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Abstract

This work describes the development of enantioselective oxidation reactions of carbonyl compounds using covalent organocatalysis. In the first part, asymmetric epoxidation of α-branched α,β-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 α,β-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 thesis 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 (+)-2β,4-dihydroxy-1,8-cineole, a predicted terpenoid metabolite in mammals. Preliminary investigations on the α-benzoyloxylation of α-branched aldehydes and α-branched enals using this catalytic system demonstrated significant potential of the method for the enantioselective formation of oxygenated quaternary stereocenters.