5
80 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
Hydrolysis of Steroidal Esters Catalysed by
Tetracyanoethylene$
James R. Hanson,* Cavit Uyanik and Kudret Yildirim
1998, 580±581$
School of Chemistry, Physics and Environmental Science, University of Sussex, Brighton,
Sussex BN1 9QJ, UK
Tetracyanoethylene has been shown to be a mild catalyst which possesses some stereoselectivity, for the hydrolysis of
the esters of steroidal alcohols.
Tetracyanoethylene (TCNE) is well-known as a dienophile
1
in Diels±Alder reactions. Recently it has attracted interest
allowing dierentiation between various esters. Furthermore
TCNE is a relatively mild reagent and hence other acid-
catalysed reactions might be less likely to occur.
as a p-acid and it has been shown to act as a catalyst for
2
,3
the cleavage of epoxides.
We have studied the stereo-
chemistry of the methanolysis of steroidal epoxides catalysed
The optimum conditions for the hydrolysis were estab-
lished with cholesteryl acetate 1 as the substrate. Since this
was not suciently soluble in methanol, toluene was used
as a co-solvent. A temperature of 50 8C and a reaction
period of eight hours gave a satisfactory yield. There was
no detectable hydrolysis in the absence of the catalyst. The
hydrolysis of a range of steroidal esters were then investi-
gated. The extent of hydrolysis in an eight hour period is
given in Table 1. The C-3b, C-6b and C-17b positions
represent sites of diering steric hindrance in which the
axial C-6b position is the most hindered. The esters were
4
by TCNE and we have shown that the reaction may be
aected by the neighbouring group participation of hydroxy
5
groups. We have also used the reagent to catalyse some
cyclization and rearrangement reactions of sesquiterpene
6
,7
epoxides. In the course of these studies we have observed
varied from acetate through propionate to trimethylacetate
(
1
pivaloate). The alcohols were identi®ed by their H NMR
spectra in particular by the change in the chemical shift of
the CH(OAc) resonance when it was replaced by a CH(OH)
group.
Comparison of the results of hydrolysis of the C-3b, C-6b
and C-17b-acetates in 6, 9 and 18 and of the 17-acetate,
1
7b-propionate and 17b-pivaloate, 12, 16 and 17 shows
that the reaction is susceptible to steric hindrance from
both the alcohol and acid components. Furthermore when
the hydrolysis of the 3b-acetate 6 was carried out in the
sterically more hindered solvent isopropanol at 50 8C, the
reaction was very slow and only 8.5% hydrolysis occurred.
Consequently TCNE may be used as an alternative to
mildly basic conditions for dierentiating between esters at
various centres on the steroid framework.
The hydrolysis of 3b-acetoxycholest-5-en-7-one 3 led to
a substantial amount of the acid-catalysed elimination
1
product, cholesta-3,5-dien-7-one 5 identi®ed by its H NMR
spectrum. On the other hand the conditions were not
suciently vigorous to bring about the dienone:phenol
rearrangement of 14 or of the elimination and backbone
8
rearrangement of the tertiary 5a-hydroxy group in 18.
In conclusion we have shown that tetracyanoethylene may
be used as a mild catalyst for the hydrolysis of steroidal
esters with the potential to distinguish between sites and
esters of dierent steric hindrance. It may have more general
application as a reagent for the catalysis of ester hydrolysis.
Experimental
4
General experimental details have been described previously.
General Procedure for the Hydrolysis of Esters.ÐThe steroid
3
500 mg) was dissolved in methanol (10 cm ) or toluene±methanol
(
(
3
1:1) (10 cm ) and treated with tetracyanoethylene (100 mg) and
the hydrolysis of some steroidal acetates through what is
probably a p-acid catalysed ester exchange. As a bulky
reagent, unlike the proton, we considered that TCNE might
aord some steric control over the acid catalysed hydrolysis
warmed to 50 8C for 8 h. The reaction was monitored by TLC (the
reaction time may be varied depending on the ester). The solvent
was evaporated under reduced pressure. The residue was absorbed
on silica and chromatographed in an increasing gradient of ethyl
acetate in light petroleum. The steroids were identi®ed by compari-
1
son of their H NMR spectra with known samples and in particular
4.5±5.0) to a CH(OH)
signal (ꢀ ca.
*To receive any correspondence.
by the change of the CH(OAc) resonance (ꢀ
H
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
resonance (ꢀ 3.5±4.0) and by the loss of a COCH
H
3
H
2.0). The % yields for the standard reaction time of 8 h are given in
Table 1.