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), electronic absorption, and circular dichroism spectra of 4-alkyl- and 4-aryl-dihydropyrimidones 1-5 are calculated by semiempirical (AM1, INDO/S), ab initio (HF/6-31G, CIS/6-31G, RPA/6-31G), and density functional theory (B3LYP/6-31G) methods. These calculations allow an assignment of the absolute configuration by comparison of simulated and experimental CD spectra. Although the ab initio methods greatly overestimate electronic transition energies, the general appearance of the experimental CD spectra is quite nicely reproduced by these calculations. Thus, comparison of experimental with calculated CD spectra is a reliable tool for the assignment of the absolute configuration. For 4-methyl derivatives 1, the first enantiopure DHPM examples with no additional aromatic substituent, the stereochemistry at C4 provided by the theoretical results is confirmed by X-ray structure determination of the diastereomeric salt 6. Additional support is the consistent HPLC elution order found for all investigated DHPMs on a cellulose-derived chiral stationary phase.
Uray
G
G
Institut für Chemie, Karl-Franzens Universität Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Verdino
P
P
Belaj
F
F
Kappe
C O
CO
Fabian
W M
WM
D002120:Calcium Channel Agonists / Q000737:chemistry; D002121:Calcium Channel Blockers / Q000737:chemistry; D002942:Circular Dichroism; D008958:Models, Molecular; D011744:Pyrimidinones / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013816:Thermodynamics
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D011744:Pyrimidinones