Computational Insight Into the Enantioselectivity of Homoboroproline Catalyzed Asymmetric Aldol Reaction
Computational Insight Into the Enantioselectivity of Homoboroproline Catalyzed Asymmetric Aldol Reaction
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DOI：
10.1002/slct.201901737
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发表时间：
2019-07-23
期刊：
影响因子：
2.1
通讯作者：
Erdem, Safiye S.
中科院分区：
文献类型：
--
作者：
Dulger, Habibe;Sari, Ozlem;Erdem, Safiye S.
手性氨基硼酸及其衍生物在酶抑制剂、抗癌药和分子传感器等领域有着广泛的应用。它们还作为有效的催化剂吸引了人们的注意。最近合成了一种新的基于脯氨酸的氨基硼酸衍生物--高硼脯氨酸，并证明其在不对称羟醛缩合反应中是有效的催化剂。本研究首次阐明了该反应的机理。在丙酮中，考虑到烯胺中间体和醛的不同取向，采用密度泛函理论(DFT)方法，采用PCM/M06-2X/6-31G(d，p)方法对可能的取代机理进行了模拟。探索了每个反应机理的势能面，建立了确定反应速率和对映体选择性的步骤。计算的对映体过量值(~gt；99%)与实验值(93%，95%)符合较好。对选择性决定步骤的过渡态结构的详细研究表明，天然键轨道(NBO)分析证实了选择性是由硼和醛氧之间的吸引作用造成的。这些结果为解释高硼脯氨酸催化的不对称羟醛缩合反应中对映体选择性的起源提供了依据。
Chiral amino boronic acids and their derivatives have a wide range of applications including enzyme inhibitors, anti-cancer agents and molecular sensors. They also draw attention as effective catalysts. Recently, a new proline based amino boronic acid derivative, homoboroproline, was synthesized and demonstrated to be an efficient catalyst in an asymmetric aldol reaction. The reaction mechanism has been elucidated in the present study for the first time. Considering different orientations of the enamine intermediate and the aldehyde, potential alternative mechanisms were modeled with density functional theory (DFT) calculations via PCM/M06-2X/6-31G(d,p) method in acetone. The potential energy surface of each mechanism was explored to establish the rate-determining and enantioselectivity-determining steps. The calculated enantiomeric excess values (>99%) were found to be in agreement with the experimental values (93%, 95%). The detailed investigation of the transition state structures of the selectivity-determining step has revealed that attractive interactions between boron and aldehyde oxygen are responsible for the selectivity confirmed by natural bond orbital (NBO) analysis. The results provide insight into the origin of enantioselectivity in asymmetric aldol reaction catalyzed by homoboroproline.