Reactions of Terminal Alkynes to Form Aryl- and Alkenylalkynes Sonogashira Coupling

2 Reactions of Terminal Alkynes to Form Aryl- and Alkenylalkynes (Sonogashira Coupling) 

Direct introduction of sp carbon to alkynes by the reaction of Cu acetylides with aryl and alkenyl halides to form arylalkynes and alkenylalkynes is known as the Castro reaction [1]. Later it was found that coupling of terminal alkynes (1-alkynes) with halides proceeds more smoothly by using Pd catalysts. There are two methods of Pd-catalyzed coupling, hi 1975 direct coupling of 1-alkynes catalyzed by a phosphine-Pd(O) complex in the presence of amines was reported by Heck and Cassar as an extension of the Heck reaction to 1-alkynes [2,3]. In the same year, Sonogashira and Hagihara found that the addition of Cul as a co-catalyst gave better results, and the Pd(0)-CuI-catalyzed reaction is called the 

Sonogashira reaction [4,5], A comprehensive review on Pd-catalyzed alkynylation was published recently by Negishi and Anastasia [6], Facile Pd(0)-CuI-catalyzed coupling of aryl and alkenyl halides with 1-alkynes is used extensively for the preparation of arylalkynes or enynes. 

The reaction is explained by the following mechanism. At first, Cul activates 1-alkynes 1 by forming the Cu acetylides 6, which undergo transmetallation with arylpalladium halides to form the alkynylarylpalladium species 7, and reductive elimination to give 2 is the final step. However, the coupling proceeds even in the absence of Cul under certain conditions, and it may be possible to form the alkynylarylpalladium species 7 directly from 1-alkynes. As another less likely possibility, carbopalladation of a triple bond with Ar-Pd-X (or insertion of the triple bond to Ar-Pd-X) generates the alkenylpalladium 8 which undergoes dehydropal-ladation to afford disubstituted alkynes 2. In this mechanism, Cul plays no role. The mechanism of -H elimination of alkenylpalladium to form alkynes is not clearly known. 

1 Aryl-Alkynyl Coupling (Sonogashira Reaction) Reaction Conditions and Catalysts 

---