Phenomena asymmetric induction

Striking examples of this phenomenon are presented for allyl and homoallyl alcohols in Eqs. (5) to (7). The stereodirection in Eq. (5) is improved by a chiral (+)-binap catalyst and decreased by using the antipodal catalyst [60]. In contrast, in Eq. (6) both antipode catalysts induced almost the same stereodirection, indicating that the effect of catalyst-control is negligible when compared with the directivity exerted by the substrate [59]. In Eq. (7), the sense of asymmetric induction was in-versed by using the antipode catalysts, where the directivity by chiral catalyst overrides the directivity of substrate [52]. In the case of chiral dehydroamino acids, where both double bond and amide coordinate to the metal, the effect of the stereogenic center of the substrate is negligibly small and diastereoface discrimination is unsuccessful with an achiral rhodium catalyst (see Table 21.1, entries 9 and 10) [9]. 

Absolute asymmetric synthesis refers to the situation in which an asymmetric induction occurs in the absence of an externally imposed source of chirality [5]. Such reactions are invariably carried out in the crystalline state, where the asymmetric influence governing the enantioselectivity derives from the spontaneous crystallization of an achiral compound in a chiral space group. This phenomenon, which is analogous to the spontaneous crystallization of racemates as... 

Normally, additions depicted by model C lead to the highest asymmetric induction. The antiperiplanar effect of OR substituents can be very efficient in the Houk model B ( , , , , ) however it plays no role in model C. Furthermore, the Houk model B must be considered in all cycloaddition-like reactions. The Felkin-Anh model A is operative for nucleophilic additions other than cuprate additions ( ). The epoxidation reactions are unique as they demonstrate the activation of one diastereoface by a hydroxy group which forms a hydrogen bridge to the reagent ( Henbest phenomenon ). The stereochemical outcome may thus be interpreted in terms of the reactive conformations 1 and 2 where the hydroxy function is perpendicular to the olefinic plane and has an optimal activating effect. 

After the pioneering work of Louis Pasteur and Emil Fischer in the middle and at the end of the nineteenth century, respectively, it still took more than fifty years before chemists started to discuss transition state models together with polar and steric effects to gain more insight into the phenomenon of asymmetric induction. Even first observations in organic synthesis of enantioselectivities comparable to those of enzymes in the late fifties and sixties of the 20 century did not convince the chemical community and the term asymmetric synthesis was regarded a mechanistic curiosity rather than a practical way to synthesize compounds of high enantiomeric purity. 

A chiral catalyst is not necessarily in enantiopure form. Deviation from the Unear relationship, namely non-linear effect , is sometimes observed between the enantiomeric purity of the chiral catalysts and the optical yields of the products (Figure 8C.2). The convex deviation—which Kagan [35a] andMikami [36) independently refer to as positive non-linear effect (abbreviated as (+)-NLE) and what Oguni refers to as [35c] asymmetric amplification —is currently attracting much attention for achieving a higher level of asymmetric induction that exceeds the enantiopurity of the non-racemic (partially resolved) catalysts. In turn, (-)-NLE stands for the opposite phenomenon of concave deviation, namely negative non-linear effect. 

Asymmetric induction during the reduction of 4-(48) was observed when a surface-modified carbon cathode was used.70 Optical yields were low but the effect of the chiral amino acid bound to the carbon surface was proved to be a true surface phenomenon. Induction of chirality by homogeneous rather than surface-bound agents has also been studied.71 All the isomeric acetylpyridines (48) were reduced in the presence of three different chiral alkaloids. Both carbinol products 2- and 4-(49) were shown to possess induced chirality, but the 3-carbinol (49) had none under any of the conditions tried. More rapid protonation of the intermediate was proposed to account for the lack of induced chirality. Optimization of optical yields was done.72 The pinacols (50) formed along with 49 were found to have no induced chirality. Optical yields have been as high as 50%.73 The role of electroabsorption was found to be important in the reduction of 2-(48).74 Product distributions were noted as a function of surfactant present in the electrolyte, carbinol 49 being favored... 

In cathodic reactions, adsorption effects would be expected to arise predominantly from adsorbed cations. Perhaps the most interesting phenomenon ascribable to adsorption of cations is the asymmetric induction observed when cathodic reduction of a prochiral substrate is performed in the presence of a chiral cation (Gourley et al., 1967 Homer and Degner, 1948). Table 18 summarizes a few selected cases of this reaction type (for reviews see Homer et al., 1972 Eberson and Homer, 1973) just to illustrate the scope of the reaction. The structural variables affecting the optical yield are unfortunately too complex to cover here. 

The phenomenon has also been referred to as "double asymmetric induction." (9) We have used the term double stereodifferentiation, first introduced by Izumi and Tai (1J)) in order to avoid confusion in cases involving racemates. 

An interesting circumstance develops when two of these techniques are combined in the same reaction, such as when the second reactant also contains a chirality element e.g., when a chiral nucleophile reacts with a chiral carbonyl compound) the chirality elements of each reactant may influence stereoselectivity either in concert or in opposition. This phenomenon is known [58,59] as double asymmetric induction. A simple illustration is shown in Scheme 1.4 and involves the reaction of... 

In order to understand the phenomenon of double asymmetric induction, we need to have a clear picture of the inherent selectivities of each of the chiral partners in closely related single asymmetric induction processes. Consider for example the kinetically controlled aldol addition reactions shown in Scheme 1.5... 

Asymmetric induction The preferential formation of one enantiomer or diastereo-mer over another, due to the influence of a stereogenic element in the substrate, reagent, catalyst, or environment (such as solvent). Also, the preferential formation of one configuration of a stereogenic element under similar circumstances. When two reactants of a reaction are stereogenic, the stereogenic elements of each reactant may operate either in concert (matched pair) or in opposition (mismatched pair). This phenomenon is known [58,59] as double asymmetric induction, or double diastereoselection. See Section 1.5. 

Optical activity in biopolymers has been known and studied well before this phenomenon was observed in synthetic polymers. Homopolymerization of vinyl monomers does not result in structures with asymmetric centers (The role of the end groups is generally negligible). Polymers can be formed and will exhibit optical activity, however, that will contain centers of asymmetry in the backbones [73]. This can be a result of optical activity in the monomers. This activity becomes incorporated into the polymer backbone in the process of chain growth. It can also be a result of polymerization that involves asymmetric induction [74, 75]. These processes in polymer formation are explained in subsequent chapters. An example of inclusion of an optically active monomer into the polymer chain is the polymerization of optically active propylene oxide. (See Chap. 5 for additional discussion). The process of chain growth is such that the monomer addition is sterically controlled by the asymmetric portion of the monomer. Several factors appear important in order to produce measurable optical activity in copolymers [76]. These are (1) Selection of comonomer must be such that the induced asymmetric center in the polymer backbone remains a center of asymmetry. (2) The four substituents on the originally inducing center on the center portion must differ considerably in size. (3) The location... 

The importance of the structure of the BSA molecule on the asymmetric induction is obvious from the phenomenon that the optical yield in the reduction depends largely on the pH of the reaction solution. Dramatic changes in optical yields were observed at pH 3-4 and 7-9, which were attributed to the change in the three dimensional structure of BSA. In addition, the stereoselectivity decreased markedly in a solution of BSA denatured by 0.8 M urea. These results support the idea that the complexation between BSA and the substrate is crucial for asymmetric reduction especially when the concentration of BSA is high. It was suggested that complexation... 

If a chiral center exists in close proximity to a carbonyl, it will influence the approach of an incoming nucleophile, and one face of the carbonyl is likely to be preferred over the other. This phenomenon is known as asymmetric induction. For example, one face of 2-methylcyclopentanone is partially blocked by the methyl group so nucleophilic attack occurs mostly on the opposite face in order to avoid steric hindrance in the transition state. The two possible transition states (attack from top face or bottom face) are diastereomeric and thus are not equal in energy. The transition state with the nucleophile approaching away from the methyl group is more stable (i.e., lower in energy), so that product will be formed faster and this is the major product observed. 

It is some ten years since the subject of asymmetric synthesis and its bearing on the selective production of optically active compounds in nature has been fully reviewed. It was surveyed by McKenzie (82) in 1932 its relationship to the phenomenon of asymmetric induction was discussed in some detail by the present author (123) in 1933 and, finally, the posi-... 

---