Pd-catalyzed alkylation of halogen-substituted steroids with organozinc compounds

Article abstract of DOI:10.1134/S107042800806002X

A general procedure has been developed for the introduction of hydrophobic alkyl groups into positions 6, 3, and 17 of steroid molecules via palladium-catalyzed Negishi reaction of halogen-substituted steroids with benzyl- and alkylzinc halides.

Full text of DOI:10.1134/S107042800806002X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 6, pp. 785–790. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © G.V. Latyshev, N.V. Lukashev, I.P. Beletskaya, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 6,
pp. 797–801.
Dedicated to Prof. M. Yus on his 60th anniversary
Pd-Catalyzed Alkylation of Halogen-Substituted Steroids
with Organozinc Compounds
G. V. Latyshev, N. V. Lukashev, and I. P. Beletskaya
Faculty of Chemistry, Moscow State University, Vorob’evy gory 1, Moscow, 119992 Russia
e-mail: lukashev@aha.ru
Received August 13, 2007
Abstract—A general procedure has been developed for the introduction of hydrophobic alkyl groups into
positions 6, 3, and 17 of steroid molecules via palladium-catalyzed Negishi reaction of halogen-substituted
steroids with benzyl- and alkylzinc halides.
DOI: 10.1134/S107042800806002X
The use of organolithium and organomagnesium
compounds for the introduction of alkyl or aryl substit-
uents into various positions of steroid molecules gen-
erally requires protection and subsequent deprotection
at positions 3, 17, or others of the steroid skeleton,
where oxo or hydroxy groups are usually present.
Recently proposed synthetic approaches to aryl- and
vinyl-substituted steroid derivatives, based on Pd-cata-
lyzed cross-coupling reactions [1], do not imply the
necessity of introducing protecting groups; however, in
this case only the corresponding 3-Δ3- or 17-Δ16-tri-
fluoromethanesulfonates or halides derived from
17-oxo steroids should be used as initial compounds.
Cross-couplings of some related compounds with
organozinc [2–5], organoboron [2, 6–11], or organotin
compounds [5, 12–15] were reported previously. Such
trifluoromethanesulfonates are readily available from
the corresponding oxo derivatives according to Stang
[16]; 17-iodosteroids can be obtained from 17-oxo-
steroid hydrazone [17]. The application scope of the
above procedures for the introduction of aryl or vinyl
groups is strongly restricted; furthermore, mixtures of
products can be formed when enolization of the sub-
strate is ambiguous.
It is known that substitution at positions 4 and 6 of
androstane skeleton may give rise to enhanced aro-
matase inhibitor activity [18]. We recently proposed
for the first time to use 4-bromo-Δ4- and 6-chloro-
(bromo)-Δ4,6-steroids as substrates in Pd-catalyzed
arylation with arylboronic acids [19, 20] and Sonoga-
shira ethynylation [21]. Preliminary experiments
showed that some of the 6-aryl- and 6-ethynylsteroids
thus obtained exhibit a strong inhibitory effect on
MCF-7 tumor cells (breast cancer) and revealed
a correlation between the size of the hydrophobic sub-
stituent on C6 and antitumor activity.
Taking into account the above stated, we made
an attempt to modify steroid molecules via introduc-
tion into the 6-position of sterically hindered hydro-
Scheme 1.
X
X
X
Y
Y
Y
Me
Me
Me
Me
Me
Me
Pd(PPh3)2Cl2 (10%)
DMF, 20°C
+
RCH2ZnBr
+
O
O
O
Br
I, II
R
IIIa–IIIf
IV
I, IIIa–IIIe, IV, XY = O; II, IIIf, X = Ac, Y = OAc; III, R = Ph (a), 2-ClC6H4 (b, f), 4-MeC6H4 (c), 2-MeOC6H4 (d), Me3Si (e).
785

LATYSHEV et al.
786
Scheme 2.
R
I
Me
Me
Pd(PPh3)2Cl2 (10%)
DMF, 20°C
Me
Me
+ RCH2ZnBr
O
O
V
VIa–VIc
R = Ph (a), 2-ClC6H4 (b), Me3Si (c).
phobic substituents, both aryl and alkyl, with a view
to estimate antitumor activity of the modified com-
pounds. In the present communication we describe
a general procedure for the introduction of hydro-
phobic alkyl groups into positions 6, 3, and 17 of
steroid molecules. It is usually very difficult to intro-
duce alkyl groups into molecules of organic halogen
compounds in the presence of palladium catalysts and
alkylboronic acids, for the latter are much less reactive
than aryl- and vinylboronic acids. For this purpose, it
is best to use benzylzinc compounds that are readily
available from the corresponding benzyl bromides by
the action of activated zinc [22].
Raising the amount of Pd(PPh3)2Cl2 to 10 mol %
allowed us to attain 100% conversion in DMF both at
100°C (6 h) and at room temperature (16 h), and
6-benzylandrosta-4,6-diene-3,17-dione (IIIa) was iso-
lated in 88% yield as the only product. Under anal-
ogous conditions, we performed reactions with sub-
stituted benzylzinc bromides, including those having
substituents in the ortho position. The reaction with
sterically hindered trimethylsilylmethylzinc chloride
smoothly afforded 94% of steroid allylsilane IIIe. On
the other hand, pentafluorobenzylzinc bromide having
an electron-withdrawing pentafluorophenyl group and
allylzinc chloride failed to react with halosteroids
under the same conditions.
Anomalously high sensitivity of the reaction to the
nature of bromosteroid should be noted. The reactions
with 6-bromosteroids occurred fairly readily, while
even traces of the corresponding 4-benzyl derivative
were not detected in the reaction with vinylogous
4-bromoandrost-4-ene-3,17-dione under the optimal
conditions. No cross-coupling was observed in the re-
action of the same substrate in THF with 4-methoxy-
phenylzinc chloride obtained from the corresponding
Grignard compound.
The best results (the highest yield of compound
IIIa) in the reaction of 6-bromoandrosta-4,6-diene-
3,17-dione (I) with benzylzinc bromide (5 mol % of
[Pd], 100°C, 6 h) were obtained using polar solvents,
dimethylformamide being preferred. The reaction was
accompanied by formation of 3–5% of side hydrode-
halogenation product, androsta-4,6-diene-3,17-dione
(IV) (Scheme 1). The most efficient catalyst precursor
was Pd(PPh3)2Cl2 (see table). Strong electron-donating
sterically hindered and bidentate ligands turned out to
be weakly effective. Unexpectedly high efficiency was
observed in the presence of heterogeneous Pd/C cata-
lyst in combination with PPh3 (yield 75%).
Vinyl iodides are generally more reactive than vinyl
bromides in cross-coupling processes. However, the
Yields of compound IIIa in the cross coupling of 6-bromoandrosta-4,6-diene-3,17-dione (I) with benzylzinc bromidea
Catalyst
Pd(PPh3)4
Yield,b %
Catalyst
Yield,b %
68
83
48
45
Pd(dba)2/BINAPc
01
23
11
75
d
Pd(PPh3)2Cl2
Pd(dppb)Cl2
e
Pd(Cy3P)2Cl2
Pd(dba)2/2t-Bu3PH+ BF4–
Pd(dppf)Cl2
Pd/C+2PPh3
a
b
c
d
e
5% [Pd], DMF, 100°C, 6 h; 1–5% of compound IV is formed as by-product.
According to the 1H NMR data.
dba stands for dibenzylideneacetone, and BINAP, for 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene.
dppb stands for 1,4-bis(diphenylphosphino)butane.
dppf stands for 1,1′-bis(diphenylphosphino)ferrocene.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

Pd-CATALYZED ALKYLATION OF HALOGEN-SUBSTITUTED STEROIDS
787
Scheme 3.
OR'
OR'
Me
Me
Pd(PPh3)2Cl2 (10%)
DMF, 20°C
Me
Me
+
RCH2ZnBr
R
I
VII, VIII
IXa–IXd
VII, IXa–IXc, R′ = Ac; VIII, IXd, R′ = H; IX, R = Ph (a), 2-ClC6H4 (b), 4-MeC6H4 (c, d).
reactions of benzylzinc bromides with 17-iodosteroids
V and VI were characterized by a lower rate than
with bromosteroids I. Even after stirring for 40 h at
20°C, the reaction mixture obtained from iodosteroid
V, excess benzylzinc bromide, and 10 mol % of
Pd(PPh3)2Cl2 contained 83% of cross-coupling product
VIa and 17% of initial steroid V (Scheme 2). The
conversion of V in the reaction with o-chlorobenzyl-
zinc bromide in DMF was 70% in 64 h, other condi-
tions being equal. Further increase of the amounts of
the catalyst and organozinc reagent or raising the tem-
perature did not result in increased conversion. The
conversion of iodide V was complete in the reaction
with more active Me3SiCH2ZnCl, and 17-(trimethyl-
silylmethyl)androsta-4,16-dien-3-one (VIc) was isolat-
ed by column chromatography in 98% yield.
argon, and the mixture was stirred for 6 h at 20°C
(benzyl bromides) or for 16 h at 80°C (trimethylsilyl-
methyl chloride).
Halogen-substituted steroids I, II [20], and VIII
[23] were synthesized by known methods.
17-Iodoandrosta-4,16-dien-3-one (V). A solution
of 5.0 g (16.6 mmol) of 3-methoxyandrosta-3,5-dien-
17-one, 4.1 ml of triethylamine, and 11.6 ml
(23.9 mmol) of hydrazine hydrate in 96% ethanol was
stirred for 2 h on heating under reflux. The mixture
was diluted with methylene chloride and washed with
water, and the organic phase was dried over Na2SO4
and evaporated on a rotary evaporator. 3-Methoxy-
androsta-3,5-dien-17-one hydrazone, 4.55 g (87%),
thus obtained was then used without additional puri-
fication.
Despite the lack of steric hindrances, cross-cou-
pling of 17-acetoxy-3-iodoandrosta-3,5-diene (VII)
with benzylzinc bromides was fairly slow. Neverthe-
less, compounds IXa–IXc were formed as the only
products and were isolated in good yields (Scheme 3).
Steroid VIII possessing a free hydroxy group reacted
with excess 4-methylbemzylzinc bromide to give com-
pound IXd.
Iodine, 6.9 g (27.2 mmol), was added in small
portions under vigorous stirring to a solution of 4.04 g
(12.9 mmol) of 3-methoxyandrosta-3,5-dien-17-one
hydrazone and 18 ml of triethylamine in 81 ml of
anhydrous dioxane. The mixture was stirred for 30 min
at room temperature, an aqueous solution of Na2SO3
was added, the product was extracted into methylene
chloride, and the extract was washed with water, dried
over Na2SO4, and evaporated on a rotary evaporator.
The residue was dissolved in 30 ml of 96% ethanol,
3 ml of 48% hydrobromic acid was added, and the
mixture was stirred for 4 h at room temperature,
diluted with methylene chloride, washed with water,
dried over Na2SO4, and evaporated on a rotary evap-
orator. The residue was subjected to chromatography
on silica gel using methylene chloride–diethyl ether
(20:1) as eluent. Yield 3.31 g (65%), yellow needles,
mp 169°C (from MeOH); published data [7]: mp 165–
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded from
solutions in CDCl3 on a Bruker Avance 400 spec-
trometer at 400 and 100 MHz, respectively. The
MALDI-TOF spectra were obtained on a Bruker
Daltonics Ultra-Flex instrument in dithranol. The prod-
ucts were isolated by column chromatography on silica
gel (0.040–0.063 mm, Merck).
Organozinc compounds were prepared by the action
of metallic zinc on organic halogen compounds in
DMF [22]. Zinc dust, 156 mg (2.4 mmol), was dis-
persed in DMF, and 50.8 mg (0.2 mmol) of iodine was
added. When the yellow color disappeared, the corre-
sponding organic halogen compound was added under
1
168°C. H NMR spectrum, δ, ppm: 6.12 m (1H),
5.73 m (1H), 2.48–2.24 m (4H), 2.21–2.10 m (1H),
2.06–1.93 m (2H), 1.91–1.82 m (1H), 1.80–1.61 m
(4H), 1.56–1.41 m (2H), 1.29–0.93 m (3H), 1.20 s
(3H), 0.77 s (3H).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

LATYSHEV et al.
788
trum, δC, ppm: 219.4, 199.6, 162.3, 137.8, 136.6,
134.2, 133.3, 129.9, 129.5, 127.9, 126.8, 121.7, 50.8,
48.8, 48.2, 36.8, 36.4 (2C), 35.6, 33.9, 33.5, 31.2,
21.2, 19.9, 16.3, 13.7. MALDI-TOF mass spectrum:
m/z 409.18 [M + H]+. C26H30ClO2. Calculated: [M + H]
409.19.
3-Iodoandrosta-3,5-dien-17-yl acetate (VII).
A solution of 200 mg (0.5 mmol) of 3-iodoandrosta-
3,5-dien-17-ol (VIII), 12.2 mg (0.1 mmol) of 4-di-
methylaminopyridine, 102 mg (1.0 mmol) of acetic
anhydride, and 0.51 g (5.0 mmol) of triethylamine in
2 ml of methylene chloride was stirred for 24 h at
room temperature. The mixture was diluted with
methylene chloride, washed with three portions of
water, dried over Na2SO4, and evaporated on a rotary
evaporator. The residue was purified by column chro-
matography using CH2Cl2 as eluent. Yield 183.5 mg
6-(4-Methylbenzyl)androsta-4,6-diene-3,17-dione
(IIIc). Yield 36.9 mg (95%), amorphous substance.
1H NMR spectrum, δ, ppm: 7.05 d (2H, J = 8.1 Hz),
7.00 d (2H, J = 8.1 Hz), 5.98 br.s (1H), 5.89 s (1H),
3.54 d (1H, J = 15.7 Hz), 3.48 d (1H, J = 15.7 Hz),
2.55–2.35 m (4H), 2.29 s (3H), 2.16–1.96 m (3H),
1.88 m (1H), 1.69 m (3H), 1.52–1.24 m (4H), 1.10 s
(3H), 0.95 s (3H). 13C NMR spectrum, δC, ppm: 219.3,
199.5, 162.2, 137.7, 135.8, 135.7, 135.0, 129.1, 128.1,
122.2, 50.8, 49.0, 48.2, 38.8, 36.8, 36.3, 35.6, 34.0,
33.5, 31.3, 21.3, 20.9, 20.0, 16.2, 13.7. MALDI-TOF
mass spectrum: m/z 389.23 [M + H]+. C27H33O2. Cal-
culated: [M + H] 389.25.
1
(83%), colorless crystals. H NMR spectrum, δ, ppm:
6.54 m (1H), 5.34 m (1H), 4.60 m (1H), 2.70–2.53 m
(2H), 2.23–2.10 m (2H), 2.02 s (3H), 1.81–1.45 m
(7H), 1.44–0.98 m (6H), 0.96 s (3H), 0.81 s (3H).
Reactions of alkylzinc halides with halosteroids
I, II, V, VII, and VIII (Negishi reaction. General
procedure). A solution of the corresponding organozinc
compound in DMF, 0.1 ml (0.2 mmol), was added
under argon to a suspension of 0.1 mmol of halosteroid
I, II, V, VII, or VIII and 7.0 mg (0.01 mmol,
10 mol %) of Pd(PPh3)2Cl2 in 1.9 ml of DMF, and the
mixture was stirred for 16–24 h at room temperature.
The mixture was diluted with 15 ml of methylene
chloride, washed with water (5×10 ml), dried over
anhydrous Na2SO4, and evaporated under reduced
pressure. The residue was dissolved in 1.5 ml of
methylene chloride, and the solution was subjected to
column chromatography on silica gel using methylene
chloride–diethyl ether (20:1) as eluent (unless other-
wise stated).
6-(2-Methoxybenzyl)androsta-4,6-diene-3,17-di-
one (IIId). Yield 33.8 mg (84%), amorphous sub-
1
stance. H NMR spectrum, δ, ppm: 7.17 t.d (1H, J =
7.7, 1.7 Hz), 6.97 d.d (1H, J = 7.7, 1.7 Hz), 6.84 m
(2H), 5.92 br.s (1H), 5.89 s (1H), 3.81 s (3H), 3.58 d
(1H, J = 16.3 Hz), 3.47 d (1H, J = 16.3 Hz), 2.56–
2.36 m (4H), 2.15–1.97 m (3H), 1.88 d.t (1H, J = 12.8,
3.0 Hz), 1.76–1.59 m (3H), 1.50–1.24 m (4H), 1.13 s
(3H), 0.94 s (3H). 13C NMR spectrum, δC, ppm: 219.4,
200.0, 162.5, 157.1, 137.4, 134.6, 128.9, 127.5 (2C),
122.0, 120.4, 110.3, 55.3, 50.9, 49.0, 48.2, 36.8, 36.4,
35.6, 34.0, 33.5, 32.6, 31.4, 21.3, 20.0, 16.3, 13.8.
MALDI-TOF mass spectrum: m/z 405.37 [M + H]+.
C27H33O3. Calculated: [M + H] 405.24.
6-Benzylandrosta-4,6-diene-3,17-dione (IIIa).
1
Yield 33.0 mg (88%), amorphous substance. H NMR
spectrum, δ, ppm: 7.19 m (5H), 5.97 br.s (1H), 5.88 s
(1H), 3.58 d (1H, J = 15.9 Hz), 3.53 d (1H, J =
15.9 Hz), 2.44 m (4H), 2.16–2.00 m (3H), 1.89 m
(1H), 1.70 m (3H), 1.52–1.24 m (4H), 1.11 s (3H),
0.95 s (3H). 13C NMR spectrum, δC, ppm: 219.4,
199.6, 162.2, 138.9, 138.0, 134.8, 128.5, 128.2, 126.3,
122.2, 50.8, 48.9, 48.2, 39.2, 36.8, 36.3, 35.6, 33.9,
33.4, 31.2, 21.3, 19.9, 16.2, 13.7. Found, %: C 83.15;
H 7.85. C26H30O2. Calculated, %: C 83.38; H 8.07.
6-(Trimethylsilylmethyl)androsta-4,6-diene-3,17-
dione (IIIe) was synthesized using fourfold excess of
trimethylsilylmethylzinc chloride. Yield 35 mg (94%),
1
mp 179–181°C. H NMR spectrum, δ, ppm: 5.85 s
(1H), 5.81 br.s (1H), 2.58–2.30 m (4H), 2.10 m (2H),
1.98 m (1H), 1.88 m (1H), 1.75 d (1H, J = 14.5 Hz),
1.70 m (3H), 1.61 d (1H, J = 14.5 Hz), 1.46–1.15 m
(4H), 1.10 s (3H), 0.94 s (3H), 0.04 s (9H). Found, %:
C 74.33; H 9.36. C23H34O2Si. Calculated, %: C 74.54;
H 9.25.
6-(2-Chlorobenzyl)androsta-4,6-diene-3,17-dione
(IIIb). Yield 34.8 mg (85%), amorphous substance.
1H NMR spectrum, δ, ppm: 7.35 m (1H), 7.16 m (2H),
7.08 m (1H), 5.85 s (1H), 5.80 br.s (1H), 3.65 d (1H,
J = 16.7 Hz), 3.59 d (1H, J = 16.7 Hz), 2.60–2.34 m
(4H), 2.14–1.87 m (4H), 1.79–1.56 m (3H), 1.49–
1.29 m (4H), 1.15 s (3H), 0.94 s (3H). 13C NMR spec-
6-(2-Chlorobenzyl)-3,20-dioxopregna-4,6-dien-
17-yl acetate (IIIf). Yield 45.7 mg (92%), amorphous
1
substance. H NMR spectrum, δ, ppm: 7.34 m (1H),
7.15 m (2H), 7.07 m (1H), 5.84 s (1H), 5.73 s (1H),
3.65 d (1H, J = 16.7 Hz), 3.56 d (1H, J = 16.7 Hz),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008

Pd-CATALYZED ALKYLATION OF HALOGEN-SUBSTITUTED STEROIDS
789
2.93 m (1H), 2.60–2.40 m (2H), 2.28 m (1H), 2.10 s
(3H), 2.04 s (3H), 1.88–1.57 m (8H), 1.38 m (3H),
1.13 s (3H), 0.69 s (3H). 13C NMR spectrum, δC, ppm:
203.7, 199.5, 170.6, 162.5, 139.5, 136.7, 134.3, 132.9,
130.0, 129.6, 127.9, 126.8, 121.6, 96.4, 50.2, 49.1,
47.5, 37.3, 36.4 (2C), 34.1, 33.5, 31.1, 30.3, 26.4, 23.2,
21.2, 20.3, 16.3, 14.3. MALDI-TOF mass spectrum:
m/z 494.6 [M]+. Found, %: C 72.64; H 7.11.
C30H35ClO4. Calculated, %: C 72.78; H 7.13. M 494.2.
125.5, 121.5, 82.7, 51.3, 48.3, 43.6, 42.5, 36.8, 34.9,
34.2, 31.7, 31.4, 27.6, 25.9, 23.5, 21.1, 21.0, 20.6,
19.0, 12.1. MALDI-TOF mass spectrum: m/z 418.3
[M]+. Calculated: M 418.4.
3-(4-Methylbenzyl)androsta-3,5-dien-17-ol (IXd)
was synthesized using fourfold excess of benzylzinc
bromide. Reaction time 72 h. Yield 32.6 mg (86%),
1
mp 133–135°C. H NMR spectrum, δ, ppm: 7.06 d
(2H, J = 8.3 Hz), 7.03 d (2H, J = 8.3 Hz), 5.76 s (1H),
5.33 m (1H), 3.63 t (1H, J = 8.5 Hz), 3.27 s (2H),
2.30 s (3H), 2.18–1.55 m (10H), 1.48–1.23 m (4H),
1.16–0.94 m (4H), 0.90 s (3H), 0.76 s (3H). 13C NMR
spectrum, δC, ppm: 141.9, 136.9, 136.1, 135.4, 128.9
(2C), 128.7 (2C), 125.5, 121.6, 81.9, 51.6, 48.5, 43.6,
42.9, 36.6, 34.9, 34.2, 31.9, 31.4, 30.5, 25.9, 23.4,
21.0, 20.7, 19.0, 11.0.
17-(Trimethylsilylmethyl)androsta-4,16-dien-3-
one (VIc). Reaction time 48 h. Yield 34.8 mg (98%),
1
mp 118–121°C. H NMR spectrum, δ, ppm: 5.71 s
(
1H), 5.15 m (1H), 2.48–2.21 m (4H), 2.10–
1.93 m (2H), 1.91–1.77 m (2H), 1.75–1.55 m (4H),
1.54–1.38 m (2H), 1.33–0.92 m (5H), 1.19 s (3H),
0.74 s (3H), 0.01 s (9H). MALDI-TOF mass spectrum:
m/z 356.25 [M]+. Found, %: C 77.27; H 10.18.
C23H36OSi. Calculated, %: C 77.46; H 10.18. M 356.26.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 07-03-00619a) and by the Russian Academy of
Sciences (program OKhN-10).
3-Benzylandrosta-3,5-dien-17-yl acetate (IXa).
Reaction time 72 h. The product was purified using
methylene chloride as eluent. Yield 32.5 mg (80%),
1
REFERENCES
mp 149°C. H NMR spectrum, δ, ppm: 7.29–7.10 m
(5H), 5.76 s (1H), 5.33 m (1H), 4.59 d.d (1H, J = 7.8,
1.3 Hz), 3.31 s (2H), 2.22–2.10 m (2H), 2.02 s (3H),
1.96–1.85 m (1H), 1.80–1.71 m (2H), 1.70–0.94 m
(12H), 0.90 s (3H), 0.81 s (3H). Found, %: C 83.15;
H 8.63. C28H36O2. Calculated, %: C 83.12; H 8.97.
1. Skoda-Foldes, R. and Kollar, L., Chem. Rev., 2003,
vol. 103, p. 4095.
2. Potter, G.A., Barrie, S.E., Jarman, M., and Row-
lands, M.G., J. Med. Chem., 1995, vol. 38, p. 2463.
3. Przezdziecka, A., Kurek-Tyrlik, A., and Wicha, J., Col-
lect. Czech. Chem. Commun., 2002, vol. 67, p. 1658.
3-(2-Chlorobenzyl)androsta-3,5-dien-17-yl ace-
tate (IXb). Reaction time 72 h. The product was puri-
fied using methylene chloride as eluent. Yield 37.2 mg
(85%), glassy solid. 1H NMR spectrum, δ, ppm: 7.32 d
(1H, J = 7.3 Hz), 7.17–7.10 m (3H), 5.64 s (1H),
5.29 m (1H), 4.59 t (1H, J = 8.4 Hz), 3.44 s (2H),
2.20–1.93 m (4H), 2.02 s (3H), 1.78–0.96 m (13H),
0.91 s (3H), 0.81 s (3H). 13C NMR spectrum, δC, ppm:
171.2, 141.7, 137.6, 134.5, 134.4, 130.8, 129.4, 127.4,
126.6, 126.0, 121.7, 82.8, 51.3, 48.3, 42.5, 40.7, 36.8,
34.9, 34.1, 31.7, 31.3, 27.5, 26.2, 23.5, 21.1, 20.6,
19.0, 12.0. MALDI-TOF mass spectrum: m/z 437.5
[M – H]+. Calculated: M 437.2.
4. Arcadi, A., Burini, A., Cacchi, S., Delmastro, M.,
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3-(4-Methylbenzyl)androsta-3,5-dien-17-yl ace-
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tate (IXc). Reaction time 40 h. Yield 36.3 mg (87%),
1
glassy solid. H NMR spectrum, δ, ppm: 7.06 d (2H,
12. Skoda-Foldes, R., Pfeiffer, P., Kollar, L., Horvath, J.,
J = 8.1 Hz), 7.03 d (2H, J = 8.1 Hz), 5.76 s (1H),
5.32 m (1H), 4.59 t (1H, J = 8.4 Hz), 3.27 s (2H),
2.30 s (3H), 2.18–0.95 m (17H), 2.02 s (3H), 0.89 s
(3H), 0.81 s (3H). 13C NMR spectrum, δC, ppm: 171.2,
141.9, 136.9, 136.1, 135.4, 129.0 (2C), 128.7 (2C),
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008