Synthesis of 8-Methoxy-and 8-Methoxy-6-methylhomophthalic Anhydrides, Key Intermediates for the Synthesis of Anthracyclinones and peri-Hydroxylated Polycyclic Aromatic Compounds

A novel synthesis of 8-methoxy-(1a) and 8-methoxy-6-methylhomophthalic anhydrides (1b) is described. Oxidative aromatization of methyl 2-(2-carbomethoxy-3-oxocyclohex-1-enyl) acetate (2) using 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) or sublimed sulfur followed by methylation gave methyl (2-carbomethoxy-3-methoxyphenyl) acetate (4) (method A). Diels-Alder reaction of 6-methoxy-4-methyl-2-pyrone (5) with 1, 3-dicarboalkoxyallenes occurred with the loss of carbon dioxide to give alkyl (2-carboalkoxy-3-methoxy-5-methylphenyl) acetates (6 and 7) (method B). These esters (4, 6, and 7) were converted to the corresponding 8-methoxyhomophthalic anhydrides (1a, b) by a usual alkaline hydrolysis followed by dehydrative cyclization with acetyl chloride in dry acetone.