Nickel(II)/Salox-Catalyzed Enantioselective C–H Functionalization

Abstract

Recently, nickel catalysts have garnered considerable attention for their efficacy and versatility in asymmetric catalysis, attributed to their distinctive properties. However, the use of cost-effective and sustainable divalent nickel catalysts in C–H activation/asymmetric alkene insertion poses significant challenges due to the intricate control of stereochemistry in the transformation of the tetracoordinate C–Ni(II) intermediate. Herein, we report a Ni(II)-catalyzed enantioselective C–H/N–H annulation with oxabicyclic alkenes. This protocol offers straightforward access to chiral [2,2,1]-bridged bicyclic compounds bearing four consecutive stereocenters with high enantioselectivity (up to 96% ee). The development of a sterically hindered chiral salicyloxazoline (Salox) ligand, TMS-Salox, is key to the success of this protocol. Mechanistic investigations unveiled that a chiral Ni(III)-metalacyclic intermediate was formed through the in situ oxidation of achiral organometallic Ni(II) species and coordination of the Salox ligand. This process led to the creation of a tailored chiral pocket that guides the approach of alkenes, thereby influencing and determining the stereochemistry.

Ni(II)-catalyzed enantioselective C−H/N−H annulation with oxabicyclic alkenes using a sterically hindered chiral salicyloxazoline (Salox) ligand, TMS-Salox, was reported.