619

NEW SYNTHETIC

ROUTES

L.Mangoni

R.Caputo, Institute

TO Pa,3@-DIHYDROXY-Se-CHOLESTANE

of Organic

and L.Previtera

Chemistry, 16,

Via Mezzocannone

University

Naples

80134,

of Naples Italy

Manuscript rcceiVe:.l:l/23/75 ABSTRACT Better synthetic approaches to 2a,3$-dihydroxy-5a-cholestane and its ester derivatives, which were hitherto difficult to prepare, are reported. A satisfactory preparation of the desired trans-diequatorial 2a,3$-dibenzoate, starting from the easily available corresponding cis 2a,3a-dial, has been devised. Finally, the influence of the temperature as well as of the bulkiness of the silver carboxylate on the steric course of the Prgvost reaction have also been examined. Although

procedures

for the preparation

of all the four

diastereomeric

2,3-dihydroxy-?a-cholestanesl

-4ahave

reported,

dials 1 , 2and3acan

synthetized

2,3)

only

starting

methods

from

which

-diequatorial of its cis dium

synthesis with

are available

isomerzunder 180~

compounds better

R

=

approach

or a rather

S

of the trans(2) (so-

complicated In connection

which

of steroidal represent

a

of the diol4a.

3 C R = pivaloyl;

TBEOXDU

the only

conditions

reactions

to the preparation

b R = benzoyl;

VoZume 25, Number 5

vigorous

some results

(1,

epimerisation

cholest-b-en-3-one,

2 H;

the

in the hydroxylation

(4), we now report

1 a

either

for 24 hr), from

By contrast,

for the preparation

extremely

(3) starting

our interest

much

5a-cholest-2-ene,

2cl,3g-diol4aare

ethoxide;

be easily

been

4 d R = mesitoyl;

May, 1975

S

620

The reaction in anhydrous

of olefins

benzene

shown

(6)

diate

dioxolenium

with

ion.

In considering

such

ring which

rigid

steroid

5 such

opening

shown

the dioxolenium

reaction

(formula 5)

is cis-fused

some results

higher

temperatures

trans-diaxial Therefore,

the use

hindered

well

as higher

The results

this

as either

or the problem

has

who have

Br- or Cl- open manner.

reported

by Ellington

et al. (6)

of bulky

nucleophilic

agents

we subjected

5a-cholest-2-ene

silver

salts,

to the

including

and using as toluene

boiling

solvents

such

we have

obtained

are summarized favourable

to

action

benzoate

and mesitoate,

the most

and

the trans-diequatorial

ratio.

show that

nucleo-

and Allbutt

diastereomer

pivalate

possess

(7) with

undergo

in the trans-diaxial

to increase

and different

more

by King

such

ring mainly

might

Actually,

study

nucleophiles

to suggest

and clearly

the PrGvost

the trans-diaxial

diastereomer.

seemed

iodine

of an interme-

skeleton.

ring

either

in a detailed

(7) that

Neverthless,

has been

7

a dioxolenium

to afford

trans-diequatorial treated

opening

benzoate

6

In principle,

been

(511

an intermediate

dioxolenium

the conformationally

and silver

reaction

the nucleophilic

of 5a-cholest-2-ene,

philic

iodine

[Ithe Prgvost

to involve

the B-oriented

TDEOIDI

Of

and the

benzene

as

and xylene. in Table

diequatorial

1 to

diaxial in

diester

refluxing

ratio

toluene.

trans-diequatorial Although dered rent

of

quite

of

to

would ring

by

of

to

an

less

this

silver

these

conditions

in

we

a-oriented favoured

ring, become

the

be

consi-

the

basis

diffeof

the

that

the

dioxolenium

ring

(cf.

that

because

methyl

the

not

predicted

than

6)

the

a completely

on be

mesitoate

yield.

could

chose

it could

angular

58%

result

Actually,

structure the

using

obtained

so that

dioxolenium expected

is

et al.,

be

by

under

problem.

(cf.

exerted

a-oriented be

the

opening

dioxolenium

would

fact,

interest,

Ellington

6)

hindrance

In

diester some

trans-diaxial structure

achieved

satisfactory

approach

results

is

of

a B-oriented

of the

group.

steric

Hence,

trans-diequatorial favoured

for

an

opening

process.

Table 1. Influence of different solvents and silver salts on the Pr6vost reaction of 5a-cholest-2-ene.

silver

salt

benzoate pivalate mesitoate benzoate pivalate mesitoate

solvent

yieldt

benzene benzene benzene toluene toluene toluene

65% 84% 90% 66% 84% 92%

t Overall yield of crystallization.

Unfortunately, the

Prgvost

electrophilic of

the

the

the

molecule.

since to

ion6is its

attack

Therefore

1 2.5 2.5 1 2.5 2.5

time hr hr hr hr hr hr

diastereomeric

dioxolenium

reaction, iodine

pure

reac.

not

formation from

it was

the

2:l 1.3:1 o.g:1 1.g:1 l.l:l. 0.6:1

diesters,

after

an

intermediate

would

require

more

obtained

28,3a/2a,3B

in

hindered

in the

B-side

a different

way. which the

(7) (81,

?a-Cholestan-2a,3a-diyl-ethyl-orthobenzoate is easily

prepared

corrisponding

ride-etherate dioxolenium

dioll

quantitative

(3), bias treated

(9) and to the thus ion6silver

of the reaction diester4b

in almost

product

in 77% yield,

with

obtained

boron

was

added

afforded

the expected

of the

directely.

by only

from

trifluo-

solution

benzoate

accompanied

yield

Work

up

diequatorial

6% of the diaxial

isomer3b. Therefore,

the preparation faster dure

than

could

of the

others possibly

dials

(e.g.,

their

conversion

stereomers,

method

this

does

diol4a

hitherto

represent ) much

reported.

be extended

more

a new procedure convenient

Moreover,

to other

and

such

steroidal

a proce-

a-c