Asymmetric reaction cycle

The required chiral sulfur ylide of type 59 is formed in a reaction with a diazo compound in the presence of an achiral metal catalyst. Subsequently, asymmetric reaction of the chiral ylide 59 with the C=N double bond of the imine proceeds diastereoselectively and enantioselectively, giving the optically active aziridine 57. The chiral sulfide catalyst released is then used for the next catalytic cycle. The cat-alytically active species in the asymmetric process is the sulfide, so this concept can also be regarded as an organocatalytic reaction. 

Several organocatalysts have been recycled efficiently (selected examples are shown in Scheme 14.2). For example, the Jacobsen group has reported results from an impressive study of the recycling of the immobilized urea derivative 6, a highly efficient organocatalyst for asymmetric hydrocyanation of imines (Scheme 14.2) [11]. It was discovered that the catalyst can be recycled and re-used very efficiently - over ten reaction cycles the product was obtained with similar yield and enantioselectivity (96-98% yield, 92-93% ee). 

As if this were not enough, Soai et al. [4] also used this system to demonstrate for the first time the asymmetric amplification during autocatalysis that is inherent in the Frank model. Thus 20 mol% of (S)-9b with an ee of only 2% gave, with autocatalysis, (S)-9b with an ee of 10%. In further reaction cycles the enantiomeric excess rose from 10 through 57 to 81 and finally to 88% (Fig. 1). There was a 942-fold increase in the amount of product after four cycles. The asymmetric amplification shown by this simple selfrepli-cating system behaved, in fact, as predicted by the simple, theoretical Frank model. [18]... 

Figure 7. Concentrations of reaction products during an exhaust pulse of 3 s at 400°C with asymmetric A.-cycling (0.68s rich / 0.64s lean / 0.60s rich / 0.56s lean / 0.52s rich) during pulse. A Simulated and CO equivalents, B Measured and CO equivalent concentrations, C Measured concentrations of reaction products. The explanation of the meaning of the different arrows is given in caption of fig. 6. Oxygen equivalent peak heights A 21%, B 1.75%.

Recently it has been shown that optically active quartz crystals as asymmetric inductors become very effective in autocatalytic enantioselective reactions. Soai et al. have shown that in asymmetric autocatalysis, the action of small amounts of chiral reaction products (involved in the reaction cycle) may enhance the enantioselective excess by a factor of 94 after introduction of an intermediate into the reaction. Optically active synthetic quartz crystals were used in this reaction with ratios of 1 1.9 quartz to aldehyde and 1 2.2 quartz to diisopropyl-zinc. 

The main message that the authors would like to share with the readers of this book is as follows Elucidation of the intrinsic mechanism of generation of chirality in catalytic asymmetric reactions is a much more ambiguous task than it is commonly accepted. That is stipulated for two main reasons (1) experimental problems in the studies of catalytic cycles and (2) inevitable ambiguity in the interpretation of the computational data. 

The reaction pool of a catalytic asymmetric reaction is a sophisticated system involving numerous species that are either involved in a catalytic cycle or are off-loop species. All these species are likely to coexist in fast equilibria, which opens a possibility for various pathways to converge or return to the resting state before the catalytic cycle is completed, yielding the product and recovering the catalyst. Solvent molecules are likely to participate in these equilibria. A vast majority of these interconverting species cannot be detected experimentally due to their relative instability and/or high reactivity. 

Furthermore, most of the elementary steps that occur in the reaction pool of a catalytic asymmetric reaction are stereoselective, because usually intermediates are diastereomers having different chemical properties. It means that if we are able to observe a stereoselective transformation of some species experimentally, we cannot directly conclude that this transformation is a stereodetermining stage of the catalytic cycle, even if this transformation can lead to the correct handedness of the product. 

Recently, asymmetric reactions using chiral Lewis acids have been demonstrated to achieve several highly enantioselective carbon-carbon bondforming processes using catalytic amounts of chiral sources [64, 65]. However, chiral Lewis-acid-catalyzed asymmetric reactions of nitrogen-containing substrates are rare, probably because most chiral Lewis acids would be trapped by the basic nitrogen atoms to block the catalytic cycle. For... 

In parallel, Xu and coworkers discovered that in the presence of similar I L-tagged pyrrolidines 84c,d the reaction proceeded nearly as efficiently in the [bmimJIPFs] medium, so there is no need to dehver the acid co-catalyst (TFA) to the system because this role is obviously played by the IL fragment [96]. Catalysts 84a,b were recovered from the reactant medium by precipitation with ether, while the 84c,d/ IL systems were reused after product extraction without further purification. Four reaction cycles of catalysts 84 did not reduce reaction diastereo- and enantioselec-tivities however, the recovered catalysts gradually became less active with each cycle. Surfactant-type IL-supported asymmetric organocatalyst 84e synthesized by Luo and Cheng and coworkers in 2006 catalyzed Michael addition to nitroalkenes with high stereoselectivities in water without any additives [97]. 

Zlotin et al. synthesized the new amphiphihc (S)-proline-modified task-specific chiral ionic liquid 41, bearing hydrophobic anions for asymmetric aldol reactions in water (Scheme 8.17). This hexafluorophosphate salt gave a suspension in water, and high yields and diastereo- and enantioselectivities were observed for the reaction of cyclohexanone with aryl aldehydes. This catalyst could be recycled easily, and retained its activity and selectivity over at least five reaction cycles [43]. A similar type of catalyst was reported by Trombini et al. [44] for carrying out highly enantioselective aldol reactions in water. High enantioselectivities and... 

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