Closed-loop optimization of general reaction conditions for heteroaryl Suzuki-Miyaura coupling
Closed-loop optimization of general reaction conditions for heteroaryl Suzuki-Miyaura coupling
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DOI：
10.1126/science.adc8743
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发表时间：
2022-10-28
期刊：
影响因子：
56.9
通讯作者：
Burke, Martin D.
中科院分区：
文献类型：
--
作者：
Angello, Nicholas H.;Rathore, Vandana;Burke, Martin D.
有机反应的一般条件是重要的，但很少，并且确定它们的努力通常只考虑化学空间的狭窄区域。发现更一般的反应条件需要考虑来自与反应条件的高维矩阵交叉的大基质矩阵的化学空间的广大区域，使得详尽的实验不切实际。在这里，我们报告了一个简单的闭环工作流程，该工作流程利用数据引导的矩阵向下选择，不确定性最小化机器学习和机器人实验来发现一般反应条件。应用于杂芳基铃木-宫浦交叉偶联的具有挑战性和后果性的问题，确定了相对于先前使用传统方法开发的广泛使用的基准，平均产率加倍的条件。该研究为解决具有大搜索空间的多维化学优化问题提供了一个实用的路线图。
General conditions for organic reactions are important but rare, and efforts to identify them usually consider only narrow regions of chemical space. Discovering more general reaction conditions requires considering vast regions of chemical space derived from a large matrix of substrates crossed with a high-dimensional matrix of reaction conditions, rendering exhaustive experimentation impractical. Here, we report a simple closed-loop workflow that leverages data-guided matrix down-selection, uncertainty-minimizing machine learning, and robotic experimentation to discover general reaction conditions. Application to the challenging and consequential problem of heteroaryl Suzuki-Miyaura cross-coupling identified conditions that double the average yield relative to a widely used benchmark that was previously developed using traditional approaches. This study provides a practical road map for solving multidimensional chemical optimization problems with large search spaces.