X-C-Z ANOMERIC EFFECT AND Y-C-C-Z GAUCHE EFFECT (X,Y=O,S Z=O,N) - EVALUATION OF THE STERIC, ELECTROSTATIC, AND ORBITAL INTERACTION COMPONENTS

A combined experimental and theoretical protocol has yielded the steric, electrostatic, and orbital interaction components of the X-C-Z anomeric and Y-C-C-Z gauche interactions between O/O, S/O, O/N, and S/N heteroatoms. The anomeric effect and gauche effect have been studied in 2-substituted heterocyclohexanes and 5-substituted 1,3-diheterocyclohexanes, respectively. The composite conformational effects operating in 2- or 3-substituted diheterocyclohexanes have then been evaluated in light of the former individual effects. Low temperature C-13 NMR spectroscopy has yielded the conformational free energies and molecular mechanics (MM2) calculations have yielded the electrostatic and steric components. The orbital interaction component is obtained by difference. The orbital interaction terms of the X-C-Z anomeric effect and the Y-C-C-Z gauche effect are found to be attractive for all combinations studied. The combination of an endo and exo anomeric interaction is always found to be more favorable than the exo interaction alone. The concept of a ''reverse anomeric effect'' observed with NHR substituents is discounted. The conformational preferences in O-C-N and S-C-N fragments are attributed mainly to a large steric component that outweighs the attractive orbital interaction component. Additivity of the orbital interaction component of the anomeric and gauche effects in the 1,4-diheterocyclohexanes is observed for the systems with oxygen substituents but generally not for those with nitrogen substituents. An additional hydrogen bonding component is invoked to explain the discrepancy in the latter systems. A proposal for the additivity of orbital interaction effects is advanced.