Theoretical design of new ligands to boost reaction rate and selectivity in palladium-catalyzed aromatic fluorination.

IF 3.4 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Josefredo R Pliego
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引用次数: 0

Abstract

The development of palladium-catalyzed fluorination with biaryl monophosphine ligands has faced two important problems that limit its application for bromoarenes: the formation of regioisomers and insufficient catalysis for heteroaryl substrates as bromothiophene derivatives. Overcoming these problems requires more ligand design. In this work, reliable theoretical calculations were used to elucidate important ligand features necessary for achieving more rate acceleration and selectivity. These features include increasing the ligand-substrate repulsion and creating a negative charge in the space around the fluoride ion bonded to the palladium. The investigated L5 ligand presents these features, and the calculations predict that this ligand completely suppresses the regioisomer formation in the difficult case of 4-bromoanisole. In addition, the free energy barriers are decreased by 2-3 kcal mol-1 in comparison with the catalysis involving the AlPhos ligand. Thus, the present study points out a direction for new developments in palladium-catalyzed fluorination.

Abstract Image

提高钯催化芳烃氟化反应速率和选择性的新配体理论设计。
使用双芳基单膦配体进行钯催化氟化反应的发展面临着两个重要问题,限制了其在溴烯类化合物中的应用:形成区域异构体以及对杂芳基底物(如溴噻吩衍生物)的催化作用不足。克服这些问题需要更多的配体设计。在这项工作中,我们利用可靠的理论计算阐明了配体的重要特征,这些特征对于实现更高的速率加速和选择性是必不可少的。这些特征包括增加配体与底物的排斥力,以及在与钯结合的氟离子周围空间产生负电荷。所研究的 L5 配体具有这些特点,而且计算预测,在 4-溴苯甲醚的困难情况下,这种配体完全抑制了区域异构体的形成。此外,与 AlPhos 配体的催化作用相比,自由能垒降低了 2-3 kcal mol-1。因此,本研究为钯催化氟化反应的新发展指明了方向。
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来源期刊
CiteScore
6.60
自引率
3.30%
发文量
247
审稿时长
1.7 months
期刊介绍: This distinguished journal publishes articles concerned with all aspects of computational chemistry: analytical, biological, inorganic, organic, physical, and materials. The Journal of Computational Chemistry presents original research, contemporary developments in theory and methodology, and state-of-the-art applications. Computational areas that are featured in the journal include ab initio and semiempirical quantum mechanics, density functional theory, molecular mechanics, molecular dynamics, statistical mechanics, cheminformatics, biomolecular structure prediction, molecular design, and bioinformatics.
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