Emerging Strategies for Controlled Defluorinative Cyclization: One-Pot Synthesis of Fluoro-Substituted 4H-Pyrans or Trifluoromethyl-Substituted 2H-Pyrans.

In this work, we have successfully developed an efficient one-pot [3 + 3] defluorinative cycloaddition reaction for the synthesis of pyran derivatives from β-CF3-1,3-enynes and isoxazoles. This transformation proceeds without any metal catalysts and enables one-step pyran ring construction under mild conditions with high atom and step economy. Notably, by simply modulating the substrate structure or reaction conditions, two distinct skeletons─trifluoromethyl-substituted 2H-pyrans or fluorine-substituted 4H-pyrans─can be selectively obtained. This divergent synthesis strategy allows rapid access to a diverse library of pyran derivatives from identical starting materials, greatly enhancing synthetic efficiency and flexibility. Furthermore, the reaction features broad substrate scope, operational simplicity, and environmental friendliness. Thus, it provides a highly valuable strategy for the synthesis of bioactive molecules. The simplicity and green nature of this method render it promising for broad application in medicinal chemistry and related fields.