Synthesis of specifically deuterated 1,3-diethoxy-carbonylallylidenetriphenylphosphonium ylide

Tetrahedron Printed in

Letters,Vol.24,No.7,pp Great Britain

0040-4039/83/070743-02So3.00~0 01983 Peraamon Press Ltd.

743-744,1983

SYNTHESIS

OF SPECIFICALLY

DEUTEEATED

I,3-DIETHOXY-

CABBONYLALLYLIDENETRIPHENYLPHOSPHONIUM A. Johan H. Labuschagne Department

of Chemistry,

University

YLIDE

and David F. Schneider* Stellenbosch

of Stellenbosch,

7600, South Africa

Abstract: Methods for the specific introduction of deuterium labels in the B- and y-positions of the title allylidenephosphonium ylide, without deuterium scrambling, have been developed.

In a recent contribution'

from our laboratory

tation of the allylidenephosphonium nium ylide

ylide

(2) and ethyl propynoate, -

our detailed

investigation

specifically

deuterated

we communicated

the unusual

retro-Michael

fragmen-

(1) to yield ethoxycarbonylmethylenetriphenylphospho-

during

its condensation

of this fragmentation-condensation

allylidenephosphonium

ylides

During

with p-chlorobenzaldehyde. reaction,

the synthesis

(3) and (4) became

of the

desirable.

C02Et D

C02Et

Ph3;Lco2Et

C02Et

Ph3&k02Et

D

For the synthesis

of the B-deuterated

to ethyl 3-deuteriopropynoate synthesized

by a newly developed

method which

literature

procedures.2'3

transfer

conditions

(tetrabutylammonium

contained

ylide

a catalytic

(2) the Michael

The deuterio-ester

is, according

Ethyl propynoate

existing

oxide which

phosphonium

(5) - was envisioned.

addition

of the ylide

(2)

(2) was very efficiently

to our experience,

in dichloromethane

superior

was treated,

to the

under phase

iodide, TBAI), with a three molar excess of deuterium

quantity

of sodium deuteroxide.

After

stirring

for one hour

at room temperature, the organic phase was separated and the deuterium exchange procedure re1 twice. H n.m.r. analysis of the dried organic phase revealed that it contained ethyl

peated

3-deuteriopropynoate be isolated

(5) - with a deuterium

in almost quantitative

content

yield without

lation, we found that the B-deuteriophosphonium by the addition without

of one mole equivalent

its prior

tion conditions

isolation.

of the ylide

deuterium

yield,4

incorporation

Although

appreciable ylide

m.p.

the deuterio-ester

deuterium

ylide

of (5_)

under these reac-

148'C (from ethyl acetate),

S(CDC1,)

of >90% according

6,30

to 'H n.m.r.

analysis. Ph3kl-CO%Et

D20fiSD H-CZC-C02Et

CH2C12/TBAI

'

D-C-C-C02Et

> (2)

(5)

743

distil-

be synthesized

solution

(2) was produced

in the t&position

(5) could

loss by fractional

(3) could very conveniently -

(2) to the dichloromethane

The B-deuteriophosphonium

in 80% recrystallized

(I H, s), with specific

of >97%.

(3)

744

For the synthesis of the y-deuterated phosphonium ylide (A), acid catalyzed, regiospecific deuterium exchange of the allylidenephosphoniumylide (I) was invoked. The phosphonium ylide (l_) in dichloromethane was treated with a nine molar excess of deuterium oxide which contained half a mole equivalent of deuterium chloride. The organic phase was separated and successively treated with an equal volume of deuterium oxide, an equal volume of deuterium oxide which contained half a mole equivalent of sodium deuteroxide, and again with a fresh portion of deuterium oxide. The residue from the dried (potassium carbonate) organic phase was recrystallized from ethyl acetate to produce the y-deuteriophosphoniumylide (4) in 66% yield' with a specific deuterium 1 incorporation of >90% according to H n.m.r. analysis, m.p. 148'C S(CDCl3) 6.97 (1 H, d, .JpH 17.3 Hz).

Treatment of the organic phase with an equivalent amount of base (sodium deuteroxide),

after acid catalyzed deuterium exchange, was an essential operation in order to avoid deuterium loss.

Michael addition of the deuterated phosphonium ylide (5) to ethyl propynoate, also proved to be an efficient method for the synthesis of the y-deuteriophosphoniumylide (6). The phosphonium

Ph3:-CH-C02Et

D2° CH2C12

H-C-C-C02Et >

Ph3&-C02Et

(A)

(a)

(2,

ylide (2) in dichloromethane was treated with a five molar excess of deuterium oxide, the organic phase separated and the deuterium exchange procedure repeated twice. Separation of the organic layer was followed by -in situ treatment of the deuterated phosphonium ylide (5) with one mole equivalent of ethyl propynoate at or below room temperature. The dichloromethane solution was treated as above with half a mole equivalent of sodium deuteroxide in deuterium oxide, washed with deuterium oxide and dried. According to 'H n.m.r. analysis, the y-deuterated allylidenephosphonium ylide (f?)was produced under these reaction conditions with a regiospecific deuterium in situ Wittig condensation with incorporation of >90%. The ylide (A) was sufficiently pure for -p-chlorobenzaldehydewithout its prior isolation.

ACKNOWLEDGEMENT We thank the South African Council for Scientific and Industrial Research and the University of

I

Stellenbosch for financial support, and H.S.C. Spies for the H n.m.r. spectra.

REFERENCES AND NOTES 1.

A.J.H. Labuschage and D.F. Schneider, Tetrahedron Letters, 1982, 4235.

2.

R.K. Hill and G.R. Newkome, J. Org. Chem., 1969, 2,

3.

S.J. Cristol and A.L. Noreen, J. Org. Chem., 1976, 2,

4.

Yields were not optimized. (Received

in UK 15 December

1982)

740. 4016.