Sonogashira

The Sonogashira coupling, also known as the Sonogashira–Hagihara coupling, is a palladium-catalyzed cross-coupling reaction that forms carbon–carbon bonds between terminal alkynes and aryl or vinyl halides. It commonly employs a copper(I) co-catalyst and a base to produce aryl- or vinyl-substituted alkynes. Typical conditions use a Pd catalyst such as Pd(PPh3)2Cl2 or PdCl2(PPh3)2, a CuI co-catalyst, and a base like diisopropylamine, piperidine, or triethylamine, in solvents such as DMF, THF, or dioxane, at ambient temperature to about 80 °C.

Mechanistically, oxidative addition of the aryl or vinyl halide to Pd(0) is followed by formation of a copper acetylide from the terminal alkyne and CuI. Transmetalation transfers the alkynyl group to palladium, which then undergoes reductive elimination to yield the coupled product and regenerate Pd(0). The copper co-catalyst accelerates acetylide formation and transmetalation but can also promote side reactions such as alkyne homocoupling if conditions are not carefully controlled.

The scope includes terminal alkynes and aryl or vinyl halides, with broad functional-group tolerance that enables synthesis of various aryl- and vinyl-alkynes. Copper-free variants exist, achieved with bulky or specially designed ligands to suppress copper-mediated side reactions or using alternative catalysts.

Historically, the reaction was developed in the 1970s by Kenkichi Sonogashira and collaborators (notably Hiroshi Hagihara) at Tohoku University. It has since become a foundational method in organic synthesis, widely used in the construction of natural products, pharmaceuticals, and conjugated materials.