Cooperative catalysis of carbenes and Lewis acids for the highly enantioselective synthesis of dihydroquinolones via in situ generation of aza-ortho-quinone methide and enolate intermediates

Abstract

A highly stereoselective [4 + 2] cycloaddition reaction of aza-ortho-quinone methides (aza-o-QMs), generated in situ from stable 2-(tosylmethyl)anilines, with azolium ester enolates, generated from α-chloro aldehydes, has been developed through cooperative catalysis of a chiral N-heterocyclic carbene (NHC) and a Lewis acid. Lithium fluoride (LiF), serving as a Lewis acid catalyst, can efficiently promote the formation of chiral 3,4-disubstituted dihydroquinolone products with exceptionally high diastereo- and enantioselectivities. The catalytic reaction products can be easily converted into potentially valuable structures and bioactive molecules.