A Garratt-Braverman route to isoindolines and phthalans

Abstract

Garratt-Braverman (GB) cyclization, two Csingle bondC bond forming reaction in a single step, has been utilized to construct several isoindoline and phthalan derivatives. The precursors were the bispropargyl protected amines and ethers with one of the propargyl arm substituted with an alkene moiety. The GB cyclizations were generally carried out in presence of DBU in refluxing toluene. In case of the bispropargyl amine systems with the alkene arm substituted with electron withdrawing ester group, the cyclization occurred at room temperature. The yields of cyclization ranged from 64 to 86% which are acceptable considering the formation of two Csingle bondC bonds. The protected isoindolines could be successfully deprotected by treatment with thiophenol in presence of triethyl amine and the corresponding free amines were isolated as the TFA salts.