Greener Preparation of 5‐Ethyl‐4a‐hydroxyisoalloxazine and Its Use for Catalytic Aerobic Oxygenations

Abstract

Isoalloxazine ring systems are found in flavin cofactors in nature, and the simulation of their redox catalyses is an important task for developing sustainable catalytic oxidation reactions. Although 5‐ethyl‐4a‐hydroxyisoalloxazines are among the most promising candidates as catalyst for such purposes, the use of them for laboratorial as well as industrial synthetic chemistry has so far been quite limited presumably due to the lack of their preparation methods readily, safely, and inexpensively available. In this communication, we introduce an environmentally benign and practical preparation of 5‐ethyl‐4a‐hydroxy‐3,7,8,10‐tetramethylisoalloxazine (1EtOH) from 3,7,8,10‐tetramethylisoalloxazine (1), in which conventional synthetic requirements, including (i) operations under inert conditions, (ii) risky or expensive chemicals, and (iii) isolation of labile intermediates, have all been dissolved. In addition, we have presented that 1EtOH could be an effective catalyst for Baeyer–Villiger oxidation as well as sulfoxidation with molecular oxygen (O2) as a terminal oxidant under suitable conditions, which is the first report on aerobic oxygenations catalyzed by 5‐alkyl‐4a‐hydroxyisoalloxazines.

Molecular Editing of Flavins for Catalysis

“…Alternatively, the corresponding C4a-hydroxy analogues, stemming from addition of a molecule of water, 36 can also be applied as pre-catalysts, which are activated by acid and elimination of water. 37 Absorption and emission properties of N5-alkylated flavinium salts are similar to those of the parent isoalloxazines yet bathochromically shifted. 38 Scheme 11 Alkylation of the flavin N5-position results in flavinium salts.…”

Nature is the Cure: Engineering Natural Redox Cofactors for Biomimetic and Bioinspired Catalysis

“…Unlike nicotinamide, which most exclusively performs electrons and hydrogen/hydride transfer, flavin‐based redox cofactors such as FAD and FMN (FAD: flavin dinucleotide, FMN: flavin mononucleotide) can participate in a wide diversity of chemical reactions that are not limited to hydrogen or hydride transfer but also spans transformations such as oxidation, halogenation, C−C bond formation and reduction of alkenes and nitro groups for example . Their use in biomimetic synthetic transformations has received sustained interest and is very active field towards the design of more environmentally‐friendly oxidoreductive processes …”

Efficient Use of Photons in Photoredox/Enamine Dual Catalysis with a Peptide-Bridged Flavin–Amine Hybrid

“…Although there have been a number of reports on such flavin molecules as a photoredox catalyst for visible-light induced reactions, their catalytic activity in any dual photoredox/enamine catalysis has never been reported so far. In addition, our research group has much experience in using flavin molecules through the developments of their thermal catalysis, which are the reason for choosing them as a chromophore in this study. On the other hand, we selected light emitting diodes (LED) as a visible-light source possessing a rather narrow emission band to realize the efficient use of photons.…”