NHCs Sonogashira reaction

The first examples of NHC-Pd complexes applied to the Sonogashira reaction were reported to show a limited scope in the coupling of aryl iodides and activated aryl bromides with acetylene [23,33,52]. However, the use of A-carbamoyl-substituted heterocyclic carbene Pd(ll) complexes expanded the use to alkyl-acetylenes and deactivated aryl iodides and bromides [124] (Scheme 6.40). 

Concerning other metals, Sonogashira coupling products have also been observed in the reaction of Ag(l)-carbenes [133] and Au(I)-supported carbenes [134] in low to moderate yields, but only under harsh conditions (more than 100°C). In this regard, NHC based catalysts for Sonogashira reactions have been supported on different materials that include clays [135], polymers [136] and peptides [137]. 

Suzuki-Miyaura as well as moderate activity in the Stille reaction ([M] = SnRa) were observed. In contrast to bis(NHC) complexes, inactivity in the Sonogashira reaction was due to increased activity in the homocoupling of alkynes [Eq. (47)], an undesired side reaction. 

Through a survey of a number of Pd/ligand combinations, Pd/NHC-based systems were found to possess the desired activity. Interestingly, organic bases such as NEt3, which are commonly used in Sonogashira reactions of aryl electrophiles, were ineffective under the conditions described in Eq. 14. 

The low volatility of ionic liquids and the easy separation of catalysts (which usually remain in these polar media) have made ionic liquids an interesting alternative to typically used organic solvents. Rather unsatisfactory results have been obtained in both copper-mediated [36] and copper-free [37] Sonogashira reactions, with aryl iodides being the only aromatic electrophiles coupled at reaction temperatures between 60 and 80 °C. It should further be noted that imidazolium-based ionic liquids are not necessarily innocent solvents, but can be deprotonated in the presence of bases to generate N-heterocycUc carbenes (NHCs). 

The findings of an extensive study on NHC-based Hgands with semilabile pendant functionalities were reported by CaveU [61]. Here, better conversions were achieved in Sonogashira reactions if the complex took advantage of the donor capability of one NHC Ugand, and an additional stabihzation was induced by the presence of an N-donor pyridine. Despite long reaction times, a maximum TON of 540 was achieved (Scheme 6.12). 

In 2007, Lee and coworkers reported the synthesis of a core-shell type polymer-supported (NHC)-Pd catalyst 28 (Figure 4.8), which was used to catalyze copper-free Sonogashira reactions under ambient atmosphere [39]. The... 

The Sonogashira reaction is another reaction which is notoriously not very efiiciently catalyzed by Pd-NHC species (Eq. 3) ... 

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. 

NHC-Pd(ll) complexes have also been used in tandem reactions involving a Sonogashira couphng and hydroalkoxylation of the resulting alkyne for the synthesis of benzofurans [131] as well as sequential Heck-Sonogashira couphngs [132] (Scheme 6.44). 

Other successful examples of catalysts containing NHC ligands are found in palladium- and nickel-catalyzed carbon-carbon bond formations. The catalyst development with these metals has focused in particular on Heck-type reactions, especially the Mizoroki-Heck reaction itself [Eq. (42)] and various cross coupling reactions [Eq. (43)], e.g., the Suzuki-Miyaura reaction ([M] = and the Kumada-Corriu reaction ([M] = MgBr). " Related reactions like the Sonogashira coupling [Eq. (44)]326-329 Buchwald-... 

Catalytic Properties. In recent years, NHC ligands have led to numerous breakthroughs in different highly useful reactions such as the Heck, ° Suzu-ki, Sonogashira, Kumada and StUle couplings, aryl amination, ° and amide a-arylation, and hydrosilylation. ... 

Sonogashira coupling reactions of primary alkyl halides have been reported. " The key to this was the use of an NHC ligand with bulky alkyl groups on the two nitrogen atoms (Scheme 2.121) lAd 1.51 and ItBu 1.55. This reaction is an alternative to the classical alkylation of acetylides ions with alkyl halides, with the advantage that base-sensitive functionality is tolerated. 

Nevertheless, the group of Peris reported in 2009 that dinuclear Pd complexes with the Janus-type ditz ligand were quite effective in the sequential Sonogashira/hydroxyalkoxylation coupling leading to benzofurans (Fig. 17), with a catalytic efficiency comparable to that ofmono-NHC analogues. The reaction worked well with 2-iodobenzyl alcohol, whereas only moderate yields could be obtained with the bromo derivative and the chloro derivative was quite unreactive." ... 

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