Bharadwaz Priyam, Maldonado-Domínguez Mauricio, Srnec Martin
J. Heyrovský Institute of Physical Chemistry, The Czech Academy of Sciences Dolejškova 3 Prague 8 18223 Czech Republic
Chem Sci. 2021 Aug 23;12(38):12682-12694. doi: 10.1039/d1sc02826j. eCollection 2021 Oct 6.
Bifurcating reactions yield two different products emerging from one single transition state and are therefore archetypal examples of reactions that cannot be described within the framework of the traditional Eyring's transition state theory (TST). With the growing number and importance of these reactions in organic and biosynthetic chemistry, there is also an increasing demand for a theoretical tool that would allow for the accurate quantification of reaction outcome at low cost. Here, we introduce such an approach that fulfils these criteria, by evaluating bifurcation selectivity through the energy distribution within the reactive mode of the key transition state. The presented method yields an excellent agreement with experimentally reported product ratios and predicts the correct selectivity for 89% of nearly 50 various cases, covering pericyclic reactions, rearrangements, fragmentations and metal-catalyzed processes as well as a series of trifurcating reactions. With 71% of product ratios determined within the error of less than 20%, we also found that the methodology outperforms three other tested protocols introduced recently in the literature. Given its predictive power, the procedure makes reaction design feasible even in the presence of complex non-TST chemical steps.
分叉反应从单一过渡态产生两种不同的产物，因此是无法在传统的艾林过渡态理论（TST）框架内描述的反应的典型例子。随着这些反应在有机化学和生物合成化学中的数量不断增加且重要性日益凸显，对一种能够以低成本准确量化反应结果的理论工具的需求也在不断增长。在此，我们介绍一种满足这些标准的方法，即通过关键过渡态反应模式内的能量分布来评估分叉选择性。所提出的方法与实验报道的产物比例具有极好的一致性，并且对近50个各种不同的案例中的89%预测出了正确的选择性，涵盖周环反应、重排反应、碎片化反应、金属催化过程以及一系列三叉反应。在71%的产物比例测定误差小于20%的情况下，我们还发现该方法优于文献中最近引入的其他三种经过测试的方案。鉴于其预测能力，即使存在复杂的非TST化学步骤，该程序也使反应设计变得可行。
