Reactions of Terminal Alkynes

Because of the slightly acidic nature of the sp C-H bonds, the reaction of metal acetylides with various electrophiles is one of the most general strategies in organic transformations. Traditionally, such reactions are carried out by using alkali metal acetylides which are air and water sensitive. On the other hand, there is much interest in developing transition-metal catalyzed terminal alkyne reactions involving soft and more stable C-M bonds as reaction intermediates, because many such reactions can tolerate water. 

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Terminal alkynes undergo the above-mentioned substitution reaction with aryl and alkenyl groups to form arylalkynes and enynes in the presence of Cul as described in Section 1.1.2.1. In addition, the insertion of terminal alkynes also takes place in the absence of Cul, and the alkenylpalladium complex 362 is formed as an intermediate, which cannot terminate by itself and must undergo further reactions such as alkene insertion or anion capture. These reactions of terminal alkynes are also treated in this section. 

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]. 

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... 

For the development of the oxidative homocoupling reaction, in 1955 Chodkiewicz and Cadiot explored a Cu(I)-catalyzed heterocoupling reaction of terminal alkynes with 1-bromoalkyne in the... 

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... 

The addition of terminal alkynes to carbon-carbon double bonds has not been explored until recently, possibly because C=C double bonds are not as good electrophiles as C=N or C=0. In 2003, Carreira et al. reported the first conjugate addition reaction of terminal alkynes to C=C catalyzed by copper in water. The reaction proceeded with derivatives of Meldrum s acid in water in the presence of Cu(OAc)2 and sodium ascorbate (Eq. 4.35).59 However, this method was limited to C=C double bonds with two electron withdrawing groups. 

Recently, on the basis of the Markovnikov addition of water to alkynes, Trost et al. developed a three-component addition reaction of terminal alkynes, water, and methyl vinyl ketone, affording 1,5-diketones in DMF/water in the presence of ruthenium and indium catalysts (Eq. 4.38). 

Generally, organocopper compounds can be prepared by transmetallation between copper salts and organometallic reagents such as RLi, RMgX, and RZnX.53,53a,53b Copper alkynides can be obtained by reaction of terminal alkynes... 

Table 4 Photo-induced reactions of terminal alkynes with (PhE)2/(PhTe)2 (E = S or Se) binary system...

Acyl complexes can also result from the reaction of terminal alkynes with cationic, hydrated complexes of iron (Entry 4, Table 2.7) [47]. An electrophilic vinylidene complex is probably formed as intermediate this then reacts with water and tautomerizes to the acyl complex. 

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). 

An important contribution that developed into the catalytic use of the vinylidene complexes for the construction of carbon frameworks was reported by two research groups independently for the preparation of Fischer-type carbene complexes by the reaction of terminal alkynes with pentacarbonylchromium or tungsten species in the presence of oxygen nucleophiles. 

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... 

Besides electrophilic addition, terminal alkynes also perform acid-base type reaction due to acidic nature of the terminal hydrogen. The formation of acetylides and alkynides (alkynyl Grignard reagent and aUcylnyllithium) are important reactions of terminal alkynes (see Section 4.5.3). Acetylides and alkynides undergo nucleophilic addition with aldehydes and ketones to produce alcohols (see Section 5.3.2). 

Gold has even shown its ability as a nucleophile activator in three-component reactions of terminal alkynes, aldehydes and amines [186]. In the case of chiral amines, excellent diastereoselectivities were obtained [187] (Scheme 8.29). ... 

Dehydrogenative silylation has also been observed for terminal alkyne substrates. Doyle and co-workers reported in 1991 that a small amount (6%) of alkynylsilane was observed in the product mixture that results from reaction of phenylacetylene and Et3SiH catalyzed by Rh2(pfb)4.41 The remaining components of the product mixture resulted from hydrosilylation. Crabtree and co-workers have found that in reaction of terminal alkynes with various tertiary silanes, dehydrogenative silylation can become the predominant route, depending on reaction conditions [Eq. (7)].42... 

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

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