Asymmetric Aldols Catalysed by Proline, Its Derivatives and Related Catalysts

Asymmetric Aldols Catalysed by Proline, Its Derivatives, and Related Catalysts 

Extensive molecular dynamic simulations of proline-catalysed asymmetric aldol condensation of propionaldehyde in water have revealed that the stereoselectivity can be attributed to differences in transition-state solvation pattems. The hydrogen bond concept has been applied to design new proline-based organocatalysts. 4-Hydroxyproline derivatives bearing hydrophobic groups in well-defined orientations have been explored as catalysts in water an advantage of aromatic substituents syn to the carboxylic acid moiety has been attributed to a stabilizing transition-state hydrophobic interaction and this is supported by quantum mechanics (QM) calculations. Catalysts and solvents were screened for reaction between cyclohexanone andp-nitrobenzaldehyde. 

A series of L-proline amides with 2-aminoamidazoles have promoted inter- and intramolecular aldol reactions in high yields, ee 98% and de 98/2, in the presence of tetraflu-oroacetic acid (TEA) catalyst. 

Aldol reactions between cyclic ketones and aldehydes have been used to evaluate the excellent diastereo- and enantio-selectivities found using a multifunctional catalyst (15) featuring a prolinamide moiety, a gm-diamine unit, and a urea group. This model has also demonstrated that the choice of the anion of an achiral triazabicyclo[4.4.0]dec-5-ene-derived guanidinium salt, used as a cocatalyst for proline, allows preparation of either mti- or yn-aldol with a very high ee value.  

Chiral imidazolium salts (16) derived from tran -L-hydroxyproline have catalysed aldol reaction in [Bmim]NTf2 as solvent with near quantitative yield, dr 99 1 and ee 89% the origins of the selectivity have been discussed with reference to salts having different H-bonding potentials.  

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