Hydrogen-Bonded Networks: Molecular Recognition of Cyclic Alcohols in Enantiopure Alleno-Acetylenic Cage Receptors

Enantiopure (P)₄ - and (M)₄ -alleno-acetylenic cage (AAC) receptors form circular fourfold hydrogen-bonding networks in their closed cage conformation. Theoretical studies reveal a preferential clockwise (cw) orientation of the H-bonding array for (P)₄ -configured and counterclockwise (ccw) for (M)₄ -configured receptors (ΔE_cw-ccw =-2.6 to -3.1 kcal mol^-1 ). Solution and solid-state studies show how the H-bonding network of the receptor is expanded upon encapsulation of alcohol-containing guests. Topologies reminiscent of those found in isolated water clusters are observed: circular fourfold & docking, pentagonal, linear fivefold, and hexagonal boat-shaped. Expansion of the H-bonding network together with optimal space occupancy yields very high ligand affinities (ΔG_293 K =-9.0 kcal mol^-1 for endo-tropine). The H-bonding network in the complexes also contributes substantially to the enantioselective complexation of chiral diols, such as (R,R)- and (S,S)-trans-cyclohexane-1,2-diol.