Metal‐Free [2+2+2] Cycloaddition of Ynamides and Nitriles: Mild and Regioselective Synthesis of Fully Substituted Pyridines

Abstract

Ametal-free trimolecular [2+ +2+ +2] cycloaddition of internal ynamides and nitriles for de novo synthesis of fully substituted pyridines is disclosed. With the versatile Brønsted acid catalyst HNTf 2 ,t he mild intermolecular cyclotrimerization process proceeds with complementary chemoselectivity and excellent regioselectivity.

Triflimide (HNTf2) in Organic Synthesis

“…In 2016, Zhang, Sun, and co-workers discovered that this activation could be employed in a highly efficient [2 + 2 + 2] cycloaddition of ynamides and nitriles, leading to efficient synthesis of fully substituted pyridines. 95 In the presence of 10 mol % of triflimide, 2 equiv of ynamides and 1 equiv of nitriles participated in the cycloaddition to form 2,4-diaminopyridines with high regioselectivity at room temperature (Scheme 31).…”