Concise Total Synthesis of (−)‐Quinocarcin Enabled by Catalytic Enantioselective Reductive 1,3‐Dipolar Cycloaddition of Secondary Amides
Kan‐Lei Ji, Shufan He, Dongdong Xu, Wen‐Xin He, Jian‐Feng Zheng, Pei‐Qiang Huang
Abstract
Abstract A concise asymmetric total synthesis of (−)‐quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3‐dipolar cycloaddition reaction of N ‐heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio‐, exo ‐ and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a Rh III ‐catalyzed C−H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline‐pyrrolidine tetracyclic core unit of quinocarcin.