Functionalization of Saturated and Unsaturated Heterocycles via Transition Metal Catalyzed C-H Activation Reactions

Michael      Schnurch; Navid      Dastbaravardeh; Michael      Ghobrial; Birgit      Mrozek; Marko      D. Mihovilovic

Abstract

Heterocyclic compounds are of paramount importance in essentially all fields of chemistry and in our daily life. Therefore, the synthesis and modification of such compounds is an ever expanding field in synthetic chemistry. In recent years, all synthetic efforts were guided increasingly by the search for more atom efficient and economical methods. Transition metal catalyzed C – H activation reactions have proved to provide both: i) an increased atom efficiency since the number of functional groups required to form a desired bond can be reduced due to substitution of at least one functional group usually required in cross-coupling reactions by a C-H bond, and ii) shorter overall reaction times and a reduced number of synthetic steps which ultimately leads to more economical processes. Additionally, the C – H activation approach can be considered as an effort towards a greener chemistry, since the reduction in the number of synthetic steps in the majority of cases leads to a decrease in the amount of waste produced (silica gel, solvents, etc.) and energy consumed. The focus of this review is on the direct functionalization of both saturated and unsaturated heterocycles. Methods for the formation of C – C and carbon – heteroatom bonds will be discussed. In the case of saturated heterocycles, another focus will be put on the stereospecific functionalization of such building blocks.

Keywords: C, H Activation, direct functionalization heterocycles, metal catalysis, electronic heterocycles, electron poor heterocycles, silica gel, green chemistry, Electron Rich Heterocycles, (hetero)arenes, (hetero) arenas, furan, thiophenes, thiazoles, oxazoles, HASPO