Abstract
A longstanding problem in enantioselective catalysis concerns the transformation of
prochiral ketones into chiral amines. To date, this reaction is mainly associated
with the hydrogenation of imines or enamine derivatives using late transition metal
complexes based on chiral P-ligands. However, the one-pot reduction of a suitable
intermediate arising from the reaction of the carbonyl compounds and amine would be
much more favorable (direct reductive amination), since one step is saved. In this
account, we report on the story of the development of chiral Rh-diphosphine catalysts,
which can be used for this enantioselective transformation. For example, α-amino acids
were prepared by this methodology in up to 98% ee. Before we achieved this goal, all
possible products arising from the reaction between carbonyl component and starting
amine, like imines, enamines and N,O-acetals, and serving therefore as potential substrates, were successfully subjected
to hydrogenation. Apparently, in the direct reductive amination, different substrates
may serve as precursors for chiral amine products depending on the starting material
and reaction conditions. This matter complicates the rational design of catalysts.
Therefore, the use of high-throughput methods for identification of efficient catalysts
is recommended.
1 Introduction
2 Hydrogenation of Unsaturated and Saturated Nitrogen Substrates
2.1 Hydrogenation of Imines
2.2 Enantioselective Hydrogenation of Enamines
2.3 Hydrogenation of Saturated Nitrogen Species (N,O-Acetals and Related Compounds)
3 Direct Reductive Amination (DRA) of Carbonyl Compounds
3.1 Nonasymmetric Version
3.2 Enantioselective Direct Reductive Amination
4 Conclusions
Key words
hydrogenation - enantioselective catalysis - rhodium - amines
