Enantioselective 1,6-Addition of β-Ketoester Enolates to In Situ Generated para -Quinone Methides Enabled by Cooperative Palladium and Brønsted Acid Catalysis.

We report herein an asymmetric cooperative process for the enantioselective 1,6-addition of β-ketoesters to in situ generated para -quinone methides with chiral Pd-aqua complexes as mixed Brønsted acid-base catalysts. Excellent yields, outstanding enantiocontrol, and good diastereoselectivity across a broad substrate range are highlights of this transformation. The utility of this reaction is further demonstrated by a facile scale up and subsequent complexity-increasing modifications.