Synthesis of 7′-Arylidenespiro[indoline-3,1′-pyrrolizines] and 7′-Arylidenespiro[indene-2,1′-pyrrolizines] via [3 + 2] Cycloaddition and β‑C–H Functionalized Pyrrolidine

The
acetic acid catalyzed three-component reaction of pyrrolidine,
aromatic aldehydes, and 3-arylideneoxindolin-2-ones in refluxing toluene
afforded functionalized 7′-arylidenespiro­[indoline-3,1′-pyrrolizines]
in good yields and with high diastereoselectivity. The similar three-component
reaction with 2-arylidene-1,3-indanediones also gave 7′-arylidenespiro­[indene-2,1′-pyrrolizines]
in good yields. However, the reaction with 3-phenacylideneoxindoles
resulted in a mixture of spiro­[indoline-3,1′-pyrrolizines]
and 7′-arylidene-substituted spirooxindoles in moderate yields.
The reaction mechanism included generation of azomethine ylides, β-C–H
functionalization of pyrrolidine, and sequential [3 + 2] cycloaddition.
The obtained spirooxindole derivatives were investigated by in vitro
evaluation against mouse colon cancer cells CT26 and human liver cancer
cells HepG2 by MTT assay.