NMR vicinal JH-H from DFT theory as reliable tools for stereochemical analysis of 6-heptenyl-5,6-dihydro-2H-pyran-2-ones

A protocol for stereochemical analysis, based on the systematic comparison between theoretical and experimental vicinal ¹H-¹H NMR coupling constants, was developed and applied to a series of flexible compounds derived from the 6-heptenyl-5,6-dihydro-2H-pyran-2-one framework. The method included a broad conformational search, followed by geometry optimization at the DFT B3LYP/DGDZVP level, calculation of the vibrational frequencies, thermochemical parameters, magnetic shielding tensors, and the total NMR spin-spin coupling constants. The stereochemistry of natural and unnatural 6-heptenyl-5,6-dihydro-2H-pyran-2-ones containing diverse functional groups in the heptenyl side chain was analyzed by application of the correlation between the theoretical (Jpre) and experimental ¹H-¹H NMR (Jexp). A remarkable correlation demonstrated the predictive value of this approach for the stereochemical assignment of highly flexible compounds containing multiple chiral centers.