Enantiomers insertion mechanism

The theoretical approach involved the derivation of a kinetic model based upon the chiral reaction mechanism proposed by Halpem (3), Brown (4) and Landis (3, 5). Major and minor manifolds were included in this reaction model. The minor manifold produces the desired enantiomer while the major manifold produces the undesired enantiomer. Since the EP in our synthesis was over 99%, the major manifold was neglected to reduce the complexity of the kinetic model. In addition, we made three modifications to the original Halpem-Brown-Landis mechanism. First, precatalyst is used instead of active catalyst in om synthesis. The conversion of precatalyst to the active catalyst is assumed to be irreversible, and a complete conversion of precatalyst to active catalyst is assumed in the kinetic model. Second, the coordination step is considered to be irreversible because the ratio of the forward to the reverse reaction rate constant is high (3). Third, the product release step is assumed to be significantly faster than the solvent insertion step hence, the product release step is not considered in our model. With these modifications the product formation rate was predicted by using the Bodenstein approximation. Three possible cases for reaction rate control were derived and experimental data were used for verification of the model. 

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 molecular mechanism of action of inhalation anesthetics remains a matter of controversy. The classical view is that narcosis is induced by an unspecific disruption of cell membrane lipids by insertion of the lipophilic anesthetic [95]. Studies of enantiomerically pure analogs of several of the compounds depicted in Scheme 4.42 [96] have, however, revealed clear differences between the effects of enantiomers [97] (Scheme 4.43). There is also a growing body of evidence that the anesthetic effect is at least partly because of specific interaction with proteins [98], for example potassium ion channels and central nicotinic acetylcholine receptors [99]. 

The proposed mechanism is shown in Scheme 12.10. Insertion of the palladium(0) complex into the C—I bond of 42a or 42b with retention of axial chirality gives intermediate 44. This intermediate can still provide either enantiomer of 43, depending on the facial selectivity of migratory insertion. The diastereotopic alkene faces are accessed by rotation... 

As a result of the particularities of the MAO activation method noticed so far, it has been concluded that, besides chain back-skip, a different mechanism occurs when using this cocatalyst. One possible explanation might be a reversible chain transfer reaction between the cocatalyst and the active species. As a result of the intrinsic chirality at the metal center, the catalytic system consists of two enantiomers (S and/ . Scheme 9.3). Under different polymerization conditions (i.e., different Al/Zr ratios), the coordination and insertion of the monomer can take place at the metal center of either of the two enantiomers. At higher Al/Zr ratios, a unidirectional transfer of polymer chains from Zr (enantiomer / , for example) to aluminum can be suggested, because reduced molecular weights of the polymer products have been found. Relocation of the chain from aluminum to the other enantiomer of the Ci-symmetric catalyst species (enantiomer 5, Scheme 9.3) and then back... 

The authors proposed a mechanism to explain the preferential formation of the (5)-enantiomer in the final addition product (see Scheme 5.3). Using previous literature references, they proposed the formation of an (S)-BINAP-rhodium complex, possessing an open space where the double bond of the olefin substrate coordinates with its si-face rather than its re-face, which undergoes migratory insertion to form a stereogenic carbon center whose absolute configuration is (5). This was expected to happen with all the substrates tested [10]. 

Since according to this mechanism each enantiomer R or S, independently, would produce isotactic chains, and yet exclusively syndiotactic polymer chains are formed, it has to be concluded that the active enantiomeric species enantiomerize via an intramolecular mechanism and interconvert individually after each monomer insertion. 

Although the exact mechanism of this reaction is not known,the enantiomer differentiation can be rationalized as depicted in Figure 23.2. In the model proposed by the authors, " the Rh2(/ -DOSP)4 catalyst is considered to have a D2-symmetry with two bulky groups. For the substrate rac -21 approaching from the front side, only (5)-21 would be suitably set to afford the C—H insertion/Cope... 

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