Concise Total Synthesis of (−)‐Quinocarcin Enabled by Catalytic Enantioselective Reductive 1,3‐Dipolar Cycloaddition of Secondary Amides

Abstract

AbstractA 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 RhIII‐catalyzed C−H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline‐pyrrolidine tetracyclic core unit of quinocarcin.