Ru-Catalyzed meta-Selective Aryl sp2C–H Bond Alkylation of Biologically Important Heterocycles to Access C–C Bond

Transition metal-catalyzed directing group-assisted C-H functionalization has been the centerstage in synthetic organic, medicinal, and materials chemistry program in the last few decades which allows precise site-/regio-selective creation of C–C bonds. The Lewis basic coordinating heteroatom(s), such as N-, O-, S-, and P-atom, is/are commonly present in heterocyclic scaffolds as pre-existing integral part and they function as directing atom(s)/group(s) to accomplish precise positional-selective C-H activation among analogous multiple C–H bonds of an organic molecule. After achieving the desired C-H functionalization they remain intact in the heterocyclic skeleton and can be termed as native/innate directing group. The assistance of native directing group has been frequently applied to perform ortho-C-H functionalization of heterocyclic moieties via an ortho-C-H metalation under the catalytic influence of various transition metals ranging from precious noble type to inexpensive non-noble metals. The meta-C-H functionalization of heteroaryl motifs guided by a native directing group primarily relies on Ru catalysts and has been realized through an initial ortho-C(aryl)-H ruthenation followed by para-C-H functionalization to C(aryl)-Ru bond via 'σ-bond activation'. The Ru-catalyzed meta-selective C–H bond functionalization following 'σ-bond activation' strategy is majorly centered on C-H alkylation. The present chapter discusses recent progresses made on native directing group-assisted Ru-catalyzed meta-C-H alkylation of different bio-significant heteroaryl scaffolds.