Unusual KIE and dynamics effects in the Fe-catalyzed hetero-Diels-Alder reaction of unactivated aldehydes and dienes
Unusual KIE and dynamics effects in the Fe-catalyzed hetero-Diels-Alder reaction of unactivated aldehydes and dienes
复制标题
Fe 催化未活化醛和二烯的杂狄尔斯-阿尔德反应中异常的 KIE 和动力学效应
DOI：
10.1038/s41467-020-15599-w
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发表时间：
2020
影响因子：
16.6
通讯作者：
Lung Wa Chung
中科院分区：
文献类型：
--
作者：
Yuhong Yang;Xiaoyong Zhang;Li-Ping Zhong;Jialing Lan;Xin Li;Chuang-Chuang Li;Lung Wa Chung
Hetero-Diels-桤木（HDA）反应是合成许多天然产物的重要方法。铁（III）催化剂被开发用于催化具有挑战性的未活化的醛和二烯的HDA反应，具有高选择性。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，显示铁（包括其配位模式和/或自旋状态）对该反应的动力学的影响：大大增强动态逐步过程，加宽入口通道和缩小出口通道从协调异步过渡态。此外，我们的计算和实验相结合的二级KIE研究揭示了出乎意料的大KIE值的五配位途径，即使有相当大的C-C键形成，由于平衡同位素效应的金属配位的变化。此外，空间和电子效应的计算表明，决定的C=O的α，β-不饱和醛的化学选择性，这是实验验证。我们的机理研究可能有助于设计均相，多相和生物催化剂，这一具有挑战性的反应。
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.