Optically active products synthesis

Miyafuji and Katsuki95 reported the desymmetrization of meso-tetrahydrofuran derivatives via highly enantioselective C-H oxidation using Mn-salen catalysts. The optically active product lactols (up to 90% ee) are useful chiral building blocks for organic synthesis (Scheme 8-48). 

Another achievement in recent asymmetric reaction study is the so-called chiral autocatalysis—where the product itself catalyzes its own asymmetric synthesis. In this process, the chiral catalyst and the products are the same in an asymmetric autocatalytic reaction. The separation of chiral catalyst from the product is not required, because the product itself is the catalyst. Starting from an optically active product with very low ee, this process allows the formation of a product with high ee values.106,114... 

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. 

The synthesis of 2-(trifluoromethyl) derivatives is more difficult and the compound preferentially obtained depends on the substituents and on the reaction conditions. Thus, the reaction of tryptophan with TFAA gives the 5(47/)-oxazolone without racemization." However, when this optically active product is dissolved in acetonitrile the racemic 5(47/)-oxazolone is obtained. On the other hand, treatment of the optically active compound with hot aqueous dioxane gave the isomeric 5(27/)-oxazolone (see Scheme 7.2). 

Nondestructive reactions of trisacetylacetonates of chromium(lll), cobalt(lll), and rhodium(lll) are reviewed. Halogenation, nitration, thiocyanation, acylation, formylation, chloromethylation, and aminomethylation take place at the central carbon of the chelate rings. Trisubstituted chelates were obtained in all cases except acylation and formylation. Unsymmetrically and partially substituted chelates have been prepared. Substitutions on partially resolved acetylacetonates yielded optically active products. NMR spectra of unsymmetrically substituted, diamagnetic chelates were interpreted as evidence for aromatic ring currents. Several groups were displaced from the chelate rings under electrophilic conditions. The synthesis of the chromium(lll) chelate of mal-onaldehyde is outlined. 

Careful inspection of the reported photocatalytic reactions may demonstrate that reaction products can not be classified, in many cases, into the two above categories, oxidation and reduction of starting materials. For example, photoirradiation onto an aqueous suspension of platinum-loaded Ti02 converts primary alkylamines into secondary amines and ammonia, both of which are not redox products.34) ln.a similar manner, cyclic secondary amines, e.g., piperidine, are produced from a,co-diamines.34) Along this line, trials of synthesis of cyclic imino acids such as proline or pipecolinic acid (PCA) from a-amino acids, ornithine or lysine (Lys), have beer. successfuL35) Since optically pure L-isomer of a-amino acids are available in low cost, their conversion into optically active products is one of the most important and practical chemical routes for the synthesis of chiral compounds. It should be noted that l- and racemic PCA s are obtained from L-Lys by Ti02 and CdS photocatalyst, respectively. This will be discussed later in relation to the reaction mechanism. 

D-(+)-glyccraldchyde was allowed to undergo the Kiliani-Fischer synthesis. and the reaction ran to completion. After separation of any isomers, how many optically active products were formed ... 

Asymmetric hydroboration and conceptually similar reactions involving chiral reagents have been used with great success. Their principal shortcoming is that stoichiometric quantities of chiral compounds must be invested and only rarely can these compounds be recycled. An asymmetric reaction involving a catalyst that is chiral would be a superior way to accomplish an asymmetric synthesis since, with only a small amount of chiral material, large quantities of optically active product could, in principle, be obtained. 

Recently, Sakamoto et al. reported an absolute asymmetric synthesis using the frozen chirality generated by chiral crystallization. Achiral asymmetricly substituted imide 68, which bonds between the nitrogen atom and the tetrahydronaph-tyl (TENAP) group, rotates freely at room temperature, crystallized in a chiral fashion, and the enantiomerization owing to the bond rotation was suppressed at low temperature (Scheme 33). Furthermore, the frozen molecular chirality could be transferred to optically active products in fluid solution [35]... 

Even if a molecule is achiral, chiral crystals can form by spontaneous chiral crystallization [26]. The big advantage in utilizing a crystal as a reactant is that absolute asymmetric synthesis can be achieved by solid-state photoreaction of such a chiral crystal. The initial chiral environment in the crystal lattice is retained during the reaction process, owing to the low mobility of molecules in the crystalline state, and leads to an optically active product. The process represents transformation from crystal chirality to molecular chirality. This kind of absolute asymmetric synthesis does not need any external asymmetric source in the entire synthetic procedure [9-14]. 

A measure of the interest in the biological activity of these dibenzyl-butyrolactone lignans is evinced in the recent spate of publications dealing with the total synthesis of the natural optically active products. Again, the Stobbe condensation pathway (Scheme 9) has been usefully exploited for this purpose. In a series of papers, resolution of the intermediate hemisuccinate esters (433 by chiral bases has been described (54), as has asymmetric hydrogenation (55), and the optically active lignan products synthesized in the usual way (42 - 44 45). 

It was most convenient to isolate the products after acidic conversion to cyclohexenones. Structures of the products were assigned by chemical correlation and circular dichroism and the enantiomeric purities were based on optical rotations. The selectivities obtained, although impressive for the era, are moderate at best, despite significant attempts to optimize the substrates and reaction conditions. Use of substituted cyclohexanones (29) and other aldehydes (30) lead to optically active products but the extent of enantiomeric induction in these products was not determined. This technology was used for the partial asymmetric synthesis of (+ )-mesembrine (12.1) (29) and (+ )-podocarpic acid (12.2) (31). 

Unless a resolution step is included, the a-amino acids prepared by the synthetic methods just described are racemic. Optically active amino acids, when desired, may be obtained by resolving a racemic mixture or by enantioselective synthesis. A synthesis is described as enantioselective if it produces one enantiomer of a chiral compound in an amount greater than its mirror image. Recall from Section 7.9 that optically inactive reactants cannot give optically active products. Enantioselective syntheses of amino acids therefore require an enantiomerically enriched chiral reagent or catalyst at some point in... 

In a more impressive polyene cyclization, reaction of the optically active allylic alcohol 147 with trifluoroacetic acid and ethylene carbonate followed by workup with K2CO3 in aqueous methanol furnished the optically active product 150. The reaction is initiated by a yyn-selective SN2 reaction with allylic rearrangement (Sn2 ) and proceeds through the carbonate-trapped intermediate 149. Likewise, the reaction of the enantiomer of 147 furnished the enantiomer of 150. The cyclization step was essentially enantiospecific. The process involves total asymmetric synthesis due to a single chiral center in the starting allyl alcohol [24]. 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

Optically active products formed by such reductions may serve as useful intermediates in organic syntheses. A concept for a new total synthesis of natural a-tocopherol has been proposed27 where the optically active C5 units, (5)-3-methyl-y-butyrolactone or (5)-2-methyl-y-butyrolac-tone, were used to build up the side chain. Both compounds are broadly applicable optically active building blocks for the syntheses of chiral compounds and have been prepared by stereospecific reduction of suitable unsaturated precursors. 

This efficient asymmetric synthesis was used to convert (3) into (4) with an optical purity of 86%. In this case L-phenylalanine proved to be much more efficient than L-proline. The optically active product (4) was converted into optically active estrone (6) in overall yield of 13% from (2). The intermediate... 

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