Aryl bromide-alkyne Sonogashira cross-coupling 1 -

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... 

The terminal alkyne can also be generated in situ via copper-free Sonogashira cross-coupling of trimethylsilyl acetylene (5a) and aryl halides 6 and subsequent cleavage with TBAF, caibonylation, and cyclization (Scheme 26) (20090L(11)3210). This microwave-assisted sequence allows the rapid synthesis of the title compounds in moderate to good yields. Each compound can be easily varied with exception to trimethylsilyl acetylene. The application of electron-rich aryl bromides and iodides expectedly decreases the yields. 

Synthetic strategy Copper-free Sonogashira — aryl bromide - alkyne cross-coupling... 

Keywords Aryl bromides, alkynes, Pd(l)-catalyst, ZnQ2, HN(j-Pr)2, THF, rrxim temperature, Sonogashira cross-coupling, substituted alkynes... 

Complex /c -C,N-[Pd(dmba)Cl(PTA)] (52, dmba = dimethylbenzylamine. Scheme 7.12) and Pd(OAc)2/PTA (1 3 molar ratio) were tested for catalytic Sonogashira cross-coupling reactions of aryl bromides and chlorides with terminal alkynes without the need of added copper or amines (Scheme 7.13) [55]. 

The palladium-catalyzed arylation and alkenylation of terminal alkynes with aryl or alkenyl hahdes in presence of a copper(l) co-catalyst is called Sonogashira reaction. In the same way as in the other cross-coupling reactions described before, it is possible to immobihze the alkyne or the aromatic bromides, iodides or triflates on sohd supports (Scheme 3.15). 

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