Enantioselective Reactions of Palladium Enolates

Citation

Mohr, Justin Thomas (2010) Enantioselective Reactions of Palladium Enolates. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9RF5S1C. https://resolver.caltech.edu/CaltechTHESIS:05262010-053625648

Abstract

Synthetic efforts directed at preparing certain target molecules highlight deficiencies in the synthetic technology currently available to chemists. Enolates are among the most important synthetic intermediates for synthesis, but general means for enolate functionalizations are not available for many transformations. In order to address these limitations in synthetic technology, novel enantioselective transformations are developed and applied to total syntheses of biologically active natural products.

First, to address the challenge of generating all-carbon quaternary stereocenters, a palladium-catalyzed allylic alkylation reaction is discovered and optimized for allyl enol carbonate and silyl enol ether substrate classes. Certain enolate precursors are not accessible using these substrates, and therefore a method employing racemic allyl β-ketoester substrates is developed. In addition to solving the problem of regiospecific enolate generation, these transformations are conceptually interesting due to the stereoablative enantioconvergent mechanism.

Studies of the mechanism of the above transformation suggest the intermediacy of a chiral palladium enolate. Since enolate functionalization reactions are valuable to synthetic chemistry and general protocols are rare, different electrophiles are explored in addition to the allyl electrophiles used in quaternary center formation. These studies lead to the discovery of enantioselective protonation reactions generating tertiary stereocenters.

To demonstrate the importance of enantioselective enolate functionalization reactions in synthesis, the allylic alkylation reaction is applied in the total synthesis of cassiol and the formal synthesis of platencin.

Thesis Files