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

We describe herein a conceptually novel, cooperative Brønsted acid/base catalyzed process for the conjugate addition of cyclic β‐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. Chiral palladium aqua complexes enable the enantioselective catalytic conjugate addition of chiral metal enolates from β‐keto esters to ortho‐quinone methides both formed in situ. Densely functionalized chromans with three contiguous stereogenic centers were obtained with good yields and excellent stereoselectivity. This cooperative Brønsted acid/base catalyzed process involves the activation of both nucleophile and electrophile by a single chiral catalyst.