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A key challenge is to selectively transform a specific region or site within a molecule while suppressing competing pathways, as different regio\u2010 and site\u2010isomers often show distinct properties and increase separation costs. Most strategies to achieve such control rely on homogeneous metal\u2013ligand complexes, where selectivity is regulated through ligand design. Yet, in practice, once an effective ligand framework is identified, optimization often depends on substituent\u2010group 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\u2010consuming and economically demanding. By contrast, as heterogeneous catalysts, single\u2010atom catalysts (SACs) are readily separated and recycled, and they provide complementary support\u2010derived handles for regio\u2010 and site\u2010selectivity control, including a confined microenvironment around isolated sites and wider\u2010window electronic\u2010structure tuning through metal\u2013support interactions. Such control has enabled highly regio\u2010 and site\u2010selective hydroformylation, hydrosilylation, hydroboration, hydrophosphinylation, hydrogenation, azide\u2013alkyne click chemistry, carbenoid insertion, hydrogen\u2013deuterium exchange, and difunctionalization of alkenes. In this review, we summarize recent advances in these SACs\u2010catalyzed transformations, discuss the underlying principles of selectivity control, and outline future opportunities.<\/jats:p>","DOI":"10.1002\/anie.5513543","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T15:24:14Z","timestamp":1778772254000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Regio\u2010 and Site\u2010Selective Organic Synthesis With Single\u2010Atom Catalysts"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6949-5046","authenticated-orcid":false,"given":"Xin","family":"Shang","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Science and Technology on Applied Catalysis Dalian Institute of Chemical Physics Chinese Academy of Sciences  Dalian 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