Formamides derived from N-methyl amino acids serve as new chiral organocatalysts in the enantioselective reduction of aromatic ketimines with trichlorosilane

Asymmetric reduction of N-aryl ketimines 1a-k, 43, and 45 with trichlorosilane can be catalyzed by new N-methyl L-amino acid-derived Lewis-basic organocatalysts, such as the valine-derived bisamide 3d (10 mol%), in toluene at room temperature with high enantioselectivity (<= 92% ee). The structure-reactivity investigation shows that the product configuration is controlled by the nature of the side chain of the catalyst scaffold (e.g., i-Pr vs Me, as in 3d and 6e), so that catalysts of the same absolute configuration may induce the fort-nation of the opposite enantiomers of the product. Arene-arene interactions between the catalyst and the incoming imine appear to be the prerequisite for asymmetric induction. This metal-free, organocatalytic protocol is competitive with the traditional, metal-catalyzed methodology. (c) 2005 Elsevier Ltd. All rights reserved.