Assignment of the relative and absolute stereochemistry of two novel epoxides using NMR and DFT-GIAO calculations

Considering the potential biological application of isobenzofuranones1, especially as agrochemical defensives, two novel epoxides were synthesized. The structures of these compounds were fully determined with the aid of high field nuclear magnetic resonance, infrared, mass spectrometry, and DFT theoretical calculations. Besides analyses of the 2D NMR spectra, the assignments of the nuclei at the epoxide ring were also inferred from information obtained by theoretical calculations. The calculated 1H and 13C NMR chemical shifts for eight candidate structures (Figure 1: en1-en4 and ex1-ex4) were compared with the experimental chemical shifts of 1 and 2 (Figure 2) by measuring the mean absolute errors (MAE) and by the DP4 statistical analysis2. The multiplicities of the hydrogens located at the bridge of the bicycle are distinct for epoxides 1 and 2 due to W coupling, and this feature was employed to confirm the assignment of these nuclei. The structures and relative configurations of 1 and 2 were determined by NMR spectroscopy assisted with theoretical calculations and due to the enantioselective synthesis starting from a chiral polyol (D-mannitol), the absolute configurations of the epoxides were also defined.