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

Authors: Kan-Lei Ji, Shu-Fan He, Dong-Dong Xu, Wen-Xin He, Jian-Feng Zheng*, Pei-Qiang Huang

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 dipolarophile 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.

Link: https://onlinelibrary.wiley.com/doi/10.1002/anie.202302832