Development of the Enantioselective Oxidation of Secondary Alcohols and Natural Products Total Synthesis

Citation

Bagdanoff, Jeffrey Thomas (2006) Development of the Enantioselective Oxidation of Secondary Alcohols and Natural Products Total Synthesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z94F1NQK. https://resolver.caltech.edu/CaltechETD:etd-08182005-120859

Abstract

Oxidation is a fundamental process in chemistry and biology. In synthetic chemistry, there are several methods for the asymmetric oxidation of organic substrates. Classically, these methods have focused on the delivery of a heteroatom from a reagent or catalyst to a prochiral substrate. What have historically been underdeveloped are enantioselective oxidation methods that do not involve the transfer of a heteroatom, but rather are defined by the enantioselective dehydrogenation of an organic substrate. This type of oxidative transformation was investigated using a palladium(II) catalyst system.

A palladium-catalyzed oxidative kinetic resolution of secondary alcohols was developed. Key features of the catalytic system include the use of (–)-sparteine as the source of chiral relay, and molecular oxygen as the sole stoicheometric oxidant. Under the described catalytic system, a number of benzylic and allylic alcohols have been oxidized in an enantioselective manner, to provide a ketone and residual alcohol in high enantiomeric excess and excellent yield.

Subsequent to the original system, the systematic investigation of a number of mechanistic hypotheses involving the role of exogenous bases and H-bonding additives prompted the discovery of new reaction conditions displaying greatly enhanced reactivity, selectivity, atom economy, and generality. The net result of these improvements was a catalytic system effective in oxidative desymmetrization of a number of complex meso-diols. Ultimately, these advances have permitted our method to be applied towards a number of synthetic endeavors, including the key step in the total synthesis of the natural product alkaloid (–)-lobeline.

Thesis Files