Synthesis of 3-propargyl isoindolinones by Pd/Cu-catalyzed enantioselective Heck/Sonogashira reaction of enamides

Abstract

Herein, we report an enantioselective Pd/Cu-catalyzed sequential Heck/Sonogashira coupling reaction of electron-rich enamides with terminal alkynes as substrates. This transformation proceeds smoothly to afford 3-propargyl isoindolinone derivatives bearing quaternary stereogenic centers in moderate to good yields (43–77% yield) and good to excellent enantioselectivity (up to 93% ee). Functional groups such as halogen atoms (F, Cl, and Br), thienyl, and silyl moieties are tolerated well. Synthetic transformations of the 3-propargyl isoindolinone product show the utility value of the reaction.