Part I. A refined synthetic route to a key synthon for (+)-laurencin. Part II. Studies toward development of a general method for stereocontrolled construction of conjugated (E)-enyne subunit required for (+)-laurencin

Part I. Improved sequence of reactions to camphor based lactam imide and improved diastereoselectivity of the corresponding Lewis acid promoted [2+2] cycloaddition reaction with phenyl vinyl sulfide are described. Reaction conditions were identified for efficient transformation of maleic anhydride into a fumaric acid derivative for high yielding acylation of camphor based lactam. Modified reaction conditions we utilized to achieve synthetically useful methylaluminum dichloride promoted [2+2] cycloaddition of the lactam imide with phenyl vinyl sulfide with diastereofacial selectivity of greater than 20:1.; Part II. Exploratory studies for construction of a requisite (E)-enyne subunit for (+)-laurencin are described. Allyl barium allylation, sulfoxide chelotropic elimination, anionic sulfone elimination, umplong alkylation, Stille coupling and aldol alkylation were investigated and the factors governing the selectivity of the enyne subunit geometry analyzed. A novel synthon for the stereocontrolled synthesis of ( E)-enyne subunit was identified and synthesized.