Conformational analysis and absolute configuration of Spiropyrazolones

The relative configuration of the four stereocenters of spiropyrazolones 1, epi-1 and 2 was determined by NMR-NOE analysis. It turned out that while compound 1 has the 1R*, 2S*, 3R*, 4S* relative configuration, epi-1 is the diastereoisomer at the C-4 (1R*, 2S*, 3R*, 4R* relative configuration). A full conformational analysis was performed by Molecular Mechanics (MMFF field) scan of the potential energy surface, and the best conformations were optimized by DFT calculations, including the effect of the solvent in the calculations. The absolute configuration of the three compounds was then determined by the comparison of the Electronic CD spectra with the simulated spectra obtained by TD-DFT calculations. Four different functionals were used to achieve data redundancy and a more reliable assignment. The 1R, 2S, 3R, 4S absolute configuration was determined for 1, the 1R, 2S, 3R, 4R for epi-1 and the 1S, 2R, 3S, 4R for compound 2.