Rearrangement of 18-iodo- and 20-iodopregnanes mediated by iodosyl derivatives

Article abstract of DOI:10.1039/b102688g

Conversion of 20-acetoxy-18-iodopregn-4-en-3-one 1 to the 18-iodosyl derivative by MCPBA resulted in a Wagner-Meerwein-type rearrangement with regioselective migration of the C13-C17 bond to give, in high yield, an abeo-pregnane in which C-18 was incorporated into ring D. The rearranged steroid was epoxidized in situ yielding a mixture of β and α 13,14-epoxides (3 and 4) which were characterized spectroscopically and by X-ray crystallography. When (20R)-20-iodopregn-4-en-3-one 9a was used as substrate, regioselective migration of the C16-C17 bond gave the D-homoandrostane with incorporation of C-20 into ring D in up to 95% yield. The 20S epimer 9b however, gave a mixture of substitution and rearrangement products. The crystal structures of the deacetylated β-epoxide 3 (5), the methanolysis product of α-epoxide 4 (7) and 20-iodopregnanes 9a and 9b are reported.

Full text of DOI:10.1039/b102688g

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Rearrangement of 18-iodo- and 20-iodopregnanes mediated by
iodosyl derivatives†
Daniel Nicoletti,a Alberto A. Ghini,a Ricardo F. Baggio,b M. Teresa Garlandc and
Gerardo Burton*a
1
a Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales,
Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, 1428 Buenos Aires, Argentina.
E-mail: burton@qo.fcen.uba.ar. Fax: 54-11-4576-3385
b Departamento de Física, Comisión Nacional de Energía Atómica, Avda del Libertador 8250,
(1429)Buenos Aires, Argentina
c Departamento de Física, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile,
Avda. Blanco Encalada 2008, Casilla 487-3, Santiago, Chile
Received (in Cambridge, UK) 22nd March 2001, Accepted 11th May 2001
First published as an Advance Article on the web 18th June 2001
Conversion of 20-acetoxy-18-iodopregn-4-en-3-one 1 to the 18-iodosyl derivative by MCPBA resulted in a
Wagner–Meerwein-type rearrangement with regioselective migration of the C13–C17 bond to give, in high yield,
an abeo-pregnane in which C-18 was incorporated into ring D. The rearranged steroid was epoxidized in situ
yielding a mixture of β and α 13,14-epoxides (3 and 4) which were characterized spectroscopically and by X-ray
crystallography. When (20R)-20-iodopregn-4-en-3-one 9a was used as substrate, regioselective migration of the
C16–C17 bond gave the D-homoandrostane with incorporation of C-20 into ring D in up to 95% yield. The 20S
epimer 9b however, gave a mixture of substitution and rearrangement products. The crystal structures of the
deacetylated β-epoxide 3 (5), the methanolysis product of α-epoxide 4 (7) and 20-iodopregnanes 9a and 9b are
reported.
C or D,6,7 under the mild reaction conditions associated with
carbocation generation by peracid oxidation of an 18-iodo
steroid (Scheme 1); these compounds present enhanced mobil-
Introduction
The oxidation of alkyl iodides with peracids gives rise to a
hypervalent iodine substituent with high nucleofugacity, which
readily experiences substitutions, eliminations or rearrange-
ments.1 The type of reaction, as determined by product distri-
bution, is dependent on substrate structure and solvent, thus
primary iodides give mainly displacement products, although
carbocationic shifts have been observed when substitution at
the iodine-bearing carbon is sterically hindered (e.g., treatment
of neopentyl iodide with MCPBA gives only 2-methylbutan-2-
ol and the corresponding m-chlorobenzoate).2 In a previous
publication we described the preparation of ketals and
hemiketals by attack of a ketone carbonyl oxygen on a hyper-
electrophilic carbon bearing the iodosyl moiety; the intermedi-
ates in these reactions, generated by MCPBA oxidation of
δ- and γ-iodo ketones, were the cyclic oxocarbenium ions.3
6-Oxa-5α-pregnanes and 18-hydroxy-20-oxopregnanes (as
18,20-hemiketals) were obtained in good yields and with high
stereoselectivity under mild conditions.
Scheme 1
ity of the steroid skeleton and often show interesting biological
properties.8
As a further application of iodosyl intermediates as masked
carbocations we now describe their use in Wagner–Meerwein-
type rearrangements using steroidal iodides as substrates. These
particular Wagner–Meerwein rearrangements involve the
generation of a carbocation next to a bicyclic system, followed
by a 1,2-shift of an adjacent C–C bond to generate a new
carbocation with modification of the bicyclic framework.4,5 We
were specially interested in the possibility of generating modi-
fied steroids with expanded rings by inclusion of C-18 into ring
Results and discussion
As starting material we chose the readily available (20R)-20-
acetoxy-18-iodopregn-4-en-3-one 1. It was expected that, at
variance with the 20-keto analog used previously,3 the lower
nucleophilicity of the ester-type oxygen at C-20 would not give
rise to a cyclic oxocarbenium ion, thus allowing for rearrange-
ment of the steroid ring system. Treatment of 1 with an excess
of MCPBA in different solvent systems resulted in regioselec-
tive migration of the C13–C17 bond (Table 1, entries 1–3). In
all cases the expected olefin 2 was epoxidized in the reaction
medium, yielding the 13,14-epoxide mixture 3 and 4. Formation
of the epoxides was evident in the 13C NMR spectrum of
the mixture where two pairs of resonances for non-protonated
† Electronic supplementary information (ESI) available: AM1 calcu-
lated structures for the most stable conformers of the iodosyl derivative
of 18-iodopregnane 1; the C-18 carbocation derived from 1 and the
iodosyl derivative of 20R-iodopregnane 9a. See http://www.rsc.org/
suppdata/p1/b1/b102688g/
DOI: 10.1039/b102688g
J. Chem. Soc., Perkin Trans. 1, 2001, 1511–1517
This journal is © The Royal Society of Chemistry 2001
1511

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Table 1 Reaction of iodopregnanes with MCPBA
MCPBA
Time
(t/h)
Temp
(θ/ЊC)
Entry
Substrate
(equiv.)
Solventa
Product (yield, %)b
1
2
3
4
5
6
7
8
9
1
6
6
A
B
C
D
A
E
C
D
A
E
3
2
3
1
3
3
3
1
3
3
5
25
0
25
0
25
25
25
0
25
25
25
3 ϩ 4 (1 : 1.5, 77)
3 ϩ 4 (1 : 1.5, 60)
3 ϩ 4 (1 : 3, 81)
10 (50); 11 (45)
10 (75); 11 (8)
10 (81)
1
1
8c
2.8
5
9a
9a
9a
9a
9b
9b
9b
9b
5
8c
2.8
5
12 (80)
11 (22); 14 (23); 13 (54)
10 (40); 13 (44)
10 (42); 13 (49)
12 (11); 15 (49)
10
11
5
8c
C
a A, ButOH–THF–water (3 : 2 : 1); B, ButOH–Cl2CH2–water (3 : 2 : 1); C, dry methanol; D, Cl2CH2 saturated with water; E, THF–water (3 : 1).
b Yields correspond to isolated products. c Dry MCPBA was used.
carbons appeared at δC 63.8/62.3 and 64.7/63.1, the latter pair
being more intense in all cases. Although regioselectivity of
bond migration was not dependent on the solvent used, stereo-
selectivity of the subsequent epoxidation and the overall yield
increased when the reaction was carried out in dry methanol
(Table 1, entry 3).‡
Fig. 1 Displacement ellipsoid diagrams14 for a) (20R)-20-hydroxy-
13β,14β-epoxy-17(13→18)-abeo-pregn-4-en-3-one 5 and b) (20R)-20-
acetoxy-14α-hydroxy-13β-methoxy-17(13→18)-abeo-pregn-4-en-3-one
7, showing the numbering scheme used. Displacement ellipsoids drawn
at a 40% probability level.
The structures of epoxides 3 and 4 were established based on
the following evidence. Attempts to separate the epoxide mix-
ture by column chromatography were partially successful, yield-
ing only small amounts of the major product 4. However, upon
treatment with 5% NaOH in THF–MeOH products could be
separated by flash chromatography on silica gel. The minor
component 3 gave the deacetylated derivative 5 which was crys-
tallized and its structure determined to be the 13β,14β-epoxide
by X-ray diffraction analysis (Fig. 1a). Reacetylation of 5 gave
epoxide 3, the 13C resonances for carbons 13 and 14 being
identical with those observed for the minor constituent in the
mixture described above. The major component 4 gave a
deacetylated derivative lacking the characteristic epoxide
signals observed previously. This compound was assigned
structure 6 which would arise from the in situ cyclization of
the deacetylated epoxide (Scheme 2). This was indicative of
the α stereochemistry for epoxide 4. Diagnostic resonances
for ether 6 were the two non-protonated carbons at δC 83.8
and 74.6 assigned to C-13 and C-14 respectively; the down-
field shifts (compared with 4) indicated opening of the
epoxide. The resonance of H-20 in the 1H NMR spectrum
showed coupling only to the vicinal methyl (H-21); a model
of compound 6 had a ca. 90Њ dihedral angle for H-17/H-20,
Scheme 2
hence no observable coupling is expected between these
hydrogens.§
Confirmation of the structure of 4 came from the meth-
anolysis of the original epoxide mixture. The resulting two
methoxy alcohols could be separated and the major product 7,
derived from 4, gave adequate crystals for X-ray diffraction
analysis which showed its structure as the 13β-methoxy-14α-
hydroxy derivative (Fig. 1b), the expected product arising from
trans axial cleavage of the 13α,14α-epoxide. Methanolysis of
the minor β-epoxide 3 also resulted in the expected trans axial
§ The resonance for H-20 in the 1H NMR spectrum of the C-20
epimeric ether obtained by deacetylation of the epoxide derived
from (20S)-20-acetoxy-18-iodopregn-4-en-3-one appeared as a double
quartet with J = 3.3 and 6.5 Hz.
‡ Reaction of the epimeric (20S)-20-acetoxy-18-iodopregn-4-en-3-one
with MCPBA under the same conditions showed no differences in the
regioselectivity of the rearrangement.
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J. Chem. Soc., Perkin Trans. 1, 2001, 1511–1517

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cleavage product, the 13β-hydroxy-14α-methoxy derivative 8.
This was evident in the 500 MHz NOESY spectrum of 8 which
showed strong correlations of the methoxy group hydrogens (at
δ 3.34) with H-7α (δ 1.45), H-16α (δ 1.72) and H-7β (δ 1.98),
clearly establishing its position at C-14 with the α stereo-
chemistry.
The above results are in agreement with the occurrence of a
regiospecific Wagner–Meerwein-type rearrangement in the
iodosyl derivative of 18-iodopregnane 1 with migration of the
C13–C17 bond and formation of a 17(13→18)-abeo-pregnane.
Due to the bulk of the iodoso group its most favourable
orientation would be anti to the C13–C14 bond, a concerted
pathway5 (sp3 alignment) would result in migration of that
bond with formation of a bicyclo[4.3.1] product. The experi-
mental findings thus are consistent with a non-concerted (sp2
alignment) pathway via a free carbocation on C-18 that may
adopt the appropriate alignment for migration of the C13–C17
bond (ring D expansion).¶
Fig. 2 Displacement ellipsoid diagrams14 for a) (20R)-20-iodopregn-
4-en-3-one 9a and b) (20S)-20-iodopregn-4-en-3-one 9b, showing
the numbering scheme used. Displacement ellipsoids drawn at a 40%
probability level.
The rearrangement of the structurally related 19-iodo-
androst-5-enes by peracid oxidation has been reported to give a
complex mixture of products of poor synthetic value; however,
this was probably due to the homoallylic nature of the iodine
substituent in those compounds.9
Scope
To expand the scope of this methodology, we carried out
MCPBA oxidation on secondary steroidal iodides, namely, the
epimeric iodopregnanes 9a and 9b. These compounds may be
easily prepared from 3-oxo-22,23-dinorchol-4-enoic acid and
separated by flash chromatography.10 The absolute configur-
ation of the major product of the reaction at C-20 was estab-
lished as 20S by X-ray crystallography (Fig. 2). Pregnanes
carrying a good leaving group at C-20 easily give Wagner–
Meerwein-type rearrangements under a wide variety of condi-
tions.11 Thus, reaction of 9a or 9b with MCPBA under the
conditions indicated in Table 1 gave a mixture of substitution
and/or rearrangement products depending on the configuration
of the iodine-bearing carbon, i.e. the 20R-iodopregnane 9a gave
only rearrangement products 10–12 (Table 1, entries 4–7), while
for the 20S-iodo epimer substitution products 13–15 predomin-
ated (Table 1, entries 8–11).
AM1 calculations on the iodosyl derivatives of 20-iodo-
pregnanes 9a and 9b showed that the most stable conformer
of the 20R epimer had its side chain orientated in the ideal
antiperiplanar alignment for the observed migration of the
C16–C17 bond.|| The predicted stereochemistry at C-20 for the
resulting products 10–12 was in agreement with the experi-
mental result, thus supporting a concerted Wagner–Meerwein-
type rearrangement (sp3 alignment) similar to that postulated
for the 20β-tosylates.11a On the other hand, the possible con-
formers of the C-20 carbocation resulting from loss of the
iodoso group did not show adequate alignment of the C16–C17
bond for the occurrence of a non-concerted rearrangement.
Similar calculations on the iodosyl derivative of the 20S-
iodopregnane did not favour the antiperiplanar alignment of
the C16–C17 bond. The fact that, on the one hand, the substi-
tution products showed retention of configuration at C-20 and,
on the other, the rearrangement product was the same as for the
20R epimer strongly suggests that the dominant mechanism in
this case involves the C-20 carbocation, which is consistent with
the more complex mixture of products obtained. The observed
rearrangement would thus follow a non-concerted pathway
(sp2 alignment).**
Conclusions
The experimental results presented herein illustrate that iodosyl
derivatives may act as masked carbocations and can be used as
substrates for Wagner–Meerwein-type rearrangements via con-
certed or non-concerted mechanisms. This methodology is a
¶ See electronic supplementary information at http://www.rsc.org/
suppdata/p1/b1/b102688g/
|| The I–C20–C17–C16 torsion angle of the most stable conformer
(171.9Њ) is very close to the experimental value of Ϫ178.3Њ for the same
angle in the 20R-iodopregnane 9a as determined by X-ray crystal-
lography (Fig. 2a).
** It should be noted that nucleophile attack on a steroidal C-20 sp2
carbon occurs from the less hindered α-face. Furthermore, if the
rearrangement were to occur by a concerted pathway the C-17 epimers
of compounds 10–12 should result.
J. Chem. Soc., Perkin Trans. 1, 2001, 1511–1517
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useful alternative that avoids the drastic acid media and/or
heavy metals classically used in these reactions.
127–129 ЊC (from acetone–PriOH–hexane) (Found: C, 73.9; H,
8.4. C23H32O4 requires C, 74.2; H, 8.7%); [α]D ϩ79.2 (c 0.53 in
CHCl3); λmax (MeOH)/nm 240 (ε/dm3 molϪ1 cmϪ1 12650); νmax
(KBr)/cmϪ1 1733 (C᎐O, acetate), 1669 (C᎐C–C᎐O), 1455, 1384,
᎐
᎐
᎐
Experimental
Mps were taken on a Fisher–Johns apparatus and are uncor-
1263 (C–O, acetate), 1042 and 742; δH (200 MHz) 1.09 (3H, s,
10-H3C), 1.16 (3H, d, J = 6.4, 20-H3C), 2.03 (3H, s, acetate),
4.78 (1H, dq, J20,21 = 6.4, J20,17 = 4.8, 20-H) and 5.72 (1H, br s,
4-H); δC (50 MHz) 16.7 (C-19), 17.3 (C-21), 21.2 (acetate), 21.3
(C-11), 24.6 (C-16), 26.4 (C-15), 27.8 (C-7), 30.1 (C-18), 32.7
(C-6), 33.7 (C-12), 33.9 (C-2), 35.3 (C-8), 35.5 (C-1), 38.0
(C-10), 41.6 (C-17), 45.3 (C-9), 63.1 (C-14), 64.7 (C-13), 73.5
(C-20), 124.3 (C-4), 169.8 (acetate), 170.2 (C-5), 199.5 (C-3);
m/z (EI) 372.2303 (Mϩ. C23H32O4 requires M, 372.2301), 330
(M Ϫ 42, 3), 312 (M Ϫ AcOH, 14%), 294 (M Ϫ AcOH Ϫ H2O,
5), 161 (20), 91 (29) and 43 (100).
Continued elution with the same solvent yielded a mixture
of epoxides 3 and 4 (0.121 g, 56%) in a 1.2 : 1 ratio (13C NMR).
Identity of β-epoxide 3 was confirmed by comparison (1H
and 13C NMR, TLC) with an authentic sample obtained as
described below.
rected. IR spectra were recorded in KBr pellets on a Nicolet
1
Magna IR 550 FT-IR spectrometer. H and 13C NMR spectra
were measured on a Bruker AC-200 (200.13 and 50.32 MHz) or
AM-500 (500.13 and 125.72 MHz) NMR spectrometer for
samples in deuteriochloroform (using tetramethylsilane as
internal standard). J-Values are given in Hertz. Electron-impact
mass spectra (EI) were measured in a GC-MS Shimadzu
QP-5000 mass spectrometer at 70 eV by direct inlet. Electron-
impact high-resolution mass spectra were obtained in a VG
ZAB BEQQ mass spectrometer. [α]D-Values are given in 10Ϫ1
deg cm2 gϪ1. Semiempirical calculations were performed with
Hyperchem 5.1 (Hypercube Inc.). All solvents used were
reagent grade. Solvents were evaporated at θ ≈ 45 ЊC under
reduced pressure. Extractive work-up included exhaustive
extraction with the solvent indicated, washing successively
with brine and water, drying with anhydrous sodium sulfate,
and evaporation of the solvent. Flash chromatography was
performed on silica gel Merck 9385 (40–63 µ). Reversed-
phase column chromatography was performed on octadecyl-
functionalized silica gel (Aldrich). Homogeneity of all com-
pounds was confirmed by TLC.
Method B. To a solution of MCPBA (55%) (0.54 g contain-
ing 1.72 mmol) in a mixture of ButOH (12 cm3), CH2Cl2 (1.0
cm3) and water (4.0 cm3) was quickly added a solution of 1
(0.140 g, 0.289 mmol) in CH2Cl2 (7.0 cm3). The solution was
stirred for 2 h at 0 ЊC and 10% aq. NaHSO3 (10 cm3) was added.
Work-up as above and purification by flash chromatography
(ethyl acetate–hexane, 20 : 80) gave a mixture of epoxides 3 and
4 (0.065 g, 60%) in a 1 : 1.5 ratio (by 13C NMR).
Dry MCPBA was prepared by passing a solution of MCPBA
(55% in dry CH2Cl2) through anhydrous sodium sulfate (dried
at 325 ЊC for 4 h). The resulting solution was kept for 4 h with
anhydrous sodium sulfate and transferred directly to the reac-
tion flask. The solvent was evaporated by passage of a stream
of nitrogen and the solid obtained was dried for 1 h at 25 ЊC
and 5 × 10Ϫ4 mmHg.
Method C. To a solution of dry MCPBA [from 1.69 g of
MCPBA (55%) containing 5.37 mmol] in dry MeOH (10 cm3)
was quickly added a solution of 1 (0.325 g, 0.671 mmol) in dry
MeOH (20 cm3). The solution was stirred for 3 h at room
temperature and 10% aq. NaHSO3 (10 cm3) was added. After
dilution with water, extractive work-up with ethyl acetate as
above gave a residue, which was purified by flash chromato-
graphy (ethyl acetate–hexane, 20 : 80) to yield a mixture of
epoxides 3 and 4 (0.2027 g, 81%) in a 1 : 3 ratio (by 13C NMR).
(20R)-20-Acetoxy-18-iodopregn-4-en-3-one 1
(20R)-20-Acetoxy-18-iodopregn-4-en-3-one
1 was obtained
from (20R)-20-hydroxypregn-4-en-3-one by conversion to
the corresponding 18-iodo derivative with diacetoxyiodo-
benzene–iodine10 and acetylation with an excess of acetic
anhydride–pyridine (1 : 1). Purification by reversed-phase flash
chromatography (MeOH–water, 75 : 25) gave pure acetate 1 as
(20R)-20-Hydroxy-13ꢀ,14ꢀ-epoxy-17(13→18)-abeo-pregn-4-en-
3-one 5 and (20R)-14ꢁ-hydroxy-13ꢀ,20-epoxy-17(13→18)-abeo-
pregn-4-en-3-one 6
an amorphous solid; νmax (KBr)/cmϪ1 1730 (C᎐O, acetate), 1672
᎐
(C᎐C–C᎐O), 1454, 1372, 1242 (C–O, acetate) and 1083; δ (200
᎐
᎐
H
To a solution of the mixture of epoxides 3 and 4 (1 : 1.5) (0.165
g, 0.443 mmol) in MeOH (12.5 cm3)–THF (12.5 cm3) was added
5% aq. NaOH (2.0 cm3) and the mixture was stirred for 18 h at
room temperature under a nitrogen atmosphere. The resulting
solution was neutralized with 5% aq. HCl, concentrated in
vacuo, diluted with water, and extracted with ethyl acetate. The
solvent was evaporated and the residue was purified by flash
chromatography (ethyl acetate–hexane, 30 : 70) to give cyclic
ether 6 (0.082 g); mp 178–180 ЊC (from MeOH) (Found C, 76.0;
H, 9.4. C21H30O3 requires C, 76.3; H, 9.2%); [α]D ϩ82.3 (c 0.56
in Cl3CH); λmax (MeOH)/nm 244 (ε/dm3 molϪ1 cmϪ1 13650);
νmax (KBr)/cmϪ1 3473 (OH), 1662 (C᎐C–C᎐O), 1455, 1284 and
1049 (C–O–C); δH (200 MHz) 1.14 (3H, d, J = 6.3, 20-H3C),
1.17 (3H, s, 10-H3C), 4.04 (1H, q, J = 6.3, 20-H) and 5.74 (1H,
d, J = 1.2, 4-H); δC (50 MHz) 18.3 (C-19), 21.7 (C-11), 21.7
(C-15), 21.8 (C-21), 24.8 (C-7), 27.2 (C-16), 31.7 (C-12), 32.4
(C-6), 33.8 (C-2), 35.4 (C-1), 36.6 (C-18), 38.6 (C-10), 40.6
(C-8), 41.7 (C-17), 46.2 (C-9), 74.6 (C-14), 78.2 (C-20), 83.8
(C-13), 123.1 (C-4), 172.1 (C-5), 200.0 (C-3); m/z (EI) 330.2192
(Mϩ. C21H30O3 requires M, 330.2195), 312 (M Ϫ H2O, 14%),
294 (M Ϫ 2H2O, 7), 284 (M Ϫ H2O Ϫ CO, 7), 270 (17), 124
(29), 55 (98) and 43 (100).
MHz) 1.19 (3H, s, 10-H3C), 1.22 (3H, d, J = 6.1, 20-H3C), 2.04
(3H, s, acetate), 3.06 (1H, d, Jgem = 11.0, 18-Ha), 3.36 (1H, d,
Jgem = 11.0, 18-Hb), 4.85 (1H, m, 20-H) and 5.74 (1H, br s, 4-H);
δC (50 MHz) 7.3 (C-18), 17.2 (C-19), 19.2 (C-21), 20.5 (C-11),
22.0 (acetate), 23.8 (C-15), 24.8 (C-16), 31.6 (C-7), 32.5 (C-6),
33.8 (C-2), 35.5 (C-1), 35.9 (C-8), 38.4 (C-10), 39.7 (C-12),
43.4 (C-13), 53.6 (C-9), 55.1 (C-14), 55.3 (C-17), 72.3 (C-20),
124.0 (C-4), 170.0 (C-5), 170.1 (acetate), 199.1 (C-3); m/z (EI)
357.2422 (M Ϫ I. C23H33O3 requires m/z, 357.2430), 297
(M Ϫ I Ϫ AcOH, 27), 279 (5), 173 (13), 105 (11) and 43 (100).
᎐
᎐
Reaction of (20R)-20-acetoxy-18-iodopregn-4-en-3-one 1 with
MCPBA: (20R)-20-acetoxy-13ꢀ,14ꢀ-epoxy-17(13→18)-abeo-
pregn-4-en-3-one 3 and (20R)-20-acetoxy-13ꢁ,14ꢁ-epoxy-
17(13→18)-abeo-pregn-4-en-3-one 4
Method A. To a solution of MCPBA (55%) (1.08 g contain-
ing 3.44 mmol) in a mixture of ButOH (24 cm3), THF (2.0 cm3)
and water (8.0 cm3) was quickly added a solution of 1 (0.28 g,
0.578 mmol) in THF (14 cm3). The solution was stirred for 3 h
at room temperature and 10% aq. NaHSO3 (20 cm3) was added.
The reaction mixture was diluted with ethyl acetate and the
organic layer was washed successively with 10% aq. NaHSO3
and brine, dried with Na2SO4, and the solvent was evaporated.
Fractionation of the residue by flash chromatography (ethyl
acetate–hexane, 20 : 80) gave α-epoxide 4 (0.045 g, 21%); mp
Continued elution (ethyl acetate–hexane, 40 : 60) gave 20-
hydroxy epoxide 5 (0.051 g); [α]D ϩ63.6 (c 0.51 in CHCl3); λmax
(MeOH)/nm 244 (ε/dm3 molϪ1 cmϪ1 11410); νmax (KBr)/cmϪ1
3415 (OH), 1669 (C᎐C–C᎐O), 1448, 1355 and 875; δ (200
᎐
᎐
H
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MHz) 1.10 (3H, s, 10-H3C), 1.14 (3H, d, J = 6.3, 20-H3C), 3.56
(1H, dq, J20,21 = 6.3, J17,20 = 3.5, 20-H) and 5.73 (1H, br s, 4-H);
δC (50 MHz) 16.8 (C-19), 18.4 (C-11), 20.5 (C-21), 21.2 (C-18),
28.2 (C-16), 29.6 (C-15), 31.3 (C-7), 33.1 (C-6), 33.6 (C-12), 33.8
(C-2), 35.3 (C-1), 38.9 (C-10), 39.5 (C-8), 40.4 (C-17), 51.2
(C-9), 62.5 (C-14), 64.0 (C-13), 71.5 (C-20), 124.1 (C-4), 169.7
(C-5), 199.2 (C-3); m/z (EI) 330.2193 (Mϩ. C21H30O3 requires
M, 330.2195), 312 (M Ϫ H2O, 2%), 294 (M Ϫ 2H2O, 2%), 279
(8), 149 (29), 55 (92) and 43 (100).
s, acetate), 3.05 (3H, s, OCH3), 5.12 (1H, dq, J20,21 = 6.2,
J20,17 = 9.5, 20-H) and 5.73 (1H, s, 4-H); δC (50 MHz) 17.6
(C-19), 19.0 (C-21), 19.3 (C-11), 21.1 (C-16), 21.6 (acetate), 25.3
(C-7), 25.9 (C-15), 32.6 (C-6), 33.9 (C-2), 34.4 (C-12), 35.5
(C-1), 36.9 (C-17), 38.6 (C-18), 38.7 (C-8), 38.9 (C-10), 46.3
(C-9), 47.7 (OMe), 73.2 (C-20), 73.9 (C-14), 76.3 (C-13), 123.3
(C-4), 170.6 (acetate), 171.1 (C-5), 199.5 (C-3); m/z (EI) 404
(Mϩ, 27%), 372 (M Ϫ MeOH, 6), 354 (M Ϫ MeOH Ϫ H2O, 4),
344 (M Ϫ AcOH, 5), 326 (M Ϫ AcOH Ϫ H2O, 12), 312
(M Ϫ AcOH Ϫ MeOH, 59), 294 (22), 137 (22), 124 (46), 55 (41)
and 43 (100).
Crystal structure determination of 20-hydroxy epoxide 5
Continued elution with the same solvent gave 14-methoxy
alcohol 8 (0.047 g); mp 209–211 ЊC (from acetone); νmax (KBr)/
cmϪ1 3604 (OH), 1727 (C᎐O, acetate), 1672 (C᎐C–C᎐O), 1456
Single crystals of 20-hydroxy epoxide 5 in the form of large
plates were obtained from acetone. They were conveniently cut
and mounted into glass fibre under a protective coating of inert
oil.
᎐
᎐
᎐
and 1379; δH (500 MHz) 1.16 (3H, s, 10-H3C), 1.26 (3H, d,
J = 6.3, 20-H3C), 2.09 (3H, s, acetate), 3.34 (3H, s, OCH3), 5.62
(1H, dq, J20,21 = 6.3, J20,17 = 9.2, 20-H) and 5.70 (1H, s, 4-H); δC
(50 MHz) 18.6 (C-19), 19.7 (C-21), 20.4 (C-11), 21.5 (acetate),
22.4 (C-15), 27.4 (C-7), 29.0 (C-16), 33.5 (C-6), 33.7 (C-12), 34.0
(C-2), 34.1 (C-18), 35.6 (C-1), 37.8 (C-8), 38.9 (C-10), 40.1
(C-9), 46.4 (C-17), 52.5 (OMe), 72.0 (C-13), 74.0 (C-20), 78.2
(C-14), 123.1 (C-4), 170.5 (acetate), 171.0 (C-5), 199.8
(C-3); m/z (EI) 404.2558 (Mϩ. C24H36O5 requires M, 404.2562),
386 (M Ϫ H2O, 1%), 326 (M Ϫ H2O Ϫ AcOH, 7.5), 312
(M Ϫ AcOH Ϫ MeOH, 3), 294 (3), 137 (22), 124 (11), 57 (22)
and 43 (100).
Crystal data. C21H30O3, M = 330.45, space group P212121 (no.
19), a = 7.976(3), b = 9.399(4), c = 4.084(11) Å, V = 1805.5(14)
Å3, Z = 4, Dx = 1.22 g cmϪ3, F(000) = 720, µ(Mo-Kα) = 0.08
mmϪ1 (no absorption corrections applied), T = 293 K, colour-
less blocks, 0.28 × 0.22 × 0.18 mm, Siemens R3m diffrac-
tometer, ω/2θ scans, θ-range: 1.69 to 24.99Њ. The structure
was solved by direct methods12 and refined by full matrix
least squares13 in F 2 with 1851 independent reflexions to
give R1 = 0.053, wR2 = 0.090 for 1053 observed reflexions
[I > 2σ(I)] and 249 parameters refined.††
Crystal structure determination of 13-methoxy alcohol 7
(20R)-20-Acetoxy-13ꢀ,14ꢀ-epoxy-17(13→18)-abeo-pregn-4-en-
3-one 3
Single crystals of 13-methoxy alcohol 7 in the form of large
plates were obtained from acetone. They were conveniently cut
and mounted into glass fibre under a protective coating of inert
oil.
To a solution of 20-hydroxy epoxide 5 (0.025 g, 0.076 mmol) in
CH2Cl2 (2.0 cm3) were added acetic anhydride (0.85 cm3, 9
mmol), triethylamine (1.5 cm3, 11 mmol) and DMAP (0.003 g,
0.025 mmol). The mixture was stirred for 18 h at 5 ЊC, diluted
with CH2Cl2, washed with 5% aq. NaHCO3 and dried with
sodium sulfate. Evaporation of the solvent gave β-epoxide 3
(0.027 g); mp 112–115 ЊC (from Pri2O) (Found: C, 74.4; H, 8.9.
C23H32O4 requires C, 74.2; H, 8.7%); [α]D ϩ65.2 (c 0.53 in
CHCl3); λmax (MeOH)/nm 240 (ε/dm3 molϪ1 cmϪ1 12600);
νmax (KBr)/cmϪ1 1734 (C᎐O, acetate), 1674 (C᎐C–C᎐O), 1452,
1376, 1245 (C–O, acetate), 1045 and 852; δH (200 MHz) 1.10
(3H, s, 10-H3C), 1.14 (3H, d, J = 6.4, 20-H3C), 2.02 (3H, s,
acetate), 4.71 (1H, dq, J20,21 = 6.4, J20,17 = 4.9, 20-H) and 5.72
(1H, br s, 4-H); δC (50 MHz) 16.8 (C-19 and C-21), 18.4 (C-11),
20.8 (C-18), 21.2 (acetate), 28.1 (C-16), 29.6 (C-15), 31.2 (C-7),
33.0 (C-6), 33.5 (C-12), 33.8 (C-2), 35.3 (C-1), 38.0 (C-8), 38.9
(C-10), 39.4 (C-17), 51.1 (C-9), 62.3 (C-14), 63.8 (C-13), 73.6
(C-20), 124.1 (C-4), 169.5 (acetate), 170.6 (C-5), 199.0 (C-3);
m/z (EI) 330 (M Ϫ 42, 3%), 312 (M Ϫ AcOH, 14), 296 (2), 284
(5), 189 (5), 124 (11), 55 (42) and 43 (100).
Crystal data. C24H36O5, M = 404.53, space group P212121 (no.
19), a = 7.518(2), b = 16.476(6), c = 17.818(8) Å, V = 2207.2(14)
Å3, Z = 4, Dx = 1.22 g cmϪ3, F(000) = 880, µ(Mo-Kα) = 0.08
mmϪ1 (no absorption corrections applied), T = 293 K, colour-
less blocks, 0.32 × 0.20 × 0.17 mm, Siemens R3m diffrac-
tometer, ω/2θ scans, θ-range: 1.68 to 25.00Њ. The structure was
solved by direct methods12 and refined by full matrix least
squares13 in F 2 with 2773 independent reflexions to give
R1 = 0.053, wR2 = 0.090 for 1248 observed reflexions [I > 2σ(I)]
and 302 parameters refined.††
᎐
᎐
᎐
Crystal structure determination of (20R)-20-iodopregn-4-en-3-
one 9a and (20S)-20-iodopregn-4-en-3-one 9b
(20R)-20-Iodopregn-4-en-3-one 9a and (20S)-20-iodopregn-4-
en-3-one 9b were obtained as previously described.10 Crystals
of both epimers were obtained by very slow evaporation of a
saturated acetone solution. After a few days, quite dissimilar
crystals were obtained: while those of compound 9b grew as
very thin plates emerging out of a central nucleus, in a very
crowded crystalline conglomerate, those of compound 9a grew
as isolated pinacoidal prisms. In both cases it was necessary to
cut the X-ray specimens out of the available material in order to
reduce their size to make them suitable for X-ray analysis.
(20R)-20-Acetoxy-14ꢁ-hydroxy-13ꢀ-methoxy-17(13→18)-abeo-
pregn-4-en-3-one 7 and (20R)-20-acetoxy-13ꢀ-hydroxy-14ꢁ-
methoxy-17(13→18)-abeo-pregn-4-en-3-one 8
To a solution of the mixture of epoxides 3 and 4 (1 : 1.5) (0.175
g, 0.47 mmol) in dry MeOH (40 cm3) was added 0.5 M meth-
anolic sulfuric acid (1.0 cm3). The solution was stirred for 1 h at
room temperature, neutralized with saturated aq. NaHCO3,
and concentrated in vacuo to a fifth of its volume. The residue
obtained after extractive work-up with ethyl acetate was frac-
tionated by flash chromatography (ethyl acetate–hexane,
20 : 80) to yield 13-methoxy alcohol 7 (0.082 g); mp 215–217 ЊC
(from acetone) (Found: C, 71.2; H, 9.1. C24H36O5 requires C,
Crystal data of compound 9a. C21H31IO, M = 426.36,
orthorhombic, space group P212121 (no. 19), a = 7.887(3),
b = 12.510(2), c = 20.083(6) Å, V = 1981.4(9) Å3, Z = 4,
Dx = 1.43 g cmϪ3, F(000) = 872, µ(Mo-Kα) = 1.620 mmϪ1 (no
absorption corrections applied), T = 293 K, crystal dimensions
0.40 × 0.40 × 0.28 mm, Siemens R3m diffractometer, ω/2θ
scans, θ-range: 1.95 to 25.48Њ. The structure was solved by
direct methods12 and refined by full matrix least squares13 in F 2
with 2681 independent reflexions to give R1 = 0.0319,
wR2 = 0.0785 for 2312 observed reflexions [I > 2σ(I)] and 211
parameters refined. Flacks parameter (C: correct, I: inverted
chirality) C = Ϫ0.01(4), I = 0.99(4); this parameter should be
71.3; H, 9.0%); νmax (KBr)/cmϪ1 3422 (OH), 1727 (C᎐O,
acetate), 1663 (C᎐C–C᎐O), 1452, 1251 and 1076; δ (200 MHz)
1.20 (3H, s, 10-H3C), 1.25 (3H, d, J = 6.2, 20-H3C), 2.03 (3H,
᎐
᎐
᎐
H
†† CCDC reference numbers 161559–161562. See http://www.rsc.org/
suppdata/p1/b1/b102688g/ for crystallographic files in .cif format.
J. Chem. Soc., Perkin Trans. 1, 2001, 1511–1517
1515

View Article Online
close to zero for the correct structure and close to one if the
and water, and dried with Na2SO4. Evaporation of the solvent
chirality is inverted.15††
and fractionation by flash chromatography (ethyl acetate–
hexane, 10 : 90) yielded chlorobenzoate 11 (0.009 g, 8%).
Continued elution with ethyl acetate–hexane (30 : 70) gave the
D-homoandrostenone 10 (0.056 g, 75%). Both compounds
were identical (NMR, TLC) with those obtained above.
Crystal data of compound 9b. C21H31IO, M = 426.36, ortho-
rhombic, space group P212121 (no. 19), a = 6.696(2),
b = 11.819(32), c = 24.686(7) Å, V = 1953.7(10) Å3, Z = 4,
Dx = 1.45 g cmϪ3, F(000) = 872, µ(Mo-Kα) = 1.643 mmϪ1 (no
absorption corrections applied), T = 293 K, crystal dimensions
0.42 × 0.38 × 0.10 mm, Siemens R3m diffractometer, ω/2θ
scans, θ-range: 1.65 to 24.97Њ. The structure was solved by
direct methods12 and refined by full matrix least squares13 in
F 2 with 2071 independent reflexions to give R1 = 0.0557,
wR2 = 0.1426 for 1198 observed reflexions [I > 2σ(I)] and 211
parameters refined. Flacks parameter (C: correct, I: inverted
chirality) C = Ϫ0.02(8), I = 0.90(8).15††
Method C. To a solution of MCPBA (55%) (0.310 g contain-
ing 0.99 mmol) in THF (5.0 cm3)–water (5.0 cm3) was quickly
added a solution of 9a (0.085 g, 0.199 mmol) in THF (10 cm3).
The resulting solution was stirred for 3 h at room temperature
and 10% aq. NaHSO3 (10 cm3) was added. The reaction mix-
ture was diluted with ethyl acetate and the organic layer was
washed successively with saturated aq. NaHCO3, brine and
water, and dried with Na2SO4. Evaporation of the solvent
followed by purification by flash chromatography (ethyl acetate–
hexane, 30 : 70) yielded the D-homoandrostenone 10 (0.051 g,
81%) identical (NMR, TLC) with that obtained above.
Reaction of (20R)-20-iodo-pregn-4-en-3-one 9a with MCPBA:
17aꢀ-hydroxy-17ꢁ-methyl-D-homoandrost-4-en-3-one 10 and
17aꢀ-(3-chlorobenzoyloxy)-17ꢁ-methyl-D-homoandrost-4-en-3-
one 11
Reaction of (20R)-20-iodopregn-4-en-3-one 9a with MCPBA–
MeOH: 17aꢀ-methoxy-17ꢁ-methyl-D-homoandrost-4-en-3-one
Method A. To a solution of dry MCPBA [from 0.411 g of
MCPBA (55%) containing 1.31 mmol] in CH2Cl2 (20 cm3)–
water (0.125 cm3) was quickly added a solution of (20R)-20-
iodopregn-4-en-3-one 9a (0.200 g, 0.47 mmol) in CH2Cl2 (20
cm3). The resulting solution was stirred for 1 h at 0 ЊC and 10%
aq. NaHSO3 (10 cm3) was added. The organic layer was washed
successively with saturated aq. NaHCO3, brine and water, and
dried with Na2SO4. Evaporation of the solvent followed by
flash chromatography (ethyl acetate–hexane, 10 : 90), gave
chlorobenzoate 11 (0.096 g, 45%); mp 210–213 ЊC (from Pri2O)
(Found: C, 73.9; H, 7.9. C28H35ClO3 requires C, 73.9; H, 7.8 %);
[α]D ϩ108Њ (c 0.6 in CHCl3); λmax (MeOH)/nm 236 (ε/dm3 molϪ1
12
To a solution of dry MCPBA [from 0.381 g of MCPBA (55%)
containing 1.21 mmol] in dry MeOH (5.0 cm3) was quickly
added a solution of 9a (0.065 g, 0.152 mmol) in dry MeOH (10
cm3). The solution was stirred for 3 h at room temperature and
10% aq. NaHSO3 (10 cm3) was added. The reaction mixture
was diluted with water and exhaustively extracted with ethyl
acetate. Evaporation of the extract followed by purification
by flash chromatography (ethyl acetate–hexane, 3 : 97) gave
D-homoandrostenone 12 (0.040 g, 80%); mp 141–142 ЊC (from
acetone) (Found: C, 79.6; H, 10.6. C22H34O2 requires C, 80.0; H,
10.4%); [α]D ϩ50.5 (c 0.6 in CHCl3); λmax (MeOH)/nm 244
(ε/dm3 molϪ1 cmϪ1 15500); νmax (KBr)/cmϪ1 1678 (C᎐C–C᎐O),
cmϪ1 21700); νmax (KBr)/cmϪ1 1719 (C᎐O, benzoate), 1672
᎐
᎐
᎐
(C᎐C–C᎐O), 1460, 1287, 1259, 1126, 1078, 969, 742 and 696
᎐
᎐
1453, 1233, 1184 and 1099 (C–O, OMe); δH (200 MHz) 0.84
(3H, s, 13-H3C), 0.96 (3H, d, J17,21 = 6.1, 17-H3C), 1.17 (3H, s,
10-H3C), 2.21 (1H, d, J17a,17 = 10.1, 17a-Hα), 3.74 (3H, s, OCH3)
and 5.72 (1H, br s, 4-H); δC (50 MHz) 11.3 (C-18), 17.5 (C-19),
19.2 (C-21), 19.9 (C-11), 23.4 (C-15), 31.4 (C-16), 32.8 (C-7),
33.6 (C-6), 33.8 (C-17), 33.9 (C-2), 35.1 (C-1), 35.4 (C-8), 37.5
(C-12), 38.7 (C-13), 39.9 (C-10), 49.9 (C-14), 53.5 (C-9), 62.2
(OMe), 96.1 (C-17a), 123.4 (C-4), 171.3 (C-5), 199.4 (C-3); m/z
(EI) 330 (Mϩ, 35%), 315 (M Ϫ 15, 4), 298 (M Ϫ MeOH, 10),
288 (M Ϫ 42, 8), 256 (M Ϫ 42 Ϫ MeOH, 7), 124 (30), 105 (25),
85 (60) and 55 (100).
(aromatic); δH (200 MHz) 0.84 (3H, d, J17,21 = 6.1, 17-H3C), 1.04
(3H, s, 10-H3C), 1.15 (3H, s, 13-H3C), 4.60 (1H, d, J17a,17 = 10.6,
17a-Hα), 5.72 (1H, br s, 4-H) and 7.30–8.00 (4H, m, ArH);
δC (50 MHz) 12.5 (C-18), 17.5 (C-19), 18.6 (C-21), 19.8 (C-11),
23.4 (C-15), 31.3 (C-16), 31.9 (C-17), 32.7 (C-7), 33.1 (C-6), 33.8
(C-2), 35.1 (C-8), 35.4 (C-1), 36.8 (C-12), 38.6 (C-10), 38.8
(C-13), 49.5 (C-14), 53.2 (C-9), 86.8 (C-17a), 123.5 (C-4), 127.7
(C-6Ј), 129.5 (C-5Ј), 129.7 (C-2Ј), 129.8 (C-1Ј), 132.3 (C-4Ј),
134.5 (C-3Ј), 165.2 (ArCO2), 170.5 (C-5), 199.2 (C-3); m/z (EI)
454.2275 (Mϩ. C28H25ClO requires M, 454.2275), 412 (12%),
298 (M Ϫ C7H4ClO2, 43), 256 (17), 161 (20), 175 (43), 139 (100),
111 (35) and 55 (39).
Continued elution with ethyl acetate–hexane (30 : 70) gave
the D-homoandrostenone 10 (0.074 g, 50%); mp 178–180 ЊC
(from Pri2O) (Found: C, 79.5; H, 10.5. C21H32O2 requires C,
79.7; H, 10.2%); [α]D ϩ69.6 (c 0.6 in CHCl3); λmax (MeOH)/nm
242 (ε/dm3 molϪ1 cmϪ1 14700); νmax (KBr)/cmϪ1 3448 (OH),
Reaction of (20S)-20-iodopregn-4-en-3-one 9b with MCPBA
Method A. Reaction of iodopregnane 9b (0.180 g, 0.42
mmol) with MCPBA as for the epimeric 20-iodopregnane 9a
(method A), and fractionation by flash chromatography (ethyl
acetate–hexane, 10 : 90), yielded a mixture of chlorobenzoates
1
1666 (C᎐C–C᎐O), 1453, 1284, 1238 and 1056; δ (200 MHz)
᎐
᎐
H
11 and 14 (0.0792 g, 45%) in a 1 : 1.3 ratio (by H NMR), the
0.85 (3H, s, 13-H3C), 0.96 (3H, d, J17,21 = 6.2, 17-H3C), 1.16
(3H, s, 10-H3C), 2.71 (1H, d, J17a,17 = 10.6, 17a-Hα) and 5.72
(1H, br s, 4-H); δC (50 MHz) 11.5 (C-18), 17.6 (C-19), 19.2
(C-21), 20.1 (C-11), 23.5 (C-15), 31.4 (C-16), 32.9 (C-6), 32.9
(C-7), 33.5 (C-17), 33.9 (C-2), 35.2 (C-8), 35.5 (C-1), 37.2
(C-12), 38.8 (C-10), 38.8 (C-13), 49.6 (C-14), 53.4 (C-9), 85.2
(C-17a), 123.4 (C-4), 171.2 (C-5), 199.4 (C-3); m/z (EI) 316
(Mϩ, 18%), 301 (M Ϫ CH3, 6), 283 (M Ϫ CH3 Ϫ H2O, 43), 274
(6), 175 (20), 69 (100) and 43 (94).
latter identified upon hydrolysis as described below. Continued
elution with ethyl acetate–hexane (30 : 70) gave (20S)-20-
hydroxypregn-4-en-3-one (13) (0.072 g, 54%) identical (NMR,
TLC) with an authentic sample. To the mixture of chloroben-
zoates 11 and 14 obtained above (0.040 g, 0.088 mM) in THF
(2.0 cm3)–MeOH (2.0 cm3) was added aq. 5% NaOH (0.5 cm3)
and the solution was stirred for 12 h at room temperature, then
was neutralized with 5% aq. HCl and exhaustively extracted
with ethyl acetate. Fractionation by flash chromatography
(ethyl acetate–hexane, 10 : 90) gave D-homoandrostenone 10
(0.012 g) identical (NMR, TLC) with that obtained above.
Continued elution (ethyl acetate–hexane, 30 : 70) yielded (20S)-
20-hydroxypregn-4-en-3-one (13) (0.0125 g), identical with an
authentic sample.
Method B. To a solution of MCPBA (55%) (0.370 g contain-
ing 1.18 mmol) in a mixture of ButOH (12.0 cm3), THF (2.0
cm3) and water (4.0 cm3) was quickly added a solution of 9a
(0.100 g, 0.234 mmol) in THF (6.0 cm3). The resulting solution
was stirred for 3 h at room temperature and 10% aq. NaHSO3
(10 cm3) was added. The reaction mixture was diluted with ethyl
acetate, washed successively with saturated aq. NaHCO3, brine
Method B. Reaction of iodopregnane 9b (0.071 g, 0.167
mmol) with MCPBA as for the epimeric 20-iodopregnane 9a
1516
J. Chem. Soc., Perkin Trans. 1, 2001, 1511–1517

View Article Online
(method B) followed by fractionation by flash chromatography
(ethyl acetate–hexane, 20 : 80), gave the D-homoandrostenone
(10) (0.021 g, 40%). Continued elution with the same solvent,
gave (20S)-20-hydroxypregn-4-en-3-one (13) (0.023 g, 44%).
Both compounds were identical (NMR, TLC) with those
obtained above.
Acknowledgements
This work was supported by grants from Agencia Nacional
de Promoción Científica y Tecnológica (Argentina) PICT
00607, Universidad de Buenos Aires and CONICET
(Argentina).
Method C. Reaction of iodopregnane 9b (0.071 g, 0.167
mmol) with MCPBA as for the epimeric 20-iodopregnane 9a
(method C), followed by fractionation by flash chromatography
(ethyl acetate–hexane, 20 : 80), gave D-homoandrostenone 10
(0.022 g, 42%). Continued elution with ethyl acetate–hexane
(30 : 70) gave (20S)-20-hydroxypregn-4-en-3-one (13) (0.026 g,
49%). Both compounds were identical (NMR, TLC) with those
obtained above.
References
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2 T. L. Macdonald, N. Narasimhan and L. T. Burka, J. Am. Chem.
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4 For a review see J. R. Hanson, in Comprehensive Organic Synthesis,
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1977, 110, 3377.
Reaction of (20S)-20-iodopregn-4-en-3-one 9b with MCPBA–
MeOH
Reaction of 20-iodopregnane 9b (0.060 g, 0.141 mmol) with
MCPBA in dry MeOH as for the epimeric 20-iodopregnane 9a
followed by purification by flash chromatography (ethyl
acetate–hexane, 3 : 97), gave D-homoandrostane 12 (0.005 g,
11%), identical (NMR, TLC) with that obtained above.
Continued elution with the same solvent gave (20S)-20-
methoxypregn-4-en-3-one 15 (0.023 g, 49%); mp 157–159 ЊC
(from acetone) (Found: C, 79.9; H, 10.6. C22H34O2 requires C,
80.0; H, 10.4%); [α]D ϩ93.0 (c 0.56 in CHCl3); λmax (MeOH)/
nm 244 (ε/dm3 molϪ1 cmϪ1 14600); νmax (KBr)/cmϪ1 1676
9 R. Sicinski and W. J. Szczepek, Tetrahedron Lett., 1987, 28, 5729.
10 D. Nicoletti, A. A. Ghini and G. Burton, An. Asoc. Quim. Argent.,
1998, 86, 336.
11 (a) M. Leboeuf, A. Cavé and R. Gouterel, Bull. Soc. Chim. Fr., 1969,
1619; M. Leboeuf, A. Cavé and R. Gouterel, Bull. Soc. Chim. Fr.,
1969, 1624; M. Leboeuf, A. Cavé and R. Gouterel, Bull. Soc. Chim.
Fr., 1969, 1628; (b) F. B. Hirschmann, D. M. Kautz, S. S. Deshmane
and H. Hirschmann, Tetrahedron, 1971, 27, 2041; (c) B. Krieger and
E. Kaspar, Chem. Ber., 1967, 100, 1169; (d) L. Ruzicka, K. Gätzi
and T. Reichstein, Helv. Chim. Acta, 1939, 22, 626; (e) H. E. Stavely,
J. Am. Chem. Soc., 1940, 62, 489.
12 G. M. Sheldrick, SHELXS-97, Program for Structure Resolution,
University of Göttingen, Germany, 1997.
13 G. M. Sheldrick, SHELXL-97, Program for Structure Refinement,
University of Göttingen, Germany, 1997.
(C᎐C–C᎐O), 1465, 1370, 1193 and 1098 (C–O, OMe); δ (200
᎐
᎐
H
MHz) 0.70 (3H, s, 13-H3C), 1.15 (3H, d, J = 6.2, 20-H3C), 1.19
(3H, s, 10-H3C), 3.29 (3H, s, OCH3), 3.20 (1H, dq, J20,21 = 6.2,
J20,17 = 5.6, 20-H) and 5.73 (1H, br s, 4-H); δC (50 MHz) 12.4
(C-18), 17.2 (C-19), 18.3 (C-21), 20.7 (C-11), 23.9 (C-15), 25.6
(C-16), 31.9 (C-7), 32.8 (C-6), 33.8 (C-2), 35.2 (C-8), 35.6 (C-1),
38.5 (C-10), 38.6 (C-12), 43.1 (C-13), 53.7 (C-9), 55.6 (C-14),
55.6 (OMe), 56.8 (C-17), 78.9 (C-20), 123.7 (C-4), 171.3 (C-5),
199.4 (C-3); m/z (EI) 330 (Mϩ, 9%), 315 (M Ϫ CH3, 2), 298
(M Ϫ MeOH, 4), 288 (3), 256 (3), 124 (33), 105 (25), 91 (14) and
59 (100).
14 G. M. Sheldrick, SHELXTL-PC version 5.0, Siemens Analytical
X-ray Instruments Inc., Madison, Wisconsin, USA, 1994.
15 H. D. Flack, Acta Crystallogr., Sect. A, 1983, 39, 876.
J. Chem. Soc., Perkin Trans. 1, 2001, 1511–1517
1517