Palladium-Catalyzed Enantioselective Addition of Chiral Metal Enolates to In Situ Generated ortho-Quinone Methides

We describe herein a conceptually novel, cooperative Bronsted acid/base catalyzed process for the conjugate addition of cyclic beta-keto esters to ortho-quinone methides both generated in situ. Upon hemiacetalization, densely functionalized chiral chromans with two adjacent quaternary and additionally a tertiary stereogenic center were obtained with very good diastereoselectivity (up to >95:5 d.r.) and typically excellent enantioselectivity (up to >99% ee). The striking feature and key to success is the dual catalytic activation of both nucleophile and electrophile in two separate cycles with a single chiral catalyst.