Enantioselective Synthesis of Atropisomeric Biaryls by Pd-Catalyzed Asymmetric Buchwald-Hartwig Amination

Angew Chem Int Ed Engl. 2021 Sep 27;60(40):21718-21722. doi: 10.1002/anie.202108747. Epub 2021 Aug 25.


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.

Keywords: amidines; amination; asymmetric catalysis; atropisomerism; palladium.

Publication types

  • Research Support, Non-U.S. Gov't