LETTER
Lewis Acid-Catalyzed Reductive Amination of Carbonyl Compounds
1619
–
(7) For tandem reactions, see: Tietze, L. F. Chem. Rev. 1996, 96,
115.
+
O
MXn
O
MXn
(8) (a) McDonald, F. E.; Gleason, M. M. J. Am. Chem. Soc.
1996, 118, 6648. (b) Hojo, M.; Nagayoshi, M.; Fujii, A.;
Yanagi, T.; Ishibashi, N.; Miura, K.; Hosomi, A. Chem. Lett.
1994, 719.
(9) (a) Blackwell, J. M.; Sonmor, E. R.; Scoccitti, T.; Piers, W.
E. Org. Lett. 2000, 2, 3921. (b) Hojo, M.; Murakami, C.;
Fujii, A.; Hosomi, A. Tetrahedron Lett. 1999, 40, 911.
(c) Kobayashi, S.; Yasuda, M.; Hachiya, I. Chem. Lett. 1996,
407. (d) Ojima, I.; Kogure, T.; Nagai, Y. Tetrahedron Lett.
1973, 2475.
R1
R2
R1
path a
R2
1
1
path b
–
–
MXn
MXn
+
+
Me2HSiO NR3R4
Me2(R3R4N)SiO
R1
H
R1
R2
R2
3
4
– MXn
– MXn
(10) Recently, a few research groups have developed the direct
reductive amination with hydrosilanes: (a) Apodaca, R.;
Xiao, W. Org. Lett. 2001, 3, 1745. (b) Chen, B.-C.;
Sundeen, J. E.; Guo, P.; Bednarz, M. S.; Zhao, R.
Tetrahedron Lett. 2001, 42, 1245. (c) Dubé, D.; Scholte, A.
A. Tetrahedron Lett. 1999, 40, 2295; in the latter two works,
a stoichiometric amount of a promoter was used unlike the
present method.
(11) Stepwise (indirect) reductive amination with hydrosilanes
including the preformation of the imine intermediates has
been also reported, see ref 9c and: Chandrasekhar, S.;
Reddy, C. R.; Ahmed, M. Synlett. 2000, 1655.
+
2
1/m (Me2SiO)m
Scheme 2
–
TiCl4
TiCl4
+
(0.2 equiv.)
Me2(Et2N)SiO
H
PhCH2OSi(NEt2)Me2
2aa
CH2Cl2
0 °C to rt
36 h
5
Ph
H
4'
Scheme 3
(12) (Diethylamino)dimethylsilane (1a) can be prepared from
chlorodimethylsilane and 2 equiv of diethylamine in 81%
yield.
(13) The reactions using several Lewis acids (CH2Cl2, r.t., 36 h)
gave the following results. Lewis acid (equiv), yield of 2aa:
TiCl4 (0.1), 75%; TiCl4 (0.2), 84%; SnCl4 (0.2), 53%;
TMSOTf (0.2), 40%; InCl3 (0.1), 70%; BiCl3 (0.1), 20%;
Yb(OTf)3 (0.1), 26%.
Acknowledgement
This work was partly supported by CREST, Science and Technolo-
gy Corporation (JST). We thank Dow Corning Toray Silicone Co.
Ltd. and Shin-Etsu Chemical Co. Ltd. for a gift of organosilicon
compounds.
(14) General procedure for the TiCl4-catalyzed reductive
amination: To a solution of 1 (1.20 mmol) and a carbonyl
compound (1.00 mmol) in CH2Cl2 (1.0 mL) at 0 °C was
added TiCl4 (1.0 M in CH2Cl2, 0.20 mL, 0.20 mmol). The
mixture was stirred for 10 min and warmed to r.t. After 36 h,
the reaction mixture was treated with 0.1 M HCl (20 mL) for
10 min and washed with t-BuOMe (3 10 mL). The aqueous
layer obtained was alkalized with 1.0 M aqueous NaOH (ca
5 mL) and extracted with t-BuOMe (3 10 mL). The
combined organic layer was dried over Na2SO4 and
evaporated. The product obtained was proved to be almost
pure by 1H NMR analysis. When ZnI2 or Ph3CClO4 was used
as a catalyst, 1 and a carbonyl compound were added to a
suspension of ZnI2 or Ph3CClO4 in CH2Cl2.
(15) We also found that the TiCl4 (0.2 equiv)-catalyzed reaction
among Et2NSiMe3, PhMe2SiH, and benzaldehyde
(1.2:1.2:1) gave 2aa in 66% yield.
(16) Ipaktschi et al. have proposed that the LiClO4-mediated
reaction of aldehydes with aminotrimethylsilanes gives
iminium salts: Saidi, M. R.; Heydari, A.; Ipaktschi, J. Chem.
Ber. 1994, 127, 1761.
References and Notes
(1) Studies on Organosilicon Chemistry. No. 155.
(2) (a) Hutchins, R. O.; Hutchins, M. K. Comprehensive
Organic Synthesis, Vol. 8; Trost, B. M.; Fleming, I., Eds.;
Pergamon Press: Oxford, 1991, 25. (b) Hutchins, R. O.;
Natale, N. R. Org. Prep. Proced. Int. 1979, 11, 201.
(c) Lane, C. F. Synthesis 1975, 135.
(3) (a) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.;
Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849;
and references therein. (b) Shibata, I.; Suwa, T.; Sugiyama,
E.; Baba, A. Synlett 1998, 1081.
(4) Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem.
Soc. 1971, 93, 2897.
(5) Miura, K.; Nakagawa, T.; Suda, S.; Hosomi, A. Chem. Lett.
2000, 150.
(6) For the tandem reactions using multifunctional silicon
reagents, see: (a) Frost, L. M.; Smith, J. D.; Berrisford, D. J.
Tetrahedron Lett. 1999, 40, 2183. (b) Zacuto, M. J.;
Leighton, J. L. J. Am. Chem. Soc. 2000, 122, 8587.
Synlett 2001, No. 10, 1617–1619 ISSN 0936-5214 © Thieme Stuttgart · New York