Asymmetric Synthesis of 2,2-Difluorotetrahydrofurans through Palladium-Catalyzed Formal [3+2] Cycloaddition

Abstract

The asymmetric synthesis of 2,2-difluorinated tetrahydrofurans was accomplished via enantioselective formal [3+2] cycloaddition catalyzed by palladium. The asymmetric reaction between gem-difluoroalkenes and racemic vinyl epoxides or vinylethylene carbonates resulted in the formation of enantioenriched 2,2-difluorotetrahydrofurans with an enantioselectivity up to 98 %. Notably, the reaction used the readily available (R)-BINAP as the ligand at a low loading and yielded a wide variety of difluorinated products in moderate to high yields. Both chiral diastereomers could be obtained in a single sequence.

Keywords: asymmetric cycloaddition; gem-difluoromethylation; palladium; vinyl epoxide; vinylethylene carbonate.