Epoxidation amino acid derivatives

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. 

The reaction of amino acid derivatives with epoxides has been explored to some extent in a recent study by Pascal.2082 Cyclic products are obtained, as shown in Eq. (036a). 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Chiral pyrrolidine derivatives, proline, and amino acid-derived imidazolidinones mediate the asymmetric epoxidation of ,/i-unsalurated aldehydes. Protected a,a-diphenyl-2-prolinol catalyses the asymmetric formation of 2-epoxyaldehydes, with hydrogen peroxide or sodium percarbonate as the oxygen sources, with 81-95% conversion with up to 96 4 dr and 98% ee.204... 

Similar to the epoxides, the most frequently encountered synthetic transformation for aziridines is nucleophilic ring-opening, whereby carbon- and heteroatom-based nucleophiles are comparably important. As an example of the former type, aziridine-2-carboxylates 100 can be ring-opened with higher order cuprates to give the protected amino acid derivatives 101, corresponding to attack at the less-substituted aziridine carbon [95TL151],... 

Alder reactions, 1,3-dipolar cycloadditions (Jen et al. 2000), and conjugate additions of electron rich aromatic and heteroaromatic compounds can be catalyzed using chiral amino acid derived imidazolidinones as catalysts (Scheme 17 Eqs. 35-38 Paras and MacMillan 2001, 2002 Austin and MacMillan 2002 Brown et al. 2003b). In addition, highly enantioselective epoxidations (Marigo et al. 2005b) and cyclopropana-tions (Kunz and MacMillan 2005) have recently been developed. 

The chiral titanated bislactim ether 104 undergoes 1,2-addition to a,(3-unsaturated aldehydes. With enal 105, it gives adduct 106, the epoxidation and subsequent hydrolysis of which forms the branched-chain amino-acid derivative 107 [84] (Scheme 13.42). 

Since epoxides potentially will react with a variety of amino acids, many products may be formed if they are incorporated into affinity labels. However at present affinity labels containing epoxides have been shown to modify either glutamate or aspartate residues in pepsin, lysozyme, those phosphate isomerase and j -glucosidase. The only other residue which has as yet been modified by epoxides is methionine 192 of chymotrypsin. In general, the other possible products should be similar in stability to derivatives formed by haloketones. Therefore the methods for identification of the amino acid derivatives formed by reaction with epoxides closely parallel those described in connection with haloketones ( 5.3.2). 

Several methods for the epoxidation of a,(3-unsaturated carbonyl compounds have been reported. The use of amino acid derivatives or peptides as chiral ligands for epoxidation continues to be an active area of investigation. The use of silica bound poly-L-leucine, 21, with sodium percarbonate appears to be an excellent route to enantiomerically pure keto... 

The Swern conditions were applied to a number of substrates with different functional and protecting groups, such as sugar derivatives, protected amino acid derivatives, tartaric acid derivatives, and optically active synthetic intermediates. Both acid-sensitive (epoxide, acetonide, silyl, NBoc, NCBz) and alkaline-sensitive groups (Ac, Bz, ester, silyl) were found to be completely unaffected. The proposed mechanism begins with tautomerisation of the amide to the hydroxy imine, followed by reaction with the dimethylchlorosulfonium species. The resulting oxysulfonium species 63 collapses when treated with base to regenerate DMSO and produce the nitrile. 

Chiraldex B-DA Nitrogen heterocyclics, heterocyclics, some lactones, aromatie amines, sugars, amino acid derivatives, bicyclie eompounds and epoxides. 

Recent work has improved enantiomeric excess of epoxida-tion reaction by use of metalloporphyrins having two chiral naphthyl groups, one above and one below the porphyrin plane. This asymmetric reaction seems to arise from chiral interaction between the chiral element of the catalyst and the achiral substrate in the transition state. Doubly strapped chiral porphyrins 17 are obtainable from the coupling of a,) ,a,) -tetralds-(2-aminophenyl)porphyrin and amino-acid derivative.- " Chiral space above and below the porphyrin plane results in moderately enantio selective epoxidation. Since then, various kinds of chiral porphyrins have been synthesized as catalysts for the oxygenation of organic substrates. 

The stereoselective synthesis of awri-P-amino-a-hydroxy acid derivatives using nucleophilic epoxidation of 1-arytlthio-l-nitroalkenes has been reported (Eq. 4.41).54... 

When a nonproteinogenic unsaturated amino acid was subjected to the Sharpless asymmetric epoxidation, 49 was formed (87TL3605). It is known that AAs are converted with phosgene into A-carboxy-a-amino acid anhydride (NCA) derivatives. Unexpectedly, A-protected dehydroaspartic acid gave l,3-oxazine-2,6-dione-4-carboxylic acid under such conditions (88CL1473). 

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