Organo- and copper- multi-catalyzed pseudo four-component access to gem-difluorohydrins

A new efficient multi-catalytic pseudo four-component strategy combining an aldehyde, a keto-acid and two equivalents of a fluorinating agent has been designed. Thanks to the combined effects of a secondary amine as organocatalyst and a copper catalyst, highly volatile gem-difluorinated intermediates can be produced and trapped in situ by a chemo-compatible decarboxylative aldolization providing a rapid access to original gem-difluorinated aldol building blocks.

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