Diastereoselective Construction of 3-Aminooxindoles with Adjacent Stereocenters: Stereocontrolled Addition of -Substituted Allylindiums to Isatin Ketimines

The diastereoselective construction of 3-allyl-3-aminooxindoles that have two adjacent stereocenters has been achieved by the In-promoted Barbier-type addition of -substituted allylic halides to the C=N bond of isatin ketimines. The reactions of cinnamyl-, crotyl-, and geranylindium compounds with isatin ketimines proceeded in either aqueous or alcohol solution. The addition of a cyclohexenylindium species to an isatin ketimine was carried out in N,N-dimethylformamide (DMF), and the addition of ethyl 4-bromocrotonate to an isatin ketimine in EtOH gave oxindole-based -amino acid scaffolds. In all of these processes, the reaction conditions were screened to obtain the respective 3-allyl-3-aminooxindoles with very high stereoselectivity. In addition, plausible TS models are proposed, and representative synthetic transformations were carried out by using the oxindole-based -amino acid scaffolds. Furthermore, the stereochemistry of representative compounds were unequivocally established by single-crystal X-ray structure analysis.