Inverse conjugate additions of acrylic amides and esters with F/Cl/O/N-nucleophiles and CF <sub>3</sub> <sup>+</sup> reagents
Xiaoxiao Liu, Yuan Kou, Hao Wu, Tongxin Liu, Qingfeng Liu, Zhiguo Zhang, Xingjie Zhang, Guisheng Zhang
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, H 2 O, H 2 18 O, RCO 2 H, 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 CF 3 -containing amides/esters. The broad substrate scope, excellent functional-group tolerance, and versatile late-stage derivatizations as well as the biologically and functionally important CF 3 -containing products demonstrated the potential applications of this protocol in materials, agrochemicals, and pharmaceutical chemistry.