Wang L, et al. Advanced Synthesis and Catalysis, 2019, 361(10), 2354-2359.
A copper-catalyzed C-H difluoroacetylation protocol utilizing ethyl bromodifluoroacetate as the CF₂ source was developed for the selective functionalization of quinoxalin-2(1H)-ones at the C-3 position. The reaction employs [Cu(CH₃CN)₄]PF₆ (7.5 mol%) as the catalyst and 1,10-phenanthroline hydrate (20 mol%) as the optimal ligand, with K₂CO₃ as base in CH₃CN under an argon atmosphere at 110 °C. Ethyl bromodifluoroacetate serves as a practical and commercially available difluoroacetylating agent, enabling the efficient synthesis of a broad range of functionalized difluoroacetylated quinoxalinones in moderate to good yields. Optimization studies revealed that the reaction did not proceed in the absence of the ligand, and both the base and solvent had significant effects on product yield-K₂CO₃ and CH₃CN being optimal. Alternative ligands and copper sources resulted in markedly reduced efficiency, underscoring the critical role of both catalyst and ligand selection. This methodology provides a straightforward route for the synthesis of difluoroacetylated heterocycles, which are of interest for pharmaceutical development, and demonstrates the valuable synthetic utility of ethyl bromodifluoroacetate in direct C-H bond functionalization strategies.
Duan J, et al. Organic & Biomolecular Chemistry, 2022, 20(9), 1883-1887.
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