J . Org. Chem. 2001, 66, 7741-7744
7741
Dir ect Red u ction of Alcoh ols: High ly Ch em oselective Red u cin g
System for Secon d a r y or Ter tia r y Alcoh ols Usin g
Ch lor od ip h en ylsila n e w ith a Ca ta lytic Am ou n t of In d iu m
Tr ich lor id e
Makoto Yasuda, Yoshiyuki Onishi, Masako Ueba, Takashi Miyai, and Akio Baba*
Department of Molecular Chemistry, Graduate School of Engineering, Osaka University,
2
-1 Yamadaoka, Suita, Osaka 565-0871, J apan
Received J une 21, 2001
The direct reduction of alcohols using chlorodiphenylsilane as a hydride source in the presence of
a catalytic amount of indium trichloride is described. Benzylic alcohols, secondary alcohols, and
tertiary alcohols were effectively reduced to give the corresponding alkanes in high yields. A
compound bearing both primary and secondary hydroxyl groups was reduced only at the secondary
site to afford the primary alcohol after workup with Bu NF. This system showed high chemose-
4
lectivity only for the hydroxyl group while not reducing other functional groups that are readily
reduced by standard reducing systems. Thus alcohols bearing ester, chloro, bromo, or nitro groups,
+
which are sensitive to LiAlH
chlorodiphenylsilane/InCl
silyl ether is initially formed and then, with InCl
which accelerates the desiloxylation with donation of the hydrogen to the carbon.
4
or Zn/H , were selectively reduced only at the hydroxyl sites by the
3
system. NMR studies revealed the reaction course. The hydrodiphenyl-
acting as a Lewis acid, forms an oxonium complex,
3
In tr od u ction
duced to alkanes.7 Additionally, this direct pathway
shows the selective reduction that took place only at the
hydroxyl moiety without influence on other functional
groups.
Alcohols are versatile organic compounds reagents and
can be used as precursors for other classes of organic
molecules in synthetic chemistry. A representative trans-
formation of alcohols is deoxygenation to alkane. Since
a hydroxyl group is a poor leaving group, it should be
generally activated before treating with a reducing
reagent. Tosylation or thiocarboxylation are generally
employed for activation.1 Although a few direct reduc-
tions of alcohols have been reported, there are some
problems to be solved. Nickel-catalyzed hydrogenation of
Resu lts a n d Discu ssion
Dir ect Red u ction of Alcoh ols by Hyd r osila n e/
In d iu m Ch lor id e. We chose a simple aliphatic alcohol
1a for an initial trial to investigate the reducing system.
,2
6
Our previous system,
3
chlorodimethylsilane/InCl , did not
8
work, as shown in Table 1, entry 7. As the reactivity of
hydrosilane strongly depends on the substituent on the
silicon center, a variety of hydrosilanes were tested.
Among hydrosilanes examined, chlorodiphenylsilane
alcohols requires high temperature and pressure (250 °C,
50 atm). Only alcohols that can generate stable car-
bocations are reduced using strong acidic media. The
hydride reagents generally need the aid of excess amounts
of Lewis acids. In this context, the development of an
3
1
4
showed high activity with a catalytic amont of InCl
3
at
refluxing temperature in dichloroethane (entry 1). The
reaction using chlorodiphenylsilane without InCl gave
a low yield of decane 2 (entry 2).10 Neither Group 13
catalyst, AlCl , nor BF ‚OEt , was effective with chloro-
9
5
efficient reducing system for direct deoxygenation of
alcohols under catalytic and mild conditions is strongly
desired. We have recently reported the deoxygenation of
alcohols using chlorodimethylsilane with a catalytic
3
3
3
2
diphenylsilane (entries 3 and 4) probably because of their
instability to alcohols. Indium trichloride, on the other
hand, tolerates protic conditions and can in fact be used
6
amount of a Lewis acid. The reducing system is strictly
limited to only benzylic alcohols.
In this paper, we report the effective methodology for
direct reduction of alcohols, in which a wide variety of
secondary or tertiary alcohols are chemoselectively re-
(
7) The direct reduction of primary alcohols by hydrosilane with a
catalyst was recently reported. (a) Gevorgyan, V.; Liu, J .-X.; Rubin,
M.; Benson, S.; Yamamoto, Y. Tetrahedron Lett. 1999, 40, 8919-8922.
b) Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J .-X.; Yamamoto, Y. J .
(
Org. Chem. 2000, 65, 6179-6186.
(
1) Comprehensive Organic Syntheses; Trost, B. M., Ed.; Pergamon
(8) The reaction under higher temperature was not carried out
because of the low boiling point of chlorodimethylsilane (ca. 35 °C).
(9) In some cases, phenylsilanes are reported to have higher
reactivity than alkylsilanes. Matsuda, I.; Fukuta, Y.; Tsuchihashi, T.;
Nagashima, H.; Itoh, K. Organometallics 1997, 16, 4327-4345.
Press: Oxford, U.K., 1991; Vol. 8, pp 811-826.
(
(
(
(
2) Hartwig, W. Tetrahedron 1983, 39, 2609-2645.
3) Wojcik, B.; Adkin, H. J . Am. Chem. Soc. 1933, 55, 1293-1294.
4) Gribble, G. W.; Leese, R. M. Synthesis 1977, 172-176.
5) For example: (a) Brewster, J . H.; Osman, S. F.; Bayer, H. O.;
4 4 3
(10) As is well-known, LiAlH , NaBH , or Bu SnH were not effective
Hopps, H. B. J . Org. Chem. 1964, 29, 121-123. (b) Lau, C. K.;
at all as hydride sources, although they are generally used for reduction
of the corresponding tosylates or thiocarbonates in an ionic or radical
manner. Barton, D. H. R.; McCombie S. W. J . Chem. Soc., Perkin
Trans. 1 1975, 1574-1585 and ref 1.
Dufresne, C.; B e´ langer, P. C.; Pi e´ tr e´ , S.; Scheigetz, J . J . Org. Chem.
1
986, 51, 3038-3043.
6) Miyai, T.; Ueba, M.; Baba, A. Synlett 1999, 182-184.
(
1
0.1021/jo0158534 CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/29/2001