ORGANIC
LETTERS
2
012
Vol. 14, No. 18
842–4845
Indium-Catalyzed Reductive Bromination
of Carboxylic Acids Leading to Alkyl
Bromides
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Toshimitsu Moriya, Shinichiro Yoneda, Keita Kawana, Reiko Ikeda,
Takeo Konakahara, and Norio Sakai*
Department of Pure and Applied Chemistry, Faculty of Science and Technology, Tokyo
University of Science (RIKADAI), Noda, Chiba 278-8510, Japan
Received August 4, 2012
ABSTRACT
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The combination of 1,1,3,3-tetramethyldisiloxane (TMDS) and trimethylbromosilane (Me SiBr) with a catalytic amount of indium bromide (InBr )
undertook direct bromination of carboxylic acids, which produced the corresponding alkyl bromides in good to excellent yields. The reducing
system was tolerant to several functional groups.
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Alkyl bromides are useful building blocks that can be
converted to various compounds such as amines, ethers,
alcohols, aldehydes, and ketones. However, a direct
conversion from carboxylic acids has not been studied to
date. Generally, the conventional method for the bromina-
tion of carboxylic acids requires a multistep procedure
involving the initial reduction of a carboxylic acid with
lithium aluminum hydride (LAH) and a subsequent
nucleophilic substitution using a hydrogen halide or a
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and nitriles. Although a number of methods have been
developed for the synthesis of alkyl bromides, a single-step
bromination from other functional groups has not been
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studied extensively. Achievement of the method is quite
valuabletothe aspectsof decreasing the synthetic steps and
the environmental load of organic synthesis. Thus far,
several groups have established direct bromination with
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phosphorus halide. In addition, a poor chemoselectivity
to other functional groups and the moisture sensitivity of
LAH lower the synthetic utility.
The reductive conversion of various functional groups
by a combination of indium(III) salt and a hydrosilane has
been developed by several groups. For example, Baba’s
group has reported the reductive transformation of
(
1) For review, see: (a) Chambers, R. D.; James, S. D. In Compre-
hensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon
Press: Oxford, 1979; Vol. 1, p 493. (b) Bohlmann, R. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford,
1
991; Vol. 6, pp 203ꢀ223.
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9
10
(
2) For selected papers for the functional group transformation
alcohols, aryl/alkyl ketones/aldehydes, and acid chlorides.
from alkyl bromides, see: (a) Koziara, A.; Osowska-Pacewicka, K.;
Zawadski, S.; Zwierzak, A. Synthesis 1985, 202. (b) Yabe, O.; Mizufune,
H.; Ikemoto, T. Synlett 2009, 1291. (c) Williamson, A. J. J. Chem. Soc.
852, 4, 229.
(
(
5) (a) Aizpurua, M. J.; Lecea, B.; Palomo, C. Can. J. Chem. 1986, 64,
2342. (b) Kabalka, G. W.; Wu, Z.; Ju, Y. Tetrahedron Lett. 2000, 41,
161. (c) Das, B.; Srinivas, Y.; Holla, H.; Laxminarayama, K.;
1
5
3) For reviews, see: Spargo, P. L. In Comprehensive Organic Functional
Narender, R. Tetrahedron Lett. 2007, 48, 6681.
(6) (a) Corre, L. M.; Emmanual, G.; Deit, L. H. J. Chem. Soc., Chem.
Commun. 1989, 313. (b) Li, Z.; Sheng, C.; Yang, C.; Qiu, H. Oppi Briefs
Group Transformations; Katritzky, A. L., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon: New York, 1995; Vol. 2, pp 2ꢀ36.
(4) (a) Jung, M. E.; Hatfield, L, G. Tetrahedron Lett. 1978, 19, 4483.
2
007, 39, 608.
(
b) Cainelli, G.; Contento, M.; Manescalchi, F.; Plessi, L. Synthesis
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983, 306. (c) Ferreri, C.; Costantino, C.; Chatgilialoglu, C.; Boukherroub,
(7) Bilger, C.; Royer, R.; Demerseman, P. Synthesis 1988, 902.
(8) Yasuda, M.; Onishi, Y.; Ueba, M.; Miyai, T.; Baba, A. J. Org.
Chem. 2001, 66, 7741.
R.; Manuel, G. J. Organomet. Chem. 1998, 554, 135. (d) Firouzabadi,
H.; Iranpoor, N.; Ebrahimzadeh, F. Tetrahedron Lett. 2006, 47, 1771.
(
(
(
e) Klein, M. S.; Zhang, C.; Jiang, L. Y. Tetrahedron Lett. 2008, 49, 2638.
f) Nieddu, G.; Luca, D. L.; Giacomelli, G. Synthesis 2008, 3937.
g) Imura, Y.; Shimojuh, N.; Kawano, Y.; Togo, H. Tetrahedron 2010,
(9) Miyai, T.; Ueba, M.; Baba, A. Synlett 1999, 182. (b) Onishi, Y.;
Ogawa, D.; Yasuda, M.; Baba, A. J. Am. Chem. Soc. 2002, 124, 13690.
(10) Inoue, K.; Yasuda, M.; Shibata, I.; Baba, A. Tetrahedron Lett.
2000, 41, 113.
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6, 3421.
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0.1021/ol302168q r 2012 American Chemical Society
Published on Web 09/13/2012