Titanium complexes alkyl peroxides

If we consider the d0 metal-N,JV-dialkylhydroxylamino complexes (79), (80) and (81) as valid models for the reactive but unstable alkyl peroxide species Mo02(OOR)2, VO(OOR)3 or V203(00R)4, and Ti(OOR)4 presumably involved in catalytic oxidations, the low activity of vanadium and titanium for the epoxidation of simple alkenes could be interpreted by the fact that these alkenes cannot displace the O.O-bonded alkyl peroxide groups in the coordinatively saturated Vv- and Tiiv-alkyl peroxide species, whereas allylic alcohols can displace the alkyl peroxide groups by forming bidentate allylic alkoxides as in equation (75).162... 

Although exotic, the structure of the proposed titanium peroxide has been confirmed independently. In 1996, the first X-ray crystal structure of a titanium alkyl peroxide was reported [17]. This structure clearly shows an rf bonding mode for the peroxo ligand. The authors demonstrated the capacity of their titanium alkyl peroxo complex to oxidize nucleophiles, which indicated the electrophilic... 

Indeed, several interesting procedures based on three families of active catalysts organometallic complexes, phase-transfer compounds and titanium silicalite (TS-1), and peroxides have been settled and used also in industrial processes in the last decades of the 20th century. The most impressive breakthrough in this field was achieved by Katsuki and Sharpless, who obtained the enantioselective oxidation of prochiral allylic alcohols with alkyl hydroperoxides catalyzed by titanium tetra-alkoxides in the presence of chiral nonracemic tartrates. In fact Sharpless was awarded the Nobel Prize in 2001. 

The workers proposed that alkyl hydroperoxides and aqueous hydrogen peroxide interact with TS-1 in a similar manner, forming titanium alkyl peroxo complexes and titanium peroxo complexes, respectively. However, the titanium alkyl peroxo complexes were not active because the substrate could not enter the void due to steric effects. Consequently, no activity was possible for either alkane hydroxylation or alkene epoxidation. Comparison with Ti02-Si02/alkyl hydroperoxide for alkane and alkene oxidation indicated that this material was active because the oxidation took place on the surface and not in the pores. Figures 4.4 and 4.5 show the possible mechanisms in operation for the oxidation of alkenes and alkanes with a TS-1/hydrogen peroxide system. 

In this context it is worth noting that neither the titanium(IV) tartrate catalyst nor other metal catalyst-alkyl hydroperoxide reagents are effective for the asymmetric epoxidation of unfunctionalized olefins. The only system that affords high enantioselectivities with unfunctionalized olefins is the manganese(III) chiral Schiff s base complex/NaOCl combination developed by Jacobsen [42]. There is still a definite need, therefore, for the development of an efficient chiral catalyst for asymmetric epoxidation of unfunctionalized olefins with alkyl hydroperoxides or hydrogen peroxide. 

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. 

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