SHARPLESS ASYMMETRIC EPOXIDATION * Enantioselective epoxidation of allylic alcohols using t-butyl peroxide, titanium tetra-iso-propoxide, and optically pure

diethyl tartrate. * The asymmetric epoxidation of an allylic alcohol to yield a 2,3-epoxy alcohol with high enantiomeric excess. * This enantioselective reaction is carried out in the presence of tetraisopropoxytitanium and an enantiomerically pure dialkyl tartratee.g. (+) or (-)-diethyl tartrate (DET)using tert-butyl hydroperoxide as the oxidizing agent. * The catalyst is a dimer of [Ti(tartrate)(OR)2].

A model for the catalytically active species in the Sharpless epoxidation reaction is formulated as a dimer ,where two titanium centers are linked by two chiral tartrate bridges. At each titanium center two isopropoxide groups of the original tetraisopropoxytitanium-(IV) have been replaced by the chiral tartrate ligand. As the reaction proceeds, the two remaining isopropoxide groups at one titanium center are replaced by the allylic alcohol (the substrate) and tertbutyl hydroperoxide (the oxidizing agent) to give the complex. Titanium-(IV) is suitable for such a reaction since it can form four covalent, but still reactive bonds, two bonds to bind the ends of two chiral bidentate tartrate ligands, one bond to the oxidizing agent, and one to the allylic alcohol substrate. The titanium thus serves as a template for the reactants; with the aim of the chiral ligands it has become a chiral template. The reactants are arranged geometrically in such a way to permit a facial selection, resulting in an enantioselective epoxidation step. Furthermore the tetraisopropoxytitanium-(IV) acts as a Lewis acid by coordinating to the other oxygen centeri.e. O-2 in the scheme belowof the t-butyl peroxy-ligand; as a result the oxygen center O-1 becomes more electrophilic. The Sharpless Epoxidation's success is due to five major reasons. First, epoxides can be easily converted into diols, aminoalcohols or ethers, so formation of chiral epoxides is a very important step in the synthesis of natural products. Second, the Sharpless Epoxidation reacts with many primary and secondary allylic alcohols. Third, the products of the Sharpless Epoxidation frequently have enantiomeric excesses above 90%. Fourth, the products of the Sharpless Epoxidation are predictable using the Sharpless Epoxidation model. Finally, the reactants are commercially available and relatively cheap.

Selectivity The chirality of the product can be predicted using the following mnemonic. Draw the double bond of interest lying flat. Draw a rectangle that around the double bond is in same plane as the carbons of the double bond. Towards the bottom right corner, draw the allylic alcohol. Place the other substituents in the appropriate corners. In this orientation, the (-) diester tartrate preferentially interacts with the top half of the molecule, and the (+) diester tartrate preferentially interacts with the bottom half of the molcule. This model seems to be valid despite substitution on the olefin. Selectivity decreases with larger R1, but increases with larger R2 and R3.

Illustrations The product of allylic 1,2-diols is incorrectly predicted by the above model

More Examples