A simple one-step synthesis of N-substituted isoindolin-1-ones. Diastereofacially selective protonation of an intermediate isoindolinol

Abstract

α-Amino acids and their methyl esters, arylamines, heterocyclic amines and, less efficiently, aryl substituted aliphatic amines, react with o-phthaldialdehyde in the presence of acetic acid to give N-substituted isoindolin-1-ones in excellent yield; deuteriation studies implicate an isoindolinol intermediate and, when α-amino acids are used, provide evidence of its diastereofacially selective protonation.