Magnetisation transfer NMR spectroscopy in a kinetic and mechanistic study of fluoride transfer from tetra-n-butylammonium difluorotriphenylsilicate (TBAT)

Abstract

Tetra-n-butylammonium difluorotriphenylsilicate (ⁿBu₄NPh₃SiF₂, known as TBAT) is a pentacoordinate silicon-based fluoride source, commonly used in nucleophilic fluorinations and as an anionic initiator. The mechanism via which TBAT transfers the fluoride is not understood, but prior studies have shown that the process is rapid with respect to standard in situ NMR spectroscopic measurements. We used two ¹⁹F magnetisation transfer NMR techniques to interrogate the process directly: ¹⁹F chemical exchange saturation transfer (CEST) to examine whether TBAT dissociates into fluorotriphenylsilane (Ph₃SiF, FTPS) and tetra-n-butylammonium fluoride (ⁿBu₄NF, TBAF) in solution; and ¹⁹F inversion transfer to interrogate the kinetics and mechanism of fluoride transfer from TBAT.

We first derived analytical solutions which describe the kinetics of ¹⁹F magnetisation transfer in mixtures of TBAT and the appropriate fluoride acceptors, in the inversion transfer experiments. These kinetic models enabled the interrogation of the transfer pathways in the systems, as the dependence of the magnetisation transfer rate between the spins on concentrations of the involved species varies between the proposed mechanisms in each system.

CEST experiments showed that in THF and MeCN, TBAT dissociates reversibly into FTPS and TBAF. The degree of dissociation is low and the spins exchange rapidly at 300 K. Depending on the amount of adventitious water, TBAF may be involved in further equilibria or decompose. Tetra-n-butylammonium bifluoride (ⁿBu₄NF₂, TBABF) is likely formed in either case.

Preliminary inversion transfer experiments showed a very rapid exchange between TBAT and FTPS in their equilibrium mixture in THF. An inherent temporal instability was observed, whereby the rate of exchange between the spins increased over time in closed systems (under N2 atmosphere). Upon screening of potential stabilising conditions, it was found that two additives, 2,6-di-tert-butylpyridine and 3 ̊Å̱ molecular sieves, reversed the trend when used concurrently, slowing down the reaction until temporal stability of exchange rate in the system was reached. The effect of concentration of FTPS under these conditions (at a constant concentration of TBAT) showed that both dissociative and direct pathways proceed in parallel. The dissociative pathway was also confirmed in the non-stabilised system by observing an initial decrease of the inversion transfer rate in a rapid titration of a concentrated solution of TBAT with small aliquots of FTPS.

Inversion transfer between TBAT and 2-naphthalenyl fluorosulfate (ArOSO2F, ARSF) was detected in MeCN at 300 K, and inhibited to below the detection limit upon addition of exogeneous FTPS (~4 mM). At 335 K, progressive inhibition of the exchange was observed in solutions of TBAT and ARSF in MeCN due to decomposition of TBAT and hence formation of FTPS.

Overall, we postulate that the fluoride transfer from TBAT occurs via both dissociative and direct transfer pathways proceeding in parallel, and that the contributions of these pathways are dependent upon the conditions (solvent, temperature, adventitious water, nature and concentration of the fluoride acceptor etc.).

Moreover, ¹H diffusion analysis of TBAT in THF-d₈ and MeCN-d₃ indicated strong ion pairing, confirmed by the observation of nuclear Overhauser effect (NOE) between the ¹H spins of ⁿBu₄N⁺ and Ph₃SiF₂₋. .