Copper-Catalyzed Enantioselective Synthesis of Oxazolines from Aminotriols via Asymmetric Desymmetrization

A copper-catalyzed enantioselective transformation of tris(hydroxymethyl)aminomethane-derived aminotriols was developed to provide multisubstituted oxazolines with a tetrasubstituted carbon center. The present transformation consisted of sequential reactions involving mono-sulfonylation of aminotriols, subsequent intramolecular cyclization to afford prochiral oxazoline diols, and sulfonylative asymmetric desymmetrization of resultant oxazoline diols. In addition, the kinetic resolution process would be involved in the sulfonylative asymmetric desymmetrization step, which would amplify the enantiopurities of the desired products. Various aminotriols were tolerated in the present reaction, affording the desired oxazolines in good to high yields with excellent enantioselectivities. The synthetic utility of the present reaction was demonstrated by the transformation of the optically active oxazoline into a chiral alpha-tertiary amine motif.