New mode of asymmetric induction for enantioselective radical N-heterobicyclization via kinetically stable chiral radical center

Enantioselective radical N-heterobicyclization of N-allylsulfamoyl azides has been developed via metalloradical catalysis (MRC). The Co(II)-based catalytic system can homolytically activate the organic azides with varied electronic and steric properties for asymmetric radical N-heterobicyclization under mild conditions without the need of oxidants, allowing for the stereoselective construction of chiral [3.1.0]-bicyclic sulfamoyl aziridines in excellent yields with high diastereoselectivities and enantioselectivities. The key to achieving the enantioselective radical process relies on catalyst development through ligand design. We demonstrate that the use of new-generation D2-symmetric chiral bridged amidoporphyrin ligand HuPhyrin with judicious variation of the alkyl bridge length can dictate both the reactivity and selectivity of Co(II)-based MRC. We present both experimental and computational studies that shed light on the working details of the unprecedented mode of asymmetric induction consisting of enantioface-selective radical addition (RA) and stereospecific radical substitution (RS). We showcase the synthetic applications of the resulting enantioenriched bicyclic aziridines through a number of stereospecific transformations.