Aryl bromides terminal alkyne arylation

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253). The 1-bromo-1,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347[254], Enol tritlates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256] Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

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). 

Conditions based on stoichiometric amounts of silver oxide have been developed by Mori et al. for the synthesis of arylated alkynes from terminal alkynes and aryl iodides. Under such conditions, neither silylated alkynes nor aryl bromides or triflates did not undergo coupling (Scheme 10.78).129,130... 

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). 

Neutral alkynylcopper compounds are not prepared by transmetalation of alkynyllithium compounds. Rather, they are obtained by partially deprotonating terminal alkynes with amines and capturing the ammonium acetylide formed at equilibrium with Cul (—> R-C=C-Cu + R3NH I example Figure 16.7). Copper(I) cyanide couples with aryl iodides and -bromides in a similar fashion as alkynylcopper compounds (which may well be conceived as their carba analogs). 

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... 

Sodium tetraalkynyl aluminate salts can be prepared from sodium aluminum hydride 172 and four equivalents of a terminal alkyne. The sodium tetraalkynyl aluminate salts are air stable and easily handled. The fairly reactive alkynyl substituent can be transferred in a cross-coupling mode to aryl bromides such as 5-bromopyridine. All four alkynes are transferrable from one aluminate salt [82]. 

Cross-coupling of acetylenes with aryl halides E)-alkenylarenes. (E)-Atkenyl-zirconium compounds (1), obtained by hydrozirconation of terminal alkynes, react smoothly with aryl bromides and iodides in the presence of 10 mole % of Nl[P(CeH5)3]4 to form (E)-alkenylarenes (2) in yields generally of 70-95%. ... 

JV-carbamoyl-substituted heterocyclic carbene/Pd(II) complexes in the presence of PPh3 and Cul are reported to mediate the cross-coupling of aryl iodides with terminal alkynes at very mild temperature [67]. The system is compatible with aryl bromides however, the temperature then required is 80 °C. In all reactions, the addition of 1 mol% of phosphine increased the yield of product. The role of the phosphine ligand is not completely understood but may facilitate the initial generation of a Pd(0) species. 

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