Copper–Catalyzed Cyclopropanol Ring Opening Csp3–Csp3 Cross–Couplings with (Fluoro)Alkyl Halides

摘要

Novel and general copper-catalyzed cyclopropanol ring opening cross-coupling reactions with difluoroalkyl bromides, perfluoroalkyl iodides, monofluoroalkyl bromides, and 2-bromo-2-alkylesters to synthesize various β-(fluoro)alkylated ketones are reported. The reactions feature mild conditions and excellent functional group compatibility, and can be scaled up to gram scale. Preliminary mechanistic studies suggest the involvement of radical intermediates. The difluoro-alkyl-alkyl cross-coupling products can also be readily converted to more valuable and diverse gem-difluoro-containing compounds by taking advantage of the carbonyl group resulting from cyclopropanol ring opening.