Tetracylic hemiacetals 14-24 were synthesized and their isomeric equilibria in DMSO-de at 50°were studied by nmr techniques. Substitution of polar groups at the Cg-exo position caused the equilibrium to shift toward the lesser stable ß isomer. This shift is interpreted on the basis of a stabilization of the ß isomer through polar attraction between the electropositive carbon, C9, and the electronegative oxygen of the nearby hydroxyl group. Halogen or mesyl substituents at C9 cause a stabilization of 0.4-0.5 kcal/mol while hydroxyl imparts about 0.2-kcal/mol stabilization. These results are significant in understanding the forces responsible for hemiacetal and conformational equilibria.Recent evidence has clearly shown that the position of conformational equilibria of pyranose derivatives and multisubstituted cyclohexanes cannot be predicted reliably on the basis of additive conformational free energies and anomeric effects. Pyranose derivatives substituted at Ci with negative substituents, such as acetate, benzoate, and especially halogen, invariably prefer that conformation in which the Ci substituent is axial, regardless of the fact that this often forces substituents at the other positions into axial conformations.1-3 An extreme situation is encountered in the case of tri-O-acetyl-and tri-O-benzoyl-jS-D-xylopyranosyl chloride, which at equilibrium contains 80 and 98%, respectively, of the 1C conformer in which the three acetate (benzoate) groups, as well as the chlorine at Ci, are all axial.1 23 According to Durette and Horton,3 this would not have been predicted on the basis of conformational free energies4•5 and the anomeric effect of the chloro group.6In the case of trifluoroacetoxycyclohexane the equilibrium is 80% in favor of the equatorial conformer, but, with two such substituents situated 1,4-trans, the equilibrium is only 55% in favor of the diequatorial conformer.7 Stabilization of the diaxial conformer through polar attraction between an electropositive carbon and the electronegative substituent at the Ci axial position as shown was suggested to account for this phenomenon.7 The substantial stability of diaxial conformers of trans-1,2 and trans-1,4 disubstituted cyclohexanes is further confirmation of the complexity of the interactions involved.8 Under circumstances where several interacting groups are present, predic-(1) C.

No abstract