Redox-Neutral Nickel-Catalyzed Selective Hydroalkynylation of Internal Alkyne and Its Application in Anticancer Agent Discovery†

Abstract

Herein, an unprecedented nickel-catalyzed regioselective hydroalkynylation of unsymmetrical internal alkynes was realized with steric hindered resistance selectivity via the cyano-directing group strategy. Significantly, the resulting 1,3-enyne products could be effectively employed in the synthesis of novel nitrogen-containing tricyclics compounds, that provided the potential candidate compound 8a (IC₅₀ = 2.6—6.1 μmol/L) for the anti-tumor cell proliferation activity. Therefore, this work not only improves the transition-metal- catalyzed hydroalkynylation strategy of internal alkynes, but also exhibits versatility of 1,3-enynes in the construction of the complex bioactive chemical space.