8572
J. Am. Chem. Soc. 1997, 119, 8572-8573
Table 1. Deoxygenation of Primary and Secondary Alcohols
Single-Step Process for the Reductive
Deoxygenation of Unhindered Alcohols
Andrew G. Myers,* Mohammad Movassaghi, and Bin Zheng
DiVision of Chemistry and Chemical Engineering
California Institute of Technology
Pasadena, California 91125
ReceiVed May 30, 1997
The importance of methodology for the reductive deoxygen-
ation of alcohols can be gauged by the widespread use of the
Barton deoxygenation reaction in synthetic organic chemistry.1
This two-step procedure involves initial acylation of an alcohol
with a reagent such as thiocarbonyldiimidazole followed by
reductive cleavage of the resultant thiocarbonyl compound with
tri-n-butyltin hydride. As an outgrowth of recent methodologi-
cal studies,2 we report the development of a process for the
reductive deoxygenation of unhindered primary and secondary
alcohols that proceeds in a single step without using metal
hydride reagents.
The new method involves the transformation of an alcohol
to a monoalkyl diazene2,3 and proceeds by Mitsunobu displace-
ment4 of the alcohol with o-nitrobenzenesulfonylhydrazine
(NBSH)5 followed by in situ elimination of o-nitrobenzene-
sulfinic acid. In prior work, displacement by NBSH was shown
to lead to efficient reductive transposition of allylic and
propargylic alcohols to form alkenes and allenes, respectively,
by a sigmatropic elimination reaction.2 The present study
concerns the transformation of non-allylic (non-propargylic)
alcohols, for which literature precedent, most notably the work
of Kosower et al.,6 suggested that the proposed monoalkyl
diazene intermediates would decompose by a free-radical
mechanism to form deoxygenated products. This expectation
was realized experimentally, as demonstrated by the examples
of Table 1, and represents a valuable new method for the
reductive deoxygenation of alcohols. The following experi-
mental procedure is illustrative: diethylazodicarboxylate (DEAD,
183 µL, 1.16 mmol, 2.00 equiv) was added to a deoxygenated
solution of triphenylphosphine (304 mg, 1.16 mmol, 2.00 equiv)
a Isolated yields; yield in parentheses obtained by gas chromatog-
raphy. b NMM used as the solvent. c Neopentyl alcohol (2.0 equiv) was
added. d Mitsunobu product (-30 °C) added to a solution of toluene
at reflux. e Dioxygen was introduced prior to diazene formation at 23
°C; methyl sulfide workup.
(1) (a) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans.
1 1975, 1574. (b) Barton, D. H. R.; Motherwell, W. B.; Stange, A. Synthesis
1981, 743. (c) Barton, D. H. R.; Hartwig, W.; Hay-Motherwell, R. S.;
Motherwell, W. B.; Stange, A. Tetrahedron Lett. 1982, 23, 2019. (d)
Hartwig, W. Tetrahedron 1983, 39, 2609.
(2) (a) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492. (b)
Myers, A. G.; Zheng, B. Tetrahedron Lett. 1996, 37, 4841.
(3) For diazenes as intermediates in applications to synthetic organic
chemistry, see: (a) Szmant, H. H.; Harnsberger, H. F.; Butler, T. J.; Barie,
W. P. J. Am. Chem. Soc. 1952, 74, 2724. (b) Nickon, A.; Hill, A. S. J. Am.
Chem. Soc. 1964, 86, 1152. (c) Corey, E. J.; Cane, D. E.; Libit, L. J. Am.
Chem. Soc. 1971, 93, 7016. (d) Hutchins, R. O.; Kacher, M.; Rua, L. J.
Org. Chem. 1975, 40, 923. (e) Kabalka, G. W.; Chandler, J. H. Synth.
Commun. 1979, 9, 275. (f) Corey, E. J.; Wess, G.; Xiang, Y. B.; Singh, A.
K. J. Am. Chem. Soc. 1987, 109, 4717. (g) Myers, A. G.; Kukkola, P. J. J.
Am. Chem. Soc. 1990, 112, 8208. (h) Myers, A. G.; Finney, N. S. J. Am.
Chem. Soc. 1990, 112, 9641. (i) Guziec, F. S., Jr.; Wei, D. J. Org. Chem.
1992, 57, 3772. (j) Wood, J. L.; Porco, J. A., Jr.; Taunton, J.; Lee, A. Y.;
Clardy, J.; Schreiber, S. L. J. Am. Chem. Soc. 1992, 114, 5898.
(4) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Hughes, D. L. Org. React.
1992, 42, 335.
and N-(4-chlorobenzoyl)-3-(2-hydroxyethyl)-5-methoxy-2-me-
thylindole (Table 1, entry 1, 200 mg, 0.58 mmol, 1 equiv) in
anhydrous tetrahydrofuran (THF, 4.0 mL) at -30 °C. After
20 min, a solution of NBSH (378 mg, 1.74 mmol, 3.00 equiv)
in THF (2.0 mL) was added. The reaction mixture was stirred
at -30 °C for 2 h and then warmed to 23 °C to induce diazene
formation. After 2 h, the orange reaction mixture was concen-
trated. Purification of the residue by flash column chromatog-
raphy on silica gel (5% ethyl acetate in hexanes) afforded the
deoxygenated product as an off-white solid (165 mg, 87%, mp
70-71 °C).7
The method is found to work well for unhindered alcohols,
but sterically encumbered and â-oxygenated alcohols (diiso-
propylidene-D-galactopyranose, glycerol acetonide, thymidine)
(5) Myers, A. G.; Zheng, B.; Movassaghi, M. J. Org. Chem. In press.
(6) (a) Kosower, E. M. Acc. Chem. Res. 1971, 4, 193. (b) Tsuji, T.;
Kosower, E. M. J. Am. Chem. Soc. 1971, 93, 1992.
(7) The indicated stoichiometries are recommended, as fewer equivalents
of reagents may lead to incomplete conversion of substrate.
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