biostudies-literatureUnknown146(28)Tsitopoulou MUniversit?t Basel1,4-Palladium migration has been widely used for the functionalization of remote C-H bonds. However, this mechanism has been limited to aryl halide precursors. This work reports an unprecedented Pd⁰-catalyzed cyclobutanation protocol producing valuable fused cyclobutanes starting from cycloalkenyl (pseudo)halides. This reaction takes place via alkenyl-to-alkyl 1,4-Pd migration, followed by intramolecular Heck coupling. The method performs best with cyclohexenyl precursors, giving access to a variety of substituted bicyclo[4,2,0]octenes. Reactants containing an <i>N</i>-methyl or methoxy group give rise to fused azetidines or oxetanes, respectively, via the same mechanism. Kinetic and deuterium-labeling studies point to a rate-limiting C(sp³)-H activation step.Journal of the American Chemical Society18811-18816https://www.ebi.ac.uk/biostudies/studies/S-EPMC11258686biostudies-literature1,4-Pd Migration-Enabled Synthesis of Fused 4-Membered Rings.PMC11258686Thesmar PBaudoin OClemenceau ATsitopoulou Mfalse1,4-Pd Migration-Enabled Synthesis of Fused 4-Membered Rings.1,4-Palladium migration has been widely used for the functionalization of remote C-H bonds. However, this mechanism has been limited to aryl halide precursors. This work reports an unprecedented Pd⁰-catalyzed cyclobutanation protocol producing valuable fused cyclobutanes starting from cycloalkenyl (pseudo)halides. This reaction takes place via alkenyl-to-alkyl 1,4-Pd migration, followed by intramolecular Heck coupling. The method performs best with cyclohexenyl precursors, giving access to a variety of substituted bicyclo[4,2,0]octenes. Reactants containing an <i>N</i>-methyl or methoxy group give rise to fused azetidines or oxetanes, respectively, via the same mechanism. Kinetic and deuterium-labeling studies point to a rate-limiting C(sp³)-H activation step.2024-01-01T00:00:00Z2024 Jul2025-04-06T22:43:07.827Z2025-04-06T22:43:07.827ZS-EPMC112586863896858110.1021/jacs.4c04701