Isoindole cycloadditions part 3: the synthesis of 'windscreen wiper' and other N-bridge cavity systems

<p dir="ltr">The thermal addition of <i>N</i>-carbobenzyloxyisoindole (<i>N</i>-Z isoindole) <b>11a</b>, generated by the reaction of 3,6-di(2-pyridyl)-<i>s</i>-tetrazine <b>9</b> with <i>N</i>-Z 7-azabenzonorbornadiene <b>8a</b>, onto dimethyl tricyclo[4.2.1.0^2.5]nona-3,7-diene-3,4-dicarboxylate <b>17</b> occurred site selectively at the cyclobutene π-bond to form a stereoisomeric mixture of 1 : 1-adducts <b>18</b> and <b>19</b>, in which the bent-frame isomer <b>19</b> was dominant (ratio 5 : 1). In contrast, <i>N</i>-benzyl tetrafluoroisoindole <b>11c</b> reacted with <b>17</b> only under high-pressure conditions (14 kbar, RT, 4 days) to afford 1 : 1-adducts at the cyclobutene site, in which the extended-frame isomer <b>18c</b> was dominant and the accompanying bent-frame product <b>19c</b> reverted to starting materials soon after isolation. These same stereoselectivities were used to prepare "windscreen wiper" compound <b>28c</b> having two mobile <i>N</i>-benzyl substituents attached to a rigid scaffold by the reaction of <i>N</i>-benzyl tetrafluoroisoindole <b>11c</b> with tetramethyl tetracyclo[4.4.1.0.^2,5.0^7.10]undeca-3,8-diene-3,4,7,8-tetracarboxylate <b>23</b>. Cavity bis-(cyclobutene-1,2-diester) <b>6</b> reacted with <i>N</i>-benzyl tetrafluoroisoindole <b>11c</b> twice over to produce cavity structure <b>36</b> with two <i>O</i>- and two <i>N</i>-benzyl bridges on the inner face, whereas the narrower cavity bis-alkene <b>32</b> stopped at the 1 : 1-addition stage. The dynamics of the Z-group in the dual adducts <b>26a</b>–<b>28a</b> are discussed briefly and key adducts and cavity systems have been structurally evaluated by X-ray crystallography, VT NMR, and molecular modeling.</p>