Terminal alkynes palladium® bromide

Kotschy et al. also reported a palladium/charcoal-catalyzed Sono-gashira reaction in aqueous media. In the presence of Pd/C, Cul, PPI13, and z -Pr2NH base, terminal alkynes smoothly reacted with aryl bromides or chlorides, such as 2-pyridyl chloride, 4-methylphenyl bromide, and so on, to give the expected alkyne products in dimethyl-acetamide (DMA)-H20 solvent. Wang et al. reported an efficient cross-coupling of terminal alkynes with aromatic iodides or bromides in the presence of palladium/charcoal, potassium fluoride, cuprous iodide, and triph-enylphosphine in aqueous media (THF/H20, v/v, 3/1) at 60°C.35 The palladium powder is easily recovered and is effective for six consecutive runs with no significant loss of catalytic activity. 

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... 

Scheme 203 provides a methodology for the conversion of aryl bromides onto 4-aryl-l,2,3-triazoles. In the given example, palladium-copper catalyzed substitution of the bromine atom in indole 1226 by trimethylsilylacetylene provides intermediate 1227. Hydrolysis of the trimethylsilyl protecting group releases terminal alkyne 1228, isolated... 

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). 

The first direct coupling of terminal alkynes with aryl iodides or bromides without palladium was reported by Wang and Li in 2006.135 Silver iodide and triphenylphos-phane in polar solvents proved to be the best catalyst combination, while potassium carbonate proved to be the better base, giving diarylacetylenes in high yields (Table 10.8). 

Terminal alkynes can be alkenylated by alkenyl triflates (bromides, iodides) in the presence of catalytic amounts of a palladium(O) complex (or a precursor thereof) and usually an additional substoichiometric amount of copper(I) iodide (Cul), and they can be arylated by aryl triflates (bromides, iodides). These reactions are called Cacchi coupling reactions if triflate reagents are employed, and Sonogashira-Hagihara coupling reactions if halides are used. 

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

The sp -sp coupling reaction can be extended to the synthesis of terminal alkynes by use of protected alkynes such as trimethylsilylacetylene (28 TMSA) or 2-methyl-3-butyn-2-ol (29), followed by subsequent removal of the protecting group (Schemes 17, 18 and 20). - - Thus, commercially available TMSA (28) reacts with aryl bromides or iodides in the presence of a palladium complex and copper(I) iodide, followed by treatment with dilute aqueous potassium hydroxide in methanol or a P source, such... 

Activated and deactivated positions in halopyridines exhibit marked difference in reactivity in palladium chemistry, whereas little difference in reactivity was observed among 2-, 4-, and 5-positions of halopyrimidines for their Sonogashira reactions [84]. While 2-iodo-4,6-dimethylpyrimidine was the most suitable substrate for preparing internal alkyne 176, the reaction of either the corresponding bromide or chloride was less efficient [85]. Good to excellent yields were obtained for the preparation of alkynylpyrimidines from most terminal alkynes with the exception of propargyl alcohols. Later reports showed that... 

Terminal acetylenes dimerize to conjugated enynes in the presence of catalytic amounts of palladium(II) acetate and the hindered phosphine tris(2,6-dimethoxyphenyl)phosphine. 1-Octyne, for instance, affords the enyne 36 5. Palladium-catalysed condensations of 1-alkynes RC=CH (R=Ph or CH2OH) with vinyl bromide, ( )-2-bromostyrene, iodobenzene and 2-bromopyridine to yield 37, 38, 39, and 40, respectively (Scheme 1), have been reported (see also References 27 and 28). The palladium[tetrakis(triphenylphosphine)]-catalysed alkynylation of 1,1-dichloroethene with terminal alkynes 41 (R = pentyl, 3-chloropropyl, Ph or SiMes) results in the eneynes 42. ... 

We could thus expect that this reaction terminated the palladium- and nor-bornene-catalyzed reaction sequence in place of the acrylic ester or terminal olefins in general. Considerable difficulties were met, however, because the alkyne interacted with all the palladium complexes of the sequence, giving rise to a number of by-products. Starting from 1 equivalent of aryl iodide, 2 equivalents of alkyl bromide, 1 equivalent of norbornene, 0.3 equivalents of aryl-acetylene, 8 equivalents of KOAc, and 0.1 equivalent of Pd(OAc)2 and adding gradually 2 equivalents of alkyl bromide and 0.7 equivalents of arylacetylene (to keep the concentration of the latter low) satisfactory results were obtained. Equation 30 reports the reaction withp-fluoroiodobenzene, n-propyl bromide, and phenylacetylene, which gave a 79% yield (71% with iodobenzene) [37]. 

It is well known that alk-2-ynones can be prepared from a copper(i) alkyne and an acyl halide. Now the troublesome metallation step can be avoided by direct reaction of the terminal alkyne with the acyl chloride in triethylamine containing copper(l) iodide and bis(triphenylphosphine)palladium(ii) chloride as catalysts. Cyanohydrins and propargyl bromides form alkynyl ethers which rearrange on treatment with lithium di-isopropylamide to form ar-allenic ketones (Scheme 59). ... 

Thorand, S. and N. Krause. 1998. Improved procedures for the palladium-catalyzed coupling of terminal alkynes with aryl bromides (Sonogashira coupling). J Org Chem 63 8851. 

---