Studies Toward A Total Synthesis Of Phomactin A : A Tandem Ring-closing Metathesis Approach/

This dissertation describes work by myself, Christopher L. Hamblett and Professor James L. Leighton toward a total synthesis of phomactin A. Our approach required the synthesis of a tandem ring-closing metathesis substrate, the cyclization of which would form three of the four rings in phomactin A. The tandem metathesis substrate included two double bonds for the initiation and termination of metathesis respectively and one triple bond and one cycloolefin to act as relays in the tandem reaction. The most challenging aspect of the metathesis substrate's synthesis was the creation of a very hindered cyclopentenyl ether, synthesized by the reaction of a functionalized acetal with trimethylaluminum in a regio- and stereoselective alkylative cleavage. The configuration of the quaternary stereocenter was the opposite of the relative stereochemistry that was desired and expected, causing revision of the synthetic strategy to include an epimerization after the alkylative cleavage reaction. This epimerization has not been successfully applied at the time of this writing, although model studies indicate its feasibility. Preliminary metathesis experiments on a substrate epimeric to the desired system were carried out to give a promising mixture of compounds requiring further purification and analysis.