Rongalite-Mediated Transition Metal- and Hydride-Free Chemoselective Reduction of α-Keto Esters and α-Keto Amides.

A transition metal- and hydride-free protocol has been developed for the chemoselective reduction of α-keto esters and α-keto amides using rongalite as a reducing agent. Here, rongalite acts as a hydride-free reducing agent via a radical mechanism. This protocol offers the synthesis of a wide range of α-hydroxy esters and α-hydroxy amides with 85-98% yields. This chemoselective method is compatible with other reducible functionalities such as halides, alkenes, amides, and nitriles. The use of inexpensive rongalite (ca. $0.03/1 g), mild reaction conditions, and gram-scale synthesis are some of the key features of this methodology. Also, cyclandelate, a vasodilator drug, has been synthesized in gram scale with 79% yield.

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

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.

Rongalite-induced transition-metal and hydride-free reductive aldol reaction: a rapid access to 3,3'-disubstituted oxindoles and its mechanistic studies.

A transition-metal and hydride-free reductive aldol reaction has been developed for the synthesis of biologically active 3,3'-disubstituted oxindoles from isatin derivatives using rongalite. In this protocol, rongalite plays a dual role as a hydride-free reducing agent and a C1 unit donor. This transition metal-free method enables the synthesis of a wide range of 3-hydroxy-3-hydroxymethyloxindoles and 3-amino-3-hydroxymethyloxindoles with 79-96% yields. One-pot reductive hydroxymethylation, inexpensive rongalite (ca. $0.03/1 g), mild reaction conditions and short reaction time are some of the key features of this synthetic method. This protocol is also applicable to gram scale synthesis.