Mechanism of nucleophilic fluorination promoted by bis‐<i>tert</i>‐alcohol‐functionalized crown‐6‐calix[4]arene

Pliego, Josefredo R.

doi:10.1002/qua.25648

Cited by 10 publications

(4 citation statements)

References 68 publications

(66 reference statements)

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“…In recent years, the increased importance of organofluorine compounds has induced research toward the development of reagents and catalysts for more effective fluorination reactions [22][23][24][25][26][27][28][29][30][31][32][33][34][35]. An example is the tetramethylammonium fluoride.…”

Section: Introductionmentioning

confidence: 99%

Reactivity and stability of ion pairs, dimers and tetramers versus solvent polarity: SNAr fluorination of 2-bromobenzonitrile with tetramethylammonium fluoride

Dalessandro

Pliego

2020

Theor Chem Acc

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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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Section: Introductionmentioning

confidence: 99%

Reactivity and stability of ion pairs, dimers and tetramers versus solvent polarity: SNAr fluorination of 2-bromobenzonitrile with tetramethylammonium fluoride

Dalessandro

Pliego

2020

Theor Chem Acc

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“…However, due to the formation of aggregates in the solution phase, this effect could be difficult to observe with 1,4-benzenedimethanol . For another structures able to avoid dimerization, such as the BACCA (Figure ), such an effect is important for explaining quantitatively the observed catalysis. ,, …”

Section: Introductionmentioning

confidence: 99%

“…18 For another structures able to avoid dimerization, such as the BACCA (Figure 1), such an effect is important for explaining quantitatively the observed catalysis. 13,15,20 Although theory and experiments have shown that the combined functionalities in a single molecule with cation and anion interaction leads to superior catalysis, these newly designed structures involve more molecular complexity. 10 An alternative to this approach is to make the groups with cation and anion interaction to be present in different molecules, which would involve simpler structures.…”

Section: ■ Introductionmentioning

confidence: 99%

Nucleophilic Fluorination with KF Catalyzed by 18-Crown-6 and Bulky Diols: A Theoretical and Experimental Study

2020

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The activation of potassium fluoride for nucleophilic fluorination of alkyl halides is an important challenge because of the high lattice energy of this salt and its low solubility in many polar aprotic solvents. Crown ethers have been used for increasing the solubilization of KF during several decades. Nevertheless, these macrocycles are not enough to produce a high reaction rate. In this work, theoretical methods were used for designing a synergic combination of bulky diols with crown ethers able to accelerate this kind of reaction. The calculations have predicted that the bulky diol 1,4-Bis(2-hydroxy-2-propyl)benzene, which has distant hydroxyl groups, is able to catalyze nucleophilic fluorination in combination with 18-crown-6 via two hydrogen bonds to the SN2 transition state. Experimental studies following the theoretical predictions have confirmed the catalytic effect and the estimated kinetic data point out that the bulky diol at 1 mol L–1 in combination with 18-crown-6 is able to produce an 18-fold increase in the reaction rate in relation to crown ether catalysis only. The reaction produces 46% yield of fluorination after 24 h at moderate temperature of 82 °C, with minimal formation of the side elimination product. Thus, this work presents an improved method for fluorination with KF salt.

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“…As examples, crown ethers were introduced early for catalysis of fluorination, although long reaction time is needed. More recently, penta(ethylene glycol) was also shown to be effective, and new supramolecular catalysts combining crown ether and calix-arenes were developed. − In this area, theoretical methods are playing an important role for understanding details on how these molecules work, and new structures, named hydro-crowns, were design and computationally supported as superior phase-transfer catalysts. ,,− …”

Section: Introductionmentioning

confidence: 99%

Free Energy Profile of a Model Palladium Catalyzed Fluorination of Aryl Bromide with Cesium Fluoride

Pliego

2019

J. Phys. Chem. A

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Addition of fluorine to aromatic rings has increased in importance in the past decade in view of the increased role of organofluorine compounds in the design of new pharmaceuticals. Palladium catalyzed nucleophilic fluorination of unactivated aryl halides using salts such as cesium fluoride was achieved with the use of bulky biaryl monophosphine ligand. Simple monophosphine palladium complexes were not able to promote this reaction, which is attributed to the difficult reductive elimination step and the formation of dimers of the PdL(Ph)(F) intermediate. The use of theoretical methods for reliable design of new ligands requires the knowledge of the complete free energy profile of the catalyzed reaction. Otherwise, predictions may not be observed. In this work, a complete free energy profile of a model palladium catalyzed fluorination (trimethyl phosphine ligand), including the precatalyst decomposition mechanism (allylpalladium chloride), was investigated using a reliable theoretical method, the mPW2-PLYP double-hybrid functional, which was compared with the DLPNO–CCSD(T) benchmark method. The results suggest that palladium(π-cinnamyl) chloride is not a good precatalyst, while the monophosphine palladium complex bonded to an alkene should work better. The transmetalation step raises the overall barrier for the reductive elimination by 4.3 kcal mol–1 in the case of monophosphine catalyst, making the reaction difficult (ΔG ⧧ = 34.1 kcal mol–1), even in the case of no dimerization of the monophosphine palladium fluoride complex. Thus, success of a ligand to promote palladium catalysis requires not only a monophosphine ligand that avoids dimerization but also a strong repulsion to both phenyl and fluorine bonded to the palladium in the PdL(Ph)(F) complex.

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Mechanism of nucleophilic fluorination promoted by bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene

Cited by 10 publications

References 68 publications

Reactivity and stability of ion pairs, dimers and tetramers versus solvent polarity: SNAr fluorination of 2-bromobenzonitrile with tetramethylammonium fluoride

Reactivity and stability of ion pairs, dimers and tetramers versus solvent polarity: SNAr fluorination of 2-bromobenzonitrile with tetramethylammonium fluoride

Nucleophilic Fluorination with KF Catalyzed by 18-Crown-6 and Bulky Diols: A Theoretical and Experimental Study

Free Energy Profile of a Model Palladium Catalyzed Fluorination of Aryl Bromide with Cesium Fluoride

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