Chiral enantioselective catalysis

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... 

The Diels-Alder reaction of nonyl acrylate with cyclopentadiene was used to investigate the effect of homochiral surfactant 114 (Figure 4.5) on the enantioselectivity of the reaction [77]. Performing the reaction at room temperature in aqueous medium at pH 3 and in the presence of lithium chloride, a 2.2 1 mixture of endo/exo adducts was obtained with 75% yield. Only 15% of ee was observed, which compares well with the results quoted for Diels-Alder reactions in cyclodextrins [65d]. Only the endo addition was enantioselective and the R enantiomer was prevalent. This is the first reported aqueous chiral micellar catalysis of a Diels-Alder reaction. 

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

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. 

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. 

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... 

There are a number of examples of enantioselective catalysis with a zinc catalyst. The use of zinc as a catalyst in the Diels-Alder reaction of (R,R)-4,6-dibenzofurandiyl-2,2 -bis(4-phenylox-azoline) with cyclopentadiene shows high enantioselectivity. Chiral amplification is observed in the... 

Surface faceting may be particularly significant in chiral heterogeneous catalysis, particularly in the N i/P-ketoester system. The adsorption of tartaric add and glutamic acid onto Ni is known to be corrosive and it is also established that modifiers are leached into solution during both the modification and the catalytic reaction [28]. The preferential formation of chiral step-kink arrangements by corrosive adsorption could lead to catalytically active and enantioselective sites at step-kinks with no requirement for the chiral modifier to be present on the surface. 

The synthesis of chiral dendrimers from various building blocks, their - difficult - structure determinations, and their - potential - use in physiological applications, in bioassays, and in enantioselective catalysis are reviewed. 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

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