Copper homocoupling reactions

Kang et al. compared the organolead homocoupling reactions catalyzed by either copper or palladium sources.95 Both reactions proceed at room or moderate temperature. Yields were good with both metal catalysts, although differences were noted both in the solvent and the amount of catalyst employed. The reactions with copper(i) iodide... 

Recently, the catalytic use of Cu(I) salts was applied to the aryl-aryl and aryl-vinyl couplings and to the allylation of furans and thiophenes, even without the benefit of such activation. In parallel with the use of Cu(I) salts, the reactivity of stoichiometric amounts of Cu(II) was estabhshed for the homocoupling of vinyltins" °°. Copper nitrate was found to be particularly efficient, leading to the cyclotrimerization of l-bromo-2-stannylaUcenes . Lately, the use of catalytic amounts of CuCla was shown to be superior to the use of Cu(I) salts for achieving these homocoupling reactions . ... 

Alkenylstannanes can be subjected to a homocoupling reaction by a copper(II)-mediated anodic oxidation [Eq.(14c)J [132b]. 

However, the use of basic anions is not the sole approach followed to obtaining basic ILs. Liquid salts bearing this additional property can be prepared also by incorporation of a basic center into the cation. This approach generally affords more thermally stable ILs than those based on basic anions, which frequently present relatively low decomposition temperatures. Basic ionic liquids bearing aliphatic or aromatic amines on the side chain(s) have been synthesized and, recently, some of these have been used as both the solvent and base for Heck, copper free Sonogashira, and for homocoupling reactions of terminal alkynes (Figure 4.2). 

Reproduced from Chen L, Betsegaw E, Lemma BE, Rich JS, Mack J. Freedom a copper-free, oxidant-free and solventfree palladium catalysed homocoupling reaction. Green Chem 2014 16 1101-3. With permission from the Royal SocBty of Chemistry. 

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. 

It should be pointed out that the homocoupling of alkyl halides could be completely eliminated when the CuI/PPhs complex vras used. The cycloalkylation of 5-bromo-l,2-epoxypentane with highly reactive copper, which was generated from lithium naphthalenide and CuI/PPhs, gave a 37 1 mixture of cyclopentanol and cyclobutylmethanol in excellent yield (87%) with no evidence of any homocoupling reaction. 

Tris-di-yne macrobicyclic compounds 241-243 have been obtained in [166] from the corresponding C -symmetric tripodal precursors with terminal aUsyne bonds using their copper(I)-cata-lyzed homocoupling reactions by Scheme 2.144. 

Symmetrical biaryls are important intermediates for synthesising agrochemicals, pharmaceuticals and natural products (1). One of the simplest protocols to make them is the Ullmann reaction (2), the thermal homocoupling of aryl chlorides in the presence of copper iodide. This reaction, though over a century old, it still used today. It has two main disadvantages, however First, it uses stoichiometric amounts of copper and generates stoichiometric amounts of CuL waste (Figure 1, left). Second, it only works with aryl iodides. This is a problem because chemicals react by their molarity, but are quantified by their mass. One tonne of iodobenzene, for example, contains 620 kg of iodo and only 380 kg of benzene . 

Cyclobutane was also prepared from 1,4-dichlorobutane in 70% yield via a gas-phase reaction with potassium/sodium vapor at 190-270 C/0.1 Torr.8 It has recently been found that activated copper(0) was able to induce a homocoupling of 1,4-diiodobutane at —70 "C in tetrahydro-furan to cyclobutane in a meager 14% yield.9... 

A classic example is the homocoupling of aryl iodides in the presence of copper, known as the Ullmann reaction (Figure 1.17). This reaction gives symmetric biaryls,... 

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. 

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 ... 

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