Enantioselectivity of asymmetric

Since the discovery and development of highly efficient Rh catalysts with chiral diphosphites and phosphine-phosphites in the 1990s, the enantioselectivity of asymmetric hydroformylation has reached the equivalent level to that of asymmetric hydrogenation for several substrates. Nevertheless, there still exist substrates that require even further development of more efficient chiral ligands, catalyst systems, and reaction conditions. Diastereoselective hydroformylation is expected to find many applications in the total synthesis of complex natural products as well as the syntheses of biologically active compounds of medicinal and agrochemical interests in the near future. Advances in asymmetric hydrocarboxylation has been much slower than that of asymmetric hydroformylation in spite of its high potential in the syntheses of fine chemicals. 

Reetz and coworkers developed a highly efficient method for screening of enantioselectivity of asymmetrically catalyzed reactions of chiral or prochiral substrates using ESI-MS [60]. This method is based on the use of isotopically labeled substrates in the form of pseudo-enantiomers or pseudo-prochiral compounds. Pseudo-enantiomers are chiral compounds which are characterized by different absolute configurations and one of them is isotopically labeled. With these labeled compounds two different stereochemical processes are possible. The first is a kinetic separation of a racemic mixture, the second the asymmetric conversion of prochiral substrates with enantiotopic groups. The conversion can be monitored by measuring the relative amounts of substrates or products by electrospray mass spectrometry. Since only small amounts of sample are required for this method, reactions are easily carried out in microtiter plates. The combination of MS and the use of pseudo-enantiomers can be used for the investigation of different kinds of asymmetric conversion as shown in Fig. 3 [60]. 

Based on the recent impressive progress made on asymmetric hydrolysis, the design and bio-transformation of the optically active ethyl 2,2-difluoro-3-hydroxyoctanoate 78 and synthesis of optically active fluorinated [6]-gingerol derivatives are reported [82]. The following criteria were used in the search for a practical route to chiral ethyl 2,2-difluoro-3-hydroxyoctanoate with a high -value (1) the search of an additive to enhance the enantioselectivity of asymmetric hydrolysis by lipases, and (2) the modification of ethyl 2,2-difluoro-... 

Incorporation of substituted BINOL ligands improved the enantioselectivity of asymmetric Baeyer-Villiger oxidations of prochiral cyclobutanones with CHP and... 

Kumar, A. Oehme, G. Roque, J. R. Schwarze, M. Selke, R., Increase in the Enantioselectivity of Asymmetric Hydrogenation in Water Influenced by Surfactants or Polymerized Micelles. ... 

Table 12-4 The Scope of Regio-and Enantioselectivity of Asymmetric Hydroformylation3...

Application of subcritical gaseous CO2 to an organic liquid causes the liquid phase to expand noticeably, due to extensive dissolution of the CO2 into the liquid phase (131). This expansion is accompanied by a reduction in the liquid phase viscosity, an increase in the solubility of H2 in the liquid, and an increase in the mass transfer rates from the gas to liquid phase. There is evidence that this can affect the enantioselectivity of reactions in viscous liquids. The enantioselectivity of asymmetric hydrogenation of unsaturated carboxylic acids in a viscous ionic liquid was shown to be strongly affected by CO2 expansion of the liquid, the enantioselectively being improved for one substrate (atropic acid) and decreased for another (tiglic acid). The results were explained in terms of the solubility and rate of transfer of H2 gas into the expanded ionic liquid (23). The same effect was not observed in expanded methanol. 

Wynne D, Olmstead MM, Jessop PG. Supercritical and liquid solvent effects on the enantioselectivity of asymmetric cyclopropanation with tetrakis[l-[(4-tert-butylphenyl)sulfonyl]-(25)-pyrrolidinecarboxylate]dirhodium(II). J Am Chem... 

The historic discovery of Rh complexes of chiral bisphosphites and phosphine-phosphites dramatically raised the enantioselectivities of asymmetric hydrocarbonylation from -50% ee to almost quantitative values in the first half of the 1990s. The successes with Rh catalysts seemed to replace the earfier used Pt catalysts which often suffered from extensive side reactions such as hydrogenation and isomerization, and low selectivity to fso-aldehydes. At this stage, asymmetric hydroformylation has reached the level of enantioselectivity of asymmetric hydrogenation, the most studied asymmetric reaction. 

Ijima Y, Matoishi K, Terao Y et al. (2005) Inversion of enantioselectivity of asymmetric biocat-alytic decarboxylation by site-directed mutagenesis based on the reaction mechanism. Chem Common 877-879... 

The sense of enantioselection in other reactions can be also analyzed using the conclusions made above. Thus, the structurally rigid Rh complex of (R, R)-QuinoxP ligand (147) always has the bulky tert-hutyl substituent in the upper left quadrant, and the sense of enantioselection of asymmetric hydrogenation (stereoselection in octahedral Rh(III) complexes) is consistent with that of asymmetric addition of arylboronic acids to enones (stereoselection in square planar Rh(I) complexes) (Scheme 1.35). ... 

In contrast, as shown above, the asymmetric environment around the Rh atom changes when the geometry of the Rh-(S)-BINAP complex (148) transforms from octahedral to square planar. Accordingly, whereas the sense of enantioselection of asymmetric hydrogenation catalyzed by 147 is the same as in the case of 148, an opposite sense of enantioselection is observed in the asymmetric addition of phenylboronic acid to cyclic enones catalyzed by 147 and 148. ... 

Water is the medium where all biological reactions take place, including oxidation reactions, but it is a rather unfamiliar solvent for chemists who tend to avoid it, often in an over-prudent approach. When H2O2 and O2 are used as oxidants, water is present as a by-product and this prompted the investigation of catalytic asymmetric oxidation reactions in water. The hydrophobic effect, which consists of the tendency for organic species to self-assemble in water, is the most peculiar effect of this solvent and operates both on apolar catalysts and organic substrates. This overall "squeeze out" effect produces, in several cases, positive effects on both the catalytic activity and the enantioselectivity of asymmetric reactions, as described in the following examples of stereoselective oxidation. 

Numerous studies have demonstrated the solvent influence on enzyme enan-tioselectivity, and sometimes the enantiopreference may even be reversed by medium engineering. For instance, the enantioselectivity of asymmetric reduction of prochiral ketones catalyzed by T. ethanolicus ADH can be controlled by changing the reaction medium containing either organic solvents or ionic liquids [93]. Reversal of the enantioselectivity was reported for S. cerevisiae-catalyzed reduction of hydrophobic phenyl w-propyl ketone by means of the... 

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