Data-driven design of Next Generation Cross-Coupling catalysts by Ligand Parameterisation: A Combined Experimental and Computational Approach.

在复杂分子的合成中，与已经富含官能团的化合物反应的能力提出了持续的挑战。这在催化转化中尤其如此，并且是贱金属介导的反应的主要限制。在这项合作工作的初步结果已经确定了非常低的金属负载量（0.5摩尔%），同时显示出显着的官能团的宽容高度有效的铜催化剂。我们的设计是基于双齿配体含有一个N-杂环卡宾（NHC）和一个半不稳定的第二配位位点，产生可分离的和空气稳定的铜配合物。本项目的主要目的是设计改进的配体，具有广泛的适用性和效率在一系列的交叉偶联反应。而不是繁琐的优化研究，为每种类型的亲核试剂，我们提出的分类和参数化的双齿配体使用新的动态描述符。预测的命中将通过实验验证，以开发一套铜催化剂，以形成具有高官能团耐受性的芳基-O，芳基-N和芳基-CF 3键。总的来说，这项工作将提供一个定量的洞察力配体的性质，铜介导的转化和最终的国家的最先进的催化系统，在精细化工行业中最常用的转换之一的理解。

In the synthesis of complex molecules, the ability to react already functional group rich compounds presents an ongoing challenge. This is particularly true in catalytic transformations, and a major limitation of base metal mediated reactions. Preliminary results in this collaborative work have identified highly effective copper catalysts at very low metal loadings (0.5 mol %) while displaying remarkable functional group tolerance. Our design is based on bidentate ligands containing an N-heterocyclic carbene (NHC) and a hemilabile second coordination site that produces isolable and air stable copper complexes.The main purpose of this project is to design improved ligands with broad applicability and efficiency in a range of cross-coupling reactions. Instead of tedious optimisation studies for each type of nucleophile, we propose the classification and parametrisation of bidentate ligands using novel dynamic descriptors. Predicted hits will be validated experimentally to develop a suite of copper catalysts to form aryl-O, aryl-N and aryl-CF3 bonds with high functional group tolerance. Overall, this work will provide a quantitative insight to ligand properties, an improved understanding of copper-mediated transformations and ultimately state-of-the-art catalytic systems for one of the most commonly employed transformations in fine chemical industry.