-Difluorination of Methylenecyclopropanes (MCPs) Featuring a Wagner-Meerwein Rearrangement: Synthesis of 2-Arylsubstituted -Difluorocyclobutanes.

The geminal difluorocyclobutane core is a valuable structural element in medicinal chemistry. Strategies for -difluorocyclobutanes, especially the 2-substituted cases, are limiting and often suffer from harsh reaction conditions. Reported herein is a migratory -difluorination of aryl-substituted methylenecycloproanes (MCPs) for the synthesis of 2-arylsubstituted -difluorocyclobutanes. Commercially available Selectfluor (F-TEDA-BF) and Py·HF were used as the fluorine sources. The protocol proceeds via a Wagner-Meerwein rearrangement with mild reaction conditions, good functional group tolerance, and moderate to good yields. The product could be readily transformed to -difluorocyclobutane-containing carboxylic acid, amine, and alcohol, all of which are useful building blocks for biologically active molecule synthesis.