Isolation and Reactivity of Trifluoromethyl Iodonium Salts.
Isolation and Reactivity of Trifluoromethyl Iodonium Salts.
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三氟甲基碘盐盐的分离和反应性。
DOI：
10.1021/acscentsci.6b00119
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发表时间：
2016-05-25
影响因子：
18.2
通讯作者：
Toste FD
中科院分区：
文献类型：
--
作者：
Brantley JN;Samant AV;Toste FD
将三氟甲基（CF 3）官能团策略性地并入治疗剂或农用化学剂中是用于改变其相关物理化学性质（例如，代谢稳定性、亲脂性和生物利用度）。亲电三氟甲基化已成为将CF 3部分安装到一系列分子结构上的重要方法，特别是CF 3 λ3-碘烷，由于其独特的反应性和易于处理而引起了人们的极大兴趣。由这些高价碘试剂介导的三氟甲基化通常需要通过外源性刘易斯酸或布朗斯台德酸活化;因此，在这些转化中引起的推定中间体是阳离子CF 3碘鎓。到目前为止，这些碘离子还没有被分离出来，也没有对其固有反应性进行研究（这促使人们猜测这些物质是无法接触到的）。更完整地理解CF 3碘鎓的机理相关性对于开发涉及λ3-碘烷的新的三氟甲基化策略至关重要。在这里，我们证明了CF 3碘鎓盐很容易从常见的λ3-碘烷前体制备，并在环境条件下表现出显着的持久性。这些试剂是各种三氟甲基化反应的胜任亲电体，并且它们的反应性使人想起当使用刘易斯酸活化CF 3碘烷时观察到的反应性。因此，我们的研究结果表明，在λ3-碘烷介导的三氟甲基化过程中，CF 3碘鎓中间体的机理相关性。CF 3碘鎓盐的分离也提供了将它们更普遍地用作机械探针的独特机会。本文报道了三氟甲基碘鎓盐的分离。探索它们的反应性对于开发治疗剂和农用化学剂的稳健途径具有意义。
The strategic incorporation of the trifluoromethyl (CF3) functionality within therapeutic or agrochemical agents is a proven strategy for altering their associated physicochemical properties (e.g., metabolic stability, lipophilicity, and bioavailability). Electrophilic trifluoromethylation has emerged as an important methodology for installing the CF3 moiety onto an array of molecular architectures, and, in particular, CF3 λ3-iodanes have garnered significant interest because of their unique reactivity and ease of handling. Trifluoromethylations mediated by these hypervalent iodine reagents often require activation through an exogenous Lewis or Brønsted acid; thus, putative intermediates invoked in these transformations are cationic CF3 iodoniums. These iodoniums have, thus far, eluded isolation and investigation of their innate reactivity (which has encouraged speculation that such species cannot be accessed). A more complete understanding of the mechanistic relevance of CF3 iodoniums is paramount for the development of new trifluoromethylative strategies involving λ3-iodanes. Here, we demonstrate that CF3 iodonium salts are readily prepared from common λ3-iodane precursors and exhibit remarkable persistence under ambient conditions. These reagents are competent electrophiles for a variety of trifluoromethylation reactions, and their reactivity is reminiscent of that observed when CF3 iodanes are activated using Lewis acids. As such, our results suggest the mechanistic relevance of CF3 iodonium intermediates in trifluoromethylative processes mediated by λ3-iodanes. The isolation of CF3 iodonium salts also presents the unique opportunity to employ them more generally as mechanistic probes. The isolation of trifluoromethyl iodonium salts, putative intermediates in common trifluoromethylations, is reported. Probing their reactivity has implications for developing robust routes to therapeutic and agrochemical agents.