Direct Synthesis of C4-Acyl Indoles via C-H Acylation

Org Lett. 2024 Jun 14;26(23):4998-5003. doi: 10.1021/acs.orglett.4c01658. Epub 2024 Jun 5.

Abstract

The direct synthesis of C4-acyl indoles deprived of C2 and C3 substituents has proven to be challenging, with scarce efficient synthetic routes being reported. Herein, we disclose a highly site-selective palladium-catalyzed C-H acylation for the construction of C4-acyl indoles via a Catellani-Lautens cyclization strategy. In addition, we systematically studied the ortho C-H acylation mechanism of iodoaniline through density functional theory (DFT) calculations and combined experimental results to elucidate the principle of high chemoselectivity brought by triazine benzoate as an acylation reagent.