Tandem β-fragmentation-hydrogen abstraction reaction of alkoxy radicals in steroidal systems

Article abstract of DOI:10.1021/jo962252h

A number of tertiary or hemiacetalic steroidal alcohols, 2-hydroxy-3,4-dinor-2,3-secocholestan-5-one 2,5-hemiacetal (1), 2β,3β-dihydro-3'H-cyclopropa[2,3]-cholestan-5α-ol (7), 3β-phenyl-5α-hydroxycholestan-2-one (10), 5α-hydroxycholestan-3-one (15), 3β,5α-dihydroxycholestan-7-one 3-acetate (21), and 4,4-dimethyl-19-hydroxy-5α-cholestan-3-one 19,3-hemiacetal (27) have been prepared in order to test a new tandem β-fragmentation-hydrogen abstraction reaction. The alkoxy radicals generated by irradiation of these alcohols with visible light in the presence of (diacetoxyiodo)-benzene, iodine, and molecular oxygen undergo a β-fragmentation reaction followed by peroxidation of the C-radical formed. The peroxy radical reacts further with iodine to give an alkoxy radical and iodoxyl radical (IO^.). The new alkoxy radical can produce intramolecular functionalization of suitably positioned carbons by hydrogen abstraction through a six-membered cyclic transition state to give tetrahydrofurans or can be intramolecularly trapped by carbonyl groups suitably disposed so as to generate a new alkoxy radical that can afford γ-lactones by β-fragmentation.

Full text of DOI:10.1021/jo962252h

J . Org. Chem. 1997, 62, 2975-2981
2975
Ta n d em â-F r a gm en ta tion -Hyd r ogen Abstr a ction Rea ction of
Alk oxy Ra d ica ls in Ster oid a l System s
Alicia Boto, Raimundo Freire, Rosendo Herna´ndez, and Ernesto Sua´rez*
Instituto de Productos Naturales y Agrobiologı´a del CSIC, Carretera de La Esperanza 3,
38206-La Laguna, Tenerife, Spain
Mar´ıa S. Rodr´ıguez
Departamento de Quı´mica Orga´nica, Universidad de La Laguna, Tenerife, Spain
Received December 3, 1996X
A number of tertiary or hemiacetalic steroidal alcohols, 2-hydroxy-3,4-dinor-2,3-secocholestan-5-
one 2,5-hemiacetal (1), 2â,3â-dihydro-3’H-cyclopropa[2,3]-cholestan-5R-ol (7), 3â-phenyl-5R-hy-
droxycholestan-2-one (10), 5R-hydroxycholestan-3-one (15), 3â,5R-dihydroxycholestan-7-one 3-acetate
(21), and 4,4-dimethyl-19-hydroxy-5R-cholestan-3-one 19,3-hemiacetal (27) have been prepared in
order to test a new tandem â-fragmentation-hydrogen abstraction reaction. The alkoxy radicals
generated by irradiation of these alcohols with visible light in the presence of (diacetoxyiodo)-
benzene, iodine, and molecular oxygen undergo a â-fragmentation reaction followed by peroxidation
of the C-radical formed. The peroxy radical reacts further with iodine to give an alkoxy radical
and iodoxyl radical (IO•). The new alkoxy radical can produce intramolecular functionalization of
suitably positioned carbons by hydrogen abstraction through a six-membered cyclic transition state
to give tetrahydrofurans or can be intramolecularly trapped by carbonyl groups suitably disposed
so as to generate a new alkoxy radical that can afford γ-lactones by â-fragmentation.
Sch em e 1
Radical tandem reactions as a methodology for linking
two or more synthetic operations in a single step have
received considerable attention in recent years for the
preparation of complex molecules.1
In previous papers, we have reported the radical
â-fragmentation of oxabicyclic hemiacetals, using hyper-
valent organoiodine reagents as a convenient synthesis
of medium-sized and spiro-lactones by ring-expansion
reaction.2 During the past few years, we have also
examined the use of these reagents in a related â-frag-
mentation of carbohydrate anomeric alkoxy radicals.3
In one of our earliest models, the steroidal hemiacetal
12b (Scheme 1), we observed that when the reaction was
performed by irradiation with visible light in the presence
of (diacetoxyiodo)benzene (DIB) and iodine under argon
with rigorous exclusion of air only the mixture of unsat-
urated lactones 2a ,b2b was obtained in 85% yield. Nev-
ertheless, in the presence of oxygen a new compound 3
was formed in moderate yield (Table 1, entries 1 and 2).
Compound 6 was prepared in 77% overall yield by the
sequence shown in Scheme 2 involving lactone reduction
with LiAlH4 to the diol 4, J ones reagent5 oxidation, and
methylation of the resulting diacid 5 with diazomethane.
A plausible mechanism for the formation of ether 3 is
outlined in Scheme 3. The alkoxy radical I initially
formed underwent â-fragmentation through C5-C10 to
provide a C10 radical II. Under argon, radical II was
stabilized by elimination to give the mixture of olefins
2a ,b. Notwithstanding, under an oxygen atmosphere the
radical II was stereoselectively peroxidated with inver-
sion of configuration to afford peroxy radical III. The
formation of peroxy radicals during these reactions has
been proved by intramolecular trapping with suitably
positioned functions, e.g., double bonds and carbonyl and
carboxyl groups.6 Homolysis of the hydroperoxide O-O
bond led to alkoxy radical IV, which underwent hydrogen
abstraction from C7 to give the tetrahydrofuran deriva-
tive 3.7 This transformation of peroxy radicals into
1
It was evident from H and 13C NMR spectroscopy that
a new oxygen bridge was formed between C10 and C7.
Since the crystals of compound 3 were not suitable, its
structure and stereochemistry were confirmed by single-
crystal X-ray diffraction of the diester derivative 6.4
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) For reviews see: (a) J asperse, C. P.; Curran, D. P.; Fevig, T. L.
Chem. Rev. 1991, 91, 1237-1286. (b) Curran, D. P. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Oxford, 1991; Vol. 4, pp 779-831. (c) Motherwell, W. B.; Crich, D. Free
Radical Chain Reactions in Organic Synthesis; Academic Press: San
Diego, 1992. (d) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl.
1993, 32, 131-163.
(2) (a) Freire, R.; Marrero, J . J .; Rodr´ıguez, M. S.; Sua´rez, E.
Tetrahedron Lett. 1986, 27, 383-386. (b) Arencibia, M. T.; Freire, R.;
Perales, A.; Rodr´ıguez, M. S.; Sua´rez, E. J . Chem. Soc., Perkin Trans.
1 1991, 3349-3360. (c) Arencibia, M. T.; Salazar, J . A.; Sua´rez, E.
Tetrahedron Lett. 1994, 35, 7463-7466.
(4) The author has deposited the atomic coordinates for this
structure with the Cambridge Crystallographic Data Centre. The
coordinates can be obtained, upon request, from the Director, Cam-
bridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2
1EZ, UK.
(5) Bowers, A.; Halsall, T. G.; J ones, E. R. H.; Lemin, A. J . J . Chem.
Soc. 1953, 2548-2560.
(3) (a) Armas, P.; Francisco, C. G.; Sua´rez, E. Angew. Chem., Int.
Ed. Engl. 1992, 31, 772-774. (b) Armas, P.; Francisco, C. G.; Sua´rez,
E. J . Am. Chem. Soc. 1993, 115, 8865-8866. (c) Armas, P.; Francisco,
C. G.; Sua´rez, E. Tetrahedron Lett. 1993, 34, 7331-7334. (d) Francisco,
C. G.; Gonza´lez, C. C.; Sua´rez. E. Tetrahedron Lett. 1996, 37, 1687-
1690.
(6) (a) Boto, A.; Betancor, C.; Prange´, T.; Sua´rez, E. Tetrahedron
Lett. 1992, 33, 6687-6690. (b) Boto, A.; Betancor, C.; Herna´ndez, R.;
Rodr´ıguez, M. S.; Sua´rez, E. Tetrahedron Lett. 1992, 33, 4865-4868.
(c) Boto, A.; Betancor, C.; Prange´, T.; Sua´rez, E. J . Org. Chem. 1994,
59, 4393-4401. (d) Boto, A.; Betancor, C.; Herna´ndez, R.; Rodr´ıguez,
M. S.; Sua´rez, E. J . Org. Chem. 1995, 60, 8209-8217.
S0022-3263(96)02252-9 CCC: $14.00 © 1997 American Chemical Society

2976 J . Org. Chem., Vol. 62, No. 9, 1997
Boto et al.
Ta ble 1a
reagentb (mmol)
I2 (mmol)
P (atm)
T (°C)
time (h)
products (yield, %)
b
entry
substrate
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1
1
7
7
7
DIB (1.1)
DIB (1.1)
DIB (3.7)
DIB (2.5)
DIB (2.5)
DIB (3.5)
DIB (2.0)
HgO (3.0)c
DIB (3.5)
DIB (2.5)
HgO (3.1)c
DIB (2.0)
DIB (2.5)
DIB (1.5)
HgO (5.0)c
HgO (5.0)c
DIB (1.5)
DIB (1.5)
DIB (1.5)
Hg(OAc)2 (1.5)
LTA (3.0)
HgO (3.0)
1.0
1.0
2.0
1.5
1.5
1.4
1.2
1.6
1.5
2.0
1.4
1.0
1.5
1.0
3.0
3.0
1.0
1.0
1.0
1.0
1.0
1.0
air (1)
O2 (1)
Ar (1)
O2 (3)
O2 (5)
O2 (10)
air (1)
air (1)
O2 (3.5)
air (1)
air (1)
O2 (3)
O2 (10)
air (1)
air (1)
O2 (3)
O2 (1)
O2 (5)
O2 (10)
O2 (10)
O2 (10)
O2 (10)
40
40
40
40
40
rt
40
40
40
40
rt
40
rt
40
45
45
1
1.3
1
2a ,b (38), 3 (29)
2a ,b (14), 3 (35)
8 (71)
8 (21), 9 (30)
8 (18), 9 (39)
8 (20), 9 (26)
13 (10), 14 (16)
13 (17), 14 (20)
14 (49)
17 (2), 18 (3)
16 (28), 18 (23)
16 (10), 17 (13), 18 (10)
16 (4), 17 (19), 18 (7)
25(10)
1
1.75
1.3
2
1
1
0.75
1
0.5
3
5
3
1.5
3
2
4
4
7
10
10
10
15
15
15
15
21
21
21
27
27
27
27
27
27
25 (9)
25 (12)
40-45
40-45
40-45
40-45
40-45
40-45
28 (42), 29 (18)
28 (23), 29 (46)
28 (11), 29 (51)
28 (13), 29 (56)
28 (21), 29 (48)
28 (18), 29 (39)
2
2
a
All reactions were irradiated with two 100 W tungsten-filament lamps in cyclohexane solution; those under pressure were performed
in a borosilicate Griffin-Worden pressure vessel (Kontes-767100). Per mmol of substrate. c Using CCl4 as solvent. DIB ) (diacetoxy-
iodo)benzene. LTA ) lead tetraacetate.
b
Sch em e 2
Sch em e 3
alkoxy radicals deserves some comment. The homolytic
cleavage of the weak O-O bond catalyzed by acids or low-
valent transition metals is a very well-documented
process and has synthetic and biological importance.8 In
our case, the cleavage may be catalyzed by iodine
according to the following equation.
ROO• + I2 f ROI + OI•
Iodoxyl radical (OI•) has been detected in the vapor
phase during the ozonolysis of the halogen9 and postu-
lated to be formed in solution by irradiation using a high-
pressure mercury lamp of red mercury(II) oxide and
iodine.10 It is also worth noting here that the reaction
occurs with absolute diastereoselectivity with the oxygen
attack taking place with inversion of configuration at C10.
Presumably, the steroidal framework helps to direct the
incoming oxygen on steric grounds.
With the dual purpose of examining the scope of the
reaction and gaining insight into its mechanism, we have
prepared several steroidal models (see Table 1). Alcohol
7 was synthesized by Simmons-Smith reaction on 5R-
hydroxycholest-2-ene11 also in order to investigate if the
peroxy radical could be added to the 2,3-cyclopropane
ring, but under the conditions shown in Table 1 (entries
3-6) only the cyclodecenone derivative 8 and the ether
9 were obtained. The photolysis was performed under
different oxygen pressures, the best yield of tetrahydro-
furan 9 being obtained at 5 atm (Table 1, entry 5)
(Scheme 4). Increasing oxygen pressure from 5 to 10
atm does not enhance the yield (compare entries 5 to 6,
Table 1).
(7) For a recent review on intramolecular free-radical abstraction
see: Majetich, G.; Wheless, K. Tetrahedron 1995, 51, 7095-7129.
(8) Porter, N. A. In Organic Peroxides; Ando, W., Ed.; Wiley:
Chichester, 1992; pp 139-143.
(9) Downs, A. J .; Adams, C. J . In Comprehensive Inorganic Chem-
istry; Bailar, J . C., Emele´us, H. J ., Nyholm, R., Trotman-Dickenson,
A. F., Eds.; Pergamon Press: Oxford, 1973; Vol. 2, pp 1380-1383.
(10) Suginome, H.; Wang, J . B. J . Chem. Soc., Perkin Trans. 1 1990,
2825-2829.
(11) Clayton, R. B.; Henbest, H. B.; Smith, M. J . Chem. Soc. 1957,
1982-1993.

Reaction of Alkoxy Radicals in Steroidal Systems
J . Org. Chem., Vol. 62, No. 9, 1997 2977
Sch em e 4
Sch em e 8
Sch em e 5a
a
Key: (a) BH3‚THF, 0 °C f rt, 10 h; NaOH, H2O2, rt, 1 h; (b)
PCC, CH2Cl2, rt, 2 h.
Sch em e 6
Sch em e 9a
Sch em e 7
a
Key: (a) H2O2, NaOH, MeOH, rt, 3 h; (b) Ac2O, Py, rt, 15 h;
(c) (PhSe)2, NaBH4, EtOH, 4 °C, 10 min.
γ-lactone 18 confirms the mechanism proposed for the
tetrahydrofuran (Scheme 3) since the intervention of an
alkoxy radical intermediate at C10 is necessarily involved.
As shown in Scheme 8, the addition of this alkoxy radical
to the carbonyl group at C3 generates a new alkoxy
radical that, in turn, undergoes a â-fragmentation to give
γ-lactone 18.
Previous observations from our laboratory6d in which
5-hydroxy-5R-cholestan-2-one (19) under these conditions
underwent a C10 radical peroxidation and a subsequent
addition of the peroxy radical to the C2 carbonyl group
followed by â-fragmentation (Scheme 8) to give a â-peroxy
lactone 20 also provide good support for the proposed
mechanism.
The â-hydroxy ketone 21 was synthesized, starting
from 22 through epoxidation with 30% hydrogen peroxide
and reduction13 of the oxirane 24 with sodium phenylse-
lenide14 (Scheme 9), in order to trap the alkoxy radical
with a carbonyl group at C7 in the same place where the
hydrogen abstraction takes place. As expected, a γ-lac-
tone 25 is obtained during the photolysis of 21 although
in low yield (Table 1, entries 14-16) (Scheme 10).
The synthesis of the steroidal model 10 was realized
as shown in Scheme 5. The known homoallylic alcohol
116c by oxidative hydroboration afforded diol 12, which
on treatment with PCC led to 10 in good yield. Photolysis
of 10 under air in the presence of DIB or HgO and iodine
(entries 7 and 8) gave a mixture of two products 13 and
14 (Scheme 6). Irradiation at 3.5 atm of oxygen pressure
gave the best result for tetrahydrofuran 14 formation
(Table 1, entry 9). However, somewhat unexpectedly, we
have not isolated any compound coming from an abstrac-
tion of the benzylic proton at C3.
When we applied this methodology to steroidal hydroxy
ketone 156c (Scheme 7) we obtained a γ-lactone 18 in low
yield apart from the diketone 16 and the tetrahydrofuran
17 (Table 1, entries 10-13).12 The formation of this
(13) Miyashita, M; Suzuki, T.; Yoshikoski, A. Tetrahedron Lett. 1987,
28, 4293-4296.
(14) (a) Sharpless, K. B.; Lauer, R. F. J . Am. Chem. Soc. 1973, 95,
2697-2699. (b) Haraguchi, K.; Tanaka, H.; Maeda, H.; Itoh, Y.; Saito,
S.; Miyasaka, A. J . Org. Chem. 1991, 56, 5401-5408.
(12) For a preliminary communication see: Boto, A.; Herna´ndez,
R.; Sua´rez, E. Tetrahedron Lett. 1994, 35, 2597-2600.

2978 J . Org. Chem., Vol. 62, No. 9, 1997
Boto et al.
Sch em e 10
Sch em e 11. Tr a n sition Sta tes of H-C1 a n d H-C19
Hyd r ogen Abstr a ction (Hyd r ogen s a n d th e Sid e
Ch a in Ar e Om itted for Cla r ity)a
This reaction may have interesting applications in
synthetic organic chemistry. We have used it in a short
and efficient synthesis of A and A′ rings of limonin (26)
and related compounds.15
a
Key: (a) see Table 1.
since a hydrogen abstraction at this latter position should
be favored. Futhermore, the distances between the
alkoxy radical and the abstractable hydrogens, measured
in a minimized structure, are very similar (O‚‚‚H-C1 )
2.4 Å and O‚‚‚H-C19 ) 2.6 Å), and both are within the
range where this reaction occurs.19 Nevertheless, the
energy of the six-membered transition state for the
H-C19 intramolecular hydrogen abstraction calculated
by using a MM2 forcefield model20 was found to be 6.4
kcal/mol higher than the corresponding energy of the
transition structure for the abstraction of the H-C1, and
this can explain the observed regioselectivity of the
reaction (Scheme 11).
Limonin, the principal limonoid constituent of Citrus
seeds, has been known for over 100 years.16 However, it
was not until 1960 that its structure was fully deter-
mined.17 Although in the course of this structure eluci-
dation much interesting chemistry has been developed,
relatively little attention has been directed to its syn-
thesis.18
The hemiacetal 27 was prepared according to a previ-
ously reported procedure2b (Scheme 11). Reaction of 27
with the system DIB/I2 at different oxygen pressures
(Table 1, entries 17-19) gave, apart from the expected
spirolactone 28,2b a new compound 29 with the same A
and A′ ring system as limonin. As shown in Table 1, the
yield of 29 increases with increasing oxygen pressure,
reaching 51% at 10 atm (Table 1, entry 19). Various
reagent systems were also studied (Hg(OAc)2/I2, LTA/I2,
and HgO/I2), the best yield (56%) being obtained with Hg-
(OAc)2/I2 at 10 atm of oxygen pressure (Table 1, entry
20).
Although the reaction yield is moderate it compares
favorably with that obtained in a multistep synthesis
using a similar starting material.18b
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined with
a hot-stage apparatus and are uncorrected. Optical rotation
measurements were recorded at room temperature in CHCl3.
IR spectra were recorded in CHCl3 solutions. NMR spectra
were determined at 200 or 400 MHz for 1H and 50.3 MHz for
13C for CDCl3 solutions in the presence of TMS as internal
standard. Mass spectra were determined at 70 eV. Merck
silica gel 60 PF254 and 60 (0.063-0.2 mm) were used for
preparative thin-layer chromatography (TLC) and column
chromatography, respectively. Circular layers of 1 mm of
Merck silica gel 60 PF254 were used on a Chromatotron for
centrifugally assisted chromatography. Commercial reagents
and solvents were analytical grade or were purified by
standard procedures prior to use. All reactions involving air-
or moisture-sensitive materials were carried out under an
argon atmosphere. Photolyses under oxygen pressure were
performed in a borosolicate Griffin-Worden pressure vessel
(Kontes K-767100). The spray reagent for TLC was vanillin
(1 g) in H2SO4-EtOH (4:1; 200 mL). (Diacetoxyiodo)benzene
(DIB) 98% was purchased from Aldrich.
The structure of 29 was confirmed by spectroscopic
data, the chemical shift and shape of the signals of the
protons at C1, C2, and C19 being identical with those found
in the downfield portion of the 1H NMR spectra of limonin
derivatives.18b
At first sight it is not clear why the alkoxy radical at
C4 abstracts exclusively a hydrogen at C1 and not at C19,
(15) Freire, R.; Herna´ndez, R.; Rodr´ıguez, M. S.; Sua´rez. E. Tetra-
hedron Lett. 1987, 28, 981-984.
(16) For reviews see: (a) Dreyer, D. L. In Fortschritte der Chemie
Organischer Naturstoffe; Zechmeister, L., Ed.; Springer-Verlag: Wien,
1968; Vol. 26, pp 190-244. (b) Taylor, D. A. H. In Fortschritte der
Chemie Organischer Naturstoffe; Herz, W., Grisebach, H., Kirby, G.
W., Eds.; Springer-Verlag: Wien, 1984; Vol. 45, pp 1-102. (c) Connolly,
J . D.; Overton, K. C.; Polonsky, J . In Progress in Phytochemistry;
Reinhold, L., Liwschitz, Y., Eds.; Interscience: London, 1970; Vol. 2,
pp 385-484.
Gen er a l P r oced u r e: P h otolysis of 2-Hyd r oxy-3,4-d i-
n or -2,3-secoch olest a n -5-on e 2,5-H em ia cet a l (1) u n d er
Oxygen . A solution of hemiacetal 12b (173 mg, 0.46 mmol) in
cyclohexane (46 mL) containing (diacetoxyiodo)benzene (DIB)
(17) (a) Arigoni, D.; Barton, D. H. R.; Corey, E. J .; J eger, O.; Caglioti,
L.; Dev, S.; Ferrini, P. G.; Glazier, E. R.; Melera, A.; Pradhan, S. K.;
Schaffner, K.; Sternhell, S.; Templeton, J . F.; Tobinaga, S. Experientia
1960, 16, 41-49. (b) Arnott, S.; Davie, A. W.; Robertson, J . M.; Sim,
G. A.; Watson, D. G. Experientia 1960, 16, 49-51.
(18) (a) Schlatter, H. R.; Lu¨thy, C.; Graf, W. Helv. Chim. Acta 1974,
57, 1044-1055. (b) Lu¨thy, C.; Schlatter, H. R.; Graf, W. Helv. Chim.
Acta 1974, 57, 1060-1066. (c) Emmer, G.; Graf, W. Helv. Chim. Acta
1981, 64, 1398-1406.
(19) Brun, P.; Waegell, B. In Reactive Intermediates; Abramovitch,
R. A., Ed.; Plenum Press: New York, 1983; Vol. 3, pp 367-426.
(20) (a) Dorigo, A. E.; Houk, K. N. J . Org. Chem. 1988, 53, 1650-
1664. (b) Dorigo, A. E.; McCarrick, M. A.; Loncharich, R. J .; Houk, K.
N. J . Am. Chem. Soc. 1990, 112, 7508-7514.

Reaction of Alkoxy Radicals in Steroidal Systems
J . Org. Chem., Vol. 62, No. 9, 1997 2979
(164 mg, 0.51 mmol) and I2 (117 mg, 0.46 mmol) was irradiated
with two 100 W tungsten-filament lamps while air was
bubbled through the mixture, at 40 °C for 1 h. The reaction
mixture was then poured into a 10% aqueous sodium thiosul-
fate solution and extracted with dichloromethane. The organic
layer was washed with brine, dried (Na2SO4), and concentrated
under reduced pressure. Column chromatography of the
residue (benzene-EtOAc, 80:20) gave lactone 3 (52 mg, 0.13
mmol, 29%) and a mixture of two products that was rechro-
matographed (benzene-hexanes, 80:20), yielding lactone 2a 2b
(35 mg, 0.093 mmol, 20%) and lactone 2b2b(31 mg, 0.083 mmol,
18%). Lactone 3: mp 90-91 °C (from n-pentane); [R]D +24°
NMR 7.35 (d), 8.47 (d), 12.16 (q), 12.22 (t), 16.17 (q), 18.81
(q), 21.12 (t), 22.71 (q), 22.97 (q), 24.04 (t), 24.34 (t), 26.47 (t),
28.16 (d), 28.37 (t), 32.39 (t), 34.47 (t), 35.85 (d), 35.98 (d), 36.24
(t), 36.34 (t), 38.67 (s), 39.68 (t), 40.22 (t), 42.60 (s), 46.59 (d),
56.40 (d), 56.42 (d), 73.61 (s); MS m/ z (rel intensity) 400 (M+,
4), 385 (5) 382 (8), 367 (7), 332 (100), HRMS calcd for C28H48O,
400.3705, found 400.3711. Anal. Calcd for C28H48O: C, 83.92;
H, 12.08. Found: C, 83.69; H, 12.25.
P h ot olysis of 2â,3â-Dih yd r o-3′H -cyclop r op a [2,3]-
ch olesta n -5r-ol (7). See full experimental details for entries
3-6 of Table 1 in the Supporting Information. Compound 8:
mp 122.5-124.5 °C (from MeOH-EtOAc); [R]D -28.3° (c )
(c ) 0.130); IR 1755, 1725 cm-1 1H NMR 0.64 (3H, s), 0.82
;
1
0.3); IR 1690 cm-1; H NMR 0.36 (1H, m), 0.69 (3H, s), 0.86
(6H, d, J ) 6.5 Hz), 0.88 (3H, d, J ) 6.4 Hz), 1.23 (3H, s),
2.65, 3.01 (2H, ddd, J ) 3.9, 3.7, 14.6 Hz), 3.88 (1H, m), 4.11
(1H, m), 4.64 (1H, t, J ) 10.9 Hz); 13C NMR 12.61 (q), 18.78
(q), 21.17 (t), 22.56 (q), 22.82 (q), 23.89 (t), 23.96 (t), 28.04 (q),
28.14 (d), 28.59 (t), 35.59 (d), 36.28 (t), 37.08 (t), 38.99 (t), 39.51
(t), 41.82 (t), 44.40 (s), 46.42 (d), 53.37 (d), 55.35 (d), 57.89 (d),
66.23 (t), 75.74 (d), 80.86 (s), 174.25 (s); MS m/ z (rel intensity)
390 (M+, 45), 362 (1), 347 (10), 333 (6), 318 (25), 302 (17), 277
(2), 275 (60), 247 (19), 205 (13); HRMS calcd for C25H42O3
390.3133, found 390.3124. Anal. Calcd for C25H42O3: C, 76.86;
H, 10.84. Found: C, 76.69; H, 10.91. Photolysis was also
performed with DIB/I2 under O2 (1 atm) (Table 1, entry 2).
(1R,1′R,3S,3aS,5aR,6R,8aS,8bS)-[6-(1′,5′-Dim eth ylh exyl)-
1-[(m eth oxycar bon yl)m eth yl]-3,5a-dim eth yldecah ydr oin -
(6H, d, J ) 6.7 Hz), 0.90 (3H, d, J ) 8.0 Hz), 1.54 (3H, s), 4.92
(1H, d, J ) 6.6 Hz); 13C NMR 11.93 (q), 13.26 (d), 14.00 (q),
14.38 (t), 14.90 (d), 18.92 (q), 22.71 (q), 22.97 (q), 23.98 (t),
25.47 (t), 25.95 (t), 27.81 (t), 28.16 (d), 29.81 (t), 35.88 (d), 36.28
(t), 39.21 (t), 39.66 (t), 40.04 (d), 40.94 (t), 42.83 (s), 46.54 (t),
56.05 (d), 56.25 (d), 56.41 (d), 126.90 (d), 142.45 (s), 214.31
(s); MS m/ z (rel intensity) 398 (M+, 14), 383 (4), 380 (9); HRMS
calcd for C28H46O 398.3549, found 398.3577. Anal. Calcd for
C28H46O: C, 84.35; H, 11.64. Found: C, 84.57; H, 11.47.
Compound 9: amorphous; [R]D +2° (c ) 0.14); IR 1690 cm-1
;
1H NMR -0.13 (1H, m), 0.62 (3H, s), 0.88 (6H, d, J ) 6.6 Hz),
0.94 (3H, d, J ) 6.4 Hz), 1.27 (3H, s), 2.86 (1H, t, J ) 11 Hz),
3.05 (1H, dd, J ) 4.3, 13.8 Hz), 3.82 (1H, m); 13C NMR 12.79
(q), 13.60 (t), 14.63 (d), 17.10 (d), 18.96 (q), 21.20 (t), 22.71 (q),
22.96 (q), 24.00 (t), 24.30 (t), 28.17 (d), 28.76 (t), 29.95 (q), 35.74
(d), 36.41 (t), 39.66 (2 × t), 41.89 (t), 42.09 (t), 44.27 (s), 45.75
(d), 49.41 (t), 53.66 (d), 55.31 (d), 56.59 (d), 78.71 (d), 83.62
(s), 213.63 (s); MS m/ z (rel intensity) 414 (M+, 27), 399 (3),
396 (3); HRMS calcd for C28H46O2 414.3498, found 414.3505.
Anal. Calcd for C28H46O2: C, 81.09; H, 11.19. Found: C,
81.21; H, 11.05.
d en o[4,5-c]fu r a n -3-yl]a cetic Acid Meth yl Ester (6).
A
solution of lactone 3 (40 mg, 0.10 mmol) in dry THF (10 mL)
was treated with LiAlH4 (39 mg, 1.0 mmol) and stirred at rt
for 45 min. The mixture was treated dropwise with saturated
aqueous sodium sulfate. The precipitate was filtered off and
washed thoroughly with diethyl ether, and the filtrate and the
washing were combined, dried (Na2SO4), and evaporated under
reduced pressure. Chromatotron chromatography of the resi-
due (hexanes-EtOAc, 60:40) gave diol 4 (38 mg, 0.096 mmol,
96%), which was dissolved in acetone and treated with an
excess of J ones reagent5 at rt. The mixture was stirred for 1
h and then poured into water and extracted with dichlo-
romethane. The organic layer was dried and concentrated as
usual. To a solution of the crude diacid 5 in ether was added
an excess of diazomethane in ether. The mixture was stirred
for 15 min and the solvent evaporated under reduced pressure.
The residue was purified by chromatotron chromatography
(benzene-EtOAc, 90:10) to give ester 6 (35 mg, 0.077 mmol,
80%): mp 61-63 °C (from MeOH); [R]D -11° (c ) 0.20); IR
3â-P h en ylch olesta n e-2r,5r-d iol (12). 3-Phenylcholest-
2-en-5R-ol (11)6c (150 mg, 0.32 mmol) in dry THF (10 mL) was
treated with a 1 M solution of borane in THF (2 mL, 2 mmol),
which was added dropwise at 0 °C under argon. The solution
was allowed to reach rt and stirred for another 10 h and then
was cooled in ice, and water was slowly added until evolution
of hydrogen ceased. Afterwards, a 3 M aqueous solution of
NaOH (3 mL) was added in one portion, and 30% hydrogen
peroxide (3 mL) was dripped under vigorous stirring. The ice
bath was removed, and the mixture was stirred for 1 h at rt
and then poured into 5% aqueous HCl and extracted with
dichloromethane. The organic layer was washed with water
and brine, dried, and evaporated as previously described.
Chromatotron chromatography (hexanes-EtOAc, 80:20) yielded
3â-phenylcholestane-3R,5R-diol6c (30 mg, 0.063 mmol, 20%)
and 3â-phenylcholestane-2R,5R-diol (12) (95 mg, 0.2 mmol,
61%). Diol 12: mp 169-171 and 177.8-179.5 °C (from
1725 cm-1 1H NMR 0.67 (3H, s), 0.85 (6H, d, J ) 6.2 Hz),
;
0.91 (3H, d, J ) 6.4 Hz), 1.41 (3H, s), 2.27 (1H, d, J ) 13.1
Hz), 2.39 (1H, d, J ) 13.1 Hz), 2.47 (1H, dd, J ) 14.9, 7.5 Hz),
2.54 (1H, dd, J ) 14.9, 3.9 Hz), 3.94 (1H, ddd, J ) 3.9, 7.6, 9.3
Hz); 13C NMR 12.51 (q), 18.87 (q), 21.46 (t), 22.63 (q), 22.86
(q), 23.96 (t), 24.18 (t), 26.30 (q), 28.06 (d), 28.79 (t), 35.65 (d),
36.33 (t), 39.34 (t), 39.58 (t), 40.26 (t), 43.10 (t), 44.28 (s), 46.01
(d), 51.37 (q), 51.54 (q), 52.63 (d), 55.25 (d), 57.90 (d), 78.32
(d), 81.74 (s), 171.42 (s), 171.95 (s); MS m/ z (rel intensity) 450
(M+, 15), 435 (4), 432 (6), 418 (4), 403 (3), 400 (8), 390 (3), 387
(7), 377 (100), 361 (8), 337 (14), 319 (17), 303 (24); HRMS calcd
for C27H46O5 450.3345, found 450.3336. Anal. Calcd for
C27H46O5: C, 71.95; H, 10.29. Found: C, 72.05; H, 10.41.
2â,3â-Dih yd r o-3′H-cyclop r op a [2,3]ch olesta n -5r-ol (7).
The Simmons-Smith reagent (70 mg) in dry ether (0.25 mL)
was treated with a catalytic amount of I2 and stirred at rt until
the brown color disappeared. Then, diiodomethane (125 µL,
500 mg, 1.87 mmol) and 5R-hydroxychlolest-2-eno11 (230 mg,
0.60 mmol) were added. The mixture was stirred under argon
at reflux temperature for 5 h, cooled at rt, and filtered. The
solid residue was washed with diethyl ether, and the combined
organic layers were poured into aqueous ammonium chloride
and washed successively with aqueous sodium bicarbonate and
brine. After drying and evaporation in the usual way, followed
by chromatotron chromatography (hexanes-EtOAc, 98:2),
compound 7 (177.5 mg, 0.44 mmol, 74%) and a small amount
of starting material (29.3 mg, 0.08 mmol, 13%) were obtained.
Compound 7: mp 99-101 °C (from MeOH); [R]D +11.6° (c )
1
EtOAc); [R]D +2.1° (c ) 0.33); IR 3600, 3400 cm-1; H NMR
0.68 (3H, s), 0.87 (6H, d, J ) 6.6 Hz), 0.92 (3H, J ) 6.4 Hz),
1.12 (3H, s), 3.05 (1H, m), 4.03 (1H, m), 7.24-7.38 (5H, m);
13C NMR 12.09 (q), 17.32 (q), 18.59 (q), 21.17 (t), 22.49 (q),
22.75 (q), 23.81 (t), 24.03 (t), 26.00 (t), 27.94 (d), 28.19 (t), 33.36
(t), 33.98 (d), 35.75 (d), 36.10 (t), 39.43 (t), 39.82 (t), 39.90 (t),
40.71 (s), 42.32 (t), 42.65 (s), 45.96 (d), 47.60 (d), 56.02 (d),
56.16 (d), 71.25 (d), 73.25 (s), 126.77 (d), 128.00 (d), 128.69
(d), 142.97 (s); MS m/ z (rel intensity) 480 (M+, 6), 462 (100),
447 (29), 444 (66), 429 (9); HRMS calcd for C33H52O2 480.396 73,
found 480.395 10. Anal. Calcd for C33H52O2: C, 82.43; H,
10.91. Found: C, 82.39; H, 10.69.
3â-P h en yl-5r-h yd r oxych olesta n -2-on e (10). Diol 12 (85
mg, 0.18 mmol) in dichloromethane (20 mL) was treated with
pyridinium chlorochromate (54 mg, 0.25 mmol) for 2 h. The
mixture was then evaporated under vacuum and purified by
column chromatography (hexanes-EtOAc, 90:10), yielding
compound 10 (74 mg, 0.15 mmol, 87%): amorphous; [R]D -5.8°
(c ) 0.17); IR 3600, 1700 cm-1; 1H NMR 0.68 (3H, s), 0.87 (6H,
d, J ) 6.6 Hz), 0.92 (3H, d, J ) 6.4 Hz), 1.03 (3H, s), 2.29 (1H,
d, J ) 13.5 Hz), 2.76 (1H, d, J ) 13.4 Hz), 4.06 (1H, dd, J )
12.7, 6.9 Hz), 7.12-7.38 (5H, m); 13C NMR 11.99 (q), 17.14
(q), 18.59 (q), 21.09 (t), 22.49 (q), 22.75 (q), 23.80 (t), 24.08 (t),
26.18 (t), 27.94 (d), 28.15 (t), 33.29 (t), 34.22 (d), 35.72 (d), 36.09
(t), 39.43 (t), 39.69 (t), 42.52 (s), 44.18 (s), 44.70 (t), 45.47 (d),
1
0.21); IR 3590 cm-1; H NMR 0.51 (2H, m), 0.64 (3H, s), 0.86
(6H, d, J ) 7 Hz), 0.89 (3H, d, J ) 7 Hz), 0.97 (3H, s); 13C

2980 J . Org. Chem., Vol. 62, No. 9, 1997
Boto et al.
48.47 (t), 52.65 (d), 55.98 (d), 56.16 (d), 73.02 (s), 126.80 (d),
128.31 (d), 128.90 (d), 138.58 (s), 210.67 (s); MS m/ z (rel
intensity) 478 (M+, 6), 460 (1), 418 (37); HRMS calcd for
C33H50O2 478.381 08, found 478.380 99. Anal. Calcd for
C33H50O2: C, 82.78; H, 10.53. Found: C, 82.51; H, 10.73.
P h ot olysis of 3â-P h en yl-5r-h yd r oxych olest a n -2-on e
(10). See full experimental details for entries 7-9 of Table 1
in the Supporting Information. Compound 13: mp 88.2-90.2
3â-Hyd r oxy-5r,6r-ep oxych olesta n -7-on e (23). To a so-
lution of 3â-hydroxycholest-5-en-7-one21 (22) (600 mg, 1.5
mmol) in MeOH (57 mL) containing 8 N NaOH aqueous
solution (0.98 mL) was added 30% hydrogen peroxide (3 mL)
portionwise 1 mL every hour. The mixture was stirred at rt
for 3 h, poured into 10% HCl, and extracted with CH2Cl2. The
organic layer was washed with water, dried (Na2SO4), and
evaporated under vacuum. Column chromatography of the
residue (benzene-EtOAc, 4:1) afforded starting material (330
mg) and epoxide 23 (132 mg, 0.32 mmol, 21%): mp 165-166.5
°C (from acetone-n-hexane); [R]D +98° (c ) 0.338); IR 3609,
°C (from MeOH-water); [R]D +131° (c ) 0.13); IR 1700 cm-1
;
1H NMR 0.72 (3H, s), 0.86 (6H, d, J ) 6.6 Hz), 0.89 (3H, d, J
) 6.2 Hz), 2.27 (1H, m), 2.46 (1H, dd, J ) 3.3, 15.4 Hz), 2.76
(1H, m), 3.11, (1H, d, J ) 12.8 Hz), 3.20 (1H, d, J ) 12.8 Hz),
3.53 (1H, dd, J ) 15.4, 12.7 Hz), 4.73 (1H, dd, J ) 12.7, 3.3
Hz), 5.13 (2H, s), 7.27-7.36 (5H, m); 13C NMR 11.92 (q), 18.67
(q), 22.55 (q), 22.80 (q), 23.77 (t), 24.83 (t), 26.77 (t), 27.92 (t),
28.01 (d), 29.69 (t), 35.70 (d), 36.11 (t), 37.60 (d), 39.50 (t), 39.61
(t), 42.85 (s), 49.26 (t), 56.04 (d), 127.71 (d), 128.15 (d), 129.00
(d), 137.54 (s), 147.02 (s), 207.59 (s), 210.03 (s), due to the slow
conformational equilibrium of the medium-sized ring, only 25
well-defined signals were observed; MS m/ z (rel intensity) 476
(M+, 5), 458 (1); HRMS calcd for C33H48O2 476.365 43, found
476.366 11. Anal. Calcd for C33H48O2: C, 83.13; H, 10.16.
Found: C, 83.05; H, 10.42. Compound 14: amorphous; [R]D
1694 cm-1 1H NMR 0.65 (3H, s), 0.85 (6H, d, J ) 6.8 Hz),
;
0.89 (3H, d, J ) 7.0 Hz), 1.01 (3H, s), 3.04 (1H, s), 3.89 (1H,
m); 13C NMR 12.01 (q), 15.48 (q), 18.65 (q), 21.10 (t), 22.49
(q), 22.75 (t), 23.77 (t), 24.81 (t), 27.92 (d), 28.24 (t), 30.77 (t),
32.76 (t), 34.98 (t), 35.81 (d), 36.01 (t), 38.68 (t), 39.33 (t), 39.59
(t), 43.25 (d), 43.93 (s), 46.73 (d), 51.87 (d), 55.21 (d), 62.98
(d), 68.12 (s), 68.59 (d), 207.84 (s); MS m/ z (rel intensity) 416
(M+, 13), 398 (16), 387 (26), 373 (53), 355 (9), 341 (16); HRMS
calcd for C27H44O3 416.329 05, found 416.327 25. Anal. Calcd
for C27H44O3: C, 77.82; H, 10.65. Found: C, 78.01; H, 10.61.
3â-Hyd r oxy-5r,6r-ep oxych olesta n -7-on e Aceta te (24).
A solution of 23 (122 mg, 0.29 mmol) in dry pyridine (2 mL)
containing acetic anhydride (1 mL) was stirred at rt for 15 h.
Workup as usual gave after chromatotron chromatography
(benzene-EtOAc, 97:3) the acetate 24 (116 mg, 0.25 mmol,
86%): mp 129.5-130.5 °C (from n-hexane); [R]D +79° (c )
0.204); IR 1732, 1694 cm-1; 1H NMR 0.66 (3H, s), 0.85 (6H, d,
J ) 6.6 Hz), 0.89 (3H, d, J ) 6.9 Hz), 1.03 (3H, s), 2.02 (3H,
s), 3.02 (1H, s), 4.91 (1H, m); 13C NMR 12.02 (q), 15.38 (q),
18.68 (q), 21.07 (t), 21.16 (q), 22.52 (q), 22.77 (q), 23.79 (t),
24.84 (t), 27.05 (t), 27.92 (d), 28.26 (t), 32.51 (t), 35.04 (t), 35.12
(s), 35.83 (d), 36.04 (t), 39.40 (t), 39.58 (t), 43.18 (d), 43.93 (s),
46.69 (d), 51.85 (d), 55.22 (d), 62.80 (d), 67.54 (s), 70.79 (d),
170.00 (s), 207.28 (s); MS m/ z (rel intensity) 458 (M+, <1),
398 (4), 371 (23); HRMS calcd for C29H46O4 458.339 61, found
458.340 54. Anal. Calcd for C29H46O4: C, 75.93; H, 10.11.
Found: C, 76.02; H, 10.23.
3â,5r-Dih yd r oxych olesta n -7-on e 3-Aceta te (21). To a
solution of diphenyl diselenide (49 mg, 0.16 mmol) in ethanol
(0.8 mL) was added NaBH4 in small portions until disappear-
ance of the yellow color was observed (15 mg, 0.39 mmol), and
then acetic acid (3.2 µL) was added. This solution was added
dropwise under argon to a solution of epoxy acetate 24 (45.8
mg, 0.1 mmol) in ethanol (2.1 mL), previously cooled to 4 °C
with a water-ice bath. Once the addition was over, stirring
continued for 10 min. The mixture was then poured into brine
and extracted with CH2Cl2 and the residue purified by chro-
matotron chromatography (hexanes-EtOAc, 85:15) to give the
acetate of enone 22 (5.2 mg, 0.012 mmol, 12%) and alcohol 21
(35 mg, 0.076 mmol, 76%): mp 220-222 °C (from acetone-
n-hexane); [R]D +41° (c ) 0.186); IR 3594, 1716 cm-1; 1H NMR
0.65 (3H, s), 0.86 (6H, d, J ) 6.4 Hz), 0.91 (3H, d, J ) 6.4 Hz),
1.25 (3H, s), 2.02 (3H, s), 2.04 (1H, d, J ) 13.1 Hz), 2.78 (6H,
d, J 13.1 Hz) 5.11 (1H, m); 13C NMR 12.06 (q), 16.17 (q), 18.73
(q), 21.34 (q), 21.69 (t), 22.50 (q), 22.74 (q), 23.79 (t), 24.98 (t),
26.53 (t), 27.95 (d), 28.45 (t), 30.20 (t), 35.63 (d), 36.11 (t), 38.83
(t), 39.35 (s), 39.41 (t), 39.65 (t), 42.80 (s), 47.02 (d), 48.75 (d),
50.16 (d), 52.67 (t), 54.93 (d), 70.49 (d), 79.11 (s), 170.84 (s),
210.34 (s); MS m/ z (rel intensity) 460 (M+, 1), 442 (<1), 400
(4), 382 (7); HRMS calcd for C29H48O4 460.355 26, found
460.354 45. Anal. Calcd for C29H48O4: C, 75.59; H, 10.51.
Found: C, 75.68; H, 10.69.
+142° (c ) 0.11); IR 1705 cm-1 1H NMR 0.71 (3H, s), 0.87
;
(6H, d, J ) 6.4 Hz), 0.92 (3H, d, J ) 6.5 Hz), 1.39 (3H, s), 2.39
(1H, d, J ) 11.9 Hz), 2.50 (1H, dd, J ) 3.3, 15 Hz), 2.52 (1H,
dd, J ) 3.6, 11.4 Hz), 2.68 (1H, d, J ) 11.9 Hz), 3.24 (1H, dd,
J ) 15, 12.7 Hz), 3.25 (1H, m), 3.94 (1H, m), 5.15 (1H, dd, J )
3.3, 12.7 Hz), 7.3-7.4 (5H, m); 13C NMR 12.46 (q), 18.76 (q),
21.88 (t), 22.54 (q), 22.79 (q), 23.76 (t), 23.84 (t), 28.00 (d), 28.64
(t), 29.79 (q), 35.58 (d), 36.23 (t), 39.36 (t), 39.49 (t), 44.36 (s),
44.46 (d), 47.68 (t), 49.15 (t), 49.89 (t), 53.82 (d), 54.16 (d), 55.25
(d), 58.11 (d), 78.40 (d), 83.22 (s), 127.61 (d), 128.39 (d), 128.94
(d), 137.26 (s), 208.66 (s), 211.26 (s); MS m/ z (rel intensity)
492 (M+, 10), 474 (8), 450 (100); HRMS calcd for C33H48O3
492.360 35, found 492.360 43. Anal. Calcd for C33H48O3: C,
80.43; H, 9.83. Found: C, 80.53; H, 9.97.
P h otolysis of 5r-Hyd r oxych olesta n -3-on e (15). See full
experimental details for entries 10-13 of Table 1 in the
Supporting Information. Compound 16: mp 130.6-132.5 °C
(from n-hexane); [R]D +327.7° (c ) 0.36); IR 1720 cm-1 1H
;
NMR 0.71 (3H, s), 0.86 (6H, d, J ) 7.4 Hz), 0.90 (3H, d, J )
7.0 Hz), 1.73 (3H, s), 2.68 (1H, dd, J ) 14.8, 6 Hz), 2.84 (2H,
d, J ) 16 Hz), 3.49 (1H, dd, J ) 11, 14.8 Hz), 4.32 (2H, d, J )
16 Hz), 5.23 (1H, m); 13C NMR 11.87 (q), 18.60 (q), 18.93 (q),
22.53 (q), 22.75 (q), 23.63 (t), 23.97 (t), 25.65 (t), 26.90 (t), 27.86
(t), 27.97 (d), 35.61 (d), 36.06 (t), 36.61 (d), 39.18 (t), 39.47 (t),
40.37 (t), 41.46 (t), 42.12 (d), 42.82 (s), 50.20 (d), 52.08 (t), 55.79
(d), 118.63 (d), 144.62 (s), 203.77 (s), 208.94 (s); MS m/ z (rel
intensity) 400 (M+, 36), 385 (4), 382 (7); HRMS calcd for
C27H44O2 400.3341, found 400.333 64. Anal. Calcd for
C27H44O2: C, 80.94; H, 11.07. Found: C, 80.71; H, 10.85.
Compound 17: mp 64-66 °C (from MeOH); [R]D +90° (c )
1
0.07); IR 1713, 1686 cm-1; H NMR 0.72 (3H, s), 0.87 (6H, d,
J ) 6.6 Hz), 0.93 (3H, d, J ) 6.4 Hz), 1.26 (3H, s), 2.32 (1H,
dd, J ) 12.2, 2.8 Hz), 3.22 (1H, dd, J ) 12.2, 5.4 Hz), 3.54
(2H, s), 3.87 (1H, m); 13C NMR 12.55 (q), 18.71 (q), 21.18 (t),
22.54 (q), 22.80 (q), 23.82 (t), 23.82 (t), 24.93 (q), 28.00 (d),
28.64 (t), 33.58 (t), 35.55 (d), 36.20 (t), 39.15 (t), 39.46 (t), 40.50
(t), 43.83 (d), 44.27 (s), 45.39 (t), 52.89 (d), 55.22 (d), 56.78 (d),
60.02 (t), 78.18 (d), 82.25 (s), two carbons were not observed;
MS m/ z (rel intensity) 416 (M+, 22), 398 (2), 401 (2); HRMS
calcd for C27H44O3 416.329 04, found 416.329 38. Anal. Calcd
for C27H44O3: C, 77.82; H, 10.65. Found: C, 77.73; H, 10.51.
Compound 18: amorphous; [R]D -39.1° (c ) 0.27); IR 1765,
1710 cm-1; 1H NMR 0.7 (3H, s), 0.87 (6H, d, J ) 6.5 Hz), 0.90
(3H, d, J ) 6.2 Hz), 1.30 (3H, s), 3.87 (1H, d, J ) 10.3 Hz),
4.13 (1H, d, J ) 10.3 Hz); 13C NMR 7.57 (t) 11.92 (q), 18.54
(q), 19.03 (q), 22.51 (q), 22.77 (q), 23.72 (t), 23.85 (t), 23.98 (t),
25.23 (t), 27.78 (t), 27.96 (d), 28.04 (t), 33.32 (t), 35.23 (t), 35.68
(d), 35.76 (d), 35.95 (t), 39.41 (t), 39.46 (t), 42.49 (s), 48.86 (d),
51.90 (d), 56.22 (d), 89.84 (s), 176.48 (s), 204.56 (s); MS m/ z
(rel intensity) 544 (M+, 1), 417 (20), 403 (10), 399 (33), 385
(12), 99 (100), 43 (57); HRMS calcd for C27H45IO3 544.241 35,
found 544.241 68. Anal. Calcd for C27H45IO3: C, 59.53; H,
8.33. Found: C, 59.49; H, 8.41.
P h otolysis of 3â,5r-Dih yd r oxych olesta n -7-on e 3-Ace-
ta te (21). See full experimental details for entries 14-16 of
Table 1 in the Supporting Information. Lactone 25: amor-
phous; IR 1762, 1736 cm-1; 1H NMR 0.68 (3H, s), 0.87 (6H, d,
J ) 6.6 Hz), 0.93 (3H, d, J ) 6.4 Hz), 1.39 (3H, s), 2.05 (3H,
s), 2.99 (1H, s), 3.81 (1H, d, J ) 10 Hz), 3.84 (1H, d, J ) 10
Hz), 5.23 (1H, m); 13C NMR 6.09 (t), 12.19 (q), 18.77 (q), 21.04
(q), 21.48 (t), 22.52 (q), 22.77 (q), 22.92 (t), 23.83 (t), 24.36 (q),
27.97 (d), 28.16 (t), 28.56 (t), 29.22 (t), 35.58 (d), 36.14 (t), 38.83
(21) (a) Marshall, C. W.; Ray, R. E.; Laos, I.; Riegel, B. J . Am. Chem.
Soc. 1957, 79, 6308-6313. (b) Parish, E. J .; Wei, T.-Y. Synth. Commun.
1987, 17, 1227-1233.

Reaction of Alkoxy Radicals in Steroidal Systems
J . Org. Chem., Vol. 62, No. 9, 1997 2981
(t), 39.41 (t), 42.37 (d), 43.47 (t), 44.64 (s), 50.44 (d), 54.89 (d),
54.96 (d), 70.12 (d), 86.41(s), 170.47 (s), 176.77 (s), 199.76 (s);
MS m/ z (rel intensity) 542 (M+ - AcOH, 3), 539 (4), 369 (40),
319 (60), 254 (78); HRMS calcd for C27H43IO3 542.225 70, found
542.227 22. Anal. Calcd for C29H47IO5: C, 57.78; H, 7.87.
Found: C, 57.83; H, 7.98.
P h otolysis of 4,4-Dim eth yl-19-h yd r oxy-5r-ch olesta n -
3-on e 19,3-Hem ia ceta l (27). See full experimental details
for entries 17-22 of Table 1 in the Supporting Information.
Lactone 29: mp 119-120 °C (from n-pentane); [R]D -19° (c )
0.20); IR 1740 cm-1; 1H NMR 0.65 (3H, s), 0.86 (6H, d, J ) 6.5
Hz), 0.89 (3H, d, J ) 6.2 Hz), 1.12 (3H, s), 1.25 (3H, s), 2.65
(1H, dd, J ) 2.7, 17.1 Hz), 2.89 (1H, dd, J ) 3.1, 17.1 Hz),
4.03 (1H, t, J ) 2.9 Hz), 4.32 (1H, d, J ) 12.8 Hz), 4.54 (1H,
d, J ) 12.8 Hz); 13C NMR 12.22 (q), 18.82 (q), 21.18 (t), 22.67
(q), 22.79 (q), 22.94 (q), 23.74 (t), 23.94 (t), 24.67 (t), 28.04 (t),
28.13 (d), 30.90 (d), 31.92 (t), 35.50 (t), 35.57 (d), 35.80 (q),
36.24 (t), 39.36 (t), 39.60 (t), 42.73 (s), 45.26 (s), 52.32 (d), 56.12
(d), 56.27 (d), 60.61 (d), 66.24 (t), 78.00 (d), 80.82 (s), 170.78
(s); MS m/ z (rel intensity) 444 (M+, 4), 429 (100), 411 (7), 386
(5), 357 (4), 289 (28); HRMS calcd for C29H48O3 444.3693, found
444.3647. Anal. Calcd for C29H48O3: C, 78.31; H, 10.89.
Found: C, 78.52; H, 11.05.
Ack n ow led gm en t. This work was supported by the
Investigation Programme No. PB93-0171 of the Direc-
cio´n General de Investigacio´n Cient´ıfica y Te´cnica and
Programmes No. 93/030 and 93/014 of the Direccio´n
General de Universidades e Investigacio´n del Gobierno
de Canarias. A.B. thanks the Ministerio de Educacio´n
y Ciencia, Spain, for a fellowship.
Su p p or tin g In for m a tion Ava ila ble: Full description of
the experimental procedures for entries 3-22 of Table 1 (4
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O962252H