Chiral pockets

The results obtained have indicated the formation of a chiral pocket around the metal which was able to recognise selectively a single... 

The alkaloid adsorbed on the platinum surface could form a tridimensional space within which the hydrogenation reaction can preferentially occur, due to a close interaction with QN. This space was called chiral pocket in analogy to biological systems that show high differentiation ability due to shape discrimination (Figure 14.11). 

Figure 14.11 Example of the chiral pocket for the tilted surface open(5) conformation. Functional groups 1 and 2 are able to give bonding interactions, while the hydrocarbon skeleton of the alkaloid gives repulsive interactions, allowing only some molecular shapes to adjust themselves in the proximity of the quinuclidine nitrogen [244],...

The modulation of the chiral pocket, possible by O-alkylation of the hydroxylic moiety, was found to be in line with the observed experimental variations of enantio-discrimination when O-alkyl-modified cinchonidine was used as surface modifier. 

Whereas the simple bidentate nitrogen ligands proved to be rather limited, the frequent occurrence of a set of four P-phenyl or alkyl substituents, e. g., in coordinated Binap, MeO-Biphep, Josiphos or Duphos (shown, from left to right in Scheme 1.4), offered many more reporters . In this way, one can develop a more detailed NOE picture of how the complexed substrate interacts with the chiral pocket offered by these auxiliaries. From these NOE studies [97, 98] it can be shown that the atropisomeric bidentate ligands Binap and MeO-Biphep tend to have fairly classical axial and equatorial P-phenyl substituents. 

The bidentate oxazoline ligands 85 and 86 (and derivatives thereof) are excellent reporter ligands, and several studies have used NOEs to determine the nature of their chiral pockets [61, 113, 114, 126]. NOESY studies on the cations [Ir(l,5-COD)(86)]+ and several cationic tri-nudear Ir(iii)(hydrido) compounds [110], e. g. [Ir3(p3-H)(H)5(86)3] +, 87, in connection with their hydrogenation activity, allowed their 3-D solution structures to be determined. In addition to the ortho P-phenyl protons, the protons of the oxazoline alkyl group are helpful in assigning the 3-D structure of both the catalyst precursors and the inactive tri-nudear dusters. Specifically, for one of these tri-nudear Ir(iii) complexes, 87 [110], with terminal hydride ligands at d -17.84 and d -21.32 (and a triply bridging hydride at 5 -7.07), the P-phenyl and oxazoline reporters define their relative positions, as shown in Scheme 1.5. 

These NOE studies teach us that many successful P (or N...etc) auxiliaries possess a relatively rigid and intrusive chiral pocket [105, 107]. The shape of this pocket is a function of the individual chelate ligand, i. e., there is no one successful shape. 

Eq. 59), and even surprisingly high for aliphatic ketones such as 2-butanone, a substrate that offers very little steric discrimination (Eq. 60). Reagent 74 is less effective than 70 in allylations of aldehydes (e.g., 90% ee vs. >98% ee for 70 in the allylation of benzaldehyde). The superior reactivity and selectivity of 74 with ketones is ascribed in part to the lesser steric bulk of the phenyl substituent compared to the trimethylsilyl unit of reagent 70. The smaller phenyl substituent of 74 would provide a better fit for ketones in the chiral pocket of the reagent. 

A well-defined chiral pocket produced by the binaphthyl skeleton and the appended bulky 3,3 substituents, (iii) A ring structure attached to the phosphoric acid moiety to prevent free rotation at the a-position of the phosphorus center. This feature is not found in other Bronsted acids such as carboxylic and sulfonic acids (Figure 5.2). 

Williams group observed low enantioselectivities for the Michael addition of a prochiral nucleophile, ethyl 2-cyanopropionate 623, to methyl vinyl ketone 624 catalyzed by chiral platinum complexes (Scheme 8.196)." The NMR analysis indicated that these cationic Pt complexes act as Lewis acids toward nitriles. The X-ray crystal structure as well NMR analysis showed that the solvent ligand that is readily displaced by an organic substrate is situated cis to the nitrogen donor in the Pt complex and, therefore, is in a chiral pocket created by the oxazoline ring. 

Chiral pockets have been created, employing optically active ligands derived from l,2 -binaphthol. Asymmetric alkylations with nearly 70% optical yield have been realized using this method.438... 

All living organisms are chemical factories, and virtually every chemical reaction that occurs in a living system is catalyzed by special proteins called enzymes. All enzymes are globular proteins. Folding the peptide chains into a compact structure creates a chiral pocket. This is called the active site of the enzyme. The extraordinary specificity that enzymes show for their given substrate molecules is because the active site exactly matches the dimension and shape of the molecules upon which the enzyme acts. One reason enzymes speed reaction rates is that enzymes capture reacting molecules and hold them in place next to each other. Furthermore, key amino acid side chains are located in the active site of each enzyme. For example, if a reaction is catalyzed by acid, then an acidic side chain will be located in the active site, exactly where it is needed to catalyze the reaction. 

A different mechanism operates in the direct a-heteroatom functionalization of carbonyl compounds when chiral bases such as cinchona alkaloids are used as the catalysts. The mechanism is outlined in Scheme 2.26 for quinine as the chiral catalyst quinine can deprotonate the substrate when the substituents have strong electron-withdrawing groups. This reaction generates a nucleophile in a chiral pocket (see Fig. 2.6), and the electrophile can thus approach only one of the enantiotopic faces. 

Interestingly, if the separate epimers of the (ft)-PROPHOS complexes (i75-C5H< )[(R)-PROPHOS]Ru=C=CHR + are employed, then the two rotamers of the vinylidene are diastereomeric [Eq. (65)]. Consiglio and Morandini (76) found that the difference in population of these interchangeable conformers appears to be controlled by steric factors and presumably reflects the relative ability of the two rotamers to fit into the chiral pockets formed by the phosphines. 

In most of these ligands the chiral center is far removed from the site where the prochiral substrate coordinates to the transition metal, so that little diastereo-differentiation might be expected. However, the chirality of the backbone controls the conformation of the bulky diarylphosphine groups and hence generates a chiral pocket around the metal, with aryl groups in axial and equatorial positions. This imposes C2 symmetry on the complex, as shown in (22-X). Viewed from the side, such a complex can schematically be divided into sterically hindered and open quadrants (22-XI). A prochiral substrate will then naturally bind with the jr-face that leads to the product with the least steric repulsion. 

Advantage Generation of a chiral pocket around the catalytically active metal centre. 

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