Palladium-Catalyzed Benzylic C(sp³ )-H Carbonylative Arylation with Aryl Bromides

A novel, selective and high-yielding palladium-catalyzed carbonylative arylation of a variety of weakly acidic (pK_a 25-35 in DMSO) benzylic and heterobenzylic C(sp³ )-H bonds with aryl bromides has been achieved. This system is applicable to a range of pro-nucleophiles for access to sterically and electronically diverse α-aryl or α,α-diaryl ketones, which are ubiquitous substructures in biologically active compounds. The Josiphos SL-J001-1-based palladium catalyst was identified as the most efficient and selective, enabling carbonylative arylation with aryl bromides under 1 atm CO to provide the ketone products without the formation of direct coupling byproducts. Additionally, (Josiphos)Pd(CO)₂ was identified as the catalyst resting state. A kinetic study suggests that the oxidative addition of aryl bromides is the turnover-limiting step. Key catalytic intermediates were also isolated.