Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives

Autor:	Ian W. Ashworth, Andrew Beeby, Neshat Rozatian, Graham Sandford, David R. W. Hodgson
Rok vydání:	2019
Předmět:	010405 organic chemistry Chemistry General Chemistry Keto–enol tautomerism 010402 general chemistry 01 natural sciences Enol Tautomer 0104 chemical sciences Relaxation kinetics chemistry.chemical_compound Nucleophile Computational chemistry Reagent Electrophile Selectivity
Zdroj:	Chemical science, 2019, Vol.10(44), pp.10318-10330 [Peer Reviewed Journal]
ISSN:	2041-6539 2041-6520
DOI:	10.1039/c9sc04185k
Popis:	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.
Databáze:	OpenAIRE
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