Asymmetric environment

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... 

There are three main criteria for design of this catalytic system. First, the additive must accelerate the cyclopropanation at a rate which is significantly greater than the background. If the additive is to be used in substoichiometric quantities, then the ratio of catalyzed to uncatalyzed rates must be greater than 50 1 for practical levels of enantio-induction. Second, the additive must create well defined complexes which provide an effective asymmetric environment to distinguish the enantiotopic faces of the alkene. The ability to easily modulate the steric and electronic nature of the additive is an obvious prerequisite. Third, the additive must not bind the adduct or the product too strongly to interfere with turnover. 

For example in the so-called Mukaiyama aldol reaction of an aldehyde R -CHO and a trimethylsilyl enol ether 8, which is catalyzed by Lewis acids, the required asymmetric environment in the carbon-carbon bond forming step can be created by employing an asymmetric Lewis acid L in catalytic amounts. 

The question that emerges at the climax of this survey relates to the possibility of using crystalline inclusion phenomena for optical resolutions of molecular species. Can this be done effectively with suitably designed host compounds The definitely positive answer to this question has elegantly been demonstrated by Toda 20) as well as by other investigators (see Ch. 2 of Vol. 140). An optically active host compound will always form a chiral lattice. Therefore, when an inclusion type structure is induced, one enantiomer of the guest moiety should be included selectively within the asymmetric environment. 

In Fe2+, the situation is more complicated. Here the six 3d-electrons dominate the magnitude of the electric field gradient, though in a way that is determined by the lattice symmetry. If a Fe2+ ion comes in a more asymmetric environment, the quadrupole splitting decreases in general, because the lattice contribution to the electric field gradient is smaller than the electronic contribution, and has the opposite sign. 

However, the use of the heterogeneous catalysts in applicative enantioselective syntheses has a limited success. Several factors contribute to this situation (1) a long time is required to achieve an effective heterogeneous enantioselective catalyst compared with the homogeneous ones, (2) a more complex structure of the heterogeneous catalyst surface on which centers coexist with different catalytic activity and selectivity, which can lead to undesired secondary reactions, and (3) an increased difficulty to create an effective asymmetric environment and to accommodate it with the multitude of reactions that are interesting to be carried out under enantioselective restrictions. 

Me has described the use of an optically active tripodal amine, (25, 65)-2,6-bis(o-hydroxyphenyl)-l-(2-pyridyhnethyl)piperidine (68) as a potent catalyst for methano-lytic ASD of cyclic mei o-anhydrides (Fig. 16) [227], This catalyst was envisaged to adopt a helical conformation thereby providing a highly asymmetric environment for the nucleophihc teri-amine lone pair whilst also allowing activation of the anhydride substrate by the phenolic hydroxyl groups. In the event, ees up to 81% were obtained for the methanolytic ASD of a cyclic meio-anhydride when employed at the 5 mol% level for 20 h at 0 °C in toluene [227]. 

Certain alkaloids are able to effect asymmetric induction during a reduction process at a mercury cathode even when present in low concentration in an aqueous alcohol acetate buffer. Asymmetric induction under these conditions was first observed [39] during the conversion of 4-methylcoumarin to 4-methyl-3,4-dihydro-coumariit (sec page 60). Induction results because a layer of alkaloid is strongly adsorbed on the electrode surface thus permitting transfer of a proton to a carban-ion intermediate m an asymmetric environment. Up to 16% asymmetric induction has been achieved in 1-phenylethanol recovered from reduction of acetophenone in a buffer of pH 4.8 containing a low concentration of quinidine. lire pinacol formed simultaneously shows no optical activity. However quinidine is itself reduced at the potential employed so that the actual catalyst for the asymmetric process is not defined [34,40],... 

Some researchers have begun to explore the possibihty of combining transition metal catalysts with a protein to generate novel synthetic chemzymes . The transition metal can potentially provide access to novel reaction chemistry with the protein providing the asymmetric environment required for stereoselective transformations. In a recent example from Reetz s group, directed evolution techniques were used to improve the enantioselectivity of a biotinylated metal catalyst linked to streptavidin (Scheme 2.19). The Asn49Val mutant of streptavidin was shown to catalyze the enantioselective hydrogenation of a-acetamidoacrylic acid ester 46 with moderate enantiomeric excess [21]. 

Here, Vi is termed the one-fold component (periodic in 360°), V2 is the two-fold component (periodic in 180°) and V3 the three-fold component (periodic in 120°). Additional terms are required to account for bond rotations in asymmetric environments. Higher-order components may also be needed, but are not considered here. 

The CD features of bacteriochlorophyll a in light-harvesting bacteriochlorophy 11-protein complexes from native bacteria is more interesting and is not compatible with Boxer s experiments. Bacteriochlorophyll(Bchl)-protein complexes exhibit various CD spectral profiles, depending on the species of bacteria and their culture conditions 201 206). Thus, CD of Bchl arises from the asymmetric environment in which the Bchl is situated, and from the specialized arrangement which affords a specific interaction between Bchl molecules, as well as from the asymmetry of Bchl... 

Cinchona alkaloids, naturally ubiquitous /3-hydroxy tertiary-amines, are characterized by a basic quinuclidine nitrogen surrounded by a highly asymmetric environment (12). Wynberg discovered that such alkaloids effect highly enantioselective hetero-[2 -I- 2] addition of ketene and chloral to produce /3-lactones, as shown in Scheme 4 (13). The reaction occurs catalytically in quantitative yield in toluene at — 50°C. Quinidine and quinine afford the antipodal products by leading, after hydrolysis, to (S)- and (/ )-malic acid, respectively. The presence of a /3-hydroxyl group in the catalyst amines is not crucial. The reaction appears to occur... 

The CD in the d-d bands of the blue copper protein (Fig. 23-8) arises in part from the fact that within the protein the copper ion is in an asymmetric environment. For a similar reason, the aromatic amino acids of proteins often give rise to circular dichroism. 

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