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.