Innate C-H trifluoromethylation of heterocycles
Innate C-H trifluoromethylation of heterocycles
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DOI：
10.1073/pnas.1109059108
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发表时间：
2011-08-30
影响因子：
11.1
通讯作者：
Baran, Phil S.
中科院分区：
文献类型：
--
作者：
Ji, Yining;Brueckl, Tobias;Baran, Phil S.
化学工业的几乎每个领域都对杂芳族体系三氟甲基化的直接方法有着极高的需求。在这里，我们报告了使用台式稳定三氟甲基自由基源的通用程序的发现，该程序在各种缺电子和富杂芳族系统上广泛发挥作用，并表现出高官能团耐受性。该 C-H 三氟甲基化方案操作简单（避免气态 CF3I），可扩展，可在环境温度下进行，可直接用于未受保护的分子，并被证明可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且正交的反应性也在复杂的天然产物和药剂中进行了研究。最后，初步数据表明，C-H 三氟甲基化的区域选择性可以通过明智的溶剂选择进行微调。
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 CF3I), 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.