analogues in green, synthetically useful transformations
Dichloroindium hydride was first generated by transmeta-
lation between indium trichloride and tributyltin hydride,5a,b
but it can be produced as well by reduction of the halide
with NaBH4 in acetonitrile5c or DIBAL-H in THF5d-f or
transmetalation with triethylsilane in acetonitrile5g or diphen-
ylsilane in THF.5h Although we observed that all methods
are suitable to perform reduction of azides, the most
convenient one was by far the transmetalation between InCl3
and Et3SiH, in terms of both product yields and ease of
procedure and workup.
(Scheme 1).8,9 Of course, the first, simplest test of this project
Scheme 1
Therefore, all of the reactions reported in Table 1 were
normally carried out by adding the azide (1 equiv) to an
was to verify whether dichloroindium hydride could act as
an effective, mild reducing agent capable of converting
simple organic azides to the corresponding amines.
Table 1. Reduction of Azides 1 to Amines 2 with
Dichloroindium Hydride (1.1 equiv) in Acetonitrile at 0 °C
(3) (a) Ranu, B. C. Eur. J. Org. Chem. 2000, 2347. (b) Takami, K.;
Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K. Org. Lett. 2001,
3, 1997. (c) Bandini, M.; Cozzi, P. G.; Garelli, A.; Melchiorre, P.; Umani-
Ronchi, A. Eur. J. Org. Chem. 2002, 3243. (d) Gotov, B.; Kaufmann, J.;
Schumann, H.; Schmalz, H.-G. Synlett 2002, 361. (e) Iasuda, M.; Yamasaki,
S.; Onishi, Y.; Baba, A. J. Am. Chem. Soc. 2004, 126, 7186. (f) Bandini,
M.; Fagioli, M.; Melloni, A.; Umani-Ronchi, A. AdV. Synth. Catal. 2004,
346, 573. (g) Juan, S.; Hua, Z.-H.; Qi, S.; Ji, S.-J.; Loh, T.-P. Synlett 2004,
829. (h) Cho, D. H.; Jang, D. O. Tetrahedron Lett. 2004, 45, 2285. (i) Lu,
J.; Ji, S.-J.; Loh, T.-P. Chem. Commun. 2005, 2345.
(4) (a) Ranu, B. C.; Samanta, S. Tetrahedron Lett. 2002, 43, 7405. (b)
Ranu, B. C.; Das, A.; Hajra, A. Synthesis 2003, 1012. (c) Inoue, K.; Ishida,
T.; Shibata, I.; Baba, A. AdV. Synth. Catal. 2002, 344, 283. (d) Shibata, I.;
Kato, H.; Ishida, T.; Yasuda, M.; Baba, A. Angew. Chem., Int. Ed. 2004,
43, 711.
(5) (a) Miyai, T.; Inoue, K.; Yasuda, M.; Shibata, I.; Baba, A.
Tetrahedron Lett. 1998, 39, 1929. (b) Inoue, K.; Sawada, A.; Shibata, I.;
Baba, A. Tetrahedron Lett. 2001, 42, 4661. (c) Inoue, K.; Sawada, A.;
Shibata, I.; Baba, A. J. Am. Chem. Soc. 2002, 124, 906. (d) Takami, K.;
Yorimitsu, H.; Oshima, K. Org. Lett. 2002, 4, 2993. (e) Takami, K.; Mikami,
S.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. Tetrahedron 2003, 59, 6627.
(f) Takami, K.; Mikami, S.; Yorimitsu, H.; Shinokubo, H.; Oshima, K. J.
Org. Chem. 2003, 68, 6627. (g) Hayashi, N.; Shibata, I.; Baba, A. Org.
Lett. 2004, 6, 4981. (h) Hayashi, N.; Shibata, I.; Baba, A. Org. Lett. 2005,
7, 3093. For other radical reactions involving indium metal, see: (i) Miyabe,
H.; Ueda, M.; Nishimura, A.; Naito, T. Org. Lett. 2002, 4, 131. (j) Miyabe,
H.; Naito, T. Org. Biomol. Chem. 2004, 2, 1267. For other radical reactions
involving organoindium reagents, see: (k) Usugi, S.-I.; Tsuritani, T.;
Yorimitsu, H.; Shinokubo, H.; Oshima, K. Bull. Chem. Soc. Jpn. 2002, 75,
841. (l) Takami, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2004, 6, 4555.
(m) Takami, K.; Usugi, S.-I., Yorimitsu, H.; Oshima, K. Synthesis 2005,
824.
entry
compd
R
time (min)
yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a
b
c
d
e
f
4-MeO-C6H4
4-NC-C6H4
4-Cl-C6H4
4-I-C6H4
4-MeOCO-C6H4
4-O2N-C6H4
4-O2N-C6H4
1-naphthyl
4-MeCO-C6H4
PhSO2
15
15
15
15
30
15
15
90
overnight
210
180
15
15
60
96
97
95
88
83
63
f
99b
70
g
h
i
j
k
l
g
i
j
60b
80
PhCO
71
Ph(CH2)3
Ph(CH2)2
1-naphthyl
PhSO2
55c
56c
70d
82d
75d
90
60
PhCO
a Yields are for pure amines isolated after workup and/or chromatography.
b Reaction carried out at -20 °C. c Reaction carried out with 2 equiv of
hydride. d Reaction carried out in the presence of triethylborane (0.2 equiv).
(6) (a) Benati, L.; Nanni, D.; Sangiorgi, C.; Spagnolo, P. J. Org. Chem.
1999, 64, 7836. (b) Benati, L.; Leardini, R.; Minozzi, M.; Nanni, D.;
Spagnolo, P.; Strazzari, S.; Zanardi, G.; Calestani, G. Tetrahedron 2002,
58, 3485. (c) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni,
D.; Scialpi, R.; Spagnolo, P.; Zanardi, G.; Rizzoli, C. Org. Lett. 2004, 6,
417. (d) Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem. 2005, 70, 3046.
(7) (a) Frankel, M.; Wagner, D.; Gertner, D.; Zikha, A. J. Organomet.
Chem. 1967, 7, 518. (b) Samano, M. C.; Robins, M. J. Tetrahedron Lett.
1991, 32, 6293. (c) Poopeiko, N. E.; Pricota, T. I.; Mikhailopulo, I. A.
Synlett 1991, 342. (d) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc.
1993, 115, 3328; (e) Kim, S.; Joe, G. H.; Do, J. Y. J. Am. Chem. Soc.
1994, 116, 5521. (f) Kim, S.; Do, J. Y. J. Chem. Soc., Chem Commun.
1995, 1607. (g) Kim, S.; Kim, S. S.; Seo, H. S.; Yoon, K. S. Tetrahedron
1995, 51, 8437. (h) Dang, H.-S.; Roberts, B. P. J. Chem. Soc., Perkin Trans.
1 1996, 1493. (i) Kim, S.; Yeon, K. M.; Yoon, K. S. Tetrahedron Lett.
1997, 38, 3919. (j) Hornemann, A. M.; Lundt, I. J. Org. Chem. 1998, 63,
1919. (k) Montevecchi, P. C.; Navacchia, M. L.; Spagnolo, P. Eur. J. Org.
Chem. 1998, 1219. (l) Hays, D. S.; Fu, G. C. J. Org. Chem. 1998, 63,
2796. (m) Moreno-Vargas, A. J.; Vogel, P. Tetrahedron Lett. 2003, 44,
5069.
acetonitrile solution of dichloroindium hydride (1.1 equiv),
generated in situ by stirring anhydrous indium trichloride
(1.1 equiv) and triethylsilane (1.1 equiv) in acetonitrile (4
mL) for 5 min at 0 °C.5g The resulting mixture was stirred
at 0 °C until disappearance of the starting material. The final
crude product was quenched with an acid aqueous solution
and extracted with diethyl ether to remove the silane residues.
The aqueous phase was neutralized and extracted with diethyl
ether to give the amine, which was in a few cases eventually
purified by column chromatography.10,11
(10) Under the reaction conditions all azides were totally inert toward
both triethylsilane and InCl3 alone. All of the products reported in Table 1
are commercially available compounds, and their identification was based
on spectral comparison with authentic samples.
(11) Interestingly, in many cases, foils of indium metal, unequivocally
identified by SEM-EDAX analysis, separated from the mixtures during the
first aqueous workup, thus allowing recovery of part of the precious reagent.
This observation has never been reported in previous HInCl2-mediated
reactions. Since separation of In metal is strictly linked to the workup stage,
we think it is not tied in with the radical mechanism but it might rather
arise from hydrolysis of the intermediate indium amides.
(8) Azides have been recently reduced by reaction with indium metal:
(a) Reddy, G. V.; Rao, G. V.; Iyengar, D. S. Tetrahedron Lett. 1999, 40,
3937. (b) Lee, J. G.; Choi, K. I.; Koh, H. Y.; Kim, Y.; Kang, Y.; Cho, Y.
S. Synthesis 2001, 81.
(9) Very recently, tributylgermyl radicals have also been shown to add
to aryl azides yielding germylaminyl radicals and thence reduced amines.
See: Benati, L.; Bencivenni, G.; Leardini, R.; Minozzi, M.; Nanni, D.;
Scialpi, R.; Spagnolo, P.; Zanardi, G. J. Org. Chem., 2006, 71, 434.
2500
Org. Lett., Vol. 8, No. 12, 2006