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A general, convenient, and friendly route for preparing a versatile building block of isocyanides from primary amines is developed. Difluorocarbene, generated in situ from decarboxylation of chlorodifluoroacetate, reacts efficiently with primary amines to produce isocyanides. Various primary amines are well tolerated, including aryl, heteroaryl, benzyl, and alkyl amines, as well as amine residues in amino acids and peptides. Late-stage functionalization of biologically active amines is demonstrated, showing its practical capacity in drug design and peptide modification.

We report herein a strategy of ammonium hydrogen-bonding-assisted α-F elimination from Cu–CF3 compounds that generates R3N·HF reagents in situ. Combining this strategy and Cu(III)–CF3 chemistry with alkynes, dual fluorination and trifluoromethylation of terminal alkynes is enabled by a single Cu(III)–CF3 compound assisted by a tertiary amine with excellent regio- and stereoselectivity. This strategy also enables the development of other reaction types involving trapping of the in situ-formed R3N·HF reagents by other electrophilic groups and can be used for the late-stage functionalization of estrone derivatives.

One-step concurrent fluoro-trifluoromethylation across the triple bond of arylacetylenes in a syn mode is enabled by the collaboration of (phen)CuIII(CF3)3 and CsF that produces chemo-, regio-, and stereoselectively (Z)-α-fluoro-β-CF3 styrenes. This method can be extended to achieve syn-oxy-trifluoromethylation and syn-aryl-trifluoromethylation of alkynes using phenoxides, alkoxides, or phenylboronic acid in place of CsF. It opens up new opportunities for preparing various functionalized trifluoromethylated Z-alkenes and demonstrates the potential of Cu(III)–CF3 complexes in organic synthesis.

Chemoselective access to either γ-ketoesters with a quaternary all-carbon α-stereogenic center or γ-keto nitriles is described by copper-catalyzed aerobic reaction of styrenes with α-cyanoesters. Formal oxo-enolation or oxo-cyanomethylation of styrenes is achieved via a sequence of addition of enolate (or cyanomethyl) radical to olefin and oxidation of the resulting radical adduct. This method starts from abundant and cheap feedstock under aerobic conditions, without any prefunctionalization or the production of stoichiometric metal salts waste, making it very attractive for practical use.

The novel cascade photoredox/iodide catalytic system enables the alkene to serve as a radical acceptor capable of achieving aminodifluoroalkylation of alkenes. Cheap iodide salts play a vital role in this reaction, which could tune carbocation reactivity through reversible C-I bond formation for controlling reaction selectivity, and a series of competitive reactions are completely eliminated in the presence of multiple reactivity pathways. The present dual catalytic protocol affords a very convenient method for direct synthesis of various difluoro-γ-lactams from simple and readily available starting materials under mild reaction conditions.