Tandem oxidative acetalization-intramolecular Diels-Alder reactions of 2-methoxyphenols. Simple synthesis of bicyclo[2.2.2]octenone derivatives

Intramolecular Diels-Alder reactions of in situ generated masked o-benzoqui nones are described. Oxidation of methyl vanillate (2) in the presence of a llyl alcohol (1a), trans-crotyl alcohol (1b), cinnamyl alcohol (1c), and ho moallyl alcohol (1d) resulted in the formation of masked o-benzoquinones 8a -d that underwent intramolecular Diels-Alder reactions under reaction condi tions to furnish adducts 14a-d in 53-75% yields. This tandem oxidative acet alization-intramolecular Diels-Alder process was extended to other 2-methox yphenols such as 2-methoxy-4-methylphenol (3), guaicol (4), methyl isovanil late (5), methyl syringate (6), and 2,6-dimethoxy-4-methylphenol (7) to obt ain adducts 15a-d, 16a-c, 17a-d, 18a-d, and 19a-d, respectively. While intr amolecular Diels-Alder reactions of the masked o-benzoquinones 10a, 12d, an d 13d were found to be less efficient, the masked o-benzoquinones 9a-d, 10b , 10c, 11a-d, 12a-c, and 13a-c furnished the desired products in 38-80% yie lds. Masked o-benzoquinones 21a-d generated from 2 and substituted acrylic acids 20a-d underwent intramolecular Diels-Alder reactions to provide the t ricyclic lactones 22a-d in 32-40% yields.