Synthesis of functionalized chiral ammonium,imidazolium, and pyridinium-based ionic liquids derived from (−)-ephedrine using solvent-free microwave activation. Applications for the asymmetric Michael addition

An efficient procedure for the synthesis of functionalized chiral ammonium, imidazolium, and pyridinium-based ionic liquids derived from (1R, 2S)-ephedrine using solvent-free microwave activation has been described. Good yields were obtained in very short reaction time. These chiral ionic liquids were used as chiral reaction media for the asymmetric Michael addition, giving good yields and moderate enantioselectivities.     

功能化的离子液体: 手性离子液体的合成与应用

手性在化学中占有重要地位. 利用离子液体特殊的结构可调性质, 将手性引入到离子液体结构中, 可以获得具有手性的离子液体, 从而可能广泛应用于手性合成、手性分离、手性催化等领域. 汇总了至今报道的手性离子液体, 从离子液体功能化设计的角度探讨其合成方法. 针对手性离子液体可能的发展方向, 再次强调了由天然手性源设计合成离子液体遵循的三个标准.     

Natural terpene derivatives as new structural task‐specific ionic liquids to enhance the enantiorecognition of acidic enantiomers on teicoplanin‐based stationary phase by high‐performance liquid chromatography

We present the specific cooperative effect of a semisynthetic glycopeptide antibiotic teicoplanin and chiral ionic liquids containing the (1R ,2S ,5R )‐(–)‐menthol moiety on the chiral recognition of enantiomers of mandelic acid, vanilmandelic acid, and phenyllactic acid. Experiments were performed chromatographically on an Astec Chirobiotic T chiral stationary phase applying the mobile phase with the addition of the chiral ionic liquids. The stereoselective binding of enantiomers to teicoplanin in presence of new chiral ionic liquids were evaluated applying thermodynamic measurements and the docking simulations. Both the experimental and theoretical methods revealed that the chiral recognition of enantiomers in the presence of new chiral ionic liquids was enthalpy driven. The changes of the teicoplanin conformation occurring upon binding of the chiral ionic liquids are responsible for the differences in the standard changes in Gibbs energy (ΔG ⁰) values obtained for complexes formed by the R and S enantiomers and teicoplanin. Docking simulations revealed the steric adjustment between the chiral ionic liquids cyclohexane ring (chair conformation) and the β‐d ‐glucosamine ring of teicoplanin and additionally hydrophobic interactions between the decanoic aliphatic chain of teicoplanin and the alkyl group of the tested salts. The obtained terpene derivatives can be considered as “structural task‐specific ionic liquids” responsible for enhancing the chiral resolution in synergistic systems with two chiral selectors.     

Enantioseparation of mandelic acid enantiomers in ionic liquid aqueous two-phase extraction systems

In the past decade, ionic liquids have received great attention owing to their potential as green solvent alternatives to conventional organic solvents. In this work, hydrophobic achiral ionic liquids (1-butyl-3-methylimidazolium-hexafluorophosphate([bmim][PF₆]), 1-octyl-3-methylimidazolium tetrafluoroborate([omim][BF₄])) were used as solvents in chiral liquid-liquid extraction separation of mandelic acid (MA) enantiomers with β-cyclodextrin (β-CD) derivatives as hydrophilic chiral selectors preferentially forming complexes with (R)-enantiomers. Factors affecting the separation efficiency were optimised, namely the type of the extraction solvents and β-CD derivatives, concentrations of the β-CD derivatives and MA enantiomers, pH, and temperature. Excellent enantioseparation of MA enantiomers was achieved in the ionic liquid aqueous two-phase extraction systems under the optimal conditions of pH 2.5 and temperature of 5°C with the maximum enantioselectivity (α) of 1.74. The experimental results demonstrated that the ionic liquid aqueous two-phase extraction systems with a β-CD derivative as the chiral selector have a strong chiral recognition ability, which might extend the application of ionic liquids in chiral separation.     

Synthesis and characterization of novel chiral imidazolium and pyridinium ionic liquids derived from tartaric acid and 2-oxazolidinone

Abstract

Novel chiral imidazolium and pyridinium ionic liquids based on tartaric acid and 2-oxazolidinone were designed. Symmetrical dicationic ionic liquids based on tartaric acid have been synthesized and characterized. These chiral ionic liquids were designed by employing very short and simple methods. Incorporation of alkyl halide over tartaric acid and 2-oxazolidinone is an important step. N-methyl imidazole and pyridine were used for preparation of quaternary salts. These ionic liquids have been evaluated for the asymmetric sulfide oxidation. Chiral ionic liquids based on tartaric acid showed superior chiral inducing property as compare to 2-oxazolidinone based chiral ionic liquids.     

Mandelate and prolinate ionic liquids: synthesis, characterization, catalytic and biological activity

A group of quaternary ammonium mandelates and l-prolinates, as ionic liquids, were synthesized and characterized. The prepared salts were soluble in water and showed high surface activity. The described synthesis of l-prolinate was simple and the obtained ionic liquid contained a chiral anion. l-Prolinate in CH₂Cl₂ was employed for the asymmetric Michael addition of a ketone to nitrostyrene. A yield of 60%, enantioselectivity (upto 50% ee), and good diastereoselectivity (syn/anti ratio of up to 90:10) were obtained for the asymmetric addition of cyclohexanone. These novel ionic liquids proved to be very effective anti-microbial and anti-fungal agents, especially didecyldimethylammonium l-prolinate. Additionally, it was found that phytotoxicity can be a useful tool in assessing the optical forms of ionic liquids.     

Pyrrolidine-based chiral pyridinium ionic liquids (ILs) as recyclable and highly efficient organocatalysts for the asymmetric Michael addition reactions

A novel series of pyrrolidine-based chiral pyridinium ionic liquids (ILs) have been developed by using commercially available (S)-(2-aminomethyl)-1-N-Boc-pyrrolidine. These chiral ILs have been found to be recyclable and efficient organocatalysts for the asymmetric catalytic Michael addition reactions of ketones to nitroolefins with high yields, high enantioselectivies, and diastereoselectivies.     

Combinatorial synthesis of functionalized chiral and doubly chiral ionic liquids and their applications as asymmetric covalent/non-covalent bifunctional organocatalysts

A facile combinatorial strategy was developed for the construction of libraries of functionalized chiral ionic liquids (FCILs) including doubly chiral ionic liquids and bis-functional chiral ionic liquids. These FCIL libraries have the potential to be used as asymmetric catalysts or chiral ligands. As an example, novel asymmetric bifunctional catalysts were developed by simultaneously incorporating functional groups onto the cation and anion. The resultant bis-functionalized CILs showed significantly improved stereoselectivity over the mono-functionalized parent CILs.     

Symmetry Breaking in Chiral Ionic Liquids Evidenced by Vibrational Optical Activity

Ionic liquids (ILs) are receiving increasing interest for their use in synthetic laboratories and industry. Being composed of charged entities, they show a complex and widely unexplored dynamic behavior. Chiral ionic liquids (CILs) have a high potential as solvents for use in asymmetric synthesis. Chiroptical methods, owing to their sensitivity towards molecular conformation, offer unique possibilities to study the structure of these chiral ionic liquids. Raman optical activity proved particularly useful to study ionic liquids composed of amino acids and the achiral 1‐ethyl‐3‐methylimidazolium counterion. We could substantiate, supported by selected theoretical methods, that the achiral counterion adopts an overall chiral conformation in the presence of chiral amino acid ions. These findings suggest that in the design of chiral ionic liquids for asymmetric synthesis, the structure of the achiral counter ion also has to be carefully considered.     

Ionic Liquids Beyond Simple Solvents: Glimpses at the State of the Art in Organic Chemistry

Within the last 25 years ionic liquids have written a tremendous success story, which is documented in a nearly uncountable amount of original research papers, reviews, and numerous applications in research and industry. These days, ionic liquids can be considered as a mature class of compounds for many different applications. Frequently, they are used as neoteric solvents for chemical tansformations, and the number of reviews on this field of research is huge. In this focused review, though, we are trying to evaluate the state of the art of ionic liquid chemistry beyond using them simply as solvents for chemical transformations. It is not meant to be a comprehensive overview on the topic; the choice of emphasis and examples rather refects the authors’ personal view on the field. We are especially highlighting fields in which we believe the most fundamental developments within the next five years will take place: biomass processing, (chiral) ionic liquids from natural sources, biotransformations, and organic synthesis.     

Synthesis of novel spiro imidazolium salts as chiral ionic liquids

A library of 13 novel chiral spiro imidazolium salts has been synthesized. The effects of N-substituents and counteranions on the melting point of spiro bis(imidazolium) salts are studied in efforts toward the development of room temperature chiral ionic liquids.     

Chiral ionic liquids based on abietane

A number of chiral ionic liquids were synthesized by reaction of 12-chloromethylabieta-8,11,13-trien-18-oic acid methyl ester with N-alkylimidazoles.     

手性离子液体的合成及其应用

近年来对离子液体的研究已取得了显著进展,并已在许多领域得到了广泛应用。手性离子液体(CILs)作为离子液体家族新成员,引起越来越多的兴趣。本文综述了手性离子液体的合成以及应用,并对以后的研究方向作了展望。     

Functionalized Chiral Ionic Liquids: A New Type of Asymmetric Organocatalysts and Nonclassical Chiral Ligands

By judiciously anchoring functional groups onto chiral ionic liquids, functionalized chiral ionic liquids (FCILs) are emerging as a new type of asymmetric organocatalysts and nonclassical chiral ligands. This Focus Review highlights the applications of FCILs from the viewpoint of asymmetric catalysis. We focus mainly on the de novo designed and synthesized FCILs which likely still maintain the typical ionic liquids properties, and in a few cases relevant ionic liquid immobilized chiral catalysts are briefly discussed.     

Synthesis of novel chiral imidazolium-based ionic liquids derived from isosorbide and their applications in asymmetric aza Diels-Alder reaction

A novel family of chiral imidazolium-based ionic liquids containing a chiral moiety and a free hydroxyl function has been designed and synthesized using isosorbide as a biorenewable substrate. These chiral ionic liquids were found to catalyze the aza Diels-Alder reaction to give good yields and moderate diastereoselectivities. Chiral ionic liquids are recycled while their efficiency is preserved.     

Synthesis and properties of ionic liquids derived from the 'chiral pool'

New chiral ionic liquids have been synthesised which are directly derived from the 'chiral pool' and therefore readily available in kg scale; NMR-measurements indicate that these liquids may be interesting solvents for enantioselective reactions and useful in chiral separation techniques.     

First application of chiral ionic liquids in asymmetric Baylis-Hillman reaction

The first example of the use of chiral ionic liquids as reaction media in the asymmetric Baylis-Hillman reaction was described using N-alkyl-N-methylephedrinium salts. Good yields and significant enantiomeric excesses were obtained.     

New tagged naplephos ligands for asymmetric allylic substitutions under traditional and unconventional conditions

This paper demonstrates the versatility of the class of chiral ligands naplephos, which has been further refined by preparing new ‘tagged’ versions for selective use in polar media (e.g., ionic liquids). These modified types, along with the best performing original varieties, have been examined in two Pd-catalysed asymmetric processes involving C-C and C-N bond formation. High ees have been achieved in traditional solvents, while the experiments performed in ionic liquids confirm the difficulty of predicting the outcome of a reaction in these media and the general decrease in the catalytic performance.     

Asymmetric reduction of aromatic ketones in pyridinium-based ionic liquids

The asymmetric reduction of aromatic ketones has been studied in pyridinium-based room temperature ionic liquids, namely, 1-ethyl-pyridinium tetrafluoroborate, [EtPy]⁺[BF₄]⁻ and 1-ethyl-pyridinium trifluoroacetate, [EtPy]⁺[CF₃COO]⁻. Ionic liquids were employed as solvents, while (R)-BINOL and (R)-BINOL-Br were used as chiral promoters. The effects of solvent, reaction time, temperature, catalyst loading and substituents were investigated. The reduction could be easily carried out in both ionic liquids with lower catalyst loading. 1-Ethyl-pyridinium tetrafluoroborate was recycled and reused efficiently.     

Room Temperature Ionic Liquids in Asymmetric Hetero-Ene Type Reactions: Improving Organocatalyst Performance at Lower Temperatures

Room temperature ionic liquids (RTILs) have been widely used as (co)solvents in several catalytic processes modifying, in most of the cases, the catalyst activity and/or the selectivity for the studied reactions. However, there are just a few examples of their use in hydrogen bonding organocatalysis. In this paper, we show the positive effect of a set of imidazole-based ionic liquids ([bmim]BF₄ and [hmim]PF₆) in the enantioselective addition of formaldehyde tert-butylhydrazone to prochiral α-keto esters catalyzed by a sugar-based chiral thiourea. Reactions performed in the presence of low percentages of RTILs led to an increase of the catalyst activity, thereby making possible to work at lower temperatures. Thus, the chiral tert-butyl azomethyl tertiary alcohols could be obtained with moderate to good conversions and higher enantioselectivities for most of the studied substrates when using up to 30 vol% of [hmim]PF₆ as a cosolvent in processes performed in toluene.