Nickelocene as an Air- and Moisture-Tolerant Precatalyst in the Regioselective Synthesis of Multisubstituted Pyridines

Ni(COD)(2) -catalyzed cycloaddition reactions to access pyridines have been extensively studied. However, this catalyst typically requires drying procedures and inert-atmosphere techniques for the reactions. Herein, we report operationally simple nickel(0) catalysis to access substituted pyridines from various nitriles and 1,6-diynes without the aid of air-free techniques. The Ni-Xantphos-based catalytic manifold is tolerant to air, moisture, and heat while promoting the [2 + 2 + 2] cycloaddition reactions with high reaction yields and broad substrate scope. In addition, we disclose that not only the steric effect but also the frontier molecular orbital interactions can play a critical role in determining the regiochemical outcome of nickel-catalyzed [2 + 2 + 2] cycloaddition for the synthesis of substituted pyridines.

Automated summary

The nickel-catalyzed cycloaddition reactions for accessing pyridines have been extensively studied. A new nickel(0) catalysis method was reported, which allows for the synthesis of substituted pyridines from various nitriles and 1,6-diynes without the need for air-free techniques. The Ni-Xantphos-based catalytic manifold shows tolerance to air, moisture, and heat, and promotes high reaction yields with a broad substrate scope. Additionally, it was found that both steric effects and frontier molecular orbital interactions play critical roles in determining the regiochemical outcome of the nickel-catalyzed cycloaddition reactions for synthesizing substituted pyridines.