Aldol reaction, aqueous media enantioselectivity

To extend the operation period of prolinamide-derived IL-supported catalysts, bis-amides 58a-e were synthesised from (25, 4R)-4-hydro yproline and various diamines. C2-Symmetric compounds 58c-e bearing p-phenyle-nediamine, l,2-diaminocyclohexane or 1,2-diphenyl ethylenedia-mine ° structural units exhibited excellent catalytic performance in asymmetric cross-aldol reactions between ketones 8 and aldehydes 9 in the aqueous medium and could be recycled 15 times without any decrease of activity or loss of enantiocontrol. Furthermore, bis-amide 58e efficiently catalysed aldol reactions of acetone with a-ketoesters 62 to afford a-hydrojqr-y-ketoesters 63 in a nearly quantitative yield, yet with moderate enantioselectivity (Scheme 10.14). 

In 2013, the Rahman group studied the application of various polar tripeptides for the direct aldol reaction of substituted aromatic aldehydes and aliphatic ketones in an aqueous medium. In the course of their investigations histidine-containing peptide 35 showed the best results for the aldol reactions due to stabilising hydrogen bonding of the side chains of the peptide catalyst (Scheme 13.22b). This catalytic system could be further extended to aldoketoreductase-based mimetic octapeptides for the preparation of chiral p-hydro)yketones in excellent yield and diastereoselectivity and good enantioselectivity. ... 

The group of Moutevelis-Minakakis reported in 2014 the preparation and application of a series of tripeptides containing proline, phenylalanine and tert-butyl esters of different amino acids (see 36, Scheme 13.22c) for the asymmetric aldol reaction of aromatic aldehydes and various substituted ketones in both aqueous and organic medium. The authors assume in the proposed transition-state model, besides the well-known enamine activation, a stabilisation of the aldehyde via hydrogen-bond interactions of the two amide protons of the tripeptide with the carbonyl group of the aldehyde. The desired adducts were isolated in good to excellent yields and with very good diastereoselectivities and enantioselectivities. ... 

L-Threonine-derived catalysts were demonstrated to be remarkably effective for the direct aldol reaction. Lu et al. investigated the potential of serine and threonine analogs in the direct asymmetric aldol reaction in aqueous medium [28]. While L-serine and L-threonine were found to be ineffective, sUylated threonine and serine derivatives were wonderful catalysts for the direct aldol reaction of cyclohexanone and aromatic aldehydes in the presence of water, affording the aldol adducts in excellent yields and with nearly perfect enantioselectivities. L-Serine-derived 9a was inferior to the corresponding threonine-based catalysts. The reaction could be extended to hydroxyacetone, and sy -diols were obtained with very good enantioselectivities (Scheme 3.6). Subsequently, Teo and coworkers also employed silylated serine catalysts for the same reaction [29]. Very recently, Cordova et al. [30] reported a co-catalyst system consisting of 8a and l,3-bis[3,5-bis(trifluoromethyl)phenyl]thiourea, and applied such catalytic pairs to the direct aldol reaction between ketones and aromatic aldehydes both cyclic and acycUc ketones were found to be suitable substrates. 

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