Transition metal-free functionalization of 2-oxindoles via sequential aldol and reductive aldol reactions using rongalite as a C1 reagent

Abstract

A sequential one-pot classical aldol, transition-metal and hydride-free reductive aldol reaction is reported here for C(sp3)- H functionalization of 2-oxindoles using the multifaceted reagent rongalite. Here, rongalite functions as a hydride-free reducing agent and double C1 unit donor. This protocol enables the synthesis of a wide range of 3-methylindoline-2-ones and 3-(hydroxymethyl)-3-methylindolin-2-ones from 2-oxindoles (65–95% yields), which are the synthetic precursors for many natural products. Some of the important aspects of this synthetic approach include one-pot methylation and hydroxymethylation, low-cost rongalite (ca. $0.03 per 1 g), mild reaction conditions and applicability to gram-scale synthesis.