Transition metal-catalyzed C-H/C-C activation and coupling with 1,3-diyne.

ABSTRACT

This review provides a broad overview of the recent developments in the field of transition metal-catalyzed C-H/C-C bond activation and coupling with 1,3-diyne for assembling alkynylated heterocycles, bis-heterocycles, and 1,3-enynes. Transition metal-catalyzed inert bond (C-H/C-C) activation has been the focus of attention among synthetic chemists in recent times. Enormous developments have taken place in C-H/C-C bond activation chemistry in the last two decades. In recent years the use of 2π-unsaturated units as coupling partners for the synthesis of heterocycles through C-H/C-C bond activation and annulation 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 to render bis-heterocycles in a straightforward manner. The C-H bond activation and coupling with 1,3-diyne has been very much explored in recent years. However, the development of strategies for the use of 1,3-diynes in the analogous C-C bond activation chemistry is less explored. Earlier methods employed to assemble bis-heterocycle used heterocycles that were preformed and pre-functionalized via transition metal-catalyzed coupling reactions. The expensive pre-functionalized halo-heterocycles and sensitive and expensive heterocyclic metal reagents limit its broad application. 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 cost economic. Hence, this strategy of C-H activation and subsequent reaction with 1,3-diyne could be used 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 investigate these unexplored domains.