C(3)-Aryl isoindolinones: a PTSA-mediated access and improved synthesis of (±)-nuevamine.

We achieved a facile and scalable synthesis of N(2)-free C(3)-aryl isoindolinones in three steps from the corresponding phthalimides and electron-rich aromatic compounds. The reduction of one of the two carbonyls in N(2)-2-nitrobenzyl phthalimides with sodium borohydride followed by organo-catalysed (PTSA, 10 mol%) condensation with electron-rich aromatic compounds furnished C(3)-aryl isoindolinones. The subsequent removal of the 2-nitrobenzyl group under neutral photolytic conditions delivered N(2)-free C(3)-aryl isoindolinones in excellent overall yields. The intramolecular version of condensation delivered tetracyclic isoindolinones, for example nuevamine, in excellent yields with an extremely favourable E-factor, thus paving the way for the scalable and green synthesis of the alkaloid and its analogues. [ABSTRACT FROM AUTHOR]