Titanium isopropoxide epoxide ring opening

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 titanium(IV) species. When stoichiometric amounts of titanium 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(OPr )4. The use of Ti(OBu )4 in place of Ti(OPr )4 has been prescribed as a means to reduce this problem (the t-butoxide being a poorer nucleophile). Fortunately, a better solution now exists in the form of the catalytic version of the reaction which uses only 5-10 mol % of titanium 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 tom the epoxidations summarized in Table 3. 

Aymmetric ring-opening reactions of other meso epoxides using catalysts derived from trimethylsilyl azide with titanium isopropoxide are described (3). 

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. 

The turn of the millenium will see the 20th anniversary of the seminal discovery of the asymmetric epoxidation [1, 2] of ally lie alcohols catalysed by titanium(IV) isopropoxide and tartrate esters. The utility of this transformation largely results from the regio- and stereocontrol possible in subsequent nucleophilic ring opening reactions of the derived epoxy alcohols. Thus, a sequence of asymmetric epoxidation, epoxide opening and further functionalisation leads to a diverse array of molecules in enantiomerically pure form. In comparision, asymmetric epoxidation of unfunctionalised alkenes [3] has yet to match the enantioselectivities which the Ti-tartrate system can deliver with allylic alcohols. The recent discovery of other asymmetric epoxidation reactions [4] suggests that a number of practical options may eventually become available. 

Bao and co-workers also reported enantioselective ring-opening ami-nolysis of epoxide, 93, with benzylamine, 94, catalyzed by the titanium isopropoxide-BINOL-water system (BlNOL=l,l -bi-2-naphthol-96) in toluene (reaction 7.16) [66]. Titanium isopropoxide-isopropanol, 96, system also used by Kim et al. for asymmetric methallylation of ketones (reaction 7.17) with high yield and enantioselectivity [67]. 

Asymmetric Epoxidation Reactions. While Ti(0-i-Pr)4 clearly has the capacity to bring about the nucleophilic ring-cleavage of 2,3-epoxy alcohols (see above), it remains the preferred species for the preparation of the titanium tartrate complex central to the Sharpless asymmetric epoxidation process (see, for example, eq 7). Since f-butoxide-mediated ring-opening of 2-substituted 2,3-epoxy alcohols (a subclass of epoxy alcohols particularly sensitive to nucleophilic ring-cleavage) is much slower than by isopropoxide, the use of Ti(0-f-Bu)4 is sometimes recommended in place of Ti(0-i-Pr)4. However, with the reduced amount of catalyst that is now needed for all asymmetric epoxidations, this precaution appears unnecessary in most instances. 

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