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 Se-77 NMR parameters for the obtained benzisoselenazolones were measured and theoretically calculated at the DFT level of theory using B97-2 hybrid functional and ccpVTZ basis set. The DFT Se-77 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 approximate to +/- 180 degrees), and it is in agreement with those observed in crystals (X-ray). The calculation predicts a much higher sensitivity for the Se-77 chemical shift of the conformation than for the corresponding C-13 data. In the Se-77 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 H-1 NMR spectra, the benzisoselenazole derived from epi-9-amino-deoxyquinine induced splittings of the amino acid signals, thus allowing for discrimination of the enantiomers. (C) 2013 Elsevier Ltd. All rights reserved.