Chirality amino acid complexes

A major advantage that nonenzymic chiral catalysts might have over enzymes, then, is their potential ability to accept substrates of different structures by contrast, an enzyme will select only its substrate from a mixture. Striking examples are the chiral phosphine-rhodium catalysts, which catalyze die hydrogenation of double bonds to produce chiral amino acids (10-12), and the titanium isopropoxide-tartrate complex of Sharpless (11,13,14), which catalyzes the epoxidation of numerous allylic alcohols. Since the enantiomeric purities of the products from these reactions are exceedingly high (>90%), we might conclude... 

A chiral amino-acid/copper complex is bound to a silica- or polymeric stationary phase and copper ions are included in the mobile phase to ensure there is no loss of copper. Amino acids then may be separated by the formation of diastereomeric copper complexes. Water stabilizes the complex by coordinating in an axial position. Steric factors then determine which of the two complexes is more stable. One of the water molecules is usually sterically hindered from coordinating with the copper. i ... 

Kim, Chin, and co-workers have described a highly interesting oxyanion hole mimic that transforms L-amino acids to D-amino acids [97]. The mechanism involves stabilization of the enolate intermediate by an internal hydrogen bond array generated by urea group (Scheme 4.14). In the presence of an external base, such as triethylamine, the receptors readily promote the epimerization of a-amino acids, favoring the D-amino acids due to unfavorable steric interactions in the receptor-L-amino acid complex. These receptors can also be viewed as chiral mimics of pyridoxal phosphate [98]. 

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. 

Other chiral phases include those based on proteins, cellulose triacetate, amino acids complexed with copper and chiral crown ethers. 

Hayashi et al.74 described a process of kinetic resolution in the coupling of Grignard reagents R Mgx (having a chiral center at the point of attachment to the metal) with various alkenyl halides under the influence of chiral phosphine-nickel complexes. Chiral amino acid derivatives (35) were used as ligands. 

The last example reflects in a modest way the importance of the study of stereoisomerism. Biological conversions represent a glorious array of diastereomeric reactions and interactions a given chiral amino acid is metabolized but its enantiomer is not a certain complex drug (often a chiral molecule) alleviates pain but its enantiomer is inactive and subdc changes in structure alter a given chiral compound s action completely in the human body. 

One reason for an otherwise apparently excessive interest in Co(trien)X2+ systems is the use of ds-Co(OH)(trien)(OH2)2+ in the hydrolysis of amino acid esters, amino acid amides and peptides785 to form cis-px- and cis-/J2-Co(trien)(aa)2+ (aa = amino acid) complexes.16 In principle, a peptide could be degraded in a stepwise manner and each amino acid residue successively characterized. By the introduction of a chiral center into the backbone of the trien moiety, it was hoped to make such reactions stereoselective. Consequently, while fully A-alkylated trien systems have been widely investigated for M11 central ions, the C-alkylated trien systems have been almost exclusively the reserve of the Co111 chemist (Table 11). 

A kinetic resolution is a chemical reaction in which one enantiomer of a racemate reacts faster than the other. Most kinetic resolutions of pharmaceutical compounds are catalyzed processes. Catalysts used in a kinetic resolution must be chiral. Binding of a chiral catalyst with a racemic material can form two different diastereomeric complexes. Since the complexes are diastereomers, they have different properties different rates of formation, stabilities, and rates of reaction. The products form from the diastereomeric substrate-catalyst complexes at different rates. Therefore, a chiral catalyst is theoretically able to separate enantiomers by reacting with one enantiomer faster than the other. The catalysts used in kinetic resolutions are often enzymes. Enzymes are constructed from chiral amino acids and often differentiate between enantiomeric substrates. 

The design of receptors 32-34 was based on the attachment of chiral amino acid chains to benzo-18-crown-6 ether [64]. These molecules were able, upon the addition of cesium salts of amino acids, to form sandwich complexes and distinguish between enantiomers of the substrate added. The enantioselective... 

A Derivatives of 1 1 complexes As a result of the chirality of ai-[P2-W17O61]10- (Figure 5) solutions of [ Ce(o i-P2Wi706i)(H20)4 2]14 contain enantiomeric pairs of monomers in equilibrium with the meso dimer. Addition of chiral amino acids to such solutions causes a doubling of the 31P-NMR resonances as a result of diastereomer formation presumably caused by coordination of the amino acid to the rare-earth cation (Sadakane et al., 2001). No splitting was observed when similar experiments were carried out with complexes of the achiral a2 isomer. Formation constants for the two diastereomers of the complexes with L-proline were estimated as 7.3 1.3 and 9.8 1.4 M-1. The corresponding proline complex of achiral [Ce W C i)]7- has a formation constant of 4.5 0.1 M-1 (Sadakane et al., 2002). 

The use of mixed micelles for chiral recognition was discussed in Section 5.3.3, using cyclodextrins. In addition to cyclodextrins, however, metal-amino acid complexes can also be used in a mixed mode arrangement. Bile salts are naturally occurring chiral surfactants that can be used as alternatives to, or in addition to, SDS for chiral recognition. In the presence of SDS, the migration times are faster. Table 5.5 shows initial operating conditions that can be used in chiral CE as a start to methods development.40... 

Nitro compounds are also useful starting materials, because a nitro group can be readily converted to a carbonyl group or to amino functionality. Addition reactions of nitroalkane have been reported by Yamaguchi [13b], Shibasald [6a], Bako and Toke, Corey, Hanessian, and Kanemasa [21]. For example, Kanemasa used their chiral Lewis acid complex 35 for the reaction of 36 with nitromethane (Scheme 18). The reaction proceeded with the aid of the amine co-catalyst, affording the product 37 with high enantioselectivity. This system was also applicable to the reaction of malononitrile [2 le]. 

The photolysis of chiral amino carbene complexes of type 31 [14] in the presence of alcohols leads diastereoselectively to products of type 32 and thus opens an efficient access to a wide range of natural and non-natural amino acid derivatives in optically active form [15]. These reactions proceed via the intermediates 33 and 34, the products being formed by highly diastereoselective protonation of 34 (Scheme 9). 

Kobayashi and co-workers. used zirconium-based bromo-BINOL complex for the catalytic enantioselective Mannich-type reaction. The o-hydroxyphenyl imine 3.36 chelates the Zr(IV)(BrBINOL)2 to form the activated chiral Lewis acid complex A. The ketone acetal 3.37 reacts with the Lewis acid complex A to give the complex B. The silyl group is then transferred to the 3-amino ester to form the product 3.38 and the catalyst Zr(BrBINOL)2 is regenerated, which is ready for binding with another imine molecule (Scheme 3.16). 

Co(trien)(NH3)2] + has been isolated, and only the meso trans isomers (197-198) with two different axial ligands, remain to be distinguished. There is also an extensive chemistry of N and C-alkylated derivatives of (178 180) as cA-[Co(OH)(trien)(OH2)] assists the hydrolysis of amino acid esters, amino acid amides, and peptides to form cis-fi (194) and cA-jS2-[Co(OA0(trien)] + (195)(( A = amino acid) complexes. Chiral alkylated trien ligands have the potential for chiral stereospecificity in such reactions. 

Photolysis of chiral amino carbene complexes in the presence of alcohols gives amino acid esters, again with a very high diastereoselectivity. Irradiation of aminocarbenes in the presence of 2,4,5-trichlorophenol produced optically active, activated, a -amino 2,4,5-trichlorophenoxide esters. Related intramolecular reactions of carbenes having a pendant alcohol afford lactones. For example, aldol condensation of (17)... 

In addition, OPEN is an efficient chiral solvating agent for determination of the enantiomeric excess in the H NMR analysis of various chiral mono- and dicarboxylic acids including a-arylpropanoic and a-halo carboxylic acids. The chemical-shift non-equivalence (S A) in certain diastereomeric complexes is greater than 0.05 ppm. A DPEN/Pd(II) complex can be used for determination of enantiomeric excess of the non-protected chiral amino acids by H and C NMR analysis. For example, Pd[(S,S)-dpen](D20)2 and racemic alanine with a base forms the square-planar complex (eq 14). The 5 A of H-NMR resonance in the diastereomeric complexes in D2O is 0.056 ppm, while this complex hardly dissolves in D2O. 

Glusker, J. P., Carrell, H. L., Job, R., and Bruice, T. C. Mechanism for chiral recognition of a prochiral center, and for amino acid complexation to a Co(III) tetramine. The crystal structure, absolute configuration and circular dichro-ism of A(-)436-/ -[ (25 95)-2,9-diamino-4,7-diazadecanecobalt(III)aminomethyl-malonate] perchlorate monohydrate. J. Amer. Chem. Soc. 96, 5741-5751 (1974). 

Djordjevic et al.464 have described the synthesis and characterization of amino acid complexes MoO(02)2Leq(OH2) (192) and the X-ray structures of the Gly, Ala, and Pro derivatives. Chiral ligands such as (R)/(S)-(194), (R)/(S)-(195), and (RR,S)/(R,SR)-(196) form Mimoun complexes, MoO(02)2L and MoO(02)2L(OH2). IR and 31P NMR data, as well as the X-ray structure of pentagonal bipyramidal MoO(02)2(R,R,.S -196)(OH2), indicate the presence of equatorial phos-phoryl donors.465,466 Enantioselectivity in the stoichiometric epoxidation of pro-chiral olefins was marginal (<10%) except in the case of the binaphthyl derivatives (L - 195) where e.e. s of up to 39% were recorded.4 Related structures are observed for phosphine oxide458,467 and chelate complexes such as MoO(02)2 OE(iPr)2CH2CH2OMe (197, E = P, As) 458 468 An efficient bipha-sic catalytic epoxidation system based on MoO(02)2(OPR3) (R = -dodecyl) has been developed and the activity of related complexes assessed.460 Earlier attempts to produce aqueous oxidants included the synthesis of water-soluble bpy derivatives.469,470... 

Asymmetric Hydrogenation. Rhodium complexes of the type Rh(diene)(diphos )+, where diphos is a chiral bidentate diphosphine ligand, are catalyst precursors for the asymmetric hydrogenation of certain prochiral olefins (15). Asymmetric hydrogenation of a-acylaminoacrylates, for example, affords chiral amino acid derivatives, some of which have medicinal utility such as L-DOPA. 

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