Palladium-free Sonogashira reaction

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

Interesting is the development of concept of copper-free Sonogashira reaction in which Cul catalyst was not used (Scheme 2.15). In these reactions, coupUng products 47 in various yields were still obtained (Table 2.14), probably due to the presence of trace amounts of copper in palladium reagent. When copper catalyst-free reaction was carried out with copper milling balls as a source of copper, yields increased to 31-88% (Table 2.15). Finally, copper vials in combination with copper balls as a source of copper afforded respectable yields in the range of42-90% (Table 2.16). 

Both binuclear and trinuclear oxalamidinate palladium complexes were employed by Rau, Walther and coworkers [79] in copper-free Sonogashira reactions. The peculiarity of the system was seen to reside in the presence of chemical bridges that allowed electronic communication between metal centers (Scheme... 

Miura et al. reported the first palladium-free Sonogashira coupling reaction of aryl iodides or vinyl iodides with terminal allqmes in the presence of a copper iodide/triphenylphosphine/potassium carbonate catalyst system (Scheme 15.14). o-Iodo-acetanilide derivatives react with l-allg nes smoothly even at room temperature in the presence of a copper iodide/AT-methylpyrrolidine-2-carboxamide catalyst system (Scheme Various... 

Ruiz J, Cutillas N, Lopez F, Lopez G, Bautista D (2006) A copper- and amine-free Sonogashira reaction of aryl halides catalyzed by l,3>5-triaza-7-phosphaadamantane palladium systems. Organometallics 25 5768-5773... 

A potentially interesting development is the microwave-assisted transition-metal-free Sonogashira-type coupling reaction (Eq. 4.10). The reactions were performed in water without the use of copper(I) or a transition metal-phosphine complex. A variety of different aryl and hetero-aryl halides were reactive in water.25a The amount of palladium or copper present in the reaction system was determined to be less than 1 ppm by AAS-MS technique. However, in view of the recent reassessment of a similarly claimed transition-metal-free Suzuki-type coupling reaction, the possibility of a sub-ppm level of palladium contaminants found in commercially available sodium carbonate needs to be ruled out by a more sensitive analytical method.25 ... 

Although the Sonogashira reaction is normally performed with a copper cocatalyst, a copper-free, one-pot procedure for direct coupling with l-aryl-2-trimethylsilylacetylenes has been developed <2005T2697>. The procedure uses a mixture of palladium acetate and tri(o-tolyl)phosphine as catalyst in the presence of tetra- -butylammonium chloride... 

Generally, the Sonogashira coupling reaction is achieved by a palladium-copper catalyzed reaction of aryl or vinyl halide and terminal alkyne [70-72], The presence of the copper co-catalyst is an obstacle, however, towards the metallodendritic approach of the system. In this context, only a few examples of copper-free procedures have been reported [73-77], involving for instance, in situ Pd(0) complex formation with bulky phosphines [78]. 

In 2006, Li and Wang reported the palladium-free, silver-catalyzed Sonogashira-type coupling of aryl halides and terminal alkynes. The reaction proceeds in high yield in the presence of catalytic silver iodide, triphenylphosphine, and potassium carbonate. Although the mechanism remains unclear, it is evident that the silver acetylide has a role, as the acetylide is formed on mixing of the reagents (Scheme 1.54).122... 

It was also found that the Sonogashira reaction [69] takes place under aqueous alkaline conditions in the presence of the PS-PEG-supported palladium complex 59 [95]. The combination of the resin catalyst 59, cesium hydroxide [96], and water is essential to promote high yielding coupling of 69. Using copper-free conditions, a one-step preparation of the benzofurans 70 was achieved in water via coupling of 2-iodophenol 68 (X=OH) and the terminal alkynes (Scheme 23). 

Scheme 14 Ligand-free palladium-catalyzed Heck and Sonogashira reactions in the PASS-flow reactor (yields refer to purified products T5AA=tetrabutylammonium acetate NMP=i r-methylpyrrolidinone)...

In this chapter, we discuss selected literature on palladium catalysts (or catalyst precursors) for the Heck, Suzuki and Sonogashira reactions. The review covers simple homogeneous palladium complexes, Ugand-free palladium catalytic systems, stable palladium colloids and particles and supported palladium catalysts. It focuses on the role of palladium nanoparticles (as catalyst precursors or formed in situ during the course of the reaction) from a mechanistic point of view. 

Generally speaking, palladium-free catalysts for Sonogashira reactions must be regarded with extreme caution, since it is known that cross-couphng reactions can be performed when only ppb levels of palladium are present in some inorganic bases [91]. 

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