Optically selective activation

Halpern has shown that this predominant isomer exhibits negligible activity towards the oxidative addition of hydrogen. The minor isomer, which could be detected in solution for DIPAMP but not for CHIRAPHOS, reacts far more rapidly with hydrogen and is responsible for producing the major enantiomer of the hydrogenation product. The optical selectivity is thus due to this difference in reaction rates and not simply to the preferred manner of coordination of the alkene to the rhodium-diphosphine species.259,260 The precise reasons for this large difference in the rates of reaction of the two diastereoisomers with hydrogen are not yet known. The full mechanism is shown in Scheme 14. 

It is noteworthy that, at normal temperature and hydrogen pressure, these systems not only give optical selectivities very close to 100%, but also show activities well up in the range previously thought to be attainable only by enzymes. That this is possible with such comparatively simple transition metal complexes indicates how prodigal Nature has been in constructing its own catalysts. 

Carbamate and amide groups have been found to be stable under these coupling conditions73. In the presence of TiCLt or SnCLt, chiral a-keto amides 36 react with allyl-silane to produce, after hydrolysis, optically active tertiary alcohols 37 with extremely high optical selectivity (equation 23)74. The addition reaction appears to occur from the Si face of the carbonyl group. In a similar manner, a high degree of stereoselectivity is obtained from the reactions of A-Boc-a-amino aldehydes 38 with 2-substituted allylsilanes (equation 24)75. 

Activation of the enantiopure (f )-BINOL-Ti(OPr )2 catalyst (2) was investigated by further addition of (i )-BINOL (Sch. 23, Table 3). The reaction proceeded quite smoothly to provide the carbonyl-ene product in higher chemical yield (82.1 %) and enantioselectivity (96.8 % ee) than without additional BINOL (94.5 % ee, 19.8 %) (Run 2 compared with Run 1). Comparison of results from enantiomer-selective activation of the racemic catalyst (89.8 % ee, R) (Table 2, Run 4) with those from use of the enantio-pure catalyst (with (96.8 % ee, R) or without (94.5 % ee, R) activator) enabled calculation that that the reaction catalyzed by the (/ )-BINOL-Ti(OPr )2/(/ )-BINOL complex R,R)-2 ) would be 26.3 times faster than that catalyzed by the (5)-BINOL-Ti(OPr )2 (2) in the racemic case (Sch. 24a). Indeed, kinetic studies show that the reaction catalyzed by the (i )-BINOL-Ti(OPr )2/(i )-BINOL complex (R,R)-2 ) is 25.6 times faster than that catalyzed by (R)-BINOL-Ti(OPr )2 (2). These results imply that the racemic ( )-BINOL-Ti(OPr )2 (2) and the half-molar amount of (i )-BINOL assemble preferentially into the (R)-BINOL-Ti(OPr )2/(R)-BINOL complex ((R,R)-2 ) and unchanged (S)-BINOL-Ti(OPr )2 (2). In contrast, the enantiomeric form of the additional chiral ligand ((5)-BINOL) activates the (R)-BINOL-Ti(OPr )2 (2) to a lesser extent (Run 3), thus providing the carbonyl-ene product in lower optical (86.0 % ee, R) and chemical (48.0 %) yields than does (R)-BINOL. 

However, problems frequently arise in the comparison of calculated frequencies with optical spectra. Since infrared and Raman measurements are subject to optical selection rules, only frequencies associated with certain active phases of a phase-frequency curve are observed. In certain cases, a mode may have frequencies that lie outside the range of optical measurements, or it may have no optically active phases. For exainple, the skeletal deformation and torsional modes for an infinite and isolated polyethylene chain in the trans-configuration have optically active phases that correspond to zero frequency (36). 

Optical activity generation using CPL relies on an optically selective excitation, which electronically activates one enantiomer in a racemic mixture, leading to either photodestruction or photoderacemization. The generation of optically active products through interaction with a chiral photosensitizer requires the input of only a small amount of chiral information, and this type of process is quite efficient in terms of the amplification of chiral centers. Indeed, the low concentrations of sensitizer that are often required, coupled with good turnover numbers, renders this process very attractive in these terms. 

In some cases, a simple tosylation can be equally regioselective, especially when one of the hydroxyl substituents is more sterically hindered then the other. This approach served as a key step in an expeditious approach towards naproxen 217 (Scheme 55). The primary alcohol function of the optically active diol 214, of 98% ee, was selectively activated with tosyl chloride [135]. The resulting to-sylate, upon treatment with NaH, underwent smooth cycHzation to the epoxide 215. Hydrogenolysis proved to be highly facial selective, delivering the primary alcohol 216 in high enantiopuxity. A final Jones oxidation then furnished naproxen of 96% ee. 

Complexes of different dendrimers with rhodium that contained ferrocenyl phosphine ligands on the surface, 52-53, were also active in hydrogenation. They catalyzed dimethylacetone hydrogenation at an optical selectivity of 98%, which is comparable to the selectivity of a low molecular weight analogue [113, 123, 124]. 

A ruthenium complex with the dendrimer BINAP ligand obtained from aromatic polyethers 55 catalyzed hydrogenation of 2-[p-(2-methylpropyl)phe-nyl] acrylic acid to ibuprofen at an optical selectivity of 99% in a methanol-toluene solution the activity of the dendrimer complex was twice as high as that of a low molecular weight analogue [138],... 

A rhodium complex with the dendrimer polyether ligand with (S -N (p-tolylsulfonyl)-2-diphenylethylenediamine in the core proved to be active in asymmetric proton-transfer hydrogenation of acetophenone in formic acid to (S)-methyl phenyl carbinol at a selectivily above 95%. The catalyst was reused, and the activity of macromolecular complexes with dendrimers of higher generations decreased much more slowly, while the optical selectivity was retained [139], This also confirms the stabilization of the active site by the dendrimer environment in such macromolecular complexes. 

Many of the chiral bidentate phosphines synthesized in the last years have also been tested for enantioselective ketone reduction. Some of the results achieved are compiled in Table 2. The influence of phosphine structure on optical selectivity and catalytic activity is considerable, but a reliable correlation could not yet be found. It seems that chiral bidentate 6w(diphenyl)phosphines, like prophos forming 5-membered chelate rings with the rhodium atom and used with great success for the hydrogenation of dehydroaminoacids, are not suitable for ketone reduction because of very low reaction rates. 

Thus, PDT started and continues as a treatment for solid tumors. However, there are also munerous other applications in use clinically or under pre-clinical or clinical investigations [5], as listed in Table 1. These applications exploit the different biological mechanisms that can be selectively activated, depending on the PDT treatment parameters. The invention of the laser and optical fibers in the 1960 s was also important for the development of PDT although non-laser sources can be used, the ability to deliver high intensity laser light to almost any site in flie body is critical for many applications. 

Zhang Y-J, He X-P, Hu M, Li Z, Shi X-X, Chen G-R (2011) Highly optically selective and electrochemically active chemoscaisor for copper(II) based on triazole-linked glucosyl anthraquinone. Dyes Pigments 88 391-395... 

Resolution hy optically selective adsorption. Optically selective adsorption of a racemate on a solid optically active adsorbent. 

Interrupted diastereoisomeride formation. Interrupted optically selective combination of a racemate with an opticsilly active substance. 

Interrupted asymmetric catalysis. Interrupted optically selective reaction of. a racemate with a symmetrical substance under the intermolecular influence of an optically active catalyst. 

Asymmetric synthesis (eliminative). Optically selective formation of new centers of stable dissymmetry under the intramolecular directing influence of an optically active grouping, the latter being subsequently eliminated from the product. 

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