Process Development of CuI/ABNO/NMI-Catalyzed Aerobic Alcohol Oxidation

An improved Cu/nitroxyl catalyst system for aerobic alcohol oxidation has been developed for the oxidation of functionalized primary and secondary alcohols to aldehydes and ketones, suitable for implementation in batch and flow processes. This catalyst, which has been demonstrated in a >50 g scale batch reaction, addresses a number of process limitations associated with a previously reported (MeObpy)CuI/ABNO/NMI catalyst system (MeObpy = 4,4′-dimethoxy-2,2′-bipyridine, ABNO = 9-azabicyclo[3.3.1]nonane N-oxyl, NMI = N-methylimidazole). Important catalyst modifications include the replacement of [Cu(MeCN)4]OTf with a lower-cost Cu source, CuI, reduction of the ABNO loading to 0.05–0.3 mol%, and use of NMI as the only ligand/additive (i.e., without a need for MeObpy). Use of a high flash point solvent, N-methylpyrrolidone, enables safe operation in batch reactions with air as the oxidant. For continuous-flow applications compatible with elevated gas pressures, better performance is observed with acetonitrile...

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