Catalytic C–F Bond Activation at Room Temperature: Enolate Cross‐Couplings Enabled by [Pd(1‐MeNAP)TFA] ₂ and LiHMDS

ABSTRACT Due to their exceptional stability, only few transition metal catalysts are capable of activating C─F bonds for C–C‐coupling reactions, usually under harsh conditions or with highly reactive nucleophiles. We herein report that a methyl naphthyl (MeNAP) palladium trifluoroacetate/ t BuBrettPhos catalyst with lithium bis(trimethylsilyl)amide (LiHMDS) as the base enables α‐arylations of in situ generated enolates with non‐activated aryl fluorides. The reaction proceeds under mild conditions at room temperature and extends to ketone, ester, nitrile, and even amide enolates. DFT calculations reveal that the coordination of lithium salts to the fluorine atom decisively facilitates the insertion of Pd into the C─F bond, explaining why this so far elusive reaction is now possible at such exceptionally mild conditions.