Synthesis of 2,2-Difluorinated 4-Isoflavanols/4-Thioisoflavanols via a Base-Catalyzed [4 + 2] Annulation Reaction of gem-Difluoroolefins.

DBU-catalyzed sequential intermolecular and intramolecular nucleophilic addition reactions between gem-difluoroolefins and o-hydroxy/mercapto benzaldehydes have been developed to provide a [4 + 2] annulation strategy for facile synthesis of gem-difluorinated isoflavanol derivatives. The competitive addition-elimination reaction of gem-difluoroolefins with nucleophiles was avoided under mild conditions, affording 2,2-difluorinated 4-isoflavanols or 2,2-difluoriated 4-thioisoflavanols in good to excellent yields.