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.

Abstract

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.