High‐Entropy Catalyst Activated Molecular Oxygen for Oxidative Coupling Under Ambient Conditions

ABSTRACT Molecular oxygen (O 2 ) activation to generate reactive oxygen species (ROS) underpins catalytic oxidative coupling processes, yet conventional methods rely on external energy inputs that hinder sustainability. Here, we first demonstrate that the multielement synergistic nonnoble high‐entropy sulfide nanocrystal (HESNCs) with rich self‐generated lattice distortions enables spontaneous oxygen (O 2 ) activation to generate superoxide radicals (•O 2 − ) under ambient conditions, driving diverse oxidative coupling reactions (S─N, C─S, C─N) with high catalytic activity and exceptional stability (> 300 days). Meanwhile, this HESNCs‐driven field‐free catalytic protocol achieves pharmaceutical synthesis with excellent yields (> 90%), scalable to mol‐scale production, showing great potential for industrial applications. The experimental and computational analyses reveal that severe intrinsic lattice distortions in HESNCs tailor d‐band centers and reinforce Pauli repulsion, enabling electron transfer from organic donors (e.g., amines) to O 2 to produce •O 2 − and donor radicals (Don•). Subsequent •O 2 − ‐induced substrate oxidation to form coupling‐active intermediates (Sub•), which combine with Don• to yield oxidative coupling products while reducing •O 2 − to water. Our work establishes a new “electron donor‐assisted high‐entropy catalysts (HECs)‐mediated” ambient‐condition O 2 activation paradigm for realizing oxidative coupling reactions without external energy input.