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

Intermolecular Diels−Alder reactions of masked <i>o</i>-benzoquinones, i.e., 6,6-dimethoxy-2,4-cyclohexadienones <b>5</b>−<b>7</b> and <b>21</b>−<b>24 </b>generated from 2-methoxyphenols <b>1</b>−<b>3 </b>and <b>17</b>−<b>20</b>, respectively, with electron-deficient dienophiles leading to highly functionalized bicyclo[2.2.2]octenones are described. The masked <i>o</i>-benzoquinones (MOBs) <b>5</b>−<b>7</b> underwent Diels−Alder cycloadditions with methyl acrylate, methyl methacrylate, and methyl vinyl ketone to provide bicyclo[2.2.2]octenones <b>13a</b>−<b>c </b>to <b>15a</b>−<b>c</b> (direct method) in low to moderate yields with the concomitant formation of considerable amounts of dimers <b>9</b>−<b>11</b>. 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 <b>1</b>−<b>4</b>, oxidation and Diels−Alder reaction, and debromination has been developed. The oxidation of bromophenols <b>17</b>−<b>20</b> produced MOBs <b>21</b>−<b>24</b> which are stable enough to be isolated. The MOBs <b>21</b>−<b>24</b> underwent cycloaddition with electron-deficient dienophiles in a very efficient manner to afford the corresponding cycloadducts <b>25a</b>−<b>c </b>to<b> 28a</b>−<b>c</b> in good to high yields without self-dimerization. When the cycloadducts <b>25a</b>−<b>c </b>to<b> 28a</b>−<b>c</b> were treated with either Bu<sub>3</sub>SnH/AIBN or tributylammonium formate−palladium reagent, the corresponding debrominated products <b>13a</b>−<b>c </b>to<b> 16a</b>−<b>c </b>were obtained in high to excellent yields. In general, the cycloadducts <b>13a</b>−<b>c </b>to<b> 15a</b>−<b>c</b> 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.