Intermolecular Diels−Alder Reactions of Brominated Masked o-Benzoquinones with Electron-Deficient Dienophiles. A Detour Method to Synthesize Bicyclo[2.2.2]octenones from 2-Methoxyphenols

Intermolecular Diels−Alder reactions of masked o-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones 57 and 2124 generated from 2-methoxyphenols 13 and 1720, respectively, with electron-deficient dienophiles leading to highly functionalized bicyclo[2.2.2]octenones are described. The masked o-benzoquinones (MOBs) 57 underwent Diels−Alder cycloadditions with methyl acrylate, methyl methacrylate, and methyl vinyl ketone to provide bicyclo[2.2.2]octenones 13ac to 15ac (direct method) in low to moderate yields with the concomitant formation of considerable amounts of dimers 911. To retard dimerization and to improve the yields of the requisite bicyclo[2.2.2]octenones, a detour method comprised of sequential bromination of 2-methoxyphenols 14, oxidation and Diels−Alder reaction, and debromination has been developed. The oxidation of bromophenols 1720 produced MOBs 2124 which are stable enough to be isolated. The MOBs 2124 underwent cycloaddition with electron-deficient dienophiles in a very efficient manner to afford the corresponding cycloadducts 25ac to 28ac in good to high yields without self-dimerization. When the cycloadducts 25ac to 28ac were treated with either Bu3SnH/AIBN or tributylammonium formate−palladium reagent, the corresponding debrominated products 13ac to 16ac were obtained in high to excellent yields. In general, the cycloadducts 13ac to 15ac were obtained in 20−40% higher yields via the detour method than those via the direct method. In both routes, the Diels−Alder reactions proceeded in a highly regio- and stereoselective manner to furnish a single cycloadduct in each case.