New methods for β-conjugate addition and β-hydroxyalkylation of enones

0040-4039/88 $3.00 + .OO Perqamon Press plc

Tetrahedron Letters.Vol.29.No.42,pp .__ 5413-5416,1988 Printed in Great Britain

NEWPQTH~DSFOR ~-CONJUGATEAODITIONMD

Sunggak

Kim* and Phil Ho Lee

Department Korea Advanced

S-Conjugate

Summary:

reaction

Institute

addition

olefins

and

and aldehydes

functionalization

namely, These is

the

conversion

approaches

capable

of

regenerate different

double

phoniosilylation

elimination

of enones

can be normally

anions

Although

methods

of enones

have

via

which

serve

at B-position

using triphenylphosphine

literature

and silylating

reversal

anion

groups

at

process,

equivalents.'

at &position,

beiny

easily

indicates

one of the promising

by the

activated

procedure.

as R-acylvinyl

as

with

in tetrahydrofuran

by dipole

functional as well

of the

developed,*

triflate

salts by one-pot

accomplished

of suitable

examination

been

Korea

phosphoniosilylation,

of trimethylsilyl

into adducts

stable

bonds.

enones

of phosphonium

of the introduction

generating

synthetic

from

Seoul 130-012,

of enones have been accomplished

5-hydroxyalkylation

of enones

consist

and Technology,

in the presence

-78 OC and subsequent

The

of Chemistry

of Science

derivated

of ylides,

p-HYWOXYALKYLATI~N0F ENONES+

ayents,

to

a number

of

that

methods

which

eliminated

involves

previously

phos-

developed

by Evans3 and Kozikowski.4

6

OTBDMS

TBDMSOTf PPh3, THF

n-BuLi

OTf- ;Ph3

Yk

(yIh,-

g

2

1. OTdijMS

0 n-BuqNF -

TMSOTf +&EwG

-

EWG

B-Conjugate Wittig

reagents

cyclopropane (2) derived in the

+Dedicated

to

of Enones

activated

derivatives

enones

salt

of trimethylsilyl (3) in good yields

to Professor

to Activated

olefins

proceeds

is of synthetic

from phosphonium

presence

alkylated

Addition

Olefins. by

importance.6

of silyl enol ether triflate

(TMSOTf)7

by one-pot

Although

several

the conjugate

pathways,b

However, (1) cleanly

5413

addition formation

we have found that react with

in tetrahydrofuran

procedure.

E.J. Corey on the occasion

the

of his 60th birthday.

of of

the ylide

activated

olefins

at -78 OC to yive

&

5414

Reaction vinyl

of the ylide

ketone

ammonium

fluoride

byproducts. Michael

gives

to another

conjugate

products.8*g

cyclohexenone

that the low yield enolate

addition

The addition

to some extent, yielding

from

at -78 OC for

via phosphoniosilylation

1 h followed

by the addition

3-(3-oxopentyl)-Z-cyclohexen-l-one

It is expected

adduct

further

(2) derived

in tetrahydrofuran

of

might

due to the presence

enolates

to

ethyl

of hexamethylphosphoric

the desired

product

in 21% yield

be resulted

vinyl

ketone

triamide

in 47% yield

to

ethyl

of an initial

vinyl

produce

(HMPA) improves

toyether

ethyl

alony with several

from tautomerism

of the unreacted

with

of tetra-n-butyl-

ketone

the

and

dialkylated

the present

reaction

with the dialkylated

products

in 20% yield. order to avoid the side reactions,

In Michael

adduct

TMSOTf

gives

with best

silylating results

ineffective

for this purpose.

and TMSOTf

in tetrahydrofuran

tetra-n-butylammonium the contamination derived

fran

agents.

and

is

Amony

gives

of dialkylated enones

of the premixed

solution

procedure,

carbonyl

compounds

olefins

results are given in Table

compounds

such

as

is

vinyl ketone

by the addition

the reaction proceeds

and

the efficiency

study,

chloride

in 7Y% yield

in hiyh yields.")

acrylonitrile

1 and illustrate

an initial

in this

of ethyl

(2) at -78 'C followed

a modified

other

activated

tested

trimethylsilyl

Using

works

with

ayents

while

o,@unsaturated

2,3-unsaturated-1,6-dicarbonyl

well

silylating

of trappiny

3-(3-oxopentyl)-2-cyclohexene-l-one

products.

with

the possibility

recommended,

at -78 OC to the ylide

rapidly, yielding

experimental

several

generally

Thus, the addition

fluoride

several

we considered

The

vinyl

of

without

of ylides

cleanly present

and

method

sulfone.

some

and the applicability

of

the present method.

8-Hydroxyalkylation reaction

of enones

of enones.

of

Enones.

to activated

Encouraged olefins,

As far as we are aware,

intermediates

prior to the formation

been

that the similar

reported

trimethylsilyl The betiane Reaction for

10

present

method

of the ylide followed

hydroxybenzylated yield.

TMSOTf

in quenching contamination

the

results

no successful

reports

of oxaphosphetane

intermediate

obtained

in

the possibility have appeared

with

silylatiny

in the boron-Wittiy

conjugate

addition

of 6-hydroxyalkylation for quenchiny

agents,

reaction

betaine

althouyh

it has

has been quenched

with

chloride."

intermediates

min

by

we have studied

is based

with TMSOTf, (2) with by

the

cyclohexenone

on the

Wittiy

an equimolar addition

of

amount

betaine

(4) in 29% yield

of the

intermediate,

Wittiy

pr0duct.l'

of ylides

yielding

with

of phosphonium

of benzaldehyde

tera-n-butylammonium

is found to be much more effective the

reaction

and facile elimination

together

with

aldehydes,4

in tetrahydrofuran

fluoride the

at

Wittiy

than t-butyldimethylsilyl the

desired

In the case of

product usiny

quenchiny

salts via desilylation.

-78

product triflate

in 72% yield

aliphatic

at -78 OC

OC

rives

B-

(5) in 21% (TBUMSUTP) without

aldehydes,

the it is

5415

Table 1. @-Conjugate Addition of Enones to Activated Olefins

enone

isolated yield, Xa

product

activated olefin

0

6

EWG CH2=CHCOCH2CH3

EWG=COCH2CH3

79 (21)b

CH2=CHCOC6H5

=COCgH5

CH2=CHCOOCH2CH3

=COOCH2CH3

58 (0)b

CH2=CH-SO2C6H5

=S02CgH5

68 (0)b

CH2=CH-CN

=CN

58

(wb

0

6/

WG CH2=CHCOCH2CH3

EWG=COCH2CH3

CH2=CHCOOCH2CH3

68

=COOCH2CH3

64

LEWG CH2=CHCOCH2CH3

EWG=COCH2CH3

CH2=CH-CN

73 (70:30)=

=CN

77 (85:15)'

a the yields are based on enones. b the reactions are performed in the absence of TMSOTf. 'the ratio of trans/cis isomer.

Table 2. B-Hydroxyalkylationof Enones

enone

RCHO

2-cyclopenten-l-one

C6H5CHO

2-cyclohexen-l-one

a

isolated yield, 'Za 57

CH3(CH2)7CH0

54

c-C6H11CH0

63

C6H5CHO

72

CH3(CH2)7CH0

63

carvone

C6H5CHO

48 (8)b

4-hexen-3-one

C6H5CHO

68

c-C6HllCHO

60

the yields of a-hydroxyalkylatedenones.

b

the yield of the recovered starting material

5416

preferred

to add an aldehyde

and TMSUTf

use of an equimolar

mixture

corresponding

enol ethers

Table

2.

aromatic

silyl

The

present

aldehydes.

Acknowledgment. support

method

well

and simultaneously results

that

results

and acyclic

the ylide

to steric

Institute

enones

(2) does

because

formation

the

of the

are summarized with

aliphatic

not react with

in and

ketones

reasons.

of Science

to Dr. Sung Soo Kim for experimental

References

in the

Some experimental

due possibly

the Korea Advanced

and we are grateful

separately

and TMSOTf

in both cyclic

it is noteworthy

and cyclohexanone

We thank

aldehydes

to some extent.13

works

However,

such as acetophenone

to the ylide

of aliphatic

and Technology

for financial

assistance.

and Notes

1. For reviews, see: (a) J. C. Stowell, Chem. Rev., 84, 409 (1984). (b) 0. Hoppe,Anyew. Chem. Int. Ed. Engl.,g, 2. (a) K. Kondo

and A. J. Mura, T.

F.

48,

Tetrahedron

Ibid.,

3187

and H. E. Morton,

Ginsberg,

Tetrahedron

Jr., J. Org. Chem., 41,

Weingartner,

Larcheveque, Piers

932 (1984).

and D. Tunemoto,

Ibid., 47,

Lett.,

1007

2506 (1976).

Lett.,

2506

(1975).

(1976).

(d)

A.

Uebal,

(1977).

(e) C. Shih and J. S. Swenton,

J. Org.

Chem., 3,

2229

(1982).

3437

(lY7Y).

(h) H. J. Cristau,

0. A. Bennett,

M. L. F. Bakuzis, T.

Cuviyny,

Ibid., 4217

(q) U.

M.

(1981).

(f) E.

U. Sunay,

and S.

and C. Nianyoran,

Ibid.,

Liotta,

B. Chabaud,

and

and

1527 (1983).

3. D. A. Evans,

K. M. Hurst, and J. M. Takacs, J. Am. Chem. Sot., I&l,

4. (a) A. P. Kozikowski

and S. H. Jung, J. Org. Chem., 51,

and S. H. Jung, Tetrahedron 5. G. M. Kosolapoff

6. (a) H. J. Bestman Finkelhor,

Lett.,

and L. Maier,

1973 and references

Phosphorous

Compounds",

Lett.,

Lett.,

Angew.

Chem.,

154

3781

(1972).

3,

in 68% yield 10. The ylide

(b) A. P. Kozikowski

Wiley

Intersciences,

Vol. 3,

(c) M. J.

ketone

(1962). Devos,

(b) P. A. Grieco L. Hevesi,

and R. S.

P. Bayet,

and A.

3911 (1986).

7. For an excellent review, see: H. Emde et al., Synthesis, vinyl

3467 (1978).

(1986).

3227 (1986).

"Organic

and F. Seng,

8. (a) M. E. Jung, Tetrahedron, phenyl

3402

cited therein.

Tetrahedron

Krief, Tetrahedron

9. When

(b) T. Cohen,

(c) P. Bakuzis,

32_, 3 (1976).

was used as an activated

in the absence

of TMSOTf,

1 (1982).

(b) R. E. tiawley, Synthesis, olefin,

as shown in Table

(2) did not react with ethyl acrylate

the desived

777 (1976). product

was obtained

1.

in the absence

of TMSUTP.

11. A. Pelter, D. Buss, and A. Pitchford, Tetahedron Lett., 5093 (1985). 12. The use of TBDMSOTf cyclohexenone 13. The formation

in

as a trapping

agent was totally

ineffective,

yieldiny

26% yield toyether with the Wittig product in 3Y% yield.

of a small amount

of aldol products was also observed.

(Received in Japan 22 August 19881

B-hydroxybenylated