Dearomative [2 + 2] photocycloaddition to difluoro bicyclo[2.1.1]hexane bioisosteres.

The development of complex fluorinated bicyclic scaffolds as benzene bioisosteres has emerged as a powerful strategy in drug discovery, yet efficient and general synthetic routes to these structures remain limited. Here, we report a visible-light-driven, energy transfer (EnT)-catalyzed dearomative [2 + 2] photocycloaddition that converts heteroaromatic-containing gem-difluoro alkenes into complex difluorinated bicyclo[2.1.1]hexane bioisosteres. This method operates under mild conditions, exhibits broad heteroaromatic compatibility, and delivers the desired products in good yields with excellent diastereoselectivity. Mechanistic studies are consistent with an energy transfer pathway involving triplet-state diradical intermediates. This work provides a complementary and conceptually new approach to fluorinated bioisosteres that are otherwise difficult to access via classical difluorocarbene insertion or conventional cycloaddition strategies.