Ti-tartrate complex

There are several Ti-tartrate complexes present in the reaction system. It is believed that the species containing equal moles of Ti and tartrate is the most active catalyst. It promotes the reaction much faster than Ti(IV) tetraalkoxide alone and exhibits selective ligand-accelerated reaction.9... 

An important improvement in the asymmetric epoxidation process is the finding, reported in 1986, that by adding molecular sieves to the reaction medium virtually all reactions can be performed with a catalytic amount (5-10 mol %) of the Ti-tartrate complex [3]. Previously, only a few structural classes of allylic alcohols were efficiently epoxidized by less than stoichiometric amounts of the complex, and most reactions were routinely performed with stoichiometric quantities of the reagent. 

This section presents a summary of the currently preferred conditions for performing Ti-catalyzed asymmetric epoxidations and is derived primarily from the detailed account of Gao et al. [4]. We wish to draw the reader s attention to several aspects of the terminology used here and throughout this chapter. The terms Ti-tartrate complex and Ti-tartrate catalyst are used interchangeably. The term stoichiometric reaction refers to the use of the Ti-tartrate complex in a stoichiometric ratio (100 mol %) relative to the substrate (allylic alcohol). The term catalytic reaction (or quantity) refers to the use of the Ti-tartrate complex in a catalytic ratio (usually 5-10 mol %) relative to the substrate,... 

The second stoichiometry consideration is the ratio of catalyst to substrate. As noted in the preceding section, virtually all asymmetric epoxidations can be performed with a catalytic amount of Ti-tartrate complex if molecular sieves are added to the reaction milieu. A study of catalyst/substrate ratios in the epoxidation of cinnamyl alcohol revealed a significant loss in enantioselectivity (Table 6A.2) below the level of 5 mol % catalyst. At this catalyst level, the reaction rate also decreases, with the consequence that incomplete epoxidation of the substrate may occur. Presendy, the recommended catalyst stoichiometry is from 5% Ti and 6% tartrate ester to 10% Ti and 12% tartrate ester [4],... 

The concentration of substrate used in the asymmetric epoxidation must be given consideration because competing side reactions may increase with increased reagent concentration. The use of catalytic quantities of the Ti-tartrate complex has greatiy reduced this problem. The epoxidation of most substrates under catalytic conditions may be performed at a substrate concentration up to 1 M. By contrast, epoxidations using stoichiometric amounts of complex are best run at substrate concentrations of 0.1 M or lower. Even with catalytic amounts of the complex, a concentration of 0.1 M may be maximal for substrates such as cinnamyl alcohol, which produce sensitive epoxy alcohol products [4]. 

Ti(IV) isopropoxide [Chemical Abstracts nomenclature 2-propanol, Ti(4+) salt], is the Ti species of choice for preparation of the Ti-tartrate complex in the asymmetric epoxidation process. The use of Ti(IV) f-butoxide has been recommended for reactions in which the epoxy alcohol product is particularly sensitive to ring opening by the alkoxide [18]. The 2-substituted epoxy alcohols are one such class of compounds. Ring opening by f-butoxide is much slower than by i-propoxide. With the reduced amount of catalyst that now is sufficient for all asymmetric epoxidations, the use of Ti(0-f-Bu)4 appears to be unnecessary in most cases, but the concept is worth noting. 

The epoxides (11) derived from 2-substituted allylic alcohols (10) are particularly susceptible to nucleophilic attack at C-3, a reaction that is promoted by Ti(lV) species [18]. When stoichiometric amounts of Ti-tartrate complex are used in these epoxidations, considerable product is lost via opening of the epoxide before it can be isolated from the reaction. 

The primary nucleophilic culprit is the isopropoxide ligand of the Ti(0-i-Pr)4. The use of Ti(0-r-Bu)4 in place of Ti(0- -Pr)4 has been prescribed as a means to reduce this problem (the r-butoxide being a poorer nucleophile) [18]. Fortunately a better solution now exists in the form of the catalytic version of the reaction that uses only 5-10 mol % of Ti-tartrate complex and greatly reduces the amount of epoxide ring opening. Some comparisons of results from reactions run under the two sets of conditions are possible from the epoxidations summarized in Table 6A.3 [2,4,18,33-38]. 

Dimethylallyl alcohol was epoxidized with better than 90% ee (entry 1) but in low yield when a stoichiometric amount of the Ti-tartrate complex was used. However, when a catalytic amount of the complex was used and an in situ derivatization employed, the p-nitrobenzoate (>98% ee after recrystallization) and / -toluenesulfonate (93% ee) were isolated in yields of 70 and 55%, respectively. 

The rationale that explains the kinetic resolution of the 1-monosubstituted allylic alcohols predicts that a 1,1-disubstituted allylic alcohol will be difficult to epoxidize with the Ti-tartrate catalyst. In practice, the epoxidation of 1,1-dimethylallyl alcohol (88) with a stoichiometric quantity of the Ti-tartrate complex is very slow, and no epoxy alcohol is isolated... 

Much of the experimental success of asymmetric epoxidation lies in exercising proper control of Eq. 6A.4 [6]. Both TI(OR)4 and Ti(tartrate)(OR)2 are active epoxidation catalysts, and because the former is achiral, any contribution by that species to the epoxidation will result in loss of enantioselectivity. The addition to the reaction of more than one equivalent of tartrate, relative to Ti, will have the effect of minimizing the leftward component of the equilibrium and will suppress the amount of Ti(OR)4 present in the reaction. The excess tartrate, however, forms Ti(tartrate)2, which has been shown to be a catalytically inactive species and will cause a decrease in reaction rate that is proportional to the excess tartrate added. The need to minimize Ti(OR)4 concentration and, at the same time, to avoid a drastic reduction in rate of epoxidation is the basis for the recommendation of a 10-20 mol % excess of tartrate over Ti for formation of the catalytic complex. After the addition of hydroperoxide and allylic alcohol to the reaction, the concentration of ROH will increase accordingly, and this will increase the leftward pressure on the equilibrium shown in Eq. 6A.4. Fortunately, in most situations this shift apparently is extremely slight and is effectively suppressed by the use of excess tartrate. A shift in the equilibrium does begin to occur, however, when the reaction is run in the catalytic mode and the amount of catalyst used is less than 5 mol % relative to allylic alcohol substrate. Loss in enantioselectivity then may be observed. This factor is the basis of the recommendation for use of 5-10 mol % of Ti-tartrate complex when the catalytic version of asymmetric epoxidation is used. 

The [3-hydroxy amines are a class of compounds falling within the generic definition of Eq. 6A.6. When the alcohol is secondary, the possibility for kinetic resolution exists if the Ti-tartrate complex is capable of catalyzing the enantioselective oxidation of the amine to an amine oxide (or other oxidation product). The use of the standard asymmetric epoxidation complex (i.e., T2(tartrate)2) to achieve such an enantioselective oxidation was unsuccessful. However, modification of the complex so that the stoichiometry lies between Ti2 (tartrate) j and Ti2(tartrate)1 5 leads to very successful kinetic resolutions of [3-hydroxyamines. A representative example is shown in Eq. 6A.11 [141b,c]. The oxidation and kinetic resolution of more than 20 secondary [3-hydroxyamines [141,145a] provides an indication of the scope of the reaction and of some... 

Before 1986, asymmetric epoxidations frequently were performed by using a stoichiometric amount of the Ti-tartrate catalyst relative to the amount of allylic alcohol. This technique was necessary to obtain a reasonable reaction rate for the epoxidation as well as to drive the reaction to completion. The report in 1986 recommending the addition of activated molecular sieves to the reaction milieu makes it possible to use only catalytic amounts of the Ti-tartrate complex for nearly all asymmetric epoxidations. 

Although the recovery of the polytartrate ligand by filtration amounts to about 90%, the Ti recovery levels are significantly lower (34). The fact that part of the Ti remains in the solution means that the binding of Ti to the anchored ligand is less efficient than it is to the ligand in solution. It seems unlikely that the polymeric nature of the ligand allows the formation of the same 2 2 Ti tartrate complexes that are formed in solution. Moreover, no recycle experiments have provided evidence that the catalyst is reusable. 

The rate is first order with respect to allyl alcohol, Ti(tartrate), and the hydroperoxide oxidizing agent, and is inhibited by alcohol. The rate expression is consistent with the reaction sequence (Fig. 1.17). The Ti(tartrate) complex is formed by removal of two alkoxide ligands, and then the remaining two alkoxide ligands are displaced by TBHP and the allyl alcohol. The order of displacement is immaterial so fhe "loaded complex can be reached by either pathway shown. 

Copper, titanium, cobalt and iron substituted mesoporous silicas (Cu-, Ti-, Co-, and Fe-HMS) were synthesized with dodecylamine surfactant as templating reagent. Three assembled pathways were used to bond Ti tartrate complex over mesoporous silicas (HMS). The above described catalysts were characterized by XRD and FT-IR, their metal loadings were measured by chemical analysis method. In catalytic testing, Cu-HMS and especially Fe-HMS show the best catalytic activity for hydroxylation of phenol with H2O2 in the presence of water. Ti-HMS and especially Ti tartrate complex assembled HMS catalysts exhibit the best epoxidative activity for catalyzing epoxidation of styrene with rcrt-butyl hydroperoxide. 

The enantioselective oxidation with Ti-tartrate complexes has proven to have further important uses in different oxidation processes. Thus as an example, Kagan has reported that these oxidation conditions can be utilized in the enantioselective conversion of sulfides into sulfoxides (Equation 13) [83],... 

---