Chiral templates amino acids

The sequence of Ugi-4CR + hydrolysis of the amino substituent has been employed in the stereoselective synthesis of chiral a-amino acid derivatives, by using a chiral amine component. Then the chiral template was covalently bound in close proximity to the newly synthesized chiral center. The amine residue of the product must be removable under mild conditions to avoid decomposition of the desired product. Chiral a-ferrocenylamines have been employed with some success [34], but the most useful auxiliaries were carbohydrate amines [35]. 

A number of functionalized chiral, nonracemic amino acids can be prepared using ethyl pyroglutamale as a chiral template. Silverman reduced ethyl pyroglutamate (5.4J) to the alcohol (5.42) with lithium borohydride.23 This was followed by treatment with bromine and triphenylphosphine to give 5-bromomethyl-2-pyrrolidinone, 5.48. Similarly prepared were 5-chloromethyl-2-pyrrolidinone (5.50) 5-fluoro-methyl-2-pyrrolidinone (5.52) and, 5-cyanomethyl-2-pyrrolidinone.23 In all cases, reaction with HCl and isolation via ion exchange chromatography gave the 5-halo-4-aminopentanoic acid [5-bromo-4-aminopentanoic acid 5.49) 5-chloro-... 

Significantly, the acidic conditions for release of the amino acid derivatives from the chiral template gives access to arylglycines, even those carrying electron-withdrawing substituents, e.g., a chlorine atom, which arc prone to ready racemization under basic conditions. 

In conclusion, the use of glycosylamincs as chiral templates in the Ugi reaction provides an efficient and highly stereoselective access to both l- and D-amino acids. 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

As explained above in Section n, incorporation of chiral amino acids in the linker arms between the template and the hgating hydroxamate groups not only allows one to determine the directionality of the hehcal twist, but also permits one to modify the chelator properties such as buUciness, hydrophobicity and receptor selectivity. 

Chirality can be introduced at two possible sites on the basic tripodal structures replacing the tripodal template by a chiral template or modifying each arm with a chiral component, usually as amino acids, between the template and the ligating groups. Incorporation of amino acids inevitably introduced an amide bond known to promote intricate H-bonding networks. The latter can be applied to the various templates described so far. 

Eujii Y, Matsutani K, Kikuchi K. Formation of a specific coordination cavity for a chiral amino-acid by template synthesis of a polymer Schiff-base cobalt(III) complex. Chem Commun 1985 415-417. 

Williams and Fegley (40) utilized his chiral template (Section 3.2.3) as a chiral dipolarophile in the concise synthesis of 5 -( )-cucurbitine, a naturally occurring amino acid isolated from species of pumpkin, that acts as a growth inhibitor to... 

For the total synthesis of aminodeoxy sugars from nonsugar precursors, it is logical to turn to amino acids as primary sources of chiral templates. The challenge is to find innovative and stereocontrolled methods of chain extension reactions that lead to higher-carbon aminodeoxy sugars. 

Microwave-assisted Diels-Alder reactions of 9-substituted anthracenes with 2-acetamidoacrylate in DMF generate conformationally constrained bicyclic bisaryl a-amino acid derivatives with high regioselectivity.138 The Sc(OTf)3-catalysed Diels-Alder reaction of anthracenes with methyl vinyl ketone does not proceed via an electron-transfer process from anthracenes to the MVK-Sc(OTf)3 complex.139 (-)-(/ )-9-(l,2-Dimethoxyethyl)anthracene has been used as a chiral template in the Diels-Alder/retro-Diels-Alder sequence for the synthesis of a,j3-unsaturated lactams.140... 

Using an elegant approach, Che et al. prepared chiral mesoporous silica using bio-inspired surfactants [63]. The trimethylammonium group of the quaternary amine used as a surfactant in the synthesis of MCM-41 (CTAB) was replaced by L-alanine. The chirality of the amino acid in the polar head of the surfactant induces chirality in the micelle used as template (see Figure 3.15). This simple modification in the surfactant allowed the preparation of the first chiral mesoporous silica with tunable pore size and ordered porosity. A key step in this synthesis is the transfer of the chirality from the surfactant to the solid, which was accomplished by electrostatic interaction between the terminal amino acid and the... 

As with another class of compounds, the scale of synthesis and time required at the research stage before product can be made influence which method is finally used. At small scale, a plethora of methods exist to prepare amino acids, in addition to isolation of the common ones from natural sources. The majority of these small-scale reactions rely on the use of a chiral auxiliary or template. At larger scale, asymmetric hydrogenation and biocatalytic processes come into their own. For the amino acids approaching commodity chemical scales, biological approaches, either as biocatalytic or total fermentation, provide the most cost-efficient processes. 

Camphor and camphor-derived analogues are used frequently as chiral auxiliaries in asymmetric synthesis (cf Chapter 23). There have been numerous reports in the use of camphor imine as templates to direct enantioselective alkylation for the synthesis of a-amino acids, a-amino phos-phonic acids, a-substituted benzylamines, and a-amino alcohols (e.g., Scheme 5.9).43 47 Enantiomeric excesses of the products range from poor to excellent depending on the type of alkyl halides used. 

Use of existing chiral compounds as starting materials or templates in a stoichiometric fashion. The use of existing chiral compounds as a source of chiral center is popular among organic chemists. Natural amino acids have been extensively used for this purpose (4). While this method is most convenient, it is limited by the availability and die cost of the existing chiral pool. 

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