N-heterocyclic carbene and photocatalyst-catalyzed rapid access to indole ketones radical C(sp)H acylation

• Published in: Green chemistry : an international journal and green chemistry resource : GC Vol. 26; no. 9; pp. 5397 - 548
• Main Authors: Nie, Guihua, Tu, Ting, Liao, Tianhui, Liu, Donghan, Ye, Wenjun, Ren, Shi-Chao
• Format: Journal Article
• Published: 07.05.2024
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/d4gc00653d

The direct C(sp 3 )H functionalization reactions enable the development of green and streamlined synthetic routes for structurally complex molecules by circumventing the pre-activation of the substrates. Herein, we disclose an atom- and step-economic synthetic approach for rapid access to both -(2-indolyl) ketones and -(3-indolyl) ketones, which are privileged structures in bioactive molecules and organic synthesis, though generally prepared by bespoke multi-step strategies. The reaction proceeded via direct acylation of indole benzylic C(sp 3 )H bond under the NHC and photocatalyst catalysis. The mild conditions, broad substrate scope, and predictable regioselectivity among multiple potential reactive sites enable efficient access to -indolyl ketones from readily available 2- or 3-alkyl-substituted indoles. Furthermore, the competitive reaction at the 2- or 3-benzylic position of the 2,3-dialkyl-substituted indoles was systematically studied. Further transformation and bioactivity studies of the obtained -(2- or 3-indolyl) ketones highlight the potential utility of this method. Carbene and photocatalyst-catalyzed rapid access to indole ketones via radical C(sp 3 )H acylation.