Oxidative acetylenic homocoupling

Because all currently known mechanisms of oxidative acetylenic homocouplings are very specific to single reaction conditions, e.g. pH or oxidation state of the used copper salt, this section summarizes the most reasonable mechanistic ideas proposed for the commonly utilized coupling procedures. 

It must be emphasized that current mechanistic understanding of copper-mediated oxidative acetylenic couplings is unsatisfactory. Several studies have shown the strong dependency of the mechanism on the experimental setup, suggesting highly complex coherences and interactions. Nevertheless, the mechanistic idea of Bohlmann et al. described above still provides the most accepted picture for Glaser-type oxidative acetylenic homocouplings. 

Scheme 6.1 (A) Synthesis of radialenes 1 by oxidative acetylenic homocoupling [17], and (B) Synthesis ofTTF based [18]annu-lenes 2 and 3 by Pd-mediated homocoupling [25], Reagents and conditions (a) TBAF, THF (b) [Cu(OAc)2], 02, py/PhH (c) Cul, [PdCI2(PPh3)2], Et3N.

It should be noted that most presentations of the Glaser and related acetylene homocouplings show a simpler mechanism involving base-catalyzed formation of a copper(I) acetylide 8, oxidation to copper(ll) acetylide 9, and homocoupling of the resultant acetylenic radical 10 to afford... 

Oxidative acetylenic coupling to produce 1,3-diynes is an important reaction with broad applications. Despite tremendous improvements in homocoupling processes, notably the Hay procedure, the construction of un-symmetrical conjugated diynes from two different terminal allqmes has only been recently reported. In 2009, Lei and co-workers described a copper/ nickel-co-catalyzed aerobic cross-coupling method that tolerated a variety of functional groups such as amides, halides and free propargylic alcohols (Scheme 9.24). ... 

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 ... 

It has proven possible to add oxidatively highly activated copper metal ( Rieke copper ) to alkynyl bromides in moderate yields, to furnish acetylenic copper compounds (equation 44)10. Bubbling oxygen through the system resulted in the formation of homocoupling products. 

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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