Glaser-type 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]. 

Glaser-type reactions yield compounds 151 and 152 containing thiophene-bisacetylene-thiophene units that were characterized by X-ray crystal analysis <2006EJO5264>. Unfortunately, these compounds are obtained only in low yields (<10%). 

Scheme 1. General description of (a) the oxidative Glaser-type homocoupling reaction and (b) nonoxidative Cadiot-Chodkiewicz heterocoupling (X= Br, I).

The main driving forces behind the development of new tertiary phosphine palladium complexes for C(sp )—C(sp) couplings have been (i) a reduction or elimination of side reactions, such as Glaser-type homocouplings (ii) the development of environmentally friendly reaction protocols, such as copper-free reactions in benign solvents (iii) the improvement of catalyst stabihty and activity [higher turnover number (TON) and turnover frequency (TOP)] and (iv) a cost reduction by using less-expensive aryl bromides, or even aryl chlorides under mild reaction conditions, for example, at ambient temperature. 

The homo-coupling of terminal alkynes is a frequent side reaction in Sonogashira and Heck-type alkynylation reaction. However, this reaction can be optimized to obtain Glaser-type products in good yields. The power of this reaction has been demonstrated in the synthesis of a wheel-like structure by Hoger and colleagues (Experimental Procedure below). ... 

Controlled oxidation of organometallic species may lead to the creation of a C-C bond. In acetylene chemistry, the Glaser reaction and its variations [29] are among the most ancient reactions of this type, and rely on the oxidation by air (or cupric ions) of alkynyl copper(I) species generated in situ. These very mild conditions allow the use of a large range of terminal alkynes, such as ethynylated heterocycles (Figure 7a) [26b]. 

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 Cadiot-Chodkiewcz and Glaser reactions are the synthetic reaction with acetylene type compounds. As the acetylene compounds easily form stable organo-copper compounds, these acetylenecopper compounds react directly with halides to afford the acetylene derivatives. This synthetic reaction is called the Castro reaction [43]. For example, as shown in eq. (22.22), aryl compounds having functional groups such as OMe, NO2 and COOH are able to condense with copper acetylides... 

Ethynylcopper compounds, isolated or generated in situ, play a fundamental role in acetylene synthesis. The reactions basically are of three types the Glaser and Cadiot-Chodkiewicz oxidative couplings employed in polyacetylene synthesis, and the Castro coupling for preparing arylacetylenes (for comprehensive reviews of these reactions see ref. 9). 

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