Organocatalytic Approaches to Asymmetric Oxidation: Epoxidation of a-Branched Enals and a-Benzoyloxylation of Carbonyl Compounds

This work describes the development of enantioselective oxidation reactions of carbonyl compounds using covalent organocatalysis. In the first part, asymmetric epoxidation of a-branched a,ß-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 a,ß-disubstituted and a-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 a-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 (+)-2ß,4-dihydroxy-1,8-cineole, a predicted terpenoid metabolite in mammals.