Aryl triflates with terminal alkynes

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253]. The 1-bromo-l,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347(254]. Enol triflates 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]. 

Aryl triflates, like aryl halides, can undergo Pd-catalyzed coupling reactions with terminal alkynes (Scheme 14), and bromoallenes react with terminal alkynes - or acetylene under similar conditions to form allenynes (Schemes 15 and 16). 

Linstrumelle and co-workers reported that vinyl and aryl halides or triflates react very rapidly with terminal alkynes, without addition of copper salt, and lead to high yields of eneynes and aryl acetylenes by using Pd(PPh3)4 as a catalyst. The nature of the amine is critical for the success of the coupling (Scheme 3, [Pd] I). However,... 

A well-established method for the synthesis of internal alkynes 34 is the Pd/Cu-catalyzed coupling of vinyl halides, aryl iodides, bromides, or triflates with terminal acetylenes 33 (Scheme 12). Nevertheless, this method suffers not only from the need for large amounts of catalyst (1-5 mol % Pd and 1-10 mol % Cul) but also from the need of higher temperatures for the aryl bromides. 

In 1991 Ortar and colleagues published a general procedure for tbe carbonylative Sonogashira couplings of vinyl triflates with terminal acetylenes [28]. Various alkynyl ketones were produced in moderate to good yields (Scheme 5.5). However, this methodology failed in the case of activated alkynes or aryl triflates. 

The formation of disubstituted alkynes by coupling of terminal alkynes, followed by intramolecular attack of an alcohol or amine, is used for the preparation of benzofurans and indoles. The benzo[il)]furan 356 can be prepared easily by the reaction of o-iodophenol with a terminal alkyne[262]. The 2-substituted indole 358 is prepared by the coupling of 2-ethynylaniline (357) with aryl and alkenyl halides or triflates, followed by Pd(ll)-catalyzed cycliza-tion[263]. 

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). 

TMS group is used for protection of terminal alkynes. However, alkynylsilanes themselves can be used for the coupling with aryl and alkenyl triflates using Pd-CuCl as a catalyst [74], Thus the internal alkyne 160 is prepared by stepwise reactions of two different triflates 157 and 159 with trimethylsilylacetylene (134) via 158. 

The carbonylation of aryl iodide in the presence of terminal alkynes affords acyl alkynes. Bidentate ligands such as DPPF give good results [241]. When PI13P is used, phenylacetylene is mainly converted to diphenylacetylene. The alkynyl ketones 488 are prepared by the reaction of the alkenyl triflate 487 with phenylacetylene and CO [242],... 

Terminal alkynes can be alkenylated by alkenyl triflates (bromides, iodides) and aryl-ated by aryl triflates (bromides, iodides). These reactions are called Cacchi coupling reactions if the reaction is catalyzed by Cu(I) and Pd(0) and if triflate reagents are employed, Sonogashira-Hagihara coupling reactions if the reaction is catalyzed by Cu(I) and Pd(0) and halides are employed as substrates, and Stephens-Castro coupling reactions for the more specialized case of the noncatalyzed coupling of copper acetylides with aryl halides. 

A milder route to arylacetylenes is the Sonogashira reaction, the direct cross-coupling of terminal alkynes with aryl halides or aryl triflates in the presence of catalytic amounts of Pd(PPh3)4 or (PPh3)2PdCl2 and using cuprous iodide as a cocatalyst in... 

Alkynylarenes. The catalyst system, usually in combination with a mild base (trialkylamine or KjCOj), is used to couple terminal alkynes with aryl iodides and triflates. A large rate enhancement is observed when an iodide salt is added, as shown in a synthesis of 1,2-bis(trimethylsilylethynyl)benzene. ... 

Several types of functionalized alkenyl(aryl)iodonium salts have been prepared by the addition of hyperva-lent iodine reagents to alkynes. Reactions of terminal alkynes with iodosylbenzene and triflic acid proceed as a highly stereoselective anti-addition to afford ( )-(P-trifluoromethanesulfonyloxyaIkenyl)phenyliodonium triflates 310 in high yield (Scheme 2.90) [446-448], Similar products were obtained Ifom the reactions of internal alkynes and parent acetylene [447],... 

Oxidative addition of aryl haUdes to an electron-rich paUadium(O) species depends substantially on the nature of the C(sp )—X bond. Relatively weak bonds, as in aryl iodides or triflates, lead to a faster oxidative addition, but the activations of stronger bonds, as in aryl bromides-and especially chlorides-require very good donor ligands. This dependence of oxidative addition rates on the nature of the electrophile in multistep reactions may lead to different rate-deterriiiiittig steps. Apart from the nature of the aromatic substrate, the possible interaction of the terminal alkyne starting material and the internal alkyne product with the metal center of the catalyst can alter the kinetics of oxidative addition. The kinetics of addition of... 

The last Pd(0) catalyzed cross-coupling reaction covered in this chapter is the Sonogashira coupling. It involves transmetallation of an alkynyl-Cufl) species to Pd followed by coupling to an aryl or vinyl iodide or triflate. The Cu(I) alkynyl complex is created in situ by the reaction of a terminal alkyne with Cul in the presence of trieth-ylamine. The reaction is most commonly used to create diaryl alkynyl products. 

Cross-coupling reactions of alkynes. Terminal alkynes undergo high yield Pd(0) catalyzed coupling reaction (72-76) with organic electrophiles. The electrophiles include vinyl, aryl, and heteroaryl halides (72-75) vinyl triflates (77J8) aryl (56,78) and heteroaryl triflates (75,78) and polyfluorophenyl perfluoroalkane sulfonates (79). Several examples are shown in equation 23 - 27 (respectively references 78,72,73,78,79). 

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