Alkyl Arylacetates in Cascade Reactions with 2-Cyanobenzaldehydes for the Synthesis of 3-Substituted Isoindolinones

Herein we report the use of alkyl arylacetates as pro-nucleophiles in cascade reactions with 2-cyanobenzaldehydes leading to the formation of novel 3-substituted isoindolinones, a heterocyclic scaffold found in many natural products and bioactive synthetic compounds. The reaction proceeds under very mild conditions, generally affording good to excellent yields. We also demonstrated that diastereoselectivity is dependent on the presence of strong electron-withdrawing substituents at the aromatic ring of the nucleophile. Kinetic investigations were performed by UV-vis stopped-flow methods, indicating a clear dependence of the reaction rate on the nucleophilic reactivity of the carbanionic intermediates.