Asymmetric Synthesis of 3,3-Disubstituted Oxindoles from N-Aryl Oxindole Derivatives bearing C-N Axial Chirality

We have newly designed N-aryl oxindole with C-N axial chirality as a common intermediate for diastereoselective and divergent synthesis of a variety of 3,3-disubstituted oxindoles bearing a C3 stereogenic center. High diastereoselectivities (up to >95:<5) were observed with orthomonosubstituted N-aryl oxindole systems through transformations including nucleophilic addition, alkylation, and cycloaddition. Facile removal of the p-(benzyloxy) aryl moiety in axially twisted amides was achieved by a mild, two-step sequence. We also describe the first synthesis of an enantiomerically pure C-N axially chiral N-aryl isatin from the corresponding N-aryl oxindole, which was synthesized by an asymmetric intramolecular Buchwald-Hartwig N-arylation.