Science of Synthesis

Burmester, C.; Haß, O.; Faust, R., Science of Synthesis, (2008) 43, 225.

The widely used palladium-catalyzed cross-coupling reaction between terminal alkynes and sp2-hybridized carbon atoms was first introduced by Sonogoshira and co-workers in 1975 and is therefore known as the Sonogashira reaction.[‌1‌] They observed that the addition of palladium(0) to the copper-mediated Stephens–Castro reaction[‌2‌] dramatically improved the applicability of this reaction since the conditions were considerably milder compared to the often harsh Stephens–Castro conditions. The catalyst loading is typically low, usually around 5 mol% or less. The reactions are conducted using mostly amines as solvents, although sometimes other cosolvents are used. Much mechanistic work has been done on this crucial reaction and it is now widely believed that the reaction involves two catalytic cycles. In the first, the copper cycle, the terminal alkyne reacts with copper(I) iodide in the presence of a base (usually an amine) to form copper acetylides. In the second cycle, a palladium(0) species [often generated in situ from palladium(II) precatalysts] inserts into the carbon—halogen bond of an organohalide to form an organopalladium(II) halide. Transmetalation of the copper acetylide delivers, in addition to a copper halide, the alkyne onto the palladium(II) center. Finally, a reductive elimination leads to C—C bond formation between the organo group and the alkyne and regenerates the palladium(0) catalyst. For more detailed mechanistic analyses the reader is referred to numerous reviews and textbooks on this topic.[‌3‌–‌6‌]

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References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8e, 888.