Terminal alkynes Sonogashira coupling reaction

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

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]. 

Based on these results, conditions for alkyl-Sonogashira coupling reactions were developed. Primary alkyl halides reacted with terminal alkynes catalyzed by 5 mol% of complex 24a and Cul in the presence of substoichiometric amounts of Nal for bromides or Bu4NI for alkyl chlorides (entry 29) [73]. The latter serves to catalyze the in situ generation of more reactive alkyl iodides under the reaction conditions. The internal alkyne products were isolated in 57-89% yield. The Sonogashira coupling can also be combined to the Kumada reaction described above. a,o)-Chloroalkyl bromides underwent the Kumada coupling first selectively... 

A variety of structurally diverse 2-alkynyl benzo[Z>]furans were synthesized by a tandem Pd/C- and Cul-catalyzed tandem Ullmann/Sonogashira coupling reaction from gem-dibromovinyl substrates and terminal alkynes <07OL2955>. 

Pettier LR, Peyrat JF, Alami M, Brion JD (2004) Unexpected tandem sonogashira-carbo-palladation-sonogashira coupling reaction of benzyl halides with terminal alkynes a novel four-component domino sequence to highly substituted enynes. Synlett 1503-1508... 

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

Alkyne cross-coupling reactions over the last 25 years have become one of the most valuable assets in the synthetic chemist s toolbox. The now famous Sonogashira coupling (50, 114) of terminal alkynes with aryl or vinyl halides is readily achieved with a palladium catalyst, a copper(l) cocatalyst, and amine base. In the catalytic cycle (Scheme 14a), copper-and palladium-alkyne complexes are the key intermediates that lead to coupling of R and R units via the alkyne. Analogously, the Stille coupling... 

Another example of carbonylative Sonogashira coupling reactions with iodi-nium iodide and 1-alkynes was published by Ma and colleagues in 2001 [32]. Under mild conditions, iodine-substituted alkynones were produced in good yields (Scheme 5.9). Both aromatic, aliphatic and heterocyclic terminal acetylenes can be applied as their substrates. 

By the combination of two consecutive Sonogashira coupling reactions, the synthesis of internal alkynes, such as bisaryl-alkynes and arylalkenyl-alkynes, can be achieved. Because the terminal silyl group is inert to further coupling under the standard Sonogashira conditions, it must be removed prior to the second coupling step by common methods (e.g., TBAF or basic conditions eq 17).34... 

A reductive 1,8-didehydroxylation of l,2-dialkynyl-3,4-bis(diphenyl-methylene)-cyclobutenes 56, which themselves were prepared from 1,2-dibromocyclobut-l-ene 55 and the appropriate terminal alkyne by a Sonogashira coupling reaction, provided the deeply colored [4]radialenes 57a-d [50, 51]. A remarkable feature of 57 is the fast rotation around the cumulenic bonds at ambient temperature, with AG values of 13.7 (b, -20 °C), 14.9 (c, 0°C), and 17.8 (d, 27 °C) kcal mol" in chlorinated solvents. The bond rotation process was explained as proceeding through a diradical intermediate 58, that is, the geometrical isomerizations at the two cumulenic units occur independently (Scheme 4.13). 

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 ... 

The coupling of terminal alkynes with aryl or alkenyl halides catalysed by palladium and a copper co-catalyst in a basic medium is known as the Sonogashira reaction. A Cu(I)-acetylide complex is formed in situ and transmetallates to the Pd(II) complex obtained after oxidative addition of the halide. Through a reductive elimination pathway the reaction delivers substituted alkynes as products. 

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. 

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