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Discovery of a Difluoroglycine Synthesis Method through Quantum Chemical Calculations

preprint
submitted on 08.01.2020 and posted on 09.01.2020 by Tsuyoshi Mita, Yu Harabuchi, Satoshi Maeda
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 decomposition paths of the target product and propose 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 seemingly most promising path led to the discovery of a synthesis method for the difluoroglycine derivative. 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.

Funding

Grant-in-Aid for Scientific Research (C) (No. 18K05096)

JST-CREST (No. JPMJCR14L5)

JST-PRESTO (No. JPMJPR16N8)

JST-ERATO (No. JPMJER1903)

JSPS-WPI

Astellas Foundation for Research on Metabolic Disorders

History

Email Address of Submitting Author

smaeda@eis.hokudai.ac.jp

Institution

Hokkaido University

Country

Japan

ORCID For Submitting Author

0000-0001-8822-1147

Declaration of Conflict of Interest

The authors declare no competing interests.

Exports