In recent years, an advanced method has started to complement and even substitute cross-coupling chemistry, namely direct arylation methods, often referred to as C-H activation reactions. The advantage of this type of transformation is that either the organometallic species or the (pseudo)halide component can be substituted by substrates containing a reactive C-H bond instead. This method helped avoiding such pre-functionalization, shortening synthetic pathways significantly, which is more time-, resource-, and energy efficient. Heterocycles are especially suitable for C-H activation chemistry since the different C-H bonds present are significantly different in reactivity due to the presence of the heteroatom(s). C-H activation reactions of several heterocycles have been described to contribute to the synthesis of many compounds which are potential biologically active. The application of C-H activation in the synthesis plan not only reduced reaction steps but also help the synthesis of variation products became much more convenient. On the first project, a ligand free C-H activation on the thiazole scaffold was modified by using bromide coupling partners. Especially, a rare N-endo benzyl protected 2-aminothiazole was also submitted to directed arylation successfully by the new method. Structure of selective products of those arylations was confirmed indirectly due to the oxidative deprotection since their NMR profiles were unprecedent and unpredictable. Next project, naringenin and hesperetin derivatives were synthesized by protection and reduction. Since the reduction was followed by de-protection hence the target was changed afterwards. Reduced bisprotected products were synthesized instead. 12 compounds were evaluated regarding their bioactivities on E. amylovora bacteria. Move on to the third project, an efficient method of direct arylation on benzo[b]furan as well as benzo-fused heterocycles in general was developed. The method showed high regio-selectivity and good yields with readily palladium catalyst and phosphine ligands. Last but not least, a scope of benzofuran neolignans was synthesized via both coupling reaction and C-H activation. 40 synthesized compounds (38 new ones) were screened for anti-inflammantory activities afterward. Up to 15 compounds displayed significant activity on NF-B inhibition with IC50 values less than 10M. 3 compounds showed promising activity on LXR- activation. With 18 active compounds out of 40 tested scaffolds, the hit rate represents a remarkable 45%.