Novel chiral ionic liquid (CIL) assisted selectivity enhancement to (L)-proline catalyzed asymmetric aldol reactions

Abstract

Melhoras significativas nos rendimentos químicos (até 88%), estereosseletividades (> 99:1) e excessos enantioméricos (até 98%) foram observadas em reações aldólicas assimétricas catalisadas por (L)-prolina, quando líquidos iônicos quirais baseados em prolina (CILs) foram usados como aditivos. Diferentes proporções de DMSO/H 2 O como solvente, e líquidos iônicos quirais (CILs) com cátions quirais com diferentes comprimentos de cadeia, foram investigados.A significant improvement of the chemical yields (up to 88%), stereoselectivity (> 99:1) and enantiomeric excesses (up to 98%) of (L)-proline catalyzed direct asymmetric aldol reaction was found when proline based chiral ionic liquids (CILs) were added as additives. Different ratios of DMSO/H 2 O as solvent and chiral ionic liquids (CILs) with chiral cations of different chain length were investigated. Keywords: aldol reaction, asymmetric synthesis, chiral ionic liquids, chiral additive IntroductionRoom temperature ionic liquids (RTILs) including chiral ionic liquids (CILs) have received growing attentions both from theoretical research and actual productions due to their tuneable features for various chemical tasks and their advantages as homogeneous support, reaction media, etc.1,2 Since the first example of chiral ionic liquid reported by Howarth et al. 3 in 1997, a large number of CILs bearing chiral cations, anions or seldom both were reported by other groups. 4,5 Previous studies have shown that in many asymmetric reactions the use of CILs as reaction media or catalyst can enhance the yield and/or selectivity significantly. [6][7][8] As most of the asymmetric reactions were carried out using metal/chiral catalysts as chiral sources, which are relatively expensive or environmental unfriendly, searching for a catalyst which is easy to obtain and environmentally benign for the asymmetric reactions is of great significance. In our previous work, a series of (L)-proline based CILs were proved to have the potential to provide a strong chiral environment by 19 F NMR study. 9 In this article, a series of reactions were carried out to investigate the catalytic properties of these (L)-proline based CILs, and very high chiral selectivity was obtained.Aldol reaction has been a typical asymmetric reaction used in the search of efficient asymmetric catalyst, especially for environmental friendly and metal-free organic catalyst. [10][11][12][13] Since CILs used as catalyst in aldol reaction by Luo et al. 14 in 2007, many CILs were developed as catalysts for asymmetric reactions. However, in asymmetric reactions where CILs cannot be applied as catalysts, using CILs as the solvent to investigate the chiral inducing capabilities has rarely been reported. Here we chose the asymmetric aldol reactions as our initial focus to examine the applications of CILs in asymmetric reactions. (L)-Proline and its structural analogs were found to be good catalyst for aldol reaction, [15][16][17][18][19] and (L)-proline combined with ILs were also proved to be an efficient catalytic ...

Supramolecular Interactions Based on Ionic Liquids for Tuning of the Catalytic Efficiency of (l)-Proline

“…Thus, it is clear that in this reaction the IL is not an innocent partner. − As reported for the addition of water, the presence of the IL has a significant influence on the outcome of the reaction suppressing the formation of side reactions and enhancing the reaction rate . Regarding the enantioselectivity, an enhancement of the asymmetric induction was observed when larger amounts of IL were used, reaching 62% e.e.…”

Preparation, Characterization, and Structure Trends for Graphite Intercalation Compounds Containing Pyrrolidinium Cations

“…All Py cations employed were synthesized as bromide salts according to literature methods, , and their structures were confirmed using 1 H-1D nuclear magnetic resonance (NMR) (see the SI, Section 1). The [Na­(en) 1.0 ]­C 15 precursor for ion exchange was prepared according to a previously published method. , …”

Rapid and Efficient Uncatalyzed Knoevenagel Condensations from Binary Mixture of Ethanol and Water

“…[1][2][3] It is one of the most useful reactions to form C-C bonds, generally used to assist the synthesis of several compounds with biological relevance 4 and other possible applications, such as drugs, [5][6][7][8][9][10] natural products, 11,12 and polymers. [13][14][15] Weak bases, such as amines and basic salts, usually catalyze these reactions.…”