Asymmetric Addition Reactions to Imines

The synthesis of a-branched amines caught our attention, as these compounds exhibit parhcular biological activity. In several of our ongoing projects involving the synthesis of biologically achve compounds, we required the asymmetric synthesis of a-branched chiral amines. a-Branched amines can be prepared by various routes, all performed in an asymmetric fashion. Currently, enzymatic and chemical separation of racemic a-branched amines and also diastereoselective methods still play a major role on an industrial scale [25]. However, due to poor separation by the latter methods and for economic reasons, catalytic approaches will be favored. 

Recently, various methods have been applied to synthesize a-branched amines. In general, imines serve as valuable starhng materials since organyl groups or hydrogen can be delivered enantiospecifically at the C=N double bond. 

The catalytic asymmetric preparation of a-chiral amines, by addition of organo-metallic reagents to C=N bonds, is one of the most important reactions in homogeneous catalysis [26]. However, the catalytic asymmetric addition of simple alkylmetals has been achieved only in recent years. 

When we entered the field, Tomioka et al. had just introduced the dialkylzinc addition to N-sulfonylimines in the presence of chiral amidophosphine-copper(II) complexes, producing high levels of enantioselectivity (up to 94% ee) [27]. At the 

Enantiomerically pure diarylmethylamines are important intermediates in the synthesis of biologically active compounds such as 28 or 29 (Fig. 2.1.3.8). Among several drug candidates, Cetirizine hydrochloride (28) stands out as a commercially important nonsedative antihistamine agent. Binding studies indicate that 

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Chiral phosphoric acids powerful organocatalysts for asymmetric addition reactions to imines (S. J. Connon, 2006) [5a]. 

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