SYNTHESIS VIA VINYL SULFONES .45. INTRAMOLECULAR OXYGEN VERSUS CARBON ALKYLATION OF NAPHTHOATE ESTERS - A CAVEAT ON THE MECHANISTIC ASPECTS OF NEOCARZINOSTATIN CHEMISTRY

Alpha-hydroxy naphthoate esters are shown to be capable of undergoing intramolecular alkylation at carbon as well as at both oxygen centers. Basic reaction conditions favor intramolecular oxygen alkylation of the phenol moiety in addition to intramolecular carbon alkylation leading to spirolactones. Chemistry in neutral or acidic media appears to proceed via gamma-oxo ketene acetal intermediates that are converted to products derived from addition of water followed by cleavage of the resultant orthoacid. Gamma-oxo ketene acetal intermediates derived from naphthoate esters are at least 40 times more reactive than those derived from simple beta-keto esters. These studies give credence to the proposal that the alpha-hydroxy naphthoate moiety in neocarzinostatin is capable of participation during the epoxide-opening reaction. Mechanistic consequences of such participation are discussed.