Biomimetic Flavin-Catalyzed Aldehyde Oxidation

Abstract

The oxidation of alkyl and aryl aldehydes to their corresponding carboxylic acids has been achieved through the action of a biomimetic bridged flavin catalyst. The reaction uses readily available 35% aqueous hydrogen peroxide and is operationally simple. The oxidation is a green and sustainable reaction, obviating chlorinated solvents with minimal byproducts.

Biomimetic flavin-catalysed reactions for organic synthesis

“…20 The hydroperoxyflavin derived from 3b and H 2 O 2 undergoes reaction with aldehyde to form a peroxohemiacetal. The proposed mechanism is shown in Scheme 14.…”

Catalytic Amine Oxidation under Ambient Aerobic Conditions: Mimicry of Monoamine Oxidase B

“…As both mechanisms require discrete steps prior to the ratecontributing CÀHcleavage,itisnotable that no intermediates accumulate to observable populations.C À Hc leavage in the context of adirect hydride transfer has also been suggested. [9] However,s uch as ynchronous event would not be consistent with the 15 NKIE measured for amine oxidation by MAOB , thus pointing to an absence of synchronicity between CÀH cleavage and sp 2 !sp 3 nitrogen atom re-hybridization. [10] Finally,H C transfer from the substrate to the flavin has been suggested.…”

“…[13] Accordingly,i nsight gained from studying model cofactors is av alid strategy to unlocking mechanistic problems in flavoenzymology.P ioneering work on primary amines by various groups supported the polar, proton-transfer mechanism, but the low turnover, tendency of catalysts to decompose,a nd requirement of heating in an enriched O 2 atmosphere for several days meant that they are perhaps of limited relevance to biological processes. [14] We, [15] and others, [16] have previously applied cationic flavin catalysts in biomimetic monooxygenase contexts,aswell as donor-acceptor chemistry, [17] and now report the oxidation of biologically pertinent amines as av ehicle to understanding MAOm echanism.…”

Unusual non‐enzymatic flavin catalysis enhances understanding of flavoenzymes

“…Hydroperoxyflavins recently have been shown to promote the formation of heteroaromatic pyridines and benzothiazoles at ambient temperature in methanol and in the presence of molecular oxygen [8]. This report joins other work describing synthetic flavins capable of catalyzing the oxidation of amines, sulfides and aldehydes [9–11]. These synthetic oxidation reactions take advantage of the redox potential of flavins as “green” catalysts while removing the enzyme portion of flavoenzymes which can be more susceptible to denaturation under varied solvent conditions.…”