Mechanism of the Copper‐Free Palladium‐Catalyzed Sonagashira Reactions: Multiple Role of Amines

Amines used as bases in copper‐free, palladium‐catalyzed Sonogashira reactions play a multiple role. The oxidative addition of iodobenzene with [Pd 0 (PPh 3 ) 4 ] is faster when performed in the presence of amines (piperidine>morpholine). Amines also substitute one ligand L in trans ‐[PdI(Ph)(L) 2 ] (L=PPh 3 , AsPh 3 ) formed in the oxidative addition. This reversible reaction, which gives [PdI(Ph)L(R 2 NH)], is favored in the order AsPh 3 >PPh 3 and piperidine>morpholine. Two mechanisms are proposed for Sonogashira reactions, depending on the ligand and the amine. When L=PPh 3 , its substitution by the amine in trans ‐[PdI(Ph)(PPh 3 ) 2 ] is less favored than that of the alkyne. A mechanism involving prior coordination of the alkyne is suggested, followed by deprotonation of the ligated alkyne by the amine. When L=AsPh 3 , its substitution in trans ‐[PdI(Ph)(AsPh 3 ) 2 ] by the piperidine is easier than that by the alkyne, leading to a different mechanism: substitution of AsPh 3 by the amine is followed by substitution of the second AsPh 3 by the alkyne to generate [PdI(Ph)(amine)(alkyne)]. Deprotonation of the ligated alkyne by an external amine leads to the coupling product. This explains why the catalytic reactions are less efficient with AsPh 3 than with PPh 3 as ligand.