Photocatalytic prins-like indole addition of tryptophol C2 with aldehydes and ketones

Abstract

Introducing functional groups at the C2 position of indole is useful and important for the synthesis of complex indole-based pharmaceuticals and polymeric materials. In this study, a novel photocatalytic Prins-like indole addition was developed, enabling cross-coupling between the C2 position of tryptophol and carbonyl groups of aldehydes and ketones. This reaction was facilitated by an intramolecular ligand-to-metal charge transfer (LMCT) process initiated through cerium-based photocatalysis, which excited an indole alkanol to generate an alkoxy radical. This alkoxy radical promoted selective cleavage of the indole C2 sp² C–H bond via a 1,5-hydrogen atom transfer (1,5-HAT) pathway, thereby forming a carbon-centered radical at the C2 position. The resulting carbon radical subsequently underwent nucleophilic addition to aldehydes or ketones, affording secondary alcohols from aldehydes and tertiary alcohols from ketones. This article describes an efficient photocatalytic radical-based transformation analogous to the Prins reaction and provides a practical synthetic approach for constructing alcohol functionalities adjacent to the C2 position of indoles.