Titanium complexes oxidation with

A titanium complex (1) with a salen ligand is an efficient catalyst for the enan-tioselective epoxidation of alkenes with hydrogen peroxide as the terminal oxidant. The participation of a titanium-peroxo species, activated by hydrogen bonding, in the reaction, has been postulated.73... 

Cotton etal. [14] described an asymmetric synthesis of esomeprazole. Esomeprazole, the (S)-enantiomer of omeprazole, was synthesized via asymmetric oxidation of prochiral sulfide 5-methoxy-2-[[(4-methoxy-3,5-dimethyl pyridin-2-yl)methyl]thio]-lH-benzimidazole 1. The asymmetric oxidation was achieved by titanium-mediated oxidation with cumene hydroperoxide in the presence of (S,S)-diethyl tartarate (DET). The enan-tioselectivity was provided by preparing the titanium complex in the presence of sulfide 1 at an elevated temperature and/or during a prolonged preparation time and by performing the oxidation of sulfide 1 in the presence of amine. An enantioselectivity of 94% ee was obtained using this method. 

Thorium oxybromide, 1 54 Tin, as reducing agent for complex tungsten(VI) chlorides in preparation of complex potassium chlorotungstates(III), 6 149 Tin compounds, halomethyl derivatives, by the diazomethane method, 6 37 (CH8) 2 (CH2C1) SnCl, 6 41 Tin (IV) iodide, 4 119 Titanium, powder by reduction of titanium (IV) oxide with calcium, 6 47... 

The synthesis of 1,2-dithietes was extensively described by Zoller in CHEC-II(1996) <19%GHEC-II(1B)1113>, and the literature until 1995 was summarized. Since that time, a few interesting procedures have been reported. The oxidation of the titanium complex 224 with sulfuryl chloride in benzene gave 3,4-dimethoxycarbonyl-l,2-dithiete 225 in 66% yield. Macrocyclic compounds 226 and 227 were isolated as by-products (Equation 46) <1998JOC8192, 1999PS431>. 

Figure 2. Projected structure of the chelate/complex of hydrous titanium (IV) oxide with macromolecular carbohydrate...

Titanium-catalyzed oxidations with 35% aqueous H2O2 using Schiff-base (salen) titanium 0x0 complexes as catalysts showed very high activity [28]. The oxidation of methyl phenyl sulfide required only 0.1mol% of catalyst. The use of chiral salen complexes gave low enantioselectivity (<20% ee). 

The most practical method that is used in the industrial synthesis of esomeprazole involves titanium-catalyzed oxidation with an alkyl hydroperoxide, and a dialkyltartrate as chiral ligand, in an organic solvent such as dichloromethane. A variety of oxidoreductases are known to catalyze the enantioselective oxidation of prochiral sulfides, usually as whole-cell biotransformations in aqueous media, but no simple metal complexes have been shown to be effective in water and the development of practical systems employing aqueous hydrogen peroxide as the primary oxidant is still an important challenge. In this context it is worth mentioning the enantioselective sulfoxidation of prochiral sulfoxides catalyzed by the semisynthetic peroxidase, vanadium-phytase, in an aqueous medium. 

Perhaps because of inadequate or non-existent back-bonding (p. 923), the only neutral, binary carbonyl so far reported is Ti(CO)g which has been produced by condensation of titanium metal vapour with CO in a matrix of inert gases at 10-15 K, and identified spectroscopically. By contrast, if MCI4 (M = Ti, Zr) in dimethoxy-ethane is reduced with potassium naphthalenide in the presence of a crown ether (to complex the K+) under an atmosphere of CO, [M(CO)g] salts are produced. These not only involve the metals in the exceptionally low formal oxidation state of —2 but are thermally stable up to 200 and 130°C respectively. However, the majority of their carbonyl compounds are stabilized by n-bonded ligands, usually cyclopentadienyl, as in [M(/j5-C5H5)2(CO)2] (Fig. 21.8). 

Asymmetric epoxidation is another important area of activity, initially pioneered by Sharpless, using catalysts based on titanium tetraisoprop-oxide and either (+) or (—) dialkyl tartrate. The enantiomer formed depends on the tartrate used. Whilst this process has been widely used for the synthesis of complex carbohydrates it is limited to allylic alcohols, the hydroxyl group bonding the substrate to the catalyst. Jacobson catalysts (Formula 4.3) based on manganese complexes with chiral Shiff bases have been shown to be efficient in epoxidation of a wide range of alkenes. 

Physical properties of binary or ternary Ru/Ir based mixed oxides with valve metal additions is still a field which deserves further research. The complexity of this matter has been demonstrated by Triggs [49] on (Ru,Ti)Ox who has shown, using XPS and other techniques (UPS, Mossbauer, Absorption, Conductivity), that Ru in TiOz (Ti rich phase) adopts different valence states depending on the environment. Possible donors or acceptors are compensated by Ru in the respective valence state. Trivalent donors are compensated by Ru5+, pentavalent acceptors will be compensated by Ru3+ or even Ru2+. In pure TiOz ruthenium adopts the tetravalent state. The surface composition of the titanium rich phase (2% Ru) was found to be identical to the nominal composition. 

Use of D2 yielded CD4, and methane was formed from reaction of the complex with just H2. The water produced in the reaction hydrolyzes the titanium complex to an inactive cluster Cp6Ti608 containing bridging oxide ligands. 

Although the reaction of a titanium carbene complex with an olefin generally affords the olefin metathesis product, in certain cases the intermediate titanacyclobutane may decompose through reductive elimination to give a cyclopropane. A small amount of the cyclopropane derivative is produced by the reaction of titanocene-methylidene with isobutene or ethene in the presence of triethylamine or THF [8], In order to accelerate the reductive elimination from titanacyclobutane to form the cyclopropane, oxidation with iodine is required (Scheme 14.21) [36], The stereochemistry obtained indicates that this reaction proceeds through the formation of y-iodoalkyltitanium species 46 and 47. A subsequent intramolecular SN2 reaction produces the cyclopropane. 

Recently, Feng and co-workers reported an asymmetric sulfide oxidation" catalyzed by titanium complexes bearing HydrOx ligands, for example, 576 (Scheme 8.199). ° Enantioselectivities approached a level of synthetic utility for oxidation of aryl alkyl sulfides 632 although the yields of the sulfoxide 633 were poor due to overoxidation to the sulfone 634. The overoxidation is especially significant for reactions with high enantioselectivity. 

Oxidation of the enantiotopic electron pairs at sulfur, mediated by chiral titanium complexes, to yield chiral sulfoxides with high enantiomeric excess14. 

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