Carbene-Catalyzed Alkylation of Carboxylic Esters via Direct Photoexcitation of Acyl Azolium Intermediates

• Published in: ACS catalysis Vol. 11; no. 5; pp. 2925 - 2934
• Main Authors: Ren, Shi-Chao, Lv, Wen-Xin, Yang, Xing, Yan, Jia-Lei, Xu, Jun, Wang, Fang-Xin, Hao, Lin, Chai, Huifang, Jin, Zhichao, Chi, Yonggui Robin
• Format: Journal Article
• Language: English
• Published: American Chemical Society 05-03-2021
• Subjects: N-heterocyclic carbene; ketone synthesis; acyl azolium; photocatalyst-free; reductive-radical-coupling reaction
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/acscatal.1c00165

A carbene-catalyzed reductive coupling reaction of carboxylic esters and substituted Hantzsch esters is disclosed. Key steps of this reaction include one-electron reduction of a carbene catalyst-bound acyl azolium intermediate to generate the corresponding radical intermediate for subsequent alkylation reactions. The reaction is promoted by irradiation with visible light without the involvement of transition-metal photocatalysts. Mechanistic studies suggest that direct photoexcitation of the in situ formed acyl azolium intermediate is likely responsible for this light-induced one-electron-reduction process. Photoexcitation converts the acyl azolium intermediate to a single-electron oxidant, enabling single-electron oxidation of Hantzsch esters to generate radical intermediates. Our reactions work well for a broad range of aryl carboxylic ester and Hantzsch ester substrates. Sophisticated structures, including those present in medicines, can be incorporated into ketone molecules using our approach via very mild conditions that tolerate various functional groups.