Stereocontrolled [3+2] Cycloaddition of Donor–Acceptor Cyclopropanes to Iminooxindoles: Access to Spiro[oxindole-3,2′-pyrrolidines]

A novel stereocontrolled assembly of spiro­[oxindole-3,2′-pyrrolidines] via [3+2]-cycloaddition of donor–acceptor cyclopropanes to electron-poor ketimines, iminooxindoles, was developed. The method allows for efficient employment of common readily available donor–acceptor cyclopropanes, functionalized with ester, keto, nitro, cyano etc. groups, and N-unprotected iminooxindoles. The stereospecificity of the initial SN2-like imine attack on a cyclopropane molecule together with a high diastereoselectivity of further C–C bond formation facilitate a rapid access to spiro­[oxindole-3,2′-pyrrolidines] in their optically active forms. Preliminary in vitro testing of the synthesized compounds against LNCaP (p53+) and PC-3 (p53−) cells revealed good antiproliferative activities and p53-selectivity indices for several compounds that are intriguing in terms of their further investigation as inhibitors of MDM2-p53 interaction.