N-heterocyclic carbene-catalyzed enantioselective synthesis of spirocyclic ketones bearing gem-difluoromethylenes

Abstract

An enantioselective construction of spirocyclic ketones featuring stereogenic carbon centers bearing the gem-difluoromethylene group has been accomplished through N-heterocyclic carbene (NHC)-catalyzed umpolung [3 + 2] annulation of enals with cyclic gem-difluoroalkyl ketones. The structure of the NHC precatalyst and the reaction temperature were found to be the key parameters for the success of this reaction. This protocol offers an alternative pathway to access a new class of structurally interesting cyclic chiral gem-difluoromethylenes, which might be potentially useful in synthetic and medicinal chemistry.