B

R = H, 4-MePh, 4-OMePh, 2-NO2Ph, 4-CF3Ph, 2-naphthyl,

H BF4

solvent, rt

0 10 recycle runs a

0 10 recycle runs a

R = Me in CH2Cl2 60 min 43%, 86% ee in [EMIm][NTf2] 2 min, 100%, 88% ee in CH2Cl2 120 min, no react/on in [EMIm][NTf2] 20 min, 100%, 95 % ee

5 recycle runs

Scheme 3.14 Imidazolium- and onium-tagged ligands and organocatalysts

Noteworthy, through a judicious choice of the counteranion many imidazolium-tagged organocatalysts displayed ILs characteristics (i.e. melting point below 100 °C, thermal stability, viscosity and phase behaviour) so that they can be viewed as chiral ionic liquids (cILs) able to provide expanded utility in asymmetric synthesis. Indeed, in addition to their use as catalysts in a variety of reaction media with enhanced recyclability due to the typical solubility features of ILs, they could also act as reusable solvents with unique chiral environments.

A variety of cILsbased on combinations of chiral cations or anions deriving from cheap and bio-renewable natural compounds as aminoacids, sugars and terpenes with an achiral counterion have been synthesized and their physical properties determined (Scheme 3.15). In the group of cILs with a chiral cation, besides those deriving from covalent introduction of imidazolium, pyridinium,

COOH

H Br"

N-Bu

COOR1

(S,R)-46a X = NTf2 N+ = NBuMe2 (S)-47a Im, R = H X = NO3, BF4,

(S,R)-46b X = BF4, N+ = N^Me (S)-47c BenzIm, R = H S)"4« R = H

+ c8h17

OTf-

BF4-

N 52

Me C6H13

H13C6 C6H13 'yT

Scheme 3.15 Chiral cations and anions for chiral ionic liquids azolinium or alkylammonium groups in suitable chiral precursors [112], others have been obtained from aminoacids or the corresponding alkyl esters by simple protonation of the nitrogen centre with acids, followed by anion methatesis when different anions are required to lower the melting point of the obtained salts [113]. More recently, cations based on protonated axially chiral spiro bis(heterocycles) or macrocycles with cyclophane-type planar chirality bearing an imidazolium ring have been designed and their promising chiral discrimination ability tested with enantiopure (S)-Mosher acid, but their optical resolution is still a challenging task [114, 115]. On the other side, easy access to cIL with chiral anions has been provided by neutralization of acidic groups of aminoacids, mandelic, lactic, quinic or camphorsulphonic acids [116, 117].

The application of these novel cILs as catalysts in asymmetric synthesis has been mainly focused on organocatalytic enamine based reactions [118] and, as an example, the addition of b-nitrostyrene to cyclohexanones in the presence of 47a or 47c and 5% of co-catalyst (TFA and salicylic acid, respectively) without any solvent afforded the nitro-adduct in 99% ee and nearly quantitative yield. As concerns the use of cILs as solvents, Leitner and coworkers have recently reported that hydrogenation of benchmark substrates in the presence of rhodium complexes with either (S)-enantiopure or racemic BINAP proceeded with the same level of enantioselectivity when the reactions were carried out in 5:1 CH2Cl2/ [MePro][NTf2] mixture [119] (Scheme 3.16a). Using rac-BINAP the formation

MeO2C

CH2Cl2/[MePro][NTf^

MeO2C^k

CO2Me

+ Et2Zn

Scheme 3.16 Chiral ionic liquids as solvents in asymmetric reactions

CO2Me with (S)-BINAP 64% ee with rac-BINAP 67% ee

of two diastereomeric species [(R)-BINAP-Rh-MePro][NTf2] and [(S)-BINAP-Rh-MePro][NTf2] in 2.5:1 ratio was assessed by 31P-NMR spectra and the greater stability, with consequent less reactivity, of the former complex was also supported by kinetic measurements on separate BINAP enantiomers. From these data it was deduced that [MePro][NTf2] can be used as the sole source of chirality through an unprecedented and effective chiral poisoning, so that the hydrogenation is controlled by (S)-BINAP even in the presence of the racemic catalyst.

Other evidences of the still unexplored potentiality of cILs in inducing chirality came from Sharpless dihydroxylation of alkenes with K2OsO2(OH)4 and 56 as solvent, that gave the corresponding diols in yields and ees comparable with the ones obtained using classical conditions ([DHQD]2PHAL catalyst in 1:1 t-BuOH/ H2O) [116]. In the same way, cIL 51 was able to induce moderate enantioselec-tivities (61-76% ee) in copper-catalyzed addition of diethylzinc to enones [120] (Scheme 3.16b, c).

0 0

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