Abstract: Efficient and scalable methods for the C3 acylation of 2-arylindoles remain limited despite the importance of 3-acyl-2 arylindoles as versatile intermediates in medicinal and synthetic chemistry. Herein, a practical Vilsmeier−Haack acylation protocol employing readily available N,N-dialkylamides and phosphorus oxychloride is described. Systematic reaction optimization identified conditions that provide highly regioselective C3 acylation across a broad range of 2-arylindoles and acylating agents, affording the corresponding products in high isolated yields without chromatographic purification. The operational simplicity of the method, together with its broad functional-group tolerance and gram-scale applicability, makes it a practical alternative to conventional acylation protocols. The synthetic utility of the resulting 3-acyl-2-arylindoles was demonstrated by concise syntheses of representative fused indole heterocycles related to biologically active alkaloids, including fluorescent indoloquinoline, indoloisoquinoline, and carbazole derivatives.

Cite: Fedorenko N.O. , Rakhimov R.R. , Volkov E.S. , Shirinian V.Z.
Technical Note: A Practical and Scalable Method for the Preparation of 3‑Acylindole Scaffold Using N,N‑Dimethylamides via the Vilsmeier−Haack Reaction
Organic Process Research & Development. 2026. DOI: 10.1021/acs.oprd.6c00282 WOS Scopus OpenAlex

Dates:

Submitted:	Jun 21, 2026
Accepted:	Aug 18, 2026
Published print:	Aug 27, 2026
Published online:	Aug 27, 2026

Identifiers:

≡ Web of science:	WOS:001862758200001
≡ Scopus:	2-s2.0-105050626530
≡ OpenAlex:	W7204894511

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