Wambua Victor, Hirschi Jennifer S, Vetticatt Mathew J
Department of Chemistry, Binghamton University, Binghamton, New York 13902, United States.
ACS Catal. 2021 Jan 1;11(1):60-67. doi: 10.1021/acscatal.0c04752. Epub 2020 Dec 11.
A practical approach is introduced for the rapid determination of C kinetic isotope effects that utilizes a "designed" reactant with two identical reaction sites. The mechanism of the Buchwald-Hartwig amination of -butylbromobenzene with primary and secondary amines is investigated under synthetically relevant catalytic conditions using traditional molecular C NMR methodology at natural abundance. Switching to 1,4-dibromobenzene, a symmetric bromoarene as the designed reactant, the same experimental C KIEs are determined using an molecular 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.
介绍了一种快速测定碳动力学同位素效应的实用方法，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，使用天然丰度的传统分子碳核磁共振方法，研究了对溴丁基苯与伯胺和仲胺的布赫瓦尔德-哈特维希胺化反应机理。改用1,4-二溴苯，一种对称的溴代芳烃作为设计反应物，使用分子动力学同位素效应方法测定相同的实验碳动力学同位素效应。与传统方法相比，这种快速测定动力学同位素效应的方法所需的材料和时间大大减少。在不同的合成条件下，即各种卤化物和碱，研究了布赫瓦尔德-哈特维希胺化反应机理的细节。还使用这种方法评估了L-脯氨酸催化的羟醛反应的对映选择性决定步骤。我们期望这种机理方法作为一种实用技术，在合成化学家当中获得认可，以快速获得有关催化条件下合成相关反应过渡结构的高分辨率信息。
