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.