Understanding and Controlling the Mizoroki–Heck Reaction of Cyclic Enones

Pd-catalyzed Mizoroki–Heck reactions using cyclohexenone and related cyclic enones are surprisingly difficult, contrasting related reactions with acyclic-conjugated alkenes. In this report, we uncover several challenges associated with the reaction, including the decomposition of the starting materials and products during the reaction. Kinetic analysis, reaction optimization, and stoichiometric studies reveal the mechanistic origin of these challenges, and a catalyst system featuring BippyPhos as a ligand and TMP as a base is shown to promote successful reactions with a range of (hetero)­aryl bromide coupling partners.