3-Hydroxyisoindolinones from Keto Acids and Amines: A Mild One-Pot Synthesis with Amidinium and Phosphonium Salts

A wide class of 3-hydroxyisoindolinones can be prepared from o-keto acids and both alkyl and aryl amines using PyBOP, PyBrOP, HATU, HBTU, and the like, under mild conditions, typically at 5-25 °C in DCM with Et₃N as base. Both EWG- and EDG-bearing o-keto acids have been studied and the yields range from 40% up to 90%. In some cases, the intermediate activated keto ester has been isolated in crystalline form. The amine attack on the keto ester leads first to the amide formation followed by an intramolecular cyclization step, as revealed by computational mechanistic studies.