Continuous-Flow Aerobic Oxidation of Primary Alcohols with a Copper(I)/TEMPO Catalyst

A scalable, continuous-flow process has been developed to implement a homogeneous CuI/TEMPO catalyst system for aerobic oxidation of primary alcohols to aldehydes. This catalyst system is compatible with a wide range of alcohols bearing diverse functional groups. A dilute oxygen source (9% O2 in N2) is used to avoid flammable oxygen/organic mixtures. Residence times in the heated reaction zone can be as low as 5 min with activated (e.g., benzylic) alcohols. The method has been demonstrated with nine different alcohols, including one up to 100 g scale. This flow-based catalytic method exhibits significant advantages for aerobic oxidation of alcohols, including substantially shorter residence times and broader substrate scope relative to a Pd-catalyzed method that we reported recently.