CONFORMATIONAL-ANALYSIS OF 6-MEMBERED RINGS IN SOLUTION - RING PUCKERING COORDINATES DERIVED FROM VICINAL NMR PROTON PROTON COUPLING-CONSTANTS

A new method for quantitative analysis of the conformation of six-membered ring compounds in solution is presented. The method uses as a probe the endocyclic vicinal NMR proton-proton coupling constants, which are translated into the relevant conformational parameters by means of a combination of the generalized Karplus equation and the recently developed Truncated Fourier formalism (delineating the interrelation between the endocyclic torsion angles in a six-membered ring; cf.: Haasnoot, C. A. G. J. Am. Chem. Soc. 1992, 114, 882). A practical elaboration is laid down in three computational procedures which can be used to analyze the experimental couplings in terms of a single-state conformation or a two-state conformational equilibrium. Typical applications of these procedures are exemplified by conformational analyses of six-membered rings occurring in alkaloids, steroids, and sugar derivatives. The obtained conformational descriptions of these six-membered rings in solution are shown to be consistent with conformational data derived from X-ray crystallography and/or molecular mechanics. It is, therefore, concluded that the unique quantitativeness of the method allows for a superior analysis of the conformational behavior of six-membered rings in solution.