Issue 9, 2024

N-heterocyclic carbene and photocatalyst-catalyzed rapid access to indole ketones via radical C(sp3)–H acylation

Abstract

The direct C(sp3)–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 α-(2-indolyl) ketones and α-(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(sp3)–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 α-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 α-(2- or 3-indolyl) ketones highlight the potential utility of this method.

Graphical abstract: N-heterocyclic carbene and photocatalyst-catalyzed rapid access to indole ketones via radical C(sp3)–H acylation

Supplementary files

Article information

Article type
Paper
Submitted
04 Feb 2024
Accepted
18 Mar 2024
First published
19 Mar 2024

Green Chem., 2024,26, 5397-5408

N-heterocyclic carbene and photocatalyst-catalyzed rapid access to indole ketones via radical C(sp3)–H acylation

G. Nie, T. Tu, T. Liao, D. Liu, W. Ye and S. Ren, Green Chem., 2024, 26, 5397 DOI: 10.1039/D4GC00653D

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