Tribedi Soumi, Kitaura Kazuo, Nakajima Takahito, Sunoj Raghavan B
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Phys Chem Chem Phys. 2021 Sep 14;23(34):18936-18950. doi: 10.1039/d1cp02499j. Epub 2021 Aug 24.
The origin of enantioselectivity in asymmetric catalysis is often built around the differential steric interaction in the enantiocontrolling transition states (TSs). A closer perusal of enantiocontrolling TSs in an increasingly diverse range of reactions has revealed that the cumulative effect of weak noncovalent interactions could even outweigh the steric effects. While enunciating this balance is conspicuously important, quantification of such intramolecular forces within a TS continues to remain scarce and challenging. Herein, we demonstrate the utility of the fragment molecular orbital method in establishing the relative contributions of various attractive and repulsive contributions in the total interaction energy between the suitably chosen fragments in enantiocontrolling TSs. Three types of reactions of high contemporary importance, namely, axially chiral phosphoric acid (CPA) catalyzed kinetic resolution of rac-α-methyl-γ-hydroxy ester (reaction I), asymmetric dearomative amination of β-naphthols by dimethyl azodicarboxylate (IIa and IIb), and intramolecular desymmetrization of β,β-disubstituted methyl oxetanes (IIIa) and hydroxyl oxetane (IIIb), bearing a tethered alcohol (-OCHCHOH or -(CH)CHOH), are considered. In all the five reactions, the differences in the stabilizing contributions arising due to electrostatic, charge-transfer, and dispersion interactions between the catalyst and the reacting partners in the enantiocontrolling transition states are weighed against the destabilizing exchange interaction. The balancing interactions are found to be between dispersion and exchange repulsion in reaction I, a combination of charge transfer and dispersion energies offsets the repulsive energy in reaction IIb involving the electron rich anthryl groups in the catalyst, whereas the -(CF)CH 3,3'-substituent in the catalyst (reaction IIa) leads to a trade-off between dispersion and exchange energies. In reactions IIIa and IIIb, however, electrostatic and dispersion energies help compensate the repulsive interactions. These quantitative insights on the intramolecular interactions in the stereocontrolling TSs could help in the rational design of asymmetric catalysis.
不对称催化中对映选择性的起源通常围绕对映体控制过渡态（TSs）中的不同空间相互作用构建。对越来越多不同反应中对映体控制TSs的更仔细研究表明，弱非共价相互作用的累积效应甚至可能超过空间效应。虽然阐明这种平衡显然很重要，但对TS内这种分子内力的量化仍然稀缺且具有挑战性。在此，我们展示了片段分子轨道方法在确定对映体控制TSs中适当选择的片段之间总相互作用能中各种吸引和排斥贡献的相对贡献方面的效用。考虑了三种具有高度当代重要性的反应类型，即轴手性磷酸（CPA）催化的外消旋α-甲基-γ-羟基酯的动力学拆分（反应I）、偶氮二甲酸二甲酯对β-萘酚的不对称去芳构化胺化反应（IIa和IIb）以及带有连接醇（-OCHCHOH或-(CH)CHOH）的β,β-二取代甲基氧杂环丁烷（IIIa）和羟基氧杂环丁烷（IIIb）的分子内去对称化反应。在所有这五个反应中，对映体控制过渡态中催化剂与反应伙伴之间由于静电、电荷转移和色散相互作用而产生的稳定贡献差异与不稳定的交换相互作用进行权衡。发现在反应I中平衡相互作用存在于色散和交换排斥之间，在反应IIb中涉及催化剂中富电子蒽基的电荷转移和色散能量的组合抵消了排斥能，而催化剂中的-(CF)CH 3,3'-取代基（反应IIa）导致色散和交换能量之间的权衡。然而，在反应IIIa和IIIb中，静电和色散能量有助于补偿排斥相互作用。这些关于立体控制TSs中分子内相互作用的定量见解有助于不对称催化的合理设计。
