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 6 has
been achieved by copper-catalyzed iodination of the 1,3-bistriflate
ester 2a of p-tert-butylcalix­[4]­arene.
After protection of the hydroxy groups with iodomethane, diiodide 6 is subjected to halogen–lithium exchange with butyllithium,
followed by carbonation with CO2 or formylation with N-formylpiperidine and subsequent deprotection of the hydroxy
groups to give novel dicarboxylic acid 11 or dialdehyde 16 in practical yields. The iodo groups of diiodide 6 pass through the calixarene macrocycle; the activation free
energy for the conversion of the more stable syn conformer 6syn to the less stable anti conformer 6anti is ΔG⧧ = 104
kJ mol–1 at 298 K. Dialdehyde 16 shows
fast self-exchange between two equivalent species with a cone
conformation, ΔG⧧, being
63.2 kJ mol–1. Dicarboxylic acid 11 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 6 can be fixed predominantly
to anti (17a and 17b) 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-alkylated anti-1,3-diiodides provides access to
the anti-1,3-dialkylcalixarenes 19,
which is otherwise difficult
to obtain.