Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14411-5. doi: 10.1073/pnas.1109059108. Epub 2011 Aug 15.
Direct methods for the trifluoromethylation of heteroaromatic systems are in extremely high demand in nearly every sector of chemical industry. Here we report the discovery of a general procedure using a benchtop stable trifluoromethyl radical source that functions broadly on a variety of electron deficient and rich heteroaromatic systems and demonstrates high functional group tolerance. This C-H trifluoromethylation protocol is operationally simple (avoids gaseous CF(3)I), scalable, proceeds at ambient temperature, can be used directly on unprotected molecules, and is demonstrated to proceed at the innately reactive positions of the substrate. The unique and orthogonal reactivity of the trifluoromethyl radical relative to aryl radicals has also been investigated on both a complex natural product and a pharmaceutical agent. Finally, preliminary data suggest that the regioselectivity of C-H trifluoromethylation can be fine-tuned simply by judicious solvent choice.
直接的三氟甲基化方法在几乎每个化学工业领域都有极高的需求。在这里，我们报告了一种使用台式稳定三氟甲基自由基源的通用程序的发现，该程序广泛适用于各种缺电子和富电子杂芳环系统，并表现出高官能团耐受性。这种 C-H 三氟甲基化方法操作简单（避免使用气态 CF(3)I），可扩展，在环境温度下进行，可直接用于未保护的分子，并证明在底物的固有反应位置进行。三氟甲基自由基相对于芳基自由基的独特和正交反应性也在复杂的天然产物和药物试剂上进行了研究。最后，初步数据表明，通过明智地选择溶剂，C-H 三氟甲基化的区域选择性可以简单地进行微调。
