UC Santa Barbara

In order to enable detailed biological studies with the naturally occurring enantiomer and test the feasibility of our synthetic route, a large scale synthesis towards (–)-muironolide A was carried out. A series of optimizations on the synthesis of different fragments were achieved, including the diene amine and chlorocyclopropyl ketide. A newly designed chiral terpyridine was tested as a ligand in the key intramolecular Diels-Alder reaction.

In another research area of mine, chiral lithium amides derived from C2-symmetric tetraamines, acting as non-covalent chiral auxiliaries, provide a pathway to generate tetrasubstituted and quaternary carbon centers directly through the -functionalization of carboxylic acids. All chiral amines can be easily recovered by acid-base extraction with no loss of enantiomeric purity. Crystallographic, spectroscopic and computational studies elucidated the structure of an enediolate-lithium amide mixed aggregate as the origin of stereoselectivity. Using a similar aggregation process, the alkylation of ,-unsaturated carboxylic acid was also achieved with both high enantio- and regioselectivity. This method was attempted as a key step to establish the chirality in the concise synthesis of (–)-morphine, and resulted in a competing conjugate addition of dienoic acid in the presence of an activated alkyl halide. Inspired by the competition reaction, a method of enantioselective Michael-initiated ring closure was developed. Carbocyclic compounds can be synthesized in good to excellent stereoselectivities, providing a streamlined approach to the construction of densely functionalized cycloalkanes.