The concept of a chameleon activating group is considered in the context of donor–acceptor cyclopropane chemistry. When spiro-conjugated with cyclopropane, oxindole can act as an acceptor or a donor depending on the electronic nature of vicinal substituents. This dichotomy is reflected in the alteration of chemoselectivity of spiro­[oxindole-1,3′-cyclopropane] ring opening with nucleophiles.

A new synthetic approach to biologically relevant spiro[pyrrolidine-3,3'-oxindoles] was developed on the basis of the cascade transformation of 3-(2-azidoethyl)oxindoles via Staudinger/aza-Wittig/Mannich reactions. The parent azides were readily synthesized through a nucleophilic ring opening of spiro[cyclopropane-1,3'-oxindoles] with the azide ion. A series of new spiro[pyrrolidine-3,3'-oxindoles] with various (het)aryl substituents at the C2 and C5 positions of the pyrrolidine ring were synthesized. In vitro experiments revealed their high cytotoxicity toward LNCaP and PC-3 tumor cell lines.

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 S N 2-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.