The Sonogashira reaction is a cross-coupling reaction used in organic synthesis to form carbon–carbon bonds. It employs a palladium catalyst as well as copper co-catalyst to form a carbon–carbon bond between a terminal alkyne and an aryl or vinyl halide. R1: aryl or vinyl R2: arbitrary X: I, Br, Cl or OTf The Sonogashira cross-coupling reaction has been employed in a wide variety of areas, due to its usefulness in the formation of carbon–carbon bonds. The reaction can be carried out under mild conditions, such as at room temperature, in aqueous media, and with a mild base, which has allowed for the use of the Sonogashira cross-coupling reaction in the synthesis of complex molecules. Its applications include pharmaceuticals, natural products, organic materials, and nanomaterials. Specific examples include its use in the synthesis of tazarotene, which is a treatment for psoriasis and acne, and in the preparation of SIB-1508Y, also known as Altinicline, a nicotinic receptor agonist. History The alkynylation reaction of aryl halides using aromatic acetylenes was reported in 1975 in three independent contributions by Cassar, Dieck and Heck as well as Sonogashira, Tohda and Hagihara. All of the reactions employ palladium catalysts to afford the same reaction products. However, the protocols of Cassar and Heck are performed solely by the use of palladium and require harsh reaction conditions (i.e. high reaction temperatures). The use of copper-cocatalyst in addition to palladium complexes in Sonogashira's procedure enabled the reactions to be carried under mild reaction conditions in excellent yields. A rapid development of the Pd/Cu systems followed and enabled myriad synthetic applications, while Cassar-Heck conditions were left, maybe unjustly, all but forgotten. The reaction's remarkable utility can be evidenced by the amount of research still being done on understanding and optimizing its synthetic capabilities as well as employing the procedures to prepare various compounds of synthetic, medicinal or material/industrial importance. Among the cross-coupling reactions it follows in the number of publications right after Suzuki and Heck reaction and a search for the term "Sonogashira" in Scifinder provides over 1500 references for journal publications between 2007 and 2010. The Sonogashira reaction has become so well known that often all reactions that use modern organometallic catalyst to couple alkyne motifs are termed some variant of "Sonogashira reaction", despite the fact that these reactions are not carried out under true Sonogashira reaction conditions. Mechanism The reaction mechanism is not clearly understood, but the textbook