Development and Mechanistic Exploration of Rhodium-Catalyzed Biaxially Atroposelective Click Chemistry

The construction of atropisomeric biaryls has emerged as a hot topic in organic chemistry, with remarkable advances being achieved. However, these studies mainly focus on the preparation of atropisomers with a single chiral axis, while the synthesis of atropisomers with more than one axis of chirality remains relatively rare, likely owing to the formidable challenges in establishing multiple axes with exquisite chiral control. Herein, we report a rhodium-catalyzed click reaction for the construction of biaxial atropisomers, in which a wide range of readily available alkynes and azides can be assembled into structurally diverse atropisomeric triazoles bearing a pair of vicinal C–N/C–C diaxes in high yields with regio-, diastereo-, and enantioselectivity. This click chemistry features broad substrate scope, mild open-flask reaction conditions, high efficiency, and scalability. Control experiments were conducted to elucidate a reasonable mechanism involving the dehydration activation of alkynes. Additionally, detailed density functional theory (DFT) calculations and mechanistic analyses indicate key structural features of the catalytic system and their influence on the experimentally observed stereoselectivity. Together, these experimental and computational data provide mechanistic and structural insights that can further guide efforts to develop new synthetic methodologies and catalytic systems furnishing highly functionalized atropisomers.