定义Definition
薗头偶联反应是钯与亚铜共催化下，端炔与芳基或乙烯基卤化物在胺碱中偶联，生成内炔（芳基炔、烯炔）的反应。
The Sonogashira coupling joins a terminal alkyne with an aryl or vinyl halide under palladium and copper(I) co-catalysis in an amine base, giving internal alkynes (aryl alkynes and enynes).
机理Mechanism
钯循环：Pd(0) 氧化加成 Ar–X，转金属化接受炔基，还原消除得 Ar–C≡C–R。铜循环：CuI 与端炔在胺作用下生成炔铜，作为转金属化试剂把炔基交给钯。
Palladium cycle: oxidative addition of Ar–X, transmetalation to receive the alkynyl group, reductive elimination to Ar–C≡C–R. Copper cycle: CuI and the amine convert the terminal alkyne into a copper acetylide that transfers the alkynyl group to palladium.
由来Origin
薗头健吉、Y. Tohda、萩原信卫于 1975 年报道，在加入 CuI 后反应可在室温下进行。
Reported in 1975 by Kenkichi Sonogashira, Yasuo Tohda and Nobue Hagihara; adding CuI allowed the coupling at room temperature.
注意与应用Caveats and uses
有氧时炔铜易氧化偶联成二炔（格拉泽偶联副反应），需除氧；也发展了无铜条件。用于合成共轭聚合物、分子导线、天然烯二炔抗生素和药物（如他扎罗汀）。
In air copper acetylides undergo Glaser homocoupling to diynes, so oxygen is excluded; copper-free variants exist. Used for conjugated polymers, molecular wires, enediyne natural products and drugs such as tazarotene.
反应Reactions
PdCl₂(PPh₃)₂/CuI，Et₃N 或 iPr₂NH，室温至 60 °C，惰性气氛
PdCl₂(PPh₃)₂/CuI in Et₃N or iPr₂NH, room temperature to 60 °C, inert atmosphere
Pd(0) 氧化加成芳基卤化物。
Pd(0) oxidatively adds the aryl halide.
端炔与 CuI/胺生成炔铜。
The alkyne forms a copper acetylide with CuI and amine.
炔基转金属化到钯。
Transmetalation of the alkynyl group to Pd.
还原消除得到芳基炔。
Reductive elimination gives the aryl alkyne.
合成二苯乙炔。
Synthesis of diphenylacetylene.
年表Timeline
- 1975
薗头等报道 Pd/Cu 共催化偶联
Sonogashira and co-workers report Pd/Cu coupling