Transition State Force Field for the Asymmetric Redox-Relay Heck Reaction
Transition State Force Field for the Asymmetric Redox-Relay Heck Reaction
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DOI：
10.1021/jacs.0c01979
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发表时间：
2020-05-27
影响因子：
15
通讯作者：
Wiest, Olaf
中科院分区：
文献类型：
--
作者：
Rosales, Anthony R.;Ross, Sean P.;Wiest, Olaf
利用量子引导分子力学（Q2MM）方法建立了一个过渡态力场（TSFF）来描述一系列多取代烯烃的对映选择性氧化还原-接力Heck反应的立体决定迁移插入步骤。通过对151种实验确定的立体选择性的外部验证，我们表明TSFF具有很高的预测性，其R-2为0.89，MUE为1.8 kJ/mol。此外，通过将TSFF结果与DFT水平计算结果进行比较，确定了底层力场的局限性。在31例由三种TSFF预测的对映体与最初发表的值不同的情况下，证明了TSFF的新应用。对绝对构型的实验测定表明，计算预测是准确的，这表明TSFFs可以用于一类反应的绝对立体化学的快速预测。最后，利用TSFF和简单的分子相关方法进行虚拟配体筛选。两种方法都具有类似的预测性，但TSFF通过可移植性、速度和可解释性显示出更大的效用。
A transition state force field (TSFF) was developed using the quantum-guided molecular mechanics (Q2MM) method to describe the stereodetermining migratory insertion step of the enantioselective redox-relay Heck reaction for a range of multisubstituted alkenes. We show that the TSFF is highly predictive through an external validation of the TSFF against 151 experimentally determined stereoselectivities resulting in an R-2 of 0.89 and MUE of 1.8 kJ/mol. In addition, limitations in the underlying force field were identified by comparison of the TSFF results to DFT level calculations. A novel application of the TSFF was demonstrated for 31 cases where the enantiomer predicted by thee TSFF differed from the originally published values. Experimental determination of the absolute configuration demonstrated that the computational predictions were accurate, suggesting that TSFFs can be used for the rapid prediction of the absolute stereochemistry for a class of reactions. Finally, a virtual ligand screen was conducted utilizing both the TSFF and a simple molecular correlation method. Both methods were similarly predictive, but the TSFF was able to show greater utility through transferability, speed, and interpretability.