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The undesirable side-processes responsible for the fast deactivation of primary amino acid derived organocatalysts in asymmetric aldol reactions are identified. A new ionic-liquid-supported (S)-valine-/(S)-α,α-diphenylserinol-derived catalyst (9) is designed on the basis of these results and exhibits much better recyclability in asymmetric syn-aldol reactions between hydroxyacetone and aldehydes. Furthermore, this catalyst appeared to be useful for the stereoselective synthesis of the naturally occurring 1(3H)-isobenzofuran-1-one scaffold through an asymmetric syn-aldol/lactonization cascade reaction.

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.

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.

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)

A direct asymmetric aldol reaction between unmodified aldehydes and ketones was achieved using the (S)-proline/poly(diallyldimethylammonium) hexafluorophosphate heterogeneous catalytic system with enantioselectivities and yields comparable to those obtained in the (S)-proline-catalyzed reactions performed under homogeneous conditions. Recycling of the catalyst was possible at least six times without loss of activity and enantioselectivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Tetraalkylammonium and 1,3-dialkylimidazolium tetrafluoroborates and hexafluorophosphates were employed for the first time as recoverable phase-transfer catalysts in multiphase reactions of CH-acids, in particular in solid base-promoted cross-aldol condensations. The catalysts retained their catalytic activity over several reaction cycles. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)