Discovery of a Difluoroglycine Synthesis Method through Quantum Chemical Calculations

09 January 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


multi-component assembly
retrosynthetic analysis
quantum chemical calculation
automated reaction path search

Supplementary materials

Mita etal 0108 SI ChemRxiv


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