Copper-Catalyzed Reductive Ring-Cleavage of Isoxazoles: Synthesis of Fluoroalkylated Enaminones and Application for the Preparation of Celecoxib, Deracoxib, and Mavacoxib
Chao Wan, Jian-Yu Pang, Wei Jiang, Xiaowei Zhang, Xiang‐Guo Hu
Abstract
We have identified a new reactivity of copper/diamine catalysis for the reductive ring-cleavage of isoxazoles to yield fluoroalkylated enaminones. This protocol has the advantage of using commercially available reagents, ease of setting up, broad tolerance of functionality, and is regiospecific and free of defluorination and reduction of reducible functional groups. The utility was demonstrated by a one-step, regioselective synthesis of fluoroalkylated pyrazole-based drugs such as celecoxib, deracoxib, and mavacoxib.
Topics & Concepts
ChemistryRegioselectivityReagentPyrazoleYield (engineering)CatalysisCleavage (geology)Combinatorial chemistryRing (chemistry)CelecoxibCopperOrganic chemistryMedicinal chemistryMaterials scienceBiochemistryMetallurgyFracture (geology)Composite materialFluorine in Organic ChemistrySynthesis and Catalytic ReactionsClick Chemistry and Applications