Dynamic Kinetic Resolution of Flavonoids via Asymmetric Allylic Alkylation: Construction of Two Contiguous Stereogenic Centers on Nucleophiles

The extension of racemization strategies
of dynamic kinetic resolution
in organic synthesis is a longstanding challenge, especially racemizing
two or more stereogenic centers simultaneously. Through the combination
of a palladium-catalyzed asymmetric allylic alkylation and a base-promoted
retro-oxa-Michael addition, a dynamic kinetic resolution of 2,3-disubstituted
flavonoids was achieved with up to 99% enantioselectivities, and two
contiguous stereocenters (including a quaternary stereogenic center)
were constructed simultaneously on the nucleophile flavonoids. The
key feature of the reaction was a base-promoted retro-oxa-Michael
addition for fast racemization of two stereogenic centers on the nucleophiles,
which can pave the way to developing asymmetric reactions of flavonoids
through dynamic kinetic resolution.