The oxidation of 4-aza-5-prregnene-3,20-dione with benzeneseleninic anhydride. Formation and decomposition of a selenoxide intermediate

Tetrahedron Letters Bo. 51, pp 4931- 4934. OPergamon Press Ltd. 1979.Printed in Great Britain.

THE OXIDATION OF 4-AZA-5-PREGNENE-3,20-DIONE WITH BENZENESELENINICANHYDRIDE.

FORMATION AND DECOMPOSITION OF A SELENOXIDE INTERMEDIATE Thomas G. Back* and Nan Ibrahim Department

of Chemistry

The University Calgary,

Alberta,

of Calgary Canada,

T2N lN4

Abstract: The enamide moiety of the title azasteroid reacted with benzeneseleninic anhydride to afford products derived chiefly from a Pummerer-type reaction at C-6. The intermediate selenoxide was also prepared by oxidation of the corresponding selenide. Benzeneseleninic various

nitrogen

It occurred troduction

acid

(L) and benzeneseleninic

nucleophiles,

resulting

to us that enamides of new oxygen

of intermediate selenoxides3,

followed

in a number

or

by aqueous

could occur either via

elimination

substrates

through

consequent

azasteroids

interest.

preliminary

display

useful

transformationsl.

for such oxidations,

reactions

of

as in-

rearrangement

of initially

formed

workup.

biological

We therefore

investigations.

as mild oxidants

[2,3] sigmatropic

or Pummerer-type

(elimination Certain

(2) function

of synthetically

might prove interesting

functions

seleninamides2

anhydride

activity

products)

and the synthesis

chose 4-aza-5-pregnene-3,20-dione

Herein we report

(Pummerer products) of new derivatives

(?I4 as the subject

is of of our

the results.

I Azasteroid dichloromethane preparative

3 was treated with solution

t.1.c.

(40%), the epimeric

1.1 molar equivalents

for 18 h at room temperature.

(alumina) 7-hydroxy

to afford, enamidic

of benzeneseleninic The products

in order of increasing selenides

5a and 5b 6p7 --

4931

were

anhydride

(2) in

then separated

by

Rf, the keto carbinolamide

-45

(28% and 12% respectively)

and

4932

Bo. 51

the selenide 68 (16%) (Scheme I). Scheme I

0&

COCH,

+

%@+oq

8‘ 3

4

5a

R=a-OH

55

R=f3-OH

We believe that the azasteroid undergoes attack by the anhydride at C-6 to produce the corresponding selenoxide -7.

The latter compound was not isolated from the reaction mixture, but

reacted further to generate the Pummerer intermediate8, which hydrolyzed with concomitant hydration of the N-acylimine moiety to affordthe keto carbinolamide4.

Deprotonation of 8 at C-7

followed by 1,4 hydration of the resulting unsaturated N-acylimine 2 accounts for the formation of -5a and -* 5b

Furthermore, benzeneseleninicacid and diphenyl diselenide are expected byproducts

of the preceding reactions.

Their comproportionationgis known togenerate benzeneselenenic

acidlo, which in turn may react with azasteroid 3 at C-6. The formation of selenide &may be rationalized. (Scheme II). Scheme II: 6

JieOH

- - x

5a + 5b

thus

4933

Ho. 51

To verify

Treatment

route. which

the mechanism

of azasteroid

gave the desired

selenoxide

at room temperature,

2 to produce

-3 with -2.

II, we prepared

upon oxidation

thus obtained but reacts

the same products

tion of azasteroid

in Scheme

2 with benzeneselenenyl

The selenoxide

quantitative). solution

depicted

selenoxide

chloride/pyridine

1 by an independent furnished

with m-chloroperbenzoic

selenide 5,

acid (overall yield:

is stable in the solid state or in dichloromethane

readily

in the presence

5, -5a and 5b in comparable Thus, the intermediacy

yields

of seleninic

acid 1. or anhydride

to those obtained

of selenoxide

by the oxida-

1 in the latter reaction

is

confirmed. Finally, sequently, formation

we note that the selenium

the preparation

of 1 from the oxidation

of a pair of diastereoisomers.

stereoisomers

decomposed

diastereoisomeric temperature

We observed

steroid

because

of the enamidic

with similar selenoxides

rates when

for stereochemical

z

1, where

the formation the major

center.

or sigmatropic

Con-

lead to the of two

isomer could be crystalliaedll.

treated with benzeneseleninic

such reactions

and chiroptical

a chiral

of -7 as a mixture

have been reported l*, but were

of facile elimination

selenoxide

1 constitutes

of selenide 5 may, in principle,

in a ratio of ea. 2:l (nmr), from which

The two isomers

strate

atom of selenoxide

shifts.

acid.

Other

labile at or below

The greater

cannot occur, may render

thermal

room

stability

it a convenient

sub-

studies.

R-conf ig.

1

S-config.

Acknowledgements We thank Drs. A. Hogg, R. S. Roche and R. Yamdagni Natural

Sciences

References 1.

(a)

Research

Council

for financial

certain

spectra

and the

support.

and Notes

T. G. Back and S. Collins,

D. .I. Lester (d)

and Engineering

for recording

Letters,

and S. V. Ley, J.C.S. Chem. Comm.,

D. H. R. Barton,

R. Czarny,

Tetrahedron

J.C.S.

D. J. Lester

Chem. Comm.,

2661,

(1979).

276, (1978).

(c)

(b)

T. G. Back, ibid, p. 278.

and S. V. Ley, J.C.S. Chem. Comm.,

81 (1976).

D. H. R. Barton,

445,

(1977).

(e)

M.

4934

Bo. 51

[2,3] Sigmatropic rearrangementsof N-phenylseleninylintermediates have been proposed in the oxidation of hydrazones with 2 lb,ld. 3.

For reviews which describe the chemistry of selenoxides see: *.,

12, 22, (1979). (b) D. L. J. Clive, Tetrahedron,2,

(a) II.J. Reich, Act. Chem. 1049, (1978). (c) K. B.

Sharpless, K. M. Gordon, R. F. Lauer, D. W. Patrick, S. P. Singer and M. W. Young, Chem. Scripta, g,

9, (1975).

4.

N. J. Doorenbos, C. L. Huang, C. R. Tamorria and M. T. Wu, J. Org. Chem., 2&

5.

Compound 4:

2546, (1961).

m.p. 232-234'; v,,, (CHCl$ 3630, 3380, 1725, 1700 and 1660 cm-'; lH nmr (CDC13)

6 7.00(s, lH, exchanged in D20), 3.80(s, lH, exchanged in D20); m/e 329 (M+ - H20). A correct combustion analysis was obtained. Treatment with methanol and a trace of HCl effected exchange of OH for OCH3. 6.

Compound -5a:

solid foam; [aID -132" (c 0.47, CHC13); vmax (CHC13) 3580 and 3310 cm-'; &,,,,

(CH30H) 249 nm (E 15,400); IH nmr (CDC13) 6 4.05 (broad s, lH, not exchanged in D20); 13C nmr (CDCl3) 6 70.3 (assigned to C-7); exact mass, Calculated for C2BH33N03B0Se: 487.16257. Found: 487.1616. Compound 5b: and 3310 cm-l; bax

(CH30H) 67

solid foam; [o]D +46" (c 0.17, CHC13); Vmax (CHC13) 3550 nm (E 17,300);'H nmr (CDC13) 6 3.95 (d, J = 7 Hz, lH, not

exchanged in D20); 13C nmr (CDC13) 6 74.8 (assigned to C-7); exact mass, Found: 487.1630. 7.

The assignment of the 7cl-and 78-hydroxy structures to &

and &

is confirmed by the coup-

ling constants of protons at C-7 and C-S. Product -5a has J7,B too small to measure while -5b has 57,s = 7 Hz. These values are most consistent with axial-equatorialand diaxial coupling respectively. a.

Compound 5:

solid foam; [C&ID-107'

(C

0.58,

(Et20) 252 nm (E 17,000); m/e 471 CHC13); &.,,,,

(M+). A correct combustion analysis was obtained. 9.

(a) T. Hori and K. B. Sharpless, J. Org. Chem., 9,

1689, (1978). (b) H. J. Reich, S.

Wollowitz, J. E. Trend, F. Chow and D. F. Wendelborn, ibid, p. 1697. 10. Phenylselenenylatingspecies other than PhSeOH (e.g. PhSeOSePh, PhSe(O)OSePh) could also be involved in the formation of _* 6 11.

Compound L:

The mixture of diastereoisomerswas a solid foam which gavea correct combustion

analysis. lH nmr (CDC13) 6 11.80 (s) and 11.55 (s, total lH, exchanged in DzO), s at 1.20, 1.13, 0.67 and 0.60. The major diastereoisomerhad m.p. 177-179.5"; [o]D +70" (C 0.23,CHC13); Amax (CH30H) 220 nm (E 13,100) and 252 nm (E 14,000); IH nmr (CDC13) 6 11.80 (s,lH, exchanged in DzO), s at 1.20 and 0.67; m/e 487 (&, faint) and 471 (M+ - 0). 12.

(a) W. G. Salmond, M. A. Barta, A. M. Cain and M. C. Sobala, Tetrahedron Letters, 1683, (1977). (b) D. N. Jones, D. Mundy and R. D. Whitehouse, J.C.S. Chem. Comm., 86, (1970). (Received in USA 29 Angust 1979)