Recent Advances in Copper-Catalyzed Aerobic Oxidation of Alcohols in Low Melting Mixtures and Water

Oxidation reactions of primary alcohols to aldehydes are important transformations in organic chemistry, for the synthesis of fine chemicals, perfumes, organic intermediates, and pharmaceutical compounds.[1] These reactions have been traditionally carried out with toxic/expensive inorganic oxidants (permanganates o dichromates), in the presence of ligands (diamines, triazines), and usually performed in toxic, hazardous volatile organic solvents (VOCs) (e.g., toluene, CH2Cl2), which are responsible for most waste generated in the chemical industries and laboratories.[2] Low melting mixtures (LMMs),[3] closely related to deep eutectic solvents [4] are environmentally friendly eutectic mixtures of neutral compounds (e.g., carbohydrates, sugar alcohols, urea derivatives) and inorganic salts, which melt around 70 °C. In this communication, we report a novel, sustainable and selective CuCl2/TEMPO/TMEDA-catalyzed aerobic oxidation of activated alcohols to the corresponding carbonyl compounds (up to 98% yield within 4 h reaction time), working under mild conditions (room temperature or 40 °C), in D-fructose-urea LMM or bulk water as a privileged reaction medium.[5] Telescoped, one-pot two-step hybrid transformations for the direct conversion of primary alcohols either into secondary alcohols (route a) or into valuable nitroalkenes (route b), by combining oxidation processes with nucleophilic additions or with nitroaldol (Henry) reactions, respectively, will be discussed as well.