Enantiomeric selection materials

Preparation of enantiomerically enriched materials by use of chiral catalysts is also based on differences in transition-state energies. While the reactant is part of a complex or intermediate containing a chiral catalyst, it is in a chiral environment. The intermediates and complexes containing each enantiomeric reactant and a homochiral catalyst are diastereomeric and differ in energy. This energy difference can then control selection between the stereoisomeric products of the reaction. If the reaction creates a new stereogenic center in the reactant molecule, there can be a preference for formation of one enantiomer over the other. 

As was the case for kinetic resolution of enantiomers, enzymes typically exhibit a high degree of selectivity toward enantiotopic reaction sites. Selective reactions of enaiitiotopic groups provide enantiomerically enriched products. Thus, the treatment of an achiral material containing two enantiotopic functional groups is a means of obtaining enantiomerically enriched material. Most successful examples reported to date have involved hydrolysis. Several examples are outlined in Scheme 2.11. 

The ability to efficiently synthesize enantiomerically enriched materials is of key importance to the pharmaceutical, flavor and fragrance, animal health, agrochemicals, and functional materials industries [1]. An enantiomeric catalytic approach potentially offers a cost-effective and environmentally responsible solution, and the assessment of chiral technologies applied to date shows enantioselective hydrogenation to be one of the most industrially applicable [2]. This is not least due to the ability to systematically modify chiral ligands, within an appropriate catalyst system, to obtain the desired reactivity and selectivity. With respect to this, phosphorus(III)-based ligands have proven to be the most effective. 

The photoelectrochemical synthesis of amino acids from simple molecules has also been reported. Low efficiencies were observed in the conversion of mixtures of methane, ammonia and water to several amino acids on platinized TiOz Amino acids and peptides were reported when glucose replaced methane as the carbon source in a parallel experiment Higher quantum efficiencies (20-40%) were observed in the conversion of alpha-keto acids or alpha-hydroxy acids to the corresponding alpha-amino acids Moderate levels of enantiomeric selectivity (optical yields of about 50%) were reported when chiral starting materials were employed. Photoinduced Michael-like reactions were observed when alpha, beta unsaturated acids were used as substrates for the amino acid synthesis... 

Advances in preparative enantioseparation by simulated moving bed (SMB) chromatography have occurred in the last 10 years. SMB was invented in the 1960s and was used by the petrochemical and sugar industries. Now with the improvements in stationary phases and hardware it is an option for the large-scale preparation of enantiomerically pure material. The majority of the latest published data are using either amylose- or cellulose-based phases because of their selectivity. There are now examples in the literature of the commercial separation on the multi-ton scale.8... 

Carbohydrates are efficient chiral templates and have been used in the Diels-Alder reaction. Sherbum used L-ascorbic acid as a template to synthesize 305.249 Heating this compound in refluxing toluene led to a 96 4 mixture of 306 and 307 (68% yield). The chirality inherent in the carbohydrate precursor provides the needed facial selectivity that is transferred to the cycloadduct product. The use of chiral templates for preparing Diels-Alder precursors will undoubtedly increase in importance. As the need for enantiomerically pure material increases, the chiral template approach coupled with the power of the Diels-Alder reaction will be an effective combination. 

One of the major limitations of aluminosilicate zeolites is their current inability to impart shape selectivity based on molecular handedness, primarily because it is extremely difficult to make enantiomerically pure materials. Because of the relative ease of synthesizing accessible chiral channels in hybrid materials, a significant amount of attention is now being devoted to developing materials with chiral pores and studying their catalytic activity. The area has recently been reviewed by Lin. One potential problem is that chiral organics may not survive hydrothermal reaction conditions enantiomerically intact, but Williams and co-workers have shown that this is not a general problem. 

Incorporating the chirally selective material into a phenylpolysiloxane polymer raises the operating temperature significantly and, in addition, the polarizability of the phenyl group allows induced dipole interactions (ti interactions) with polar solutes. Materials based on the phenylsiloxane polymers can be used up to temperatures (conservatively) of about 180°C. These materials are suitable for the separation of enantiomers that are essentially polar but, insufficiently polar to render them involatile. Derivatives of polar substances would also separate well on phenylpolysiloxane polymer stationary phases, but the derivatizing procedure must not effect the enantiomeric ratio. 

The crucial step in an enantioselective synthesis hy Mori [219] is the pig hver esterase-catalysed hydrolysis of the corresponding acetoxy-derivative. Regrettably, the selectivity is not sufficiently high, so that the resolution has to be carried out twice to obtain enantiomerically pure material. In the final step, the alcohol function is reductively removed. 

In the area of carbocyclic nucleoside antibiotics, hydrolysis of the racemic esters 40 (R= n-Bu or ii-CeHis) by the lipase from Candida rugosa proceeds with very high enantiomeric selectivity, and from the resolved materials both enantiomers of aristeromydn were made by an established route. The authors report that a previous similar method (Vol.21, p. 182) is not as enantioselective. In a new synthesis of neplanocin A (43), the alcohol 41, derived from D-ribose, was converted to the cyclopentene 42 using an intramolecular insertion reaction of an alkylidene carbene. The new stereocentre in 42 was mostly of the wrong P-configuration, but could be corrected by a process of desilylation, oxidation and borohydride reduction. The biosynthesis of neplanocin A (43) and aristero-mycin has been reinvestigated, and the cyclopentenone 44 has been proposed as an intermediate, which is converted to aristeromycin via neplanocin A without any bifurcation. The 3-deaza-analogue 45 of 5 - or-aristeromydn has been prepared, and the antiviral activity of it and of the 7-deaza-compound (Vol.27, p. 235) are reported. ... 

Induction of chiraUty to obtain enantiomerically or diastereomericaUy enriched materials is achieved by several approaches (1) absorption of circularly polarized light by a racemate, causing different reaction rates for the enantiomers (2) reactions in chiral medium such as chiral solvent (3) the use of an enantiomerically pure sensitizer and (4) the use of enantiomerically pure materials, that is, photochem-ically reactive components attached to an enantiomerically pure auxfliary. The first two methods have not yielded product with more than a few percent enantiomeric excess (ee < 5%). Chiral sensitization has yielded, in a few select examples, moderate ee ( 15-65%), while the chiral auxiliary approach has yielded high diastereomeric excess (de). In this approach, because there is a chiral center in the reactant, the products are formed as diastereomers. Removal of the chiral auxfliary results in an enantiomerically enriched product. 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance The best examples are found m biochemical processes Most bio chemical reactions are catalyzed by enzymes Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment m which chemical reaction can take place Ordinarily enzyme catalyzed reactions occur with such a high level of stereo selectivity that one enantiomer of a substance is formed exclusively even when the sub strate is achiral The enzyme fumarase for example catalyzes hydration of the double bond of fumaric acid to malic acid m apples and other fruits Only the S enantiomer of malic acid is formed m this reaction... 

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

Because they are readily available from natural sources in enantiomerically pure form, carbohydrates are very useful starting materials for the synthesis of other enantiomerically pure substances. However, the high number of similar functional groups present in the carbohydrates requires versatile techniques for protection and deprotection. Show how appropriate manipulation of protecting groups and other selective reactions could be employed to effect the following transformations. 

A classical approach to driving the unfavorable equilibrium of an enzymatic process is to couple it to another, irreversible enzymatic process. Griengl and coworkers have applied this concept to asymmetric synthesis of 1,2-amino alcohols with a threonine aldolase [24] (Figure 6.7). While the equilibrium in threonine aldolase reactions typically does not favor the synthetic direction, and the bond formation leads to nearly equal amounts of two diastereomers, coupling the aldolase reaction with a selective tyrosine decarboxylase leads to irreversible formation of aryl amino alcohols in reasonable enantiomeric excess via a dynamic kinetic asymmetric transformation. A one-pot, two-enzyme asymmetric synthesis of amino alcohols, including noradrenaline and octopamine, from readily available starting materials was developed [25]. 

In contrast to the asymmetrization of meso-epoxides, the kinetic resolution of racemic epoxides by whole fungal and bacterial cells has proven to be highly selective (see above). These biocatalysts supply both the unreacted epoxide enantiomer and the corresponding vidnal diol in high enantiomeric excess. This so-called classic kinetic resolution pattern of the biohydrolysis is often regarded as a major drawback since the theoretical chemical yield can never exceed 50% based on the racemic starting material. As a consequence, methods... 

Selection-coupled analysis/phase segregation. One strategy for simplifying the analytical challenge is to use phase segregation. Three subclasses are possible. In the first of these, a phase transition is part of the selection process. This includes not only the familiar crystallization-induced enantiomeric enrichment discussed above but also the experiments (primarily employed in experiments directed toward the production of novel materials) such as those described by Lehn and coworkers in 2005. In this study, an acylhydrazone library was created from guanosine hydrazide and a mixture of aldehydes (Fig. 1.22) in the presence of metal ions, formation of G-quartet structures led to the production of a gel. 

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