Achiral polyether derivatives have been shown to dramatically accelerate SN2 reactions by the simultaneous activation of both the nucleophile (KF) and electrophile (sulfonate; see picture). By using ...chiral variants as catalysts, the desilylative kinetic resolution of the silyl ethers of racemic secondary alcohols has been achieved. Density functional calculations provide detailed insight into the modes of action of this type of organic promoter.
Besides their extremely useful properties as solvent, ionic liquids (ILs) are now considered to be highly instructive tools for enhancing the rates of chemical reactions. The ionic nature of the IL ...anion and cation seems to be the origin of this fascinating function of ILs as organocatalyst/promoter through their strong Coulombic forces on other ionic species in the reaction and also through the formation of hydrogen bonds with various functional groups in substrates. It is now possible to tailor-make ILs for specific purposes as solvent/promoters in a variety of situations by carefully monitoring these interactions. Despite the enormous potentiality, it seems that the application of ILs as organocatalysts/promoters for chemical reactions have not been fully achieved so far. Herein, we review recent developments of ILs for promoting the nucleophilic reactions, focusing on fluorination. Various aspects of the processes, such as organocatalytic capability, reaction mechanisms and salt effects, are discussed.
Hexaethylene glycolic vinyl imidazolium (hexaEGVIM) was supported on N-vinyl caprolactam via covalent bonds through simple copolymerization to form poly caprolactam-supported hexaethylene ...glycol-substituted imidazolium salts (PCLS-hexaEGIM). The resulting heterogeneous PCLS-hexaEGIM promoter was active, selective, and stable for aliphatic nucleophilic substitution reactions using alkali metal salts. The alkali metal salts dramatically enhanced the reactivity of this heterogeneous catalyst with easily isolable higher product yields, reducing the formation of by-products. Therefore, nucleophilic fluorination and other substitution reactions can act as highly efficient catalysts in various sulfonyloxyalkanes and haloalkanes with regard to their corresponding fluorinated products.
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•Di-cationic ionic liquids (DCILs) enhanced the reactivity of KF efficiently.•hexaEG-DHIM and hexaEG-DtOHIM DCILs were used as catalysts for SN2 fluorination.•KF/hexaEG-DHIM/t-alcohol ...combination showed excellent selectivity in the fluorination.•Tailor-made DCILs were well-designed for nucleophilic fluorination.
A tailor-made di-cationic ionic liquid (DCIL), hexaethylene glycol (hexaEG) bridged bis(2-hydroxy-2-methyl-n-propylimidazolium) dimesylate (hexaEG-DtOHIM), was prepared in 94% yield. We investigated the catalytic activity of hexaEG-DtOHIM and hexaEG-bridged bis(3-hexaEGyl imidazolium) dimesylate (hexaEG-DHIM) in nucleophilic fluorination using an alkali metal fluoride (MF) and compared their activities with a variety of mono-cationic ILs. In this reaction, these two task-specific DCILs exhibited much higher catalytic activity than mono-cationic ILs. Moreover, the hexaEG functionalized IL (e.g. hexaEG-DHIM) more effectively enhanced the reactivity of KF compared with the t-alcohol functionalized IL (e.g. hexaEG-DtOHIM). In particular, the combination of KF/hexaEG-DHIM in t-alcohol media provided excellent chemoselectivity and high chemical yields in the fluorination reaction of base sensitive substrates such as 1-(2-mesyloxyethyl)naphthalene. This protocol was shown to be generally applicable to fluorination reactions with a variety of substrates.
Anion–molecule reactions have a substantial solvent effect, which decreases with the solvent polarity. However, less solvation leads to the formation of ion pairs and higher aggregates that are ...usually less reactive. Consequently, theoretical determination of the best solvent for the reaction needs to consider all the species in equilibrium. In this report, we have investigated the wide range of solvent polarity in the S
N
Ar reaction of the tetramethylammonium fluoride (TMAF) with 2-bromobenzonitrile, as well as the formation of ion pairs, dimers and tetramers using molecular dynamics and density functional calculations with continuum solvation. Five solvents were considered: methanol, dimethylformamide, pyridine, tetrahydrofuran and benzene. The TMAF exists predominantly as free ions in methanol, as ion pairs in dimethylformamide and pyridine, and as tetramers in tetrahydrofuran and benzene. The reaction takes place through free ions in methanol, ion pairs in dimethylformamide, pyridine and tetrahydrofuran, and via dimer in benzene. The calculations suggest that dimethylformamide and pyridine are the best solvents for this reaction.
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The incorporation of alkoxy ligands within a range of alkoxyfluoroboranes and dialkoxyfluoroboranes results in fluoroborane reagents with attenuated Lewis acidity and increased ...ability to donate fluoride ion(s) when compared to boron trifluoride itself. Pinacolatoboron fluoride (pinBF), prepared in situ from BF3·OEt2 and bis(O-trimethylsilyl)pinacol, has been identified as an efficient fluoride donor which allows highly stereoselective SN1-type epoxide ring-opening (with retention of configuration) of a range of trans-β-methyl-substituted aryl epoxides to give the corresponding syn-fluorohydrins. The substrate scope of this transformation is more broad than the analogous protocol using boron trifluoride alone.
We review recent works for nucleophilic fluorination of organic compounds in which the Coulombic interactions between ionic species and/or hydrogen bonding affect the outcome of the reaction. S
2 ...fluorination of aliphatic compounds promoted by ionic liquids is first discussed, focusing on the mechanistic features for reaction using alkali metal fluorides. The influence of the interplay of ionic liquid cation, anion, nucleophile and counter-cation is treated in detail. The role of ionic liquid as bifunctional (both electrophilic and nucleophilic) activator is envisaged. We also review the S
Ar fluorination of diaryliodonium salts from the same perspective. Nucleophilic fluorination of guanidine-containing of diaryliodonium salts, which are capable of forming hydrogen bonds with the nucleophile, is exemplified as an excellent case where ionic interactions and hydrogen bonding significantly affect the efficiency of reaction. The origin of experimental observation for the strong dependence of fluorination yields on the positions of -Boc protection is understood in terms of the location of the nucleophile with respect to the reaction center, being either close to far from it. Recent advances in the synthesis of
FF-dopa are also cited in relation to S
Ar fluorination of diaryliodonium salts. Discussions are made with a focus on tailor-making promoters and solvent engineering based on ionic interactions and hydrogen bonding.
Nucleophilic fluorination of sulfonyl chlorides, acyl chlorides, and alkyl sulfonates with saturated aqueous solution of potassium bifluoride (KHF2) was studied under liquid–liquid two-phase ...conditions. Original “on-water” procedure, reported by Sharpless et al. ( J. Org. Chem. 2016, 81, 11360−11362, DOI: 10.1021/acs.joc.6b01423 ), was tested on model 1-octanesulfonyl chloride in the presence of phase transfer catalysts, some of which appeared to be beneficial for the reaction rate. Despite the high hydration energy of the fluoride ions, the catalytic system displayed numerous features typical for interfacial transportation of the nucleophilic species, being controlled by amount and structure of the catalyst, lipophilicity of the catalyst’s counterion, and rate of stirring. Besides for synthesis of acyl fluorides presence of 1 mol % of tetrabutylammonium chloride affected the selectivity of the reaction by minimizing formation of carboxylic acids and anhydrides. The presented results suggest that aqueous solutions of bifluorides (or synthetically equivalent systems accessible by acidification of alkali metal fluoride solutions) can be efficient sources of the fluoride ions under two-phase conditions, provided that rate of the intrinsic reaction is sufficiently high. The methodology supplements family of nucleophilic fluorinations, delivering a more reactive form of the solvated anions.
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