Question. The 2001 Nobel Prize in Chemistry was awarded to three organic chemists who have developed methods for catalytic asymmetric synthesis. An asymmetric (or enantioselective) synthesis is one that converts an achiral starting material into mostly one enantiomer of a chiral product. K. Barry Sharpless (The Scripps Research Institute) developed an asymmetric epoxidation of allylic alcohols that gives excellent chemical yields and greater than 90% enantiomeric excess.

The Sharpless epoxidation uses tert-butyl hydroperoxide, titanium(IV) isopropoxide, and a dialkyl tartarate ester as the reagents. The following epoxidation of geraniol is typical.

1. Which of these reagents is most likely to be the actual oxidizing agent? That is, which reagent is reduced in the reaction? What is the likely function of the other reagents?
2. When achiral reagents react to give a chiral product, that product is normally formed as a racemic mixture of enantiomers. How can the Sharpless epoxidation give just one nearly pure enantiomer of the product?
3. Draw the other enantiomer of the product. What reagents would you use if you wanted to epoxidize geraniol to give this other enantiomer?

Tert-butyl hydroperoxide is the oxidizing agent. Thecontains the oxygen-oxygen bond like in peroxyacid. Diethyl tartrate is the source of asymmetry and its function is to create a chiral transition state that is of lowest energy leading to formation of one enantiomer of product. The function of titanium (IV) isopropoxide is to act as the glue that holds all of the reagents together. Titanium holds an oxygen from each reactant, that is, from geraniol, tert-butyl hydroperoxide and diethyl tartrate and tethers them so they can react together.

All three reactants are required to make Sharpless epoxidation work but the key to enantioselective epoxidation is the chiral molecule, diethyl tartrate. When it complexes with titanium, it forms a large structure that is also chiral. When the reaction between alkene and tert-butyl hydroperoxide occurs, it occurs preferentially from one face of the alkene leading to formation of one major stereoisomer of epoxide. Without chiral diethyl tartrate in complex, the alkene could approach from one side as easily the other and a racemic mixture would be formed.

Using the enantiomer of diethyl L-tartrate called diethyl D-tartrate, would give exactly the opposite stereochemical result, that is the enantiomer of the first product.

Formation of product when diethyl D-tartrate is used