Chiral benzisoselenazolones: conformational analysis based on experimental and DFT calculated 77Se NMR

A series of new enantiomeric N-substituted benzisoselenazol-3(2H)-ones were prepared from 2-(chloroseleno)benzoyl chloride and 9-amino-deoxyquinine (both 9-native and 9-epi) as well as the other chiral primary amines. The 77Se NMR parameters for the obtained benzisoselenazolones were measured and theoretically calculated at the DFT level of theory using B97-2 hybrid functional and cc-pVTZ basis set. The DFT 77Se chemical shifts for the lowest energy conformers were in agreement with the experimental data, while the conformers of higher energy showed markedly worse fit. Interestingly, the preferred conformation for 2-(1-arylalkyl)-benzisoselenazolones is the gauche type (Se–N–C–H≈±180°), and it is in agreement with those observed in crystals (X-ray). The calculation predicts a much higher sensitivity for the 77Se chemical shift of the conformation than for the corresponding 13C data. In the 77Se NMR spectra of chiral benzisoselenazolones with added racemic or l-N-Boc-phenylglycine, chiral discrimination could not be observed mostly due to signal broadening. In the 1H NMR spectra, the benzisoselenazole derived from epi-9-amino-deoxyquinine induced splittings of the amino acid signals, thus allowing for discrimination of the enantiomers.

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