Electrophotocatalytic Decarboxylative C−H Functionalization of Heteroarenes

• Published in: Angewandte Chemie International Edition Vol. 59; no. 26; pp. 10626 - 10632
• Main Authors: Lai, Xiao‐Li, Shu, Xiao‐Min, Song, Jinshuai, Xu, Hai‐Chao
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 22.06.2020; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkylation; Carbon; Carboxylic acids; Chemical bonds; Chemistry; Chemistry, Multidisciplinary; Coupling (molecular); Couplings; Covalent bonds; C−H functionalization; Decarboxylation; Dehydrogenation; Electrochemistry; Forging; heterocycles; Heterocyclic compounds; Hydrogen evolution; Oxamic acids; Oxidants; Oxidizing agents; Photocatalysis; Physical Sciences; Protons; radical reactions; Reduction; Science & Technology; Selectivity; MILD; electrochemistry; heterocycles; radical reactions; C-H functionalization; photocatalysis; PHOTOREDOX CATALYSIS; CARBOXYLIC-ACIDS; C−H functionalization
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202002900

Decarboxylative C−H functionalization reactions are highly attractive methods for forging carbon–carbon bonds considering their inherent step‐ and atom‐economical features and the pervasiveness of carboxylic acids and C−H bonds. An ideal approach to achieve these dehydrogenative transformations is through hydrogen evolution without using any chemical oxidants. However, effective couplings by decarboxylative carbon–carbon bond formation with proton reduction remain an unsolved challenge. Herein, we report an electrophotocatalytic approach that merges organic electrochemistry with photocatalysis to achieve the efficient direct decarboxylative C−H alkylation and carbamoylation of heteroaromatic compounds through hydrogen evolution. This electrophotocatalytic method, which combines the high efficiency and selectivity of photocatalysis in promoting decarboxylation with the superiority of electrochemistry in effecting proton reduction, enables the efficient coupling of a wide range of heteroaromatic bases with a variety of carboxylic acids and oxamic acids. Advantageously, this method is scalable to decagram amounts, and applicable to the late‐stage functionalization of drug molecules. A broadly applicable electrophotocatalytic method for the direct decarboxylative C−H alkylation and carbamoylation of heteroarenes has been developed. This method combines the advantages of photocatalysis and electrochemistry to enable the functionalization of a broad range of substrates and to allow the decarboxylative C−H functionalization reactions to proceed by H2 evolution, obviating the need for oxidizing reagents and proton acceptors.