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

We report herein an asymmetric cooperative process for the enantioselective 1,6-addition of fi-ketoesters to in situ generated para-quinone methides with chiral Pd-aqua complexes as mixed Bronsted 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. '

Automated summary

In this study, an asymmetric cooperative process is reported for the enantioselective 1,6-addition of fi-ketoesters to in situ generated para-quinone methides using chiral Pd-aqua complexes as mixed Bronsted acid-base catalysts. The reaction exhibits excellent yields, outstanding enantiocontrol, and good diastereoselectivity across a wide range of substrates. The utility of this reaction is demonstrated through facile scale up and subsequent complexity-increasing modifications.