Regioselective Deprotonative Metalation of Heteroarenes with a Combination of Lithium Amide and Zinc Chloride Diamine Complex

A method for the C-2-selective deprotonative functionalization of halopyridines and other heteroarenes is described. The heteroaryllithium species generated by kinetic deprotonation is trapped by a zinc chloride diamine complex to form the heteroarylzinc species at room temperature. In this transformation, thermodynamically favorable competing reactions, including intermolecular proton transfer, halogen dance, and aryne formation, are suppressed. The resulting organozinc species were treated with electrophiles to afford the corresponding products in 44%-96% yields.