Synthesis of a steroidal cyclopropanol

Tetrahedron Letters No. 42. PP. 29%

- 39:7, 1971.

Pergamon Press.

Printed in Great Britain.

SYNTHESIS OF A STEROIDAL CYCLOPROPANOL by J.F. Templeton and C.W. Wie Faculty of Pharmacy, University of Manitoba, Winnipeg 19, Manitoba, Canada. Recently a number of synthetic methods have been developed for the prepara13 tion of cyclopropanol derivatives"". However, none are readily applicable to the formation of a fused cyclopropanol Although

parent molecule.

ring containing an existing oxygen atom of a

some steroidal cyclopropane

ether derivatives

have been

addition to an enol ether 374 , these substances can not

prepared by dihalocarbene

be converted into a halogen free cyclopropanol. Steroidal 3-ketones are readily converted into the corresponding ivatives5a.

Azeotropic

Stan-3-one(l)

removal of water from a solution of 17-acetoxy-+a-andro=

in 10% v/v 2-chloroethanol

p-toluenesulfonic

in dry benzene containing 0.1% w/v

acid gave 17P-acetoxy-3,3-bis(2-chloroethoxy)-5a-androstane

m.p. 94-5' [aID + 11' (CHC13). 2,3-unsaturated

acetal der-

enol ether6.

yielded the 2-chloroethoxy

Pyrolysis of 3-dimethoxysteroid

acetals gives the

Pyrolysis of the acetal(2) at reduced pressure

enol ether(3) m.p. 130-131°,

[aID + 44' (CHC13).

Treatment of the crude pyrolysis product with an excess of the Simmons-Smith agent' gave the 2-chloroethoxycyclopropane (CHC13).

(2)

ether(4) m.p. i29-i30°,

[a]

re-

+ 23O

Normal addition to the steroidal 2,3-double bond occurs from the

a-face5b. Schollkopfi has shown that removal of the 2-chloroethyl with n-butyl lithium. temperature

group readily occurs

Brief treatment of 4 with excess n-butyl lithium at room

yielded the heat labile product 2P,3-dihydro-2'H-cyclopropa

androstan-3@,17@dio1(5)

m.p. 145-155',

[a]D + 18' (dioxane) as a hemihydrate.

The melting point is dependent upon the rate of heating. only one substance on thin layer chromatography

3955

[2,3]-5a-

The product showed

(four systems).

Material from

3956 No.

OAc

42

No.

3957

42

a melt showed two substances on t.1.c. corresponding

Gas liquid chromatographic

and 17@-hydroxy-2a-methyl-5a-androstan-3-one(6). analysis of 5 gave one peak corresponding 3-one(6).

to 17$-hydroxy-2a-methyl-5n_androstan-

The infrared spectrum of 5 showed cyclopropyl

hydroxylic and no carbonyl absorption. had high field signals characteristic

2a-methyl-5a-androstan-3-one(6)

C-H stretching,

strong

The proton magnetic resonance spectrum of cyclopropyl

Treatment of 5 with dilute methanolic

spectrum.

to the starting material(5)

C-H resonance.

potassium hydroxide gave 17B-hydroxy-

identified by mixed melting point and infrared

This compound demonstrates

that addition of methylene

occurred to the

2,3-double bond. All reactions gave yields of 50-60%. spectroscopic

properties

with the structures

All of the above substances

(IR, PMR, MS) and elemental analyses

showed

(C,H) consistent

indicated. ACKNOWLEDGEMENTS

The authors wish to acknowledge

the support of the Medical Research

Council

of Canada for this work. REFERENCES 1.

U. Schollkspf, Angew.Chem.Internat.Edn.,

2.

C.H. DePuy, Accounts

3.

A.B. Font, Bull.Soc.Chim.(Fr.),

4.

G. Stork, M. Nussim and B. August, Tetrahedron,

5.

D.N. Kirk and M.P. Hartshorn, "Steroid Reaction Mechanisms", Publishing Company, Amsterdam. (a) p.130 (b) ch. 3.

6.

G. Karmas, J.Org.Chem., 2,

7.

H.E. Simmons and R.D. Smith, J.Am.Chem.Soc.,

2, 588 (1968).

of Chem.Res., 1, 33 (1968). 419 (1964). Supp. 8, 105 (1966).

2436 (1968). 2,

4256 (1959).

1968, Elsev i.er