1,4-Pd Migration-Enabled Synthesis of Fused 4-Membered Rings.

ABSTRACT: 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 N-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.

SUBMITTER: Tsitopoulou M 

PROVIDER: S-EPMC11258686 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature