Issue 48, 2020

What can reaction databases teach us about Buchwald–Hartwig cross-couplings?


Despite the widespread and increasing usage of Pd-catalyzed C–N cross couplings, finding good conditions for these reactions can be challenging. Practitioners mostly rely on few methodology studies or anecdotal experience. This is surprising, since the advent of data-driven experimentation and the large amount of knowledge in databases allow for data-driven insight. In this work, we address this by analyzing more than 62 000 Buchwald–Hartwig couplings gathered from CAS, Reaxys and the USPTO. Our meta-analysis of the reaction performance generates data-driven cheatsheets for reaction condition recommendation. It also provides an interactive tool to find rarer ligands with optimal performance regarding user-selected substrate properties. With this we give practitioners promising starting points. Furthermore, we study bias and diversity in the literature and summarize the current state of the reaction data, including its pitfalls. Hence, this work will also be useful for future data-driven developments such as the optimization of reaction conditions via machine learning.

Graphical abstract: What can reaction databases teach us about Buchwald–Hartwig cross-couplings?

Supplementary files

Article information

Article type
Edge Article
25 Jul 2020
19 Oct 2020
First published
20 Oct 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2020,11, 13085-13093

What can reaction databases teach us about Buchwald–Hartwig cross-couplings?

M. Fitzner, G. Wuitschik, R. J. Koller, J. Adam, T. Schindler and J. Reymond, Chem. Sci., 2020, 11, 13085 DOI: 10.1039/D0SC04074F

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