Ligand effects Sonogashira reaction

Tri-t-butyl phosphine can be more effective in the coupling of reluctant aryl bromides (Scheme 2.118). Bulky electron-rich biaryl phosphine ligands, such as 2385, can also promote the Sonogashira reaction of difficult aryl chlorides (Scheme 2.119). ° Interestingly, in this case, the presence of copper(I) salts inhibited the reaction, and the copper-free version provided better yields. Aryl tosylates, easily prepared from phenols, also couple under these conditions (Scheme 2.120). 

Figure 4.4) [29]. Similarly, this facilitation of transmetallation via organocopper species has also been suggested for Stille and Suzuki reactions [30]. However, alternative proposals of the Cu-effect have also been proposed, that is, that Cu could act as ligand scavenger or even be an inhibitor in Sonogashira reactions of aryl chlorides [31].

A palladium catalyst with a less electron-rich ligand, 2,2-dipyridyl-methylamine-based palladium complexes (4.2), is effective for coupling of aryl iodides or bromides with terminal alkynes in the presence of pyrrolidine and tetrabutylammonium acetate (TBAB) at 100°C in water.37 However, the reactions were shown to be faster in NMP solvent than in water under the reaction conditions. Palladium-phosphinous acid (POPd) was also reported as an effective catalyst for the Sonogashira cross-coupling reaction of aryl alkynes with aryl iodides, bromides, or chlorides in water (Eq. 4.18).38... 

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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