One-Pot Synthesis of Isoindolinones via Three-Component Mannich/Lactamization Cascade Reaction

Abstract

An efficient synthesis of 3-substituted 2,3-dihydroisoindolin-1-ones was achieved with good yields (up to 88%). The process features broad substrate scope, high efficiency, and simplicity, using an one-pot, three-component Mannich/lactamization cascade reaction in the absence or presence of p-toluenesulfonic acid.

GRAPHICAL ABSTRACT

Keywords:

• Cascade reaction
• isoindolinone
• lactamization
• Mannich reaction
• three-component

ACKNOWLEDGMENTS

We are grateful for financial support from the National Science and Technology Major Project “Key New Drug Creation and Manufacturing Program” (Nos. 2009ZX09103-065 and 2009ZX09301-001), the Major Project of Chinese National Programs for Fundamental Research and Development (No. 2009CB918404), and the 111 Project of the Ministry of Education (No. B07023).

Notes

^a 5a (0.2 mmol), acetone (0.8 mL), and amine 7 (0.2 mmol) were used.

^b Isolated yield.

^a 5a (0.2 mmol), cyclohexanone (0.2 mmol), 4-methoxybenzenamine (0.2 mmol), and solvent (0.5 mL) were used.

^b Isolated yield.

^a 5a (0.2 mmol), 6 (0.2 mmol), 4-methoxybenzenamine (0.2 mmol), and dichloromethane (0.5 mL) were used.

^b Regioselectivity ratio 2.5/1 (less substituted product dominantly).

^a 5 (0.2 mmol), acetone (0.8 mL), amine 7 (0.2 mmol), and the catalyst p-toluenesulfonic acid (0.04 mmol) were used.

^b Isolated yield.