First Generation Copper-Catalyzed Aerobic Oxidation Protocol

First Generation Copper-Catalyzed Aerobic Oxidation Protocol 

Our own work in the area of aerobic oxidations was inspired by the exquisite research performed on the structure and reactivity of the binuclear copper proteins (7), hemocyanin and tyrosinase, and by the seminal contribution of Riviere and Jallabert (8). These two authors have shown that the simple copper complex CuCl - Phen (Phen = 1,10-phenanthroline) promoted the aerobic oxidation of benzylic alcohols to the corresponding aromatic aldehydes and ketones (Fig. 2). 

Unfortunately, two equivalents of the copper complex have to be used to achieve good conversions and the system is severely limited to benzylic substrates. Aliphatic alcohols proved to be either unreactive or underwent competing C-C bond cleavage (9). 

Our fascination for the Riviere and Jallabert procedure prompted us to reinvestigate this system and to modify various parameters with the hope of achieving catalyst turnover and establishing a useful and efficient aerobic protocol for the oxidation of all classes of alcohols into carbonyl derivatives. 

Our initial experiments were performed on p-chlorobenzyl alcohol and employed two equivalents of CuCl Phen. It was rather disappointing to find that, beside NaOAc, all the other bases tested were far less efficient than K2C03 (10). However, during the course of these optimization studies, a dramatic influence of the solvent on the reaction rate was uncovered. For example, a 3-4-fold acceleration was obtained when toluene was substituted for benzene. In contrast, replacing benzene by m- or p-xylene resulted in a decrease in the rate 

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II. First Generation Copper-Catalyzed Aerobic Oxidation Protocol... 

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