Photoredox-Catalyzed Synthesis of 3,3-Difluoro-γ-lactams via 1,5-Hydrogen Atom Transfer-Involved Alkyne Difunctionalization and C-N Cleavage

Org Lett. 2024 Nov 8. doi: 10.1021/acs.orglett.4c03715. Online ahead of print.

Abstract

This manuscript describes the application of a 1,5-hydrogen atom transfer strategy in photoredox-catalyzed hydrodifluoroalkylation of alkynes. The approach utilizes a sequential cascade process of difluoroalkylation, 1,5-hydrogen atom transfer, C(sp3)-N cleavage, and intramolecular condensation cyclization to accomplish efficient [3 + 2] cycloaddition of readily available propargylamines with halodifluoroacetates (or halodifluoroacetamides). The reaction allows for the selective construction of polysubstituted 3,3-difluoro-γ-lactams with good functional group tolerance, and further transformations of the resulting 3,3-difluoro-γ-lactams into different building blocks are also accomplished.