stereocontrole

Streocontrole, or stereochemical control, describes the strategies used to direct the stereochemical outcome of a chemical reaction so that particular stereoisomers are formed preferentially. It distinguishes enantioselectivity, the preference for one enantiomer over its mirror image, and diastereoselectivity, the preference for one diastereomer among multiple stereochemical possibilities.

Approaches include the use of chiral catalysts or ligands that create a chiral environment (metal-catalyzed or organocatalytic), chiral auxiliaries that temporarily impart chirality, and substrate-controlled reactions where the substrate's stereochemistry biases the product. Reaction conditions such as solvent, temperature, and additives can also influence the stereochemical outcome. In some cases, racemates are converted preferentially into one enantiomer via kinetic resolution, or into one enantiomer with simultaneous racemization and selective reaction (dynamic kinetic resolution).

Outcomes are quantified by enantiomeric excess (ee) and diastereomeric ratio (dr), while overall yield remains relevant. Analytical methods include chiral chromatography and optical rotation measurements.

Common methods with notable impact include asymmetric hydrogenation using chiral metal complexes, Sharpless asymmetric epoxidation, Corey–Bakshi–Shibata (CBS) reduction, and organocatalytic enantioselective aldol and Michael-type additions. Biocatalysis with enzymes also provides high stereocontrol and can be scalable.

Streocontrol is essential in pharmaceutical and agrochemical synthesis, where single-enantiomer products can exhibit superior efficacy and safety. It underpins the synthesis of natural products and complex molecules. Challenges include catalyst cost, catalyst recovery, and achieving high levels of both enantio- and diastereoselectivity across diverse substrates.

The concept arose from early work on chirality, followed by the development of modern asymmetric catalysis in the late 20th century, led by researchers such as Ryoji Noyori and K. Barry Sharpless, establishing widespread strategies for stereochemical control in synthesis.