Synthesis of β<i>-</i>(Hetero)aryl\nKetones via Ligand-Enabled Nondirected C–H Alkylation

β-Aryl\nketones are essential structural units in\nnatural\nproducts and bioactive molecules, commonly synthesized through coupling\nreactions involving prefunctionalized arenes or via directing group\n(DG) strategies. However, these conventional methods are often inefficient,\nrequiring multiple synthetic steps that escalate both the cost and\nthe complexity of the process. The need for additional steps, such\nas directing group installation and subsequent removal, further compromises\nthe atom economy and overall efficiency. Herein, we report a palladium(II)-catalyzed\ndual ligand-enabled nondirected C–H alkylation with arene and\nheteroarene as a limiting reagent for the synthesis of β-(hetero)aryl\nketones with less chemical waste. The combined influence of 2-methyl\nquinoxaline and <i>N</i>-acetyl phenylalanine ligands imparts\nsignificant surge in selectivity, facilitating the diversification\nof drugs and natural products through C–H alkylation. Integrated\nexperimental and computational mechanistic studies demonstrate C–H\nactivation as both the regio- and rate-determining step. Interestingly,\nwhile the Pd–Ag heterobimetallic species is not directly involved\nin the 1,2-migratory insertion step, it is proposed to play a vital\nrole during the product release phase of the catalytic cycle.