regioselectivity

Regioselectivity describes the preference of a chemical reaction to form one constitutional isomer over other possible isomers when different positions in a molecule can be functionalized. It concerns the location of bond formation or substitution, not the stereochemistry of the resulting product. A reaction may be regioselective, producing a major isomer with minor amounts of others, or regiospecific, yielding essentially a single constitutional product.

Common examples illustrate how regioselectivity operates. In electrophilic addition to alkenes, hydrogen halides can add in a Markovnikov sense, placing the hydrogen on the less substituted carbon and the halogen on the more substituted carbon; under radical conditions (such as with peroxides), anti-Markovnikov addition can predominate. Hydration and hydroboration–oxidation likewise show regioselectivity: hydration typically follows Markovnikov selectivity, while hydroboration–oxidation provides anti-Markovnikov alcohols.

In electrophilic aromatic substitution, regioselectivity is governed by directing groups on the ring. Electron-donating substituents direct new substituents to the ortho and para positions, whereas electron-withdrawing groups such as nitro direct substitution to the meta position.

Regioselectivity can also arise in nucleophilic aromatic substitution, where leaving groups are replaced at positions activated by electron-withdrawing groups, often at ortho or para positions relative to activating substituents.

Factors influencing regioselectivity include electronic effects of substituents, steric hindrance, the nature of the reagents or catalysts, and reaction conditions. Understanding regioselectivity is essential for planning syntheses and achieving desired product distributions.