Asymmetric Reduction of Imines with Trichlorosilane, Catalyzed by Sigamide, an Amino Acid-Derived Formamide: Scope and Limitations

Enantioselective reduction of ketimines 6-10 With trichlorosilane can be catalyzed by the N-methyl valine-derived Lewis-basic formamide (S)-23 (Sigamide) with high enantioselectivity (<= 97% ee) land low catalyst loading, (1 - 5 mol %) at room temperature in toluene. The reaction is efficient with ketimines derived from aromatic amines (aniline and anisidine) and aromatic, heteroaromatic, conjugated, and even nonaromatic ketones 1-5, in which the steric difference between the alkyl groups R-1 and R-2 is sufficient. Simple nitrogen heteroaromatics (8a,b,d) exhibit low enantioselectivities due to the competing coordination of the reagent but increased steric hindrance in the Vicinity of the nitrogen (8c,e) results in a considerable improvement. Cyclic imines 32d-d exhibited low to modest enantioselectivities.