Tröger’s Base Twisted Amides: <i>Endo</i> Functionalization and Synthesis of an Inverted Crown Ether

Taking advantage of the unconventional reactivity of twisted mono- and bis-amides of Tröger’s base (TB), <i>rac-</i><b>6</b> and <i>rac-</i><b>7</b>, respectively, the first synthesis of a 6-<i>endo</i>-monosubstituted TB analogue, <i>rac</i>-<b>9</b>, and the first rational synthesis of a 6,12-<i>endo,endo</i>-disubstituted TB analogue, <i>rac-</i><b>11</b>, have been achieved. The bis-TB crown ether, <i>meso-</i><b>13</b>, was prepared starting from <i>rac-</i><b>7</b>. <i>Meso</i>-<b>13</b> constitutes a rare example of a crown ether with an inverted methylene bridge-to-bridge bis-TB conformation both in solution and in the solid state, resulting in a reluctance to act as a receptor for cations

A Protocol for the <i>exo</i>-Mono and <i>exo</i>,<i>exo</i>-Bis Functionalization of the Diazocine Ring of Tröger’s Base

An efficient protocol has been developed for the <i>exo-</i>mono and <i>exo</i>,<i>exo</i>-bis functionalization of Tröger’s base in the benzylic 6 and 12 positions of the diazocine ring. The lithiation of Tröger’s base using <i>s</i>-BuLi/TMEDA followed by electrophilic quench affords <i>exo</i>-mono- and <i>exo</i>,<i>exo</i>-bis-substituted derivatives of Tröger’s base in good to excellent yields. The variation of the number of equivalents of <i>s</i>-BuLi/TMEDA and the order of addition of the electrophile strongly govern the outcome of the reaction for each electrophile