Pergamon pll: S0040-4020(96)00154-8

Tetrahedron, Vol. 52, No. 24, pp. 8001-8062, 1996

Copyright O 1996 Elsevier Science Lid Printed in Great Britain. All rights reserved 0040-4020/96 $15.00 + 0.(30

T E T R A H E D R O N REPORT N U M B E R 402

THE BAYLIS-HILLMAN REACTION: A NOVEL CARBON-CARBON BOND FORMING REACTION

Deevi Basavaiah,* Polisetti Dharma Rao and Rachakonda Suguna Hyma School of Chemistry, University of Hyderabad HYDERABAD 500 046, India

Contents
1.

2. 3.

4.

5.

Introduction 1.1. Definition 1.2. Activated alkenes--Michael-type self-dimerization Intramolecular Baylis-Hillman Reaction Mechanistic Aspects 3.1. Rate enhancement 3.1.1. Hydrogen bonding 3.1.2. Substrate structure 3.1.3. Pressure, temperature, ultrasound and microwave irradiation Asymmetric Baylis-Hillman Reaction 4.1. Chiral activated alkenes 4.2. Chiral electrophiles 4.3. Chiral catalysts 4.4. Chiral solvents 4.5. Optical resolution of Baylis-Hillman adducts 4.6. Masked acrylate approach to chiral Baylis-Hillman adducts Synthetic Applications 5.1. Synthesis of stereodefined alkenes 5.1.1. Stereoselective synthesis of [E]/[Z]-allyl halides and sulphides 5.1.2. Reactions of allylic acetates, halides and sulphides 5.1.2.1. Carbon nucleophiles 5.1.2.2. Hydride as nucleophile 5.1.2.3. Heteroatom-based nucleophiles 8001

8002 8003 8005 8007 8008 8009 8009 8010 8012 8013 8013 8016 8018 8020 8020 8022 8023 8023 8024 8026 8026 8028 8029

8002

D. BASAVAIAHet al.

6. 7. 8.

5.1.3. Stereoselective rearrangements 5.1.3.1. DABCO catalyzed rearrangement of allyl esters 5.1.3.2. The Arbuzov allyl phosphite-allyl phosphonate rearrangement 5.1.3.3. Claisen ortho-ester rearrangement 5.1.3.4. Mitsunobu reaction with allylic transposition 5.1.3.5. Palladium(0)-catalyzed stereoselective carbonylation 5.2. Cycloaddition reactions 5.2.1. Diels-Alder reactions 5.2.2. Other cycloaddition reactions 5.2.3. Double cyclization of a-methylene-13-hydroxyalkanones 5.2.4. Cycloaddition reactions of ct-methylene-13-keto sulphones and esters 5.3. Diastereoselective reactions 5.3.1. Diastere0selective hydrogenation 5.3.2. Diastereoselective epoxidation and aziridination 5.3.3. Diastereoselective Michael-type addition reactions 5.3.4. Diastereoselective allylation of carbonyl compounds 5.4. Other applications 5.4.1. (+)-Sarkomycin ester Azetidinones and other lactams 5.4.2. Diazacyclophanes 5.4.3. Indolizines 5.4.4. Miscellaneous 5.4.5. Variants Conclusion Abbreviations

8032 8032 8032 8033 8034 8034 8035 8035 8036 8037 8038 8040 8040 8042 8043 8045 8047 8047 8047 8049 8050 8050 8051 8053 8053

1.

INTRODUCTION

C a r b o n - c a r b o n b o n d f o r m a t i o n is one of the most f u n d a m e n t a l reactions in organic chemistry. for the The d e v e l o p m e n t of e f f i c i e n t and s e l e c t i v e methods

c o n s t r u c t i o n of c a r b o n - c a r b o n bonds has b e e n and

continues to be

a challenging and e x c i t i n g e n d e a v o u r in organic synthesis. The forming Baylis-Hillman reaction. It reaction involves the is an emerging of carbon-carbon alkenes It has bond with all

coupling

activated

carbon e l e c t r o p h i l e s u n d e r the influence of a t e r t i a r y amine. the basic p r o p e r t i e s that an efficient synthetic m e t h o d

should have i.e.

it is selective (chemo, regio, d i a s t e r e o and enantio) , 1 e c o n o m i c a l in a t o m 2 count, requires m i l d c o n d i t i o n s and provides s y n t h e t i c a l l y useful multifunctional molecules. the good reaction has been This fascinating drawing increased describing r e a c t i o n was r e v i e w e d in still in its infancy. attention, as evidenced 1988 by by the Drewes and Roos, 3 w h e n the r e a c t i o n was number of publications Since then

various aspects of the r e a c t i o n

The Baylis-Hillman reaction

8003

including its application and cover the literature 1.1. Definition:

in the syntheses of

several

natural products. comprehensive

In this present endeavour all efforts have been

made to be

for the period 1988-1994.

The Baylis-Hillman reaction, be broadly defined as

containing carbon-carbon electrophiles influence bond between the

originating
that

from a

German patent,
formation alkenes

may
of a

"a r e a c t i o n

results

in the

u-position

of a c t i v a t e d

and carbon the

electron-deficient particularly

sp 2

carbon

a t o m under amine,

of a s u i t a b l e

catalyst,

a tertiary

producing

multifunctional

molecules"

(eq. I).

R' .XH 3o ornlne R ' ~ E W G

(1)

X'= O, NR 2

EWG = electron withdrawing g r o u p three components an activated

The Baylis-Hillman reaction involves alkene,

electrophile and tertiary amine. The research over the last decade Though Baylis and Hillman have originally used (i) pyrrocoline (2) and quinuclidine (3) Several activa-

has resulted in considerable expansion of the reaction in terms of all the three essential components. DABCO as catalysts, DABCO (diazabicyclo[2.2.2]octane)

(I) has become the catalyst of choice.

1 ted alkenes such as acrylic

2 esters, 5'6

3 acrylonitrile, 7'8 vinyl employed parafor-

ketones, 8-I0 in the

phenyl vinyl sulphone, II'12 reaction (Fig.l).

phenyl vinylsulphonate, 13 vinyl A variety of aldehydes such as

phosphonate, 14 allenic acid ester, 15'16 and acrolein 17 have been Baylis-Hillman aromatic, aliphatic, hetero aromatic, u,B-unsaturated aldehydes,

maldehyde (or formalin) and functionalized aldehydes have been employed as as electrophiles in the Baylis-Hillman reaction. 18-27 Recently, dialdehydes were also employed by the groups of Foucaud 28 and Caubere 29 in selective mono- and di- Baylis-Hillman coupling with methyl acrylate.

8004

D.B S V I H al. A A AAet

OH

R.~/COOMe
10

/~1~(Ot)2

OH

~1

O O o

,~CHO
to R

OH

OH R" ~ S03Ph

/I,,~/.OH/// ~ ~" ...if SOzPh I I 7

~ ~
"' OH 0

~R

O ~
CN 5

R ~

R'

FIGURE

The crotonic derivatives (methyl crotonate and crotononitrile) and vinyl sulfoxides that do not undergo Baylis-Hillman reaction at atmospheric pressure, were brought into the scope of the reaction at elevated pressures (eq. 2) .30'31

RCHO +

RF
=

/Ir/EWG OH DABCO ..~EWG II 9or10 K bor R 18-20h ~'R'

(2)

12

EWG EWG =

COOMe, I R

CN

i R

= R'= CH 3

Me H

SOFh

= Ph,

I R'=

The Baylis-Hillman reaction

8005

In addition to aldehydes,

~ - k e t o esters, 32-34

f l u o r i n a t e d ketones 35

and

aldimine d e r i v a t i v e s 36-38 have lis-Hillman reaction. reaction

been e m p l o y e d as e l e c t r o p h i l e s

in the Bayfor the Hill and of to the DABCO

Ketones were found to be inert u n d e r the usual conditions. the e.g. ketones into In

substrates However, the scope addition

Baylis-Hillman reaction at several

Isaacs have s u c c e e d e d in b r i n g i n g elevated pressures t e r t i a r y amines other

(Figure 2) .17,30

3 - h y d r o x y q u i n u c l i d i n e , 39

triethyl-

amine, 17 q u i n i d i n e , 3 ' 4 0 etc. have been used as catalysts

in special cases.

HO R'

WG
R=Me, Et

16

~ j~

J..( wG
NHZ
R

NZ

HO COOR'

Ref:36-38

o (cot)....-" Re,:32-34
R=oryl, olkyl 13

15 Z=tosyl, COOMe PPhz, S02Ph R=oryl HO R' k / ~EWG R

I I

R & R' = polyfluorlnoted groups

14
EWG = COOR, CN, CHO, COCH 3

FIGURE

1.2. A c t i v a t e d

alkenes

- Michael-type

self-dimerization:

In the absence of an added electrophile, as vinyl ketones, acrylonitrile, acrylic esters

the a c t i v a t e d alkenes
etc.

such as

t h e m s e l v e s act

electrophiles in our type

in these B a y l i s - H i l l m a n processes. vinyl ketones and the catalytic under

It was in fact D A B C O to

observed provide

l a b o r a t o r y that dimerization

acrylonitrile influence of

u n d e r g o Michael

c o r r e s p o n d i n g dimers 17 and 18

(eqs. 3 & 4)~ la'b

8006

D. BASAVAIAH et al.

0 (3)

17 R = aryl, alkyl

c"

DABCO N C ~ ~ C N
18

(4)

Subsequently, variety of (eq. 5).

Drewes

et

al. 42

have

reported

the

dimerization acid

of

functionalized

alkyl

acrylates and aryl

acrylates under the (19) The conditions.

influence of DABCO to obtain homo-esters of

~-methyleneglutaric

Methyl acrylate failed to dimerize under these

dimerization of ethyl and tert-butyl acrylates was also achieved under the influence of tris(dimethylamino)phosphine (TDAP) by Amri et al. 43

ROOC.,,,,,~ + j[~

COOR

DABCO

ROOC~COOR 0

(5)

R = phenyl, Recently H ~ Michael-t~e position of acrylate,

4-tolyl,

4-nitrophenyl, 44

CHMeCOOEt,

CHPhCOOMe,

et al.

reported a closely related process to the above the introduction of a substituent at under the the ~-

reaction i.e. and

~,~-unsaturated ketones using Michael acceptors such as ethyl ac~lonitrile phenyl vinyl sulphone, catalytic (DBU) using

influence of tertiary amine 1,8-diazabicyclo[5.4.0]undec-7-ene 1,3-dimethyl-2-imidazolidinone 0 WG DBU (DMI) as solvent at 185C 0

(eqs. 6 & 7).

(6)

18~C

DBU
+ 185 C

WG

(7)

EWG=COOEt, CN, SO2Ph

The Baylis-Hillman reaction

8007

2. In cases

INTRAMOLECULAR BAYLIS-HILLMAN REACTION and a c t i v a t e d a l k e n e a moieties are

where both electrophile

present in the same m o l e c u l e and are o r i e n t e d suitably, an

p o s s i b i l i t y for

intramolecular Baylis-Hillman reaction arises. Recently, Drewes et 45 al. carried out i n t r a m o l e c u l a r B a y l i s - H i l l m a n r e a c t i o n of 2-acrylyloxybenzaldehyde in presence of DABC0 in dichloromethane (eq. 8). But the and major obtained product 3 - h y d r o y m e t h y l c o u m a r i n in only 10% y i e l d

in this r e a c t i o n was a q u a t e r n a r y a m m o n i u m salt 20.

C/~o

DABCO CH2CI2

(8)

2O Previously the cases of catalyzed more ineffective. R o t h et ai.46 r e p o r t e d that an i n t r a m o l e c u l a r process and (2E)-7-oxooct-2-enoate in is In

both

(2E)-6-oxohept-2-enoate

e f f i c i e n t l y by p h o s p h i n e s rather than t e r t i a r y amines. (eq. 9), D A B C O and

the case of 6 - o x o h e p t e n o a t e

q u i n i d i n e were found to be

L i t h i u m q u i n i d i n a t e catalyzes the i n t r a m o l e c u l a r r e a c t i o n in

~?
the case of

COOEt Phosphine M e ,

COOEr

(9)

Phosphine = PBu3, PPhMez, P(i-Bu)MePh, (-)-Camp

7 - o x o o c t e n o a t e to produce the cyclic m o l e c u l e (eq. i0). Al-

though some of the c a t a l y s t s e m p l o y e d are o p t i c a l l y active no asymmetric i n d u c t i o n was observed.

appreciable

~ /

COOEtLi-Qulnidinote 23~

yield

Me,. .,0~ COOEt

(10)

8008

D. BASAVAIAHet al.

3. MECHANISTIC ASPECTS
Efforts have been expended to deduce the actual path of the reaction. efforts of the groups of Drewes, 3'39'45 Isaacs, 17'47 Kaye 48 and noteworthy. reaction Invariably, all the studies conclude that the sequence

The

Caubere 49 are Baylis-Hillman

is the outcome of an a d d i t i o n - e l i m i n a t i o n activated alkene and electrophile. and 'proposals, acrylate a plausible with

involving tertiary amine, of the experimental Baylis-Hillman i. influence of DABCO, tertiary amine

In the light m e c h a n i s m of under the

observations

coupling of methyl

benzaldehyde

as a model case, may be written as shown in the Scheme type n u c l e o p h i l i c "A", which addition of subsequently to produce DABC0) to the activated alkene enolate (methyl acrylate)

The reaction is initiated by the Michael

(e.g.

resulting in a transient makes a nucleophilic the zwitter ionic adduct after proton m i g r a t i o n The retrogradation reaction is

zwitter ionic

attack on the electrophile

(e.g. aldehyde)
of the

"B". The dipolar adduct B gives Fort et ai.49 Hoffmann

the final product tertiary amine. the overall the

followed by the e l i m i n a t i o n

studies of

point out that and Rabe

equilibrated(!) .31a'46

have even proposed "B" before

two zwitter ionic conformations elimination of DABCO 6 (Figure 3).

"B l& B~' for the adduct

v.,H~Me
Ph1~O

H~Me Ph" B

OH

+ ph.,~ COOMe
SCHEME 1

The ~Me
B

Baylis-Hillman reaction

8009

~{:)"'CHPh

<,~
BI FIGURE 3

MeOOC'C~h ~
B2

A l t h o u g h no

i n t e r m e d i a t e has so for 'A' and

b e e n isolated, 'B' is v e r y high.

probability In fact

for this

the i n t e r m e d i a c y of the species c o n s i d e r a t i o n is and Kaye.48 adduct order "B" is the kinetics

c o n s i s t e n t w i t h the results of r a t e - d e t e r m i n i n g step and the overall (eq. ii) or pseudo

k i n e t i c studies reaction (eq. 12). adduct follows

of Bode third-

F u r t h e r m o r e their

kinetic studies show that the f o r m a t i o n of second-order if the concenRecent studies "B". The is above accumu-

tration of t e r t i a r y amine is c o n s i d e r e d constant of Drewes et al. 45 also support the f o r m a t i o n of

m e c h a n i s m should be c o n s i d e r e d s p e c u l a t i v e until m o r e e v i d e n c e lated in support of it.

Rate = K o b s [ a l k e n e ] [ e l e c t r o p h i l e ] [ a m i n e ] Rate = K a [ a l k e n e ] [ e l e c t r o p h i l e ] where K a = K obs[30 amine]

3.1.

(11)
(12)

Rate

enhancement:

Generally,

the

Baylis-Hillman

coupling

of

activated

alkenes

with esters when neat

e l e c t r o p h i l e s c a t a l y z e d by DABC0 can take several weeks to evolve carried out at conditions. 3 As practical and high yields, higher room it is temperature desirable

[ ~ - h y d r o x y a l k y l a t i o n of a c r y l a t e fully] and is a very slow pressure process under

atmospheric

for any

synthetic process,

from both a

e c o n o m i c point of view,

to be a c c o m p l i s h e d r a p i d l y and with nature using In obvious option bonding, of

efforts have b e e n m a d e to circumvent this u n d e s i r a b l e The first and of catalyst of

of the B a y l i s - H i l l m a n reaction. proportions the addition, structure, effect

has b e e n tried on m a n y an occasion. such as h y d r o g e n

factors

substrate on

pressure,

temperature,

u l t r a s o u n d and m i c r o w a v e

irradiation

the rate of the

r e a c t i o n were

studied.

3.1.1. H y d r o g e n bonding: Drewes et al. 3'39'50

reported

that

the

rate

of

DABCO

catalyzed

u - h y d r o x y a l k y l a t i o n of methyl a c r y l a t e is e n h a n c e d by the

use of m e t h a n o l

8010

D. BASAVAIAHet al.

as solvent or this

using

3-hydroxyquinuclidine involvement

as a

catalyst and in case of hydrogen

wia

attributed Similar rate a-hydroxyRecently bonding in

enhancement

to the

of hydrogen bonding.

enhancement was also alkylation of Bode and Kaye have

observed by Bailey et al. 51 established the

methyl vinyl ketone using

3-hydroxyquinuclidine.

involvement of

rate acceleration affected by 48 effect. On the otherhand, position of

3-hydroxyquinuclidine

a small deuterium

the introduction of a hydroxyl group at the terminal catalyzed terminal It was shown t h a t the

alkyl acrylates on the rate of ~-hydroxyalkylation

by DABCO was studied in our laboratory. 52 for example, benzaldehyde the DABCO-catalyzed is complete in

hydroxyalkyl acrylates react faster than the corresponding alkyl acrylates reaction of 10-hydroxydecyl 6 days (78% yield) (eq. 14). acrylate with the conditions (eq. 13), whereas identical

reaction of decyl acrylate with same aldehyde under remained incomplete even after 12 days

0 OH 0 PhCHO ~i~O-/'~e CH2OHDABCO / L ~ O ' ~ B CH2OH + 6 doys Ph

(13)

O H

PhCHO i ~ " . O ~ a + '

CH3

DABCO //L~L. 12 doys Ph O/~'~8 CH3 70~ conversion

rate-enhancement of the

(14)

It is clear from these results and those of Drewes et al. 39 that hydrogen bonding does play some role in the Hillman reaction. BaylisSince nucleophilic attack of the dipolar enolate on the the hydrogen bonding can (i) by stabilizing the adduct's increase rate-enhancement: (which would

aldehyde is presumably the rate determining step, in two ways be responsible for the the tertiary amine acrylate adduct concentration),

(ii) and or by activating the aldehyde

(Figure 4).

Figure
3.1.2. Substrate structure:

A close look at the mechanism makes it clear that the groups attached

The Baylis-Hillman

reaction

8011

to the chromophore of the activated vinylic system are bound to exert some effect (acceleration/retardation) on the rate of the reaction depending on Recenttheir electron withdrawing or donating nature and steric features. ly Fort et ai.49 of acrylate esters. It is clear from their studies

studied the electronic effect on the rate of the reaction that functionalized aryl acrylor isopropyl Bode and Kaye 48 inductive effect. alkyl acrylates and (Scheme 2). than faster ethyl

alkyl acrylates react faster than simple reported that methyl acrylate reacts

ates react more readily than alkyl acrylates acrylate and attributed this fact to

electron-releasing

In our laboratory a similar observation was made in the case of ~-hydroxyalkylation of alkyl vinyl ketones. 9'I0

OH 0
Ph @ ~

X
0

X=F. CI. Br Ph

OH

COOAr

OH /~COOAr PhCHO /~"COOEt @ + 5h -3days DABCO 7 days Ph

COOEt

Ar = aryl
SCHEME 2

The degree of electrophilicity important. As one would expect, reaction more readily than aldimines,

of

the

electrophilic undergo the

component

is

aldehydes the

Baylis-Hillman During our reaction we activated

ketones or keto esters. Baylis-Hillman much faster with

search for fast reacting substrates for found that diethyl ketomalonate influence of alkenes. 33

reacts

Thus it couples with alkyl acrylates, DABCO to

acrylonitrile and methyl corresponding

vinyl ketone under the adducts in a few hours in THF (eq 15).

provide the

(0.5 h to 36 h) even when the reaction is performed

0 EtOOC .COOEt EtOOC,~COOEt+ ~EWG DABCOTHF H o ' ~ E W G

EWG = COOMe, COOEr, COOBu t , CN, COMe

(15)

8012

D. BASAVAIAHet al.

3.1.3. Pressure,

temperature,

ultrasound

and m i c r o w a v e

irradiation:

A significant

advancement

in r a t e - e n h a n c e m e n t and

of the

Baylis-Hillman effect

reaction was a c h i e v e d by processes are acrylonitrile,

Hill and Isaacs, 17'30'53 who s t u d i e d the p r e s s u r e and

of p r e s s u r e on this r e a c t i o n are h i g h l y effective. Thus,

showed that the B a y l i s - H i l l m a n c o u p l i n g p r e s s u r e s upto 2-5 K bar ~-hydroxyethylation of

h i g h l y s e n s i t i v e to

the D A B C O - c a t a l y z e d goes to

w h i c h takes 4-5 days at a t m o s p h e r i c p r e s s u r e to p r o v i d e the c o m p l e t i o n in 5 m i n u t e s (Scheme 3). and w h e n the

d e s i r e d product in g o o d yield, reactants are kept

at 2-5 K bar that

pressure ketones

A m o r e important In some better

outcome of these studies is

c r o t o n i c d e r i v a t i v e s were pressure. 30 processes were

brought into the scope of the r e a c t i o n cases they found that these p r e s s u r e

at 10 k bar accelerated

c o n t r o l l e d by the less r e a c t i v e t r i e t h y l a m i n e rather than DABCO. 17

OH CN
1 otto
4-5 days

MeCHO+ DABCO + ~'~"~CN

OH 2-5 K bar ~ C N 5 min

SCHEME

Recently,

Roos and

R a m p e r s a d h 54 have s t u d i e d the effect of

tempera-

ture and u l t r a s o u n d on the rate of D A B C O - c a t a l y z e d methyl acrylate. due to increase refluxing, sonication by gentle which may They have claimed that all that although is not

~ - h y d r o x y a l k y l a t i o n of the r a t e - a c c e l e r a t i o n

r e m a r k a b l e it is helpful w h e r e solid

reagents are involved.

T h e y also c l a i m that it is p o s s i b l e to achieve rate warming (43 C) of the r e a c t i o n m i x t u r e rather than formation of side p r o d u c t s and/or result in the

p o l y m e r i c materials.

Auge et al. nitrile with

r e p o r t e d that B a y l i s - H i l l m a n c o u p l i n g r e a c t i o n of acryloThey also n o t i c e d that (eq. 16) 55 a d d i t i o n of LiI/NaI further

b e n z a l d e h y d e c a t a l y z e d by D A B C 0 was g r e a t l y a c c e l e r a t e d with

water as a solvent.

e n h a n c e d the rate in aqueous m e d i a

CHO
+

OH
CN (16)

rt, 7-8h H20

Ph

The Baylis-Hillman reaction

8013

Bhat and

c o w o r k e r s 56

d e s c r i b e d that (eq. 17). for the Under

microwave normal

irradiation provides c i r c u m s t a n c e s acrylIt is

c o n s i d e r a b l e rate e n h a n c e m e n t hydes and a c t i v a t e d olefins amides are inert substrates

in the B a y l i s - H i l l m a n r e a c t i o n b e t w e e n aldeB a y l i s - H i l l m a n reaction. 40'57

w o r t h m e n t i o n i n g here that a c r y l a m i d e reacts w i t h 3 , 4 , 5 - t r i m e t h o x y b e n z a l d e hyde to p r o v i d e the c o r r e s p o n d i n g adduct in 40% radiation (eq. 18). yield under microwave ir-

Hill and Isaacs d e s c r i b e d the r e a c t i o n of adduct

acrylamide in only 5%

with acetone at e l e v a t e d p r e s s u r e to give the r e q u i r e d

y i e l d . 17
OH

RCHO

~[~.WG

10-40 mln
R = aryl, alkyl

mlcrowove

DABCO _

~EWG
R
(17)

; EWG = COOMe,

CN OH 0

0
H

MeO'~/CHO MeO" [ OMe

~
I I

NH 2

DABCO 2,.5 min

0Me
40%

(18)

4. ASYMMETRIC BAYLIS-HILLMAN REACTION

The B a y l i s - H i l l m a n u - h y d r o x y a l k y l a t i o n or ~ - a m i n o a l k y l a t i o n of actiusing electrophiles

v a t e d alkenes u n d e r the influence of t e r t i a r y amines such as aldehydes, p r o c h i r a l ketones, ~-keto

esters or a l d i m i n e s results a p o s s i b i l i t y for

in the c r e a t i o n of a new chiral center and there exists a s y m m e t r i c induction. Consequently,

efforts have b e e n e x p e n d e d to d e v e l o p reaction. chiral As in the case of i n f o r m a t i o n for an

an a s y m m e t r i c v e r s i o n of the

Baylis-Hillman the

any r e a c t i o n that affords chiral products, "asymmetric components research metric and Baylis-Hillman essential by reaction" can for the reaction. employing any one

lie

w i t h any one of the four

This had p r o v i d e d new avenues for of the four components, i.e.

a l r e a d y efforts have b e e n made to study the levels of asymelectrophile, t e r t i a r y amine or solvent (or a d d i t i v e ) ,

induction

a c t i v a t e d alkene,

in o p t i c a l l y active form. 4.1. Chiral a c t i v a t e d alkenes: So far only chiral alkenes. Probably, the acrylates easy have b e e n e m p l o y e d as chiral chiral a c r y l a t e s activated and the

a c c e s s i b i l i t y of

8014

D. BASAVAIAH et aL

easy removal of the chiral auxiliary from the products made this attractive. sulphones and their The use of other Quite activated a good number with and alkenes of
i.e.

approach

vinyl ketones, were such as

phosphonates

in optically active form has been hampered by chiral acrylates The first using DABCO good effect in asymmetric aldehydes. Baylis-Hillman

inaccessibility. mainly (1)-menthyl

prepared and were reactions, between catalyst.

employed to

a-hydroxyalkylation acrylate (21a)

attempt was made by Brown et al. 58 when they have carried out the reaction acetaldehyde The diastereomeric excess was only 16% (eq. 19).

0 DABCO
+ MeCHO (5 mol~)

OH
(19)
e

21a

16%

de

Subsequently, Hillman

in our laboratory, variety of (21a)]

assymmetric chiral

induction in the Baylis21a-21h [including the of (eq. 20) .40'59-61 The maximum

reaction of a

acrylates was studied the

(1)-menthyl acrylate This resulted in stereo and electronic

with aldehydes in

considerable

success and a better

understanding of

factors involved

reaction.

diastereomeric excess, the reaction of

70%, achieved in these

studies was in the case 0ppolzer's

acrylate 21h, derived from

chiral auxiliary, between 7-42%. stereomer in The chiral Baylisof DABCO by

with propionaldehyde. 62 Other chiral acrylates 21a-21g afforded the chiral Baylis-Hillman adducts with diastereomeric excess However, it was possible in many cases to 21i were employed in diastereomerically pure f o r m v i a preferential acrylates 21h and the under Hillman reaction with Jensen and Roos. 63 various aldehydes ranging major obtain the

crystallization. the influence

diastereoselective

COOR* RCHO + ~
21a-i

OH DABCO R ' ~ COOR~

(20)

Ph
R =

OPh

ONO2

TheBaylis-Hillman reaction

8015

CHtPh

CH2Np

PK 2
h

(cyC6Htl 2

Bn2

Later, Gilbert et al. 64 obtained similar results in the (1)-menthyl acrylate with a variety of aldehydes at A remarkable improvement Thus in the levels of asymmetric reactions at ved by these workers by performing the (1)-menthyl acrylate at 7.5 K bar under the influence of atmospheric excess the pressure

reaction

of

atmospheric pressure. induction was elevated achiepressures. benzaldehyde Baylis-Hillman reaction at and diastereomeric

pressure reacts with corresponding whereas the (8.5 K bar), same

DABC0 to afford the (100% de), the provides

adduct as a single diastereomer (Scheme 4).

adduct with only 22%

At elevated pressures react with

p-tolualdehyde

p-ethylbenzaldehyde corresponding excess respectively.

(1)-menthyl acrylate (-)-nopyl and

(21a) to provide the acrylates

Baylis-Hillman adducts with 87% and 94% diastereomeric (-)-Bornyl, 8-phenylmenthyl

were also employed by these workers with reasonable success.

~O

OH DB O AC
PhCHO + 21o Ph 1 otm 7 . 5 K bur

DABCO

~
100%

OH
Ph

Z2% d e

de

SCHEME

The acrylate 21j, 65-67 derived from

(R)-(+)-pantolactone,

was treated

with a variety of aldehydes under the influence of DABC0 to study the diastereoselectivity ies respectively, in the reaction. Except for benzaldehyde and chloral, which gave conventional adducts methylene-l,3-dioxan-4-ones (22) with 2 and 48% diastereomeric puritexcess (78-87%) believed

all other aldehydes gave the corresponding 2,6-dialkyl-5(23) with high diastereomeric (10-39%). These products are

but with low enantiomeric purities

to have arisen as delineated in the Scheme 5.

8016

D. BASAVAIAH et

al.

~'J~.COOR ~ 21j
I RCHO

RCHO(excess) DABCO

DABCO OH R , ~ COOR+
22 R = Ph, CCI 3
78-87% de R

0
R =

J
23

R = Me, Et, i-Pr, Bu, c-C6Hll

SCHEME 5

Recently, pheric pressure, coworkers. 68 best result

8-phenylmenthyl

acrylate

(21k)

was

employed in

Baylis-

Hillman reactions,

with a variety of aldehydes catalyzed by DABCO at atmosinduction by Drewes and 21k gave the the acrylate

to study the levels of asymmetric (eq. 21).

The reaction between chloral and (70% de)

+ CCI3CHO
21k 4.2. Chiral electrophiles: Of the various

DABCO

0 OH h~~~..
70%
de

CCI3

(21)

electrophiles only The

aldehydes have been

employed in

optically active form thus far.

diastereoselectivity

in the Baylis-

Hillman reaction of several racemic and non-racemic studied. For example, and

aldehydes with methyl reacts with both either

acrylate and methyl vinyl ketone under the influence of tertiary amine was (S)-O-(methoxymethyl)lactaldehyde methyl vinyl ketone (3HQ) predominating under the Both to afford (eqo 22) .69 methyl acrylate influence of of

DABCO or 3-hydroxyquinuclidine with the anti-isomer

mixtures of diastereomers these tertiary Similarly (S)with methyl

amines provided more or less the same 3-benzyloxybutyraldehyde

diastereoselection.

reacts under the influence of

DABCO

The Baylis-Hillman reaction

8017

OCHzOMe
.

~J~

DABCO
or 3-HQ

MeOCH20

MeOCHzO
(22)

Me~CHO

OH
z70

0
: s30

OH

R = OMe,

Me

acrylate from

to f u r n i s h the

75.5:24.5

mixture was

of

anti- a n d
and three

syn-diastereomers
converted into an centers stereogenic

which

major

anti-isomer
derivative

separated

interesting (Scheme 6).

tetrahydrofuran 70

24 w i t h

0Bn

COOMe DABCO

OBn OH COOMe +

OBn OH
COOMe

1o
,,,,,CH2I Me" " O ' ~ COOMe 24
SCHEME 6

(R)-Myrtenal

and

isopropylidine ~-hydroxyalkylation diastereoselection

( R ) - g l y c e r a l d e h y d e 64 of in acrylonitrile these

were

employed

in t h e B a y l i s - H i l l m a n bar (eq. pressure. 23). The

at 5.5 a n d 4 K is v e r y low

reactions

CN

OH

R*--CHO+ ~

DABCO R ' ~ C N

(23)

, pressure

= 5.5 K bar,

d e = 16%

R*

X/.O~-H /~on
u-amino

pressure

= 4 K bar,

de = 23~

Several derived

non-racemic

u-dialkylamino acids were

and

u-(N-acylamino)aldehydes methyl acrylate under

from chiral

reacted

with

8018

D. BASAVAIAHet al.

the influence of DABCO to provide as mixtures of anti- and ranges from 55:45 to 88:12

the c o r r e s p o n d i n g The

Baylis-Hillman diastereomeric

adducts ratio

syn-diastereomers. (eq. 24) .71'72

. -NR'R"~ RAcHo

+n ~cOOMe DABCO~ ~
R

NR'R"
OH
major

NR'R" + ~.VJ~
COOMe R = ~ OH COOMe

(24)

minor
racemic and n o n - r a c e m i c complexes acrylate high (eq.25) and and orthoaryl-

Recently,

Kundig et al. 73'74 employed complexes

substituted b e n z a l d e h y d e imine t r i c a r b o n y l c h r o m i u m catalyzed B a y l i s - H i l l m a n the case of non-racemic adducts

tricarbonylchrominum reaction with methyl aldehydes,

(eq. 26) as e l e c t r o p h i l e s

in the DABCO In

acrylonitrile.

These reactions p r o c e e d e d with e x c e p t i o n a l l y Baylis-Hillman in >98% ee.

diastereoselection.

decomplexation

afforded metal-free

(25)

Cr(CO)5
R = OMe, CI; EWG = COOMe, CN

Cr(CO)~
>95% de

(26)

NTs

~_~___~"

Cr(CO)3

CKCOh
>95% de

4.3. Chiral catalysts: Currently, affect asymmetric similarities ment of a development reactions of catalytic asymmetric The chiral to are reactions has become used to the on a challenging area for organic chemists. catalysts

often called as "chemzymes" asymmetric Baylis-Hillman

owing to reactions,

they exhibit

in their functioning

enzymes. 75'76

Develop-

chemzyme

for catalytic

The Baylis-Hillman reaction

8019

the lines of Noyori's a welcome step. commonly of

Binap-Ru

complex 77 or Corey's

oxazaborolldlne,

, .

78

is

The most tertiary including participation the

used

catalysts amine the

in the B a y l i s - H i l l m a n of this the center is reaction course of created.

reaction predicts the

are the

amines.

The p r o p o s e d tertiary step in which In

mechanism chiral

throughout

reaction fate of

Consequently, it should optically and retroOur

the structure of the the transition be able to have to use bring been

tertiary amine should have a chiral discrimination. quinidine, catalysts as A

b e a r i n g on the variety the of

state(s). about

other words if the amine is chiral, cinchonidine in

active tertiary amines necine efforts reaction. All of these

such as quinine,

employed 3'40'64

Baylis-Hillman catalyst coupling

studies have met with only

limited success.

(6S)-l-aza-4-oxabicyclo[4.3.0]nonane as the chiral . . . . 40 also resulted in low enantloselectlvltles. Quinidine catalyzed of acrylonitrile with p r o p i o n a l d e h y d e provided

the best result thus produ40 cing the desired 3 - h y d r o x y - 2 - m e t h y l e n e p e n t a n e n i t r i l e in 20% ee (eq. 27).

EtCHO +

I~

CN

Ouinidine

. ~

OH

CN

(27)

20% e e

1,4-Diaz&bicyclo[2.2.2]octane amine as catalyst chiral in the utilized C2-symmetric

(DABCO,

1) is the most

used tertiary Hirama has

Baylis-Hillman

reaction.

Recently

2,3-disubstituted

1,4-diazabicyclo[2.2.2~

0 02N'~ CHO+I ~
lo (15 mole~)

OH 0 'I'H~,5 K bo~'r02N/J'~'II( ~I
47%

I1,
ee

(28)

R
la

I Ph
lh

PhCHz ~1~1,~T
lc

R = Bn,

aryl,

TBDMS,

TBPS

8020

D. BASAVAIAHet al.

octanes obtained

(la) as catalysts for the best and result

asymmetric

Baylis-Hillman reactions. the 15 mole% of the

They

(47% ee) for

reaction between p a r a - n i t r o catalyst other

benzaldehyde (la, R=benzyl)

methyl vinyl ketone

using

(eq. 28) .79'80

It is worth mentioning here that the

chiral derivatives of diazabicyclo(2.2.2)octane, Ib & lc,have been synthesized. 81,82 However, their application for asymmetric Baylis-Hillman reaction has not yet been reported. In fact most of the amines employed are loids and are not the products of molecular aforementioned studies are modest, commercially available alkamodelling studies. Whilst the

the prospects for the rational catalyst synthesis. 83

design are encouraging given the increased understanding of the stereo and electronic requirements of asymmetric 4.4. Chiral solwents: Except in cases where methyl vinyl ketone or diethyl ketomalonate are used, no solvent is the reaction required for the with was Baylis-Hillman processes. (+)-ethyl lactate to However, obtain of acrylonitrile acetaldehyde under the influence of

()-3-hydroxyquinuclidine the adduct with only 3% ee

carried out in (eq. 29). 64

MeCHO+ H~"cN

3-HQ (+)-Ethyl lactate

OH "~/CN Me" 1]
3% e e

(29)

4.5. Optical r e s o l u t i o n of B a y l i s - H i l l m a n adducts: At present, resolved the Baylis-Hillman adducts through resolution. with high enantiomeric purity Brown et al. 84-87 sulphones and kinetically ~-methylene-8enantiomeric was also by the are accessible only

~-methylene-~-hydroxyalkanoates,

aminoalkanoates wia homogeneous hydrogenation using chiral phosphine-rhodium catalysts. excess The recovered alcohols were obtained in >90% The (S)-Binap-ruthenium diacetate
wia

( e q . 30).

complex

employed as catalyst for the kinetic resolution of methyl methylenebutanoate group of Noyori. 88 (>99% ee at 76% conversion) Bailey
et al. made

()-3-hydroxy-2-

hydrogenation

an

attempt

to resolve Baylis-

Hillman adducts wia asyrm~etric Sharpless epoxidation. 89

The Baylis-Hillman reaction

8021

R
X = OH, NHCOOBut;

Cotolyst * R
EWG = COOMe,

EWG +

_..

EWG

(30)

SO_Ph

; R = alkyl, [Ru(S)-Binap] +

aryl

Catalyst*

= [Rh(R,R)-Dipamp]< approach was also

The

biocatalytic

shown

to

be

effective

for

the and

resolution of alkanones

Baylis-Hillman

adducts.

Thus,

pseudomonas AK lipase cata-

lyzed t r a n s e s t e r i f i c a t i o n results enantiomeric excess

of racemic

~-methylene-~-hydroxyalkanoates

in the p r o d u c t i o n (eq. 31). 90

of optically active alcohols with >95%

OH COR' PseudomonosAK
R R

OH COR'
+ ee R 95%

OAc COR'
(31)

~Ac
Hexone

R = alkyl, of acetates furnished (eq. 32). 91

R' = alkyl,

O-alkyl (PLAP) c a t a l y z e d hydrolysis and alkanenitriles excess

On the otherhand pig liver acetone powder the optically active alcohols

of racemic G - m e t h y l e n e - B - h y d r o x y a l k a n o a t e s

in 46-88% e n a n t i o m e r i c

OAc R~EWG
racemic

PLAP
buffer ether

OH ~EWG R
46-88% ee EWG = COOMe,

+
CN

OAc .~WG R

(32)

R = aryl;

Recently,

A d a m et al. resolved h y d r o p e r o x i d e s and pentanoate (HRP)

of racemic

3-hydroxy-2catalyzed

methylenebutanoate

by h o r s e r a d i s h p e r o x i d a s e

via e n a n t i o s e l e c t i v e 92 (eq. 33).

reduction

OOH R/~COOMe

HRP

OOH OH R/~.COOMe + R , ~ cOOMe

(33)

racemic R = Me, Et;

(S)
>99% ee

(R)

8022

D. BASAVAIAHet al.

Recently, zation using

the racemic acid 25 was resolved via d i a s t e r e o m e r the amine-diol 26 and the absolute

crystalliwas

configuration

i Ph ii) H+ Ph
()-25
OH

OH

CO~

ii)cryst.

H Ozhl/'~ (~IIIH 3
J i) NoOH ii) H +
OH

/ ~ /COOMe Ph" ~ "~,~C,MeOH

(R)

OH ph/~/COOBul ///~ 'H+

(R)
SCHEME 7

(R)- 25

assigned. 93 ponding

The optically pure acid esters

(R)-25 was converted

into the corres-

methyl and t-butyl

(Scheme 7).

4.6. M a s k e d a c r y l a t e a p p r o a c h to chiral B a y l i s - H i l l m a n adducts: Some important methods for chiral Baylis-Hillman reactions using the masked acrylate approach are described 94-97 in the following equations (eqs. 34-36).

OR' R/~CHO + Me2I ~ C O O R ' '

R = Me, n-hexyl;

1) LDA
2) Mel / DBU R

OR'
COOR" R

OR' COOR" OH
minor

OH
major

R' = CH2OBn , CH2OMe; R " (ref. 94)

= Me, t - B u

Banfi et al.

~%~,/OH R~COOUe

i) LDA O~. I + R'CHO ii) mCPBA R' =:OOUe

(35)

R ~ = aryl

R = H,

Me

Drewes et al.

(ref. 95,96)

The Baylis-Hillman reaction

8023

0 OH Tl'~"~ COOButi)BrMgBu R~ tii)RcHO COOBut iii)CoCO~ R = ethyl, n-butyl

Papageorgiou and B e n e z r a (ref.97) 5. S Y N T H E T I C APPLICATIONS

(36)

The Baylis-Hillman reaction tion of synthetic nitrile, organic

has been increasingly drawing the attenas it provides and versatile molecules The Seve(i.e. hydroxyl,
etc.)

chemists,

with a minimum of three functional groups ketone, sulphone or phosphonate, Baylis-Hillman adducts may therefore be organic transformations directed towards sis. Moreover, ive substrates various review. ral successful examples have already been the multifunctionality to examine the were

olefin and e s t e ~

a chiral center. control.

expected to

undergo a variety of studies are being in organic syntheof 1988

involving regio- and stereochemical reported and

utilizing these fascinating molecules diastereoand

of these adducts makes them attractenantioselectivites by Drewes in his

methodologies. reaction The

Some of the initial synthetic applications of the elegantly discussed focus on the developments some of

Baylis-Hillman

following discussion will mainly

which have appeared after the publication of this review. the aspects discussed by to have Drewes are also very briefly text and for easy continuity in the

However,

mentioned in order Synthetic (i) Synthesis (iii) diastereo-

understanding.

applications have been broadly divided into of stereodefined alkenes, selective reactions and (iv) miscellaneous.
alkenes:

four sections:

( i i ) cycloaddition reactions,

5.1 S y n t h e s i s The of many

of s t e r e o d e f i n e d

trisubstituted naturally pheromones,

olefinic moiety 98-I00 biologically macrolide antibiotics,

has been active

etc.

a regular The

feature as,

occurring

compounds were

such

terpenoids, adducts

Baylis-Hillman shown to be have been stereo-

~-methylene-~-hydroxyalkanoates,

in particular,

versatile precursors

of trisubstituted alkenes. (i) nucleophilic

Two approaches adducts into substitution (SN2')

developed for the conversion of the defined trisubstituted alkenes:

Baylis-Hillman

(SN2) of the

allyl bromides obtained from the Baylis-Hillman adducts; substitution with concomitant allylic rearrangement of the Baylis-Hillman adducts. The general reactions is described in the Scheme 8. strategy

(ii) nucleophilic of the acetates SN2 and SN2' for

8024

D. BASAVAIAHet

al.

/
Nu

'~-WG

t ", OH Ewo Ew:U

OAc

R~EWG
SCHEME 8

5.1.1.

Stereoselective
conversion of

synthesis of [E]/[Z]-allyl
methyl (7) into

halides and sulphides:

(27) and Z-allyl corresponding

The halides, HCA-PPh3, mann and

3-hydroxy-2-methyienealkanoates the

2-benzenesulphonyl-3-hydroxyalkenes

using a v a r i e t y of reagents such as NBS-Me2S, HBr-H~SO., NCS-DMS, z HI-H3P04, has been w ell documented. 5 , 1 1 , 1 8 , 1 9 , 1 0 1 Re c e n t 1 y H offBuchholz have explained the origin of s t e r e o s e l e c t i v e of methyl forma28 in the HBr-H2SO 4 treatment 3-hydroxy-2-

tion of allyl bromides

.o~.
MeOOC"~
N

.
"~

..8.
~ MeOOC ~
R

8r ~

H2~.O~ H

~.oo~ "t" ~
R Br

27

H,~,==:~COOMe. R~ xCH2B r
28

eoo
SCHEME 9

:H0

~.ooc~--K3
E

methylenealkanoates According to

(27) on the basis

of m o l e c u l a r

modelling

studies. 102 of

these workers,

the zwitterion D, arising

from p r o t o n a t i o n

The Baylis-Hillman reaction

8025

(C) followed by counter

b r o m i d e ion rotation

a t t a c k in a r o u n d the

Michael

fashion,

u n d e r g o e s a 120 (E)

clock-wise

central

carbon-carbon bond

rather than a

60 c l o c k wise

r o t a t i o n as the

COOMe g r o u p is required

sterically orientation

more d e m a n d i n g than the CH2Br group, for d e p a r t u r e of the leaving g r o u p of a [Z]-double b o n d (Scheme 9).

to achieve the

(H20) , thus r e s u l t i n g in

the formation

These a r g u e m e n t s are s u p p o r t e d by the fact that by CN causes loss of (eq. 37). OH [Z]-selectivity, I02 e.g. gives a 3:1 m i x t u r e of m e t h y l e n e p r o p a n e n i t rile

r e p l a c e m e n t of COOMe [E]-allyl b r o m i d e s

3-(fur-2-yl)-3-hydroxy-2[Z] &

HBr. , / O ~ C N H2S04 ~ "~Sr + ~ B r C N

Recently synthesis of Gruiec allyl and Foucaud I03 28 and have r e p o r t e d the b r o m i d e and the [Z]-isomers,

(37)

stereoselective of a corresponding the b r o m i d e s 29 [E]-isomer

bromides

29 via m i c r o w a v e i r r a d i a t i o n

mixture of silica gel s u p p o r t e d bromides 28 (EWG=COOMe)

copper(II)

B a y l i s - H i l l m a n adducts 27 and 5 in c h l o r o b e n z e n e were o b t a i n e d as pure (EWG=CN) were p r o d u c e d as m i x t u r e s of strongly predominating.

(eq. 38). While the allyl w i t h the

(Z & E ) - i s o m e r s

OH R~EWG
27 & 5

CuBr - Si02 R~2~/ Br 2 mlcrwove oven H/ ~EWG 28 & 29 R = aryl

EWG = COOSe ( 2 8 ) ,
CN

(38)

(29)

A similar r e a c t i o n of

Baylis-Hillman

adducts

27 w i t h b e n z o t h i a z o l e

OH W~ C00Me (BtzS)' 27

PPh3 R

/~s/Btz
30

COOMe

Me

MeMgBr R~COOMe
31

R = Me,

i-Pr,

n-octyl
10

SCHEME

8026

D. BASAVAIAH et al.

disulphide-triphenylphosphine

(30)

afforded in

the corresponding allyl quantitative useful acrylate (Scheme 10). 104

sulphides These derivatives

with

[Z]-stereochemistry subsequently

almost

yields.

sulphides were

converted into

(31) by treatment with Grignard reagents 5.1.2. R e a c t i o n s of a l l y l i c acetates, The allyl acetates, philes. halides or Hillman adducts undergo substitution stereoselectivity. nucleophiles, thiolate processes

h a l i d e s and sulphides:

sulphides

derived

from the

Baylis-

reactions with a variety with high

of nucleoregio- and

These processes have been shown to proceed hydride and heteroatom-based formation olefin. of

The various nucleophiles employed so far include carbon nucleophiles such as amines, These are trisubstituted products that Baylisresult in may be Wittig-type ion, bromide ion, triethyl phosphite etc. compounds with a In either case, major the

ions, phenolate result in the

olefinic moiety or a terminal attractive and Hillman adducts. considered reaction. 5.1.2.1. as this has been

one of the

applications of moiety

Out of these processes, attractive alternatives

those reactions to the well

the stereoselective

formation of a trisubstituted olefinic

known

Carbon nucleophiles:

The reactions In fact, eared the first

of

allyl acetates,

halides and sulphides derived

from

the Baylis-Hillman adducts with carbon nucleophiles have been well s t u d i e d reported use of the Baylis-Hillman reaction, after its discovery, emanated from the protocol utilization of this in the that appstereoten years laboratory of

Drewes and

dealt with the

selective synthesis of [2E]-integerrinecic acid a natural product with trisubstituted olefinic moiety. 5 Subsequently Drewes et al~ 01'I05-I09 have carried out stereoand regioselective addition of carbon nucleophiles to various allyl (32) via the reagents in derived from ethyl acetoacetate and malonate halides and allyl acetates. Amri and coworkers have prepared 2-methylenealkanoate with Grignard treatment of ethyl 2-acetoxymethylprop-2-enoate presence of copper the synthesis of (I) salts. II0 They have [2E]-alkenoates derivatives

extended the same strategy to 2-methylene-3-acetoxy-

(33) by treating OAc

nBu/1"~COOEt n'BuMgCl/LiCuBr=.~COOEt (n-Bu)2CuLiR'/~ COOF't

THF/-48C
32
R = H SCHEME 11 R = Me,Ph

Et20/-7~ c

~ B ~
33

The Baylis-Hillman reaction

8027

alkanoates w i t h d i k e t o n e s as esters 34

di-n-butyllithium in the

cuprate

(Scheme ii). K2CO 3

Iii

Use

of 1,31,5-keto

nucleophiles

p r e s e n c e of

provided

(eq. 39) .112

t~

0Ac

COOMe
+

3 Et ~ COMe E/COMe KzCO ~COMe EtOH/reflux H/~^~'COOMe

34

(39)

Bauchat et al. I13 have c a r r i e d out reactions of a c e t a t e s 35 with carbanions g e n e r a t e d f r o m 1,3-diketone, methyl c y a n o a c e t a t e or a nitroalkane

by treatment w i t h p o t a s s i u m c a r b o n a t e or provide t r i s u b s t i t u t e d olefins w i t h

p o t a s s i u m f l u o r i d e on alumina to These products were

[E]-selectivity.

s u b s e q u e n t l y t r a n s f o r m e d into useful 7-1actones and 6 - 1 a c t o n e s

(Scheme 12).

R~ k . 1

COOMe

CH2(COR')2 CH(COR,)2 K2CO3-AI20~ orKF'-AI203

OAc COOMe MeCH2NO.__2 R KzCO3-AIz03 35 or KF-AI203

,,~COOMe
CHMeNO2 I R=2-furyl

R=2-furyl, Ph

L
MeHOCH~
SCHEME

Me
12

Recently,

we have u s e d

G r i g n a r d reagents as n u c l e o p h i l e s and observ-

ed a r e m a r k a b l e reversal of s t e r e o s e l e c t i v i t y b e t w e e n esters and nitriles.

OH R/~ EWG AcCI/Py OAc R

~'R'
37

EWG=COOMe R"

EWG=CN
aryl 13

CN
major

~R'
38
minor

35,36
R, R' = a l k y l ,
SCHEME

8028

D. BASAVAIAHet al.

Thus

treatment

of

3-acetoxy-2-methylenealkanoates (36) produced

(35)

with

Grignard of

reagents p r o v i d e d (38) p r e d o m i n a n t l y

[2E]-alk-2-enoates (Scheme 13). 114

(37), while the similar

reaction

3-acetoxy-2-methylenealkanenitriles

[2Z]-alk-2-enenitriles

Very recently Heerden and coworkers I15 reported a convenient sis of m u l t i f u n c t i o n a l stereodefined dienes using Baylis-Hillman (39), derived from ~ , ~ - u n s a t u r a t e d OH aldehydes (eq.40).

syntheadducts

/~EWG+ R 39

,_.~,COOEt N~
R ~COOEt ~

~ ; ~ H'r'EWG
.,~1 <,,~COOEt
(40)

R
;

R,/ "COOEt
[E]

EWG = COOMe

R = Me, Ph ; R ! = Me, allyl 5.1.2.2.

EWG = CN

[Z]

Hydride as nucleophile:
converted into the u-methylene-B-aceand 2-bromomethyl-2-alkenoates [2E]-2-methylalkenoa18,19

Hoffmann and Rabe have successfully toxyalkanoates tes and 2 - m e t h y l e n e a l k a n o a t e s Recently we have s u c c e s s f u l l y nucleophile. I16 Thus, oates 35 with LAH:Et0H LAH:Et0H provided (i:i)

respectively by treatment with LiEt3BH.

used LAH:Et0H reagent as a source of hydride of methyl u - m e t h y l e n e - B - a c e t o x y a l k a n [2E]-2-methylalk-2(41) en-l-ols (36) with gave e x c l u s i v e l y

the treatment

40 while similar reaction of u - m e t h y l e n e - ~ - a c e t o x y a l k a n e n i t r i l e s [2Z]-2-methylalk-2-enenitriles

(Scheme 14).

OAc CH20H R/~-'~ " LAH-EtOH(1:1) WG LAH-EtOH (1:1 ) EWG=CN EWG=COOMe R

CN

40

35,36
R = alkyl,
SCHEME aryl

41

14 was amply 43 of demonstrated [Z]-nuciferol by the (Scheme

The

efficacy

of

this

methodology

synthesis of 15) .116

[E]-nuciferol

42 and a p r e c u r s o r

WG=COOMe

WG=CN

CN
42 SCHEME

15

43

The Baylis-Hillman reaction

8029

5.1.2.3.

Heteroatom-based nucleophiles:
substiThus [E]on [E]-allyl bromide 44 (R=Me) using thiolate ions.

Normant and coworkers I17 carr&ed out a series of n u c l e o p h i l i c tution reactions the reaction b e t w e e n bromide 44 and lithium p h e n y l t h i o l a t e

yielded the

'ph "%,
44 PhNH2 or I)PhNHMgCI
ii)H20

/02Ph
"SPh 45 NHPh sO2Ph 48
47

NoSMe /~02Ph L 45 + "SMe 46 20:80

4v
sulphide 45 and 45 exclusively. [E]-methyl discussed

SCHEME 16
But this sulphide 46 when the possible 45 p r o v i d e d a 20:80 mixture of sodium methylthiolate. for the observation. amide sulphide treated with mechanism

They have also

Similar reaction of 44 with aniline to give SN2 product Recently, on of aliphatic 47 in 78% yield

in excess or its c h l o r o m a g n e s i u m (Scheme 16). have carried out n u c l e o p h i l i c of these reactions NHR' ~,,./

gave a mixture of SN2 and SN2' products

47 and 48 which slowly equilibrate

H o f f m a n n and Buchholz

additiThe

and aromatic primary amines to allyl bromides (SN2 or SN2' process) In some cases both processes R ~ COOMe

28. 102

product d i s t r i b u t i o n be solvent dependent. R ~ COOMe

was found to

were found to be opera-

/ ~ - - - - " NHR'

KzC05

HzNR'

~'~Br 28

MeCN

K2CO~ Pet. ether

H2NR'

COOMe

I
I

R, R'= alkyl, aryl

R'= alkyl
R = alkyl' aryl

I
I

49 SCHEME 17

50

8030
rive. However, in

D. BASAVAIAHal. et
acetonitrile In contrast, the SN2 products were formed with high

regioselectivity. produced.

in petroleum ether,

the SN2' products were lactami(49 and 50) in

Thus obtained B-amino acid esters were saponified and

zed to yield novel ~-alkylidene and u-methylidene-B-lactams good yields (Scheme 17). 102 Sodium sulphite, and 53. The molecules phenylsulphinate

and carboxylic acid salts were used

as nucleophiles to produce the corresponding trisubstituted olefins 51, 52 51 and 53 are important synthons for orally active Renin inhibitor A-72517, and kijanolide respectively (Scheme 18). 118-121

No,so,
Ph

NoOACreflux / MeOH RA/_~,.COOMe or HCOOH / NEt3 MeCN I PhSOzNo L',,,OCOR" 53

L
"-s
51 03No

oq MeOH

R=Ph R'=Me
IR'=Et

R=R"=Me
A-72517 (Renin inl~ibitor)

. ~ 52

COOEt ~SOzPh
18
anion with

Top holf of Kijonolide

SCHEME
The reaction of acetoxybutanoate

t-butylperoxylate

ethyl

2-methylene-3(Scheme 19)

( e q . 41) and ethyl 2-bromomethylbut-2-enoate

were studied by Mailard and coworkers. 122 They found that both provide the

~
presence of

OAc

COOEt t-BuO0

,/~COOEt
~,. 54 OOBu t
Howeve~ the allyl the by

(41)

~-attack products 54 and 55 with low yields. polyethyleneoxide 400. 122

t-butyl 55 in

peroxide 55 was obtained in 45% yield when the reaction was carried out in Subsequently ester 56 molecule heating was converted into the benzene. 123,124 corresponding glycidic

OOBut ,/~COOEt
" B r

t-BuO0

~COOEt
55

benzene heot

C~OOEt
Me Me

56

SCHEME

19

The Baylis-Hillmanreaction
Treatment of ethyl thiol provided ethyl [Z]-2-benzylidene-3-bromopropionate

8031
with t-butylwhich

[2Z]-2-benzylidene-3-(t-butylthio)propionate acid (57). 125

was hydrolyzed and hydrogenated in presence of (S)-2-benzyl-3-(t-butylthio)propionic

chiral catalyst to produce This acid is useful

intermediate for inhibitors of renin and retrovirus protease. Ph

t - B u - - S . . . . . ~ ~'H

~COOH 57 The acetate 35 ing [E]-allyl (R=Ph) was stereoselectively Thus the converted into correspond 35 with (58) predominantly [E]amino compounds. treatment of acetate [E]-amine

either primary or secondary amines produced while the treatment of resulting azide 59 with PPh_/THF/H20 allyl amine 60 (Scheme 20). 126j
OAc

35 with sodium azide followed by reduction of the gave exclusively the primary

ph~ 35

COOMe

Me2NH
58

INoN3

Ph

--

COOMe

PPh3

Ph

COOMe

59 SCHEME 20

60

Recently, substitution

the acetates 35 and 36 were found to undergo a nucleophilic reaction when treated with magnesium bromide to produce

corresponding allyl bromides, [Z]-28 and [E]-29 with high stereoselecti127 vity. This reaction could prove to be an attractive alternative for the synthesis of [Z]-allyl bromides 28
OAc

(Scheme 21).

R ~Br
28

EWG=COOMe

R
35,36

EWG

EWG=CN

R/~/""Br CN
major

R " B r
minor

R = aryl,

alkyl 21

[E]-29

[Z]-29

SCHEME

8032

D. BASAVAIAHet al.

5.1.3. Stereoselectiwe The

rearrangements:
adducts, being reactive substituted allylic rearrangement

Baylis-Hillman

alcohols undergo various reactions involving stereoselective to produce stereodefined trisubstituted alkenes. 5.1.3.1. DABCO catalyzed

rearrangement

of allyl esters:
Manson transposition

During the mechanistic

studies of the Baylis-Hillman reaction,

and Emslie observed DABC0 catalyzed stereoselective allylic of 2-methylene-3-alkylcarbonyloxyalkanoates oxymethylalk-2-enoates (61) with high

to provide the 2-alkylcarbonyl 128 [E]-selectivity (eq. 42).

R

"'

0,sc0i,.F
reflux MeOlC 0 major

'

+ [Z]-isomer

(42)

61
R = aryl ; R' = Me, Et, CH=CH2, 5.1.3.2. The phosphites CH2CO2Et

The Arbuzov allyl phosphite-allyl

Baylis-Hillman on adducts 27 and

phosphonate
5 afforded

rearrangement:
the corresponding rearThe in the presence phosphonates

treatment with diethyl phosphorochloridite These phosphites phosphonates

of triethylamine. 64 and [E]-allyl

62 and 63 underwent the Arbuzov [Z]-allyl 65 respectively (Scheme 22). 129

rangement on heating to produce stereoselectively

OH R
27,5

[ Et,~N=

0P(0Et)2

] ' "~

~)EWG

(0Et)2

62,63

64 EWG=COOMe [ Z ] - m a j o r 65 EWG=CN [E]-major

R = alkyl, alkenyl, SCHEME 22

aryl

allyl phosphonates 64 and 65 are synthetically substituted from the synthesis 1,3-butadienes. Baylis-Hillman In fact, the was adducts 66

attractive

precursors 67 in

of the

allyl phosphonate efficiently trienes and

derived tetraenes

utilized

(Scheme 23).

of, stereochemically 26

pure substituted

The Baylis-Hillman reaction

8033

h,,,..,~~COOM" i)CIP(OEt)2 p w . " , ~ ~ cOOMe

ii)heot
66

OH

67

"PO(OEt)= I i)LDA
ii)iPrCHO COOMe

SCHEME

23

Recently produces

we

observed

that

the and

reaction

of

triethyl and

phosphite

with

3-acetoxy-2-methylenealkancates phosphorylmethylalk-2-enenitriles (Scheme 24). 130

3-acetoxy-2-methylenealkanenitriles [2E]-2-diethyl in high stereoselectivity

[2Z]-2-diethylphosphorylmethylalk-2-enoates respectively

Oc A

P(OEt)~/80C

R~EWG 35, 36
R = alkyl,

EWG=CN

R~CN + H~CN H/--~--PO(OEt)2 R/--~--PO(OEt)2

[El-major [Z]-minor
+

~P(OEt)3/80_ c E GC O e W =O M
aryl

H,~_~COOMe

R~
24

PO(OEt)2

R~COOMe H/--'~--PO(OEt)2
[E]-minor

[Z]-major
SCHEME

5.1.3.3.

Claisen ortho-ester rearrangement:

Recently

we have developed 69
via

stereoselective the 5 (eq 43) .131

synthesis

of

ethyl of

[4Z]-4-cyanoalk-4-enoates ester rearrangement methyl alkenoates observation

Johnson-Claisen

rearrangement

3-hydroxy-2-methylenealkanenitriles as mixture of

However,

Claisen ortho27 produced Similar with tri-

of methyl 3-hydroxy-2-methylenealkanoates [E]- and [Z]- isomers coworkers in

(eq. 44). 132

was also made by Drewes and

the Claisen ortho-

ester rearrangement of alkyl 3-hydroxy-2-methylenepropionates ethyl orthopropionate (eq. 45). 133

O H .,~CN R
5

CH3C(OEt)3 C HC O (o) 2 s O Hc t 14~Pc

R = alkyl,
aryl

H C Ot OE ~NCN R
[z]-69

(43)

8034

D. BASAVALM4 et al.

OH R COOEt H ~ .~COOMe CH3C(OEt)3 R C2HsCOOH(cot. H~~COOMe ) + 14~Pc 27 R = alkyl, a r y l OEt OH .~ EtO OEt EtCOOH t Phil, COOR [3.3] COOR

/~/CfM)Et
COOMe

(44)

(45) [Z]-major [E]-minor

.P

R = Me,

CHPhCOOMe,

CHMeCOOEt,

5.1.3.4. Hitsunobu reaction with a11ylic transposition: Recently, adducts 27 ducts. or C h a r e t t e and Cote I18 have o b s e r v e d that the B a y l i s - H i l l m a n conditions gave unusual pro[E]-

(R=Et), u n d e r M i t s u n o b u r e a c t i o n p r o d u c t s could be

These

s e l e c t i v e l y t r a n s f o r m e d into either 70 (Scheme 25).

[Z]-mono p r o t e c t e d 2 - a l k y l i d e n e - l , 3 - p r o p a n e d i o l s

OH ~COOMe Et
27

PPh3,DEAD E t / ~ O O M e + R'COOH,THF - 4 0 to OC COR'

aryl

OCOR' ~COOMe Et Traces

R t = alkyl,

R'--4-CeH'N02/

k'kk R'=mesltyl

",,,

[EI-7o

SCXENE e 5

[zl-7o

5.1.3.5. Palladium(O)-catalyzed stereoselective carbonylation: Y a m a m o t o and c o w o r k e r s 13'134 have studied the p a l l a d i u m ( 0 ) - c a t a l y z e d stereoselective c a r b o n y l a t i o n of the c a r b o n a t e s 71 d e r i v e d from 71 corres(EWG= p o n d i n g B a y l i s - H i l l m a n adducts 27, 5 and 8. While the c a r b o n a t e s

OCOOR' ~EWG R 71
EWG = COOMe, CN,

Pd(OAc)z-2PPh3 R ~ EWG CO, 15 h /~'COOR' ~-~Tr'S03Ph R = alkyl~ R I = Me, Et

(46)

The Baylis-Hillman reaction

8035

COOMe) the

gave the 71

corresponding the carbonate

[E]-alkylidinesuccinates exhibited 71 product (R=isobutyl,

predominantly (E/Z=1:6). gave

the On

carbonate

(R=isobutyl,

EWG=CN)

[Z]-selectivity EWG=SO~Ph)

otherhand,

stereo-

chemically pure 5.2.

[E]-configurated

(eq. 46).

C y c l o a d d i t i o n reactions: The a p p l i c a t i o n of the B a y l i s - H i l l m a n

adducts

as

hetero

dienes

or

precursors

of

dienes,

and dienophiles

for

the D i e l s - A l d e r

cycloaddition

reactions was initiated and expanded by the group of Hoffmann. 5.2.1.

D i e l s - A l d e r reactions:

In a series of reports Diels-Alder dimerizations

Hoffmann and of a v a r i t e y

coworkers of dienes

described 73-75,

the in situ
via

generated

stereoselective d e h y d r a t i o n with MsCI-DABCO-DMAP of the c o r r e s p o n d i n g B a y l i s - H i l l m a n adducts 27,72,7. 20'135'136 The e l i m i n a t i o n of water has always resulted in the exclusive formation of [E]-double bond. The dienes 75 g e n e r a t e d from adduct 7 (EWG = S02Ph) were r e a s o n a b l y stable and

OH

27,72,7 R = alkyl, aryl

73-75

76-78

EWG

COOMe COMe

(76) (77) (78)

5-10 2-4 I00

: 1 : 1 : 0

EWG/~~.,,.

S02Ph

79 ~'XR I
SCHEME 26

allowed and 74

full

characterization. 136 In contrast dimerized spontaneously had been in the The d i m e r i z a t i o n Stereoselectivity

the dienes under

73

(EWG = COOMe) conditions

i.e. para-

(EWG = COMe)

dehydration

(Scheme 26). selective.

highly

regioselective

formation of dimers However,

76 and

77 from

the dienes 73 and 74 was moderate while the dienes with regard to sulphonyl to roof like cyclohexene Recently, and alkyl groups. 136 ring (79) (Scheme 26). in all these dimeric products

75 always gave trans-78 the alkenyl group with respect

has always been endo o r i e n t e d

the first e n a n t i o s e l e c t i v e

synthesis of m i k a n e c i c

acid

(+)-

8036

D. BASAVAIAH et al.

(83),

a terpene dicarboxylic

acid in 92% enantiomeric

excess was achieved

in our laboratory. 137 ring in situ the (74% de) generated upon hydrolysis of

This was accomplished wia double stereodifferentiathe diesters 82a-c from (25-74% hexane de). followed The diester by

Diels-Alder dimerization of the chiral dienes 81 followed by

82c

recrystallization

hydrolysis 81a-c were adducts

furnished the

(+)-mikanecic acid in 92% ee.

The chiral dienes

from the corresponding optically active Baylis-Hillman with mesyl

80a-c wia dehydration by the treatment (Scheme 27).

ox

chloride-triethylamine

usc,

co

Me
80

NEt3
81

CC,.~OOH HO0 83

i)KOH ill) recryst. RO0 82

COOR~ *C/~'~

SOzNPr~z
a b

S02N(cyCsHt 1)
2 c

SCHEME

27

Earlier racemic

Hoffmann

and

coworkers

described

simple

synthesis

of

mikanecic acid

wia the in situ

Diels-Alder

dimerization of the

diene generated from t-butyl 2-bromomethylbut-2-enoate. 6'138 5.2.2.

Other c y c l o a d d i t i o n reactions:

Hoffmann 34 has achieved a simple synthesis of 1,3-butadiene dehydration (85) from the corresponding with MsCI-DABCO-DMAP from either (Scheme 28).

2,3-dimethoxycarbonyladduct 84 wia

Baylis-Hillman

this diene had been or acrylonitrile lidinoisobutene

The previous syntheses of 2,3-butanedione (4 steps; 23% yield) 139 The diene 85 undergoes cycloaddition reaction with pyrro-

(8 steps) 140 which are cumbersome. to yield the adduct 86.

an inverse electron demand Diels-Alder

The Baylis-Hillman reaction

8037

,,~,,,. COO+Me [~.- COOMe

DABCO

HO COOMe

./V~,.COOMe U,CI-DABCO
OMAP (cat)
84

COOMe

COOMe 85

85

-t-

rt

MeOOC" v
SCHEME 28 86

Weichert and Hoffmann 141 have synthesized the eudesmane precursor

90

wia an inverse electron demand intramolecular [4+2] cycloadditon

of the triene 89, generated in situ from the mesylate Hillman adduct 87 (Scheme 29) .
Me

reaction Baylis-

88

of the

~~
OAc

Me

OH

v~CHO

/~"S02Ph DABCO OAc 87 OAc S02Ph

MsCI.EtNiPr2 -2oc. 20 h

OAc

Me

OMs

Py.170 C OAc
88

S02Ph

Toluene Sealed tube Me

SOzPh

S02Ph
Me

89

90

l
EUDESMANE
SCHEME

29 butadiene-l,3-dicarboxylate 91

Oda

and coworkers have

synthesized

using Baylis-Hillman reaction as the in polymerization reactions. 142

key step

and utilized this molecule

ROOC~,~,,~COOR

91 5.2.3. Double cyclization of a-methylene-B-hydroxyalkanones: The Baylis-Hillman adducts 72 when heated in a high boiling aromatic intermolecular dehydrative double cyclization to

hydrocarbon, undergo an

8038

D. BASAVAIAHet al.

produce functionalized 6,8-dioxabicyclo[3.2.1]octanes (92) 143 (Scheme 30). However, the stereoselectivity in these processes was very poor. The 6,8dioxabicyclo[3.2.1]octane moiety constitutes the basic framework of a number of pheromones, e.g. frontalin, exo- and endo-brevicomins, u-multistriatin, etc. OH 0

R.~O

+ R ~

"~H20

OH O
72 R = H, Me, Et, l-Bu, CH2CH2Ph
SCHEME 30

92

5.2.4. Cycloaddition reactions of G-methylene-B-keto sulphones and esters: Synthetically attractive u-methylene-~-keto sulphones 9312 and ~OH 0

.~WG R

CrOa H2504,MezCO,H20
- 78 oc
R = alkyl, aryl ;

R~ E W G

(47)

EWG = SO2Ph (93) EWG = t-BuOOC (94)

methylene-B-keto esters 94144 were prepared from the corresponding BaylisHillman adducts via modified Jones oxidation procedure (eq. 47). These

PhSO~s02Ph OEt

P h S O ~
SCHEME

+ 31

~O02ph

The Baylis-Hillman reaction

8039

molecules processes

93

(R=Me) and 94 participate

in

variety

of

cycloaddition

(Scheme 31 and 32).

~ooh% ~x ~oo~ i~.~

MeCN,r-t 3-20h
94

tBUOORC~~

R=Et, The

n-Pr,

i-Bu, 93

CH2CH2Ph SCHEME 32 was efficiently 12

R=alkyl, utilized in

aryl the synthesis

sulphone

(R=Me)

of racemic frontalin 95

(Scheme 33).

PhS02~O + ~,~ HO 93

THF,7h PhS02 H ~

I
H
SO2Ph

4
95

78~

" ~o--~"o~

o--

SCHEME 33 Recently, hydrolysis Adam et al. 145 have achieved the synthesis of 3-isopropylBaylis-Hillman adduct This ~-methylenepropiolactone 2-methylenepropiolactone
via

96 from the corresponding

followed by 8-1actonization.

OH ~COOMe

OH ~ KOHC O O H i i ) i) T+ H~
96

ko

o 400 C -COz 98 SCHEME 34

~+
97

8040

D. BASAVAIAH et al.

96

was

utilized 8-1actones

as

an

equivalent with

to

isopropylallene of dienes the desired

in cyclic

Diels-Alder first alkenes the 98

cycloaddition spiro (Scheme 34).

reactions

a variety

to produce

97 and then on pyrolysis

Quite recently, cycloaddition

Kanemasa on the

and

Kobayashi 146 imines, while

carried out adducts 27.

1,3-dipolar The dipoles dipoles

anti-

reactions

Baylis-Hillman

employed are nitrile oxides and nitrile free form or as Lewis acid complexes. undergo
syn-selective

and are employed either in dipoles showed purity

The Lewis acid coordinated free isooxazolines

cycloaddition in r e a s o n a b l y

selectivities

but moderate.

Thus the adducts,

99 and pyra-

zolines 100 were obtained 35) .

high d i a s t e r e o m e r i c

(Scheme

/
~ - - Q , COOMe

Ph

N--NCOOMe R' COOMe

R , ~
OH +

R
R'-C~N-O

R
+ OH

R'-C--N-'N-Ph
OH

--%,..,,COOMe

R'~@~
OH 99

R R = Me, Et, Ph

27

Ph / ~--~.,,,, COOMe

100

OH

R l= Ph, 4-OMePh,
35

t-Bu

SCHEME

5.3. D i a s t e r e o s e l e c t i v e reactions: The B a y l i s - H i l l m a n substrates selectively. adducts, being chiral molecules, reactions can be suitable for a variety of reactions The d i a s t e r e o s e l e c t i v i t y epoxidation, that create chiral of several centers diastereo such as, homoadditions,
etc.

genous hydrogenation,

Michael

type conjugate

has been studied using these substrates. 5.3.1.

D i a s t e r e o s e l e c t i w e hydrogenation:

Hydrogenation formation of aldol catalyst alternative

of the

Baylis-Hillman purpose, chiral

adducts

4 and 6 If

results

in

the an 147

derivatives for the

of the type 101. enolate

an efficient

chiral

is d e v e l o p e d

this route could

addition

prove to be
to aldehydes,

to the conventional

which suffers

several disadvantages

(Scheme 36).

The Baylis-Hillman reaction

8041

OH OH R ' ~ COR'

R.~COR'
4,6

H2

syn-lOl
+ OH
R
/~COR'

oldol
reoctlon

RCHO+

~'0R'

R = alkyl

aryl

anti-101 SCHEME 36

R~ = O-alkyl, a l k y l

U t a k a and c o w o r k e r s 148 r e p o r t e d the f e r m e n t i n g Baker's yeast m e d i a t e d reduction of B a y l i s - H i l l m a n adducts 72 w h i c h p r o c e e d e d w i t h h i g h selection. and anti- p r o d u c t s were p r o d u c e d in 1:1.2 ratio (eq. 48). enantiosyn-

The s y n - d i a s t e r e o m e r s were o b t a i n e d w i t h >98% ee and the

OH 0
R R

nuO
. = R

OH 0
(48
.

72
R = Et,

>98% ee n-Bu, n-pentyl carried out

67-98% e e

Brown homogeneous using

and

c o w o r k e r s 84-87 of

have

the

diastereoselective 27 (X=OH, in R'=OMe) almost

hydrogenation

Baylis-Hillman as catalysts,

adducts which

Rh+-diphosphine

complexes

resulted

f o r m a t i o n of the a n t i - d i a s t e r e o m e r s . Chiral catalysts, such as 88 or [ R h ( N B D ) ( R , R - d i p a m p ) ] B F 4 8 4 ' 8 7 are e m p l o y e d to effect Binap-Ru(OAc) 2 kinetic r e s o l u t i o n (cf.4.5) . Subsequently, Y a m a m o t o et al. 37'38 and Sato 149 et al. carried out similar reactions on adducts 15 (X=NHCOOMe, R'=OMe) and 72 (X=OH, R'=Me) (Scheme 37).
OH O OH O

exclusive

91

: 9

R= Et )[Rh(COD)dppb~ R,=Me

NHCOOMe

OH

p h ~ , ~ COOMe E
94%

Btnap
Ru(OAc )2 R

~
R'

[Rh(dppb)]*

R ~ R ,
anti

de

anti R' = OMe

15, 27 & 72

X = NHCOOMe;

X = OH; R ! = OMe; R = M e , P h , 2 - f u r y l
SCHEME 37

8042

D. BASAVAIAH et al.

5.3.2. Diastereoselective epoxidation and aziridination: The B a y l i s - H i l l m a n selective molecules adducts 72 and 27 were found to undergo

syn-

epoxidation under Sharpless e p o x i d a t i o n conditions producing 102 and 103 respectively. 51'89'150 However, there was no reaction

OH / ~
R 102
R = Me,

OH

OH

COMeTBHP-Ti(OPrl)4 . ~ W G CHCI2,- ~ R 1C
72,27,5 i-Pr, IEWC=C N
Et,

TBHP-Ti(OPRI)4. ~ C O O R ' CHCIz._I~C R

103 RI= t-Bu, i-Pr

cyclohexyl

tTBHP-Ti(OPH), NOREACTION
SCHEME 38

with

nitriles

(Scheme (20-34%)

38).

The

epoxidation conditions the

was

found

to

be

less

stereoselective

under basic

(H202-NaOH or TBHP-NaOH). hydroxy esters 27 keto epoxides (R =

Sodium h y p o c h l o r i t e aryl) and nitriles

(NaOCI) 28 converts

5 (R=aryl)

into the c o r r e s p o n d i n g (R = Ph) and 48%

184 and

the acetoxy ester 35 into acetoxy epoxide 105 in which case the diastereoselectivity was found to be 68% (R= 4-CIC6H 4) (Scheme 39).

OR'

OAc

R 104 R = aryl

R'=H
; EWG = COOMe,

R 27,5,35
CN

R'-- OAc

R
105
4-CIC6H 4

R = Ph,

SCHEME

39

Lithium t-butylperoxide exclusively

was used for 106.

stereoselective While the free

epoxidation

of

sulphones 7 and their silyl derivative 108 as major products

alcohols gave

the syn-epoxides I07, the silyl ethers p r o d u c e d 151 (eq. 49).

anti-epoxides

TheBaylis-Hillmanreaction
OR' R / ~
7,106
7 (R = H )

8043

OR' SO2Ph LiOOBu R / ~ t

107
25

OR' SO2Ph + R / ~ , . ,
108
:

SOzPh

(49)

1 major

R = Me, n-Pr,

i-Pr

106 (R =Si i-Pr3) minor

Stereoselective aziridination of 3-hydroxy-2-methylene-4-methylpentanoate and its acetate using 3-acetoxyaminoquinazolin-4(3H)-one (Scheme 40) .152 is described H o w e v e ~ yields of the resulting aziridines are very poor.

Q MeOOC ./Nkk ~
R= OH R
.

HO,.,.~

MeOOC%/NX k
+
-

iPr

6:1

iPr Q M eOOq...///N~ AcO~

iPr
I

iPr. ~ O O M e
R= OAc MeOO~//~

O
+

AcO% iPr
SCHEME 40

9:1

5.3.3. Diastereoselective Michael-type addition reactions: Perlmutter and Tabone 153 carried out nucleophilic addition of benzylamine onto the adducts 27 which proceeded with modest diastereoselectivity

COOMe ~ R OR'
27,109

COOMe COOMe PhCH2NH2 Ph~ N H " R Phv N H ~ R MeOH g A :y S + anti OR' syn OR'
major
R = Me, Ph, a-Py ; R' = H,

minor
TBDMS

COOMe

~.

i)TBAF

H2

CO0 G

.-"

Ph , / ~ . _ _ ~ 0

TBDMSO
anti -110

OME,rt
SCHEME 41

OH

CH2CIz,HzO PTC

111

,~
OH

8044
in methanol to produce reversal

D.B S V I et al. A A AA H
the desired products as a The 4:1 separable mixture resulted in TBDMS ether a d d i t i o n becomes highly into into the correscataly-

of anti- and syn-isomers. Change of solvent to t e t r a h y d r o f u r a n a lowering and 109. of stereoselection. if the hydroxy is diastereoselective ponding azetidinone (z 99%) 111 converted transformed

Thus o b t a i n e d anti-amino ester 110 was (Scheme 41). The B a y l i s - H i l l m a n

adducts 27 also u n d e r g o Michael reaction with hydroxyester

the p h a s e - t r a n s f e r

zed d i a s t e r e o s e l e c t i v e vity was obtained

stabilized 112. 154

carbanion derived carried

from dimethyl malonate p r o d u c i n g out in acetonitrile

Good stereoselectiwere carried

in these additions,

especially

for the reactions

(syn:anti = 15-20:1).

When the reactions

MeOOC COOMe Ph MeOOC/~~ OH mojor + MeOOC COOMe

COOMe ~Ph OH KF 2"7 NoH + 18-Crown-6 CH2(COOMe) THF 2 MeCNor DMSO

MeOOC~ C O e OM
0 "/ ~0"

<Ph

MeOOC~ @
OH
minor 112

Ph

MeOOC~ C O e OM
0"" "0"
113 ~Ph

S C H E M E 42

out in tetrahydrofuran

using sodium hydride

as the base,

the lactones

113

were obtained as m a j o r products

along with small amount of 112

(Scheme 42).

C ~ MeOO
27

OH

t.BuPhzSiO CISiPh2Bu% MeO0 C ~ imidozole OMF

114

OH OH i)R[.HSnBu~ M eOOC',,,,,.,/~ +MeOOC,~ '" " PhMe,hv,20 C .=ii)HCI/MeOH R/ R"

116

i)KOH/MeOH/H20 il)ClSiMe~/NEt~
iii)CsH11CHO.TfOSiMe3(cot') iv)recryst, from pentone

R = t-Bu,

c-C6Hll,

n-C8H17

C6HII R~Bu~SnH PhMe,hv,20C

C6H 11
. .=

O
115

"%Me

0~"" Me

K2C03 MeOORO ~
MeOH

OH . =

SCHEME 43

117

The Baylis-Hillman reaction

8045

Giese et al .155'156 showed that the conjugate either the silyl ethers oxan-4-ones (R=Me) ethers as 117 proceeds major with 114 or high along free (115) derived from the corresponding stereoselection with 115 radical the minor after deprotection,

addition of radicals to Baylis-Hillman adduct 27 esters 116

2-cyclohexyl-5-methylene-6-methyl-l,3-di(Scheme 43). Thus the silyl

114 produced, products

the erythro-~-hydroxy

5-methylidene-l,3-dioxan-4-ones (>99% de). Similar derivatives (118)

yielded

threo-isomers whereas the only threo-8-hydroxy esters

on the corresponding 157 (eq. 50). silyl and

addition

(of Baylis-Hillman

adduct derived from acrylonitrile

phenyl vinyl sulphone)

resulted in low selectivity

OTBDPS
EWG

~
of alkyl radicals adduct

OTBDPS
t-BuI

~ W G

(50)

Bu~SnH

118 EWG =

CN,

SO2Ph
diastereoselective pure addition Baylis-Hillman (eq. 51).

Recently Kundig and coworkers 158 studied to racemic and

enantiomerically

(119) which afforded the syn-isomer as major product

OMe NHTs I

OMe NHTs

OMe NHTs +

bneev eznh~ ,
>98% ee

~
~k

( 1" 5)
anti 14%
>98% ee

(S)-(+)-119

syn 75%

~k

5.3.4. Diastereoselective allylation of carbonyl compounds: The allyl bromides 28 and 29 undergo Drieding-Schimdt reaction 159'160 producing lactones stereochemically defined ~-methylene-~,~-disubstituted-~-butyro161-163 (Scheme 44). 120

~Br
R, 0

COOMe

Br

R'CHO

29
Cr(ll)or Sn-AI R'

~~
0

Cr(ll)orSn-AI

syn-120
R & R i = alkyl,
SCHEME 44

anti-120
aryl

8046

D. BASAVAIAH e t aL

It was recently shown by Masuyama et al. 164 that adducts (allyl alcohols) can directly be converted butyrolactones (120) with high the catalyst (eq. 52).
R

the into

Baylis-Hillman a-methylene-y = as

diastereoselectivity

using PdCI2(PhCN)

HO COOR I/ PdCI2tPhCN) SnCI2 DM/-H20 R'

syn 120

(52)

RI ,
anti

O 120 minor
Ph ; R " = Me, Et

major
R = n-Bu, cyclohexyl, 4 - ( C O O M e ) C 6 H 4 ; R ~= Me,

n-Bu,

The allyl bromide 122 was extensively used in the synthesis of a-methylene-~-butyrolactones, 160 lactams 165'166 and several other compounds. 167 This ~-bromomethyl acrylate was prevously synthesized via routes that are either circuitous or low yielding. 168'169 The for Baylislarge Hillman reaction provides a simple and efficient procedure scale synthesis of allyl bromide 122 (Scheme 45) .23'24

HCHO+ //"~COOEt

~DABCO H O ' ~ ' ~ C O O E t

121
SCHEME 45

HBr-H2SO4or B r / ~ PBrs 122

C00t

[E]-AIIyI bromides the zinc or chromium(II)

44

were

employed by

Normant and coworkers 170 in allylation of alde-

mediated diastereoselective

SO2Ph Zn or Cr(;0
R 44 R = Me, n - P r , i-Bu

SO2PhOH R'
R 123 ; R' = alkyl,

SO2P OH h R'
R R

S02Ph OH R'

alkenyl,

aryl

SO2Ph OH
KH
""

R'
123
R'

IHF"
124
= Ph, SCHEME Pentyl 46

The Baylis-Hillman reaction

8047

hydes Some

to provide of these

syn-homoallyl into

alcohol

123 were

exclusively transformed, pure

or

predominantly. (after stereo-

syn-hydroxy-sulphones

chemical purification) tetrahydrofurans 124

diastereomerically

2,3,4-trisubstituted

(Scheme 46).

5.4. Other applications: The Baylis-Hillman compounds, such as, ethyl diazacyclophanes, 5.4.1. the

adducts were also ester of

employed
etc.

in the synthesis lactones,

of

()-sarkomycin,

lactams,

indolizines,

liquid crystals,

()-Sarkomycin ester:

Ethyl u-acetoxymethylacrylate mixed ester of elaborated, in accordance

was

employed acid

in 125,

the preparation which in turn ethyl ester

of was of

#-methyleneglutaric agent. 43

with Scheme 47, into

126, the

()-sarkomycin,

0 AcO'/~ COOEt LiCH2COOBt , ~ COOEt HPO(OEt)2 (/~OEt)2 u ~p~ tAcz 0 HO k'v/COOBut 125 0 ~ Et00C 126 /
SCHEME 47

an antitumor

~tOOC" v ~,COOBut INaH II 0 HCHO.(Et0)2P'~ Et00C"

0

.,.COOEt 121

5.4.2. A z e t i d i n o n e s and other lactams: Villieras et al. have synthesized ~-hydroxymethylazetidinones conjugate addition of (eq. 53) .171 Treatment acrylonitrile hydrazine gave 131. ed 2-pyrrolidines 129

127, via

primary amines to Baylis-Hillman adduct 121 of the Baylis-Hillman adduct 128, obtained from with amines produced 1,3,4-trisubstitutor methyl 130 and

and ethyl pyruvate, polyfunctionalized

(eq 54)~ 72 Similar reaction with hydrazine perhydro-l,2-pyridazin-3-ones exhibited no diastereoselection.

These reactions

HO/"'/ I I

COOEt

RNH 2
R=alkyl

MeOH , ~ ~ 0 reflux R
127

OH

(53)

121

8048

D. BASAVAIAHet al.

HO~ / M e
tOoc~CN + RNH2 R =

MeOH

Me HO~
u'~'w"
129 R

CN
(54)

I I

128

alkyl

HO~ /Me

O~CN H
130

M ~ CN H
131

Bittmann et al. reported the enantioselective synthesis of ilmofosine (132) analogue using Baylis-Hillman adduct 121173 as the starting m a t e r i a l

CH3OCH2

~
the

SC,eH33
0

O-P-OCH2CH2N(CH3) I 3

o132 Recently, lactones Perlmutter two steps a n d M c C a r t h y 21 h a v e using reported synthesis of the key

133 i n

Baylis-Hillman

reaction

as the

step

(Scheme 48).

MeO0

WG or oq. Borox

OH 133 EWG = COOMe,

SCHEME CN, 48 COMe

WG

Recently, methylcoumarin dimethylamine

Drewes
via

and coworkers 45 have synthesized Baylis-Hillman acrylate followed and methyl

3-dimethylaminoreaction by between of addition

DABCO-catalyzed

0-benzylsalicylaldehyde

and hydrogenolysis

(Scheme 49).

Previously,

3-(2-formyl-

phenoxy)methylcoumarin (134) was isolated in Hillman reaction between salicylaldehyde and cowokers. 174 OH

9% yield from the Baylisacrylate ester by Kaye and

ii)HNMe2

-~-

~OCH2Ph
49

Pd-C

"-0

SCHEME

The Baylis-Hillman reaction

8049

134 Foucaud and Brine successfuly alkanoates 175 50. into converted 3-aryl-3-hydroxy-2-methylene135 according to Scheme 3-arylidene-3,4-dihydrocoumarins

OH , ~
Ar

COOMeCI-'~-OH ~------~OH COOMe Z~tS~' C I ~ ~ / A r

HO
S C H E M E 50

CI "0 1 / ~ ~ 3 5

0 Ar

Ar = aryl

5.4.3. Diazacyclophanes: The acetate 137 of the mono adduct 136 upon reaction with TiC14 and zinc gave a diacetate 138, which in turn furnished the diaza[7,2-7,2]paracyclophane 139 when treated with aqueous ammonia (Scheme 51) .176 On the otherhand, the diacetate 141 of bis-adduct 140 on treatment with

OH

OAc

OHC"

136

OHC"

137

I TiCI4- Zn ~ C O O M e ~.~ ~.~c /COOMe

M,00c-f

<

"If

t_r__/

139

M e 0 0 C / Ac0~
S C H E M E 51

138

aqueous ammonia gave the diaza[7,7]paracyclophane pound. The diazacyclophane for 90h gave acetonitrile 176 52). diazamacrobicycle

(142) as a 143 in 98%

single 141 yield

comin

142 when refluxed with the

diacetate

(Scheme

8050
OH

D. BASAVAIAHal. et
OAc

COOMe

OH

OAc

141

loq NH 3

MeOO~COOMe MeCN MeOOC~~COOMe reflux. M.00c~>~ ~c00M. MeOOC~COOMe MeO0: ~ / N C O O M e ~

141
90h

143 SCHEME 52 5.4.4. I n d o l i z i n e s : Bode and Kaye 57'177 have synthesized zines 146 using the Baylis-Hillman carbaldehyde and activated alkenes Thus the methyl vinyl 'ketone.

142
several 2-substituted from indoliobtained acetates 146 pyridine-2acrylonitrile heated path.

adduct 144

such as acrylate esters, indolizines

corresponding

145 when

(120C)i provided the 2-substituted mal cyclization presumably proceeds

(Scheme 53). This ther-

(~cHo fEwo o~co

EWG = COOMe, CN, COMe

through an addition-elimination

~o,
WG
144

,c2o

,,
145

OAc

'2&

EWG
146 SCHEME 5.4.5. 53

_Aco

Miscellaneous:

Recently,

E1

Gaied

and

coworkers 178

have u t i l i z e d

121,

122

and

compounds derived from 122 in the synthesis of l-bromo-2,3-epoxy-2-ethoxycarbonylpropane and stereodefined B-bromo-~-substituted acrylates (Scheme 54). The same strategy was adopted by Calderon et al, in their approaches towards the synthesis of fimbrolides. 179

The Baylis-Hillman reaction

8051

X ~

COOEt Br2

X-~l~

COOEt Bose =

)),,h/,COOEt

lZl t 122 TBAF/H20

Br

COOEt

X = OAc,

F,

Cl,

Br, 54

I~ C H 2 C O O E t

SCHEME

Drewes et al.

have

described

simple esters

stereoselective (147) using

synthesis

of

2 -alkylidene- 4 - carboxyglut aric 180 adducts (Scheme 55).

acid

Baylis-Hillman

OH dceOH "COOEr l OCOCHzCO'Et LDA ... COOMe , ~ C O O M e DCC R/ ~ R

I I

MeOOC"

.,,~ R ~ OH v " COOEt

147

R= alkyl, aryl
SCHEME

55

Recently,

Baylis-Hillman adducts have been utilized for the synthesis important synthons for the synthesis of poly-

of aldehydes 148 and 149, ether etheromycin.181'182 I

Ph

.0 I ~'But

t-Bu--Si--0
" T "

CHO OTMS

Ph
148 Recently Baylis-Hillman adducts 149

150 have been employed for synthesis of a novel side chain liquid-crystal polymers. 183 Roos and coworkers184 isolated a novel product 151 in the 2-phthalimidopropanal Baylis-Hillman coupling reaction of with methyl acrylate. 0

NC~ O ( C H 2 ~ ~ 150
EWG
6.

OH EWG
COOMe

~ O O M e . II 0 151
adducts are obtained

II

COOMe

= CN,

Variants:.

It is worth mentioning ments have been described.

that the Baylis-Hillman

by using catalysts other than amines.

Some of the very important develop-

8052

D. BASAVAIAHet al.

The first of its kind was reported in 1968 by Morita et al. 185 have used tricyclohexylphosphine vated olefins with aldehydes (eq. 55) but the yields are very low.

They

as the catalyst for the coupling of acti-

Rc,o + ~

WG

P(cYC'H"hR~EWG
CN

OH

(55)

R = alkyl, aryl ; EWG = COOMe, Imagawa et al. 186 have reported nitrile by employing tributylphosphine (eq. 56). OH

higher yields in the case of acryloand triethylaluminium as catalyst

RCHO+
R = alkyl, a r y l Rhodium(I) and ruthenium(II) complexes were

CN

(56)

employed as

catalysts

in the reaction between alkyl vinyl ketones and aldehydes to produce umethylene-~-hydroxyalkanones (eq. 57).149, 187-189

0 [~ RCHO+ R' RhH(PPh~)4

(or) RuHz(PPh~) 4 R"

OH 0 /[,,~ /[L
~" ~R'

0/~~ +
R' R'

(57)

R = alkyl,aryl Triphenylphosphine Kahn (eq 58) .190 mediated

; R q = alkyl of methyl for the acrylate large with scale was achieved by Bertenshaw and

reaction

butyraldehyde and tosylamine or carbamates dimerization of acrylate esters. 0

Phosphines were used as catalysts 191

[~

RCHO+ ZNH + z
Z = tosyl, t-BUOOC,

R'
COOCH2Ph

PPh3 iPrOH
40 oC, 40 h

NHZ 0 _./J.,,./JL,,._ w ~] "R

Ph; R I = ONe,

(58)

; R = n-Pr,

Recently, complex

Roos et al. 192 reported reaction of

the

rhodium-chiral bis-phosphine with propanal which (eq. 59). OH

catalyzed

methyl vinyl ketone

produced the Baylis-Hillman adduct in 22% ee.

tCHO+

[[]/.COMe[Rh(I)-(-)-DIOP] V ~

COMe
ee

(59)

22%

The Baylis-Hillman reaction

8053

Conclusion:

The Baylis-Hilln~n started of attracting and the significantly reactions reaction the this advanced

reaction, attention

originating of organic in

from a German Patent in 1972 chemists the in 1980's and has the there of of as demonstrated review. by a number Though components

in the last ten years described rapidly

applications

is expanding A of

it is still at an early stage because catalyst is yet for to asymmetric evolve. synthesis witness

is much to learn about the reaction mechanism and the three reaction. reaction suitable chiral construction carbon-carbon certainly that fascinating bonds

Baylis-Hillman Applications are beginning in organic and more make this more

in diastereo-

and enantioselective represent the coming reaction a forefront years which will

to emerge and will chemistry. advances in this

of research ultimately

We believe

will

reaction one of the most useful reactions

Abbreviations: Binap CAMP COD DABCO DBU DCC DEAD DIBAL DIOP

in organic chemistry.

2,2'-bis(diphenylphosphino)-l,l'-binaphthyl o-anisylcyclohexylmethylphosphine cycloocta-l,5-diene 1,4-diazabicyclo[2.2.2]octane 1,8-diazabicyclo[5.4.0]undec-7-ene 1,3-dicyclohexylcarbodiimide diethylazodicarboxylate diisobutylaluminum butane hydride 2,3-O-isoprpylidene-2,3-dihydroxy-l,4-bis(diphenylphosphino)1,2-bis(anisylphenyl)phosphinoethane 4-N,N-dimethylaminopyridine 1,3-dimethyl-2-imidazolidinone dimethyl sulphide group 1,4-diphenylphosphinobutane electron-withdrawing hexachloroacetone ()-3-hydroxyquinuclidine horseradish peroxidase 3-chloroperbenzoic methanesulfonyl norbornadiene N-bromosuccinimide N-chlorosuccinimide 1-naphthyl pig liver acetone powder acid

DIPAMP DMAP DMI DMS dppb EWG HCA 3-HQ HRP mCPBA Ms NBD NBS NCS Np PLAP

8054

D. BASAVAIAHet al.

TBDMS TBHP TBPS TDAP

t-butyldimethylsilyl t-butyl hydroperoxide t-butyldiphenylsilyl tris(dimethylamino)phosphine trifluoromethylsulfonyl triisopropylsilyl trimethylsilyl

Tf
TIPS TNS

Acknowledgements:
We would like to thank our former coworkers Drs.V.V.L.Gowriswari, T.K. Bharathi, A.K.D. Bhavani and P.K.S.Sarma, and present coworker Dr.S.Pandiaraju who have contributed to the work described in this review. We gratefully acknowledge the help of our coworkers Drs. P. Rama Krishna, S. Bhaskar raju and Mr. K. Muthukumaran during the time of writing this review. We are grateful to UGC (New Delhi) and CSIR (New Delhi) for funding our research on Baylis-Hillman reaction. PDR and RSH thank UGC (New Delhi) for their research fellowships.

REFERENCES
I. 2. 3. 4. 5. 6. 7. 8. 9. 10. ii. 12. 13. 14. 15. 16. 17. Trost, B.M.; Science, Trost, B.M.; Science, Drewes, 1983, 219, 245. 1991, 256, 1471. 1988, 44, 4653. 1972 , Chem. I, 1982,

S.E.; Roos, G.H.P.; Tetrahedron,

Baylis, A.B.; Hillman, M.E.D.; Abstr. , 197Z, 77, 34174q. Drewes, 2079. S.E.; Emslie,

German Patent 2155113, Soc., Chem., Perkin Int.

N.D.; J. Chem. Angew.

Trans.

Hoffmann, 795. Basavaiah, Amri, Basavaiah, Basavaiah, Auvray, 5095.

H.M.R.; Rabe, J.; D.; Gowriswari, D.; Gowriswari, D.; Bharathi,

Ed. Engl., 1987,

1983, 22,

V.V.L.; Synth.

Commun., 1986,

17, 587. 27, 2031. Commun., 27,

H.; Villieras,

J.; Tetrahedron Lett., T.K.; Gowriswari, J.F.;

27, 4307. 1986, Synth. Lett.,

V.V.L.; Tetrahedron Lett., V.V.L.;

1987, 17, 1893. P; Knochel, P.; Normant, Tetrahedron 1991, 1986,

Weichert,

A.; Hoffmann,

H.M.R.; J. Org. Chem., K.; Yamada, H.;

56, 4098. T.; Tetrahedron, 1990, 2003. T.; 20,

Wang, S.-Z.; Yamamoto, 1992, 48, 2333. Amri, H.; E1 Gaied, 659. Tsuboi, Tsuboi, S.; Kuroda, Isaacs,

Takahashi,

M.M.; Villieras,

J.; Synth.

Commun., 1988,

S.; Takatsuka,

S.; Utaka, M.; Chem. 1993, 58, 5952.

Lett., T.;

H.; Takatsuka,

S.; Fukawa,

Sakai,

Utaka, M.; J. Org. Chem., Hill, J.S.;

N.S.; Tetrahedron Lett.,

1986,

27, 5007.

The Baylis-Hiliman reaction

8055

18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.

Rabe, J.; Hoffmann, 796. Hoffmann, Poly, 3701. Perlmutter, Fikentscher, 107, Byun, 1371. Strauss, 128185v. Janecki, Drewes, 1989, Foucaud, T.; Synth. 7781s. Drewes,

H.M.R.; Angew.

Chem., Chem., H.M.R.;

Int. Ed. Engl., 1985, 50, 3849. Chem.,

1983,

22,

H.M.R.; Rabe, J.; J. Org. D.; Hoffmann,

W.; Schomburg,

J. Org.

1988,

53,

P.; McCarthy, R.; Hahn,

T.D.; Aust.

J. Chem.,

1993, 46, 253. Abstr., 1987, 1987, 17, 291 35, 116,

E.; Kud, A.; Oftring,

A.; Chem. Commun.,

S.E.; Loizou, Reddy,

G.; Roos, G.H.P.; Synth.

H.-S.;

K.C.; Bittman, M.N.;

R.; Tetrahedron

Lett.,

1994, 1992,

C.R.; Galbraith,

Faux, A.F.; Chem. 23, 641.

Abstr.,

Commun., N.D.;

1993,

S.E.; Emslie, A.; Rouille, Isaacs,

Khan, A.A.; Roos, G.H.P.; 1990, 787. COmmun., 1988,

Synth.

commun.,

19, 959. E.; Synthesis, M.C.; Caubere, E.L.M.; Voss, P.; Synth. B.M.W.; 1992, 22, 1265.

Fort, Y.; Berthe, Hill, J.S.; a) van Rozendaal, 1993, 49, 6931.

N.S.; J. Chem. Res.(S),

330. H.W.; Tetrahedron, Soc., Chem. Left.,

Scheeren,

b) Ando, D.; Bevan, Commun., 32. 33. 34. 35. Basavaiah, 1987, Basavaiah, Grundke, a) Bull. b) Idem, 36. 37. 38. 39. 40. 41. Golubev, Izw. 1992,

C.; Brown,

J.M.; Price, D.W.; J. Chem. V.V.L.; Commun., 1987,

592. T.K; Gowriswari, V.V.L.; Synth. M.V.; Khim., Tetrahedron 1989,

D; Bharat~hi,

28, 4351. D.; Gowriswari, A.S.; Akad. 19, 2461. A.V.; 1994, C.; Hoffmann, Rus. Acad. H.M.R.; Chem. Bet., 1992, 41, 2193. Set. 1992, 2763; Chem. 1984, Chem. Abstr., 120, A.F.; 1461. Fokin,

Galakhov, Sci., Nauk.

Kolomiets,

120, 54166y. Perlmutter, Yamamoto, 61, 319. Takagi, Ameer, 1988, M.; Yamamoto, 'F.; Drewes, 18, 495. V.V.L.; D.; Ph.D. Thesis, University of Hyderabad, T.K.; India, K.; Tetrahedron, S.E.; Freese, S.; 1991, Kaye, 47, 8869. P.T.; Synth. Commun., P.~ Teo, C.C.; Tetrahedron Lett., Takagi, M.; Tsuji, J.; Bull. 25, 5951. Soc. Jpn., 1988, K.;

Gowriswari,

1989. a) Basavaiah, Left., 1987, b) Basavaiah,

Gowriswari,

V.V.L.;

Bharathi,

Tetrahedron T.K.;

28, 4591. V.V.L.; Dharma Rao, P.; Bharathi,

D.; Gowriswari,

8056

D. BASAVAIAHet al.

J. Chem.

Res. (S), 1995,

267. Karodia, N.; Synth.

commun., Lett.,

42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68.

Drewes,

S.E.; Emslie,

N.D.;

1990j 1989,
Lett.,

20, 30, 1992, J.S.;

1915. Amri, H.; Rambaud, 7381. Hwu, J.R.;

M.; Villieras, G.H.;

J.; T e t r a h e d r o n C.-T.;

Hakimelahi,

Chou,

Tetrahedron

33, 6469. Drewes,

Synth.

S.E.; Njamela,
Commun.,

O.L.; Emslie, 23, 2807.

N.D.; Ramesar,

N.; Field, 1992,

1993,

Roth,

F.; Gygax,

P.; Frater,

G.; Tetrahedron Lett.,

Org. Chem.,

33, 1045.

Hill, J.S., Fort, 1988,

Lett.,

Isaacs,

N.S.; J. Phys. Caubere,

1990,

3, 285. 48, 6371.

Commun.,

Bode, M.L.; Kaye, Y.; Berthe, 18, 1565. M.; 1990, Marko, Drewes, Bailey,

P.T; Tetrahedron Lett., M.C.; S.D; Emslie, Ollis,

1991,

32, 5611. 1992,

Synth.

P.; Tetrahedron,

S.E.; Freese,

N.D.; Roos, G.H.P.; Rasmussen, 1990,

I.E.;

W.D.;

P.R.;

Tetrahedron

31, 4509. P.K.S.;

Synth. Commun.,

Basavaiah, Isaacs, Auge, Kundu,

D.; Sarma,

20, 1611. 23, 1261. 1994, R.; 35, 7947. S.V.; Bhat,

N.S.; Tetrahedron, Rampersadh, Mukherjee, 444. Kaye,

1991,

47, 8463.
Commun. , 1993, Lett.,

Roos, G.H.P.; M.K.;

P.; Synth. S.B.; Balu,

J.; Lubin, 1994, J.M.;

1986,

N.; Lubineau,

A.; T e t r a h e d r o n N.;

Padmakumar,

Synlett,

Bode, M.L.; Brown,

Lett.,

P.T.; J. Chem. I.;

Soc.,

Perk~n Trans.

I, 1993,

1809.

Cutting, 27, 3307.

Evans,

P.L.;

Maddox,

P.J.;

Tetrahedron

Basavaiah, Sarma, Basavaiah, Basavaiah,

Tetrahedron

D.; Dharma Rao, P.; Sarma, Ph.D. thesis, D,; Pandiaraju, D.; Gowriswari,
Lett.,

P.K.S.;

unpublished

results.

P.K.S.,

University

of Hyderabad, results. P.K.S.;

India, 1993. Rao, P.;

S.; unpublished V.V.L.;

S. Aft.

Sarma,

Dharma

1990,

31, 1621.
J. Chem.,

Jensen, Gilbert,

K.N.; Roos; G.H.P.; A.; Heritage, Emslie, T.W.; N.D.;

1992, 45,

112.
Asymmetry, Chem. Bet.,

Isaacs, Karodia,

N.S.; N.;

Tetrahedron:

1991, 2, 969. Drewes, S.E.; 1990, 123,

Khan, Field, Khan,

Synth.

A.A.; J.S.;

1447. S.E.; J.S.; A.A.; Ramesar, N.; N.; 23,

Khan, A.A.; Emslie, N.D.; Drewes, Chem. Bet., 1993, 126, 1477. Drewes, Drewes, 1215. S.E.; S.E.; Emslie, Emslie, N.D.; N.D.; Field, Khan,
Tetrahedron Lett.,

A.A.; Ramesar,
Commun.,

1993,

34, 1205. 1993,

The Baylis-HiUman reaction

8057

69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96.

Drewes, 1065. Drewes, 2455.

S.E.; S.E.;

Manickum, Njamela,

T.; Roos, O.L.;

G.H.P.;

Synth.

Commun., Bet.,

1988,
1990,

18, 123,

Roos,

G.H.P.; 1991,

Chem.

Manickum, Drewes, Kundig,

Lett.,

T. ; Roos, G.; Synth.

Commun.,

21, 2269.
Commun.,

S.E.; Khan, A.A.; 1993, 34, 7049.

Rowland,

K.; Synth.

1993,

23, 183.

E.P.; Xu, L.H.; Romanens, P.; Xu, L.H.; Schnell, 1989, B.;

P.; Bernardinelli,
Synlett,

G.; Tetrahedron 413.

Kundig, Waldrop, Corey, Noyori, Corey,

Am.

1994,

M.M.; Science, R.; Takaya,

245, 354. 1990, 62, 1209. 1990, 23, 345. C.-P.; Singh, V.K.; J .
Chem. Res.,

E.J.; Pure E Appl. E.J.; Bakshi,

Soc. , 1987,

Chem.,

H.; Acc.

R.K.; Shibata, 109, 7925.

S.; Chen,

Chem.

Oishi, Oishi, 1241.

T.; Hirama, M.; Tetrahedron Lett., 1992, T.; Oguri, H.; Hirama, M.; Tetrahedron: K.B.; Tetrahedron A.; Yoneyama,
Lett.,

33, 639. Asymmetry, 32, 4853.

~symmetry,

1995,

6,

Oi, R.; Sharpless, Soai, 359. Ojima, Brown, Brown, 2179. Brown, Brown,
J. Org.

1991,

K.; Oshio, I.(Editor), J.M.;

H.; Tetrahedron:

1992,

3,

Catalytic Asymmetric

Synthesis, Chem.

VCH Publishers 1985, 578. 28,

inc., New York,

1993. I.; J. Chem. Prior,

Int. Soc., Commun.,

Cutting,

J.M.; James, J.M.; Angew. J.M.; Chem. M.; M.;

Chem.,

A.P.;
Chem., Soc.

L.M.; T e t r a h e d r o n
Ed. Engl.,

Lett.,

1987,

1987,

26, 190. R.; Takaya, H.;

Rev.,

1993,

25. K.; Noyori,

Kitamura, Bailey, Burgess, Adam, Drewes, Banfi,

Chem.

Kasahara,

I.;

Manabe, P.R.;

1988, 53, 708. Staton, I.; Ashton,

Asymmetry,

Marko,

I.E.;

Ollis,

W.D.;

Tetrahedron:

1991,

2, 495.
Chem.,

K.; Jennings, Hoch, U.; 1993,

L.D.; J. Org. Saha-Moller, 32, 1737. N.D.; Field,

1990,

55, 1138. 24, 917. P.;

Angew. Chem.,

Basavaiah, W.;

D.; Dharma Rao,

P.; Synth. Commun., C.R.; J.S.;

1994,

Schreier,

Int. Ed. Engl., Tetrahedron:

S.E.; Emslie, L.; Colombo,

Kahn, A.A.;

Ramesar,

N.;
Soc.,

Asymmetry,

1992,

3, 255. C.; Scolastico, G.; Roos, C.; J. Chem.

Synth. Synth.

L.; Gennari,

Commun.,

Brand,

1983, 1112. M.; Drewes, S.E.; Loizou, S.E.; Emslie,

G.H.P.;

Commun., Commun.,

1987, 17, 795. Brand, M.; Drewes,

N.D.; Khan, A.A.;

8058

D. BASAVAIAHet al.

1991,

21, 727. C.; Benezra, McGuirk, Rickards, W.; Chem. P.R.; C.; T e t r a h e d r o n Lett., Helquist, P.; R.D.; J.
Org.

97. 98. 99.

Papageorgiou, Marfat, 3888.

Chem.

1984,

25, 1303. 1979, 44,

A.;

Chem.,

Herlt, A.J.;

R.W.; Thomas,
Rew.,

East,

P.D.; J. Chem. Soc.,

Commun. , 1993,

1497. 1993, 1993, 93, 1673. 93, 1699. R.; Chem. Rew., M.S.;
Acta,

100. a) Fenical, b) Garson, c) D'Auria, 101. Ameer,

M.J.; C h e m Rew., M.V.; Minale,

L.; Riccio, 1143.

Helv.

1993,

93, 1839.

F.; Drewes,

S.E.; Houston-McMillan, I, 1985, H.M.R.;

Chim.

Kaye, 1991,

P.T.; J. Chem. 74, 1213. 15, 943. 353, 405. ; R.L.; J.

Soc., P e r k l n Trans.

102. Buchholz, 103. Gruiec, 105. Ameer,

Chem.

R.; Hoffmann,

A.; Foucaud, F.; Drewes,

A.; Moinet, S.E.;

C.; New. J. Chem.,

Chem.,

1991, 1988, Mann

104. Calo, V.; Lopez,

Soc.,

L.; Pesce, G.; J. Organomet. Esmlie, N.D.; Kaye, I, 1983, 2293.

P.T.;

P e r k i n Trans.

106. Ameer,

F.; Drewes, S.E.; Houston-McMillan, J. Chem., 1986, 39, 57. S.E.; Field, S.E.; Kaye, J.S.; Kaye, P.T.; 1987, J.;

M.S.;

Kaye,

P.T.; S. Afr. J. Chem., D.G.;

107. Ameer. F.; Drewes, 1985, 38, 35. 108. Ameer, 109. Drewes, F,; Drewes, Roos, G.H.P.; 110. Amri, H.; 384, i.

P.T.; S. Aft. G.;

Loizou, 40, 35.

Malissar, 1986,

S. Aft.

J. Chem,.

S.E.; Slater-Kinghorn, Rambaud, M.;

B.J; Synth. J.

Commun., Organomet.

16, 603. 1990,

Villieras,

Chem.,

Iii. Amri, H.; Rambaud, M.; Villieras, J.; Tetrahedron, 1990, 112. Beltaief, I, ; Amri, H.; Synth. Commun., 1994, 24, 2003. 113. Bauchat, P.; Le Rouille, E.; Foucaud, A.; 1991, 267~ Chem. Abstr., 1991, 115, 91980b. 114. Basavaiah, D.; Bhavani, Commun. , 1994, 1091. 115. Heerden, F.R.; 24, 2863. 116. Basavaiah, Huyser, A.K.D.; J.S.; P.K.S.; Sarma, P.K.S.; C.W.;
Bull. Chim.

46, 3535.
Soc. Fr., Chem.

J. Chem.
Synth.

Soc.,

Holzapfel, J. Chem.

Commun.,1994,

D.; Sarma,

Soc.,

Chem.

Commun. , 1992,

955.

117. Auvray, P.; Knochel, P.; Normant, J.F.; Tetrahedron, 1988, 44, 6095. 118. Charette, A.B.; Cote, B.; T e t r a h e d r o n Lett., 1993, 34, 6833. 119. Roush, W.R.; Brown, H.; D.; B.B.; J. Org. Chem., 1993, 58, 2151. D.A.; M.; D.; Zydows~y, Maillard, Maillard, T.M.; B.; B.; 120. Mazdiyasni, 121. Colombani,
Synth.

T e t r a h e d r o n Lett., Commun.,

Konopacki, D.B.; 1993, 34, 435.

Dickman,

Navarro, C.; Degueil-Castaing, 1991, 21, 1481. Degueil-Castaing, M.; Colombani,

122. Navarro,

C.;

The Baylis-Hillman reaction

8059

Synth. Commun., 1993, 23, 1025. L23. Colombani, D.; Maillard, B.; J. Chem.

Soc., Chem.,

Chem.

Commun.,

1994, H.; 1995,

1259.
Jpn.

L24. Colombani,
Kokai

D.; Maillard,

B.; J. Org. M.;

1994,
Chem.

59, 4765.
Abstr.,

L25. Konno, M.; Yuasa,

Y.; Harada,

Miura,

T.;

Kumobayashi,

Tokyo K o h o JP 06,172,300(94,172,300):

112

55724g. [26. Foucaud,

Chem.

A.; D.;

E1

Guemmout, Bhavani,

F.;

Bull.

Soc.

Chim.

Ft.,

1989,

403.

Abstr.,

1990,

112, 76324k. A.K.D., Pandiaraju, 1994, S.; Sarma, P.K.S.;

127. Basavaiah,
Synlett,

1995,

3, 243. N.D.; Tetrahedron, R.; Synthesis, 50, 12001. 1990, 799. (in. press). 1995, Loizou,
Chem. Soc.

128. Mason,

P.H.; Emslie,

129. Janecki,

T.; Bodalski,

130. Basavaiah, 132. Pandiaraju, 133. Drewes, 134. Yamamoto, 58, 3397. 135. Hoffmann, 136. Hoffmann, 137. Basavaiah, 1994, 138. Hoffmann, 140. a) Bellus, b) Bellus,
Acta,

D.; Pandiaraju,

S.; T e t r a h e d r o n

131. Basavaiah D.; Pandiaraju, S.E.; Emslie, 20, 1437.

S.; T e t r a h e d r o n Lett., N.D.; Karodia, N.;

36, 757. 1995. G.;

Jpn., Synth.

S. Ph.D. Thesis,

University of Hyderabad,

Commun. , 1990,

K.; Deguchi, H.M.R.; H.M.R.; D.;

R.;

Tsuji,

J.; Bull.

1985,

Eggert, U.; Poly, W.; Angew. Weichert, A.; S.; Slawin, Sarma,

Chem.,

Int.

Ed. Engl.,

1987, 26, 1015. A.M.Z.; P.K.S.,

Acta,

Williams,
Tetrahedron

D.J.;
Lett.,

Tetrahedron,

1990, 46, 5591. Pandiaraju,

35, 4227. H.M.R.; Rabe, J.; Helg. Chim. R.L.; Yates, K.V.; D.; Weis, D.; 1984, 1973, 67, 413. 1963, 28, 828,
Helv. Chim.

139. Bailey, W.J.; Hudson, Bredow

E.T.; J. Org. H.; 1974,

Chem.

Chem.,

C.D.; T e t r a h e d r o n Lett., Sauter,

Commun.,

999.

Weis, 151.
Soc.,

C.D.;

1973, A.;

56, 3004. K.; Synth. Hoffmann,

(Kyoto),

c) Dowd, 141. Weichert, 142. Oda,

P.; Kang,

H.M.R.; 1988, 43,

J.

PerRin

Trans.

I,

1990, 2154. R.; K a g a k u N.; 208 ; Chem. H.M.R.; U.; J.

Abstr., Chem.

1988,
Soc.,

109,
Chem.

23395r. 143. Daude,

Commun.,

Eggert, 206.

U.;

Hoffmann, A.;

1988,

144. Hoffmann,

H.M.R.;

Gassner, V.O.N.; 126,

Eggert,

Chem.

Ber.,

1991,

124,

2475. 145. Adam, W.; Salagado, H.G.; Chem. 146. Kanemasa,

Ber.,

Peters, 1481.

E.-M.;
Chem.

Peters,
Jpn.,

K;. von Schnering, 1993, 66, 2685.

1993,

S.; Kobayashi,

S.; Bull.

Soc.

8060

D. BASAVAIAHet al.

147. Heathcock, 148. Utaka, 149. Sato, 347. 150. Bailey, 2687. 151. Jackson,
Lett.,

C.H.;

in Morrison, S.; Takeda,

J.D. (editor) ; Asymmetric Synthesis,

3, iii.

Academic Press, New York,

1984,

M.; Onoue, S.; Matsuda, M.; Marko,

A.; Chem. Lett.,

1987,

971. 1989, 1991, 377, 32,

I.; Shibata, I.E.; Ollis,

M.; J. Organomet. W.D.;

Tetrahedron

Chem., Lett.,

R.F.W.; R.S.;

Standen, Fawcett,

S.P.; Clegg, J.; Russel, 2031.

W.; McCamley, D.R.; Williams, 1988,

A.; Tetrahedron P.J.; J. Chem.

1992,

33, 6197.
Commun.,

152. Atkinson,

Soc,, Chem.

1994,

153. Perlmutter, 154. Lawrence~ 155. Bulliard, 1600. 156. Bulliard, 157. Giese, 158. Kundig, 4047. 159. Loffler,
Acta,

P.; Tabone, Zehnder,

M.; Tetrahedron Lett.; P.; Chem. Lett., B.; Helv. M.; Giese,

29, 949. 1991, 74,

R.M.; M.;

Perlmutter,

1992,
Chem.

305.
Acta,

M.; Zeitz, Bulliard,

H.-G.; Giese, M.; Dickhaut,

B.; Synlett, J.;

1991, R.;

423. Hassler, 116. 1995,

Helv.

B.;

Halbach,
Synlett,

C.; Hoffmann,

U.; Hinzen,

B.; Senn, M.,

1995,

E.P.; He-xu, A.; Pratt, 53, 383.

L.; Romanens, R.J.; Ruesch,

P.; Tetrahedron Lett., H.P.; Dreiding, A.S.;

36,
Chim.

1970,

160. 0hler, 1970, 161. Drewes, 162. Nokami, 163. Drewes

E.; Reininger, 9, 457. S.E.; Hoole, J.; S.E.; 1995, Y.; Tamaoka, Taylor,

K.; Schmidt, R.F.A.; T.;

Synth.

U.; Angew.
Commun.,

Chem.,

Int. Ed. Engl.,

1985,

15, 1067. S.;

Chem. Lett.~ Synth.

0gawa,

H.;

Wakabayashi, N.S.;

1986, 541. R.B.; Y.; Ramesar, Y.; Field, J.S.;

Co~mun.,

25, 321. Kurusu,

Tetrahedron Lett.,

164. Masuyama, 225. 165. Alami, 59. 166. Alami, 167. Wanner, 169. Ferris, 170. Auvray, 5091.

Nimura,

1991, 1987,

32, 28,

N.E.; Belaud, N.E.; Belaud, M.J.; Koomen,

C.; Villieras, C.; Villieras,

J.; Tetrahedron Lett., J.; Synthesis, 1988, 1993, 31,

1213. 907.

G.J.; Tetrahedron Lett., M.; Org. Syntheses, 1955, 20, 780.

1990,

168; Villieras,

J.; Rambaud,

66, 220. 1986, 27,

A.F.; J. Org. Chem., P.; Knochel,

P.; Normant, Ayed,

J.F.; Tetrahedron Lett.; T.B.; T.B.; Villieras, Villieras, J.; J.;

171. Amri, H.; E1 Gaied, M.M.; Lett., 1992, 33, 6159. 172. Amri, H.; E1 Gaied,

Tetrahedron Tetrahedron

M.M.; Ayed,

The Baylis-Hillman reaction

8061

Lett.,

L73. Reddy,

1992, 33, 7345. K.C.; Byun, H-S.;

Bittman,

R.;

Tetrahedron

Lett.,

1994,

35,

2679. L74. Bode, M.L.; English,

Chem. Abstr., 1992,

R.B.; Kaye,

P.T.; S. Aft. J Chem., 1994, 24, 2851. 1989,

1992,

45, 25,

L75. Foucaud, L76. Bauchat, L78. Ayed, 180. Mason,

i17, 37340w. A.; Brine, N.; Synth. Commun., P.; Foucaud, Kaye, P.T.; J. Chem. H.; E1 Gaied, N.D.;

A.; T e t r a h e d r o n Left.,
Soc., P e r k i n

30, 6337.
I, 1990,

L77. Bode, M.L.; 179. Calderon, 183. 181. Paterson, 4393. 182. Brzezinski, 35, 7601. 183. Hall, A.W.;
Science,

Trans.

2612.

T.B.; Amri, P.H.;

M.M.; Tetrahedron, P.; Tetrahedron, S.E.;

Synth.

1991, 1992,
Commun.,

47, 9621. 48, 5347. 1995, 1993, 25, 34,

A.; Font, J.; de March, Emslie,

Drewes,

I ; Bower, L.J.;

S.; Tillyer, D.D.; Hill,

R.D.; T e t r a h e d r o n Lett., J.W.;

Levy, D.;

Leahy, J.S.;

T e t r a h e d r o n Lett.,

1994,

Lacey,

McDonnel, T.; Roos, 120,

Chem.

D.G.;

Supramolecular

1994,

i, 21. Ramesar, N.; Manickum,

Abstr.;

184. Field,
Chem.,

J.S.;

G.H.P.;
Soc. Jpn.,

S. Afr.

J.

1993, 46,

39; Chem.

1994,

163884b. 1968, 41,

185. Morita, 2815. 186. Imagawa, 1984, 187. Sato,

K.; Suzuki, T.;

Z.; Hirose, K.;

H.; Bull. Z.;

Uemura,

Nagai,

Kawanisi,

M.~ 1985,

Synth.

Commun.,

14, 1267. S.; Matsuda, I.; Izumi, M.; Y.; Chem. Lett., 1875. 1988, 340, I., Shibata, A.M.; Sato, S.; J. Organomet. N.A.;
Chem.,

188. Matsuda,

C5-C 7 189. Moiseenkov, 1990, 113,

Ceskis,

B.; Shpiro,

Stashina, 595;

G.A.;

Zhulin,

V.M.; Izv. Akad. Nauk SSSR, Ser. Khim. ; i14922j. 190. Bertenshaw, 191. Kitazume, 192. Roos, 1251.
NOTE ADDED IN P R O O F

1990,

Chem. Abstr.,

S.; Kahn, M.; T e t r a h e d r o n Lett., 1978, 88, 89131f. C.E.; Haines, R.J.; Raab,

1989,

30, 2731. 1993, 23,

S.; Chem. Abstr.,

G.H.P.;

Synth.

Commun.,

Since appeared. 193. Marko, Tinant.

submitting

this

review,

the

following

relevant papers have

I.E.; Giles,

P.R.; Janousek,

Z.; Hindley,

N.J.; Declercq,
Trav. Chim.

J-P~

B.; Feneau-Dupont, 114, 239.

J.; Svendsen,

J.S., Recl.

P a y s - B a s , 1995,

8062

D. BASAVAIAHet al.

194. Atkinson, 195. Marson, 8107.

J. Org.

R.S.;

T e t r a h e d r o n Left.,

Fawcett, 1995,

J.; Russell, 36, 3241. Smith, C.;

D.R.;

Williams,

P.J.; 1995, 36, L.~ J.

C.M.;

Pink, J.H.;

T e t r a h e d r o n Lett.,

196. Annunziata, 197. Urabe, H.;

R.; Benaglia, 1995,

M.; Cinquini, K.;

M.; Cozzi, Kobayashi, 1995,

F.; Raimondi, K.; Sato, F.,

Chem.,

60, 4697.

Yamashita, K.; Suzuki, Org. Chem., 1995, 60, 3576. P.; Tabone, R.F.W.;

198. Perlmutter, 199. Jackson,

Soc. Perkin

M.; J. Org. Chem.,

60, 6515. A.;

J. Chem.

Standen, S.P.; Clegg, Trans. I, 1995, 141. 1995, A.;

J.

W.;

McCamley,

200. Ciganek, 201. Barrett, 1755.

E.; J. Org. Chem., A.G.M.; Kamimura,

60, 4635.
Chem. Soc., Chem. Commun.,

1995, 1995,

202. Ayed T.B.; Amri, 51, 9633.

H.; E1 Gaied,

M.M.; Villieras, ; Tetrahedron,

(Received 29 January 1996)