Carestia Anthony M, Ravelli Davide, Alexanian Erik J
Department of Chemistry , The University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599 , USA . Email:
PhotoGreen Lab , Department of Chemistry , University of Pavia , Viale Taramelli 12 , 27100 Pavia , Italy . Email:
Chem Sci. 2018 May 14;9(24):5360-5365. doi: 10.1039/c8sc01756e. eCollection 2018 Jun 28.
The site selectivities of intermolecular, aliphatic C-H bond functionalizations are central to the value of these transformations. While the scope of these reactions continues to expand, the site selectivities remain largely dictated by the inherent reactivity of the substrate C-H bonds. Herein, we introduce reagent-dictated site selectivity to intermolecular aliphatic C-H functionalizations using nitrogen-centered amidyl radicals. Simple modifications of the amide lead to high levels of site selectivity in intermolecular C-H functionalizations across a range of simple and complex substrates. DFT calculations demonstrate that the steric demand of the reacting nitrogen-centered radical is heavily affected by the substitution pattern of the starting amide. Optimization of transition state structures consistently indicated higher reagent-dictated steric selectivities using more hindered amides, consistent with experimental results.
分子间脂肪族C-H键官能团化反应的位点选择性是这些转化反应价值的核心所在。尽管这些反应的范围不断扩大，但位点选择性在很大程度上仍由底物C-H键的固有反应活性所决定。在此，我们利用含氮酰胺基自由基将试剂导向的位点选择性引入到分子间脂肪族C-H官能团化反应中。对酰胺进行简单修饰就能在一系列简单和复杂底物的分子间C-H官能团化反应中实现高水平的位点选择性。密度泛函理论（DFT）计算表明，参与反应的含氮自由基的空间需求受到起始酰胺取代模式的严重影响。过渡态结构的优化始终表明，使用位阻更大的酰胺时，试剂导向的空间选择性更高，这与实验结果一致。
