Quantifying the Reactivity of a Remarkably Long-Lived Difluorinated Enol in Acidic Methanol via Solution Kinetics and Electronic Structure Calculations

Abstract

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Toluene Dioxygenase-Catalyzed Synthesis and Reactions of cis-Diol Metabolites Derived from 2- and 3-Methoxyphenols

“…Ethenol and prop-1-en-2-ol are sufficiently long-lived in a dilute solution of an aprotic solvent, at room temperature, to allow the NMR spectra of these species to be recorded. An O -deuterated enol with two fluorine atoms on the α-carbon has a half-life greater than 2 weeks in neutral methanol- d 4 . Cyclohexa-1,3-dienol has a half-life of 5 s, further demonstrating the longevity of enols in aqueous media.…”

“…An O-deuterated enol with two fluorine atoms on the α-carbon has a half-life greater than 2 weeks in neutral methanol-d 4 . 52 Cyclohexa-1,3-dienol has a half-life of 5 s, 53 further demonstrating the longevity of enols in aqueous media. However, the proton transfer is greatly facilitated in protic solvents, with most studies undertaken in water as solvent, catalyzed both by acid and base.…”

Reactions of Aldehydes and Ketones and their Derivatives

“…A DFT study of a simple model, 2,2-difluoroethenol, indicates that there are significant differences in timing of the protonation TS compared with the non-fluorinated enol. 288 Keto-enol tautomerization of 3-hydropyridazine derivatives has been investigated using DFT: the 2-hydropyridazin-3-one tautomer is typically found to be the most stable. 289 Triethylgallium has been used as a non-nucleophilic base to generate enolates from ketones, both cyclic and acyclic, without forming carbonyl addition products.…”

Atom Efficient Synthesis of Selectively Difluorinated Carbocycles through a Gold(I)-Catalyzed Cyclization

“…A more atom efficient cyclization based on difluorinated enol acetal nucleophiles would therefore be an attractive approach. While such species have proved effective substrates in sigmatropic rearrangements, their reactivity as nucleophiles has not been exploited in synthesis . We envisioned that these species could be utilized in a divergent synthetic strategy to afford either difluorinated diols or pyrans through a gold­(I)-catalyzed cyclization (Scheme ).…”