Improved Methodology for the Preparation of Chiral Amines

eductive amination of a prochiral ketone or an N-α-MBA ketimine. It also represents
the first documented use of ytterbium for reductive amination. The initial mechanistic
investigations elaborated on here suggest an imine isomerization pathway promoted
by Yb(OAc) 3 allowing enhanced diastereoselectivity during reductive amination. A
future study will be required to elaborate on these initial mechanistic proposals, would
likely require computational analysis and include the investigation of chiral and other
achiral Lewis acid derivatives. Investigation of heterogeneous hydrogenation catalysts
prepared by different methods or supported on different materials (e.g. carbon
nanostructures, alumina, etc.), could provide further beneficial insights. Finally, the
general phenomenon of in situ promoted imine isomerization, with Yb(OAc) 3 , would
be expected to have a beneficial impact on the study of imine/enamine chemistry in
general, e.g. in conjunction with enantioselective organocatalysis.
7.3. References:
[1] (a) R. W. Hoffmann, Chem Rev. 1989, 89, 1841. (b) K. W. Lee, S. Y. Hwang, C.
R. Kim, D. H. Nam, J. H. Chang, S. C. Choi, B. S. Choi, H. -W. Choi, K. K. Lee, B.
So, S.W. Cho, H. Shin, Org. Process Res. Dev. 2003, 7, 839.
[2] (a) M. B. Eleveld, H. Hogeveen, E.P. Schudde, J. Org. Chem. 1986, 51, 3635; (b)
A. L. Gutman, M. Etinger, G. Nisnevich, F. Polyak, Tetrahedron: Asymmetry 1998, 9,
4369.
[3] G. Siedlaczek, M. Schwickardi, U. Kolb, B. Bogdanovic, D. G. Blackmond, Catal. Lett.
1998, 55, 67.
[4] (a) A. Kraynov, A. Suchopar, L. D'Souza, R. Richards, Physical Chemistry
Chemical Physics, 2006, 8, 1321. (b) T. Bürgi, A. Baiker Acc. Chem. Res. 2004, 37,
909. (c) M. Studer, H. –U. Blaser, C. Exner, Adv. Synth. Catal. 2003, 345, 45.
[5] For advances in the diastereoselective reduction of (R)- or (S)-α-MBA ketimines,
see: (a) D. E. Nichols,C. F. Barfknecht, D. B. Rusterholz, J. Med. Chem. 1973, 16,
480. (b) J. E.Clifton, I. Collins, P. Hallett, D. Hartley, L. H. C. Lunts, P.D. Wicks, J.
Med. Chem. 1982, 25, 670. (c) M. B. Eleveld, H. Hogeveen, E. P. Schudde, J. Org.
Chem. 1986, 51, 3635-3642. (d) G. Bringmann, J. –P. Geisler, Synthesis 1989, 608.
(e) E. Marx, M. El Bouz,J. P. Célérier, G. Lhommet, Tetrahedron Lett. 1992, 33,
4307. (f) N. Moss, J. Gauthier, J. –M. Ferland, Synlett 1995, 142. (g) G. Lauktien, F. –
139