Kucharski Maciej M, Watson Allan J B, Lloyd-Jones Guy C
School of Chemistry, University of Edinburgh David Brewster Road Edinburgh EH9 3FJ UK
School of Chemistry, University of St Andrews North Haugh, St Andrews KY16 9ST UK.
Chem Sci. 2023 Dec 7;15(12):4331-4340. doi: 10.1039/d3sc05776c. eCollection 2024 Mar 20.
Tetra--butylammonium difluorotriphenylsilicate (TBAT) is a conveniently handled anhydrous fluoride source, commonly used as a surrogate for tetra--butylammonium fluoride (TBAF). While prior studies indicate that TBAT reacts rapidly with fluoride acceptors, little is known about the mechanism(s) of fluoride transfer. We report on the interrogation of the kinetics of three processes in which fluoride is transferred from TBAT, in THF and in MeCN, using a variety of NMR methods, including chemical exchange saturation transfer, magnetisation transfer, diffusion analysis, and 1D NOESY. These studies reveal ion-pairing between the tetra--butylammonium and difluorotriphenylsilicate moieties, and a very low but detectable degree of fluoride dissociation, which then undergoes further equilibria and/or induces decomposition, depending on the conditions. Degenerate exchange between TBAT and fluorotriphenylsilane (FTPS) is very rapid in THF, inherently increases in rate over time, and is profoundly sensitive to the presence of water. Addition of 2,6-di--butylpyridine and 3 Å molecular sieves stabilises the exchange rate, and both dissociative and direct fluoride transfer are shown to proceed in parallel under these conditions. Degenerate exchange between TBAT and 2-naphthalenyl fluorosulfate (ARSF) is not detected at the NMR timescale in THF, and is slow in MeCN. For the latter, the exchange is near-fully inhibited by exogenous FTPS, indicating a predominantly dissociative character to this exchange process. Fluorination of benzyl bromide (BzBr) with TBAT in MeCN- exhibits moderate progressive autoinhibition, and the initial rate of the reaction is supressed by the presence of exogenous FTPS. Overall, TBAT can act as a genuine surrogate for TBAF, as well as a reservoir for rapidly-reversible release of traces of it, with the relative contribution of the pathways depending, , on the identity of the fluoride acceptor, the solvent, and the concentration of endogenous or exogenous FTPS.
四丁基二氟三苯基硅酸铵（TBAT）是一种易于处理的无水氟源，通常用作四丁基氟化铵（TBAF）的替代物。虽然先前的研究表明TBAT与氟受体反应迅速，但对于氟转移的机制知之甚少。我们报告了使用多种核磁共振方法，包括化学交换饱和转移、磁化转移、扩散分析和一维核Overhauser效应光谱（1D NOESY），对在四氢呋喃（THF）和乙腈（MeCN）中氟从TBAT转移的三个过程的动力学进行的研究。这些研究揭示了四丁基铵和二氟三苯基硅部分之间的离子对作用，以及非常低但可检测到的氟解离程度，然后根据条件进行进一步的平衡和/或诱导分解。TBAT和氟代三苯基硅烷（FTPS）之间的简并交换在THF中非常迅速，其速率随时间固有增加，并且对水的存在非常敏感。添加2,6-二叔丁基吡啶和3 Å分子筛可稳定交换速率，并且在这些条件下，解离性和直接氟转移均显示为并行进行。在THF的核磁共振时间尺度上未检测到TBAT和2-萘基氟硫酸盐（ARSF）之间的简并交换，而在MeCN中则较慢。对于后者，外源FTPS几乎完全抑制了交换，表明该交换过程主要具有解离性。在MeCN中用TBAT对苄基溴（BzBr）进行氟化表现出适度的渐进自抑制，并且反应的初始速率受到外源FTPS存在的抑制。总体而言，TBAT可以作为TBAF的真正替代物，以及痕量TBAF快速可逆释放的储存库，这些途径的相对贡献取决于氟受体的身份、溶剂以及内源性或外源性FTPS的浓度。
