Regio- and Site-Selective Organic Synthesis With Single-Atom Catalysts

Organic synthesis underpins the manufacture of pharmaceuticals, agrochemicals, and advanced materials. A key challenge is to selectively transform a specific region or site within a molecule while suppressing competing pathways, as different regio- and site-isomers often show distinct properties and increase separation costs. Most strategies to achieve such control rely on homogeneous metal-ligand complexes, where selectivity is regulated through ligand design. Yet, in practice, once an effective ligand framework is identified, optimization often depends on substituent-group modification, which allows only a relatively narrow tuning range of the electronic environment. Moreover, both ligand design and substituent modification require significant synthetic effort and extensive screening, making such tuning time-consuming and economically demanding. By contrast, as heterogeneous catalysts, single-atom catalysts (SACs) are readily separated and recycled, and they provide complementary support-derived handles for regio- and site-selectivity control, including a confined microenvironment around isolated sites and wider-window electronic-structure tuning through metal-support interactions. Such control has enabled highly regio- and site-selective hydroformylation, hydrosilylation, hydroboration, hydrophosphinylation, hydrogenation, azide-alkyne click chemistry, carbenoid insertion, hydrogen-deuterium exchange, and difunctionalization of alkenes. In this review, we summarize recent advances in these SACs-catalyzed transformations, discuss the underlying principles of selectivity control, and outline future opportunities.