Dynamic Kinetic Resolution of Flavonoids via Asymmetric Allylic Alkylation: Construction of Two Contiguous Stereogenic Centers on Nucleophiles
Lixia Liu, Wen‐Jun Huang, Qing‐Xian Xie, Bo Wu, Chang‐Bin Yu, Yong‐Gui Zhou
Abstract
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.