ORGANIC
LETTERS
2003
Vol. 5, No. 10
1773-1776
Indium-Mediated Reduction of
Hydroxylamines to Amines
Stefano Cicchi, Marco Bonanni, Francesca Cardona, Julia Revuelta, and
Andrea Goti*
Dipartimento di Chimica Organica “Ugo Schiff”, UniVersita` di Firenze,
Via della Lastruccia 13, I-50019 Sesto Fiorentino (FI), Italy
Received March 12, 2003
ABSTRACT
A novel and simple procedure for reduction of hydroxylamines to the corresponding amines by means of indium powder in aqueous media
is reported. Applicability to one-pot reactions and isoxazolidine N−O bond reduction is also demonstrated. A catalytic version of the process
using 2−5% In in the presence of other metals (Zn, Al) has been successfully developed.
In the past decade, indium metal has emerged as a suitable
and valuable reagent for accomplishing organometal addi-
tions to carbonyl and related compounds under Barbier
conditions in aqueous media.1 More recently, the huge
potential of indium powder as a broad scope reducing agent
for organic compounds has also been disclosed by Moody,
Ranu, and others.2 Many functional groups have served as
appropriate substrates for reductions with indium. Notable
examples are the reductions of nitroaromatics,2a,b,l azines,2a,c
oximes,2a,e 1,2-dibromides,2f R-halocarbonyl compounds,2g
benzyl halides,2g azides,2l,p N-oxides,2n,s,w nitrostyrenes,2o 1,1-
dibromoalkenes,2h and propargyl ethers, amines and esters.2i
The efficiency of In(0) as a reducing agent has been related
to its uncommonly low first ionization potential (5.8 eV),
which makes, in this respect, indium closer to alkaline metals
than to metals of groups 12-14. However, indium metal is
inert toward water and acid solutions, allowing its use in
aqueous media and making this metal an optimal “green
chemistry” reagent for reduction and allylation reactions.
In this Letter we report our results in the reduction of
hydroxylamines by indium metal. Being involved in the
chemistry of nitrones,3 we were interested in developing new
methods for reduction of N-O bonds of N,N-disubstituted
hydroxylamines and isoxazolidines, which are key intermedi-
ates deriving, respectively, from nucleophilic additions4 and
1,3-dipolar cycloadditions5 to nitrones. Conversion of isox-
(2) (a) Pitts, M. R.; Harrison, J. R.; Moody, C. J. J. Chem. Soc., Perkin
Trans. 1 2001, 955-977. (b) Moody, C. J.; Pitts, M. R. Synlett 1998, 1028.
(c) Moody, C. J.; Pitts, M. R. Synlett 1998, 1029-1030. (d) Moody, C. J.;
Pitts, M. R. Synlett 1999, 1575-1576. (e) Harrison, J. R.; Moody, C. J.;
Pitts, M. R. Synlett 2000, 1601-1602. (f) Ranu, B. C.; Guchhait, S. K.;
Sarkar, A. Chem. Commun. 1998, 2113-2114. (g) Ranu, B. C.; Dutta, P.;
Sarkar, A. J. Chem. Soc., Perkin Trans. 1 1999, 1139-1140. (h) Ranu, B.
C.; Samanta, S.; Guchhait, S. K. J. Org. Chem. 2001, 66, 4102-4103. (i)
Ranu, B. C.; Dutta, J.; Guchhait, S. K. J. Org. Chem. 2001, 66, 5624-
5626. (j) Ranu, B. C.; Samanta, S.; Das, A. Tetrahedron Lett. 2002, 43,
5993-5995. (k) Lim, H. J.; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y.
Tetrahedron Lett. 1998, 39, 4367-4368. (l) Lee, J. G.; Choi, K. I.; Koh,
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Srinivas, R.; Ramalingam, T. Synlett 2000, 1447-1449. (p) Reddy, G. V.;
Rao, G. V.; Iyengar, D. S. Tetrahedron Lett. 1999, 40, 3937-3938. (q)
Miyai, T.; Ueba, M.; Baba, A. Synlett 1999, 182-184. (r) Baek, H. S.;
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2000, 41, 8097-8099. (s) Jeevanandam, A.; Cartwright, C.; Ling, Y. C.
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(1) Reviews: (a) Li, C.-J.; Chan, T.-H. Tetrahedron 1999, 55, 11149-
11176. (b) Paquette, L. A. In Green Chemistry-Frontiers in Benign
Chemical Syntheses and Processes; Anastas, P. T., Williamson, T. C., Eds.;
Oxford University Press: Oxford, 1998; pp 250-264. (c) Cintas, P. Synlett
1995, 1087-1096.
10.1021/ol034434l CCC: $25.00 © 2003 American Chemical Society
Published on Web 04/22/2003