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

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.