Photoinduced Copper-Catalyzed Asymmetric C(sp3)-H Alkynylation of Cyclic Amines by Intramolecular 1,5-Hydrogen Atom Transfer

The development of a mild and general method for C(sp(3))-H functionalization of cyclic amines has been an ongoing challenge. In this work, we describe the copper-catalyzed enantioselective C(sp(3))-H alkynylation of unactivated cyclic 2-iodo-benzamide under photo-irradiation by intramolecular 1,5-hydrogen atom transfer (HAT). The employment of a new bisoxazoline diphenylamine ligand, in conjunction with 1,1 '-bi-2-naphthol, which significantly improved the reduction potential of the copper complex, was the key to success of this chemistry. Mechanistic and computational studies supported that the new copper complex served the dual role as a photoredox and coupling catalyst, the reaction went through a radical process, and the intramolecular 1,5-HAT process was involved in the rate-limiting step. Apart from the broad substrate scope including unprecedented benzocyclic amines, this method also showed excellent diastereoselectivity in 2-monosubstituted cyclic amines via substrate control.

Automated summary

This study successfully developed a mild and general method for C(sp(3))-H functionalization of cyclic amines. By utilizing intramolecular 1,5-hydrogen atom transfer (HAT) under photo-irradiation, the enantioselective C(sp(3))-H alkynylation of unactivated cyclic 2-iodo-benzamide was achieved. The use of a new bisoxazoline diphenylamine ligand in combination with 1,1'-bi-2-naphthol significantly improved the reduction potential of the copper complex. This method not only demonstrates a broad substrate scope, including unprecedented benzocyclic amines, but also exhibits excellent diastereoselectivity in 2-monosubstituted cyclic amines via substrate control.