Oxidant- and Base-Free, Copper-Catalyzed Difluoromethylation of Haloalkynes.

We report herein a highly efficient copper-catalyzed protocol for the transformation of haloalkynes to the corresponding difluoromethylated alkynes. This scalable protocol exhibits a broad substrate scope and excellent functional group tolerance, enabling the late-stage difluoromethylation of bioactive molecules. Additionally, the strategy of utilizing the difluoromethylalkynes in gram-scale reactions and multiple transformations has proven to be highly valuable in synthetic chemistry.

Aryl Radical Enabled, Copper-Catalyzed Sonogashira-Type Cross-Coupling of Alkynes with Alkyl Iodides.

Despite the success of Sonogashira coupling for the synthesis of arylalkynes and conjugated enynes, the engagement of unactivated alkyl halides in such reactions remains historically challenging. We report herein a strategy that merges Cu-catalyzed alkyne transfer with the aryl radical activation of carbon-halide bonds to enable a general approach for the coupling of alkyl iodides with terminal alkynes. This unprecedented Sonogashira-type cross-coupling reaction tolerates a broad range of functional groups and has been applied to the late-stage cross-coupling of densely functionalized pharmaceutical agents as well as the synthesis of positron emission tomography tracers.

Fluoroamide-Directed Regiodivergent C-Alkylation of Nitroalkanes.

Herein, by exploiting different activation modes of fluoroamides, we achieved α- and δ-C(sp3)-H alkylation of nitroalkanes with switchable regioselectivity. Cu catalysis enabled the interception of a distal C-centered radical by a N-centered radical to couple nitroalkanes and unactivated δ-C-H bonds. In addition, imines generated in situ by fluoroamides were trapped by nitroalkanes to realize the α-C-H alkylation of amides. Both of those scalable protocols have broad substrate scopes and good functional group tolerance.