School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, China.
Shenzhen Grubbs Institute, Department of Chemistry and Guangdong Provincial Key Laboratory of Catalytic Chemistry, Southern University of Science and Technology, Shenzhen, 518055, China.
Nat Commun. 2020 Apr 15;11(1):1850. doi: 10.1038/s41467-020-15599-w.
Hetero-Diels-Alder (HDA) reaction is an important synthetic method for many natural products. An iron(III) catalyst was developed to catalyze the challenging HDA reaction of unactivated aldehydes and dienes with high selectivity. Here we report extensive density-functional theory (DFT) calculations and molecular dynamics simulations that show effects of iron (including its coordinate mode and/or spin state) on the dynamics of this reaction: considerably enhancing dynamically stepwise process, broadening entrance channel and narrowing exit channel from concerted asynchronous transition states. Also, our combined computational and experimental secondary KIE studies reveal unexpectedly large KIE values for the five-coordinate pathway even with considerable C-C bond forming, due to equilibrium isotope effect from the change in the metal coordination. Moreover, steric and electronic effects are computationally shown to dictate the C=O chemoselectivity for an α,β-unsaturated aldehyde, which is verified experimentally. Our mechanistic study may help design homogeneous, heterogeneous and biological catalysts for this challenging reaction.
Hetero-Diels-Alder (HDA) 反应是许多天然产物的重要合成方法。我们开发了一种铁(III)催化剂，用于催化高选择性的未活化醛和二烯的具有挑战性的 HDA 反应。在这里，我们报告了广泛的密度泛函理论 (DFT) 计算和分子动力学模拟，这些计算和模拟表明了铁（包括其配位模式和/或自旋态）对反应动力学的影响：极大地增强了动态分步过程，拓宽了入口通道，缩小了协同异步过渡态的出口通道。此外，我们结合计算和实验的次级 KIE 研究揭示了即使在相当大的 C-C 键形成的情况下，五配位途径的 KIE 值也出乎意料地大，这是由于金属配位变化引起的平衡同位素效应。此外，计算表明空间位阻和电子效应对α,β-不饱和醛的 C=O 化学选择性有影响，这在实验中得到了验证。我们的机理研究可能有助于设计用于该挑战性反应的均相、多相和生物催化剂。
Zotero 插件
