Proline catalysis derivatives

Simple L-alanine, L-valine, L-norvaline, L-isolecucine, L-serine and other linear amino acids [ 121 ] or chiral amino acids with a binaphthyl backbone [ 122] and peptides have also been used as asymmetric catalysts [123,124,125,126]. Solid-supported proline-terminated peptides have been used for heterogeneous catalysis of the asymmetric aldol reaction [ 127]. Apart from proline and derivatives, other cyclic compounds such as 5,5-dimethyl thiazolidinium-4-car-boxylate (DMTC) [128], 2-fert-butyl-4-benzyl imidazolidinones [129], (l/ ,25)-2-aminocy-clopentanecarboxylic acid [130], (5 -5-(pyrrolidin-2-yl)tetrazole, (5)-l,3-thiazolidine-4-car-boxylic acid, (5)-5,5-dimethyl-l,3-thiazolidine-4-carboxylic acid, and (5)-hydroxyproline are effective catalysts in asymmetric aldol reactions [126,131,132,133,134,135]. 

This overview about developments in the field of proline-catalysis unfortunately cannot take into full account the vast field of proline-derived catalysts, such as diarylprolinols, 4-silo)yprolines or proline-silyl-ether, to name only a few. These are covered in subsequent chapters of this volume. Furthermore, other great improvements have been made by using immobilised proline catalysts, such as PEG-supported proline or polyelectrolyte-bound pro-line. Going one step further, supported proline catalysts are then applicable in the striving field of continuous-flow reactions. Recent examples include aldol, a-amination reactions and Michael reactions under such conditions. ... 

The chiral auxiliaries anchored to the substrate, which is subjected to diastereoselective catalysis, is another factor that can control these reactions. These chiral auxiliaries should be easily removed after reduction without damaging the hydrogenated substrate. A representative example in this sense is given by Gallezot and coworkers [268], They used (-)mentoxyacetic acid and various (S)-proline derivates as chiral auxiliaries for the reduction of o-cresol and o-toluic acid on Rh/C. A successful use of proline derivates in asymmetric catalysis has also been reported by Harada and coworkers [269,270], The nature of the solvent only has a slight influence on the d.e. [271],... 

Aldehydes bearing a-hetero substituents also typically afford anti products, and the general solution to syn selective a-heteroatom substituted aldehyde-aldehyde aldol processes via enamine catalysis also still remains to be discovered. Nevertheless, the anti process is remarkably useful because a variety of highly substituted aldehydes can be accessed in a single operation using only very inexpensive catalysts, such as proline 6 or the phenylalanine-derived imidazohdinone 46 (Scheme 21) [114, 116, 117, 119-121, 188]. 

As previously noted (Scheme 1), prior to the explosion of interest in iminium ion catalysis as a platform for the activation of a,P-unsaturated carbonyl compounds in 2000, Yamaguchi [29-33] and Taguchi [34] showed that proline derived bi-func-tional catalysts could provide an effective platform for the ion-pair controlled conjugate addition of malonates and nitroalkanes to a, 3-unsaturated ketones with good levels of stereocontrol. 

Very recently the group of Resmini described the development of imprinted microgels mimicking a class I aldolase in the catalysis of the aldol condensation between 4-nitrobenzaldehyde and acetone [79]. They prepared highly crosslinked microgels (80 mol%) based on /V,/V -methyIenebisaery 1 amide as the crosslinker and containing as catalytically active monomer a proline derivative (Fig. 5). 

Notwithstanding the progress in other reaction types, the main thrust in organo-catalysis research centers is on enantioselective catalysis applications [109,110], of which amine-based asymmetric catalysts form the majority [111]. Most of the reactions proceed via the enamine catalytic cycle (Figure 3.38a) or via imonium intermediates. The most common (and most successful) catalysts for such reactions are proline derivatives. Thanks to its secondary amine functionality and relatively high pKa value, proline (pyrrolidine-2-carboxylic acid) is a good... 

Other chiral grafting species which were linked to mesoporous pure silica phases in order to study chiral catalysis reactions include alkaloids and alkaloid derivates (cinchona and ephedrine ), bis(oxazoline), amino alcohols, proline... 

Proline derivatives form enamine intermediates to activate the HOMO of a nucleophile. In contrast, iminium salts are generated with MacMillan s catalyst to activate the LUMO of an electrophile. The formation of the enamine intermediate from proline is reminiscent of the general catalysis of class 1 aldolase in enzymatic catalysis [21]. 

One of the reasons this reaction is so useful is that the products happen to be derivatives of the less readily available (J )-proline. But, as with chiral auxiliaries, if you use a chiral reagent you need a full equivalent of the source of enantiomeric purity (here, (-)-sparteine) which can get prohibitively expensive on a large scale. It is for this reason that the real pinnacles of achievement in asymmetric synthesis make use of asymmetric catalysis, which we turn to next. 

L-Proline could be used as an effective catalyst via dual-enamine-iminium-catalysis modes. Pyrrolidine was ineffective, indicative of the crucial role of proline s carboigrlate moiety. The Meldrum s acid derivatives could be postfunctionalised via methanolysis and in situ decarboig lation to produce complex 1,5-dicarbonyl compounds. This strategy was applied towards the synthesis of polycyclic chromene derivatives (38, Scheme 5.43). ... 

Even though the use of (S)-proline (1) for the synthesis of the Wieland-Miescher ketone, a transformation now known as the Hajos-Parrish-Eder-Sauer-Wiechert reaetion, was reported in the early 1970s, aminocatalysis - namely the catalysis promoted by the use of chiral second-aiy amines - was rediscovered only thirty years later. The renaissance of aminocatalysis was prompted by two independent reports by List et al. on the asymmetric intermolecular aldol addition catalysed by (S)-proline (1) and by MacMillan et al. on the asymmetric Diels-Alder cycloaddition catalj ed by a phenylalanine-derived imidazolidinone 2. These two reactions represented the archetypical examples of asymmetric carbonyl compound activation, via enamine (Figure ll.lA) and iminium-ion (Figure 11.IB), respectively. 

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