The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

Abstract

The synthesis of various 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones was realized following a simple three-step process. The protocol utilized the photodecarboxylative addition of readily available carboxylates to N-(bromoalkyl)phthalimides as a versatile and efficient key step. The initially obtained hydroxyphthalimidines were readily converted to the desired N-diaminoalkylated 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones via acid-catalyzed dehydration and subsequent nucleophilic substitution with the corresponding secondary amines. The procedure was successfully applied to the synthesis of known local anesthetics (AL-12, AL-12B and AL-5) in their neutral forms.

Keywords

• anesthetics
• arylmethylenedihydroisoindolinones
• photochemistry
• photodecarboxylation
• phthalimide