The 2001 Nobel Prize in Chemistry was awarded to three organic chemists who have developed methods for catalytic asymmetric syntheses. 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 tartrate ester as the reagents. The following epoxidation of geraniol is typical. <
of reactions> (a) 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? (b) 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? (c) Draw the other enantiomer of the product. What reagents would you use if you wanted to epoxidize geraniol to give this other enantiomer?

Verified step by step guidance

1. Identify the reagents involved in the Sharpless epoxidation: tert-butyl hydroperoxide, titanium(IV) isopropoxide, and diethyl L-tartrate.
2. Determine which reagent is most likely to be the oxidizing agent. tert-Butyl hydroperoxide is the oxidizing agent as it provides the oxygen for the epoxidation reaction.
3. Understand the roles of the other reagents. Titanium(IV) isopropoxide acts as a catalyst, and diethyl L-tartrate is a chiral ligand that induces asymmetry in the reaction.
4. Explain how the Sharpless epoxidation gives one enantiomer. The chiral ligand (diethyl L-tartrate) creates a chiral environment around the titanium catalyst, leading to the formation of one enantiomer preferentially.
5. To draw the other enantiomer of the product, invert the stereochemistry at the epoxide carbon centers. To obtain this enantiomer, use diethyl D-tartrate instead of diethyl L-tartrate in the reaction.

Key Concepts

Asymmetric Synthesis

Asymmetric synthesis refers to the process of creating a chiral molecule from an achiral precursor, resulting in a predominance of one enantiomer over the other. This is crucial in organic chemistry as many biological systems are sensitive to the chirality of molecules. The Sharpless epoxidation is a prime example, where specific reagents and conditions are used to favor the formation of one enantiomer, achieving high enantiomeric excess.

Oxidizing Agents

An oxidizing agent is a substance that gains electrons in a chemical reaction, causing another substance to be oxidized. In the context of the Sharpless epoxidation, tert-butyl hydroperoxide acts as the oxidizing agent, facilitating the conversion of the allylic alcohol to an epoxide. Understanding the role of oxidizing agents is essential for predicting reaction outcomes and mechanisms in organic synthesis.

Enantiomeric Excess

Enantiomeric excess (ee) is a measure of the purity of a chiral product, defined as the difference in the amounts of each enantiomer present in a mixture. It is expressed as a percentage and indicates how much one enantiomer is favored over the other. In the Sharpless epoxidation, achieving greater than 90% enantiomeric excess demonstrates the effectiveness of the method in producing predominantly one enantiomer, which is vital for applications in pharmaceuticals and other fields.