Manganese-Catalyzed Radical 6-endo Azacyclization of 2-Alkynylbenzamide for the Synthesis of 3-Hydroxylisoquinolin-1,4-dione

Abstract

Backgroup: The versatile 2-alkynylbenzamde has been reported to produce many privileged skeletons, like isoquinolin-1-ones, isocoumarin-1-imines, isoindolin-1-ones, and isobenzofuran-1-imines. Recently, we reported the projected transformation using copper salt (CuCl2) as a catalyst under O2 atmosphere. To expand the scope of reaction we used another inexpensive metal salt MnO2 as catalyst Methods: The paper aims at exploring a manganese-catalyzed reaction of 2-alkynylbenzamide under O2 balloon for the synthesis of 3-hydroxylisoquinolin-1,4-dione. Results: Results on reaction scope shows the 10 mol% MnO2 in O2 atmosphere and DCE solvent catalyzed the cyclization of 2-alkynylbenzamide to produce 3-hydroxylisoquinolin-1,4-diones in 40-68% isolated yields. The reaction proceeds through a regioselective N-center radical 6-endo-dig aza-cyclization pathway. Conclusion: We have developed a manganese-catalyzed cyclization of 2-alkynlbenzamide for the synthesis of 3-hydroxylisoquinolin-1,4-diones under O2 balloon. It is believed that the N-center radical-based 6-endo dig aza-cyclization proceeded in a regioselective manner.