Oxidative Cleavage of Indoles Mediated by Urea Hydrogen Peroxide or H₂O₂ in Polar Solvents

Abstract

The oxidative cleavage of indoles (Witkop oxidation) involving the use of H2O2 or urea hydrogen peroxide in combination with a polar solvent has been described. Among these solvents, 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) stands out as the one affording the corresponding 2‐ketoacetanilides generally in higher yields The protocol described has also enabled the oxidation of different pyrroles and furans derivatives. Furthermore, the procedure was implemented in a larger‐scale and HFIP was distilled from the reaction mixture and reused (up to 4 cycles) without a significant detriment in the reaction outcome, which remarks its sustainability and applicability.

Protein cysteine S-glycosylation: oxidative hydrolysis of protein S-glycosidic bonds in aqueous alkaline environments

“…The pH decrease favors dissolution of silver nanoclusters @Ag and the formation of reactive oxygen species (ROS) (He et al 2011 , 2012 ; Rong et al 2018 ). The complicated redox processes, involving silver ions and silver nanoclusters, might explain the enhanced oxidation of Cys, Met, and Trp residues (Bellmaine et al 2020 ; Llopis et al 2021 ) observed in tryptic peptides originating from Procedures 1–4, compared to the level of Model D oxidation (ESM_Table S2). This phenomenon is particularly evident in the data for Procedure 3 executed in 2 M aqueous urea, which likely favors ROS-related oxidation as reported elsewhere (Yang et al 2010 ).…”

Dehydrogenation of N‐Heterocyclic Compounds Using H2O2 and Mediated by Polar Solvents

“…In a first attempt, NH‐free indolines were submitted to the oxidation reaction and as depicted in the Scheme 3, the conversions were quite good, but unfortunately, only a low percentage was due to the formation of the corresponding indole. Besides the product and indoline, different oxidation products, some of them coming from oxidative cleavage of indoles, [11a] were observed by NMR and GC‐MS. The fact of obtaining some conversion, encouraged us to run the reaction with the corresponding more nucleophilic N ‐methylated analogues.…”

A Consecutive Ring-Expansion Strategy towards the Macrocyclic Core of the Solomonamide Natural Products

“…Upon completion, the aqueous solution was extracted with dichloromethane and the organic layer was dried over MgSO4 and concentrated in vacuo. 7 .…”