Carbonylative Sonogashira Coupling in the Synthesis of Ynones: A Study of "Boomerang" Phenomena

The behaviour of several organophosphino-palladium complexes immobilized on mesoporous silica during the palladium-catalyzed synthesis of propynone by carbonylative Sonogashira coupling was studied, particularly concerning leaching/redeposition phenomena. The results demonstrated that this cross-coupling reaction is catalyzed by soluble species. Furthermore, it is shown that the palladium leaching is not initiated by the oxidative addition step but rather by palladium-decoordination from grafted ligand. Despite this decoordination, catalyst performance after recycling is adequate. Additionally, several parameters linked either to catalyst preparation or reaction procedures were shown to reduce leaching allowing one to achieve metal contamination levels close to the recommendation of the European Agency for the Evaluation of Medicinal Products. Interestingly, this heterogeneous palladium-catalyzed procedure is fully selective toward the formation of ynones, allowing the preparation of various target compounds.