Acetylides coupling reactions, 1-haloalkynes

More often such bromo- and iodoalkynes are employed with another synthetic goal in mind, namely, in the Cadiot-Chodkiewicz reaction for the formation of symmetric or asymmetric 1,3-diynes by reaction of the haloalkyne with a terminal alkyne (Figure 13.25). Additional reagents essential for the success of this reaction are one equivalent or more of an amine and a substoichiometric amount of Cul. As with the Cacchi and Stephens-Castro coupling reactions of Section 13.3.4, a Cu-acetylide is the reactive species in the Cadiot-Chodkiewicz coupling. It is formed in step 1 of the mechanism illustrated in Figure 13.25. 

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

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 ... 

Although there are cases in which the use of a cuprous acetylide rather than a terminal acetylene is preferred, the use of a terminal acetylene is much easier and, as described later, more common. The reaction between a terminal alkyne and a haloalkyne using catalytic amounts of a Cu(I) salt in an amine base is known as the Cadiot-Chodkiewicz coupling (Scheme 9.23) [175]. 

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