HFIP/BF₃·Et₂O Synergistic Catalysis Enables Intramolecular Alkyne Cyclization to Coumarins

We have successfully developed a novel synergistic catalytic system employing hexafluoroisopropanol (HFIP)/BF₃·Et₂O for intramolecular alkyne cyclization, which enables efficient construction of coumarin frameworks. This metal-free protocol features mild reaction conditions and exceptional substrate generality. The methodology has been directly applied to the synthesis of pharmacologically important natural products and drug molecules. Systematic mechanistic investigations have uncovered the cooperative catalytic mechanism of HFIP in this transformation, providing new fundamental principles for reaction design.