Transition Metal-catalyzed C-H /C-C Activation and Coupling with 1, 3-diyne

Abstract

This review focuses on providing a broad overview of the recent developments in the field of transition metal-catalyzed C-H bond activation and coupling with 1,3-diyne for assembling alkynylated heterocycles and bis-heterocycles. In recent years the use of 2π-unsaturated units as coupling partners for the synthesis of heterocycles through C-H bond activation and an-nulation sequence has received immense attention. Among the unsaturated units employed for assembling heterocycles, the use of 1,3-diynes has garnered significant attention due to its ability in rendering the straightforward bis-heterocycles. Earlier methods employed to assemble bis-heterocycle include the use of preformed and pre-functionalized heterocycles via transi-tion metal-catalyzed coupling reactions. The expensive pre-functionalized halo-heterocycles and sensitive & expensive heterocyclic metal reagents limit its use. However, the transition metal-catalyzed C-H activation obviates the need for expensive heterocyclic metal reagents and pre-functionalized halo-heterocycles. The C-H bond activation strategy makes use of C-H bonds as functional groups for effecting the transformation. This renders the overall synthetic sequence both step and costs economic. Hence, this strategy of C-H activation and subsequent reaction with 1,3-diyne is useful for the larger-scale synthesis of chemicals in the pharmaceutical industry. Despite these advances, there is still the possibility of exploration of earth-abundant, and cost-effective first-row transition metals (Ni, Cu, Mn. Fe, etc.) for the synthesis of bis-heterocycles. Moreover, the Cp* ligand free, simple metal salt mediated synthesis of bis-heterocycles is also less explored. Thus, more exploration of reaction conditions for the Cp* free synthesis of bis-heterocycles is called for. We hope this review will inspire scientists to explore the unexplored domains.

Ru(II)-Catalyzed Regioselective Redox-Neutral [4 + 2] Annulation of N-Chlorobenzamides with 1,3-Diynes at Room Temperature for the Synthesis of Isoquinolones

“…1,3-Diynes constitute an important building block often encountered as well as utilized in the synthesis of many natural products of biological importance . In recent years, with significant developments in the area of C–H activation/functionalization, 1,3-diynes are used as effective coupling partners for the synthesis of important heterocycles and bis-heterocycles (Scheme b) . However, issues such as chemoselectivity, regioselectivity, and mono- vs di-annulation make the use of 1,3-diynes a challenging task.…”