Enantioselectivities in ionic liquids

C4C im][PF6] [CgCdmHBFJ [C4py][CBuH12] Rhodocarborane + (/ )-BINAP Acetophenone Benzylformate 12 bar, 50°C enantioselectivity in ionic liquid much higher than in THF product isolated by distillation. [38]... 

Zhu and coworkers [22] reported an asymmetric hydrogenation of aromatic ketones in the presence of a rhodacarborane-based chiral catalyst 17, which was derived from rhodacarborane precursor 16 and (R)-BINAP, in ionic liquids (Scheme 7.5). The hydrogenations of acetophenone in the presence ofthe catalyst precursor 16 and (R)-BINAP (0.001 0.0015 for acetophenone) were performed in the ionic liquid medium such as [omim][BF4], [brnim lh7,, or a new hquid salt comprised of 1-carbododecaborate ions and N-n-butylpyridinium (BP) ions, [BP][CB1XioHi2], and tetrahydrofuran (THF) at 50°C under H2 (12atm) for 12h. As shown in Table 7.5, the catalytic activities and enantioselectivities in ionic liquids (entries 1-3) were higher in comparison with those obtained in TH F (entry... 

Maruyama T, Yamamura H, Kotani T et al (2004) Poly(ethylene glycol)-lipase complexes that are highly active and enantioselective in ionic liquids. Oig Biomol Chem 2 1239-1244... 

Kim performed similar transesterifications, observing that lipases were up to 25 times more enantioselective in ionic liquids ([bmim][PF6] and [emim]piF4]) than in conventional organic solvents. ... 

A number of enantioselective hydrogenation reactions in ionic liquids have also been described. In all cases reported so far, the role of the ionic liquid was mainly to open up a new, facile way to recycle the expensive chiral metal complex used as the hydrogenation catalyst. 

Irimescu and Kato have recently described an interesting example of enzymatic KR in ionic liquids instead of organic solvents (Scheme 7.4) [12]. The resolution with CALB is based on the fact that the reaction equilibrium was shifted toward the amide synthesis by the removal of water under reduced pressure. Nonsolvent systems have been also employed in this enantioselective amidation processes, reacting racemic amines with aliphatic acids. The best reaction conditions for the conversion of acids to amides was observed using CALB at 90 °C under vacuum. Meanwhile, no... 

Details of the first stereoselective hydrogenation in ionic liquids were published by the group of Chauvin [68], who reported the enantioselective hydrogenation of the enamide a-acetamidocinnamic acid in the biphasic system [BMIM][SbF6]/ iPrOH (ratio 3 8) catalyzed by [Rh(cod) (-)-diop ][PF6]. The reaction afforded (S)-N-acetylphenylalanine in 64% enantiomeric excess (ee) (Fig. 41.4). The product was easily and quantitatively separated and the ionic hquid could be recovered, while the loss of rhodium was less than 0.02%. 

Biocatalysts also operate in ionic liquids [28]. The ones that have been most widely investigated are the lipase family of enzymes. For example, Candida Antarctica lipase B immobilized in [bmim][BF4] or [bmim][PFe] under anhydrous conditions is able to catalyse transesterifications at rates comparable to those observed in other solvents. Certain lipase mediated enantioselective acylations have even resulted in considerable improvements in enantiomeric excesses... 

Earle, M. J., McCormac, P. B. Seddon, K. R. Diels-Alder reactions in ionic liquids a safe recyclable green alternative to lithium perchlorate-diethyl ether mixtures. Green Chem., 1999, 1(1), 23-25 Doherty, S. Goodrich, P. Hardacre, C. et al. Marked enantioselectivity enhancements for Diels-Alder reactions in ionic liquids catalysed by platinum diphosphine complexes. Green Chem., 2004, 6(1), 63-67. 

Unusually high diastereoselectivity and enantioselectivity in Diels-Alder reactions were achieved in ionic liquids at room temperature (131). The selectivity rivals that of the reaction in conventional solvents, for which a low temperature (e.g., — 78°C) is needed. Furthermore, the rate of the reaction is much higher in the ionic liquids than in the conventional solvents, because the reaction is carried out at room temperature in ionic liquids. 

A chiral phase transfer catalyst was dissolved in ionic liquid media for the enantioselective Michael reaction of dimethyl malonate with l,3-diphenylprop-2-en-l-one with K2CO3 203). The phase-transfer catalyst was a chiral quininium bromide (Scheme 20). The reaction proceeded rapidly with good yield and good enantioselectivity at room temperature in all three ionic liquids investigated, [BMIM]PF6, [BMIM]BF4 and [BPy]BF4. In the asymmetric Michael addition, the enantioselectivity or the reaction in [BPy]Bp4 was the same as in conventional organic solvents. 

Enantioselective hydrogenation in ionic liquids is worthy of attention because of the prospects for efficient reuse of metal complexes with expensive chiral ligands. The opportunities and challenges involved in the application of ionic liquids for chiral synthesis have been assessed recently 213). 

Remarkable activity and enantioselectivity in asymmetric hydrogenation of aromatic ketones were reported when ionic liquids were used as solvents for a rhodacarborane catalyst precursor having an alkene ligand, [closo-l,3 p-(ri -3-CH2= CHCH2CH2) -3-H-3-PPh3-3,l,2-RhC2B9Hio] 215). In ionic liquids... 

Proteases have also been successfully used in ionic liquids. Papain mediated the enantioselective hydrolysis of a number of amino acid esters in an 80 20 mixture of [BMIm][BF4] and water [68]. The reaction rate was approx. 50% of that in aqueous buffer and equal to that in aqueous mixtures containing 70- 80% of solvents such as acetonitrile or tert-butyl alcohol. 

Rather less attention has been paid to enzymatic oxidations in ionic liquids. Chloroperoxidase (CPO) catalyzed the chemo- and enantioselective sulfoxidation of thioanisole (Figure 10.21) in aqueous mixtures containing up to 50% [HOEtMe3N] [citrate] or [MMIm][Me2P04] [145]. 

M. Onaka, Efficient lipase-catalyzed enantioselective acylation in an ionic liquid solvent system. In Ionic Liquids as Green Solvents, R. D. Rogers, K. R. Seddon, Eds., ACS Symposium Series Vol. 856, ACS Washington D.C., 2003, p 251. 

The Kotsuki group investigated the effect of high-pressure conditions on the direct proline-catalyzed aldol reaction [79a], a process which, interestingly, does not require use of DMSO as co-solvent. Use of high-pressure conditions led to suppression of the formation of undesired dehydrated by-product and enhancement of the yield. Study of the substrate range with a range of aldehydes and ketones revealed that enantioselectivity was usually comparable with that obtained from experiments at atmospheric pressure. Additionally, proline catalyzed aldol reactions in ionic liquids, preferably l-butyl-3-methylimidazolium hexafluorophosphate, have been successfully carried out [79b,c]. 

A chiral pyridine-bisoxazoline ( PYBOX ) ligand has been combined with indium (III) triflate to produce an enantioselective catalyst for allylation of a wide variety of aldehydes in ionic liquids 183 ees of >90% were obtained, and extraction and reuse of the catalyst-ionic liquid combination saw this figure hold up to >80% on the fourth recycle. 

Whilst in some cases near-stoichiometric amounts of reagents can be used [16], the excess (5-10 equiv.) of ketone reagent is preconceived in order to ensure convenient kinetics and conversion. Reactions can be run typically at room temperature [20] in a polar aprotic solvent such as CHC13, or in THF or i-PrOH. The presence of water was noted to be beneficial in some cases [21]. In ionic liquids, such as in [bmim]BF4, a low (5 mol%) catalyst concentration can be applied, while the enantioselectivity of the alkylation is modest in this solvent [22]. The ionic liquid-derived hybrid catalyst 10, used neat with a small amount of trifluoroacetic acid (TFA) as co-catalyst, affords quantitatively 4, though in a remarkably high dr syn/anti = 99/1) and ee (99%). It should be noted that this catalyst can easily be recovered by extraction, and re-used without loss of activity. 

The epoxidation of alkenes, both racemic and enantioselective, has been extensively studied in ionic liquids and Table 5.3 provides a summary of these reactions. Although no transition metal is involved, the base-catalysed epoxidation of electrophilic alkenes in ionic liquids is worth briefly mentioning. Depending on the substrate and the reaction conditions, ,/ -unsaturated carbonyl compounds were oxidised with aqueous H2O2 in [C4Ciim][BF4] or [C4Ciim][PF6] within minutes under mild conditions and no hydrolysis products were observed.120-221 The extraction of the products with scC02 instead of conventional solvents was demonstrated to be feasible, albeit on a small scale.1231... 

The catalytic asymmetric epoxidation of alkenes offers a powerful strategy for the synthesis of enantiomerically enriched epoxides and enantioselective oxidation reactions in ionic liquids have been summarised previously.[39] Complexes based on chiral salen ligands - usually with manganese(III) as the coordinated metal - often afford excellent yields and enantioselectivities and the catalytic cycle for the reaction is depicted in Scheme 5.5 J40 ... 

As in many other areas of catalysis in ionic liquids, the research of the past years in ionic liquid supported olefin metathesis has been dominated by demonstrating the general feasibility in this reaction medium. With the development of the task-specific complexes new prospects have been opened and the improved recyclability of these compounds relative to the common metathesis catalysts is impressive. Apart from more active and stable catalysts, the development of enantioselective catalysts and of continuous processes are likely to be the next goals. 

Enantioselective fluorination is commonly conducted with chiral agents such as quinine-based [N-F]+ compounds, and these have been successfully utilised in ionic liquids.115,161 Very good yields and selectivities have been obtained in the enantioselective fluorination of /Nkctoesters catalysed by the chiral palladium complex 57, see Scheme 9.2. l l Depending on the substrate employed, substantial acceleration of the reaction rate relative to that in ethanol was observed with yields and selectivities comparable to those obtained in water or ethanol. The reaction rate was found to depend on both the length of the alkyl substituent of the imidazolium cation as, well as on the type of anion present, whereas the selectivity was not affected by such variations. The products were extracted from the ionic liquid phase with diethyl ether, and in that manner catalytic activity was maintained for up to ten cycles. 

Lou, W.-Y., Zong, M.-H., Liu, Y.-Y., and Wang, J.-F. 2006. Efficient enantioselective hydrolysis of D,L-phenylglycine methyl ester catalyzed by immobilized Candida antarctica lipase B in ionic liquid containing systems. Journal of Biotechnology, 125 64—74. 

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