INFLUENCE OF CHIRAL LIGANDS

The introduction of chiral ligands on a reagent or a catalyst induces asymmetry that will be transmitted to the corresponding diastereoisomeric transition states. In most of the cases, the ligands favor rigidified chelates, and there are only a few low-energy conformers to consider. 

Rigidified binuclear zinc chelates are formed, and their asymmetry promotes the facial diastereodifferentiation of the aldehyde carbonyl group in a highly enantiose-lective reaction ( 2.5.1,6.5.1). Chiral aminoalcohols and diamines are the most efficient ligands to promote asymmetric conjugate additions of lithio- or magne-siocuprates to a,p-unsaturated carbonyl compounds [112] ( 7.10.1). 

These considerations have been used to design new rhodium ligands [114, 115]. For instance, Achiwa and coworkers replaced the phenyl R groups of ligand 41 with cyclohexyl groups. The usefulness of the corresponding complexes is quite broad ( 7.1.1.1). 

Up to this point, the discussion has focused on the existence of just a single stereogenic center or asymmetry element on the substrate, the reagent or the catalyst. However, reacting systems may include more stereocenters or asymmetry elements located either on the same partner or on other components. The presence of the added elements of asymmetry can influence the relative energies of the various transition states and either augment or erode the diastereodifferentiation observed when a similar reaction is performed in the presence of a single asymmetry element. For the sake of simplicity, only the case of double diastereodifferentiation will be considered here. Two possibilities arise  

When the substrate bears two centers of chirality, Tolbert and Ali [118] introduced the notion of cooperativity in asymmetric induction as a criterion of concertedness of reaction mechanism. In cooperative reactions, the introduction of the two identical stereocenters at independent sites of a symmetric molecule, will induce higher asymmetric induction than expected by simple additivity. To a first approximation, the ffee-energy difference between these transition states is dou- 

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In addition to the enhanced rate of hydroalumination reactions in the presence of metal catalysts, tuning of the metal catalyst by the choice of appropriate ligands offers the possibility to influence the regio- and stereochemical outcome of the overall reaction. In particular, the use of chiral ligands has the potential to control the absolute stereochemistry of newly formed stereogenic centers. While asymmetric versions of other hydrometaUation reactions, in particular hydroboration and hydrosi-lylation, are already weU established in organic synthesis, the scope and synthetic utiHty of enantioselective hydroalumination reactions are only just emerging [72]. 

The solvent employed in asymmetric catalytic reactions may also have a dramatic influence on the reaction rate as well as the enantioselectivity, possibly because the solvent molecule is also involved in the catalytic cycle. Furthermore, the reaction temperature also has a profound influence on stereoselectivity. The goal of asymmetric hydrogenation or transfer hydrogenation studies is to find an optimal condition with a combination of chiral ligand, counterion, metal, solvent, hydrogen pressure, and reaction temperature under which the reactivity and the stereoselectivity of the reaction will be jointly maximized. 

The influences of the ligand-to-metal ratio, reaction temperature and syngas pressure on the enantioselectivity and regioselectivity were also studied. A multi-substrate screening approach has recently been used by Dow Chemical Company to identify the best catalyst for the hydroformylation of vinyl acetate. Here, the chiral phosphite Kelliphite, 5 (Fig. 1) gave enantioselectivity up 88% ee and excellent regioselectivity for the branched isomer [24,25]. 

An order of effectiveness has been established and a mechanism proposed for the removal of iron from ferritin by several 3-hydroxy-4-pyridinone chelators. The removal of iron from ferritin is, as one would expect, considerably slower than from calcein or doxorubicin (cf. above) or from transferrin. Rate constants are between 1.5 x 10 s and 7.5 x 10 s for removal of iron from ferritin by a series of hexadentate ligands each consisting of three substituted A-hydroxypyrimidinone or A-hydroxypyrazinone units, the rate decreasing with increasing substituent bulk. The slowest rate approximates to that for removal of iron from ferritin by desferrioxamine. The influence of chirality on the kinetic barrier provides insight into the detailed mechanism of removal in these systems.Slow removal of iron from ferritin by chelators should be contrasted with rapid reductive removal. ... 

When all chiral units have unknown configuration, both the relative and absolute configuration need to be determined. This situation is encountered in many asymmetric reactions performed under the influence of chiral catalysts or external chiral ligands. 

Hayashi et al.74 described a process of kinetic resolution in the coupling of Grignard reagents R Mgx (having a chiral center at the point of attachment to the metal) with various alkenyl halides under the influence of chiral phosphine-nickel complexes. Chiral amino acid derivatives (35) were used as ligands. 

The greater versatility of rhodium catalysts 21) and the promising results obtained in the first experiments in asymmetric hydroformylation 5,22 24) encouraged research in this field. A great number of substrates have been hydroformylated and a relatively large number of chiral ligands have been used. Furthermore, the influence of the reaction conditions on the optical yield has been investigated for some substrates. 

Tetrahedral Four-Coordinate T-4 In contrast to the chemistry of carbon compounds, and some main group compounds such as the structure shown in Figure 5.4, Werner-type T-4 coordination complexes are too labile to isolate in solution as individual enantiomers. The presence of chiral ligands can influence the racemic (diastereomeric) equilibrium and make the preparation and isolation of... 

Burgess et al. (128) reported the catalyst screening of a 96-member array of catalytic systems L20 on a C-H insertion reaction of substrate 9.77 (Fig. 9.32), a transformation usually catalyzed by rhodium (138) or copper salts (139) in the presence of chiral ligands (140). The stereochemical outcome was measured on the diastereomeric couple 9.79-9.80, obtained following uncatalyzed oxidation of 9.78 (Fig. 9.32), to simplify the determination of the chiral products while evaluating the stereoselectivity of the tricycle formation. The stereoselectivity of the C-H insertion was not significantly influenced by the presence of the (L)-methyl ester (128). 

The influence of solvent and additives on yield and selectivity has been examined.The conjugate addition of dimethyl cuprate in the presence of a chiral ligand, such as 144, is an example. The use of chiral ligands with Mgl2/l2 and BuaSnl gave conjugate addition products with a,(3-unsaturated amides with... 

Under the influence of chiral phosphine-transition meted complexes, a-amino ketones are hydrogenated to the corresponding optically active y9-amino alcohols (Scheme 16). Biologically active amino alcohols are obtainable in >90% ee by the Rh- and Ru-catalyzed homogeneous hydrogenation [43e, 54-56] using 55 or 56 as ligands. 

The enantioselective hydrogenation of imines is a powerful approach to the synthesis of chiral secondary amines. The series of complexes 7 (Scheme 5) either with or without the 3-H F -substituent and containing various anions was synthesized to investigate the influence of the ligand substitution pattern and the anion on the catalytic efficiency in SCCO2 [23]. As expected, the substitution in the ligand increased the solubility of the complexes, but had very little impact on the enantioselectivity. The anion, however, did not only exhibit an effect on... 

Ohno et al. developed an enantioselective alkylation by the use of a C2-sym-metric disulfonamide as a chiral ligand[ 19,20,21 ]. They designed the chiral catalyst based on the concept that coordination of an electron-withdrawing chiral ligand to the Lewis acid, Ti(0-z-Pr)4, enhances the catalytic activity. Actually, the acidity of the disulfonamide has an influence on the enantioselectivity and fluorine-containing disulfonamides, especially trifluoromethylsulfonamide, were found to be the best choice of chiral catalyst (Scheme 7). It should be noted that a decrease in the amount of chiral ligand from 0.02 equiv. to 0.0005 equiv. has no effect on the yield and ee and the turnover reached 2,000. Also in the alkylation of aliphatic aldehydes, very high enantioselectivities can be attained. 

Unlike the above, the two hydrogen atoms labeled Ha and Hb in propane 184 are homotopic because a C2 operation converts one into the other, so that they are considered to be equivalent in all possible ways. Even if one of these hydrogen atoms is replaced by a substituent other than methyl and hydrogen, resultant molecule is not chiral. Homotopic groups remain indistinguishable under chiral influence, i.e., in the presence of chiral ligands. 

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