Functionalization of five-membered heterocycles with two heteroatoms

Five-membered heteroarenes with two heteroatoms, including oxazole, thiazole, imidazole, pyrazole, and isoxazole are indispensable for the development of new biologically active compounds and organic functional materials. Consequently, C-H functionalization of this family of heterocycles has been intensively studied, focusing on the regioselectivity of the reaction. By taking advantage of the electronic and steric environment of the C-H bonds on the heterocyclic cores, several transition metal-catalyzed C-H functionalization strategies have been developed without using directing groups. This chapter reviews the types of substituents that can be added to these heteroarene cores and their appropriate coupling partners. In addition, mechanistic hypotheses and the critical factors that are key for regioselectivity are summarized. Ultimately, this review aims to provide a perspective on the practical strategies used to prepare these substituted heteroarene compounds and the challenges observed in the C-H functionalization of five-membered heteroarenes.