J. Heyrovský Institute of Physical Chemistry, The Czech Academy of Sciences , Dolejškova 3 , Prague 8 18223 , Czech Republic.
J Am Chem Soc. 2020 Feb 26;142(8):3947-3958. doi: 10.1021/jacs.9b12800. Epub 2020 Feb 12.
The selective functionalization of C-H bonds is one of the Grails of synthetic chemistry. In this work, we demonstrate that the selectivity toward fast hydroxylation or radical diffusion (known as the OH-rebound and dissociation mechanisms) following H-atom abstraction (HAA) from a substrate C-H bond by high-valent iron-oxo oxidants is already encoded in the HAA step when the post-HAA barriers are much lower than the preceding one. By applying the reactive mode composition factor (RMCF) analysis, which quantifies the kinetic energy distribution (KED) at the reactive mode (RM) of transition states, we show that reactions following the OH-rebound coordinate concentrate the RM kinetic energy on the motion of the reacting oxygen atom and the nascent substrate radical, whereas reactions following the dissociation channel localize most of their kinetic energy in H-atom motion. These motion signatures serve to predict the post-HAA selectivity, and since KED is affected by the free energy of reaction and asynchronicity (factor η) of HAA, we show that bimolecular HAA reactions in solution that are electron transfer-driven and highly exergonic have the lowest fraction of KED on the transferred H-atom and the highest chance to follow rebound hydroxylation. Finally, the RMCF analysis predicts that the H/D primary kinetic isotope effect can serve as a probe for these mechanisms, as confirmed in virtually all reported examples in the literature.
C-H 键的选择性功能化是合成化学的圣杯之一。在这项工作中，我们证明了当高价铁氧氧化剂从底物 C-H 键中抽去 H 原子（称为 HAA）后，后 HAA 势垒远低于前 HAA 势垒时，HAA 步骤中已经编码了对快速羟化或自由基扩散（称为 OH 回弹和离解机制）的选择性。通过应用反应模式组成因子（RMCF）分析，该分析量化了过渡态反应模式（RM）处的动能分布（KED），我们表明，OH 回弹后反应集中了 RM 动能在反应氧原子和新生成的底物自由基的运动上，而离解通道后的反应则将大部分动能集中在 H 原子的运动上。这些运动特征可用于预测 HAA 后的选择性，并且由于 KED 受反应自由能和 HAA 的异步性（因子 η）的影响，我们表明溶液中电子转移驱动的高度放能双分子 HAA 反应具有最低的转移 H 原子上的 KED 分数和最大的回弹羟化机会。最后，RMCF 分析预测 H/D 主动力学同位素效应可以作为这些机制的探针，这在文献中几乎所有报道的实例中都得到了证实。
