Una nuova classe di 3-amminoisotiazol S-ossidi chirali : sintesi, assegnazione della configurazione assoluta tramite calcoli teorici e analisi computazionale del meccanismo di ossidazione

A solution of 1a,b in CH2Cl2 with an equimolecular amount of (+) or (-)-2b was irradiated at 400W, 80°C. Sulfoxides (R)- and (S)-3a,b were produced in 70-80% overall yield and 44-55% ee together with little amount of sulfone (8-10%) after 1h. (-)-2a gave much slower reactions. In order to determine the absolute configuration (AC) of the new 3-aminosubstituted isothiazole S-oxides, we simulated [2,3] the ECD spectrum of (+)-3-aminomethyl isothiazole S-oxide, (+)-3b in the range 380-200 nm, both in the gas phase and ethanol at the TDDFT/B3LYP/aug-cc-pVDZ level of calculation. To this end we used (S)-3b which exists almost as a single conformer at the DFT/B3LYP/6-31G* level of calculation. In Figure are reported the experimental (black line) ECD spectrum of (+)-3b and predicted ECD spectra of (S)-3b, taking into account the first 30 excited states both in the gas phase and ethanol. In the gas phase (green line), even if the positions and intensities of predicted ECD bands do not perfectly match the experimental data, the experimental spectrum shows a sequence of negative, positive, negative Cotton effects which is reproduced in the theoretical spectrum, indicating the (+)/(S) correlation. Including the ethanol effect (red line), significantly improves the agreement between calculated and experimental data, strongly supporting the (+)/(S) configurational correlation.We can conclude that (+)-3b, which is the major enantiomer formed when using (+)-2b as the oxidant, possesses (S) AC.