Enhanced nucleophilic fluorination and radiofluorination of organosilanes appended with potassium-chelating leaving groups

Abstract

Here we aimed to explore the feasibility of enhancing the fluorination of organosilanes by appending potassium-chelating groups to the substrates. For this purpose, eight organosilanes were prepared in which a linear or cyclic leaving group, with putative potassium-chelating ability, was attached covalently to a congested silicon atom via an ether linkage to serve as a potential nucleophilic assisting leaving group (NALG). Organosilicon-NALGs with expected strong potassium-chelating capability enhanced reactions with potassium fluoride in acetonitrile to produce organofluorosilanes without any need to separately add phase transfer reagent. Similar rate enhancements were also observed with cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min, β+ = 97%) in the presence of potassium carbonate in MeCN-0.5% H2O. This study found that metal-chelating NALG units can accelerate fluorination and radiofluorination reactions at sterically crowded silicon atoms.

Dynamic/Thermochemical Balance Drives Unusual Alkyl/F Exchange Reactions in Siloxides and Analogs

“…Although the experiments show the occurrence of exchange reactions for SO 2 F 2 , the kinetics of the set of reactions (2) shows that formation the SO 3 F − via the pentacoordinated species (reaction 2b) is far more favorable than the exchange reaction 2a (Figure 1). This result is opposite to what was observed for NF 3 where the pentacoordinated pathway was not observed.…”

“…A recent report has described a facile sequential exchange of methyl groups by fluorine in the gas-phase reaction of trimethylsiloxide ions (Me 3 SiO − ) and NF 3 . 1 This unusual reaction is particularly interesting because very few cases have been shown for the possible fluorination of organosilanes 2 and because it provides a potential pathway for the functionalization of molecular precursors of sol−gel processes that find enormous applications in the synthesis of silicon-containing glasses, gels, ceramics, and nanomaterials. 3−5 Although the gas-phase ion chemistry of silyl anions leading to the formation of siloxide ion is well established, 6−8 the reactivity of siloxide ions has not been extensively investigated.…”

Designing Silylated l‐Amino Acids using a Wittig Strategy: Synthesis of Peptide Derivatives and 18F‐Labelling

“…The 18 F‐labelling of organosilylated compounds is currently achieved using K[ 18 F] in the presence of Kryptofix® K2.2.2 . The fluorination of hydrosilylated “prosthetic compounds” such as 3 (X = H) and 4 has been carried out by heating between 30 and 100 °C in the presence of a small quantity of acid such as AcOH , .…”

18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

“…In a recent study, the leaving group SiFA methodology was combined with the nucleophile assisting leaving group (NALG) strategy to generate Si-appended potassium-chelating SiFA-based leaving groups [ 34 , 35 ]. In the absence of added Kryptofix 2.2.2, the facilitation of 18 F-fluorination in the presence of cyclic crown ethers such as in 17 compared to acyclic polyethers or alkoxide leaving groups was clearly established.…”