Ionic Sonogashira reaction

Sonogashira reaction) or terminal acetylenes (Heck reaction) in ionic liquids using a cleaning bath. The authors proposed that a Pd-bis-carbene complex, shown in Scheme 6, was formed and was consequently reduced into Pd black in both reactions, with palladium particle sizes of 1-12 nm, as determined by TEM. 

Sugimoto A, Sumino Y, Takagi M et al (2006) High throughput evaluation of the production of substituted acetylenes by the Sonogashira reaction followed by the Mizoroki-Heck reaction in ionic liquids, in situ, using a novel array reactor. Tetrahedron Lett 47 6197-6200... 

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 use of ionic liquids and flow chemistry technologies attract increasing attention. Consequently, these novel tools have also been successfully used in carbonylative Sonogashira reactions by Ryu and colleagues [38, 39]. Various al-kynones were synthesized in moderate to good yields at a low pressure of CO in n-butyl methyl imidazolium hexafluorophosphate. The microreactor-based flow system was compared with typical batch conditions, and higher yields could be achieved with flow system (Scheme 5.13). 

Scheme 5.13 Pd-catalyzed carbonylative Sonogashira reaction in ionic liquids...

A copper-free Sonogashira coupling reaction in ionic liquids and its application to a microflow system for efficient catalyst recycling, Org. Lett. 4, 10 (2002) 1691-1694. 

However, the use of basic anions is not the sole approach followed to obtaining basic ILs. Liquid salts bearing this additional property can be prepared also by incorporation of a basic center into the cation. This approach generally affords more thermally stable ILs than those based on basic anions, which frequently present relatively low decomposition temperatures. Basic ionic liquids bearing aliphatic or aromatic amines on the side chain(s) have been synthesized and, recently, some of these have been used as both the solvent and base for Heck, copper free Sonogashira, and for homocoupling reactions of terminal alkynes (Figure 4.2). 

Palladium-eatalyzed reaction of bicyclic hydrazines 175 with allyltributylstannane 176 in ionic liquid provided a facile method for the synthesis of substituted l,2,4-triazole-3,5-dionecyclopentenes 177 <05SL2273>. Sonogashira coupling of 3-mercaptopropargy 1-1,2,4-triazoles 178 with various aryl iodides led to the regioselective synthesis of 6-benzylthiazolo[3,2-()] 1,2,4-triazoles 179 <05TL1607>. 

Other biphasic C—C bonding reactions were carried out with fluorous solvents, for instance Suzuki- and Sonogashira-couplings [124] or ethene or propene oligomerizations [125, 126], Further new solvent systems use ionic liquids for the linear dimerisation of 1-butene to octenes [127] or the hydrovinylation of styrene with a combination ionic liquid/supercritical carbon dioxide [128] (cf. Section 7.4). 

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