Coupling terminal alkynes with

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. ... 

Scheme 5.13 Regioisomers from coupling terminal alkynes with CO2...

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

A cross-coupling reactions of terminal alkynes with terminal alkenes 32 supported on Merrifield-resin (Scheme 4.5) in the presence of Grubs ruthenium initiator [Cl2(PCy3)2Ru = CHPh] provided efficient access to supported 1,3-dienes 33 which were transformed into octahydrobenzazepinones 34 via MeAlCl2 catalyzed Diels-Alder reaction [27]. 

Related to these strategies, Fe(OTf)3/TfOH cocatalyzed the coupling reaction of terminal alkynes with benzylic alcohols in the absence of base by means of a sp-sp C-C bond formation (Scheme 16) [32]. 

The coupling of terminal alkynes with aryl or alkenyl halides catalysed by palladium and a copper co-catalyst in a basic medium is known as the Sonogashira reaction. A Cu(I)-acetylide complex is formed in situ and transmetallates to the Pd(II) complex obtained after oxidative addition of the halide. Through a reductive elimination pathway the reaction delivers substituted alkynes as products. 

There are a number of procedures for coupling of terminal alkynes with halides and sulfonates, a reaction that is known as the Sonogashira reaction.161 A combination of Pd(PPh3)4 and Cu(I) effects coupling of terminal alkynes with vinyl or aryl halides.162 The reaction can be carried out directly with the alkyne, using amines for deprotonation. The alkyne is presumably converted to the copper acetylide, and the halide reacts with Pd(0) by oxidative addition. Transfer of the acetylide group to Pd results in reductive elimination and formation of the observed product. 

The coupling of terminal alkynes with organic halides, known as the Castro-Stephens-Sonogashira reaction, has wide applications in synthesis. The most widely used method is the Sonogashira coupling, using a combination of palladium and copper as the catalyst.13 Recently,... 

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. 

Recently, Pal et al. found that (.S )-prolinol could facilitate the coupling reaction of terminal alkynes with 3-iodoflavone under palladium-copper catalysis in aqueous DMF to give 3-alkynyl substituted flavones of potential biological interest (Eq. 4.17). The coupling of iodobenzene with terminal alkynes at room temperature in water without any cosolvent was completed within 30 minutes, affording the desired product in good yield.36... 

Amatore et al. developed an aqueous cross-coupling reaction of terminal alkynes with 1-iodoalkynes using a water-soluble Pd(0) catalyst prepared in situ from Pd(OAc)2 and sulfonated triphenylphosphine P(C6H4 — m-SCENa (TPPTS) without Cu(I) promoter, giving diynes with moderate yields (43-65%)(Eq. 4.22) 42... 

Another example of the addition of terminal alkynes to C=N in water is the coupling of alkynes with in-situ-generated A-acylimines (Eq. 4.32) and A-acyliminium ions (Eq. 4.33). In 2002, Li et al. developed a coupling reaction of alkynes with A-acylimines and A-acyliminium ions mediated by Cu(I) in water to generate propargyl amide derivatives.57 Either an activated imine derivative or imininum derivative was proposed as the intermediate, respectively. 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

Dolphin has employed the Sonogashira coupling of terminal alkynes with zinc(II)-10-iodo-5,15-diphenylporphyrin (126) to prepare a series of alkynyl derivatives 127 [87], and similar syntheses of p-alkynyl porphyrins have been described [88]. 

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). 

Cross-coupling of terminal alkynes with aryl and vinyl halides are usually carried out in organic solvents, such as benzene, dimethylformamide or chloroform with a palladium-based catalyst and a base scavenger for the hydrogen halide. Copper(I) iodide is a particularly effective co-catalyst allowing the reaction to proceed under mild conditions. 

Halogen atoms. The introduction of side-chains on 9-trifluoromethyl-paullone 409 can be accomplished applying a Stille coupling (Scheme 86, Section 5.2.1.1 (2005EJM655)). Similarly, a Heck reaction of iodo 409 with terminal alkenes under standard conditions affords 2-substituted paullones 413 exclusively as E-isomers. The reaction of terminal alkynes with 409 in the presence of cuprous iodide and a palladium catalyst in triethylamine furnishes the 2-alkynyl-paullones 412 (2000BMCL567). 

Scheme 9.12 Rh(l)-catalyzed coupling of terminal alkynes with allylamine - Catalytic cycle.

The Sonogashira reaction is a C-C coupling reaction of terminal alkynes with aryl or vinyl halides in presence of Pd(0) metal and/or Cu(i) catalyst. These compounds are useful in synthesizing species having pharmaceutical... 

Bisethynylation of yic-dichloroethylenes.u Enediynes can be prepared by the palladium-catalyzed coupling of terminal alkynes with v/c-dichloroethylenes, particularly with the ds-isomer (equation I). 

Cross-coupling Reactions of Terminal Alkynes with Organic Halides... 

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