siteselectivity

Siteselectivity, more commonly called site selectivity, describes the preferential reaction at one location within a molecule when multiple possible reactive sites are present. It is a central concept in organic synthesis because different sites can yield different products with distinct properties, you, or reaction outcomes.

In electrophilic aromatic substitution, site selectivity is governed by substituents on the ring. Electron-donating groups such as alkyl or methoxy activate the ring and direct electrophilic attack to the ortho and para positions, while electron-withdrawing or strongly deactivating groups tend to direct to the meta position. These directing effects help predict which regioisomer will be formed and in what ratio, though actual outcomes can be influenced by reaction conditions and catalysts.

Beyond EAS, site selectivity is important in other reaction classes. In transition-metal–catalyzed C–H activation and functionalization, a proximal directing group (for example, a carbonyl, amide, or pyridine) can bind the metal and steer activation to a specific ring position or chain carbon, often yielding ortho- or beta-selective transformations. Steric factors also play a major role; bulkier substituents can block certain sites and shift the outcome toward less hindered positions. Solvent, temperature, catalyst design, and ligands can further modulate regioselectivity.

Site selectivity is distinct from chemoselectivity (choice among different functional groups) and enantioselectivity (stereochemical outcome). It is widely used to streamline synthesis, enabling late-stage functionalization and the preparation of regioisomerically enriched products.