Enantiomerically Pure Products

Whereas racemic a-ionone is accessible in large amounts, there are only a few methods for the targeted preparation of the individual enantiomers. There is 

18 The enantiomers ofa-ionone have distinctly different scents. 

Woodward was the first to separate the enantiomers of a-ionone. He converted racemic a-ionone into its menthylhydrazone and separated the diastereo-mers by fractional crystallisation. 20 recrystaUisations were necessary in order to obtaui the (R)-enantiomer in 1 % yield. [65] 

The best approach at present starts from (R)-a-damascone, and uses an rorolrSZrntffinthefn-ststep,benzyl 

The enantiomerically pure a-ionones are also available by enzymatic resolution of ionols, as described below for a-irones. [66,67] 

---

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... 

Chiral chemical reagents can react with prochiral centers in achiral substances to give partially or completely enantiomerically pure product. An example of such processes is the preparation of enantiomerically enriched sulfoxides from achiral sulfides with the use of chiral oxidant. The reagent must preferential react with one of the two prochiral faces of the sulfide, that is, the enantiotopic electron pairs. 

Although modern transition state hypotheses may be adequate in special cases, the majority of aldol additions leading to enantiomerically pure products are still rationalized by the classical six-membered chelate transition state models40. 

As oxidation also converts the original chiral terpene-derived group to an alcohol, it is not directly reusable as a chiral auxiliary. Although this is not a problem with inexpensive materials, the overall efficiency of generation of enantiomerically pure product is improved by procedures that can regenerate the original terpene. This can be done by heating the dialkylborane intermediate with acetaldehyde. The a-pinene is released and a diethoxyborane is produced.204... 

The Prelog-Djerassi lactone (abbreviated here as P-D lactone) was originally isolated as a degradation product during structural investigations of antibiotics. Its open-chain equivalent 3 is typical of the methyl-branched carbon chains that occur frequently in macrolide and polyether antibiotics. The compound serves as a test case for the development of methods of control of stereochemistry in such polymethylated structures. There have been more than 20 different syntheses of P-D lactone.24 We focus here on some of those that provide enantiomerically pure product, as they illustrate several of the methods for enantioselective synthesis.25... 

The production of enantiomerically pure products is of great importance in chemical industry. The most desirable way to obtain these products is by chiral catalysis. Homogeneous complexes can often be used as chiral catalysts however, because of their difficult regenerability, the development of heterogeneous chiral catalysts by immobilization of these complexes is difficult but highly desired. 

As depicted in Scheme 6, when an alkene-containing Grignard reagent is used, the resulting enantiomerically pure product (e.g., (S)-28) can be subjected to 6 mol% lb to afford the corresponding opticallypure carbocycle (S)-29 in 65% yield. 

A final word needs to be said about the supposedly unique features of enzymes, namely, their ability to produce enantiomerically pure products. This is not the place to speculate about the stereospecificity of enzymes, a problem that has been discussed elegantly by Comforth (15). It cannot be denied that the high (>99.9%) enantiomeric purity achieved by enzymes may be uniquely useful in the case of liquid products. However, when crystalline products are obtained in an asymmetric synthesis and the e.e. exceeds 80%, crystallization to enantiomeric purity without excessive loss of material is routinely achieved. 

Due to the requirement of obtaining enantiomerically pure products through environmentally friendly technologies, the development of new methods in asymmetric catalysis is becoming an important approach to asymmetric synthesis. Asymmetric hydrogenation is one of the most applied catalytic reactions for the... 

Hence, a reaction of Type I will involve a racemic or achiral/me,t(9 nncleophile which will react enantioselectively with an achiral acyl donor in the presence of a chiral catalyst, while on the other hand, a reaction of Type II will associate an achiral nncleophile and a racemic or udm lmeso acyl donor in the presence of a chiral catalyst. In both cases, when a racemic component is implicated the process constitntes a KR and the maximum theoretical yield of enantiomerically pure product, given perfect enantioselectivity, is 50%. When an achiral/mera component is involved, then the process constitutes either a site-selective asymmetric desymmetrisation (ASD) or, in the case of tt-nucleophiles and reactions involving ketenes, a face-selective addition process, and the maximum theoretical yield of enantiomerically pure product, given perfect enantioselectivity, is 100%. 

These chiral building blocks are incorporated into the target molecules in such a way that the configuration at the stereo centers remains unchanged. Since the relative configuration of newly produced centers of chirality can be controlled, virtually any enantiomerically pure product can be built around the chiral starting molecule. In the case of pheromones, chirality has a similar influence on their biological activity while one enantiomer attracts the insect species, the other may act as a repellent. ... 

A descriptor for an enzyme active site that permits binding of a family of related compounds (e.g., mimics of the reaction intermediate) that can be derived from the initial binding and conformational changes in the substrate. This concept arose from the observation that a number of monoterpene cyclases were incapable of discriminating between enantiomers of the reaction intermediate, even though the enzyme catalyzes the synthesis of an enantiomerically pure product from an achiral substrate. An example is trichodiene synthase which catalyzes the cyclization of farnesyl diphosphate to trichodiene. 

There have been more than 20 different syntheses of P-D-lactone.132 We will focus here on some of those which provide enantiomerically pure product, since they illustrate several of the methods for enantioselective synthesis.133... 

The ability to catalyze reactions leading to enantiomerically pure products is one of the most important features of enzymes. Therefore there is a special need for the analysis of optical activity of substrates or products of bio catalytic conversions. The methods for the estimation of enantioselectivity of bioconversions can be divided into five general classes ... 

Comparison of the rates of conversion of the pure enantiomers. This approach is possible with all analytical methods described below. The main disadvantage is the need for the enantiomerically pure products. 

The focus in this section is the electrophilic a-functionalization of 2,2-dimethyl-l,3-dioxan-5-one. Various reactions have been carried out, such as alkylations, aldol additions, Mannich reactions, and transition metal-catalyzed reactions. Conditions were described for diastereoselective transformations, or auxiliary controlled diastereoselective transformations, providing enantiomerically pure products, and enantioselectively catalyzed reactions using organo-catalysts. 

In recent work, a homochiral substituent has been incorporated into the reactant to allow the separation of enantiomerically pure products. Thus, the homochiral reactant 288, prepared from (5)-1-phenylethylamine, gave a pair of diastereoisomers (289) and (290) that were separated by chromatography and identified via X-ray crystallography (178). The nitrile imine was generated by the hydrazonyl chloride-base route. The reaction showed only modest stereoselectivity that favored 289 when silver carbonate was used as the base but it was found that this was reversed when triethylamine was used. However, this was not the case for a related reaction (179). 

There is an increasing trend towards the production of enantiomerically pure products so as to minimise side-effects of drugs. 

Several enzymatic processes have been developed. The DSM-Andeno method uses porcine pancreatic lipase, which selectively hydrolyses the (R)- +) glycidol with purities of at least 97% enantiomeric excess, suitable for subsequent chemical processing to prodnce enantiomerically pure products. 

For obtaining both the product and the remaining substrate in high enantiomeric excess in one reaction step, the E-value needs to be high, usually around or over 100. If the E-value is lower, isolation of the products and substrates followed by renewed reactions with these can be used in an iterative manner until sufficiently enantiomerically pure products are obtained. 

The hydroformylation of styrene in triethyl orthoformate is slower than that observed in benzene, but a 98% ee is obtained, since racemization of the product acetal does not occur. Hydrolysis of the acetal to the aldehyde can be accomplished without racemization. A number of other substrates are hydroformylated in the presence of triethyl orthoformate. The reactions are slower, but with all substrates tried except norbomene, enantiomerically pure products can be obtained. 

Discussion Amino acids are often utilized as sources of chiral information in the synthesis of enantiomerically pure products. In the present synthesis, however, it is the abnormal enantiomer tf-prolinc that is required, a compound 14 times as expensive as the natural 5 enantiomer. 

---