Stereoselectivity

Stereoselectivity refers to the outcome of a chemical reaction in terms of which stereoisomer is formed preferentially. It encompasses enantioselectivity, where one enantiomer is favored, and diastereoselectivity, where one diastereomer among diastereomers is favored. In reactions that create several stereocenters, the overall outcome is described by enantiomeric excess (ee) and diastereomeric ratio (dr).

The origins of stereoselectivity lie in the structure of the transition state. Factors such as the presence of chiral catalysts or auxiliaries, substrate-controlled effects, and steric or electronic interactions influence which stereochemical path is lower in energy. Stereoselective strategies include asymmetric synthesis using chiral catalysts (enantioselective hydrogenations, Sharpless epoxidation, organocatalysis) and the use of chiral auxiliaries (for example, Evans-type oxazolidinones) to direct the configuration of newly formed stereocenters. Reactions may be governed by kinetic control, which favors the fastest-formed product, or thermodynamic control, which favors the most stable one.

Measurements and analysis of stereoselectivity rely on ee and dr. Enantiomeric excess quantifies the imbalance between enantiomers, while diastereomeric ratio compares diastereomers. Analytical methods include chiral chromatography and NMR techniques using chiral solvating agents.

Examples of celebrated stereoselective methodologies include the Sharpless epoxidation and the Sharpless dihydroxylation for enantioselective installation of oxygen functionality, and asymmetric hydrogenation and aldol reactions that establish stereocenters with high selectivity. These approaches underpin the synthesis of optically active pharmaceuticals, agrochemicals, and natural products, where precise stereochemistry is often essential for activity and safety.