When not to rely on Boltzmann populations. Automated CASE‐3D structure elucidation of hyacinthacines through chemical shift differences

• Published in: Magnetic resonance in chemistry 2020-02, Vol.58 (2), p.139-144
• Main Author: Navarro‐Vázquez, Armando
• Format: Article
• Language: English
• Subjects: Chemical bonds; Chemical equilibrium; Configurations; Coupling (molecular); Couplings; DP4; GIAO; Hydrogen bonding; NMR; Nuclear magnetic resonance; Organic chemistry; stereochemistry; Structural elucidation; Three dimensional models
• ISSN: 0749-1581; 1097-458X
• DOI: 10.1002/mrc.4951

An Akaike Information Criterion (AIC) procedure (CASE‐3D) has been successfully applied to the NMR based configurational assignment of reported hyacinthacines (1–3,5–8), recently target of configurational analysis using the popular DP4+ methodology. The present analysis makes use of reported 1H and 13C shifts and, in some particular cases, a few 3JHH couplings. The difficulty in proper computational prediction of relative energies, in molecules capable of inter‐molecular hydrogen bonding, introduces large errors in the prediction of conformationally averaged NMR properties in methods based on Boltzmann averaging such as DP4 or DP4+. In contrast CASE‐3D conformational amplitudes are free parameters in the model. Here we show that the CASE‐3D conformational model selection strategy, when combined with a larger energy cutoff in the molecular‐modelling conformational exploration, was sufficient to correctly assign the relative configuration in five of seven cases. Introduction of more information, either by supplementing 1H and 13C data with a few J‐couplings, or using a cutoff based on computed DFT energies for the definition of the conformational ensembles, allowed the safe assignment of configuration for all compounds. CASE‐3D determination of relative configuration in polyhydroxilated compounds.