Design and Application of a Screening Set for Monophosphine Ligands in Cross-Coupling
Design and Application of a Screening Set for Monophosphine Ligands in Cross-Coupling
复制标题
DOI：
10.1021/acscatal.2c01970
复制
发表时间：
2022-06-16
期刊：
影响因子：
12.9
通讯作者：
Sigman, Matthew S.
中科院分区：
文献类型：
--
作者：
Gensch, Tobias;Smith, Sleight R.;Sigman, Matthew S.
在反应发现中，离散反应参数（例如催化剂结构）的搜索空间通常没有被系统地探索。我们开发了一套工具来帮助寻找膦配体的最佳催化剂。虚拟库 kraken 代表单齿 P(III)-配体化学空间，被用作将离散配体表示为连续变量的基础。使用降维和聚类技术，我们提出了由 32 个市售配体组成的磷化氢优化筛选集 (PHOSS)，可以完全、均匀地对该化学空间进行采样。我们介绍了该筛选集在识别各种交叉偶联反应的活性催化剂中的应用，并展示了化学空间的均匀分布采样如何促进活性催化剂的识别。此外，我们证明了当已知活性催化剂很少时，配体空间的接近度如何成为进一步探索配体的有用指南。
In reaction discovery, the search space of discrete reaction parameters such as catalyst structure is often not explored systematically. We have developed a tool set to aid the search of optimal catalysts in the context of phosphine ligands. A virtual library, kraken, which is representative of the monodentate P(III)-ligand chemical space, was utilized as the basis to represent the discrete ligands as continuous variables. Using dimensionality reduction and clustering techniques, we suggested a Phosphine Optimization Screening Set (PHOSS) of 32 commercially available ligands that samples this chemical space completely and evenly. We present the application of this screening set in the identification of active catalysts for various cross-coupling reactions and show how well-distributed sampling of the chemical space facilitates identification of active catalysts. Furthermore, we demonstrate how proximity in ligand space can be a useful guide to further explore ligands when very few active catalysts are known.