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

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).

Journal

JOURNAL OF ORGANIC CHEMISTRY

Year

2023

Volume

88

Issue

3

Pages

1299-1318

ISSN

0022-3263

eISSN

1520-6904

DOI

10.1021/acs.joc.2c00716

WoS UID

WOS:000821480300001