Chiral reagents and catalysts

More examples are found for varied oxidation processes mainly for various epoxidations carried out by metal catalysts bearing F-modified ligands, such as porphyrins,139 Ru perfluoroacetylacetonate salt,140 or salen complexes,141 142 or using the 3 selenium compound as catalyst.143 The potential for enantioselective transformations offering an easy way to recover precious chiral reagents and catalysts was demonstrated in enantioselective epoxidation using fluorous chiral salen... 

The thiolester portion is always derived from natural cysteine so there is a chiral pool element present in all syntheses. Because there are four consecutive chiral centres in the main portion of the molecule, just about every strategy has been employed by someone more chiral pool, chiral reagents and catalysts, chiral auxiliaries attached to substrate or reagent, and sometimes combinations of these. 

Atropisomeric biaryls, in particular binaphthyls, play an important role in the chemistry of molecular recognition1-. There arc also many applications in synthetic chemistry as chiral reagents and catalysts (for some reviews, see refs 5-7). Their stereoselective synthesis from chiral substrates or with chiral catalysts is described in Section B.2. This section will, therefore, only present syntheses of practical importance. 

Both enantiomers of binaphthol have found many uses as chiral reagents and catalysts. Thus, they modify reducing agents (e.g., lithium aluminum hydride) for the reduction of ketones to chiral secondary alcohols (Section D.2.3.3.2.) or react with aluminum, titanium or boron compounds to give chiral Lewis acids for asymmetric Diels-Alder reactions (Section D. 1.6.1.1.1.3.) and ene reactions (Section D.I.6.2.). They have also been used as chiral leaving groups in the rearrangement of allyl ethers (Section D.l.1.2.2.) and for the formation of chiral esters with a-oxo acids (Section D. 1.3.1.4.1, and many other purposes. 

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

There are two possible approaches for the preparation of optically active products by chemical transformation of optically inactive starting materials kinetic resolution and asymmetric synthesis [44,87], For both types of reactions there is one principle in order to make an optically active compound we need another optically active compound. A kinetic resolution depends on the fact that two enantiomers of a racemate react at different rates with a chiral reagent or catalyst. Accordingly, an asymmetric synthesis involves the creation of an asymmetric center that occurs by chiral discrimination of equivalent groups in an achiral starting material. This can be done either by enan-tioselective (which involves the reaction of a prochiral molecule with a chiral substance) or diastereoselective (which involves the preferential formation of a single diastereomer by the creation of a new asymmetric center in a chiral molecule) synthesis. 

Scheme 7.2. Chiral ligands and catalysts in enantioselective 1,4-additions of Grignard reagents.

Since the early times of stereochemistry, the phenomena related to chirality ( dis-symetrie moleculaire, as originally stated by Pasteur) have been treated or referred to as enantiomericaUy pure compounds. For a long time the measurement of specific rotations has been the only tool to evaluate the enantiomer distribution of an enantioimpure sample hence the expressions optical purity and optical antipodes. The usefulness of chiral assistance (natural products, circularly polarized light, etc.) for the preparation of optically active compounds, by either resolution or asymmetric synthesis, has been recognized by Pasteur, Le Bel, and van t Hoff. The first chiral auxiliaries selected for asymmetric synthesis were alkaloids such as quinine or some terpenes. Natural products with several asymmetric centers are usually enantiopure or close to 100% ee. With the necessity to devise new routes to enantiopure compounds, many simple or complex auxiliaries have been prepared from natural products or from resolved materials. Often the authors tried to get the highest enantiomeric excess values possible for the chiral auxiliaries before using them for asymmetric reactions. When a chiral reagent or catalyst could not be prepared enantiomericaUy pure, the enantiomeric excess (ee) of the product was assumed to be a minimum value or was corrected by the ee of the chiral auxiliary. The experimental data measured by polarimetry or spectroscopic methods are conveniently expressed by enantiomeric excess and enantiomeric... 

A large proportion of NCEs will have one or more chiral centres. Only single enantiomers can be used nowadays, whereas previously a racemic mixture would have been tested. Different enantiomers produce different pharmacological responses, with one enantiomer usually being more active by at least an order of magnitude. There has been considerable debate on the administration of racemates versus the single active enantiomer or eutomer however, the current trend is to develop only the active optical isomer. The synthetic route employed will, if required, have to utilise chiral-specific reagents and catalysts or the compound will have to be purified after synthesis. With this type of compound, an additional specification or limit is required for the presence of the inactive enantiomer. ... 

The synthesis of optically active selenium-containing reagents as well as their application to stereoselective synthesis is of high current interest. Several products also contain a selenium functionality and their use as chiral ligands and catalysts in asymmetric reaction is promising. Various reactions of this type are known and some recent developments in this novel area are summarized here. 

Enantioselective Reduction of Imines and Ketoxime O-Ethers. In addition to the reduction of prochiral ketones, chiral oxazaborolidines have been employed as enantioselective reagents and catalysts for the reduction of imines (eq 11) and ketoxime O-ethers (eq 12) - to give chiral amines. It is interesting to note that the enantioselectivity for the reduction of ketoxime O-ethers is opposite that of ketones and imines. For more information, see 2-Amino-3-methyl-l,l-diphenyl-I-butanol. 

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