Rapid Evaluation of the Mechanism of Buchwald–Hartwig Amination and Aldol Reactions Using Intramolecular 13C Kinetic Isotope Effects,ACS Catalysis

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Rapid Evaluation of the Mechanism of Buchwald–Hartwig Amination and Aldol Reactions Using Intramolecular 13C Kinetic Isotope Effects
ACS Catalysis ( IF 11.3 ) Pub Date : 2020-12-11 , DOI: 10.1021/acscatal.0c04752
Victor Wambua ₁ , Jennifer S Hirschi ₁ , Mathew J Vetticatt ₁

Affiliation

A practical approach is introduced for the rapid determination of ¹³C kinetic isotope effects that utilizes a “designed” reactant with two identical reaction sites. The mechanism of the Buchwald–Hartwig amination of tert-butylbromobenzene with primary and secondary amines is investigated under synthetically relevant catalytic conditions using traditional intermolecular ¹³C NMR methodology at natural abundance. Switching to 1,4-dibromobenzene, a symmetric bromoarene as the designed reactant, the same experimental ¹³C KIEs are determined using an intramolecular KIE approach. This rapid methodology for KIE determination requires substantially less material and time compared to traditional approaches. Details of the Buchwald–Hartwig amination mechanism are investigated under varying synthetic conditions, namely a variety of halides and bases. The enantioselectivity-determining step of the l-proline catalyzed aldol reaction is also evaluated using this approach. We expect this mechanistic methodology to gain traction among synthetic chemists as a practical technique to rapidly obtain high-resolution information regarding the transition structure of synthetically relevant reactions under catalytic conditions.

中文翻译：

使用分子内 13C 动力学同位素效应快速评估 Buchwald-Hartwig 胺化和羟醛反应的机制

介绍了一种实用的方法来快速测定¹³ C 动力学同位素效应，该方法利用具有两个相同反应位点的“设计”反应物。在合成相关的催化条件下，使用传统的分子间¹³ C NMR 方法在天然丰度下研究了叔丁基溴苯与伯胺和仲胺的 Buchwald-Hartwig 胺化机制。切换到 1,4-二溴苯，一种对称的溴芳烃作为设计的反应物，相同的实验¹³ C KIE 使用内部分子 KIE 方法。与传统方法相比，这种快速测定 KIE 方法所需的材料和时间要少得多。在不同的合成条件下，即各种卤化物和碱，研究了 Buchwald-Hartwig 胺化机制的细节。所述的对映选择性确定步骤升-脯氨酸催化的醛醇缩合反应是使用这种方法也进行评价。我们希望这种机械方法在合成化学家中获得牵引力，作为一种实用技术，可以快速获得有关催化条件下合成相关反应的过渡结构的高分辨率信息。

更新日期：2021-01-01

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