A Brønsted acid-catalyzed thioacid addition to in situ-generated aldimine for the synthesis of isoindolinones with the N,S-acetal framework

Abstract

A facile methodology was demonstrated for the synthesis of isoindolinones containing the N,S-acetal framework by employing a Brønsted acid catalyst with a three-component reaction. The reaction proceeded via the addition of thioacid to in situ-generated aldimine followed by lactamization, which involved the formation of one C–S bond and two C–N bonds under easily controlled and ambient reaction conditions. A variety of substituted isoindolinones were synthesized with up to 99% yields. Furthermore, the importance of this methodology was also justified by a gram-scale synthesis and demonstration of some interesting synthetic transformations.