Tetra-O-benzylated calix[8]arenes with C4 symmetry

The first procedure for the selective partial O-alkylation of p-tert-butylcalix[8]arene 1 affording well defined products is described. Treatment of 1 with p-X-benzyl bromides (X = H, Me, tert-Bu, NO2, CN) and K2CO3 in THF/DMF gives the corresponding 1,3,5,7-tetrabenzyl ethers 2-6 having C4 symmetry. Their structures were firmly established by FAB(+) MS, 1H- and 13C-NMR. Variable temperature NMR studies evidenced conformational flexibility for 2-6. A possible rationale is proposed in order to explain the origin of the 1,3,5,7-substitution pattern.