Unveiling the Potential of Nonactivated 1,3-Enynes for Controllable Divergent Gold-Catalyzed Cycloaddition with Cyanamides

Nonactivated 1,3-enynes react with cyanamides under gold(I)-catalyzed conditions. This divergent interplay proceeds as 4 + 2-bimolecular or 2 + 2 + 2-trimolecular cycloadditions and affords 2-aminopyridines, 1-aminoisoquinolines, and 2,4-diaminopyrimidines. The impact of catalytic systems and electronic/steric parameters on reaction selectivity was studied, and these findings enable directing the cycloaddition along the desired pathway. As a result, a new highly selective modular approach to valuable 2-aminopyridines was proposed. The further synthetic potential of this methodology was demonstrated through postmodifications, including functionalizations of both the heterocyclic backbone and amino substituents.