) 148 Weber, T. (3) 411, 423; (5) 16 Webster, F.X. (3) 15 Webster, N.J.G. (7) 12 Weedon, A.C. (7) 40 Wehmeyer, R.M. (2) 187; (611) 75 Wei, T. (2) 7 Wei, Z.Y. (8) 31 Weiberth, F.J. (2) 42; (5) 18 Weidmann, H. (1) 8 Weike, Z. (4) 118 Weiner, H. (4) 146 Weinges, K. (7) 28 Weinstock, L.M. (4) 47 Weiss, H. (6ii) 3 Weissenfels, M. (8) 54 Weitzberg, M. (2) 198; (3) 273 Welch, J.T. (3) 384 Welch, S.C. (2) 71 Wells, R.J. (3) 4 Wen, X. (6ii) 235 Wender, P.A. (61) 73, 74; (7) 63, 83, 84; (9) 11 Weng, L. (7) 8 Wenkert, E. (7) 23 Werbtizky, 0. ( 5 ) 58 Westling, M. (8) 96 Weston, J.B. (1) 114
Westwood, D. (611) 57; (8) 110 Westwood, S. (3) 349 Wetzel, J.M. (2) 152 Whitby, R. (1) 51, 86; (4) 106; (6ii) 79 Whitcombe, G.P. (2) 1; (4) 147 White, A.D. (2) 1; (4) 147 White, F.H. (9) 71 White, J.D. (9) 13, 47 White, K.S. (1) 90 Whitesell, J.K. (9) 74 Whitesides, G.M. (3) 18 Whitham, G.H. (611) 264 ,Whitney, R.A. (9) 40 Whittaker, M. (61) 53 Wickenkamp, R. (1) 32; (3) 220; (6ii) 186 Wicnieski, N. (9) 33 Widener, R.K. (611) 21, 120; (7) 50 Widmer, U. (3) 166 Wiemer, D.F. (2) 129; (611) 217 Wiley, M.R. (4) 56; (611) 199 Williams, A.D. (2) 126 Williams, D.J. (3) 330; (8) 17 Williams, D.L. (8) 73 Williams, D.R. (9) 51, 71 Williams, P.H. (8) 35 Williams, R.V. (611) 178 Wilmes, R. (3) 13 Wilson, K.D. (3) 383; (611) 24 Wincott, F.E. (9) 48, 49 Winders, J.A. (3) 280 Winkler, J.D. (3) 180 Winkler, T. (8) 135 Winterfeldt, E. (9) 29 Wipf, P. (3) 373 Wirth, D.D. (7) 53 Witiak, D.T. (3) 328 Wittman, M.D. (3) 236 Wolf, P. (3) 361 Wolfe, J.F. (3) 379 Wolfe, S. (3) 178 Wolfel, G. (5) 10 Wong, H.N.C. (3) 122 Wonnacott, A. (4) 68 Woodard, R.W. (3) 403 Woodward, P.R. (3) 184, 370 Woodward, R.B. (9) 57 Worth, L., jun. (8) 78 Wrigglesworth, R. (8) 128 Wright, C. ( 9 ) 23 Wu, H. (611) 284 WU, H.-J. (7) 68
552
General and Synthetic Methods
Yamamoto, T. (3) 152; (4) 225 Yamamoto, Y. (3) 25, 94, 168, 211, 227, 230, 289, 344; (4) 51; (611) 199, 203, 204; (8) 63, 64 Yamamura, S. (9) 8, 70 Yamanoto, A. (6ii) 130 Xia, W. (6ii) 235 Yamaoka, S. (4) 115 Xie, L. (6ii) 284 Yamasaki, Y. (1) 36 Xie, Z.-F. (3) 158; (7) Yamashina, N. (1) 16; 35 (6ii) 113 Yamashita, H. (3) 172; (5) 55 Yadav-Bhatnagar, N. (4) Yamashita, S. (5) 28; (6ii) 205 217; (5) 23; (6ii) 206, Yamashita, T. (2) 145 238 Yagi, M. (8) 142 Yamashita, Y. (61) 40 Yajima, H. (3) 470, 477; Yamasuki, T. (5) 85 Yamauchi, T. (3) 56-58; (6ii) 127 Yakura, T. (3) 296 (4) 6; (6ii) 169 Yamada, J. (3) 94, 230; Yamawaki, A. (3) 293 (6ii) 199, 203, 204 Yamawaki, K. (3) 248; (4) 152 Yamada, K. (2) 48; (3) 186; (6ii) 70 Yamazaki, N. (5) 12 Yamada, S. (2) 92; (3) Yamazaki, T. (3) 103, 152; (4) 124; (8) 105 356; (6ii) 71 Yamada, T. (1) 56; (3) Yanase, M. (3) 439 Yang, C.M. (9) 40 437; (5) 69, 98; (6i) Yang, F.Z. (2) 83 69; (8) 84 Yamada, Y. (3) 109, 348; Yang, J. (3) 382; (6ii) (4) 77, 122; (5) 38, 235 48; (6ii) 89 Yang, K.E. (1) 43; (6ii) Yamagishi, K. (4) 176 134 Yamaguchi, H. (1) 39; (5) Yang, S. (4) 210 102; (6ii) 148 Yankep, E. (4) 177 Yaozhong, J. (3) 416 Yamaguchi, M. (1) 7, 45, 58, 78; (2) 52; (3) 44, Yasuda, K. (3) 189 69, 131, 164, 240, 286, Yasukouchi, T. (9) 26 342, 376; (4) 41, 44, Yasumura, M. (6ii) 242 107, 133; (6i) 17, 59; Yeates, C. (1) 51; (6ii) (6ii) 196 79; (9) 43, 44 Yamaguchi, R. (6ii) 191 Yefsah, R. (2) 154 Yamaguchi, Y. (2) 46, 47; Yeoh, B.L. (4) 105 Yi, Q. (3) 55 (3) 195 Yamakawa, K. (2) 84, 103, Yoakim, C. (4) 104; (6ii) 104; (3) 212, 304; 95 (6ii) 142; (8) 19 Yokomatsu, T. (3) 445; Yamakawa, Y. (3) 72; (8) (8) 106, 115 62 Yokota, N. (3) 2 Yamamoto, A. (4) 225; (8) Yokoyama, S. (4) 76; 61 (6ii) 89 Yamamoto, H. (2) 189; (3) Yokozawa, T. (3) 160; 22, 228; (4) 3, 22; (611) 84 Yonashiro, M. (3) 14 (6ii) 122; (7) 57 Yamamoto, K. (2) 194; Yoneda, N. (4) 176 (6ii) 88 Yonemura, H. (3) 113, 116 Yamamoto, M. (2) 48; Yonezawa, Y. (3) 454 (611) 70; (7) 56 Yoon, M.S. (2) 31 Yamamoto, N. (2) 194; Yoon, N.M. (2) 27; (4) (611) 88 13; (611) 107
WU, J.-P. (4) 137 Wu, T.-C. (6ii) 75 WU, Y.-Y. (4) 142, 143 Wyatt, P.B. (3) 479 Wynberg, H. (4) 71; (6ii) 89 Wyvratt, J.M. (4) 47
Yorozu, K. (3) 416; (8) 83 Yoshida, E. (2) 157 Yoshida, J. (1) 38; (3) 81; (6ii) 175; (8) 44 Yoshida, M. (4) 196 Yoshida, T. (2) 98; (3) 224, 248; (4) 91, 92, 152; (6ii) 126 Yoshida, Z. (2) 150; (3) 237, 259, 260; (6ii) 86 Yoshifuji, M. (6ii) 2 Yoshii, E. (3) 324 Yoshikawa, S. (3) 17; (6i) 14 Yoshikoshi, A. (3) 318; (8) 4 Yoshioka, H. (1) 52; (2) 118; (4) 184, 188 Yoshioka, K. (3) 294 You, M.-L. (6ii) 268 Youn, J. (2) 124 Young, J. (2) 123 Young, R.N. (3) 35 Yu, C.F. (6ii) 268 Yugari, U. (4) 173 Yuhara, M. (1) 56; (2) 93; (3) 463 Yus, M. (2) 49; ( 3 ) 287; (4) 109, 193; (6ii) 16-18, 30, 40, 90, 152, 264 Zahra, H.P. (3) 317 Zahra, J.P. (8) 10 Zamarlik, H. (3) 261 Zamboni, R. (3) 35 Zamir, D. (4) 181 Zapata, A. (3) 102 Zappala, M. (8) 139 Zard, S.Z. (3) 139; (4) 208 Zawadzki, S. ( 5 ) 3, 82 Zeggaf, C. (3) 457 Zeiss, H.-J. (3) 403 Zettler, M.W. (3) 297; (8) 94 Zhang, J. (3) 382; (6ii) 235 Zhang, X. (3) 309 Zhang, Y. (1) 19; (5) 22; (611) 45 Zhao, S.H. (611) 258 Zhen, Z. (3) 213 Z ~ O U ,W.-S. (8) 2 Zhou, X.-J. (3) 10, 63; (611) 280 Zhu, J. (1) 48, 49; (611) 221 Zhuang, X. (2) 9; (4) 156 Ziegler, C.B., jun. (1)
Author Index 102 Ziegler, F.E. ( 9 ) 14 Ziehler-Martin, J.F. (3) 476
Ziffer, H. ( 4 ) 123 Zimmermann, G. ( 3 ) 350
553 Zinke, P.W.
( 4 ) 59; ( 7 )
17
Zoslona, A.T. (6ii) 232 Zschiesche, R. ( 3 ) 290 Zucco, C. ( 3 ) 52, 368 Zuobi, K. ( 3 ) 279
Zupan, M. ( 4 ) 168, 169 Zwanenburg, B. (2) 68 Zweifel, G. ( 1 ) 104; ( 4 ) 5
Zwick, B.D. ( 3 ) 452 Zwierzak, A. ( 5 ) 3 , 82
