Biocompatible Indole C2 Functionalization via Transient N-Acyliminium Borate Intermediates

Abstract

In this work, we report a metal-free strategy for indole C2 functionalization in aqueous media, enabled by ion-pair catalysis via transient N-Acyliminium intermediates. This approach overcame the intrinsic instability of iminium species in water, enabling efficient coupling with indoles under mild and environmentally benign conditions. The protocol exhibited broad substrate scope, accommodated late-stage functionalization of drug molecules and tryptophan residues in peptides, and proceeded with excellent chemo-and regioselectivity while preserving stereochemical integrity. This operationally simple method provided a versatile platform for biomolecular modification with potential applications in drug discovery, therapeutic development, and chemical biology.