Asymmetric alkylation reaction by means of a chiral phase transfer catalyst.

TetrahedronLetterrNo. 40, pp 34% - 3496,

1975. PergamonPrera. Printed in Great Britain.

ASYMMETRIC AL,KYLATION REACTION BY WEANS OF A CHIRAL PHASE TRANSFER CATALYST. J-C FIAUD Laboratoire de Synth&se Asym6trique

(1). bit. 420, Universite Paris Sud, 91465 Orsay.

(Bcceired in UK 21 July 1975; accepted for publication 22 AuLuguat 1975) HIYAW's

recent work on enantioselective oxirane synthesis with the aid of a chiral

phase transfer catalyst (2) pranpted us to report our results on an alkylation reaction performed via the asymmetric catalyst (-)-N-benzyl,N-methyl according to the equation:

RX

ephedrinium bromide 2 (3),

H ,0/CHC13 /NaOH * p H-@&le2Y

fa

Z=-OEt

g

Z=-OMe

&

2 =-Me

By

H-k-OH g Ph

2 R= Me,CH2-CH=CH2,

CH2-Cm.

2 2

Y =-CH2-Ph

-2e Y =-Me

In a standard experiment, the cyclic

B-keto ester or

p-diketone 1 ( 20 nrmol)

dissolved in chloroform or dichloranethane

120 ml) together with the alkylating reagent 72.7 nmol) was vigorously stirred overnight with a mixture of loibaqueous sodium hydroxyde (20 ml) and 2 (0.2g), at rocm tanperature. The organic phase was separated, washed with water and the solvent removed. The residue was taken up into ether, whereby the catalyst 2 cristallised ( and could be further recovered). Removal of the solvent gave the crude product, a purification of which by column chranatography

(silica gel, n-hexane:ethyle

acetate 2O:l) afforded

pure compound 2. The main results are collected in the table. The enantlomeric excess values were not estimated as the optical rotation of the enantiomerically pure samples had not been known. However, it could be evaluated to 56%

in

run 1 by n.m.r. spectroscopy of 2 C Z =CMe; R =-CH2-CH=CH2) with the aid of a choral shift reagent Eu(tfacCam)3

(5).

An increase in the amount of catalyst used did not raise the value of asyrmnetrlc induction. The use of hexane instead of chloroform as a solvent afforded the products 3 with

3495

3496

No. 40

a satisfactory yield but without any trace of optical rotation.

Table 2

NT

in 2

Rx

[aI (CHC13,c

Catalyst

1

-0Et

CH2=CH-CH2Br

d

2

-OMe

CH2=CH-CH2Br

-2d

3

-CMe

CH C-CH2Br

4

-Me

5

-Me

CH2=CH-CH2Br

-2d

6

-Me

CH2=CH-CH2Br

e

Me1

1.5) of 2

Yield (%)of 2

-8.2O

85

-12.8O

75

d

-3.80

75

d

-4.60

85

With the quaternary ammonium salt &

-23.5O

90

-1.20

80

used as a catalyst (2) the reaction did

proceed but with lower degree of induction (comparison of runs 5 and 6). This is the first asymmetric alkylation reaction performed by a phase transfer catalysis, i.e. in mild conditions: weakly alkaline aqueous medium, room temperature. Other new asymmetric phase transfer catalysts are presently under investigation, in order to increase the asyranetric inductions. Acknowledgement. We are grateful to the Centre National de la Recherche Scientifique for financial support. References -and notes. 1) Equipe de recherche associee au C.N.R.S. no 559. 2) T. HIYAMA, T. MISHIMA, H. SAWADA and H. NOZAKI, .I. mner. Chem. Sot., 97, 1626,(1975). 3) The aarsonium salt 2

was prepared by quaternisation of (-)-N-methylephedrine with benzyl

bromide in toluene; the precipitated

salt was washed with n-hexane and dried: mp. 222OC,

- 5.10 (c 6.5, methanol).

t$ 81 4) K. NAKAJIMA, Nippon Kagaku gasshi , _, 5) V. SCHURIG, Inorg, a.,ll,

736 (1972).

1476 (1960).