Asymmetric organocatalysts hydroxyproline derivatives

Hydroxyproline derivatives 29-33 wherein a silylojg -, sulfonylo - or a carbamoyloxy group is attached to position four of the pyrrolidine ring appeared very useful organocatalysts for various asymmetric reactions (Figure 10.3). 

NCC6H4) did not exceed 10% at 11% ee, in the case of 4-hydroxyproline-derived catalyst 51a the yield was 59% and the ee 72%. The results highlight an important role of the auxiliary carboxy group in asymmetric catalysis and has been taken into account in further studies on the synthesis of immobilized versions of proline-derived organocatalysts. 

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. 

Alexakis et al. proposed in 2010 the use of aminals deriving from 4-hydroxyproline for the asymmetric addition of aliphatic aldehydes to vinyl sulfones." " The idea that a fluorine atom at the C4 position of these pyrrolidine-based organocatalysts could be used to favour one single reactive enamine conformation was further exploited by the same authors in 2011, designing a catalyst (28) able to afford excellent yields and enantioselec-tivities (Scheme 11.24). ... 

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