Chiral Primary Amine Catalyzed Asymmetric α-Benzylation with In Situ Generated ortho-Quinone Methides

A dual activation strategy integrating primary amine catalysis and Lewis base activation has been developed for an asymmetric alpha-benzylation reaction. Enamines derived from b-ketocarbonyls could react effectively with in situ generated ortho-quinone methides under Lewis base activation in asymmetric alpha-benzylation of beta-ketocarbonyls and a-branched aldehydes. The approach enables the creation of acyclic all-carbon quaternary stereocenters with excellent enantioselectivities and good activity.