An investigation of the kinetics and mechanism of Cu(II)-catalyzed and ligandless CuAAC reactions

沃森小组最近的工作挑战了围绕铜催化的叠氮炔环加成（CuAAC）反应的主流文献。该项目将致力于解决源于这些发现的三个关键目标。1）NaAsc的作用。Fokin之前的工作假设Cu（I）催化体系是“无配体的”，支持涉及CuSO 4和NaAsc的研究。然而，我们的小组已经发现了证据，NaAsc增强了反应，并且它可能是Cu（I）的配体。该项目将寻求确定NaAsC是否作为配体，并探测和分析其对反应动力学的影响。2）基于Cu（II）的CuAAC。围绕NaAsc效应的这些观察结果与Cu（II）促进的CuAAC反应（使用2-乙炔基吡啶）的发现一起进行。为了更好地理解这种机制模式是否具有更大的普遍性，本项目将研究M.G. Finn，如下所示：该项目将寻求使用Finn炔和Cu（II）来描述CuAAC反应，并且，如果Cu（II）催化似乎是可操作的，则将充分探索和绘制该反应。(3)炔基膦酸酯作为Cu（II）基CuAAC试剂的研究。这将旨在建立在目标2）内的任何发现的基础上，其想法是建立用于开发基于Cu（II）的CuAAC反应的一般（预测性）设计标准。

Recent work in the Watson group has challenged the prevailing literature surrounding copper-catalysed, azide alkyne cycloaddition (CuAAC) reactions. This project will aim to tackle three key aims stemming from these findings.1) The role of NaAsc. Prior work by Fokin posited that the Cu(I) catalysed system was 'ligandless', with supporting studies involving CuSO4 and NaAsc. Our group has found evidence, however, that NaAsc enhances the reaction and that it may be a ligand for Cu(I). This project will seek to establish if NaAsC is acting as a ligand and to probe and profile its effect on reaction kinetics.2) Cu(II) based CuAAC. These observations surrounding the effect of NaAsc were made alongside a discovery of a Cu(II)-promoted CuAAC reaction (using 2-ethynyl pyridine). To better understand if there is a greater generality to this mechanistic mode, this project with look at a (similarly) highly conjugated alkyne used by M.G. Finn, as shown below: This project will seek to profile the CuAAC reaction using the Finn alkyne and Cu(II), and, if Cu(II) catalysis seems operational, this reaction will be fully explored and charted.(3) Investigation of alkynyl phosphonates as Cu(II)-based CuAAC reagents. This will aim to build upon any findings within aim 2), with the idea of establishing a general (predictive) design criteria for the development of Cu(II)-based CuAAC reactions.