Orthofunctionalization

Orthofunctionalization is a term used in organic chemistry to describe a specific type of functionalization reaction. It refers to the process of introducing a functional group onto a molecule at a position that is directly adjacent to an existing functional group. This adjacency is often referred to as an ortho position in aromatic systems or an alpha position in aliphatic systems. The key characteristic of orthofunctionalization is the regioselectivity, meaning the reaction specifically targets and modifies the position next to the pre-existing functional group.

This type of reaction is often employed to build molecular complexity and to create specific structural motifs that are difficult to access through other synthetic routes. The presence of the initial functional group often directs the reactivity of the neighboring position, either through electronic effects or by acting as a directing group for a metal catalyst. Common examples include directed ortho metalation, where a strongly coordinating group on an aromatic ring directs a lithiation reaction to the adjacent ortho position, followed by trapping with an electrophile. Similarly, certain catalytic systems can activate C-H bonds adjacent to functional groups for derivatization. Orthofunctionalization is a valuable tool in the synthesis of pharmaceuticals, natural products, and advanced materials, where precise control over molecular architecture is crucial.