Mechanism of Nucleophilic Fluorination Facilitated by a Pyrene‐tagged Ionic Liquids: Synergistic Effects of Pyrene–Metal Cation π‐Interactions

Abstract

We examine the mechanism of S N 2 fluorination promoted by a pyrene-tagged ionic liquid (PIL). Comparison is made for contact ion-pair (CIP) vs. solvent-separated ion-pair (SSIP) mechanism by calculating the Gibbs free energies of pre-reaction complexes and Gibbs free energies of activation G ‡ for both processes. We find that the CIP mechanism is preferred for [PIL + MF + C 3 H 7 OMs] (M = Cs, K) system. S N 2 fluorination of the [1-Butyl-3-methylimidazolium (bmim)-CsF] system is also studied in order to estimate the efficacy of PIL vs. more conventional ionic liquid [bmim] [OMs]. The better promotion of the reaction by PIL is attributed to π interactions between the metal cation and pyrene, giving G ‡ that is smaller (by approximately 1.3 kcal/mol) than that for the [bmim-CsF] system, in excellent agreement with experimental observations.

Hydrogen Bonding in SN2 Reactions Promoted or Inhibited by Ionic Liquids: Effects of Side Chain

“…The mechanism of rate acceleration by [bmim][PF 6 ] demonstrated in Figures 3 and 5 is to be clearly understood in terms of the structure of (Pre‐bmim‐1). The anion PF 6 − acts as a Lewis base on the counter‐cation Cs + , essentially removing the latter's strong (and retarding) electrostatic influence on F − to enhance the nucleophilicity, rendering Cs + as a “ghost.” The role of the IL [bmim][PF 6 ] is in line with that demonstrated in previous works 10,12,13,33 …”

Harnessing Ionic Interactions and Hydrogen Bonding for Nucleophilic Fluorination

“…However, less than stoichiometric amounts of IL (0.5 equiv) as catalyst/promoter showed rather poor performance for the nucleophilic fluorination. The mechanism of these very interesting observations was elucidated by Lee and co-workers [24] in quantum chemical analysis. It was found that the ionic liquid anion plays a key role as a Lewis base by binding to the counter-cation K + or Cs + , thereby reducing its retarding Coulombic influence on the nucleophile F − .…”

“…Besides being considered excellent solvent for chemical reactions because of its many useful physicochemical properties such as very low vapor pressure, non-combustibility, high thermal stability, low viscosity, easy recovery and high ionic conductivity, ionic liquids (ILs) [10][11][12][13][14][15][16][17][18][19] have found further significant role as catalysts/promoters [20,21] in many chemical transformations such as S N 2 [22][23][24][25][26][27][28], Diels-Alder [29], aldol condensation [30], Heck [31][32][33], and Michael addition [34] reactions. The acceleration of reaction rates of organic reactions by IL occur by the nature of the substance comprising cation and anion.…”

“…As a "task-specific" promoter/catalyst for organic transformations to be designed, the structure of side-chain [44] of IL cation and anion would be an important determinant of the efficiency of ILs. Modification of ILs by oligoethylene glycol chain is a good example, in which the synergistic effects of the two moieties improve the overall efficiency of the promoter/catalyst (Figure 3) [24]. Another example is the design and use of pyrene-tagged IL (Figure 4) [45].…”

“…As presented in Figure 4, the pyrene moiety acts as an additional Lewis base besides the IL anion in this mechanism, further strengthening the catalytic efficiency of IL. The mechanism ( Figure 5) (pre-reaction complex → transition state → post-reaction complex) of the reaction is depicted in Figure 5: Pyrene -cation π interactions facilitate the reaction by giving π electrons to the counter-cation, further alleviating the Coulombic influence of the cation on the nucleophile [24].…”