||Suzuki–Miyaura cross-coupling reaction has arguably become one of the most efficient protocols for palladium-catalyzed carbon–carbon bond forming processes in synthetic organic chemistry. Recent success in promoting less reactive organic electrophiles, such as unactivated and sterically hindered aryl chlorides, and heteroaryl chlorides, attributes to development of electron-rich and sterically bulky phosphines and N-heterocyclic carbenes (NHCs). A brief introduction is given in Chapter 1, focusing on the most important progress in developing efficient catalyst systems and understanding on catalytically viable palladium species. Aromatic amide-derived phosphines (Aphos) have been established as the efficient P,O-type hemilabile ligands in palladium-catalyzed room-temperature Suzuki–Miyaura cross-coupling reaction of unactivated aryl chlorides with aryl boronic acids under mild basic conditions. One major contribution of this thesis work is presented in Chapter 2 on the synthesis and characterization of a number of Aphos–palladium(II) complexes, which showcase the versatile coordination modes of Aphos as P-monodentate and P,O-chelating ligands. Reactions of the purified and structurally characterized Aphos–arylpalladium(II) bromide, chloride, and acetate with aryl boronic acids at room temperature in the presence of K3PO4 confirm that transmetallation and reductive elimination steps in the catalytic cycle(s) could occur at room temperature and the halide or pseudohalide donors on the Aphos–arylpalladium(II) intermediates do not significantly influence these steps. However, sterically demanding aryl boronic acids with two ortho appendage groups failed in transmetallation reaction at room temperature, indicating reasonably good O-donor function exerted by the Aphos amide subunit. A discussion on the effect of Aphos–Pd ratio on catalytic efficiency in room-temperature coupling reaction is given in Chapter 3, along with the results of room-temperature cross-coupling of unactivated aryl chlorides with aryl boronic acids using C5-(3-NO2Ph)-Cy-Aphos as the ligand. It is believed that at elevated temperatures the P-monodentate and monoligated Pd species of Aphos should be favored. In Chapters 4–6, the Aphos–Pd system has been optimized for cross-coupling reactions of challenging coupling partners at 70–100 ºC. These include: (a) formation of biaryls from the coupling reaction of aryl tosylates with aryl boronic acids by using 0.5–3 mol% Pd(OAc)2 and C4-(p-Tolyl)-Cy-Aphos (Pd:Aphos = 1:1.5) in the presence of K3PO4·3H2O (3 equiv) in t-BuOH–H2O (10:1) at 80 ºC; (b) formation of bipyridines and related heterocycles from the coupling reaction of heteroaryl chlorides with heteroaryl boronic acids by using Pd2(dba)3 (0.5–2 mol% Pd loadings) and C4-(1-Naphthyl)-Cy-Aphos (Pd:Aphos = 1:2) in the presence of K3PO4 (3 equiv) in n-BuOH at 100 ºC; and (c) formation of benzo[b]furans from the coupling reaction of 1,1-dibromo-1-alkenes with vinyl boronic acids by using Pd2(dba)3 (2 mol% Pd loading) and C4-(2,6-Me2Ph)-Cy-Aphos (Pd:Aphos = 1:1.5) in the presence of K3PO4 (3 equiv) in NMP at 70 ºC. Overall, this thesis research presents a compilation of the most updated results on Aphos as the hemilabile P,O-type ligands in Pd-catalyzed Suzuki–Miyaura cross-coupling reactions of structurally challenging partners for efficient synthesis of biaryls, nitrogen heterocycles, and benzo[b]furans, along with characterization of the Aphos–Pd(II) complexes featuring P-monodentate and P,O-chelating coordination modes.