Acetylides oxidative coupling reactions

Although copper acetylides seem to be able to perform a nucleophilic substitution reaction at the sp-carbon atom of a bromo- or iodoacetylene (Cadiot-Chodkievicz reaction), this reaction has only rarely been used for the preparation of cyclic 1,3-diacetylenes. Copper-mediated oxidative coupling reactions (Glaser, Hay and Eglinton coupling) are more popular in this area and have attracted much attention in the construction of carbon-rich cyclic and polycyclic systems (see Chapter 13). One of the earliest carbon-rich systems of this type was the CzoHg system 19 [11,16] [Eq. (5)]. 

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. 

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]. 

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). 

Mechanism The Pd complex such as Pd(PPh3)4 activates the organic halides by oxidative addition into the carbon-halogen bond. The copper(I) halides react with the terminal alkyne and produce copper acetylide, which acts as an activated species for the coupling reactions. The oxidative addition step is followed by the transmetallation step. The proposed catalytic cycle is shown in Scheme 5.21. 

Alkynyl complexes, also known as metal acetylides, possess both rigid linear skeleton and tt-conjugation. In the structural aspect, alkynyls make excellent linear bridging units. By means of the reactions of transmetallation (see Transmetalation), poly-Pt-acetylides are readily synthesized (Scheme 24). Copper(I)-mediated oxidative coupling... 

Related techniques have been developed to prepare (Z-,Z)- (Z-, )- and ( -, )- dienes. Hydroboration of diacetylenes followed by protonolysis is a convenient route to (Z-,Z)-dienes, as in the conversion of 89 to 90. The requisite symmetrical diacetylenes are prepared by oxidative coupling with oxygen and cuprous chloride, as in the conversion of 1-cyclohexylethyne (78) to 89. Unsymmetrical conjugated dienes can be prepared by formation of a diacetylene ate complex, prepared from disiamylmethoxyborane by sequential reaction with different acetylides. A similar borane route to unsymmetrical diacetylenes uses dicyclohexyl methyl-thioborane. ... 

Haloalkynes 176 behave as reactive halides and palladium acetylides 177 are generated by oxidative addition, which undergo various coupling reactions as expected. 

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... 

Oxidation of Carbanions. Oxidative coupling of terminal alkynes to diynes (eq 1) with Cu(OAc)2 and pyridine can be carried out in MeOH or in benzene/ether. The reaction requires the presence of copper(I) salt the rate-determining step corresponds to the formation of the Cu acetylide. ... 

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