Synthesis of a phospholecarboxylic ester

Tetrahedron Letters No. 4, pp 299 - 302, 1972.

Printed in Great Eritsin.

Pergamon Prese.

SYW’lliESISOF A PHDSPHGLECARBDXYLIC ESTER Louis D. Quin and Stephen G. Borleske Paul M. Gross Chemical Laboratory, Duke University Durham, N. C. 27706. U.S.A. (Receivedin USA 13 December 1971; receivedin UK for publioation 28 December 1971) The phosphole ring system has been known for over a decade, and a number of alkyl and aryl derivatives

have been reported.

tive group is situated

However, no phosphole has yet been synthesized where a reac-

on the ring.

We have accomplished the first

pound; methyl 1-methylphosphole-3-carboxylate indications ability

am that the 4-methyl derivative

(VIII)

of such a com-

has been prepared and characterized,

can be obtained by the same method.

and

The avail-

of such compounds opens up for study a new aspect of the chemistry of this ring system.

‘Ihe carboxy group was first

installed

on the phospholene oxide ring.

Ihe anion from

H02C

--

n-BuLi THF ’

I

II

1-methyl-3-phospholene

oxide’(I)

was formed at -7S02.

After 30 min. the solution

ated and then passed through a Dowex SO-H+ ion exchange colurr. eluate,

synthesis

a mixture of acids II (65%) and III

with the acid group was readily

the nmr spectrum; each isomer had only one olefinic

olefinic

oxide structure ing a 4H doublet)

tallization

proton (68.42,

JpccH = 32 Hz).

doublet of triplets,

of the

II, where

The 3-phospholene

III was assigned to the other isomer on the basis of the simplicity

nmr spectruml.

JpccH =

‘Ihe very strong deshielding

of carbonyl and phosphoryl on the 6-proton is present.

of the methylene signals;

That

apparent from

proton in the former isomer permitted the assignment to it of structure

the combined effect

plicated

m evaporation of the aqueous

(35%) was obtained in 502 combined yield.

the double bond had rearranged into conjugation

36 Hz. JHccH = 2.6 Hz; 67.52, broad doublet,

was carbon-

(approach-

the 2-phospholene oxide system gives a more com-

Acid II was obtained in pure form (mp 214” dec) by fractional

of the mixture from methanol.

299

crys-

300

lo.

The acid mixture was subjected II proved to be particularly sired ester

IV.

accelerated

by an amine

to Fischer esterification.

easily

polymerized,

The ester

gum; evaporation

of the

as morpholine.

filtrate

Addition

a residue

left

(V) derived from acid

a property allowing its removal from the de-

Polymerization of V occurred in benzene solution such

4

of ether

at room temperature, but was

precipitated

of IV of sufficient

the

polymer

as a

purity for continuation

of

the synthesis.

COOCH3 3

IV Trichlorosilane in

3%40%

formed

VI reduction

yield,

gave

bp 4%46O

phosphine

(0.1

pan).

mp 188.4-190.4q,

a methiodide,

(+33.5 ppm relative phospholene ring,

VII

lhe

the

first

ester

known ester

had the

giving the correct

to 85% H3P04 reference)

(verified

analysis.

phospholene

nmr and ir

family, spectra

The 31P nmr signal

provided confirmation

and

of VI

of the presence of the 3atom3.

phosphorus

by nmr) at phosphorus is the same as that of a diene-phosphonous dihalide

VI

CH2C12with 1,5-diazabicyclo[S.r).O]undec-5-ene moved by filtration

after 3 hrs; the filtrate

of solvent.

Dry Ice-acetone

bath.

about 40-SO0 (0.2 szu).

lhe

residue

was rapidly

The bp of the colorless The purity

cycload-

of the dehydrohalogenation method of Mathey and

Mankowski-Favelier4 for the synthesis of phosphole VIII.

gas

proton

for the 2-phospholene would have a more deshielded

This permitted the application

stripped

expected

of the

consumed-1 mole of bromine, forming bromophosphoniumbromide VII, whose structure

rapidly

duct.

VI,

VIII

of the

The bromide was treated in benzene-

(DIN) at O”.

The hydrobromide of DBUwas re-

was washed with water to remove DBU, and then distilled

directly

into

a receiver

liquid was not measured accurately

product

so obtained

was at

least

chilled

in a

but was

95% as indicated

by

chromatography. The carbomethoxy

group

VIII is markedly less stable

introduces

considerable

instability

than 1-methylphosphole’

into

the

phosphole

and 1-benzylphosphole’.

system;

It decomposes at

room temperature, forming a dark resinous mass, but can be preserved in a Dry Ice-acetone Phosphole VIII had its

3lP nmr signal at -3.0 ppm; the downfield shift

methylphosphole (+8.57) is indicative

of electron

relative

bath

to l-

withdrawal from the ring due to Conjugation

301

No. 4

with the carbomethoxy group. glet)

The lH nmr spectrum at 60 MHzcontained the P-CH3 signal

at 61.92 and the OCH3signal

at 64.26.

The olefinic

(sin-

region was examined at 90 MHzand was

analyzable by inspection:

67.3 (1H. III, Hg, 2JpH = 38, 3J = 7.5. 4J = 2.5 Hz). _I.8 HsH4 H5H2 = 7.5, %J = 1.5 Hz), b8.3 (IH, III, HZ, lJPH = 34.5, (1H. m. H4, 3JpH = 17, 35 HsHL~ HCHL 45 = 2.5, 4J = 1.5 Hz). Of particular note are the large coupling constants of phosH2Hs H2H4 phorus with the a-protons, entirely consistent with the value (38 Hz) for the a-protons of 1-methylphosphole’,

and the strong deshielding

adjacent carbons, especially

that at C-2 (68.3).

spectrum of methyl thiophene-3-carboxylate7, similarity.

to which the spectnn

which was the base peak.

this substance is reactive

mediate for the preparation 2,3-positions. readily

effect

is also seen in the

of VIII bears a strong

The W maximum(307 mu) was considerably

shifted,

from that of 1-methylphosphole (285 mu’).

We would also like to point out synthetic lene oxide(V);

This deshielding

‘lhe mass spectrum had the expected molecular ion (m/e 156.0339; calcd for

C7HsOgP. 156.0341). as expected,

by the carbomethoxy group on the protons of

the pyrazoline

for 3-carbomethoxy-l-methyl-l-phospho-

to 1,3-dipoles.

of phospholane derivatives

As one example of several

with V to yield

utility

reactions

and is therefore

a valuable inter-

with S-membered rings fused in the

studied,

IX, mp 174.5-176”.

ethyl diazoacetate

having the correct

reacted

analysis

and the

expected nmr spectrum.

CO2CH3+ N2CHCOxCgHg +

IX

V

Acknowledgments:

We thank Joseph J. Breen for obtaining

the 31P spectra.

A Bruker HPX-10

system, purchased in part by funds provided by the National Science Foundation (Grant No. 10301). was employed.

The mass spectrum was obtained on an AS1 MS 902 Spectrometer of the

Research Triangle Mass Spectrometry Center (sponsored by Special Facilities FR-0330-01, National Institutes

of Health).

Some of this work was supported by Public Health

Service Research Grant CA-05507 of the National Cancer Institute. Science Foundation Trainee,

1968-1971.

Grant No.

S.G.B. was a National

302

No. 4

REFERENCES

1.

L. D. Quin, J. P.

2.

While this synthesis was being developed, E.,

m,

actions.

Grate,

and T. P. Barket, 2. s.

s.,

,@, 1034 (1968) .

P. Mathey and J. P. Lampin (=

1531 (1970)) reported metallation

Rend. Acad. --

of phospholenes oxides and subsequent re-

See also J. P. Lampin, F. Mathey and B. Bartet, --Bull. Sot. Chim. France, 317 (1971).

3.

L. D. Quin, J. J. Breen, and D. K. Myers, L. s.

4.

Bull. Sot. Chin. France, 4333 (1971). F. Mathey and R. Mankowski-Favelier, ----

5.

1. D. Quin, J. G. Bryson, and C. G. Moreland, J. -- Amer. e.

6.

P. Coggon, J. F. Engel, A. T. McPhail, and L. D. Quin, ibid.,

7.

S. Gronowitz and R. A. Hoffman, -Arkiv

Kemi, ,@,

s.,

$j,, 1297 (1971).

515 (1960).

E.,

8,

3308 (1969).

@,, 5779 (1970).

*