Closed-loop optimization of general reaction conditions for heteroaryl Suzuki-Miyaura coupling

Nicholas H. Angello, Vandana Rathore, Wiktor Beker, Agnieszka Wołos, Edward R. Jira, Rafał Roszak, Tony C. Wu, Charles M. Schroeder, Alán Aspuru-Guzik, Bartosz A. Grzybowski, Martin D. Burke

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)399-405
Number of pages7
Issue number6618
StatePublished - Oct 28 2022

ASJC Scopus subject areas

  • General


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