Stopped‐Flow ¹⁹F NMR Spectroscopic Analysis of a Protodeboronation Proceeding at the Sub‐Second Time‐Scale

Abstract

In‐situ NMR spectroscopic analysis of homogeneous reactions is an essential tool for mechanistic analysis in organic and organometallic chemistry. However, rapid non‐equilibrium reactions, that are initiated by mixing, require specialized approaches. We report herein on a study of the factors that ensure quantitative results in a recently‐developed technique for stopped‐flow NMR spectroscopy. The influence of some of the key parameters on quantitation is studied by 19F NMR spectroscopic analysis of the kinetics and activation parameters for the base‐catalyzed protodeboronation of highly‐reactive polyfluorinated arylboronic acids, with half‐lives as low as 0.1 seconds. The effects of spin relaxation, pre‐magnetization, heat‐transfer versus reaction enthalpy, and mixing‐efficiency are analyzed in detail. We also compare and contrast choice of pulse angle, interscan delay, and use of pseudo real‐time by interleaving, as means to achieve an optimal balance between temporal resolution and sensitivity.

New 19F NMR methodology reveals structures of molecules in complex mixtures of fluorinated compounds

“…Another frequent application of 19 F NMR comes from using fluorinated molecule as one of the reactants in studies of mechanisms and kinetics of chemical reactions. 27,28 The methodology presented here aims to make the process of structure elucidation of fluorine-containing molecules contained in (complex) mixtures more efficient. It follows the "NMR spies" approach, where 13 C labelled tags provide information about the nuclei in their vicinity, 29,30 leading to structural characterisation of molecules.…”

“…Another frequent application of 19 F NMR comes from using a fluorinated molecule as one of the reactants in studies of mechanisms and kinetics of chemical reactions. 27,28…”

19F-centred NMR analysis of mono-fluorinated compounds

“…In a similar manner, 19 F NMR has also been used for probing the mechanism and kinetics of chemical reactions, were fluorine is a convenient reporter of the processes taking place. 22,23…”

“…In a similar manner, 19 F NMR has also been used for probing the mechanism and kinetics of chemical reactions, were uorine is a convenient reporter of the processes taking place. 22,23 In support of such wide ranging activities, we have developed a 19 F-centred NMR approach for the analysis of mono-uorinated compounds, taking 19 F NMR beyond recording simple 1D NMR spectra. Put together, the information obtained allows the structure elucidation of uorine-containing molecular moieties and complete structure determination of small uorine-containing molecules.…”

Pressurized Sample Infusion

“…Nuclear Magnetic Resonance (NMR) spectroscopy offers real‐time data acquisition when equipped with a flow system [4,5] or a stopped‐flow system [6–8] . This allows for reaction intermediates to be observed, provided they are not short‐lived and produced in high enough concentrations.…”