Liang Yufan, Fu Gregory C
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125 (USA).
Angew Chem Int Ed Engl. 2015 Jul 27;54(31):9047-51. doi: 10.1002/anie.201503297. Epub 2015 Jun 12.
Fluorinated organic molecules are of interest in fields ranging from medicinal chemistry to polymer science. Described herein is a mild, convenient, and versatile method for the synthesis of compounds bearing a perfluoroalkyl group attached to a tertiary carbon atom by using an alkyl-alkyl cross-coupling. A nickel catalyst derived from NiCl2 ⋅glyme and a pybox ligand achieves the coupling of a wide range of fluorinated alkyl halides with alkylzinc reagents at room temperature. A broad array of functional groups is compatible with the reaction conditions, and highly selective couplings can be achieved on the basis of differing levels of fluorination. A mechanistic investigation has established that the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) inhibits cross-coupling under these conditions and that a TEMPO-electrophile adduct can be isolated.
氟化有机分子在从药物化学到聚合物科学等诸多领域都备受关注。本文描述了一种温和、便捷且通用的方法，通过烷基 - 烷基交叉偶联反应合成叔碳原子上连接有全氟烷基的化合物。由NiCl₂·甘醇二甲醚和吡唑啉酮配体衍生的镍催化剂可在室温下实现多种氟化烷基卤化物与烷基锌试剂的偶联反应。多种官能团与该反应条件兼容，并且基于不同程度的氟化可实现高度选择性的偶联反应。机理研究表明，2,2,6,6 - 四甲基 - 1 - 哌啶氧基（TEMPO）的存在会抑制这些条件下的交叉偶联反应，并且可以分离出TEMPO - 亲电试剂加合物。
