Enantioselective Synthesis of Atropisomeric Biaryls by Pd‐Catalyzed Asymmetric Buchwald–Hartwig Amination
Peng Zhang, Xiaomei Wang, Qi Xu, Chang‐Qiu Guo, Peng Wang, Chuan‐Jun Lu, Renrong Liu
Abstract
N-C Biaryl atropisomers are prevalent in natural products and bioactive drug molecules. However, the enantioselective synthesis of such molecules has not developed significantly. Particularly, the enantioselective synthesis of N-C biaryl atropisomers by stereoselective metal-catalyzed aryl amination remains unprecedented. Herein, a Pd-catalyzed cross-coupling strategy is presented for the synthesis of N-C axially chiral biaryl molecules. A broad spectrum of N-C axially chiral compounds was obtained with excellent enantioselectivities (up to 99 % ee) and good yields (up to 98 %). The practicality of this reaction was validated in the synthesis of useful biological molecules.