Racemate, kinetically labile

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. 

In case of a kinetically labile racemate as guest, a chiral discrimination can be observed during the course of complexation (Scheme 10.4.1, type D), reflecting the different association constants for the two enantiomeric species that inter-... 

Solid, hydrated nickel(II) salts and their aqueous solutions usually contain green [Ni(OH2)6l, the electronic absorption spectmm of which was shown in Fig. 20.21 with that of [Ni(NH3)g]. Salts of the latter are typically blue, giving violet solutimis. In aqueous solution, [Ni(NH3)g] is stable only in the presence of excess NH3 without which species such as [Ni(NH3)4(OH2)2] form. The violet chloride, bromide or perchlorate salts of [Ni(en)3] are obtained as racemates, the catimi being kinetically labile (see Section 26.2). The octahedral complexes trans-[Ni(C104-0,0 )2(NCMe)2] (21.52) and frans-[Ni(C104-< )2(py)4] illustrate the ability of perchlorate ions to act as bidentate or monodentate ligands respectively. The latter complex is discussed again later. 

Kinetically labile and inert complexes Dissociation, association and interchange Activation parameters Substitution in square planar complexes Substitution in octahedral complexes Racemization of octahedral complexes Electron-transfer processes... 

In the kinetic resolution, the yield of desired optically active product cannot exceed 50% based on the racemic substrate, even if the chiral-discriminating ability of the chiral catalyst is extremely high. In order to obtain one diastereomer selectively, the conversion must be suppressed to less than 50%, while in order to obtain one enantiomer of the starting material selectively, a higher than 50% conversion is required. If the stereogenic center is labile in the racemic substrate, one can convert the substrate completely to gain almost 100% yield of the diastereomer formation by utilizing dynamic stereomutation. 

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. 

Another example employed Mitsunobu reaction for the inversion reaction (Figure 10(b)).A single enantiomer of a (stereo)chemically labile allylic-homoallylic alcohol was obtained in 96% yield and 91% ee from the racemate through a lipase-catalyzed kinetic resolution coupled with in situ inversion under carefully controlled (Mitsunobu) conditions. Using this reaction, the algal fragrance component, (S)-dictyoprolene, was synthesized. 

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... 

The reduction of yff-ketoesters to aldols is one of the most important applications of Ru(II)-BlNAP catalysts [7]. As a special bonus, the chirally labile C2 stereogenic center can be exploited in a dynamic kinetic resolution such that racemic reactants yield only one of the four conceivable stereoisomers in high diastereomeric and enantiomeric excess. This strategy has been extended to the reduction of -ketophosphonates 10. The 3-hydroxyphosphonic acids 7 which are accessible by this route constitute promising starting materials for the synthesis of peptide analog and antibiotics [8]. 

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. 

Reaction of racemic aldehyde 245 with chiral 246 resulted in formation of the lactam 247 with 9 1 stereoselectivity in 78% yield. A dynamic kinetic resolution with epimerization of the labile stereocenter in 245 was proposed (Scheme 73) <05CC1327>. 

Consequently, the ionization process is a specific phenomenon caused by the lability of the Si-Br or Si-I bonds and the affinity of silicon for oxygen not all racemization processes involve ionic 1 1 adducts. Moreover, the case of the tin compounds shows that the ability to undergo racemization is connected with the ability to increase coordination number. Thus, since silicon, germanium, and tin compounds show similar conductimetric and kinetic behavior, we may conclude that racemization and nucleophilic substitution are both activated by nucleophiles and involve a coordination extension process as shown in Scheme 67. However, existence of the siliconium ion 209 cannot be excluded in the case of bromosilanes. 

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