A Simple Method for the Synthesis of Isoindoline Derivatives

A method for the synthesis of isoindoline derivatives was developed based on a domino reaction involving a donor-acceptor cyclopropane containing a bromomethyl group in the ortho position of the aromatic substituent and structurally varied primary amines (anilines, benzylamines, cycloalkylamines). It was shown that the resulting N-benzyl-1,3-dihydroisoindole under hydrogenolysis conditions at room temperature underwent selective cleavage of the exocyclic N–CH2Ar bond followed by in situ lactamization to form benzo[b]pyrrolizidinone. The same product was obtained in a domino reaction starting with reduction of the azidomethyl group at the ortho position of the donor aromatic substituent. Similarly, the generation of the o-2-aminoethyl group was accompanied by two successive cyclization reactions leading to the formation of benzo[e]indolizidinone.