Neshat Rozatian
Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives
Rozatian, Neshat; Beeby, Andrew; Ashworth, Ian W.; Sandford, Graham; Hodgson, David R.W.
Authors
Professor Andrew Beeby andrew.beeby@durham.ac.uk
Professor
Ian W. Ashworth
Graham Sandford
Professor David Hodgson d.r.w.hodgson@durham.ac.uk
Professor
Abstract
Fluorine-containing 1,3-dicarbonyl derivatives are essential building blocks for drug discovery and manufacture. To understand the factors that determine selectivity between mono- and di-fluorination of 1,3-dicarbonyls systems, we have performed kinetic studies of keto-enol tautomerism and fluorination processes. Photoketonization of 1,3-diaryl-1,3-dicarbonyl derivatives and their 2-fluoro analogues is coupled with relaxation kinetics to determine enolization rates. Reaction additives such as water accelerate enolization processes, especially of 2-fluoro-1,3-dicarbonyl systems. Kinetic studies of enol fluorination with Selectfluor™ and NFSI reveal the quantitative effects of 2-fluorination upon enol nucleophilicity towards reagents of markedly different electrophilicity. Our findings have important implications for the synthesis of α,α-difluoroketonic compounds, providing valuable quantitative information to aid in the design of fluorination and difluorination reactions.
Citation
Rozatian, N., Beeby, A., Ashworth, I. W., Sandford, G., & Hodgson, D. R. (2019). Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives. Chemical Science, 10(44), 10318-10330. https://doi.org/10.1039/c9sc04185k
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 16, 2019 |
Online Publication Date | Sep 16, 2019 |
Publication Date | Nov 28, 2019 |
Deposit Date | Sep 16, 2019 |
Publicly Available Date | Jan 8, 2020 |
Journal | Chemical Science |
Print ISSN | 2041-6520 |
Electronic ISSN | 2041-6539 |
Publisher | Royal Society of Chemistry |
Peer Reviewed | Peer Reviewed |
Volume | 10 |
Issue | 44 |
Pages | 10318-10330 |
DOI | https://doi.org/10.1039/c9sc04185k |
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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/
Copyright Statement
This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
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