Organocatalytic Approaches to Asymmetric Oxidation

This work describes the development of enantioselective oxidation reactions of carbonyl compounds using covalent organocatalysis. In the first part asymmetric epoxidation of α-branched αβ-unsaturated aldehydes with aqueous hydrogen peroxide is presented. An exceptionally synergistic combination of a primary cinchona alkaloid-derived amine and a chiral BINOL-derived phosphoric acid was found to promote the reaction with excellent enantiocontrol for a wide variety of αβ-disubstituted and α-monosubstituted enals. Conformational analysis of catalytically relevant intermediates using NMR and computational techniques enabled the rationalization of the absolute stereochemistry of products. The second part of this book describes a highly efficient direct catalytic asymmetric α-benzoyloxylation of cyclic ketones. The same primary amine paired with an inorganic acid was found to be an effective catalyst for a wide range of substrates. The methodology was applied to the first asymmetric synthesis of (+)-2β4-dihydroxy-18-cineole a predicted terpenoid metabolite in mammals.