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

Comprehensive Summary 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 (IC 50 = 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.