SYNTHESIS VIA VINYL SULFONES .45. INTRAMOLECULAR OXYGEN VERSUS CARBONALKYLATION OF NAPHTHOATE ESTERS - A CAVEAT ON THE MECHANISTIC ASPECTSOF NEOCARZINOSTATIN CHEMISTRY
M. Lamothe et Pl. Fuchs, SYNTHESIS VIA VINYL SULFONES .45. INTRAMOLECULAR OXYGEN VERSUS CARBONALKYLATION OF NAPHTHOATE ESTERS - A CAVEAT ON THE MECHANISTIC ASPECTSOF NEOCARZINOSTATIN CHEMISTRY, Journal of the American Chemical Society, 115(11), 1993, pp. 4483-4496
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.