Generation, stability, dimerization, and Diels-Alder reactions of masked o-benzoquinones.: Synthesis of substituted bicyclo[2.2.2]octenones from 2-methoxyphenols

Diels-Alder reactions of labile and readily dimerizing masked o-benzoquinones, i.e., substituted 6,6-dimethoxy-2,4-cyclohexadienones with electron-deficient dienophiles that resulted in the development of an efficient and reliable one-pot method for the preparation of highly functionalized bicyclo[2.2.2]octenones, are described. Oxidation of 2-methoxyphenols 8, 9, 11, 13, and 14 with (diacetoxy)iodobenzene in methanol afforded the corresponding masked o-benzoquinones 1, 2, 4, 6, and 7, which are not stable enough to be isolated and are found to dimerize under reaction conditions in a highly regio- and stereoselective manner to provide the Diels-Alder dimers 22, 23, 25, 27, and 28 respectively. On the other hand, masked o-benzoquinones 3 and 5, derived from phenols 10 and 12, respectively, were found to be quite labile and provided a complex mixture of products. However, masked o-benzoquinones 1-7, when generated in the presence of dienophiles such as methyl acrylate, methyl methacrylate, and methyl vinyl ketone, underwent highly regio- and stereoselective intermolecular Diels-Alder reactions to furnish variously substituted bicyclo[2.2.2]octenones 15-21(a-c). While the Diels-Alder reactions of masked o-benzoquinone 5 were found to be low-yielding, masked o-benzoquinones 1-4, 6, and 7 provided the desired adducts in good to high yields. Attempts are made to explain the observed regio- and stereoselectivity of these Diels-Alder reactions in terms of frontier molecular orbital theory.