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

J Org Chem. 2020 Jul 17;85(14):9096-9105. doi: 10.1021/acs.joc.0c01013. Epub 2020 Jul 1.

Abstract

Biomimetic flavin organocatalysts oxidize nitromethane to formaldehyde and NOx-providing a relatively nontoxic, noncaustic, and inexpensive source for catalytic NO2 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 NOx 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/NOx/TEMPO catalytic cycles are uniquely compatible, especially compared to other Nef and NOx-generating 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't