Enantioselectivity catalysis

To our knowledge, the results presented in this chapter provide the first example of enantioselective Lewis-acid catalysis of an organic reaction in water. This discovery opens the possibility of employing the knowledge and techniques from aqueous coordination chemistry in enantioselective catalysis. This work represents an interface of two disciplines hitherto not strongly connected. 

Clearly, there is a need for techniques which provide access to enantiomerically pure compounds. There are a number of methods by which this goal can be achieved . One can start from naturally occurring enantiomerically pure compounds (the chiral pool). Alternatively, racemic mixtures can be separated via kinetic resolutions or via conversion into diastereomers which can be separated by crystallisation. Finally, enantiomerically pure compounds can be obtained through asymmetric synthesis. One possibility is the use of chiral auxiliaries derived from the chiral pool. The most elegant metliod, however, is enantioselective catalysis. In this method only a catalytic quantity of enantiomerically pure material suffices to convert achiral starting materials into, ideally, enantiomerically pure products. This approach has found application in a large number of organic... 

The first example of enantioselective catalysis of a Diels-Alder reaction was reported in 1979 . Since then, an extensive set of successful chiral Lewis-acid catalysts has been prepared. Some selected examples will be presented here together with their mechanistic interpretation. For a more complete... 

In Chapter 2 the Diels-Alder reaction between substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-ones (3.8a-g) and cyclopentadiene (3.9) was described. It was demonstrated that Lewis-acid catalysis of this reaction can lead to impressive accelerations, particularly in aqueous media. In this chapter the effects of ligands attached to the catalyst are described. Ligand effects on the kinetics of the Diels-Alder reaction can be separated into influences on the equilibrium constant for binding of the dienoplule to the catalyst (K ) as well as influences on the rate constant for reaction of the complex with cyclopentadiene (kc-ad (Scheme 3.5). Also the influence of ligands on the endo-exo selectivity are examined. Finally, and perhaps most interestingly, studies aimed at enantioselective catalysis are presented, resulting in the first example of enantioselective Lewis-acid catalysis of an organic transformation in water. 

Effects of L- -amino acid ligands - Stepping on the tail of enantioselectivity The naturally occurring -amino acids form a class of readily available strongly coordinating ligands, which exhibit broad stmctural variation. Moreover, their availability in enantiomerically pure form offers opportunities for enantioselective catalysis. Some derivatives of these compounds have been... 

One example has already been encountered in the form of the binding constants in Table 3.2. These data form one of the first examples of compelling evidence for the involvement of attractive arene -arene interactions in determining the outcome of enantioselective catalysis. These attractive interactions have been frequently invoked as explanations for the observed enantioselectivities of... 

Of all the work described in this thesis, this discovery is probably the most significant. Given the fact that the arene - arene interactions underlying the observed enantioselectivity of ftie Diels-Alder reactions described in Chapter 3 are also encountered in other organic reactions, we infer that, in the near future, the beneficial influence of water on enantioselectivity can also be extended to these transformations. Moreover, the fact that water can now be used as a solvent for enantioselective Lewis-add catalysed reactions facilitates mechanistic studies of these processes, because the number of equilibria that need to be considered is reduced Furthermore, knowledge and techniques from aqueous coordination chemistry can now be used directly in enantioselective catalysis. 

Agbossou E., Carpentier J. E. Hapiot E., Suisse I., Mortreux A. The Aminophos-phine-Phosphinites and Related Ligands Synthesis, Coordination Chemistry and Enantioselective Catalysis Coord. Chem. Rev. 1998 I78-I80 1615-1645 Keywords stereoselective Diels-Alder reaction catalysts, aminophosphine-phosphinites, enantioselective catalysts... 

Brunner H. Right or Left in Chemistry - Enantioselective Catalysis With Transition Metal Compounds Quim. Nova 1995 18 603 07... 

Zang D. -L. and Li P. Enantioselective Catalysis of Diels-Alder Reactions Youji Huaxue 1994 14 581 (in Chinese)... 

Brunner H. Right or Left-that is the Question-Enantioselective Catalysis with Transition Metal Compounds in Adv. Catal. Des., Proc. Workshop, 2nd. 1993 245, Ed. Graziani M., Rao C. N. R., Pb. Wordl Sci. Singapore... 

Brunner H. Enantioselective Catalysis With Transition Metal Componnds. Right or Left - This Is the Qnestion Adv. Chem. Ser. 1992 230 143-152 Keywords homo-Diels-Alder reaction of norbornadiene... 

Enantioselective Catalysis with Chiral-at-Metal Complexes. 283... 

Enantioselective catalysis requires that the distance between the inductor and the substrate is not too long. Basically, the smaller the distance, the better... 

Robertson DE et al. (2004) Exploring nitrilase sequence space for enantioselective catalysis. Appl Environ Microbiol 70 2429-2436. 

Corey, E.J. Helal, C.J. (1998) Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts A New Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method. Angewandte Chemie International Edition, 37, 1986-2012. 

Catalytic transformations can be divided on the basis of the catalyst-type - homogeneous, heterogeneous or enzymatic - or the type of conversion. We have opted for a compromise a division based partly on type of conversion (reduction, oxidation and C-C bond formation, and partly on catalyst type (solid acids and bases, and biocatalysts). Finally, enantioselective catalysis is a recurring theme in fine chemicals manufacture, e.g. in the production of pharmaceutical intermediates, and a separate section is devoted to this topic. 

The same reasoning applies to the synthesis of pure enantiomers as to organic synthesis in general processes should be atom efficient and have low E factors, i.e. involve catalytic methodologies. This is reflected in the increasing attention being focused on enantioselective catalysis, using either enzymes or chiral metal complexes. 

A fascinating example of enantioselective catalysis for agrochemicals is the production of a well-known herbicide of Novartis (formerly Ciba Geigy), metolachlor (Trade name Dual... 

Enantioselective Catalysis of the Aldol Addition Reaction. There are also several catalysts that can effect enantioselective aldol addition. The reactions generally involve enolate equivalents, such as silyl enol ethers, that are unreactive toward the carbonyl component alone, but can react when activated by a Lewis acid. The tryptophan-based oxazaborolidinone 15 has proven to be a useful catalyst.148... 

As with aldol and Mukaiyama addition reactions, the Mannich reaction is subject to enantioselective catalysis.192 A catalyst consisting of Ag+ and the chiral imino aryl phosphine 22 achieves high levels of enantioselectivity with a range of N-(2-methoxyphenyljimines.193 The 2-methoxyphenyl group is evidently involved in an interaction with the catalyst and enhances enantioselectivity relative to other A-aryl substituents. The isopropanol serves as a proton source and as the ultimate acceptor of the trimethyl silyl group. 

The a,a,a,a-tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) chiral ligands have also been the basis of enantioselective catalysis of the D-A reaction. In a study using 2-methoxy-6-methylquinone as the dienophile, evidence was found that the chloride-ligated form of the catalysts was more active than the dimeric oxy-bridged form.117... 

Enantioselective catalysis of S alkylation has been achieved.91 A BINOL-phosphoramidite catalyst (o-methoxyphenyl analog) similar to that in Entry 3 in Scheme 8.7 gave good results. 

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