Advances in Ligand Development for Wacker-Type Oxidation.

Wacker-type oxidation is a cornerstone catalytic transformation for alkene-to-carbonyl conversion in organic synthesis, with immense industrial and academic impact over six decades. However, the classic Wacker-Tsuji system suffers from inherent limitations, including corrosive chloride reliance, poor regiocontrol, noble metal dependence, catalyst deactivation, and sustainability issues, which severely restrict its synthetic utility. Ligand engineering has emerged as the central strategy to revolutionize this field, yet no comprehensive review dedicated to ligand-controlled Wacker-type oxidation has been reported to date. Herein, we systematically dissect the fundamental regulatory mechanisms of ligands in Wacker-type oxidation, and provide a holistic overview of state-of-the-art advances in ligand-modulated palladium catalysis, including chloride/copper-free systems, switchable Markovnikov/anti-Markovnikov regioselectivity, and asymmetric catalysis. We further summarize ligand-enabled palladium-free oxidation based on earth-abundant metals (Fe, Co, Ru, Cu), which achieves unprecedented anti-Markovnikov selectivity inaccessible to traditional Pd catalysts. Finally, we critically outline the key unresolved challenges and future perspectives in this field, aiming to provide rational guidance for the development of next-generation efficient, selective, and sustainable Wacker-type oxidation systems.