Issue 29, 2020

Discovery of a synthesis method for a difluoroglycine derivative based on a path generated by quantum chemical calculations

Abstract

The systematic exploration of synthetic pathways to afford a desired product through quantum chemical calculations remains a considerable challenge. In 2013, Maeda et al. introduced ‘quantum chemistry aided retrosynthetic analysis’ (QCaRA), which uses quantum chemical calculations to search systematically for the decomposition paths of a target product and proposes a synthesis method. However, until now, no new reactions suggested by QCaRA have been reported to lead to experimental discoveries. Using a difluoroglycine derivative as a target, this study investigated the ability of QCaRA to suggest various synthetic paths to the target without relying on previous data or the knowledge and experience of chemists. Furthermore, experimental verification of the most promising path chosen by an organic chemist among the predicted paths led to the discovery of a synthesis method for a difluoroglycine derivative. We emphasize that the purpose of this study is not to propose a fully automated workflow. Therefore, the extent of the hands-on expertise of chemists required during the verification process was also evaluated. These insights are expected to advance the applicability of QCaRA to the discovery of viable experimental synthetic routes.

Graphical abstract: Discovery of a synthesis method for a difluoroglycine derivative based on a path generated by quantum chemical calculations

Supplementary files

Article information

Article type
Edge Article
Submitted
13 4 2020
Accepted
21 5 2020
First published
22 5 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-NC license

Chem. Sci., 2020,11, 7569-7577

Discovery of a synthesis method for a difluoroglycine derivative based on a path generated by quantum chemical calculations

T. Mita, Y. Harabuchi and S. Maeda, Chem. Sci., 2020, 11, 7569 DOI: 10.1039/D0SC02089C

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