Coupling reactions leading to diynes

Oxidative coupling of a terminal alkyne is a particularly easily performed carbon-carbon r-bond forming reaction, which results in a good yield of the symmetrical diacetylene. A widely used procedure involves the oxidation of the alkyne with air or oxygen in aqueous ammonium chloride in the presence of a copper(i) chloride catalyst (Glaser oxidative coupling). 

A modified procedure illustrated by the synthesis of a diynediol (Expt 5.27) from the acetylenic alcohol, 2-methylbut-3-yn-2-ol, uses methanol and pyridine as the solvent, the latter acting also as a complexing agent for the copper(i) ions. An alternative effective coupling system involves the use of copper(n) acetate in pyridine which does not require the use of air or oxygen. 

A coupling procedure particularly suited to the synthesis of unsymmetrical diacetylenes involves the reaction of a terminal acetylene with a 1-bromo-acetylene in the presence of a catalyst consisting of a solution of copper(i) chloride in a primary amine to which small quantities of hydroxylamine hydrochloride is added (the Cadiot-Chodkiewicz coupling). 

The organic base serves to remove the liberated protons and to assist solution of the copper(i) catalyst by the formation of a complex. Hydroxylamine hydrochloride helps to maintain an adequate concentration of copper(i) ions, which however is best kept rather low otherwise unwanted self-coupling of the bromoalkyne occurs. The reaction is illustrated in Expt 5.28 by the coupling of co-bromophenylacetylene with 2-methylbut-3-yn-2-ol. 

The coupling of terminal acetylenic compounds with the reactive allylic bromides in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and copper(i) iodide appears to be a useful route to the non-conjugated enyne system, e.g. the formation of hex-5-en-2-yn-l-ol.46 

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In addition to the previously described coupling of two diynes at a single metal center, there are examples of coupling reactions of two diynes between two metallocene fragments (complexes 22 and 23). Acidolysis of complex 22 gives the trans-3,4-dibenzyli-dene-l,6-diphenyl-l-hexen-5-yne 29 [26], The corresponding reaction of complex 23 (Fig. 10.4) does not lead to the expected radialene 30, which seems to be unstable, but forms, after an H-shift, the ds-3,4-dibenzylidene-l,6-diphenyl-l-hexen-5-yne 31 (Fig. 10.5) [26],... 

A side reaction leads to the formation of diynes if a second mol ecule of acetylide succeeds in displacing the original coupling partner from palladium, allowing reductive elimination. 

An endo-exo intramolecular cyclization of a,P-diynylsulfides is brought about by iodonium salts and leads to fused 2H-1-benzothiopyrans (Scheme 118). The reaction is successful with 1,5-, 1,6-, and 1,7 diynes and a heteroatom can be accommodated in the alkyl chain. Furthermore, a substituent can be present at the other terminal site and the iodine which is perforce introduced into the fused alicyclic ring allows elaboration by Pd-catalyzed coupling with a variety of acetylenes <1998AGE3136>. 

In the polycoupling reactions, the formation of the diyne units proceeded via a Glaser-Hay oxidative coupling route [35-38]. Despite its wide applications in the preparation of small molecules and linear polymers containing diyne moieties, its mechanism remains unclear [38-40]. It has been proposed that a dimeric copper acetylide complex is involved, whose collapse leads to the formation of the diyne product (Scheme 9). 

The catalytic intramolecular coupling of two C=C bonds at a ruthenium site leads to cyclization reactions. For example, although generally less reactive than a,co-diynes or enynes, 1,6-dienes react with [RuC12(COD)] in 2-propanol, leading to exo-methylenecyclopentanes in excellent yields [13] (Eq. 8). The mechanism suggests the formation of the ruthenacyclopentane(hydrido) intermediate 19. 

Ruthenium-catalyzed reactions involving diynes generally lead to the intramolecular oxidative coupling of the two C=C bonds. Bicyclic compounds can be synthesized in the presence of another unsaturated molecule. 

The Pd-catalyzed cross-coupling of diynylzincs, formed as shown below, with aryl halides leads to disubstituted conjugated diynes. This procedure allows great flexibility in the choice of reaction partners. 

Coupling is an important reaction of alkynes that leads to di-ynes. It occurs under a variety of condi-tions,32 but is particularly important when alkynylcopper derivatives are involved. Two classical alkyne coupling reactions involve copper derivatives. In the Glaser reaction,33 where an alkyne such as phenylacetylene reacts with basic cupric chloride (CuCl2), subsequent air oxidation gives a diyne (in this case 26 in 90% yield). 

Coupling of alkynes with organoiodides. With Cul and pyrrolidine as promoters, die reaction of 1-alkynes with iodoalkynes leads to unsymmetrical 1,3-diynes (17 examples. 

Murakami and co-workers further developed this reaction to a [4+2+2] cycloaddition [46, 47]. Cyclobutanone (52) can be effectively coupled with 1,6-diyne (53b) to afford bicyclo[6,3,0]undecadienone 54b in excellent yield (91%). Two possible mechanisms were proposed for this transformation (Scheme 10). Either pathway leads to intermediate 57c, which upon p-C elimination and reductive elimination of the four-membered ring furnishes the final product. 

Abstract Electron-rich mthenium(II) catalysts of type (C5R5)XRuL are used to perform selective carbon-carbon bond formation by combination of simple substrates such as the coupling of functional alkynes and alkenes with a variety of unsaturated molecules (alkynes, diynes, alkenes, dienes) or non-unsaturated molecules such as alcohols or water, often with atom economy. Various selective transformations are developed and can provide access to high multifunctional molecules. These reactions often proceed via an initial oxidative coupling leading to a ruthenacycle intermediate. 

Ruthenium-catalyzed reactions involving diynes generally lead to the intramolecular oxidative coupling of the two C=C bonds. Bicyclic compounds can be synthesized in the presence of another unsaturated molecule. The Cp RuCl(cod)-catalyzed reaction of 1,6- and 1,7-diynes in the presence of monoalkynes led to a [2-f2-f2] cycloaddition. Various substituted benzenes were thus produced in good yields [18-36]. The cycloaddition of unsymmetrical diynes usually favors meta-substituted products by means of judicious choice of substituents as inEq. (11) [18]. 

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