Absolute configuration in 4-alkyl- and 4-aryl-3,4-dihydro-2(1H)-pyrimidones: A combined theoretical and experimental investigation

Structural features (orientation of the carboxyl group, ring puckering), el ectronic absorption, and circular dichroism spectra of 4-alkyl- and 4-aryl- dihydropyrimidones 1-5 are calculated by semiempirical (AM1, INDO/S), ab in itio (HF/6-31G*, CIS/6-31G*, RPA/6-31G*), and density functional theory (B3 LYP/6-31G*) methods. These calculations allow an assignment of the absolute configuration by comparison of simulated and experimental CD spectra. Alth ough the ab initio methods greatly overestimate electronic transition energ ies, the general appearance of the experimental CD spectra is quite nicely reproduced by these calculations. Thus, comparison of experimental with cal culated CD spectra is a reliable tool for the assignment of the absolute co nfiguration. For 4-methyl derivatives 1, the first enantiopure DHPM example s with no additional aromatic substituent, the stereochemistry at C4 provid ed by the theoretical results is confirmed by X-ray structure determination of the diastereomeric salt 6. Additional support is the consistent HPLC el ution order found for all investigated DHPMs on a cellulose-derived chiral stationary phase.