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

Bo‐Sheng Zhang, Ze-Qiang Zhang, Tian-Jiao Guo, João C. A. Oliveira, Svenja Warratz, Bao-Jie Deng, Yiming Wang, Jun-Shi Zhou, Xue‐Ya Gou, Xi‐Cun Wang, Zheng‐Jun Quan, Lutz Ackermann

2024Organic Letters10 citationsDOIOpen Access PDF

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.

Topics & Concepts

AcylationChemoselectivityChemistryReagentCombinatorial chemistryDensity functional theoryCatalysisOrganic chemistryComputational chemistryCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsSynthesis and Catalytic Reactions