Glaser oxidative coupling reaction

Figure 11 Principle of the four-reacting centre approach to [3]catenanes. The black triangle represents a terminal acetylenic function able to react with itself in a Glaser oxidative coupling reaction.

The reaction, Glaser oxidative coupling, is a general one, but this particular technique is recommended for the more water-... 

Oxidative coupling of a terminal alkyne is a particularly easily performed carbon-carbon 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). 

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 reaction is a reaction to synthesize a conjugate diyne by an oxidative coupling reaction in the presence of a catalytic amount of copper salt. For example, a diyne is quantitatively obtained by the reaction in the presence of air as shown in eq. (22.21) [43]. 

The Glaser reaction is an oxidative coupling of terminal alkynes 1 to yield a symmetrical Z -acetylene 2 the coupling step is catalyzed by a copper salt. Closely related is the Eglinton reaction, which differs from the Glaser reaction mainly by the use of stoichiometric amounts of copper salt as oxidizing agent. 

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. 

Condensation of 2-ethynylcyclohex-l-eneylcarbaldehyde 69 with an excess of acetone gave the ketone 544 Reaction of equimolar amounts of 85 and 86 in ethereal methanolic potassium hydroxide gave the ketone 87. Oxidative coupling of 87 under Glaser conditions afforded two separable isomeric bisdehydro[15]-annulenones 88 and 89. The mono-ds isomer 88 may have the structure 90 in which... 

Oxidative homo-coupling of terminal alkynes mediated by stoichiometric (or often excess) Cu(OAc)2. A variant of the Glaser coupling reaction. 

Whereas Glaser-type oxidative coupling opens efficient synthetic pathways toward symmetrical diynes, its performance in heterocoupling is poor. The latter may be accomplished by Cadiot-Chodkiewicz coupling of terminal alkynes with 1-haloalkynes (usually 1-bromoalkynes). The reaction is conducted in the presence of an amine and catalytic amounts of a copper(I) salt. Because, in contrast with the Glaser-type reactions described above, it follows a nonoxidative reaction mechanism, oxygen is not necessary - but needs often not to be excluded (Scheme 4) [9]. 

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 oxidative coupling of acetylenes, reported originally by Glaser and subsequently modified by others, has played a major role in the development of polyacetylene chemistry. The reaction has been reviewed comprehensively, and these reviews should be consulted for details and lists of earlier references -... 

The starting material, 2-methyl-3-butyn-2-ol, is made commercially from acetone and acetylene and is convertible into isoprene. This experiment illustrates the oxidative coupling of a terminal acetylene to produce a diacetylene, the Glaser reaction. 

The synthesis of conjugated diynes via the Glaser coupling reaction " is the classical method for homocoupling of terminal alkynes. The coupling reaction is catalyzed by CuCl or Cu(OAc)2 in the presence of an oxidant and ammonium chloride or pyridine to yield symmetrically substituted diynes. " The oxidative dimerization appears to proceed via removal of the acetylenic proton, formation of an alkynyl radical, and its dimerization. 

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