Aryl halides Sonogashira coupling

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

Table 4.7 Sonogashira coupling of aryl halides with terminal acetylenes in the presence of PdCbiPPhj) catalyst [120].

There are a number of procedures for coupling of terminal alkynes with halides and sulfonates, a reaction that is known as the Sonogashira reaction.161 A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes with vinyl or aryl halides.162 The reaction can be carried out directly with the alkyne, using amines for deprotonation. The alkyne is presumably converted to the copper acetylide, and the halide reacts with Pd(0) by oxidative addition. Transfer of the acetylide group to Pd results in reductive elimination and formation of the observed product. 

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 ... 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

The Sonogashira coupling is the Pd-catalyzed coupling of aryl halides and terminal alkynes [207], which, in the appropriate cases, can be followed by the spontaneous, or easily induced,... 

Heuze et al. (34) synthesized three generations of bis(tert-butylphosphine)- and bis(cyclohexylphosphine)-functionalized Pd(II) DAB dendritic complexes that serve as copper-free recoverable catalysts for the Sonogashira coupling between aryl halides and alkynes (Scheme 9). 

Sonogashira coupling or alkynes with phenyl iodide Aryl halide and alkyne (Sonogashira) Solvent replacement Carroll and Holmes (1998)... 

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]. 

Table 4 Sonogashira coupling of aryl halide substrates with phenyl acetylenea ...

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... 

Terminal alkynes can be alkenylated by alkenyl triflates (bromides, iodides) and aryl-ated by aryl triflates (bromides, iodides). These reactions are called Cacchi coupling reactions if the reaction is catalyzed by Cu(I) and Pd(0) and if triflate reagents are employed, Sonogashira-Hagihara coupling reactions if the reaction is catalyzed by Cu(I) and Pd(0) and halides are employed as substrates, and Stephens-Castro coupling reactions for the more specialized case of the noncatalyzed coupling of copper acetylides with aryl halides. 

Another option for Sonogashira coupling as an initiator of sequential catalysis is the coupling isomerization reaction (CIR) of electron-deficient halide and 1-aryl propargyl alcohols giving rise to the formation of chalcones [115, 116]. Based upon the CIR of electron-deficient halides 163 and l-(p-bromo phenyl) propyn-l-ol (164) Muller and Braun [117] presented a consecutive... 

Copper(I) derivatives of metal diynyl complexes have proven to be useful synthetic intermediates in Cadiot-Chodkiewicz coupling reactions,290 292 and similar species are implicated in coupling of metal diynyls with aryl halides under Pd/Cu catalyzed (Sonogashira) conditions241,242 and in the Cul-catalyzed coupling reactions of metal diynyl species with other metal halides.293... 

A couple of years ago we have disclosed a new mode of alkyne activation towards isomerization as a detouring outcome of the Sonogashira coupling. As a result of coupling electron deficient (hetero)aryl halides (or a,p-unsaturated p-halo carbonyl compounds) 11 and aryl propargyl alcohols 12 a new access to 1,3-di (hetero)aryl propenones 13, i.e., chalcones, was established (Scheme 9) [77, 78]. The scope for electron deficient (hetero)aromatic halides 11 is fairly broad and even organometallic complexes like 13c can be synthesized by this sequence. 

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