ABSTRACT 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.
Shang et al. (Thu,) studied this question.