Chiral ionic liquids reactions

Scheme 5.1-17 Use of a chiral ionic liquid in a Diels-Alder reaction.

Thus far, these chiral ionic liquids do not appear to exert an influence, possibly because the structuring of the solvents around the reactions transition state is not rigid enough. These investigations are still in progress. 

Examples, like the application of enantiopure ioiuc hquids in the copper catalyzed enantioselective 1,4-addition of diethyl zinc to enones giving up to 76% ee, will not be presented [178], since here the chiral ionic liquid, CIL, acts as a ligand for a metal catalyzed reaction. 

Also the use of moisture stable ionic liquids as solvents in the Diels-Alder reaction has been carried out, and in all examples an enhanced reaction rate was observed [182,183]. The application of pyridinium-based ionic liquids allowed the utilization of isoprene as diene [184]. The chiral ionic liquid [bmim][L-lactate] was used as a solvent and accelerated the reaction of cyclopentadiene and ethyl acrylate, however, no enantiomeric excess was observed [183]. In addition several amino acid based ionic liquids have been recently tested in the Diels-Alder reaction. Similar exo. endo ratios were found but the product was obtained as racemate. The ionic liquids were prepared by the addition of equimolar amounts of HNO3 to the amino acids [185]. Furthermore, an enantiopure imidazolium salt incorporating a camphor motive was tested in the Diels-Alder reaction. No enantiomeric excess was found [186]. 

Scheme 81 Enantioselective Baylis-Hillman reaction in chiral ionic liquid 73...

Then the potential for asymmetric induction of some of these chiral ionic liquids was investigated. The aza Diels-Alder cycloaddition between the enantiomericaUy pure (/ )-imine 31 and the Danishefsky s diene 32 was chosen as model asymmetric reaction (Scheme 8). The reaction was performed at room temperature for 5 h using 0.5 equiv. of ionic liquid and 1.5 equiv. of diene. In the absence of chiral ILs, the same coupling required a Lewis acid catalyst (0.1 equiv. of ZnC ) and afforded the main product 33 in 60% yield and low diastereoselectivity (32% de). 

Scheme 8 Model asymmetric aza Diels-Alder reaction in the presence of chiral ionic liquids...

The resolution of chiral alcohols through lipase-mediated enantioselective acylation (transesterification) is one of the major industrial applications of lipases [50]. Hence, the effects of ionic liquid reaction media on the resolution of various... 

The resolution of chiral amines via lipase-catalyzed enantioselective acylation is now a major industrial process, but interest in adopting ionic liquid reaction media has been surprisingly scant. Interestingly, acids could be used as the acyl donor (Figure 10.15) rather than the usual activated ester in a range ofionic liquids. CaLB was employed as the biocatalyst, and water was removed to shift the equilibrium toward the product [130, 131]. The highest rates were found in [BMMIm][TfO], [EMIm][TfO], and [EMIm][BF4]. 

Zhou, L. and Wang, L. (2007) Chiral ionic liquid containing L-proline unit as a highly efficient and recyclable asymmetric organocatalyst for aldol reaction. Chem. Lett., 36 (5), 628-629. 

The aza-Baylis-Hillman reaction of 4-X-C6H4CH=NTs with CH2=CHCOMe, catalysed by PI13P in the newly designed chiral ionic liquid (121), derived from l-(—)-malic acid, gave products with up to 84% ee. This example represents the first highly enantioselective asymmetric reaction in which a chiral medium is the sole source of chirality.176... 

Chiral ionic liquids could become an important class of solvents,194 100 1011 which may even be relatively cheap when prepared from the natural chiral pool with anions such as lactate. However, as yet, their ability to induce enantiomeric excess in catalysed reactions has been only met with limited success.1102 1041 With increasing evidence to suggest that carbene ligands derived from ionic liquid imidazolium cations are involved in certain catalysed reactions it is likely that chiral ionic liquids that act as both solvent and ligand could prove highly useful in stereoselective reactions. Some examples of chiral cations that may lead to ionic liquids are shown in Figure 2.10. 

Some attempts have been made towards asymmetric Diels-Alder reactions by using chiral ionic liquids. However, neither with a chiral cation, viz. A r.A r-di(2. S -2 -mcthylbutaiic)imida/olium.1116 nor a chiral anion, viz. /.-lactate, 117 could any significant chiral induction be observed. However, substantial chiral induction was achieved with a chiral organic catalyst immobilised in either [C4Ciim][PF6] or [C4Ciim][SbF6], as shown in Scheme... 

In terms of chiral ionic liquids, the discussion will focus on Michael addition reactions (Figure 6.8). This reaction has been performed using lactate as... 

Figure 6.8 Asymmetric Michael addition reactions using chiral ionic liquids (a) derived from lactate, (b) derived from proline.

Chiral ionic liquids have also been used to aid enantioselective metal catalysed reactions. For example, homogeneous rhodium catalysed hydrogenations using tropoisomeric biphenylphosphine ligands have been reported using chiral ionic liquids derived from L-proline and L-valine. Enantioselectivities of up to 69% could be achieved and the catalytic system could be reused after extraction with SCCO2. 

Finally, TSOSs can also be used directly as solvents, and applications of those for which the appended entity has a chemical effect on the outcome of the reaction will be explained in more detail during the next sections. On the other hand, some are used as sole solvent and have no effects besides traditional solvent effects. This is the case of chiral ionic liquids (CILs) which have been used extensively as chiral solvents in the hope of transferring the chiral information to the reaction product. CILs could eventually be seen as TSILs where the task would be to induce chirality, despite some promising results, detailing all their features would unnecessarily lengthen this review as other authors skillfully already did [42, 43],... 

Jonathan and Mikami [49] reported a straightforward synthesis of new chiral ionic liquids bearing an imidazolium core, an easy and efficient method (6). Commercially available ethyl lactate was converted into its triflate derivative which upon reaction with 1-methylimidazole gave the triflate salt as a solid in excellent yield. Then anion metathesis was performed to obtain different anions with imidazole cation ... 

S)-Proline-modified functionalized chiral ionic liquid is useful as a recoverable catalyst for direct asymmetric reactions [95] ... 

However, also simple carbohydrates have been transformed in ILs. D-Mannitol and methyl D-glucopyranoside have been used to obtain chiral ionic liquids starting from the corresponding tosyl derivatives by reaction with 4-(dimethylamino(pyridine. A modified tosylation procedure was used in both cases. 

The hydrogenation reaction proceeds up to 80% ee to give the expected product, a doubly chiral ionic liquid bearing the enantiomeric pure (R)-camphorsulfonate anion. Ethanol has been used as diluting solvents in these reactions since the IL was too viscous for the reaction to be run under solvent free conditions. Tire concentration dependence of the chiral induction... 

Figure 11. Enantioselective aza-Baylis-Hillmann reaction in the chiral ionic liquid 11.

We have demonstrated recently that both enantiomeric forms of a novel chiral ionic liquid, R- and S-(3-chloro-2-hydroxypropyl) trimethylam-monium ffA ((R)- and S- CH rA [Tf2N] ) can be readily synthesized in enantiomerically pure form by a simple ion exchange reaction from corresponding (R)- and (S)-chloro-2-hydroxypropyl)trimethylammonium chloride salts which are commercially available (Scheme 1). ... 

Scheme 1. Preparation of a chiral ionic liquid through an ion-exchange reaction...

In an important achievement Vo-Thanh and co-workers realized that chiral ionic liquids such as 35 can act as chiral inducers for the asymmetric MBH reaction.The V-octyl-V-methylephedrinium trifluoromethanesulfonate salt 35, used as solvent in the DABCO-mediated reaction of methyl acrylate and benzaldehyde, produced the corresponding allylic alcohol in 60% yield and 44% ee after 7 days at 30 °C. 

Besides chiral catalysts, chiral reaction mediums were also explored and provided good asymmetric induction. Very recently, Leitner and coworkers performed the reactions in the chiral ionic liquid methyltrioctylammonium dimalatoborate 28 [40]. For the aza MBH reaction of MVK with N (4 bromobenzylidene) 4 toluenesulfona mide, up to 84% ee and 39% conversion were observed (Scheme 13.25). 

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