An isosparteine derivative for stereochemical assignment of stereogenic (chiral) methyl groups using tritium NMR: Theory and experiment

(N-CHDT)-(α)-isosparteinium ditosylamide can be used in conjunction with tritium NMR spectroscopy to assign the configuration of an intact stereogenic (chiral) methyl group. The S-CHDT group has a ³H chemical shift that is 49 ppb downfield of the R-CHDT resonance. The sign and magnitude of this chemical shift difference of these diastereotopic tritium nuclei are found to be in agreement with predictions made via a purely ab initio computational approach. The chemical shift difference is due to an equilibrium isotope effect originating from a novel CH₃⋯N hydrogen bond. Despite the improved tritium chemical shift dispersion, this method is not useful for determining the enantiopurity of CHDTN(Tos)₂ due to partial racemization that occurs during the derivatization step. Milder methylation conditions are described for reactions using methyl p-toluenesulfonate or methyl-d₃ triflate. These studies suggest that (-)-(α)-isosparteine is a potential new reagent for chirality analysis of methyl groups originating from suitably reactive electrophiles.