- Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl]
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This article describes the new economic decarboxylative trifluoromethylating reagent [Cu(phen)(O2CCF3)] (1; phen=1,10-phenanthroline) and the efficient difluorocarbene precursor [Cu(phen)2][O2CCF2Cl] (2). Treatment of copper tert-butoxide with phen and subsequent addition of trifluoroacetic acid or chlorodifluoroacetic acid afforded air-stable complexes 1 and 2, respectively, which were characterized by X-ray crystallography. The copper(I) ion in 1 is coordinated by a bidentate phen ligand, a monodentate trifluoroacetate group, and a molecule of CH3CN in a distorted tetrahedral coordination geometry. The molecular structure of 2 adopts an ionic form that consists of a [Cu(phen)2]+ cation and a chlorodifluoroacetate anion. Complex 1 reacted with a variety of aryl and heteroaryl halides to form trifluoromethyl (hetero)arenes in good yields. The corresponding Hammett plot exhibited a linear relationship and a reaction parameter (ρ)=+0.56±0.02, which indicated that the trifluoromethylation reaction proceeded via a nucleophilic reactive species. Complex 2 reacts with phenols to produce aryl difluoromethyl ethers in modest-to-excellent yields. Mechanistic investigations revealed that the difluoromethylation reaction proceeds by initial copper-mediated formation of difluorocarbene and subsequent concerted addition of difluorocarbene to the phenol to form a three-center transition state.
- Lin, Xiaoxi,Hou, Chuanqi,Li, Haohong,Weng, Zhiqiang
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supporting information
p. 2075 - 2084
(2016/02/12)
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- Use of fluoroform as a source of difluorocarbene in the synthesis of N-CF2H heterocycles and difluoromethoxypyridines
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Fluoroform is used as a source of difluorocarbene to convert various N-, O-, and C-nucleophiles to their difluoromethylated derivatives. Imidazole, benzimidazole, benztriazole, hydroxypyridines, and their derivatives underwent reaction at moderate temperatures and atmospheric pressure, using potassium hydroxide as base in a two-phase (water/acetonitrile) process to provide moderate to good yields of the respective products. Nitrophenols required addition of a co-solvent (methanol) to obtain good yields of products.
- Thomoson, Charles S.,Wang, Linhua,Dolbier, William R.
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- Method for synthesis of aryl difluoromethyl ethers
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This invention relates to a method for preparing difluoromethyl ethers, thiols and amines without using chlorofluorocarbon gases. The intermediates prepared by this method can be used to make certain compounds which act as PDE IV inhibitors which are useful for treating asthma and other diseases implicated with the PDE IV isozyme.
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