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 (< or = 97% ee) and 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.