Regio- And Stereo-chemical Effects in the Hydroboration of Δ2-Steroidal Allylic and Homoallylic Alcohols

Article abstract of DOI:10.1039/a702014g

A comparison between the hydroboration of δ²-steroidal 1x-allylic and 5x-homoallylic alcohols reveals that whereas both have a stereochemical directing effect, only the allylic alcohol modifies the regiospecificity of the reaction.

Full text of DOI:10.1039/a702014g

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282 J. CHEM. RESEARCH (S), 1997
J. Chem. Research (S),
1997, 282–283†
Regio- and Stereo-chemical Effects in the Hydroboration of
D2-Steroidal Allylic and Homoallylic Alcohols†
James R. Hanson,* Mansur D. Liman and Sivajini Nagaratnam
School of Molecular Sciences, University of Sussex, Brighton, Sussex BN1 9QJ, UK
A comparison between the hydroboration of D2-steroidal 1a-allylic and 5a-homoallylic alcohols reveals that whereas both
have a stereochemical directing effect, only the allylic alcohol modifies the regiospecificity of the reaction.
An allylic hydroxy group has a significant effect on the
products that are formed from an alkene by hydroboration
and oxidation with alkaline hydrogen peroxide.1–3 In cyclic
systems a significant proportion of the addition takes place
adjacent and trans to the hydroxy group of the allylic alchol.4
These effects on regioselectivity may compete with the nor-
mal stereochemical directing effects of the steroid carbon
skeleton.5,6 In order to evaluate the relative significance of
electronic and steric contributions, we compared the results
of hydroboration of the a-oriented axial allylic alcohol,
17b-acetoxy-1a-hydroxy-5a-androst-2-ene (2) and the a-ori-
ented axial homoallylic alcohol, 5a,17b-dihydroxy-
5a-androst-2-ene (3). In both cases the axial hydroxy group is
trans to the sterically directing 10b-methyl group.
using 1
M
borane in tetrahydrofuran followed by oxidation
with alkaline hydrogen peroxide. The products were sepa-
rated by chromatography on silica and the results are shown
in Fig. 1. The structures of the products were established
1
from the multiplicity of the CH(OH) resonances in the H
NMR spectrum10 and by comparison with literature data.11
The axial 2b-H of 2a,17b-dihydroxy- and 2a,5a,17b-tri-
hydroxy-5a-androstane appeared as a triplet (J 10.9 Hz) of
triplets (J 4.6 Hz) indicative of two diaxial and two axial:equa-
torial couplings. In 17b-acetoxy-1a,2a-dihydroxy-5a-andros-
tane and the corresponding triol, the 2b-H (dH 3.82 and 3.85
respectively) appeared as a doublet (J 10.9 Hz) of double-
doublets (J 2.9 and 5.2 Hz). The 1b-H of the 17b-acetate was
a doublet (dH 3.66, J 2.9 Hz). The smaller 1b:2a-coupling
constant is probably indicative of a slightly different confor-
mation of ring A brought about by hydrogen bonding in the
The substrates were prepared by literature methods.7,8,9
The hydroboration and oxidation reactions were carried out
OH
OH
R1
R1
HO
α-addition
+
R 2
HO
H
R 1
H
R1 = H
R1 = OH
(35)
R1 = H
R1 = OH
(28)
not detected
(18 as 17β-acetate)
+
H
(40 as 17β-alcohol)
1 R1 = H, R2 = O
2 R1 = OH, R2 = α-H, 17β-OAc
R1
R1
HO
β-addition
+
HO
R
1 = H
(17)
R
1 = H not detected
R1 = OH
R1 = OH
not detected
(13)
HO
α-addition
+
HO
OH
OH
OH
(20)
(29)
HO
OH
+
β-addition
3
HO
OH
OH
(8)
(30)
Fig. 1 Yields (%) of hydroboration products of androst-2-enes
1:2 glycol. The equatorial 2a-H signals were broad singlets.
The 3a,17b- and 3b,17b-dihydroxy- and 3a,5a,17b- and
3b,5a,17b-trihydroxy-5a-androstanes were known com-
pounds.11–13
*To receive any correspondence.
†This is a Short Paper as defined in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1997 283
0.77 (3 H, s, 19-H), 3.65 (1 H, t, J 8.2 Hz, 17a-H), 3.74 (3 H, s,
1b-H), 4.11 (1 H, brs, 2a-H). Irradiation of the signal at dH 0.77
produced an nOe enhancement of the signal at dH 3.74 (1.9%).
Further elution gave 1a,2a,17b-trihydroxy-5a-androstane (240
mg), needles, mp 140–142 °C (Found: C, 71.4; H, 10.3.
The influence of the allylic hydroxy group on the regio-
chemistry of the reaction can be seen in the increased propor-
tion of hydroboration of 17b-acetoxy-1a-hydroxy-5a-androst-
2-ene at C-2 compared to the unsubstituted case. However
the potential 1:3-diaxial interaction with the 10b-methyl
group reduces the trans directing effect of the hydroxy group.
On the other hand the homoallylic 5a-hydroxy group had
relatively little effect on the position of the hydroboration but
increased the proportion of b-face addition possibly through
the formation of bulky borate esters on the a-face of the
molecule.
C19H32O3 0 5H2O requires C, 71.8; H, 10.5%), vmax/cmꢀ1 3210; dH
. .
(CDCl3) 0.74 (3 H, s, 18-H), 0.79 (3 H, s, 19-H), 3.64 (2 H, m, 1b-
and 17a-H), 3.85 (1 H, ddd, J 2.9, 5.2 and 10.9 Hz, 2b-H).
(c) 5a,17b-Dihydroxyandrost-2-ene (1.2 g) was treated with 1
M
borane in THF (20 cm3) and oxidized with aqueous sodium hydrox-
ide and hydrogen peroxide as above. The products were separated
by chromatography on silica. Elution with 30% ethyl acetate:light
petroleum gave 3a,5a,17b-trihydroxyandrostane (251 mg), plates,
mp 193–195 °C (lit.,12 194–196 °C). Further elution gave
2b,5a,17b-trihydroxyandrostane (105 mg), needles, mp 207–209 °C
Experimental
.
General experimental details have been described previously.5
The steroids were crystallized from ethyl acetate or acetone:light
petroleum mixtures. 5a-Androst-2-en-17-one (1) had mp
107–108 °C (lit.,7 108–109 °C). 17b-Acetoxy-1a-hydroxyandrost-
2-ene, prepared by the treatment of 17b-acetoxy-1a,2a-epoxy-
androstan-3-one with hydrazine hydrate,8 had mp 131–
133 °C (Found: C, 75.4; H, 9.8. C21H32O3 requires C, 75.9; H, 9.7%),
(Found: C, 70.0; H, 11.0. C19H32O3 H2O requires C, 69.9; H,
10.5%), vmax/cmꢀ1 3499, 3391, 3320; dH (CDCl3) 0.74 (3 H, s, 18-H),
1.21 (3 H, s, 19-H), 3.65 (1 H, t, J 8.5 Hz, 17a-H), 4.18 (1 H, brs,
2a-H). Elution with 32% ethyl acetate:light petroleum gave
2a,5a,17b-trihydroxyandrostane (368 mg), prisms mp 201–202 °C
. .
(Found: C, 72.3; H, 10.8. C19H32O3 0 5H2) requires C, 71.9; 10.5%),
v
max/cmꢀ1 3501, 3405, 3310; dH (CDCl3) 0.74 (3 H, s, 18-H), 1.00
v
max/cmꢀ1 3510, 1734; dH (CDCl3) 0.72 (3 H, s, 18-H), 0.81 (3 H, s,
(3 H, s, 19-H), 3.64 (1 H, t, J 8.4 Hz, 17a-H), 4.10 (1 H, tt, J 4.5 and
11 Hz, 2b-H). Finally elution with 35% ethyl acetate:light petrol-
eum gave 3b,5a,17b-trihydroxy-androstane (386 mg), plates, mp
193–195 °C (lit.,13 194–105 °C).
19-H), 2.04 (3 H, s, OAc), 3.71 (1 H, brs, 1b-H), 4.59 (1 H, t, J 8 Hz,
17a-H), 5.87 (2 H, s, 2- and 3-H). 5a,17b-Dihydroxyandrost-2-ene
had mp 171–173 °C (lit.,9 171–172 °C).
Hydroboration Experiments.s(a) 5a-Androst-2-en-17-one (1)
(1 g) in dry THF (30 cm3) was treated with 1
M
borane in THF (20
cm3) under nitrogen at 0 °C for 4 h. Water (10 cm3) was added and
the solution was cooled. Aqueous 10% sodium hydroxide (20 cm3)
was added followed by the dropwise addition of 30% hydrogen
peroxide (30 cm3). The mixture was stirred overnight. Sodium sul-
fite (2 g) was added followed by acetic acid (1 cm3), water (50 cm3),
dil. hydrochloric acid (100 cm3) and ethyl acetate (100 cm3). The
mixture was stirred for a further 15 min. The organic phase was
separated, washed with water, brine and dried. The solvent was
evaporated to give a residue which was chromatographed on silica.
Elution with 25% ethyl acetate:light petroleum gave 3a,17b-di-
hydroxy-5a-androstane (370 mg), prisms, mp 221–223 °C (lit.,11
222–224 °C). Elution with 28% ethyl acetate:light petroleum gave
3b,17b-dihydroxy-5a-androstane (180 mg), needles, mp 167–
169 °C) (lit.,11 168 °C). Further elution with 30% ethyl acetate:light
petroleum gave 2a,17b-dihydroxy-5a-androstane (302 mg),
needles, mp 172–174 °C (Found: C, 77.7; H, 11.0. C19H32O2
requires C, 78.0; H, 11.0%), vmax/cmꢀ1 3490, 3382; dH (CDCl3) 0.73
(3 H, s, 18-H), 0.80 (3 H, s, 19-H), 3.63 (1 H, t, J 8.6 Hz, 17a-H),
3.77 (1 H, tt, J 4.6 and 10.9 Hz, 2b-H).
S. N. thanks the Eastern University, Sri Lanka, for study
leave and the British Council for financial assistance.
Received, 24th March 1997; Accepted, 22nd April 1997
Paper E/7/02014G
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1a,2b,17b-trihydroxy-5a-androstane (80 mg), needles, mp
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. .
152–155 °C (Found: C, 71.5; H, 10.6. C19H32O3 0 5H2O requires C,
71.8; H, 10.5%), vmax/cmꢀ1 3340; dH (CDCl3) 0.74 (3 H, s, 18-H),