Copper acetylides Cadiot-Chodkiewicz coupling

Fig. 16.33. Pd(0)-catalyzed alkynylation of a copper acetylide with a silylated ethynyl iodide in a two-step synthesis of a monosilylated 1,3-butadiyne. If the same copper acetylide is alkynylated with higher alkynyl iodides and subsequently heated with potassium carbonate in toluene, monoalkylated 1,3-butadiynes result - The Pd-free alkynylation of a copper acetylide ("Cadiot-Chodkiewicz coupling") is shown in Figure 16.9.

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 ... 

The Cadiot-Chodkiewicz coupling typically proceeds under conditions which are considerably milder than Castro-Stephens reactions. Triethylsilylacetylene 74 rapidly undergoes Cadiot-Chodkiewicz coupling with alkynyl bromide 75 to generate the unsymmetrical bisalkyne 76 in nearly quantitative yield when those two reactants are treated with catalytic cuprous chloride and catalytic ammonium hydroxide in -butylamine solution. This coupling process affords one of the best entries into compounds such as 76 and is permissive of TES and larger silylated copper acetylide species because of the lower reaction temperature. ... 

This side-reaction is most serious in the case of acetylenes RC=CH with a relatively low acidity aliphatic 1-alkynes, e.g. 1-octyne, and acetylenic alcohols HCaC(CH2)nOH with n > 2, give reduced yields (40-50%) in the coupling reaction. In many other reactions, yields are high. Since the bromoalkyne usually has the highest "added value", economical considerations prescribe the use of an excess of the free acetylene, especially when it is inexpensive, e.g. propargyl alcohol. The mechanism of the Cadiot-Chodkiewicz reaction has not been studied in detail, but is seems likely that a copper acetylide ROCCu is formed first it often appears as a yellowish suspension. 

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. " ... 

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