Directed C-H Functionalization of C3-Aldehyde, Ketone, and Acid/Ester-Substituted Free (NH) Indoles with Iodoarenes <i>via</i> a Palladium Catalyst System


TAŞKESENLİGİL Y., Aslan M., Cogurcu T., SARAÇOĞLU N.

JOURNAL OF ORGANIC CHEMISTRY, vol.88, no.3, pp.1299-1318, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 88 Issue: 3
  • Publication Date: 2023
  • Doi Number: 10.1021/acs.joc.2c00716
  • Journal Name: JOURNAL OF ORGANIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, MEDLINE, Index Chemicus (IC)
  • Page Numbers: pp.1299-1318
  • Ankara University Affiliated: No

Abstract

Pd(II)-catalyzed C-H arylations of free (NH) indoles including different carbonyl directing groups on C3-position with aryl iodides are demonstrated. Importantly, the reactions are carried out using the same catalyst system without any additional transient directing group (TDG). In this study, the formyl group as a directing group gave the C4-arylated indoles versus C2-arylation. Using this catalyst system, C-H functionalization of 3-acetylindoles provided domino C4-arylation/3,2-carbonyl migration products. This transformation involves the unusual migration of the acetyl group to the C2-position following C4-arylation in one pot. Meanwhile, migration of the acetyl group could be simply controlled and N-protected 3-acetylindoles afforded C4-arylation products without migration of the acetyl group. Functionalization of indole-3carboxylic acid (or methyl ester) with aryl iodides using the present Pd(II)-catalyst system resulted in decarboxylation followed by the formation of C2-arylated indoles. Based on the control experiments and the literature, plausible mechanisms are proposed. The synthetic utilities of these acetylindole derivatives have also been demonstrated. Remarkably, C4-arylated acetylindoles have allowed the construction of functionalized pityiacitrin (a natural product).