Determination of the Relative Stereochemistry of Flexible Organic Compounds by Ab Initio Methods: Conformational Analysis and Boltzmann-Averaged GIAO 13C NMR Chemical Shifts GIAO=gauge including atomic orbitals.

Abstract

Ab initio calculations at the Hartree–Fock level with full‐geometry optimization using the 6‐31G(d) basis set, and GIAO (gauge including atomic orbitals) ¹³C NMR chemical shifts, are presented here as a support in the study of the stereochemistry of low‐polar organic compounds having an open‐chain structure. Four linear stereoisomers, fragments of a natural product previously characterized by experimental ¹³C NMR spectra, which possesses three stereogenic centers, 11 carbon atoms, and 38 atoms in total, were considered. Conformational searches, by empirical force‐field molecular dynamics, pointed out the existence of 8–13 relevant conformers per stereoisomer. Thermochemical calculations at the ab initio level in the harmonic approximation of the vibrational modes, allowed the evaluation, at 298.15 K, of the standard Gibbs free energy of the conformers. The ¹³C NMR chemical shift of a given carbon atom in each stereoisomer was considered as the average chemical shift value of the same atom in the different conformers. The averages were obtained by the Boltzmann distribution, using the relative standard free energies as weighting factors. Computed parameters related to linear correlation plots of experimental ¹³C chemical shifts versus the corresponding computed average data allowed us to distinguish among the four stereoisomers.