## 2 Synthesis of 1,3,4-Oxadiazole Precursors
In 2009, [PERSON] et al. described a universal method for the aylation of 2-aryl-1,3,4-oxadiazoles using various aryl iodides in the presence of a copper salt catalyst and 1,10-phenanthroline (phen) as an auxiliary ligand. Products **1a-r** were obtained in satisfactory yields at elevated temperatures in a relatively short reaction time (4 h, Scheme 4; **1a-r**; 38-99%) [40]. The method could introduce aryl moieties bearing a variety of functional groups such as a ketone, ester, or nitrile, which enabled the easy formation of more functionalized oxadiazole systems. Five years later, [PERSON] et al. described a method for the efficient aylation of 2-aryl-1,3,4-oxadiazoles using a diaryliodine salt at room temperature for 15 min to obtain the desired products in high yields (Scheme 4; **2a-m**; 60-89%) [41]. The presented ligand-free copper-catalyzed direct C-H arylation offered many advantages including short reaction times, mild reaction conditions, and wide substrate scope. In 2015, [PERSON] published a method for the synthesis of 2,5-diaryl-1,3,4-oxadiazoles using aryl and heteroaryl iodides and copper(II) oxide nanoparticles as a recyclable catalyst. The reaction produced conjugated products **3a-h** in high yields (Scheme 4; **3a-h**; 70-85%) [42]. In the same year, another universal method for the aylation of 1,3,4-oxadiazoles was published by [PERSON] and co-workers describing the use of copper powder in polyethylene glycol (PEG-400) as the reaction medium for monosubstituted 1,3,4-oxadiazole and aryl iodides. This led to the production of conjugated derivatives in high yields (Scheme 4; **4a-h**; 85-89%) [43]. The procedure was simple and did not require the use of external chelating ligands or co-catalysts. Another 2015 study, by [PERSON] et al., described the aylation of 2-phenyl-1,3,4-oxadiazole using copper and palladium catalysts, an appropriate ligand (trifury!phosphine), and norbornene co-catalyst during a 24 h reaction at an elevated temperature (Scheme 4; **5**; 85%) [44]. A year later, [PERSON] et al. described the use of ultraviolet light in the direct aylation of 2-phenyl-1,3,4-oxadiazole (Scheme 4; **6a,b**; 51-54%) [45]. The photoinduced reactions proceeded under the activation of CuI catalyst at room temperature. The same year, a study by [PERSON] and co-workers showed that the combined use of a copper iodide catalyst and a 1,10-phenanthroline ligand (phen) led to the formation of 4-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)benzonitrile in satisfactory yield (Scheme 4; 7; 75%) [46]. In 2019, [PERSON] et al. reported the direct aylation of 2-phenyl-1,3,4-oxadiazole using iodobenzene. Theauthors showed that the use of an organic base, lithium _tert_-butoxide, allowed the use of a lower reaction temperature of 25 \({}^{\circ}\)C while maintaining a high reaction yield (Scheme 4; **8**; 80%) [47]. In 2020, [PERSON] and co-workers described a universal method for the preparation of extended 1,3,4-oxadiazole derivatives, using a palladium catalyst and a bifunctional (2-biphenyl)dicyclohexylphosphine ligand (CyJohnPhos) (Scheme 4; **9a-j**; 28-79%) [48]. The methodology provided a direct approach to introducing an oxadiazole core at a distant position relative to the newly formed oxygen-containing ring. More recently in 2022, a study on the direct arylation of 2-phenyl-1,3,4-oxadiazole in mild conditions under blue LED illumination was published (Scheme 4; **10**; 71%) [49]. The authors described an effective combination of a metal-polymer catalyst, composed of CuI and carbon nitride (PCN) for a variety of the C-Hylation reactions. The elaborated catalytic system allows arylation reactions in visible light at room temperature.