Titanium isopropoxide nucleophilic attack

These epoxide-opening conditions were originally developed by Sharpless and coworkers for the regiocontrolled opening of 2,3-epoxy alcohols [30]. It has been proposed that ligand exchange of the substrate with isopropoxide forms a covalently bound substrate-titanium complex (Chart 3.3). Nucleophilic attack on this complex at the 3-position is favored over attack at the 2-position. In the case of 49,... 

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. 

Cleavage ofl -epoxy alcohols.l Titanium(IV) isopropoxide (1-1.5 equiv.) not only increases the rate of reaction of nucleophiles with these alcohols but controls the regioselectivity resulting in highly selective attack at C3. Some other metal alkoxides are also effective, including Zr(0-i-Pr)4-/-PrOH and Lu(0-/-Pr)3.2... 

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