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. 

An interesting aspect of acetylene dimerization was recently added by Haley s group [25]. The outcome of the cyclization of the precursor 60 depends strongly on the catalyst used for the coupling reaction. Cu-mediated coupling conditions [Cu(OAc)2, py] formed the macrocycle 61 as a sole product in 70 % yield whereas acetylene homocoupling with [PdCl2(dppe)] furnished 61a exclusively (84%) (Scheme 6.9). 

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.

Bauerle and coworkers have synthesized a re-conjugated catenane, utilizing Cu(I) templation and a newly developed method for acetylenic homocoupling based on the reductive elimination of platinum to generate the desired C-C bond formation (Scheme 6.16) [65,66]. The C-shaped 57 was first preorganized around Cu(I), resulting in the homoleptic bis-phenanthroline complex 58. After removal... 

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... 

Pascanu V, CSrcu M, Socaci C, Terec A, Soran A, Grosu I (2013) Synthesis of cryptands with di-yne units via acetylenic homocoupling reactions of C, tripodands. Tetrahedron Lett 54 6133-6136... 

Homocoupling of terminal acetylenes first described by Glaser in 1869 [1] occurs in presence of a base, a copper(I) salt (usually CuCl) and dioxygen (Scheme la). Because of the widespread occurrence of di- and polyacetylenic structures in... 

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. 

A problem that may be encountered when using the original procedure is that some functionally substituted acetylenes do not survive the acidic reaction conditions. Furthermore, one or both undesired homocoupled diynes may be formed, and these are often difficult to separate from the desired product. A number of methods are available that minimize or circumvent these shortcomings. For example, coupling of terminal alkynes with in situ preformed copper alkynylides accommodates the cleavage-prone Me3Si moiety. " ... 

Another protected acetylene is propargyl alcohol and 2-methyl-3-butyn-2-ol (111). After coupling with halides, deprotection by alkaline hydrolysis gives 1-alkynes. Dehydro[12]annulenes 114 was synthesized from 111 as the proteeted acetylene. Monocoupling of o-dibromobenzene with 111 afforded the proteeted alkyne 112. Treatment of 112 with Pd(0)-Cul catalyst, NaOH, and quaternary ammonium chloride generates the deprotected 1-alkyne 113 in situ. Subsequent homocoupling of three molecules of 113 afforded the aimulene 114 in 36%... 

A severe limitation in the reported reaction was that substitution of the aryl group in the acetylene for a simple alkyl group resulted in low yields of the desired coupling products. The major adduct arises from a homocoupling of two norbomadienes (forming NBD dimers ). The lack of reactivity and the resulting competitive side processes had to be overcome before the reaction would be sufficiently reliable for use in synthesis. 

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