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However, the diastereocontrolled synthesis of these compounds typically requires complicated synthetic routes, indicating a need for novel methods. Here, we report a sequential C\u2212H\/C\u2212C functionalization strategy for the stereospecific synthesis of <jats:italic>cis<\/jats:italic>\u2010<jats:italic>\u03b3<\/jats:italic>\u2010functionalized cyclobutyl ketones from readily available cyclobutyl aryl ketones. Specifically, a bicyclo[1.1.1]pentan\u20102\u2010ol intermediate is generated from the parent cyclobutyl ketone via an optimized Norrish\u2010Yang procedure. This intermediate then undergoes a ligand\u2010enabled, palladium\u2010catalyzed C\u2212C cleavage\/functionalization to produce valuable <jats:italic>cis\u2010\u03b3<\/jats:italic>\u2010(hetero)arylated, alkenylated, and alkynylated cyclobutyl aryl ketones, the benzoyl moiety of which can subsequently be converted to a wide range of functional groups including amides and esters.<\/jats:p>","DOI":"10.1002\/anie.202303948","type":"journal-article","created":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T09:12:17Z","timestamp":1681377137000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Formal <i>\u03b3<\/i>\u2212C\u2212H Functionalization of Cyclobutyl Ketones: Synthesis of <i>cis<\/i>\u20101,3\u2010Difunctionalized Cyclobutanes"],"prefix":"10.1002","volume":"62","author":[{"given":"Zhoulong","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Chemistry The Scripps Research Institute  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