De novo Assembly of the Benzenoid Ring as a Core Strategy for Synthesis of the Isoindolinone Natural Products Isohericerin, Erinacerin A, and Sterenin A

Here we describe the use of the hexadehydro-Diels–Alder (HDDA) reaction for the de novo construction of the isoindolinone scaffold and its application to the synthesis of the title natural products. The key isoindolinone-forming HDDA reaction involved an unprecedented substrate motif in which an amide carbonyl group was conjugated to the 4π 1,3-diyne component. In addition, a dimethylsilyl (−SiMe2H) substituent was exploited to trigger a Fleming–Tamao–Kumada oxidation for the installation of an essential phenolic hydroxyl group.