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Here, we report a new route to functionalized \u03b3\u2010lactams through formal carbonylation of azetidines under nonprecious metal catalysis. The method leverages a copper\u2010stabilized difluorocarbene to promote site\u2010selective insertion followed by in situ hydrolysis to unmask the lactam group. In contrast to most difluorocarbene reactions that cause ring cleavage of saturated heterocycles in the presence of heat, the present system operates at a low temperature and retains the integrity of the cyclic structure. Synthesis of various drug\u2010like lactams and a therapeutic agent for diabetes highlights utility.<\/jats:p>","DOI":"10.1002\/anie.202505033","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T14:57:33Z","timestamp":1744037853000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Site\u2010Selective Carbonylation of Azetidines via Copper\u2010Catalyzed Difluorocarbene Insertion"],"prefix":"10.1002","volume":"64","author":[{"given":"Fang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Chemistry National University of Singapore  4 Science Drive 2 Singapore 117544 Republic of Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong\u2010De","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Chemistry National University of Singapore  4 Science Drive 2 Singapore 117544 Republic of 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