Synthesis, conformational properties, and molecular recognition abilities of novel prism[5]arenes with branched and bulky alkyl groups

Abstract

The direct macrocyclization to prism[5]arenes of 2,6-dialkoxynaphthalenes with branched and bulky alkyl groups has been obtained in good yields in the presence of 1,4-dihexyl-DABCO template. These novel prism[5]arenes exhibit typical D₅-symmetry and DFT calculations indicate that the homochiral all-pS (all-pR) conformation is the most stable of all the possible conformations. Prism[5]arenes crystallize as racemic mixtures (all-pS/all-pR) in centrosymmetric space groups. The eight crystal structures show C₂ point symmetry of the macrorings, with a larger opening of the cavity observed for PrS[5]^iBu, PrS[5]^MeCy and the β-form of PrS[5]^PrCy. The dynamic stereochemical inversion (from pR to pS and vice versa) of prism[5]arenes was examined by ¹H VT NMR experiments. The racemization of prism[5]arene derivatives occurs by through the-annulus-rotation of the naphthalene units. With increasing length of linear alkyl substituents from C2 to C9, the chains tend to pack at both rims, thereby diminishing the conformational freedom of the naphthalene units. The presence of branched alkyl groups at both rims of the prism[5]arenes increases the energy barrier to racemization and consequently lowers the rate of the racemization process. Prism[5]arenes bearing branched or bulky alkyl groups at both rims can form endo-cavity complexes with 1,4-dihexyl-DABCO 2²⁺ and piperazonium 3²⁺ guests. Two hosts with branched alkyl groups, PrS[5]^iPr and PrS[5]^iBu, show guest binding affinities higher than those calculated for the analogous linear PrS[5]^nPr and PrS[5]^nBu prism[5]arenes. This result can be justified on the basis of the greater conformational rigidity and preorganization of prism[5]arenes bearing branched groups.