Chemoselective Catalytic Asymmetric Synthesis of Functionalized Aminals Through the Umpolung Organocascade Reaction of α-Imino Amides.

Abstract

Chiral functionalized aminals are important core structures of natural products and pharmaceuticals. Their chemo- and regioselective catalytic, asymmetric synthesis has been realized through the umpolung reaction of α-imino amides using a catalyst we originally developed. Functionalized aminals were prepared with high chemoselectivity by treating a hemiaminal intermediate with pyridine in butanol. Evaluation of substrate scope revealed that this transformation could be achieved with a wide range of α-imino amides to produce the desired products in high yields with up to 97 % ee. A mechanistic study suggested that aminal formation proceeded through the ring opening/ring closing equilibrium of the hemiaminal skeleton.