One-pot synthesis of tetrasubstituted isoindolinones

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University of New Brunswick
The isoindolinone functionality and its derivatives are present in many naturally occurring and biologically active compounds. Tetrasubstituted isoindolinones such as 3, while a useful building block in materials as well as natural product synthesis, are particularly challenging to make. Current methods to make tetrasubstituted derivatives often require harsh conditions and expensive catalysts. Therefore, we decided to investigate a one-pot synthesis of this functional group using 5-exo-dig cyclization. Our strategy involved the intramolecular cyclization of alkynylbenzamide 1 using anhydrous conditions and trapping intermediate 2 with an electrophile. Several variables were investigated such as solvent, time, temperature, and identity of electrophile. Although the reactivity of intermediate 2 limited our choice with respect to solvents and electrophiles, we were successfully able to obtain target product 3 under certain conditions. Optimization and scope of the reaction will be discussed.