Development of methods for direct and selective transformation of inert C-H bonds into C-O, C-X, C-N, C-S and C-C bonds is extremely important in organic synthesis. Currently these chemical transformations still rely on the solvent-based protocols which regularly require toxic solvents and are often time-consuming. The objective of the proposed project is the development and optimization of the ball milling methods for the ligand-directed C–H bond functionalization mediated by various palladium(II) catalytic precursors. This objective will be achieved by using the substrates with a donor group which binds and positions the metal centre near the specific C–H bond so that C–Pd bond is formed in a process known as C–H bond activation or cyclometalation. The resulting C–Pd bond, which is far more reactive than its C–H counterparts, reacts with the secondary substrate to produce the desired C–O, C–X, C–N, C–S, or C–C bond. Prior to the transformation of C–H bonds into other functional groups, a series of ball-milling reactions between common palladium(II) precursors and substrates with different donor groups will be performed at variable temperatures to define the most convenient reaction conditions. The acquired knowledge will be applied in the C–H bond functionalization of selected substrates with commonly used oxidants and/or coupling partners in the presence of catalytic amount of palladium(II) salts. The reactions will be monitored in situ by the solid-state Raman spectroscopy, in combination with ex situ NMR, IR and X-ray experiments for unambiguous characterization of the involved reaction species, direct insight into the reaction pathways, and optimization of milling processes. The results of the proposed investigations will provide detailed insight into mechanochemical functionalization of C-H bond catalyzed by various palladium(II) compounds, and stimulate development of more efficient palladium catalysts and more mechanochemistry applications in chemical synthesis.