Enantioselective synthesis, chiroptical properties and absolute configuration of 3-aminosubstituted isothiazole S-oxides

Herein we report a mild and efficient method to synthesize chiral 3-aminosubstituted isothiazole sulfoxides taking advantage of (+)- and (−)-((8,8-dichlorocamphoryl)sulfonyl)oxaziridine under microwave irradiation. The determination of the absolute configuration of the chiral sulfoxide was achieved by theoretical calculation of the CD spectra. The reason for the observed stereoselectivity was enlightened by means of analysis of our data using DFT calculations.

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N-Benzyl-isothiazol-3-amine S-oxideC10H10N2OSEe = 55%[α]D = +50.6 (c 1, CHCl3)Source of chirality: asymmetric oxidation

N-Methyl-isothiazol-3-amine S-oxideC4H6N2OSEe = 49.6%[α]D = +69 (c 1, MeOH)Source of chirality: asymmetric oxidation

N-Benzyl-4-bromo-isothiazol-3-amine S-oxideC10H9BrN2SOEe = 65%[α]D = +152.6 (c 1, CHCl3)Source of chirality: asymmetric oxidation

N-Benzyl-5-bromo-isothiazol-3-amine S-oxideC10H9BrN2SOEe = 6.4%[α]D = +6.0 (c 1, CHCl3)Source of chirality: asymmetric oxidation

N-Benzyl-5-chloro-isothiazol-3-amine S-oxideC10H9ClN2OSEe = 5.5%[α]D = −5 (c 1, CHCl3)Source of chirality: asymmetric oxidation

3-(S)-(1-Phenylethyl)aminoisothiazole-(R)-1-oxideC11H12N2OSDe = 98%[α]D = −353.6 (c 1, CHCl3)Source of chirality: asymmetric oxidation, chiral auxiliaryAbsolute configuration: (S,R)