Asymmetric Substitution by Alkynyl Copper Driven Dearomatization and Rearomatization

Abstract Catalytic asymmetric transformations by dearomatization have developed into a widely applicable synthetic strategy, but heavily relied on the use of arenes bearing a heteroatom. In this case, the dearomatization is facilitated by the involvement of a p ‐orbital electron of the heteroatom. Different from the conventional substrate‐dependent model, here we demonstrate that the activation by a d ‐orbital electron of the transition‐metal center can serve as a driving force for dearomatization, and is applied to the development of a novel asymmetric alkynyl copper facilitated remote substitution reaction. A newly modified PyBox chiral ligand enables the construction of valuable diarylmethyl and triarylmethyl skeletons in high enantioselectivities. An unexpected tandem process involving sequential remote substitution/cyclization/1,5‐H shift leads to the formation of the enantioenriched C−N axis. A gram‐scale reaction and various downstream transformations highlight the robustness of this method and the potential transformations of the products. Preliminary mechanistic studies reveal a mononuclear Cu‐catalyzed remote substitution process.