metaselectivity

Metaselectivity is a term used in chemistry to describe the preferential formation of products in which a reaction occurs at the meta position relative to a reference substituent or directing unit. It is most commonly discussed in the context of aromatic substitution and C–H functionalization, where regioselectivity determines the site of bond formation on an aromatic ring.

In classical electrophilic aromatic substitution, substituents influence regioselectivity as ortho, meta, or para directors. Electron-donating groups tend to direct ortho and para, while electron-withdrawing groups direct to the meta position. Metaselectivity in this traditional sense therefore relates to the inherent directing effects of substituents on reaction outcome.

Beyond conventional directing effects, modern catalysis has introduced approaches to achieve meta selectivity that would not be predicted by simple directing groups. Template- or relay-assisted strategies place a metal catalyst in proximity to a meta C–H bond, enabling functionalization at the meta position even when a “directing” group would favor other sites. These methods often require a removable or traceless directing template and can employ various transition-metal catalysts under specialized reaction conditions.

Applications of metaselectivity include the synthesis of meta-substituted arenes that are difficult to access via standard directing-group chemistry, with relevance to pharmaceuticals, agrochemicals, and natural-product synthesis. Limitations include the need to install and remove directing templates, substrate compatibility, and often specialized reaction conditions. Ongoing research aims to broaden scope, improve efficiency, and simplify practical implementation of meta-selective strategies.