Electrosynthesis: A New Frontier in Aerobic Oxidation?

The formation of alcohols and carbonyl derivatives via oxidation of the corresponding Csp3–H bonds is crucial to the chemical community. Historically chemists have relied for these transformations on the use of organic or inorganic oxidants, which are often toxic and produce stoichiometric amounts of harmful waste. As we strive for a more sustainable fine chemicals synthesis, for which typically larger amounts of waste per kilogram product are produced than for commodity chemicals, the use of greener oxidants has gained increasing attention. On paper, the high abundance, O content, low price, and the production of water as the only byproduct make O2 an ideal reactant.1 In a generalized and simplified view, air or pure O2 are used in combination with a catalyst (metal complex, organocatalyst, or combinations thereof) to facilitate the formation of a carbon-centered radical, which will then react with O2. These procedures have been widely applied to a number of molecules, but remain largely limited to the functionalization of activated C–H bonds, such as benzylic, allylic, or those alpha to a heteroatom.2Unactivated aliphatic C–H bonds, on the other hand, are more difficult to oxidize; moreover, selectivity is difficult to achieve due to their typical omnipresence in organic molecules. Oxidation of such substrates is therefore currently performed by using strong oxidants such as methyl(trifluoromethyl)dioxirane (TFDO) or transition metal catalysts featuring specifically designed ligands, in combination with hydrogenperoxide (Scheme 1A).3 Unfortunately, the problematic synthesis and storage of TFDO, and the cost of ligands in the catalysts considerably hamper the application of such strategies in larger scale processes