99% to 83% over 4 cycles

Scheme 3.13 Organocatalyzed reactions in ionic liquids minimizing the leaching of toxic osmium (<0.03%) in the diol product, isolated in good yield and optical purity over six reaction cycles [96].

When hydrolytic kinetic resolution of racemic epoxides is carried out in organic solvents the catalytically active Co(III)-salen complex is usually reduced to the inactive Co(II)-form, that needs to be reoxidized before reuse. In THF/ [BMIm][PF6] 4:1 mixture, instead, the Co(III) active form was stabilized against reduction and it could be recycled up to ten times without deterioration of its performances. In the same reaction medium also a Co(II)-precursor could be used since its aerobic oxidation was greatly facilitated by the IL [97] (Scheme 3.12b).

Carbonyl-ene reaction of methyl trifluoropyruvate and olefins in the presence of In(III)-38 complex displayed marked rate acceleration, while enantioselectivity was not affected, in [C6MIm][PF6]/1,2-dichloroethane 1:1 mixture with respect to the same reaction performed in neat organic solvent and, after separation of products by extraction, the IL phase was reused for seven times without any loss of the catalyst activity [98] (Scheme 3.12c).

Organocatalytic aldol reactions, carried out in [BMIm][PF6] using l-proline, gave moderate to good yields and enantioselectivities but the catalyst performances slightly declined in successive runs after extraction of products with diethyl ether [99]. Less common guanidinium-based ILs were also tested for these reactions and products with higher optical purities were obtained at -25 °C [100]. By using L-prolinamide 39 in [BMIm][BF4] aldol adducts of acetone with aliphatic and aromatic aldehydes could be isolated in satisfactory yields and 91-99% ee (higher than in acetone) (Scheme 3.13a) [101].

Remarkable acceleration rate was evidenced in the addition of cyclohexanone to N-protected a-imino ethylglyoxylate (Scheme 3.13b) [102] and a-aminoxyla-tion of aldehydes with nitrosobenzene [103] catalyzed by proline in [BMIm][BF4].

High conversions of substrates were achieved within 15-30 min with excellent steroselectivity, maintained for up to six cycles with only minor decreases in the products yields.

In order to improve the solubility of catalysts in ILs and thus enhance their immobilization in the ionic phase, decreasing their possible leaching in the extraction solvents, different classes of chiral ligands and organocatalysts have been tagged with a suitable onium cation to give IL-supported derivatives with increased recyclability [104].

Among selected examples of the application of onium-tagged catalysts in ILs media, ferrocenyl phosphines 40a-b bearing an imidazolium moiety showed excellent performances (100% conv, 99% ee) as the native ligands in the hydrogenation of methyl acetamidoacrylate or itaconic acid in biphasic [BMIm] [BF4]/ t-butyl methyl ether system. The affinity of rhodium complex for IL phase was significantly improved and only 0.1% of metal leaching in the organic phase was detected, this value found to be 23-fold lower than that determined in the reactions with unmodified catalysts [105]. In the same way, ruthenium(p-cymene) complexes with ionic ligands 41a or 41b homogeneously dissolved in [BMIm][PF6] displayed nearly constant selectivity along 6 recycle runs in ATH of ketones with azeotropic formic acid/TEA mixture and slight higher conversions were achieved with respect to the original Noyori's catalyst in the same reaction conditions [106, 107]. Some Diels-Alder reactions of oxazolidinones and cyclopentadiene were comparatively carried out in [EMIm][NTf2] or dichloromethane in the presence of Cu(II)-bis-oxazoline catalysts and a marked improvement of reaction rate (2 vs. 60 min for N-acryloyloxazolidinone) was evidenced the IL medium, also for less reactive substrates. The IL-supported ligand 42 displayed high enantioselectivity and more effective immobilization in the ionic phase with respect to the uncharged analogue, so that it could be recycled ten times without any erosion of its performances [108] (Scheme 3.14a).

Michael addition of cyclohexanone to a number of nitroalkenes with pyrroli-dine-pyridinium organocatalyst 43 well proceeded in [BMIm][BF4] without any acid additive usually required for this reaction. In comparison with organic solvents, halved reaction times were sufficient in the IL to achieve full substrate conversion and good recyclability of 43 was also demonstrated (Scheme 3.14b). Furthermore, on the basis of the diminished selectivity observed in a parallel experiment using 43 in solvent-free conditions, the authors suggested that the IL might play an important role in stabilizing the iminium-ion transition state (evolving into the enamine intermediate) and synergistically operate with the or-ganocatalyst in the improvement of asymmetric induction [109]. Satisfactory results in [BMIm][BF4] were also obtained in the same reaction promoted by 44 [110] and aldol condensation of acetone with aromatic aldehydes catalyzed by proline salt 45, that afforded aldol adducts in yields (53-94%) and optical purities (64-93%) higher than those achieved with DMSO as solvent [111]. Both 44 and 45 could be reused up to six times without significant decrease in their activity and selectivity.

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