Inverse conjugate additions of acrylic amides and esters with F/Cl/O/N-nucleophiles and CF₃⁺ reagents.

Abstract

The conjugate additions of nucleophiles to conjugate acceptors are among the most powerful hetero-carbon bond formation reactions. The conjugate addition normally occurs via a β-nucleophilic addition, resulting in the formation of a stabilized α-carbanion intermediate that can be subsequently quenched by electrophiles or protons. Nevertheless, the inverse conjugate addition involving an α-specific nucleophilic addition remains less explored because of the electronic mismatch. In this research, we disclosed an α-specific nucleophilic addition of the nucleophiles including Py·HF, TBACl, HOR, H₂O, H₂¹⁸O, RCO₂H, and pyrazole to conjugate acceptors concurrent with a trifluoromethylation. This umpolung and inversely regioselective conjugate addition, enabled by a visible light-induced redox photocatalysis, occurred via an unusual α-nucleophilic addition other than the normal β-nucleophilic addition to efficiently generate diverse α-functionalized CF₃-containing amides/esters. The broad substrate scope, excellent functional-group tolerance, and versatile late-stage derivatizations as well as the biologically and functionally important CF₃-containing products demonstrated the potential applications of this protocol in materials, agrochemicals, and pharmaceutical chemistry.