Aryl triflates terminal alkyne arylation

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 carbonylation of aryl iodides in the presence of terminal alkynes affords the acyl alkynes 565. Bidentate ligands such as dppf give good results. When PhjP is used, phenylacetylene is converted into diphenylacetylene as a main product[4l5]. Triflates react similarly to give the alkynyl ketones 566[4I6], In... 

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). 

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]. 

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],... 

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... 

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. 

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... 

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). 

Terminal alkynes can be coupled directly to aryl, heteroaryl, and vinyl halides or triflates in the presence of a Pd-catalyst and a base, which frequently is an amine acting both as solvent and as scavanger for the respective acid formed in the reaction. The mechanism appears to involve oxidative addition of the sp2-halide or triflate to Pd(0), followed by alkynylation of the intermediate organopalladium complex and reductive elimination of the substituted alkyne. Copper(I) iodide is a particular effective cocatalyst, allowing the reaction to proceed at room temperature (91MI2). 

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. ... 

Palladium-catalyzed annulations of terminal alkynes by functionally substituted aromatic or vinylic halides or triflates often employ copper salts and most likely proceed by initial cross-coupling to produce the corresponding aryl alkyne or enyne (Eq. 1). 

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],... 

Similarly functionalized alkenyl(aryl)iodonium triflates 312 were prepared by the addition of (aryl)fluoroiodonium triflates 311 to terminal alkynes (Scheme 2.91) [45,48]. 

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,... 

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. 

---