CALCULATION OF NMR OBSERVABLES FROM COMPUTED CONFORMERS AS A TOOL OF STRUCTURE VERIFICATION - CONFIRMATION OF THE STEREOCHEMISTRY OF TRANS-METHYL 2,3-DIMETHYL-5-METHOXY-2-CYCLOHEXENE-1-CARBOXYLATE

Four different methods (MM2, Chem3D, AM1, and MNDO) have been employed to calculate all the low-energy conformers of trans- and cis-methyl 2,3-dimethyl-5-methoxy-2-cyclohexene-1-carboxylate (1 and 2). For all of these conformers, NOE effects and vicinal coupling constants have been calculated, the latter using two different Karplus-type equations. From these calculations, 12 different sets of NMR observables were computed by taking a population weighted average over all conformations. These results were then used to verify the originally assigned trans configuration of compound 1. The diastereoisomer 2 was also prepared and shown to have the cis configuration. The different methods and the main sources of error are discussed. We found the best method for our purposes to be calculation of NOE from molecular mechanics structures.