Oxidative Acetylide Coupling

The oxidative coupling of two terminal alkynes via their copper acetylide complexes to form a 1,3-butadiyne function is known variously as Glaser, Eglinton, or Hay 

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Scheme 10.7 Oxidative acetylide coupling in the formation of [3]catenanes 35 and 39 reported by Sauvage and coworkers.

The first method involves oxidative homo-coupling of bis (terminal alkynyl) complexes in the presence of a catalytic amount of a copper(I) halide and O2 as the oxidizing agent (Scheme 5.1, Eq. 5.1) [10]. The use of this catalyst system in organic synthesis is extensive and is better known as Hay s coupling reaction [11]. Extension of this methodology to organometallic synthesis was demonstrated by the conversion of trans-bis(acetylide) monomers into polymeric complexes. It is... 

The Glaser coupling reaction is carried out in aqueous ammonia or an alcohol/ammonia solution in the presence of catalytic amounts of a copper-I salt. The required copper-II species for reaction with the acetylide anion R-C=C are generated by reaction with an oxidant—usually molecular oxygen. For the Eglinton procedure, equimolar amounts of a copper-II salt are used in the presence of pyridine as base. 

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 combination of these findings with the aforementioned results of Beckhaus, Rosenthal, and Mach may also be interpreted in terms of an alternative mechanism for the polymerization of acetylene, which differs from that of Alt [12] (Scheme 10.3). In the absence of coupling, as in 11, or of twofold C—H activation as found in 12, the steps after substitution of MeiSiC=CSiMci by HC=CH and formation of Cp2Ti(i]2-HC2H) are (i) oxidative addition to give the hydrido-acetylide Cp2Ti(H)(C=CH),... 

C6HBC C.C C.C C.C C.C6H5 mw 250.28, yel ndls, mp li5—16°(browning), stable at RT for 13 months in the dark when placed on a hot metallic place it. decompd explosively with much soot. It shows no color reaction with sulfuric acid is more sol than tolan Sc (C6H.5C C)3 in polar solvs such as MeOH, ale Sc acetone. It was prepd by oxidative coupling of cuprous acetylide, C6HB.C C.C C.Cu, with CuCl2 (Refs)... 

It was shown that, on aging in air, copper(I) acetylide oxidises to this, which was also prepared independently from butadiyne. It also seems to result from reaction of copper solutions of mixed I and II valencies with acetylene. Further oxidation appears to give higher homologues. The explosive properties remain. Essentially, this is the Cu II mediated oxidative coupling, by which higher acetylenes are normally prepared synthetically, operating spontaneously. 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

As already mentioned, there have been few mechanistic examinations of the copper-catalyzed Cadiot-Chodkiewicz heterocoupling reaction. Kinetic studies with the less reactive chloroalkynes [11a] have led to the assumption, shown in Scheme 7, that coupling between alkynes and haloalkynes proceeds through initial formation of copper(I) acetylides, probably formed by an acetylenic activation process similar to that described above for oxidative homocouplings. Subsequently, two reaction pathways may be reasonable ... 

Fig. 16.30. Pd(0)-catalyzed arytation of a copper acetytide at the beginning of a three-step synthesis of an ethynyt aromatic compound. Mechanistic details of the C,C coupling Step 1 formation of a complex between the catalytically active Pd(0) complex and the arylating agent. Step 2 oxidative addition of the arylating agent and formation of a Pd(II) complex with a cr-bonded aryl moiety. Step 3 formation of a Cu-acetylide. Step 4 trans-metalation the alkynyl-Pd compound is formed from the alkynyl-Cu compound via ligand exchange. Step 5 reductive elimination to form the -complex of the arylated alkyne. Step 6 decomposition of the complex into the coupling product and the unsaturated Pd(0) species, which reenters the catalytic cycle anew with step 1.

A more general and efficient approach to alkynyl carboxylates, also thought to involve alkynyliodonium carboxylate intermediates, entails the treatment of bis(acyloxyiodo)-arenes with alkynyllithium reagents (equation 88)81. These reactions are best conducted in the presence of 2-nitroso-2-methylpropane in order to suppress oxidative coupling of the lithium acetylides by the acyloxyiodanes. 

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). 

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