Electron pull-push modulation: Substrate controlled regioselectivity switch in 1,3-dipolar cycloaddition of isatin-derived azomethine ylides with chalcones

Abstract

A switch in regioselectivity has been achieved by modulating electron pull and push during the synthesis of spiropyrrolidine-oxindole analogs through 1,3-dipolar cycloaddition of isatin derived in-situ generated azomethine ylides with chalcones. Electron-withdrawing groups on ketone termini, along with neutral or electron-withdrawing groups on aldehyde termini, favored β-attack. In contrast, electron-donating groups on aldehyde termini switch the selectivity to α-attack. Structures of regioisomers have been determined by NMR, HRMS and SC-XRD.