Molecular Recognition and Stereoselectivity: Geometrical Requirements for the Multiple Hydrogen-Bonding Interaction of Diols with a Multidentate Polyhydroxy Macrocycle

Article abstract of DOI:10.1021/ja00004a042

Resorcinol-dodecanal cyclotetramer 1 in CDCl3 forms hydrogen-bonded, 1/1 complexes with cyclohexanediols as well as with 2,4-pentane- and 2,5-hexanediol as their open-chain analogues and cyclohexanol and cis- and trans-4-tert-butylcyclohexanol.The affinities to 1 of cyclic diols (K=(1.1-10) * 10² M^-1 at 25 deg C) are significantly larger than those of open-chain diols (36-43 M^-1) and monools (8-11 M^-1).Those of regio- and stereoisomers of cyclohexanediol depend on the configuration (axial-equatorial > diequatorial) and relative positions (1,4 >> 1,2 > 1,3) of the two OH groups involved and decrease in the order cis-1,4 (K=1.04 * 10³) > cis-1,2 (2.64 * 10²) > trans-1,3 (1.81 * 10²) > trans-1,4 (1.29 * 10²) > cis-1,3 (1.24 * 10²) > trans-1,2 (1.06 * 10² M^-1); the stereoselectivities are thus cis-1,4/trans-1,4 = 8.0, cis-1,2/trans-1,2 = 2.5, and trans-1,3/cis-1,3 = 1.5.The selectivities in the diol binding are discussed in terms of multiple hydrogen bonding of diol and 1.The relatively large binding constant (K) for cis-1,4-diol with one axial and one equatorial OH group is attributed to an effective and simultaneous two-point hydrogen bonding of the two OH groups with two adjacent binding sites of 1 as a multidentate host.