Pd-Catalyzed Asymmetric Amination of Enamines: Expedient Synthesis of Structurally Diverse N-C Atropisomers

The transition-metal-catalyzed cross-coupling of enaminesis anattractive method for producing compounds with an N-C chiralaxis; however, it faces considerable challenges that remain unresolved.Herein, a palladium-catalyzed amination method was developed to constructstructurally diverse five-six biaryl and six-six nonbiarylN-C atropisomers. The reaction mechanism was explained usingdensity functional theory calculations, which showed that the mechanisminvolved the Curtin-Hammett control. N-C rotation occurredalong the reaction coordinate until an enantio-determining three-centeredreductive elimination transition structure established the stereochemistry.The developed method is highly attractive because of its broad substratescope, high stereoselectivity, simple catalytic system, good functionalgroup tolerance, and dynamic kinetic resolution.