Racemic compounds chirally labile

Racemate resolution, 1, 2 Racemic compounds alcohols, 45 chirally labile, 75 computer simulation, 79 diphosphines, 26 dynamic resolution, 75 esters, 309... 

Dynamic Resolution of Chirally Labile Racemic Compounds. In ordinary kinetic resolution processes, however, the maximum yield of one enantiomer is 50%, and the ee value is affected by the extent of conversion. On the other hand, racemic compounds with a chirally labile stereogenic center may, under certain conditions, be converted to one major stereoisomer, for which the chemical yield may be 100% and the ee independent of conversion. As shown in Scheme 62, asymmetric hydrogenation of 2-substituted 3-oxo carboxylic esters provides the opportunity to produce one stereoisomer among four possible isomers in a diastereoselective and enantioselective manner. To accomplish this ideal second-order stereoselective synthesis, three conditions must be satisfied (1) racemization of the ketonic substrates must be sufficiently fast with respect to hydrogenation, (2) stereochemical control by chiral metal catalysts must be efficient, and (3) the C(2) stereogenic center must clearly differentiate between the syn and anti transition states. Systematic study has revealed that the efficiency of the dynamic kinetic resolution in the BINAP-Ru(H)-catalyzed hydrogenation is markedly influenced by the structures of the substrates and the reaction conditions, including choice of solvents. 

When so-called kinetic resolution occurs in a system like this, one enantiomer of the racemic substrate reacts much faster than the other yielding preferentially only one diastereoisomer. The chemical yield in those systems is only 50% or less. Racemic compounds with a chirally labile stereogenic centre, however, may yield full conversion to one diastereoisomer via racemization prior to hydrogenation. 

The Pfeiffer effect is a term used to describe changes in the optical activity of solutions containing a chiral compound (the environmental substance ) on the addition of a racemic dissymmetric complex. The effect is generally attributed to a shift in the position of the equilibrium between d and l isomers for the racemic complex. The exact mechanism involved in mediating the chiral interaction is unknown. Perhaps surprisingly, both environmental substance and complex may simultaneously be cations. Studies of the Pfeiffer effect usually involve a moderately labile racemic complex [Cr(ox)3]3 is a popular choice for such studies, summarized in Table 82. Other studies of the optical activity of tris oxalates include work on photoinduced optical activity,898 photoracemization899 and the solid-state racemization of K3[Cr(ox)3]. 900 901... 

Tetrahedral Four-Coordinate T-4 In contrast to the chemistry of carbon compounds, and some main group compounds such as the structure shown in Figure 5.4, Werner-type T-4 coordination complexes are too labile to isolate in solution as individual enantiomers. The presence of chiral ligands can influence the racemic (diastereomeric) equilibrium and make the preparation and isolation of... 

P-Hydroxy sulfoximines are thermally labile and revert to their starting carbonyl compound and sulfoximine on mild thermolysis. This property has been exploited effectively as a method for the resolution of racemic chiral cyclic ketones.65 For example, the addition of the lithium salt of (+)-(S)-2b (99% ee) under kinetically controlled conditions (-78 °C) to racemic menthone gave three of the four possible diastereomeric adducts. The major two adducts resulted from attack on the menthone from the equatorial direction. These diastereomeric adducts could be readily separated by column chromatography. Thermolysis of the individual two major diastereomeric carbinols at 140 °C gave d- and /-menthone, respectively, in high enantiomeric purities (90-93% ee). This methodology has been successfully applied to the resolution of other 2-substituted cyclohexanones as well as other chiral ketones that have served as advanced synthetic intermediates for the synthesis of natural products.66-69... 

Tetrahedral complexes do not exhibit geometrical isomerism. However, they are potentially chiral just as is tetrahedral carbon. The simple form of optical isomerism exhibited by most organic enantiomers, namely four different substituents, is rarely observed because substituents in tetrahedral complexes are usually too labile" for the complex to be resolved, i.e., they racemize rapidly. However, an interesting series of cyclopentadienyliron phosphine carbonyl compounds (see Chapter 15 for further... 

Even if chirality is not a primary interest, the chemist should be aware of its presence, notably in the interpretation of NMR data for structure determination. In kinetically labile systems formed by self-assembly, the study of racemization kinetics offers vital information on the robustness of the system, and the possible mechanisms of decomposition or flagmentation. In short, what appears at first to be an extra complication in an already complex system does in fact offer the chemist new means of investigation and control over the properties of these compounds. 

A classical method for the preparation of enantiopure compounds is the resolution of racemate. However, it is much more effective to use the selective synthesis of the desired enantiopure substance via enantioselective approach. Stereoselective methods of synthesis have been widely developed in organic chemistry. The method of asymmetric synthesis has been known since the nineteenth century and asymmetric catalysis has witnessed an enormous amount of development in recent decades as shown in Chapter 3. In contrast, the asymmetric synthesis of coordination compounds has only recently become a subject of systematic investigation. This is no doubt related to the fact that the chirality of coordination compounds is a much more complex phenomenon than that of organic compounds, because of higher coordination and the multitude of possible central atoms. Furthermore, while in organic chemistry the chiral tetrahedral carbon centres can be prepared without racemization, in contrast T-4 metal centres are very often labile. In fact it is even difficult to prepare compounds with a metal centre coordinated to four different monodentate ligands, and thus the possibility of obtaining one enantiomer is excluded in most cases. 

Taking an example of a sulfur-stabilized benzyllithium compound, Hoffmann and coworkers performed two reactions of the racemic a-thio carbanion with a racemic or a chiral aldehyde [Eq. (3)] [17-19], and found that both reactions afford an identical diastereomeric ratio of the product. From these results, they have concluded that the sulfur-stabilized benzyllithium compound epimerizes faster than it reacts with the aldehyde, i.e., it is configurationally labile in THF at -78°C. 

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