Merging C-H Activation and Strain-Release in Ruthenium-Catalyzed Isoindolinone Synthesis

The merger of strain-release of 1,2-oxazetidines with carboxylic acid directed C-H activation in catalytic synthesis of isoindolinones is reported for the first time. This reaction opens a new and sustainable avenue to prepare a range of structurally diverse isoindolinone skeletons from readily available benzoic acids. The success of late-stage functionalization of some bioactive acids, and concise synthesis of biologically important skeletons demonstrated its great synthetic potential in drug discovery. Mechanistic studies indicated a plausible C-H activation/beta-carbon elimination/intra-molecular cyclization cascade pathway.

Automated summary

The study reports the first merger of strain-release of 1,2-oxazetidines with carboxylic acid directed C-H activation in catalytic synthesis of isoindolinones, providing a new sustainable pathway for preparing diverse isoindolinone skeletons and demonstrating great synthetic potential in drug discovery. Mechanistic studies revealed a plausible C-H activation/beta-carbon elimination/intra-molecular cyclization cascade pathway.