Chiral sites

The enantiomerization of phenoxyalkanoic acids containing a chiral side chain has been studied in soil using (Buser and Muller 1997). It was shown that there was an equilibrium between the R- and S- enantiomers of 2-(4-chloro-2-methylphenoxy)propionic acid (MCPP) and 2-(2,4-dichlorophenoxy)propionic acid (DCPP) with an equilibrium constant favoring the herbicidally active f -enantiomer. The exchange reactions proceeded with both retention and inversion of configuration at the chiral sites. 

To catalyze asymmetric transformations, catalytically active sites can be incorporated in different areas of a dendrimer a) chiral sites at the periphery, b) chiral sites in cavities or at the core, c) achiral sites which are surrounded by chiral branches in the interior of the dendrimer. 

Section 3 will deal with catalytic systems whose stereospecificity is mainly controlled by the chirality of the environment of the transition metal, independently of the possible chirality of the growing chain (chiral site stereocontrol). In particular, in Section 3.1 the chirality and stereospecificity of homogeneous catalytic systems based on metallocenes of different symmetries and in different experimental conditions will be reviewed. In Section 3.2 the chirality of model catalytic sites, which have been supposed for isospecific first-generation TiCl3-based and high-yield MgC -supported catalysts, is described. In Section 3.3 we will present a comparison between model catalytic sites proposed for heterogeneous and homogeneous stereospecific site-controlled catalysts. 

In the simpler cases, the discrimination between the two faces of the prochi-ral monomer may be dictated by the configuration of the asymmetric tertiary C atom of the last inserted monomer unit (chain-end. stereocontrol) or by the chirality of the catalytic site (chiral site stereocontrol). The distribution of steric defects along the polymer chain may be indicative of which kind... 

The chiral sites which are able to rationalize the isospecific polymerization of 1-alkenes are also able, in the framework of the mechanism of the chiral orientation of the growing polymer chain, to account for the stereoselective behavior observed for chiral alkenes in the presence of isospecific heterogeneous catalysts.104 In particular, the model proved able to explain the experimental results relative to the first insertion of a chiral alkene into an initial Ti-methyl bond,105 that is, the absence of discrimination between si and re monomer enantiofaces and the presence of diastereoselectivity [preference for S(R) enantiomer upon si (re) insertion]. Upon si (re) coordination of the two enantiomers of 3-methyl-l-pentene to the octahedral model site, it was calculated that low-energy minima only occur when the conformation relative to the single C-C bond adjacent to the double bond, referred to the hydrogen atom bonded to the tertiary carbon atom, is nearly anticlinal minus, A- (anticlinal plus, A+). Thus one can postulate the reactivity only of the A- conformations upon si coordination and of the A+ conformations upon re coordination (Figure 1.16). In other words, upon si coordination, only the synperiplanar methyl conformation would be accessible to the S enantiomer and only the (less populated) synperiplanar ethyl conformation to the R enantiomer this would favor the si attack of the S enantiomer with respect to the same attack of the R enantiomer, independent of the chirality of the catalytic site. This result is in agreement with a previous hypothesis of Zambelli and co-workers based only on the experimental reactivity ratios of the different faces of C-3-branched 1-alkenes.105... 

The chain-end stereocontrol for olefin polymerizations leads generally to lower stereoselectivities (differences in activation energy for insertion of the two enantiofaces generally lower than 2 kcal/mol) than the chiral site stereo-control.18131132 For this reason, the corresponding catalytic systems have not reached industrial relevance for propene homopolymerization. However, some of them are widely used for propene copolymerization with ethene. 

A completely different model of the origin of the syndiospecificity which involves the formation of a lluxional chiral site has also been proposed.147 According to this mechanism, the chirality of the growing chain determines the chirality of the fluxional site, which in turn discriminates between the two monomer enantiofaces. In particular, the assumed model site consists of a hexacoordinated metal (V) atom surrounded by four chlorine atoms assumed to be bridge bonded to other metal (i.e., Al) atoms147 149 (Figures 22a,b). 

The mechanisms for chain-end stereoselectivity (isospecific and syndiospecific) for primary monomer insertion (Section 4.1.1) present relevant analogies with the well-established mechanism of chiral site controlled stereoselectivity (Section 3). In fact, for both mechanisms, the selection between the two... 

The polymerization of monosubstituted vinyl compounds that give polymers like PS and PP produces polymer chains that possess chiral sites on every other carbon in the polymer backbone. Thus, the number of possible arrangements within a polymer chain is staggering since the number of possible isomers is 2" where n is the number of chiral sites. For a relatively short chain containing 50 propylene units the number of isomers is about 1 x lO. While the presence of such sites in smaller molecules can be the cause of optical activity, these polymers are not optically active since the combined interactions with light are negated by other similar, but not identical, sites contained on that particular and other polymer chains. Further, it is quite possible that no two polymer chains produced during a polymerization will be exactly identical because of chiral differences. 

The polymer chain end control model is supported by the observation that highly syndiotactic polypropene is obtained only at low temperatures (about —78°C). Syndiotacticity is significantly decreased by raising the temperature to —40°C [Boor, 1979]. The polymer is atactic when polymerization is carried out above 0°C. 13C NMR analysis of the stereoerrors and stereochemical sequence distributions (Table 8-3 and Sec. 8-16) also support the polymer chain end control model [Zambelli et al., 2001], Analysis of propene-ethylene copolymers of low ethylene content produced by vanadium initiators indicates that a syndiotactic block formed after an ethylene unit enters the polymer chain is just as likely to start with an S- placement as with an R-placement of the first propene unit in that block [Bovey et al., 1974 Zambelli et al., 1971, 1978, 1979]. Stereocontrol is not exerted by chiral sites as in isotactic placement, which favors only one type of placement (either S- or R-, depending on the chirality of the active site). Stereocontrol is exerted by the chain end. An ethylene terminal unit has no preference for either placement, since there are no differences in repulsive interactions. 

From Table 8 it is obvious that the resolution always increases with an increase of the number of benzene rings and that riboflavine is a more powerful selector than the nucleotides, but not as good as TAPA. An interesting experiment shows that it is not always necessary to have the selector coated or bound to the solid phase but that it can sometimes be used as well, dissolved in the mobile phase. The n-dodecyl ester of N-(2,4-dinitrophenyl)-L-alanine is able to discriminate between the enantiomers of l-aza-[6]-helicene, when used as a chiral dopant in the mobile phase in HPLC on a reversed phase column 93) (see Table 9). The usefulness of this dopant must be due to the known ability of a dinitrophenyl moiety to form CT-complexes with polycyclic aromatic hydrocarbons the presence of a chiral site near this group causes resolution of helicenes, because the steric interactions in diastereomeric complexes will be quite different. 

Structures VII and VIII are identical because rotating either one 180° in the plane of the paper makes is superposable with the other one. VII possesses a symmetry plane and is achiral. Achiral stereoisomers which have chiral centers are called meso. The meso structure is a diastereomer of either of the enantiomers. The meso structure with two chiral sites always has the (RS) configuration. 

Epimers differ in configuration about a single chiral center in molecules with more than one chiral center. Anomers are epimers in which the chiral site was formerly a carbonyl C. 

Recently, dendrimers, which are hyperbranched macromolecules, were found to be an appropriate support for polymer catalysts, because chiral sites can be designed at the peripheral region of the dendrimers (Scheme 5). Seebach synthesized chiral dendrimer 14, which has TADDOLs on its periphery and used an efficient chiral ligand in the Ti(IV)-promoted enantioselective alkylation [21]. We developed chiral hyperbranched hydrocarbon chain 15 which has six p-ami-no alcohols [22], It catalyzes the enantioselective addition of diethylzinc to aldehydes. We also reported dendritic chiral catalysts with flexible carbosilane backbones [23]. 

In the second category, a functional site adjacent to that at which an asymmetric reaction is to be effected is reacted with an optically pure reagent (the chiral auxiliary or chiral adjuvant) to give an optically pure modified reactant. In the subsequent reaction to form the new chiral site, two diastereoisomers would be formed in unequal proportions (the reaction is then said to be diastereo-selective). When the chiral auxiliary is then subsequently removed, one of the enantiomers would be present in a greater proportion [e.g. (c), where the optically pure auxiliary reacts with the carboxyl group, and the subsequent reaction is controlled by the chirality of the auxiliary]. A further point to note is that frequently the mixture of diastereoisomers may be separated readily by one of the latest chromatographic techniques (Section 2.31), in which case removal of the auxiliary leads to the isolation of the pure enantiomers. 

Case (e) is interesting because the chirality of the site, coupled with the stereospecific nature of the reaction (Section 5.2.4, p. 504) determines the chirality of the allene which has of course a chiral axis (i.e. the chirality of the chiral site has determined the chirality of the chiral axis). 

The hydroxyl group in saturated alcohols may be located on a primary carbon atom (R-CH2OH), a secondary carbon atom (R2CHOH) or a tertiary carbon atom (R3COH). The hydroxyl-carrying carbon (the a-carbon) in secondary and in tertiary alcohols may be a chiral site ( ), as shown below for ... 

The presence of branching or of functional group substitution in the carbon chain leads to the possibility of a chiral site( ). Thus compound (3) is chiral but compounds (1) and (2) are achiral, a, / -Unsaturated aldehydes (R-CH=CH-CHO) are considered in Section 5.18.2, p. 798. 

Branching in the carbon chain may lead to a chiral site ( ) thus (3) is chiral but... 

The stereoisomeric features of the intermediates and of the product of this reaction should be noted. Thus the silyl enol ether (14) can only have the (El-configuration. The product (16) has two chiral sites ( ) and the aldol is therefore a mixture of erythro/threo ketols in this case the ratio is 23 69. 

Synthesis of Chiral Phosphite Esters with Phosphorus as the Primary Chiral Site... 

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