One ambimodal transition state can lead to the formation of multiple products. However, it remains fundamentally unknown how the energy and entropy along the post-TS pathways mediate ambimodal selectivity. Here, we investigated the energy and entropy profiles along the post-TS pathways in four [4 + 2]/[6 + 4] cycloadditions. We observe that the pathway leading to the minor product involves a more pronounced entropic trap. These entropic traps, resulting from the conformational change in the dynamic course of ring closure, act as a reservoir of longer-lived dynamic intermediates that roam on the potential energy surface and have a higher likelihood of redistributing to form the other product. The SpnF-catalyzed Diels-Alder reaction produces [4 + 2] and [6 + 4] adducts with nearly equal product distribution and relatively flat energy profiles, in contrast to other cycloadditions. Unexpectedly, the entropy profiles for these two adducts are distinctly different. The formation of the [6 + 4] adduct encounters an entropic barrier acting as a dynamical bottleneck, while the [4 + 2] adduct involves a substantial entropic trap to maintain long-lived intermediates. These opposing effects hinder both product formations and likely cancel each other out so that an equal product distribution is observed.

中文翻译：

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能量和熵之间的相互作用介导了环加成反应的双峰选择性。


一个双峰过渡态会导致多个乘积的形成。然而，从 根本上来说，沿 TS 后通路的能量和熵如何介导双峰选择性仍然未知。在这里，我们研究了四种 [4 + 2]/[6 + 4] 环加成反应中沿 post-TS 通路的能量和熵分布。我们观察到，通向次要产物的途径涉及一个更明显的熵陷阱。这些熵陷阱是由闭环动力学过程中的构象变化引起的，充当在势能表面漫游的长寿命动态中间体的储存库，并且具有更高的重新分布以形成另一种产物的可能性。与其他环加成反应相比，SpnF 催化的 Diels-Alder 反应产生 [4 + 2] 和 [6 + 4] 加合物，这些加合物具有几乎相等的产物分布和相对平坦的能量分布。出乎意料的是，这两种加合物的熵分布明显不同。[6 + 4] 加合物的形成遇到了作为动力学瓶颈的熵势垒，而 [4 + 2] 加合物涉及一个实质性的熵陷阱，以维持长寿命的中间体。这些相反的效应阻碍了两种产物的形成，并可能相互抵消，从而观察到相等的产物分布。