We report herein a highly efficient Cucatalyzed protocol for the conversion of aliphatic carboxylic acids to the corresponding difluoromethylated analogues. This robust, operationally simple and scalable protocol tolerates a variety of functional groups and can convert a diverse array of acid-containing complex molecules to the alkyl-CF 2 H products. Mechanistic studies support the involvement of alkyl radicals.

We report herein the first catalytic strategy to harness amidyl radicals derived from N-chloroamides for C–C bond formation, allowing for the discovery of the first catalytic benzylic C–H difluoromethylation. Under copper-catalyzed conditions, a wide variety of N-chlorocarboxamides and N-chlorocarbamates direct selective benzylic C–H difluoromethylation with a nucleophilic difluoromethyl source at room temperature. This scalable protocol exhibits a broad substrate scope and functional group tolerance, enabling late-stage difluoromethylation of bioactive molecules. This copper-catalyzed, chloroamide-directed strategy has also been extended to benzylic C–H pentafluoroethylation and trifluoromethylation. Mechanistic studies on the difluoromethylation reactions support that the reactions involve the formation of benzylic radicals via intramolecular C–H activation, followed by the copper-mediated transfer of difluoromethyl groups to the benzylic radicals.

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We have developed an efficient synthesis of both (Z)- and (E)-chlorohaloalkenes via hydrochlorination of haloalkynes, based on two distinct hydrogen-bond-network-assisted catalytic systems: Brønsted acid catalysis and gold catalysis. Both systems offer high stereoselectivity, good chemical yields, and diverse functional group tolerance.