Aryl/vinyl halides with terminal acetylenes

Cross-coupling of aryl and vinyl halides with terminal acetylenes (the Sonogashira reaction) is among the fundamental methods of Pd-catalyzed C-C bond forming reactions. Cu-Pd co-catalysis is considered a standard requirement for this method. 

B. METAL-CATALYZED CROSS-COUPLING REACTIONS BETWEEN ARYL OR VINYL HALIDES WITH TERMINAL ACETYLENES... 

B.i. Pd-Catalyzed Cross-Coupling Reactions Between Aryl or Vinyl Halides with Terminal Acetylenes... 

As described above (Section 5.2), the Stephens-Castro reaction of alkynylcopper with aryl and vinyl halides in boiling pyridine is a useful route to aryl and vinyl acetylenes. Direct cross-coupling of organic halides, such as sp halides, with terminal alkynes is a more convenient procedure. Such a reaction is not so easy, but it can be done using a Pd-complex catalyst [41]. Especially facile Pd-catalyzed cross-coupling of aryl and alkenyl halides with terminal alkynes proceeds smoothly under mild conditions in the presence of a cocatalyst of cuprous iodide in amine solvents [Eq. (28)] [42]. This methodology is now used widely for the constiuction of conjugated arylalkyne or enyne systems [43], as described below. It is attractive from a synthetic point of view because mild reaction conditions and simplicity of the procedure are associated with recent developments in modem acetylene chemistry [44]. 

A well-established method for the synthesis of internal alkynes 34 is the Pd/Cu-catalyzed coupling of vinyl halides, aryl iodides, bromides, or triflates with terminal acetylenes 33 (Scheme 12). Nevertheless, this method suffers not only from the need for large amounts of catalyst (1-5 mol % Pd and 1-10 mol % Cul) but also from the need of higher temperatures for the aryl bromides. 

The Sonogashira cross-coupling reaction of terminal acetylenes with aryl or vinyl halides is a powerful tool for generation of carbon-carbon bonds between sp2- and sp-carbon. Numerous molecules of interest can be generated from a wide variety of aryl or vinyl halides (Scheme 3) [18-23],... 

Perfluoroalkynylcopper reagents can be prepared by metathesis reactions with the zinc or cadmium reagent (e.g., formation of 6) or by treatment of terminal (perfluoroalkyl)acetylenes with copper(I) chloride/ammonium hydroxide.69 Perfluoroalkynylcopper reagents react with aryl (e.g., formation of 7) and vinyl halides as well as undergoing oxidative dimerization reactions upon exposure to air.2... 

The coupling of terminal acetylenes to alkenyl bromides is illustrated by the preparation of 88 from (Zj-3-methylpent-2-en-4-yn-l-ol (8). For the preparation of 88, the compound 8 is coupled with ( )-l-bromo-2,6-dimethylhepta-1,5-diene (89) in the presence of Pd(PPh3)4/CuI [45] (Scheme 21). It should be noted that the Cul used is not esssential for the reaction, but apparently facilitates the coupling of vinyl and aryl halides to alkenes that are not electron deficient. 

Linstrumelle and co-workers reported that vinyl and aryl halides or triflates react very rapidly with terminal alkynes, without addition of copper salt, and lead to high yields of eneynes and aryl acetylenes by using Pd(PPh3)4 as a catalyst. The nature of the amine is critical for the success of the coupling (Scheme 3, [Pd] I). However,... 

The first palladium-catalyzed carbonylative Sonogashira coupling was reported in 1981 by Kobayashi and Tanaka [25]. Aryl, heterocyclic, and vinylic halides reacted with CO and terminal acetylenes at 120 °C and 80 bar in the presence of NEta and a catalytic amount of a palladium(II) complex to form alkynones in a 46-93 % yield (Scheme 5.3). Remarkably, aryl bromides and aliphatic alkynes were also included in the range of substrates. But NEts was used as a solvent for this transformation and a relatively high pressure of CO was needed. 

Csp-Csp Cross-coupling. The palladium and copper cocatalyzed cross-coupling between vinyl/aryl halides or triflates and terminal acetylenes, known as the Sonogashira reaction, is the most straightforward and powerful method for the construction of Csp -Csp bonds with retention of the vinyl stereochemistry and has been widely reviewed (eq 26). ... 

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