Oxidation of spiroethers with t -butyl chromate

Tetrahedron

Letters N0.58,

pp. 5057-5059,

1970.

Pergamon Press.

CDIIDATICN OF SPIRCETHERS G. F. Reynolds, Merck

G. H. Rasmusson,

Sharp & Uohme

Research

(Received in USA 6 November 1970; As both logically

the 17-spiroether')

active

facilitate

steroids,

the preparation

The conversion

ether.

Other

generated

from a reduced

We

the molecule. 17-spiroether

were

moiety

one-step

of both and permit group

to a spiroether

to the corresponding

lactone,

by a one-step

In the course

of studies

on the introduction

standard

only 4% yield

and an appreciable

We were ethers Via')

lactone, 6, III,

lactones

reaction

occurred

IVb6), Vb2)

respectively.

of

address:

to obtain

members

of the of both

function

into

38-acetoxy-2',

t-butyl

chromate

oxi-

the anticipated

II, was obtained

in

With

isolable

of Chemistry,

5057

as well.

of t-butyl

at the position

that the method

Dept.

in

of 3-(3~-acetoxy-17~-hydroxy-7-oxo-5-androsten-l7a-

that the 19-norsteroid

indicates

conversion

(5-androsten-7-one)6),

this reaction

as easily

are present

namely,

for this type of reaction

this reaction.

selectively

and VIb2)

The fact

conditions

a)Present

the scope

process,

of a 7-0~0

(23X), was isolated

thus led to investigate

to determine oxidation

amount

or be re-

reaction.

conditions5)

3'a-tetrahydrofuran-2'-Spiro-17

to the

This mode of transforma-

(5-androstene) 4) , I, the traditional

38-acetoxy-2',

acid

in this sequence

such as halides,

as a method

by reduc-

is then ring-closed

step.

substituents,

the reverse

in bio-

properties.

has been accomplished3)

oxidative

preferably

yl)propionic

USA

are of importance

must be protected

labile

thus led to explore

3'a-tetrahydrofuran-2'-Spiro-17

07065

of their biological

open chain diol which

in the molecule

when hydride

Under

New Jersey

of one group to the other would

a comparison

of compounds,

dant was employed.

and G. E. Arth

moieties

conversion

state by a subsequent

tion also has limitations

types

a simple

groups

Rahway,

and 17-spirolactone2)

to the corresponding

carbonyl

CHRCIMATB

L. Birladeanua),

Laboratories,

in Great Britain.

received in lK for publication 13 November 1970)

of the spirolactone

tion of the lactone

WITH t-BUTYL

Printed

chromate

the keto-spiroethers o- to the ether oxygen

products

in yields

Via was not noticeably is reasonably

Harvard

with other

specific.

University,

spiro-

IVa 7) , Va') affording

and the

of 4056, *@I, and 30!% aromatized Although

Cambridge,

under

the

we have made

Mass.

02138.

No.58

5058

no attempt indicated

to find optimum

Typically,

acetic

a solution

anhydride.

urated

of 200 g

of the steroid

was worked

The mixture

was refluxed

oxalic

acid solution

up and the crude product

the desired

lactone

lactone

tetroxide.")

occurring

The cooled

until

separated

in 4%

yield

The lactone resulted

IVb was formed in extensive

acetic

the course

reaction

gas evolution

was made at the selective

tion to completion

shows

mixture

as

by chromatography quantities after

of ethylacetate

but attempts

X=l-L2,Y=H2

II

x = 0,

Y'H2

IVa

Y=H2

III

x = 0,

y=o

IVb

y=o

Vb

R=CH3,Y=0

Y=H2

Via

R = H,

Y'H2

VIb

R = H,

y=o

was

from

being

with

The organic

on silica

side-reactions.

R =CH3,

was treated

sat-

solution

gel, elution in benzene.

of The

MeOH/H20.

of IVa to IVb utilizing

to some extent

Va

of the reaction

recrystallization

oxidation

tetrachloride

acid and 0.4 ml of

was complete.

AC I

of its action,

that it can be of value

Va in 4 ml of carbon

for 2-4 hrs,

with increasing

Vb was obtained

An attempt

mixture,

chromate, 5, 0.8 ml of glacial

by thin layer chromatography.

aqueous

desired

of the reaction

the selectivity

of this type.')

with 2.8 ml of t-butyl

followed

for this oxidation

by thin layer chromatography

in transformations

treated

conditions

ruthenium

to drive

the reac-

No.58

5059

References 1.

G. E. Arth,

H. Schwam,

2.

J. A. Cella,

E. A. Brown

R. D. Muir and J. 3.

E. A. Brown, used

4.

Cella,

2. E.

2. 9.

a.,

6_, 617

21, 743

Chem.,

(1963).

(1959); B. A. Brown,

ibid., 25, 96 (1960).

3,364,207

(Jan. 16, 1968) and also unpublished

procedures

laboratories.

point

compound

A.

and M. Glitzer,

and R. R. Eurtner,

U.S. Patent

in these

Melting

L. Sarett

139-140'.6)

described

Prepared

by acetylation

by R. A. Firestone

of the corresponding

and U(. Sletzinger,

U.S. Patent

3$-hydroxy

3,365,475

(Jan.

23, 1968). 5.

K. Heusler

6.

All new compounds constants c

and A. Wettstein,

Helv. --

described

in this paper

for new materials

236mu

(612,500);

Chim.

described

A-,

35,

gave

herein:

III, m.p. 273-275',

284 (1952).

satisfactory II, m.p.

[aID cHc13

analyses.

CHc13-148.3, [aID

178-180°,

-143.5,

e

236rqr (~13,000),

.&Dc13 4.26 (s,lH), 7.95 (s,3H), 8.76 (s,3H), 9.03 (s,3H), M+ 400; 160°, 7.

[a]gHC13

+50.6,

G. H. Rasmussen,

MeoH &,,,

A. Chen,

247m~

The physical

IVb, m-p.

158-

(&16,500).

G. F. Reynolds,

A. A. Patchett

and G. B. Arth,

2. s.

s.,

in press. 8.

Other

reagents

which

bromine

convert 9.

G. Cainelli, Chim. --

10.

ethers

solutions12)

B. Kamber, 518

a) L. M. Berkowitz J.

to convert

steroidal

tetroxide.

ethers

lob)

Chromic

to lactones

are chrom-

acid in acetone 11)

acid 13) have also been found

and trichloroisocyanuric

to

into esters.

Acta, 44,

Wolff,

used

acid 9 ) and ruthenium

ium trioxide-acetic buffered

have been

J.

Keller,

M. Lj. Mihailovic,

D. Arigoni

and 0. Jerger,

Helv.

(1961). and P. N. Rylander,

F. Kerwin,

F. F. wings,

2. -Am. Chem. s.,

B. B. Lewis

so, 6682

and B. Blank,

2. s.

(1963). 11.

H. B. Henbest

and E. Nicholls,

12.

N. C. Deno and N. H. Potter,

2. Am. -- Chem.

13.

E. C. Juenge

Tetrahedron

and D. A. Beal,

J. Chem. K., -=.,

227 2,

Letters,

(1959). 3550 (1967). 5819

(1968).

(1958). Chem.,

b) M. E. 28, 2729