Chiral N-Salicylidene Vanadyl Carboxylate-Catalyzed Enantioselective Aerobic Oxidation of α-Hydroxy Esters and Amides

A series of chiral vanadyl carboxylates derived from N-salicylidene-L-α-amino acids and vanadyl sulfate has been developed. These configurationally well defined complexes were examined for the kinetic resolution of double- and mono-activated 2° alcohols. The best chiral templates involve the combination of L-tert-leucine and 3,5-di-t-butyl-, 3,5-diphenyl-, or 3,4-dibromo-salicylaldehyde. The resulting vanadyl(V)-methoxide complexes after recrystallization from air-saturated methanol serve as highly enantioselective catalysts for asymmetric aerobic oxidation of α-hydroxyl-esters and amides with a diverse array of α-, O-, and N-substituents at ambient temperature in toluene. The asymmetric inductions of the oxidation process are in the range of 10 to > 100 in terms of selectivity factors ($K_{rel}$) in most instances. The previously undescribed aerobic oxidation protocol is also applicable to the kinetic resolution of C-13 taxol side chain with high selectivity factor ($K_{rel}$= 35). X-ray crystallographic analysis of an adduct between a given vanadyl complex and N-benzyl-mandelamide allows for probing the stereochemical origin of the nearly exclusive asymmetric control in the oxidation process.