Flavin Nitroalkane Oxidase Mimics Compatibility with NOx/TEMPO Catalysis: Aerobic Oxidization of Alcohols, Diols, and Ethers

Abstract

Biomimetic flavin organocatalysts oxidize nitromethane to formaldehyde and NO x providing a relatively nontoxic, noncaustic, and inexpensive source for catalytic NO 2 for aerobic TEMPO oxidations of alcohols, diols, and ethers. Alcohols were oxidized to aldehydes or ketones, cyclic ethers to esters, and terminal diols to lactones. In situ trapping of NO x and formaldehyde suggest an oxidative Nef process reminiscent of flavoprotein nitroalkane oxidase reactivity, which is achieved by relatively stable 1,10-bridged flavins. The metal-free flavin/NO x /TEMPO catalytic cycles are uniquely compatible, especially compared to other Nef and NO xgenerating processes, and reveal selectivity over flavin-catalyzed sulfoxide formation. Aliphatic ethers were oxidized by this method, as demonstrated by the conversion of (−)-ambroxide to (+)-sclareolide.

Synthesis of Nitro Alcohols by Riboflavin Promoted Tandem Nef‐Henry Reactions on Nitroalkanes

“…In a very recent paper, various flavinium salts have been proposed as catalysts to generate nitrite anions from nitromethane [9] . The nitrite anions thus formed have been used to support further NO x /TEMPO catalytic cycles for the selective oxidation of alcohols, diols and ethers.…”

Molecular Editing of Flavins for Catalysis

“…Foss et al could show in 2020 that re-oxidation of flavinium catalyst 3 with O2 closes the catalytic cycle of converting nitromethane to NO2 -. 18 In a separate cycle, the latter subsequently oxidizes TEMPOH to TEMPO + , which led to efficient CH-oxygenation of chromane substrates (Scheme 9).…”

Aerobic Oxidations via Organocatalysis: A Mechanistic Perspective

“…(41) Furthermore, utilizing 1,10-bridged flavinium catalysts to enhance the NOx cycle in TEMPO/NOx catalytic system, Thapa et al fulfilled the aerobic oxidation of ethers, alcohols, and diols toward ketones, aldehydes, and cyclic esters (Scheme 20). (46) Scheme TEMPO catalyzed oxygenation of benzyl C(sp 3 )-H bonds.…”

“…41 Scheme 23 TEMPO-catalyzed oxygenation of benzyl C(sp 3 )-H bonds Furthermore, utilizing 1,10-bridged flavinium catalysts to enhance the NO x cycle in the TEMPO/NO x catalytic system, Foss and co-workers reported the aerobic oxidation of ethers, alcohols, and diols to give ketones, aldehydes, and cyclic esters (Scheme 24). 46 TEMPO was also used to catalyze the formation of the C-C bond in the aerobic oxidation of benzylic C(sp 3 )-H bonds. 47 Stahl and co-workers used 4acetamido-TEMPO in the selective oxidation of natural lignins, and a highly effective aerobic oxidation of alcohols with high chemoselectivity was obtained.…”