Transition metal catalysts resolution

It is important that the catalysts are stable in each other s presence. Typically, kinetic resolution of the reaction is performed with an enzyme, which always will contain traces of water. Hence, MPVO catalysts and water-sensitive transition-metal catalysts cannot be used in these systems. The influence of the amount of the hydrogen acceptor in the reaction mixture during a dynamic kinetic resolution is less pronounced than in a racemization, since the equilibrium of the reaction is shifted towards the alcohol side. 

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. 

Enzymatic resolution of racemic secondary alcohols by enantiomer-selective acylation gives optically pure compounds with up to 50% yield [332], When this method is coupled with the principle of dynamic kinetic resolution (see Section 1.4.1.5), the theoretical yield increases to 100%. Thus a reaction system consisting of an achiral transition-metal catalyst for racemization, a suitable enzyme, acetophenone, and an acetyl donor allows the transformation of racemic 1-phenylethanol to the R acetates with an excellent ee (Scheme 1.93) [333]. The presence of one equiv. of acetophenone is necessary to promote the alcohol racemization catalyzed by the... 

The heading substitution reactions has been used to describe the conversion of a stereogenic center to another. Of course, this means that the substrate stereogenic center has had to be obtained by one of the reaction types outlined earlier, from the chiral pool, or by resolution. Reactions that fall into this category include epoxide and cyclic sulfate openings and iodolactonizations (Chapter 22). Perhaps the most important reaction of this type for asymmetric synthesis is allylic substitution in the presence of a transition metal catalyst. 

The same CALB preparation was appUed in many dynamic kinetic resolutions combining two types of catalysts with each other. In the presence of homogeneous transition metal catalysts that catalyze the racemization and heterogeneous acids or bases or immobilized transition metals Novozym 435 was not deactivated [1, 26-28]. This is all the more remarkable since the reactions catalyzed by these catalysts include redox reactions at elevated temperatures (>60°C). When Novozym 435 was applied for the enantioselective synthesis of cyanohydrin acetates (10) from aliphatic aldehydes (7), good results were achieved (Scheme 2.2) for this dynamic kinetic resolution (DKR) [29]. Here NaCN is used as the base for the dynamic racemic formation and degradation of the cyanohydrins (6 and 8). 

Many other deracemizahon methods based on a two-enzyme system or in the successive enzymatic resolution/base-catalyzed racemization have been reported. They are often regarded as having a reduced environmental impact, not requiring a transition metal catalyst in the racemization step [4]. 

The reactions discussed in the last sections produce enantioemiched P-stereo-genic compounds by metal-catalysed enantioselective resolutions of chiral but racemic secondary phosphines and derivatives. Another set of methods is based on desymmetrisations of achiral (but prochiral) tertiary phosphine derivatives bearing two enantiotopic groups amenable to functionahsation by chiral transition metal catalysts. 

Today, dynamic kinetic resolution of secondary alcohols by combination of enzymes with transition metal catalysts, originally developed by Williams and Backvall, are perhaps the best developed methods (33-36). Hitherto the most successful catalyst designs have been based on half-sandwich ruthenium complexes, of which the pentaphenylcyclopentadienyl ruthenium complex has been claimed as the currently best racemization catalyst. Racemization is then based on reversible conversion of the alcohol into the corresponding ketone (Fig. 21, A). The dynamic kinetic resolution of 1-phenylethanol with isopropenyl acetate in toluene in the presence of Novozym 435, performed in preparative scale, is a good example of the use of ruthenium complexes (35). Another thoroughly studied racemization method (Fig. 21, B) is based on the use of acidic resins or zeolites. Here the racemization takes place through prochiral sp car-benium ion by simultaneous elimination and addition of water (37). The use of... 

Other examples include OKR of racemic secondary alcohols (Scheme 25A), oxidative desymmetrizations of meso-diols, etc. The kinetic resolution is generally defined as a process where two enantiomers of a racemic mixture are transformed to products at different rates. Thus, one of the enantiomers of the racemate is selectively transformed to product, whereas the other is left behind. This method allows to reach a maximum of 50% yield of the enantiopure remaining sec-alcohol. To overcome this fim-itation, a modification of the method, namely dynamic kinetic resolution (DKR), was introduced. In this case, the kinetic resolution method is combined with a racemization process, where enantiomers are interconverted while one of them is consumed (e.g., by esterification. Scheme 25B). Therefore, a 100% theoretical yield of one enantiomer can be reached due to the constant equifibrium shift. In most of the proposed DKR processes, several catalytic systems, e.g., enzymes and transition-metal catalysts, work together. Both reactions (transfer hydrogenation of ketones and the reverse oxidation of secondary alcohols using ketone as a hydrogen acceptor) can be promoted by a catalyst. The process can involve a temporary oxidation of a substrate with hydrogen transfer to a transition-metal complex. 

The direct epoxidation of terminal aromatic alkenes using classic chemocatalysts, such as Jacobsen s salen transition metal catalysts, suffer from poor stereoselectivity ( -36%ee) [95] and/or imprachcal reaction temperatures of -78 °C (86% ee) [96]. To achieve opfically pure sfyrene oxide, a more universal approach is to use hydrolytic kinetic resolution following unselective epoxidation reactions, which leads to a product with high optical purity but only 50% yield [11]. 

Dynamic kinetic resolution (DKR) is a method that allows for conversion of the racemic mixture into the desired enantiomer with up to 100% of the theoretical yield. " DKR is a powerful approach to asymmetric synthesis and can be achieved by the application of transition-metal catalysts, Lewis acids, organocatalysts, or enzymes (e.g., hydrolases, dehydrogenases, haloalcohol dehalogenases, and transaminases). 

In dynamic kinetic resolution (Fig. 8.30), starting from racemic mixture when a transition metal catalyst is used beside an enzyme for racemization of the undesired enantiomer theoretically up to 100%, yields of the desired enantiomer can be achieved if ks is low enough compared to... 

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. 

Further resolution of the details of oxidative dehydrogenation requires the measurement of a catalyst s degree of reduction carried out during steady state reaction. We note that UV-visible spectroscopy offers a way to perform this measurement since many of the transition metal oxides which are active as oxidation catalysts exhibit striking color changes between their oxidized and reduced states. 

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,... 

In many catalytic systems, nanoscopic metallic particles are dispersed on ceramic supports and exhibit different stmctures and properties from bulk due to size effect and metal support interaction etc. For very small metal particles, particle size may influence both geometric and electronic structures. For example, gold particles may undergo a metal-semiconductor transition at the size of about 3.5 nm and become active in CO oxidation [10]. Lattice contractions have been observed in metals such as Pt and Pd, when the particle size is smaller than 2-3 nm [11, 12]. Metal support interaction may have drastic effects on the chemisorptive properties of the metal phase [13-15]. Therefore the stmctural features such as particles size and shape, surface stmcture and configuration of metal-substrate interface are of great importance since these features influence the electronic stmctures and hence the catalytic activities. Particle shapes and size distributions of supported metal catalysts were extensively studied by TEM [16-19]. Surface stmctures such as facets and steps were observed by high-resolution surface profile imaging [20-23]. Metal support interaction and other behaviours under various environments were discussed at atomic scale based on the relevant stmctural information accessible by means of TEM [24-29]. 

Dynamic kinetic resolution (DKR) is an attractive protocol for the production of enantiopure compounds from racemic mixtures [45]. The concept of DKR is illustrated in Scheme 5.13. In many cases, DKRs are accomplished by the combination of enzymatic resolution and transition-metal-catalyzed racemization based on hydrogen transfer. Thus, the use of Cp Ir complexes as catalysts for racemization in DKR can be anticipated. 

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