Synthesis of 3-Hydroxyisoindolin-1-ones through 1,4-Dioxane-Mediated Hydroxylhydrative aza-Cyclization of 2-Alkynylbenzamide in Water

J Org Chem. 2020 Apr 17;85(8):5312-5320. doi: 10.1021/acs.joc.9b03466. Epub 2020 Apr 7.

Abstract

In this work, 1,4-dioxane-mediated hydroxylhydrative aza-cyclization of 2-alkynylbenzamide is developed for the synthesis of 3-hydroxylisoindolin-1-ones. The transformation proceeds smoothly in water with good yields and a broad reaction scope. Mechanistic studies show that regioselective brimonative 5-exo-dig aza-cyclization, bromohydration of the resulting alkene groups, and hydrolysis of dibromo compounds are involved. Compared to the traditional methodologies, the synthetic procedure reported herein represents a cleaner route toward 3-hydroxylisoindolin-1-ones.

Publication types

  • Research Support, Non-U.S. Gov't