Secondary Alkylation of Arenes via the Borono–Catellani Strategy
Haiyun Peng, Dandan Wang, Jinxiang Ye, Ze‐Shui Liu, Zewen Zhu, X. Fu, Chang Liu, Hengjiang Cong, Hong‐Gang Cheng, Qianghui Zhou
Abstract
A modular platform technology for the synthesis of α-aryl carbonyl derivatives via Borono–Catellani-type secondary alkylation of arenes is presented. This practical method features a broad substrate scope regarding aryl boronic acid catechol esters, secondary alkyl bromides, and diversified terminating reagents (e.g., olefins, alkynes, and Zn(CN) 2 ), mild reaction conditions, and good functional-group tolerance. Importantly, the asymmetric version based on a dynamic kinetic asymmetric transformation (DyKAT) has also been realized by introducing the 1:1 diastereomeric mixture of α-bromo carboxamides bearing an Evans chiral auxiliary as the electrophiles, and constantly excellent diastereoselectivities (>20:1 d.r. ) are obtained. Notably, the obtained chiral products can be readily transformed into diversified enantioenriched α-aryl propionic acid derivatives, laying a solid foundation for the discovery of new NSAIDs. Through mechanistic studies and DFT calculations, a critical stereoretentive oxidative addition step is revealed in this Borono–Catellani secondary alkylation reaction, and the origins of stereodiscrimination of this DyKAT are well explained.