Titanium complexes amino acids

If the following glycine derived ester is deprotonated and transmetalated with the (/ ,/ )-lartaric acid derived titanium complex, and then added to butanal, the sy -a-amino-/Thydroxy ester, which is enantiomeric to the products obtained above, is formed. 

Colona and coworkers oxidized a variety of alkyl aryl and heterocyclic sulfides to the sulfoxides using t-butyl hydroperoxide and a catalytic amount of a complex (97) derived from a transition metal and the imines of L-amino acids. Of the metals (M = TiO, Mo02, VO, Cu, Co, Fe), titanium gave the highest e.e. (21%), but molybdenum was the most efficient catalyst. The sulfoxides were accompanied by considerable sulfone125. 

Complexation of an amino acid derivative with a transition metal to provide a cyanation catalyst has been the subject of investigation for some years. It has been shown that the complex formed on reaction of titanium(IV) ethoxide with the imine (40) produces a catalyst which adds the elements of HCN to a variety of aldehydes to furnish the ( R)-cyanohydrins with high enantioselectivity[117]. Other imines of this general type provide the enantiomeric cyanohydrins from the same range of substrates11171. 

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... 

Chiral titanium complexes with a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands are versatile auxiliaries in the Lewis acid catalyzed alcoholysis of racemic 4-(arylmethyl)-2-phenyl-5(477)-oxazolones 234, providing the corresponding enantiomerically enriched N-protected amino acid esters 235 (Scheme 7.73). The enantioselectivity of the reaction is dependent on the solvent, temperature, and chiral ligand. Selected examples of the alcoholysis of saturated 5(477)-oxazolones are shown in Table 7.21 (Fig. 7.23). 

The reaction of the acyclic bis(allyl)titanium complexes 16 with the imino esters 23a-c in the presence of Ti(OiPr)4 and ClTijOiPrjs at low temperatures proceeded with >98% regioselectivity and >98% diastereoselectivity and gave the corresponding T-syn-configured unsaturated a-amino acid derivatives E-24 in good yields (Scheme 1.3.11) [21, 22]. 

It is noteworthy that stereoselectivities were high, even with sterically demanding substituents at the double bond. Similarly, the treatment of the cyclic bis (allyl) titanium complexes 18 with the imino esters 23a-c afforded the corresponding B-syn-configured cyclic unsaturated amino acid derivatives -25 and the Z-syn-configured isomers Z-25 with >98% regioselectivity and >98% diaste-reoselectivity in good yields. 

Asymmetric Hydrogenation. Asymmetric hydrogenation with good enantio-selectivity of unfunctionalized prochiral alkenes is difficult to achieve.144 145 Chiral rhodium complexes, which are excellent catalysts in the hydrogenation of activated multiple bonds (first, in the synthesis of a-amino acids by the reduction of ol-N-acylamino-a-acrylic acids), give products only with low optical yields.144 146-149 The best results ( 60% ee) were achieved in the reduction of a-ethylstyrene by a rhodium catalyst with a diphosphinite ligand.150 Metallocene complexes of titanium,151-155 zirconium,155-157 and lanthanides158 were used in recent studies to reduce the disubstituted C—C double bond with medium enantioselectivity. 

It is believed that most of the transition metals are complexed to nitrogen donors, such as are found in amino acids or derivatives of chlorophyll, and that the metals with high ionic potentials, such as beryllium, boron, germanium, titanium, gallium, and major elements such as aluminum and silicon, may be bonded to oxygen donors of degraded lignin. 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

Bis-Cp titanium amino acid complexes have been synthesized in an aqueous medium by the reaction of Cp2TiCl2 with the sodium or potassium salts of the corresponding amino acids, or in non-aqueous media by the reaction of Cp2TiCl2 with the amino acids in the presence of NEt3. It has been found that in an aqueous medium the reaction is faster, and the product yields are higher.1580... 

Justification. Investigation of a number of gelatinous hydrous metal oxides (frequently called hydroxides, although their full structures are uncertain) has established ( ) that hydrous titanium (IV), zirconium (IV), iron (III), vanadium (III) and tin (II) oxides at least are capable of forming with enzymes insoluble complexes which are enzymically active. From the practical viewpoint hydrous titanium (IV) and zirconium (IV) oxides proved the most satisfactory. Comparatively high retentions of enzyme specific activity may be achieved (3, 4, 5). Such hydrous metal oxide materials have also proved to be suitable for the immobilisation of amino acids and peptides ( ), antibiotics with retention of antimicrobial activity ( ), polysaccharides J ), etc. 

A similar methodology was applied by Colonna et al. [101] to the oxidation of aryl alkyl sulfides with Bu OOH as oxidizing agent and a catalytic amount of a titanium A-salicylidene-L-amino acid complex (47) (0.1 mol equiv) in benzene at room temperature. This catalyst is not very enantioselective, and often yields mixtures of sulfoxides and sulfones. The highest enantioselectivity was achieved in the oxidation of f-butyl (p-nitrophenylthio)acetate, which gave sulfoxide in 21% ee and 25% yield. Like the Kagan reagent, but to a lesser measure, the use of a stoichiometric amount of titanium complex substantially influences the enantioselectivity, which increases from 12% (catalytic) to 21% (stoichiometric) for the oxidation of methyl p-tolyl sulfide. 

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