Designing Homogeneous Copper-Free Sonogashira Reaction through a Prism of Pd–Pd Transmetalation

[Image: see text] Simultaneous introduction of two different palladium (pre)catalysts, one tuned to promote oxidative addition to (hetero)aryl bromide and another to activate terminal alkyne substrate, leads to productive Pd–Pd transmetalation, subsequent reductive elimination, and formation of disubstituted alkyne. This conceptually novel rational design of copper-free Sonogashira reaction enabled facile identification of the reaction conditions, suitable for the synthesis of alkyl, aryl, and heteroaryl substituted alkynes at room temperature with as low as 0.125 mol % total Pd loading.