Asymmetric synthesis of modafinil and its derivatives by enantioselective oxidation of thioethers: comparison of various methods including synthesis in ionic liquids

The oxidation of 2-(benzhydrylthio)acetic acid and its derivatives was performed with various catalytic and stoichiometric enantioselective reagents, the best results being obtained with stoichiometric chiral oxaziridine 5. The use of [bmim][PF6] as a solvent with 5 gave slightly higher yields and, in the case of the model compound thioanisole, a reversal of the enantioselectivity.

Figure optionsDownload as PowerPoint slide

(S)-(+)-[2-(Diphenyl)methanesulfinyl]acetamideC15H15NO2SEe = 60%[α]D20=+14.1 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-(+)-[2-(Diphenyl)methanesulfinyl]acetic acidC15H14O3SEe = 90%[α]D20=+39.1 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

Methyl (S)-(+)-[2-(Diphenyl)methanesulfinyl]acetateC16H16O3SEe = 75%[α]D20=+15.1 (c 1.0, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)