A Highly Efficient, Preorganized Macrobicyclic Receptor for Halides Based on CH··· and NH···Anion Interactions

The preorganized, macrobicyclic azaphane (1) exhibits remarkable strong, selective fluoride
binding comparable to the most effective bis(tren) cryptands despite binding anions via only three NH
groups coupled with three CH hydrogen bond donors. The lower intrinsic affinity of CH donors is
compensated by the high degree of preorganization exhibited by azacyclophane 1. Compound 1 is prepared
via a tripod−tripod cyclization reaction between 1,3,5-tris-bromomethyl-benzene and an aliphatic tripodal
hexatosylated polyamine, followed by the reduction of the resulting bicyclic tosylamine. The crystal structures
of the bicyclic tosylamine 2 and four macrobicyclic polyammonium halide salts of 1 are reported. X-ray
studies revealed the formation of inclusive 1:1 complexes of 1 with fluoride, chloride, bromide, and iodide.
Potentiometric titrations showed very high binding constants for fluoride and chloride with a F-/Cl- selectivity
of more than five logarithmic units. The final geometry of the anion cryptates is largely determined by
optimization of NH and CH···anion interactions coupled with unfavorable anion−π repulsion for the larger
anions.