Aerobic Oxidation of PMB Ethers to Carboxylic Acids

The first aerobic protocol of direct transformation of p-methoxybenzyl (PMB) ethers to carboxylic acids efficiently with Fe(NO3)3 & sdot; 9H2O and TEMPO as catalysts at room temperature has been developed. The reaction accommodates C-Br bond, terminal/non-terminal C-C triple bond, amide, cyano, nitro, ester, and trifluoromethyl groups. Even highly selective oxidative deprotection of different benzylic PMB ethers has been realized. The reaction has been successfully applied to the total synthesis of natural product, (R)-6-hydroxy-7,9-octadecadiynoic acid, demonstrating the practicality of the method. Based on experimental studies, a possible mechanism involving oxygen-stabilized benzylic cation has been proposed. With Fe(NO3)3 & sdot; 9H2O and TEMPO as cocatalysts and oxygen as green oxidant, PMB ethers have been converted to carboxylic acids at room temperature with high efficiency and selectivity. Total synthesis of naturally occuring (R)-6-hydroxy-7,9-octadecadiynoic acid has been realized by applying this protocol as key step. A mechanism involving oxygen-stabilized benzylic cation has been proposed based on careful studies. image