Glaser coupling copper

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 Glaser Coupling (or Hay Coupling) is a synthesis of symmetric or cyclic bisacetylenes via a coupling reaction of terminal alkynes. Mechanistically, the reaction is similar to the Eglinton Reaction the difference being the use of catalytic copper(I), which is reoxidized in the catalytic cycle by oxygen in the reaction medium. 

The related Hay Coupling has several advantages as compared with the Glaser Coupling. The copper-TMEDA complex used is soluble in a wider range of solvents, so that the reaction is more versatile. 

The mechanism of the Glaser coupling and related methods is very complex and is not fully understood. Studies revealed that the mechanism is highly dependent on the experimental conditions. The early proposal involving a radical mechanism has been rejected. The currently accepted mechanism involves dimeric copper(ll)acetylide complexes. 

Cu-catalyzed Glaser coupling Preparation of symmetrical conjugated diynes and polyynes by the oxidative homocoupling of terminal alkynes in the presence of copper salts. 186... 

A common by-product in the Sonogashira reaction is the homo-coupled diyne (Scheme 2.127). This is usually due to the presence of O2. This is a long-known copper-catalysed reaetion called Glaser coupling, which is a form of homo-coupling (Section 2.10). Palladium may also catalyse this reaction. 

Scheme 15.8 Copper-mediated Glaser coupling of phenylacetylene.

Scheme 15.9 Copper-catalysed Glaser coupling of 1-alkynyl ethers.

A copper- and amine-free version of the Sonogashira reaction has also recently been achieved by employing air-stable aminophosphine ligands in the presence of an inorganic base, thus excluding the formation of Glaser coupling products. ... 

The Castro-Stephens reaction is the cross coupling of a copper acetylide (1) and an aryl or vinyl halide (2) to give a disubstituted alkyne (3). The reaction, which shares some common elements with the Sonogashira, Cadiot-Chodkiewicz, Rosenmund-von Braun, Hay, and Glaser coupling reactions, was discovered by Stephens and Castro in the early 1960s and has found some applications in synthesis. " ... 

The alkyne-alkyne coupling reaction is mostly promoted with copper-catalysts (Glaser coupling and variants). However, there are examples known for palladium-... 

GLASER - CHODKIEWCZ Acetylene Coupling Polyacetylenes from monoacetylenes in the presence of copper salts. 

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. 

All three coupling procedures are suitable to give high yields under mild reaction conditions. Many functional groups do not interfere. For the application in organic synthesis the Eglinton variant may be more convenient than the Glaser method a drawback however is the need for stoichiometric amounts of copper salt. 

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