Resolution metal complexes

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

Chromatographic resolution of metal complexes on Sephadex ion exchangers. Y. Yoshikawa and K. Yamasaki, Coord. Chem. Rev., 1979, 28, 205-229 (98). 

Optical recording systems, 6, 126 Optical resolution amine metal complexes, 2,25 Oral contraceptives iron deficiency, 6, 764 Orbital angular momentum quenching, 1,262 /-Orbital systems... 

Molecules having only a sulfoxide function and no other acidic or basic site have been resolved through the intermediacy of metal complex formation. In 1934 Backer and Keuning resolved the cobalt complex of sulfoxide 5 using d-camphorsulfonic acid. More recently Cope and Caress applied the same technique to the resolution of ethyl p-tolyl sulfoxide (6). Sulfoxide 6 and optically active 1-phenylethylamine were used to form diastereomeric complexes i.e., (-1-)- and ( —)-trans-dichloro(ethyl p-tolyl sulfoxide) (1-phenylethylamine) platinum(II). Both enantiomers of 6 were obtained in optically pure form. Diastereomeric platinum complexes formed from racemic methyl phenyl (and three para-substituted phenyl) sulfoxides and d-N, N-dimethyl phenylglycine have been separated chromatographically on an analytical column L A nonaromatic example, cyclohexyl methyl sulfoxide, did not resolve. 

T. Iwashita, Y. Mino, H. Naoki, Y. Suguira, and K. Nomoto, High-resolution proton nuclear magnetic resonance analysis of solution structures and conformational properties of muguneic acids and its metal complexes. Biochemistry 22 4842 (1983). 

Resolution via Molecular Complexes, Metal Complexes, and Inclusion Compounds ... 

The subject of asymmetric synthesis generally (214, 215) gained new momentum with the potential use of transition metal complexes as catalysts. The use of a complex with chiral ligands to catalyze a synthesis asymmetrically from a prochiral substrate is advantageous in that resolution of a normally obtained racemate product may be avoided, for example,... 

Regeneration of the oxidized form of the cofactors, while not within the frame of this chapter, is needed for several biotransformations (e.g., oxidative kinetic resolution of diols). In these procedures, transition-metal complexes have also been applied. For this task, Ru(phend)3 complex and derivatives thereof can be used, either with oxygen or in an electrochemical procedure [49-51]. 

Figure 1-13. Chiral metal chelates for enantiomer resolution by complexation gas chromatography.

Finally, other chiral donor atoms, P,As (see Problem 9) and in metal complexes have been less systematically studied than nitrogen. Inversion rates in metal ion-thioether complexes have been measured by nmr, but the species are too labile to allow a successful resolution. 

The reasons for the increasing acceptance of enzymes as reagents rest on the advantages gained from utilizing them in organic synthesis Isolated or wholecell enzymes are efficient catalysts under mild conditions. Since enzymes are chiral materials, optically active molecules may be produced from prochiral or racemic substrates by catalytic asymmetric induction or kinetic resolution. Moreover, these biocatalysts may perform transformations, which are difficult to emulate by transition-metal catalysts, and they are environmentally more acceptable than metal complexes. 

In the case of the sulphur triimide S(NBu-f)3, the dispersive Raman technique applying a double monochromator and a CCD camera was employed to obtain the information from polarized measurements (solution studies) and also to obtain high-resolution spectra by low-temperature measurements. In the case of the main group metal complex, only FT-Raman studies with long-wavenumber excitation were successful, since visible-light excitation caused strong fluorescence. The FT-Raman spectra of the tetraimidosulphate residue were similar to those obtained from excitation with visible laser lines. 

The change in bond A is comparable with that, 155- -180°, predicted by Prestegard and Chan (60) from high resolution n.m.r. spectroscopy. Their other observations on solutions, i. e. approximately S4 symmetry and dehydration of the complexed potassium agree with the crystallographic results. 13C n.m.r. spectroscopy (d>7) shows no difference between the ammonium and the alkali metal complexes and does not explain the high stability constant of the ammonium complex1). 

Kinetic resolution of racemic secondary hydroperoxides rac-16 can be effected by selective reduction of one enantiomer with employing either chiral metal complexes or enzymes (equation 10). In this way hydroperoxides 16 and the opposite enantiomer of the corresponding alcohols 19 can be produced in enantiomerically enriched form. As side products sometimes the corresponding ketones 20 are produced. 

Although the high resolution X-ray crystal analysis of 4,4 -bipyridine has not been reported, the crystal structure of 4,4 -bipyridinium chlorocuprate (22) has been discussed. Whereas the dimensions of the 4,4 -bipyridinium dication may have been distorted because of the influence of the bulky metal cation, it is interesting to note that the 4,4 -bipyridinium dication is planar with both pyridine rings lying in the same plane. In metal complexes of the parent 4,4 -bipyridine, however, the pyridine rings may be coplanar or rotated up to 40° with respect to one other. 

A process that has been studied widely in relation to phenomena such as chiral symmetry breaking, spontaneous resolution and chiral amplification is the reaction (Fig. 18) of [Co(H20)2 (OH)2Co(en)2 2](S04)2 (denoted 1) with NH4Br to give the chiral complex cA-[CoBr(NH3)(en)2]Br2 (denoted 2). This reaction is historically important, as 2 was one of the first octahedral metal complexes to be resolved into A and A stereoisomers, some years after Werner predicted that octahedral ions M(en)2XY should exist as enantiomeric pairs. 

Heterogenization of homogeneous metal complex catalysts represents one way to improve the total turnover number for expensive or toxic catalysts. Two case studies in catalyst immobilization are presented here. Immobilization of Pd(II) SCS and PCP pincer complexes for use in Heck coupling reactions does not lead to stable, recyclable catalysts, as all catalysis is shown to be associated with leached palladium species. In contrast, when immobilizing Co(II) salen complexes for kinetic resolutions of epoxides, immobilization can lead to enhanced catalytic properties, including improved reaction rates while still obtaining excellent enantioselectivity and catalyst recyclability. 

Chiral sulfoxides have emerged as versatile building blocks and chiral auxiliaries in the asymmetric synthesis of pharmaceutical products. The asymmetric oxidation of prochiral sulfides with chiral metal complexes has become one of the most effective routes to obtain these chiral sulfoxides.We have recently developed a new heterogeneous catalytic system (WO3-30% H2O2) which efficiently catalyzes both the asymmetric oxidation of a variety of thioethers (1) and the kinetic resolution of racemic sulfoxides (3), when used in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR], Optically active sulfoxides (2) are produced in high yields and with good enantioselectivities (Figure 9.3). ... 

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