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-benzoquinones are described. Oxidation of methyl vanillate (2) in the presence of allyl alcohol (1a), trans-crotyl alcohol (1b), cinnamyl alcohol (1c), and homoallyl alcohol (1d) resulted in the formation of masked o-benzoquinones 8a-d that underwent intramolecular Diels-Alder reactions under reaction conditions to furnish adducts 14a-d in 53-75% yields. This tandem oxidative acetalization-intramolecular Diels-Alder process was extended to other 2-methoxyphenols such as 2-methoxy-4-methylphenol (3), guaicol (4), methyl isovanillate (5), methyl syringate (6), and 2,6-dimethoxy-4-methylphenol (7) to obtain adducts 15a-d, 16a-c, 17a-d, 18a-d, and 19a-d, respectively. While intramolecular Diels-Alder reactions of the masked o-benzoquinones 10a, 12d, and 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% yields. Masked o-benzoquinones 21a-d generated from 2 and substituted acrylic acids 20a-d underwent intramolecular Diels-Alder reactions to provide the tricyclic lactones 22a-d in 32-40% yields.