Synthesis of bridged tricyclo[5.2.1.01,5]decanes via nickel-catalyzed asymmetric domino cyclization of enynones

The restricted availability, expense and toxicity of precious metal catalysts such as rhodium and palladium challenge the sustainability of synthetic chemistry. As such, nickel catalysts have garnered increasing attention as replacements for enyne cyclization reactions. On the other hand, bridged tricyclo[5.2.1.0(1,5)]decanes are found as core structures in many biologically active natural products; however, the synthesis of such frameworks with high functionalities from readily available precursors remains a significant challenge. Herein, we report a nickel-catalyzed asymmetric domino cyclization reaction of enynones, providing rapid and modular synthesis of bridged tricyclo[5.2.1.0(1,5)]decane skeletons with three quaternary stereocenters in good yields and remarkable high levels of regio- and enantioselectivities (92-99% ee). Tricyclo[5.2.1.0(1,5)]decanes are often found in bioactive natural products; however, their synthesis poses significant challenges. Here, the authors report a nickel-catalyzed asymmetric domino cyclization of enynones, providing a rapid and modular synthesis of bridged tricyclo[5.2.1.0(1,5)]decane skeletons.