Titanium alkoxides asymmetric epoxidation

The essence of titanium-catalyzed asymmetric epoxidation is illustrated in Figure 1. As shown there, the four essential components of the reaction are the allylic alcdiol substrate, a titanium(IV) alkoxide, a chiral tartrate ester and an aUcyl hydroperoxide. The asynunetric complex formed from these reagents de-... 

Titanium-catalyzed asymmetric epoxidation of allylic alcohols employing titanium alkoxide, an optically active tartrate ester and an alkyl hydroperoxide. A high degree of enantiomeric purity is attainable having predictable absolute stereochemistry ... 

Allylic alcohols can be converted to epoxy-alcohols with tert-butylhydroperoxide on molecular sieves, or with peroxy acids. Epoxidation of allylic alcohols can also be done with high enantioselectivity. In the Sharpless asymmetric epoxidation,allylic alcohols are converted to optically active epoxides in better than 90% ee, by treatment with r-BuOOH, titanium tetraisopropoxide and optically active diethyl tartrate. The Ti(OCHMe2)4 and diethyl tartrate can be present in catalytic amounts (15-lOmol %) if molecular sieves are present. Polymer-supported catalysts have also been reported. Since both (-t-) and ( —) diethyl tartrate are readily available, and the reaction is stereospecific, either enantiomer of the product can be prepared. The method has been successful for a wide range of primary allylic alcohols, where the double bond is mono-, di-, tri-, and tetrasubstituted. This procedure, in which an optically active catalyst is used to induce asymmetry, has proved to be one of the most important methods of asymmetric synthesis, and has been used to prepare a large number of optically active natural products and other compounds. The mechanism of the Sharpless epoxidation is believed to involve attack on the substrate by a compound formed from the titanium alkoxide and the diethyl tartrate to produce a complex that also contains the substrate and the r-BuOOH. ... 

Zrrconium(IV) and hafnium(IV) complexes have also been employed as catalysts for the epoxidation of olefins. The general trend is that with TBHP as oxidant, lower yields of the epoxides are obtained compared to titanium(IV) catalyst and therefore these catalysts will not be discussed iu detail. For example, zirconium(IV) alkoxide catalyzes the epoxidation of cyclohexene with TBHP yielding less than 10% of cyclohexene oxide but 60% of (fert-butylperoxo)cyclohexene °. The zirconium and hafnium alkoxides iu combiuatiou with dicyclohexyltartramide and TBHP have been reported by Yamaguchi and coworkers to catalyze the asymmetric epoxidation of homoallylic alcohols . The most active one was the zirconium catalyst (equation 43), giving the corresponding epoxides in yields of 4-38% and enantiomeric excesses of <5-77%. This catalyst showed the same sense of asymmetric induction as titanium. Also, polymer-attached zirconocene and hafnocene chlorides (polymer-Cp2MCl2, polymer-CpMCls M = Zr, Hf) have been developed and investigated for their catalytic activity in the epoxidation of cyclohexene with TBHP as oxidant, which turned out to be lower than that of the immobilized titanocene chlorides . ... 

The asymmetric oxidation of sulphides to chiral sulphoxides with t-butyl hydroperoxide is catalysed very effectively by a titanium complex, produced in situ from a titanium alkoxide and a chiral binaphthol, with enantioselectivities up to 96%342. The Sharpless oxidation of aryl cinnamyl selenides 217 gave a chiral 1-phenyl-2-propen-l-ol (218) via an asymmetric [2,3] sigmatropic shift (Scheme 4)343. For other titanium-catalysed epoxidations, see Section V.D.l on vanadium catalysis. 

Whereas these solid catalysts tolerate water to some extent, or even use aqueous H2O2 as the oxidant, the use of homogeneous Ti catalysts in epoxi-dation reactions often demands strictly anhydrous conditions. The homogeneous catalysts are often titanium alkoxides, possibly in combination with chiral modifiers, as in the Sharpless asymmetric epoxidation of allylic alcohols (15). There has recently been an increase in interest in supporting this enantioselective Ti catalyst. 

Two aspects of stoichiometry are important in an asymmetric epoxidation one is the ratio of titanium to tartrate used for the catalyst and the other is the ratio of catalyst to substrate. With regard to the catalyst, it is crucial to obtaining the highest possible enantiomeric excess that at least a 10% excess of tartrate ester to titanium(IV) alkoxide be used in all asynunetric epoxidations. This is important when the reaction is being done with either a stoichiometric or a catalytic quantity of the complex. There appears to be no need to increase the excess of tartrate ester beyond 10-20% and, in fact, a larger excess has been shown to slow the epoxidation reaction unnecessarily. ... 

Titanium(IV) isopropoxide Chemical Abstracts nomenclature 2-propanol, titanium(4-f-) salt) is the titanium species of choice for preparation of the titanium tartrate complex in the asymmetric epoxidation process. The use of titanium(IV) t-butoxide has been recommended for those reactions in which the epoxy alcohol product is particularily sensitive to ring opening by the alkoxide. The 2-substituted epoxy alcohols (Section 3.2.5.2) are one such class of compounds. Ring opening by t-butoxide is much slower than by isopropoxide. With the reduced amount of catalyst that now is needed for all asymmetric epoxidations, the use of Ti(OBu )4 appears to be unnecessary in most cases, but the concept is worth noting. 

In a series of papers, the application of titanium alkoxide catalysts to the synthesis of sugars has been described. Asymmetric epoxidation and kinetic resolution of (48) afforded (+)-(49) (27% >95%e.e.) and (—)-(48) (33% 72%e.e.). The ring-opening reactions of the chiral epoxides that are produced, for example, from cis- and from trans- 50) provide new routes to saccharides. The reagents also find use in the synthesis of pheromones e.g., (+)-disparlure and (+)-2,6-dimethylhepta-l,5-dien-3-ol acetate via the epoxide (52), which was obtained from the dienol (51) by using D-(—)-... 

In 1980 a useful level of asymmetric induction in the epoxidation of some alkenes was reported by Katsuki and Sharpless121. The combination of titanium (IV) alkoxide, an enantiomerically pure tartrate ester and tert-butyl hydroperoxide was used to epoxidize a wide variety of allylic alcohols in good yield and enantiomeric excess (usually >90%). This reaction is now one of the most widely applied reactions in asymmetric synthesis131. 

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