A novel recyclable prolinamide-derived ionic-liquid-supported organocatalyst of asymmetric cross-aldol reactions in aqueous medium has been developed. In its presence, aromatic aldehydes react with cyclic or linear ketones to afford chiral aldol adducts in moderate to high yields and with excellent dr (anti/syn up to 96:4) and ee (81–99 %) values that do not tend to decline over ten recycles of the catalyst. Furthermore, it allows a highly enantioselective catalytic synthesis of linear bis-aldols in aqueous medium.

A (1S,2S)-1,2-diphenylethane-1,2-diamine derivative modified with an N-(4-carboxybutyl)imidazolium cation and PF₆^– anion has been developed and applied as a recyclable organocatalyst of the asymmetric 1,4-conjugate addition of 4-hydroxy-2H-chromen-2-one to 1-substituted buten-3-ones or cyclohexen-3-one to afford corresponding Michael adducts in high yields (up to 97 %) and enantioselectivities (up to 90 % ee). The most active (S) enantiomer of the clinically useful anticoagulant warfarin was prepared in this way. The catalyst exhibited better recyclability than its known analog, which does not contain a carboxy group: it could be recycled 5 times in the reaction without a significant decrease in product yield or ee values. Gradual deactivation of the catalyst was caused by leaching during workup rather than by off-cycle reactions between the catalyst and reagents.

The first primary amine-derived organocatalyst modified with an ionic group for asymmetric Michael reactions of C-nucleophiles with α,β-unsaturated ketones was synthesized. In the presence of this catalyst and an acidic co-catalyst (AcOH), hydroxycoumarin and its sulfur-containing analogue reacted with benzylideneacetone derivatives or cyclohexenone to afford the corresponding Michael adducts in high yields (up to 97%) and with reasonable enantioselectivity (up to 80%). The catalyst could be easily recovered and efficiently reused three times, afterwards, its activity and stereodifferentiating ability gradually declined. The analysis of recovered catalyst samples by ESI-MS allowed us to detect undesirable side reactions that poisoned the catalyst, and propose an approach for its reactivation.

C₂-Symmetric (S)-prolinamides modified with ionic groups and bearing achiral diamine units were synthesized. Their potency as reusable organocatalysts for asymmetric aldol reactions of cycloalkanones or methyl ketones with aromatic (heteroaromatic) aldehydes in the presence of water was demonstrated. The 1,4-diaminobenzene-derived catalyst exhibited good catalytic performance and excellent recoverability over at least 15 reaction–regeneration cycles under the studied conditions.

The first C₂-symmetric immobilized organocatalyst for asymmetric aldol reactions containing the (1R,2R)-bis[(S)-prolinamido]cyclohexane unit tagged with two imidazolium⁺/PF₆^– ion pairs has been synthesized. In its presence, (hetero)aromatic aldehydes reacted with linear or cyclic ketones in aqueous media to yield chiral aldols with high diastereo- and enantioselectivities and the catalyst could be recovered and reused at least 10 times without any decrease in the reaction rate or selectivity.

The deactivation pathways of Jørgensen–Hayashi-type organocatalysts modified with an ionic liquid fragment in asymmetric Michael reactions of α,β-enals with C- (nitromethane, dimethylmalonate) or N-nucleophiles (N-carbobenzyloxyhydroxylamine) that involved an iminium-ion formation step were studied for the first time by the electrospray ionization mass spectrometry (ESI-MS). “Parasitic” side reactions and undesirable cation intermediates that poisoned the catalysts were identified in accordance with their m/z values as well as their relation to the reported mechanisms of Michael reactions in the presence of O-TMS-α,α-diarylprolinol (TMS=trimethylsilyl) derivatives. The proposed approach may be useful for the study of transformations of other types of organocatalysts modified with ionic groups in various organocatalytic reactions and for the development of novel robust catalysts and processes that would be suitable for large-scale industrial applications.

Chiral ionic liquids bearing O-silylated α,α-diphenyl (S)- or (R)-prolinol units tagged to the imidazolium cation were synthesized and their activity as catalysts in the Michael addition of nitroalkanes to α,β-unsaturated aldehydes was evaluated. Respective (S) or (R) adducts were obtained in the reactions in high yields (up to 95 %) and with high enantioselectivity (up to 99 % ee). Remarkably, the immobilized organocatalysts could be used five times without any decrease in product yields or ee values. (R)-Michael adducts could be easily transformed into the most active (R) enantiomers of medications Phenibut, Baclofen, and Rolipram for the treatment of CNS disorders.

O-TMS-α,α-diphenyl-(S)-prolinol derivative bearing an ionic liquid fragment was synthesized for the first time and proven to be an efficient catalyst for the asymmetric Michael reaction of aromatic α,β-unsaturated aldehydes with dialkyl malonates. The prepared catalyst can be recovered four times and used in the same reaction without a decrease in activity or a decrease in the enantioselectivity of the reaction.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Tetraalkylammonium salts bearing PF₆^– and BF₄^– anions have been recognized as recoverable phase-transfer catalysts for the synthesis of 1,1-dichlorocyclopropane and α-(trichloromethyl)carbinol derivatives from alkenes or aldehydes in the heterogeneous system KOH(s)/CHCl₃. The catalysts retained their catalytic activity over several reactioncycles.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)