SYNTHESIS VIA VINYL SULFONES .45. INTRAMOLECULAR OXYGEN VERSUS CARBONALKYLATION OF NAPHTHOATE ESTERS - A CAVEAT ON THE MECHANISTIC ASPECTSOF 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 t he phenol moiety in addition to intramolecular carbon alkylation leadi ng to spirolactones. Chemistry in neutral or acidic media appears to p roceed via gamma-oxo ketene acetal intermediates that are converted to products derived from addition of water followed by cleavage of the r esultant orthoacid. Gamma-oxo ketene acetal intermediates derived from naphthoate esters are at least 40 times more reactive than those deri ved from simple beta-keto esters. These studies give credence to the p roposal that the alpha-hydroxy naphthoate moiety in neocarzinostatin i s capable of participation during the epoxide-opening reaction. Mechan istic consequences of such participation are discussed.