Origin of the chemical-shift isotope effect. Stereochemical evidence

Abstract

The chemical shift of a fluorine-19 nucleus moves to higher field when deuterium is substituted for hydrogen either geminally (H-C-F -* D-C-F) or vicinally (H-C-C-F -* D-C-C-F). We have found that the vicinal chemical-shift isotope effect has a strong stereochemical dependence. When the H(D)-C-C-F dihedral angle is less than 90°, the isotope shift is about 0.15 ppm. When the nuclei are furthest apart, at 120 and 180°, the isotope shift increases to about 0.35 ppm. These results cannot be explained exclusively in terms of an electric-field model, which predicts an inverse dependence of the magnitude of the effect on the distance between the resonating and perturbing nuclei. Because the stereochemical dependence is similar to that observed for substituent inductive effects on the absolute magnitude of vicinal coupling constants and chemical shifts, we conclude that a major portion of the isotope shift results from vibrationally based inductive effects. Vicinal ( ) delocalization provides one mechanism for such a phenomenon.

Identifying Stereoisomers by ab-initio Calculation of Secondary Isotope Shifts on NMR Chemical Shieldings

“…Note that from the previous section, uncertainties of less than 0.020 ppm can be anticipated for the calculated relative differences in the isotope shifts. In contrast to the calculated values, the secondary isotope shifts obtained by Lambert et al [15] amount to −0.15 ± 0.06 ppm for the endo -3-deutero compound and −0.40 ± 0.06 ppm for the exo -3-deutero compound. Within the given computational and experimental uncertainties these results do not coincide.…”

“…An early example for exploring dependencies of various parameters on secondary isotope effects on 19 F chemical shieldings was conducted by Lambert et al [15]. Aiming to understand the dependence on the distance and the dihedral angle between substituted and resonating nuclei as well as on the number of substituted nuclei on secondary isotope shifts, several compounds were studied including 2-fluoronorbornanes, where 1 H in the endo -3 and exo -3 positions were substituted by deuterium (Figure 2).…”

“…As an example, for which quantum chemical calculations can actually resolve ambiguities in the literature, we would like to revisit in the second part of this work one of the first studies in which various effects on secondary isotope shifts on NMR chemical shieldings were systematically investigated. Lambert et al [15] experimentally investigated secondary isotope effects on NMR chemical shieldings on endo -2-fluoronorbornanes and fluorocyclohexanes in order to identify major influences on secondary isotope shifts. Especially the results for the endo -2-fluoronorbornanes are interesting as our results [16] suggest that in contrast to what has been assumed by Lambert et al , the synthesis chosen does not lead to the desired endo -2-fluoronorbornanes.…”

Isotopic perturbation of resonance in a homologous series of metal complexes with allylic cation character

“…15 It may be associated with the Z,syn configuration of L in a chelate, whereas the E,anti configuration in L À produces a more normal negative 3 D. This is consistent with the 180°CCCH dihedral angle in the chelates, just as 3 D F (D) in alkyl fluorides increases with the FCCH dihedral angle. 16 …”

Isotopic perturbation of resonance in a homologous series of metal complexes with allylic cation character

“…15 It may be associated with the Z,syn configuration of L in a chelate, whereas the E,anti configuration in L À produces a more normal negative 3 D. This is consistent with the 180°CCCH dihedral angle in the chelates, just as 3 D F (D) in alkyl fluorides increases with the FCCH dihedral angle. 16…”