Trio catalysis merging enamine, brønsted Acid, and metal lewis Acid catalysis: asymmetric three-component aza-diels-alder reaction of substituted cinnamaldehydes, cyclic ketones, and arylamines.

Abstract

A trio catalyst system, composed of arylamine, BINOL-derived phosphoric acid, and Y(OTf)3 , enables the combination of enamine catalysis with both hard metal Lewis acid catalysis and Brønsted acid catalysis for the first time. Using this catalyst system, a three-component aza-Diels-Alder reaction of substituted cinnamaldehyde, cyclic ketone, and arylamine is carried out with high chemo- and enantioselectivity, affording a series of optically active 1,4-dihydropyridine (DHP) derivatives are obtained in 91-99 % ee and 59-84 % yield. DHPs bearing a chiral quaternary carbon center are also obtained with good enantioselectivity and moderate yield (three examples). Preliminary mechanistic investigations have also been conducted.