Aminotrifluoromethylation of Olefins via Cyclic Amine Formation: Mechanistic Study and Application to Synthesis of Trifluoromethylated Pyrrolidines
Aminotrifluoromethylation of Olefins via Cyclic Amine Formation: Mechanistic Study and Application to Synthesis of Trifluoromethylated Pyrrolidines
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DOI：
10.1021/jacs.5b02046
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发表时间：
2015-04-15
影响因子：
15
通讯作者：
Sodeoka, Mikiko
中科院分区：
文献类型：
--
作者：
Kawamura, Shintaro;Egami, Hiromichi;Sodeoka, Mikiko
我们研究了之前报道的氨基三氟甲基化反应的机制，该反应是在铜催化剂和Togni试剂的组合存在下通过烯胺的分子内环化进行的(1)。动力学研究表明，对于Togni试剂和CuI以及底物，反应的初始速率为一级。反应过程中Togni试剂的F-19 NMR化学位移的变化表明Togni试剂、底物胺和产物氮吡啶与铜之间存在一个配位的动态平衡。ESI-MS分析提供了活性Cu（II）中间体参与催化循环的证据。总的来说，我们的结果表明，反应在Togni试剂的高价碘部分进行，该反应被Cu（II）物种作为Lewis酸催化剂激活。基于这些机理考虑，我们开发了一种高效的三氟甲基化吡咯烷衍生物合成方法。加入Et3N后，这种转变的速率显著提高。
We examined the mechanism of our previously reported aminotrifluoromethylation reaction, which proceeds via intramolecular cyclization of alkenylamines in the presence of the combination of copper catalyst and Togni reagent (1). Kinetic studies revealed that the initial rate of the reaction was first order with respect to Togni reagent and CuI, as well as the substrate. Changes of the F-19 NMR chemical shift of Togni reagent during the reaction suggested the existence of a dynamic equilibrium involving coordination of not only Togni reagent, but also the substrate amine and the product aziridine to copper. ESI-MS analysis provided evidence of involvement of reactive Cu(II) intermediates in the catalytic cycle. Overall, our results indicate that the reaction proceeds at the hypervalent iodine moiety of Togni reagent, which is activated by Cu(II) species acting as a Lewis acid catalyst. On the basis of these mechanistic considerations, we developed an efficient synthesis of trifluoromethylated pyrrolidine derivatives. This transformation exhibited a remarkable rate enhancement upon addition of Et3N.