Computed¹³C NMR Chemical Shifts via Empirically Scaled GIAO Shieldings and Molecular Mechanics Geometries. Conformation and Configuration from¹³C Shifts

Accurate (rms error ∼3 ppm) predictions of 13C chemical shifts are achieved for many of the common structural types of organic molecules through empirical scaling of shieldings calculated from gauge including atomic orbitals (GIAO) theory with a small basis set and with geometries obtained from computationally inexpensive molecular mechanics methods. Earlier GIAO calculations are shown to be much better at predicting relative chemical shifts when density functional theory with the B3LYP hybrid functional is used to account for electron correlation, in comparison with Hartree−Fock calculations. The GIAO isotropic shieldings need to be empirically scaled to achieve good numerical agreement with experimental δC. GIAO calculations with different small basis sets are compared for a set of 38 model compounds containing C, H, O, and N with MMX and MM3 force fields and B3LYP/6-31G* optimizations providing the geometries. The best MM3-based results are obtained with B3LYP/3-21G(X,6-31+G*)//MM3 calculations in which the 3-21G basis set is augmented for heteroatoms with polarization and diffuse functions. The examples of the (E)- and (Z)-2-butenes, axial and equatorial methylcyclohexanes, exo- and endo-2-norbornanols, vulgarin and epivulgarin, and chair and twist-boat forms of 3α-hydroxy-2β-(4-morpholinyl)-5αH-androstan-17-one are examined to establish whether δpred values could determine the structure if only one of each pair of structures were available to provide experimental δC values. The δpred from B3LYP/3-21G(X,6-31+G*)//MM3 calculations are adequate for addressing questions of conformation and relative stereochemistry.