Asymmetric Oxidation Synthesis of Modafinil Acid by Use of a Recyclable Chiral-at-Metal Complex

The enantioselective oxidation synthesis of chiral modafinil acid and its analogues with high enantiomeric excess has been developed by means of a chiral-at-metal strategy. Treatment of ruthenium complexes cis-[Ru(bpy)(2)Cl-2] or /-[Ru(bpy)(2)(MeCN)(2)](PF6)(2) (bpy is 2,2-bipyridine) with the appropriate prochiral thioether ligands afforded thioether complexes rac-1, /-1, rac-2, /-2, rac-3, and /-3. Diastereoselective oxidation of the thioether complexes in situ produced the corresponding sulfoxide complexes rac-1a, /-1a, rac-2a, /-2a, rac-3a, and /-3a. The configuration at the metal center in each case is stable during the coordination and oxidation reactions, and dictates the chirality of the sulfoxide ligand in the oxidation process. The chiral modafinil acids were obtained with ee values greater than 98% upon their removal from the corresponding sulfoxide complexes in the presence of TFA/MeCN. Moreover, the chiral ruthenium precursors /-[Ru(bpy)(2)(MeCN)(2)](PF6)(2) are recyclable and reusable with complete retention of the configurations.