Copper-Mediated Difluoromethylation of (Hetero)aryl Iodides and β-Styryl Halides with Tributyl(difluoromethyl)stannane
Copper-Mediated Difluoromethylation of (Hetero)aryl Iodides and β-Styryl Halides with Tributyl(difluoromethyl)stannane
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DOI：
10.1002/anie.201205850
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Olah, George A.
中科院分区：
文献类型：
--
作者：
Prakash, G. K. Surya;Ganesh, Somesh K.;Olah, George A.
Organofluorine compounds have found application in a wide variety of fields. They occur, for example, in pharmaceuticals, agrochemicals, materials, surfactants, and catalysts.[1] The selective introduction of the difluoromethyl group (CF2H) into organic molecules is of interest owing to the special biological properties of this group, such as its enhancement of membrane permeability, binding affinity, and bioavailability.[2] The CF2H functionality is isosteric and isopolar with the hydroxy (OH) group and is reasonably lipophilic.[3] At the same time, the CF2H group is weakly acidic and capable of participating in weak hydrogen-bonding interactions. Because of these properties, the CF2H group is found in various biologically active compounds, such as enzyme inhibitors, sugars,[4] and agrochemicals.[5] Several methods have been developed for the preparation of CF2H-containing compounds, including the deoxofluorination of aldehydes with SF4, N, N-diethylaminosulfur trifluoride (DAST), and derivatives of DAST.[6] The magnesium-metal-mediated reductive difluoromethylation of chlorosilanes with difluoromethyl sulfides, sulfoxides, and sulfones has been reported,[7] as has the nucleophilic introduction of a CF2H group into carbonyl compounds with difluoromethyl phenyl sulfone,[8](difluoromethyl) dimethylphenylsilane, and (chlorodifluoromethyl) trimethylsilane.[3, 9] The direct transfer of a difluoromethyl group to a heteroarene with zinc difluoromethanesulfinate (DFMS), which is believed to proceed by a radical pathway, was reported by the Baran research group.[10] However, direct access to regiospecifically difluoromethylated arenes has been a challenge until recently.Amii and co-workers reported a CuI-catalyzed three-step approach for the synthesis of difluoromethyl aromatic and heteroaromatic compounds by a CÀC coupling reaction between an aryl iodide and an α-silyldifluoroacetate, followed by hydrolysis and decarboxylation (Scheme 1).[11] Fier and Hartwig reported a one-step copper-mediated (CuI) nucleophilic difluoromethylation of iodoarenes with TMSCF2H.[12] Although the products were obtained in excellent yields, the
