Carbene-catalyzed imine reductive reaction: a new application of Breslow intermediates†

Abstract

α-Amino acids are vital structural motifs that are widely present in functional molecules. The catalytic hydrogenation and transfer hydrogenation of imines are significant methods for constructing α-amino acids. The general hydrogenation process often involves the use of numerous hazardous reagents. Here, we report a new NHC-catalyzed imine reductive reaction. The food additive acetoin is employed as a hydride source to react with the NHC catalyst, and a Breslow intermediate is then formed as a reductant to reduce the imino ester. The reaction can be further used to readily reduce various imine derivatives. Furthermore, the dengue virus inhibitor JNJ-A07 can be synthesized from the corresponding imino ester. Experimental and computational studies have been performed to disclose the reduction process. Our present study aims inspire a new avenue for the construction of α-amino acids via a mild and green reductive process.