1,3-Diiodocalix[4]arene: Synthesis by Ullmann-Type Iodination of 1,3-Bistriflate Ester of Calix[4]arene, Conformational Analysis, and Transformation into 1,3-Dicarboxy‑, Diformyl‑, and Dialkylcalix[4]arenes

A facile synthesis of 1,3-diiodocalix[4]­arene <b>6</b> has been achieved by copper-catalyzed iodination of the 1,3-bistriflate ester <b>2a</b> of <i>p</i>-<i>tert</i>-butylcalix­[4]­arene. After protection of the hydroxy groups with iodomethane, diiodide <b>6</b> is subjected to halogen–lithium exchange with butyllithium, followed by carbonation with CO₂ or formylation with <i>N</i>-formylpiperidine and subsequent deprotection of the hydroxy groups to give novel dicarboxylic acid <b>11</b> or dialdehyde <b>16</b> in practical yields. The iodo groups of diiodide <b>6</b> pass through the calixarene macrocycle; the activation free energy for the conversion of the more stable syn conformer <b>6</b>_syn to the less stable anti conformer <b>6</b>_anti is Δ<i>G</i>^⧧ = 104 kJ mol^–1 at 298 K. Dialdehyde <b>16</b> shows fast self-exchange between two equivalent species with a cone conformation, Δ<i>G</i>^⧧, being 63.2 kJ mol^–1. Dicarboxylic acid <b>11</b> adopts a cone conformation and forms a dimer in solution as suggested by ¹H NMR and X-ray crystallographic analyses. The arrangement of the iodide groups of compound <b>6</b> can be fixed predominantly to anti (<b>17a</b> and <b>17b</b>) by introducing bulky alkyl groups (e.g., propyl groups) onto the hydroxy groups. The stereospecific alkylation of the iodo groups of the resulting di-O<i>-</i>alkylated <i>anti-</i>1,3-diiodides provides access to the <i>anti</i>-1,3-dialkylcalixarenes <b>19</b>, which is otherwise difficult to obtain