LETTER
A New Molecular Iodine-Catalyzed Acetalization of Carbonyl Compounds
321
(5) Ghatak, A.; Becker, F. F.; Banik, B. K. Tetrahedron Lett.
2000, 41, 3793.
(6) Inanage, J.; Handa, Y.; Tabuchi, T.; Otsubo, K.; Hanamoto,
T. Tetrahedron Lett. 1991, 32, 6557.
synthesis of natural products where it is absolutely neces-
sary to have mild conditions, reactivity differences among
functional groups, and reagents that are compatible with
other acid-sensitive groups.
(7) General Procedure for Acetalization: The carbonyl
compound (1 mmol) was dissolved in methanol (4 mL) or
ethanol, and iodine (0.1 mmol) was added with stirring.
After the starting material was consumed as indicated by
TLC, methanol was evaporated. The crude product was
extracted with dichloromethane, washed with saturated
NaHCO3, and dried over Na2SO4 and the solvent was
evaporated. Finally the pure products were obtained by
purification through basic alumina using ethyl acetate–
hexane (10:90) as the solvent.
O
I2/MeOH
~90%
O
O
14
H3CO
OCH3
Procedure for Competitive Reduction of Two Carbonyl
Compounds: The two investigated compounds (1 mmol
each) were dissolved in dry methanol (4.0 mL), and iodine
(12.5 mg) was added. The mixture was then stirred for 1 h.
NaBH4 (80.0 mg, 2 equiv) was then added in one portion
with stirring. After the vigorous reaction subsided the
reaction mixture was refluxed for 0.5 h. The reaction mixture
was cooled, acidified (pH 3) by 1 N aqueous HCl, and
extracted with dichloromethane. The ratio of the compounds
was determined by a comparison study with known
authentic samples by NMR.
15
NaBH4/MeOH
H+, 90%
OH
Procedure for Competitive Reduction of Cinnamaldehyde
and Methyl Cinnamate: The two compounds (1 mmol each)
were dissolved in dry methanol (4.0 mL) and iodine (13 mg)
was added. The mixture was then stirred for 1 h. After this,
additional amounts of iodine (25 mg) were added and the
mixture was stirred for 5 min. Samarium powder (2.0 mmol)
was added under argon atmosphere with stirring. An
exothermic reaction with evolution of gas was observed.
After 20 min the solution was acidified (pH 3) by 1 N
aqueous HCl; saturated NaCl was then added to the reaction
mixture and extracted with dichloromethane. Drying of the
organic solution over Na2SO4 and evaporation of the solvent
gave a mixture that was analyzed by NMR.
O
16
Scheme 3
Acknowledgement
This work was supported in part by a grant received from the Robert
J. Kleberg, Jr. and Helen C. Kleberg Foundation and NIH Cancer
Center Support Grant, 5-P30-CA16672-25, in particular the shared
resources of the Pharmacology and Analytic Center Facility.
3,3-Dimethoxyandrostan-17-one(15): Androstane-3,17-
dione(14, 90 mg, 0.3 mmol) was dissolved in dry methanol
(5 mL), and iodine (0.03 mmol) was added. The solution was
stirred for 2 h. Methanol was evaporated off and the residue
was dissolved in dichloromethane and washed with 5%
NaHCO3. After being dried, the organic layer was
evaporated, and 101 mg (97%) of a semi-solid mass was
obtained. Pure product was obtained by recrystallization
from methanol, mp127 °C.
17- -Hydroxyandrostan-3-one(16): Androstane-3,17-dione
(90 mg, 0.3 mmol) was dissolved in of dry methanol (5 mL),
and iodine (0.03 mmol) was added. The solution was stirred
for 2h. When TLC indicated complete disappearance of
androstane-3,17-dione, NaBH4 (100 mg) was added and the
mixture was stirred for 1 h. Water was then added, and the
mixture was extracted with CH2Cl2. Drying of organic layer
over Na2SO4 and removal of solvent under reduced pressure
afforded 103 mg of a white solid: mp 171 °C, [ ]D +12.5 in
MeOH.2b Hydrolysis of this dimethoxy compound (MeOH,
1 N aq. HCl 30 min, room temperature). Crytallization of the
crude solid led to 17- -hydroxyandrostan-3-one (16, 76 mg,
83%).
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Synlett 2002, No. 2, 319–321 ISSN 0936-5214 © Thieme Stuttgart · New York