Compounds Related to Podophyllotoxin. XI. An Unusual Stobbe Condensation

Stobbe condensation of methyl 2-(3,′4′,5′-trimethoxybenzoyl)-4,5-methylenedioxybenzoate with dimethyl succinate gives a product which was previously regarded as methyl 1-(3′,4′,5′-trimethoxyphenyl)-4-hydroxy-6,7-methylenedioxy-2-naphthoate but which is now shown to be methyl 1-hydroxy-4-(3′,4′,5′-trimethoxyphenyl)-6,7-methylenedioxy-2-naphthoate. The revision of structure follows from the infrared absorption of the condensation product, its reluctance to methylate with diazomethane, its mode of synthesis, and its non-identity with the authentic 4-hydroxy-2-naphthoate isomer. The tetralone, methyl 1-(3′,4′,5′-trimethoxyphenyl)-4-oxo-6,7-methylenedioxy-1,2,3,4-tetrahydro-2-naphthoate, on dehydrogenation with sulfur gives the authentic 4-hydroxy-2-naphthoate isomer. Acetylation yields the corresponding 4-acetoxy-2-naphthoate. The tetralone starting material with isopropenyl acetate plus a trace of acid forms the enol acetate, which with sulfur aromatizes to the same 4-acetoxy-2-naphthoate. A reaction path by which the Stobbe condensation can give rise to the 1-hydroxy-2-naphthoate isomer is suggested.