Copper acetylide complexes

The oxidative coupling of two terminal alkynes via their copper acetylide complexes to form a 1,3-butadiyne function is known variously as Glaser, Eglinton, or Hay... 

In the polycoupling reactions, the formation of the diyne units proceeded via a Glaser-Hay oxidative coupling route [35-38]. Despite its wide applications in the preparation of small molecules and linear polymers containing diyne moieties, its mechanism remains unclear [38-40]. It has been proposed that a dimeric copper acetylide complex is involved, whose collapse leads to the formation of the diyne product (Scheme 9). 

The reactors were thick-walled stainless steel towers packed with a catalyst containing copper and bismuth oxides on a siliceous carrier. Tliis was activated by formaldehyde and acetylene to give the copper acetylide complex that functioned as the true catalyst. Acetylene and an aqueous solution of formaldehyde were passed together through one or more reactors at about 90—100°C and an acetylene partial pressure of about 500—600 kPa (5—6 atm) with recycling as required. Yields of butynediol were over 90%, in addition to 4—5% propargyl alcohol. 

Secondary acetylenic alcohols are prepared by etliynylation of aldehydes higher than formaldehyde. Although copper acetylide complexes will catalyze this reaction, the rates are slow and the equilibria unfavorable. The commercial products are prepared with alkaline catalysts, usually used in stoichiometric amounts. 

In the presence of copper acetylide complexes, the reaction of aldehydes with acetylene and secondary amines (eq. (2)) leads to propargylamines [6]. In contrast to the synthesis of butynediol, this reaction is catalyzed homogeneously. 

Mechanistic studies were undertaken to analyze the reactivity of bis-NHC systems, showing the formation of two intermediates during the first step a copper acetylide complex and an imidazoli(ni)um salt (Scheme 8.19). Interestingly, in... 

Available information on the mechanism of cyclocondensation is rather contradictory. According to one hypothesis, both the condensation of aryl halides with copper acetylides and the cyclization occur in the same copper complex (63JOC2163 63JOC3313). An alternative two-stage reaction route has also been considered condensation followed by cyclization (66JOC4071 69JA6464). However, there is no clear evidence for this assumption in the literature and information on the reaction of acetylenyl-substituted acids in conditions of acetylide synthesis is absent. 

The original Sonogashira reaction uses copper(l) iodide as a co-catalyst, which converts the alkyne in situ into a copper acetylide. In a subsequent transmeta-lation reaction, the copper is replaced by the palladium complex. The reaction mechanism, with respect to the catalytic cycle, largely corresponds to the Heck reaction.Besides the usual aryl and vinyl halides, i.e. bromides and iodides, trifluoromethanesulfonates (triflates) may be employed. The Sonogashira reaction is well-suited for the synthesis of unsymmetrical bis-2xy ethynes, e.g. 23, which can be prepared as outlined in the following scheme, in a one-pot reaction by applying the so-called sila-Sonogashira reaction ... 

Normally, copper-catalysed Huisgen cycloadditions work with terminal alkynes only. The formation of a Cu-acetylide complex is considered to be the starting point of the catalyst cycle. However, the NHC-Cu complex 18 was able to catalyse the [3-1-2] cycloaddition of azides 17 and 3-hexyne 23 (Scheme 5.6). 

The coupling of terminal alkynes with aryl or alkenyl halides catalysed by palladium and a copper co-catalyst in a basic medium is known as the Sonogashira reaction. A Cu(I)-acetylide complex is formed in situ and transmetallates to the Pd(II) complex obtained after oxidative addition of the halide. Through a reductive elimination pathway the reaction delivers substituted alkynes as products. 

More recently, a study with di- and mono-carbene Pd(II) complexes has demonstrated that the Sonogashira coupling of activated and non-activated aryl iodides can be carried out in an aqueous, aerobic medium and in the absence of amines. These results suggest that the moisture-sensitive copper-acetylide may not be present in this particular transformation, and that a Pd-acetyhde could be formed by deprotonation of the coordinated alkyne instead of transmetallation [130]. 

Catalytic forms of copper, mercury and silver acetylides, supported on alumina, carbon or silica and used for polymerisation of alkanes, are relatively stable [3], In contact with acetylene, silver and mercury salts will also give explosive acetylides, the mercury derivatives being complex [4], Many of the metal acetylides react violently with oxidants. Impact sensitivities of the dry copper derivatives of acetylene, buten-3-yne and l,3-hexadien-5-yne were determined as 2.4, 2.4 and 4.0 kg m, respectively. The copper derivative of a polyacetylene mixture generated by low-temperature polymerisation of acetylene detonated under 1.2 kg m impact. Sensitivities were much lower for the moist compounds [5], Explosive copper and silver derivatives give non-explosive complexes with trimethyl-, tributyl- or triphenyl-phosphine [6], Formation of silver acetylide on silver-containing solders needs higher acetylene and ammonia concentrations than for formation of copper acetylide. Acetylides are always formed on brass and copper or on silver-containing solders in an atmosphere of acetylene derived from calcium carbide (and which contains traces of phosphine). Silver acetylide is a more efficient explosion initiator than copper acetylide [7],... 

On the basis of DFT calculations, a catalytic cycle involving a copper vinylidene intermediate has been proposed (Scheme 9.22) [44]. The reaction is initiated by copper acetylide (138) formation. Sharpless and coworkers next invoke an unusual [3 + 3]-cycloaddition that would be forbidden by orbital symmetry, were it not stepwise. Coordination of an azide to complex 138 generates a zwitterionic complex (139). Internal nucleophilic attack of the acetylide moiety of 139 on the electrophilic... 

It has been suggested that the copper acetylides are coordination polymers, with intermolecular interaction between the C C bonds of the acetylides and copper atoms as shown in (XL) (13). The chains may be broken with tertiary phosphines (PR s) to give complexes of the type [CuC -CR(PR 3)]4. The X-ray structure of the complex [CuC CPh(PMe3)]4 has some very interesting and unexpected features (46a)-, see structure (XL). 

This activation process can be assumed to be the initial step in the formation of dinuclear copper(II) acetylide complexes, as first proposed by Bohlmann and coworkers 40 years ago (Scheme 6) [10f]. Deprotonated alkyne units 11 (or the corresponding JT-complexes 10) generated therein, stepwise displace the negatively charged counter ions of copper(II) salt dimers (12). The dinuclear copper(II) acet-ylide complex which finally results (14) collapses to the coupled product under reductive elimination of copper(I). The existence of higher-order copper acetylide... 

Cacchi- and Sonogashira-Hagihara couplings occur only if a primary, secondary, or tertiary amine is present, and it is best to have the amine present in large excess. Under these conditions the acetylene will at least form a small equilibrium concentration of the corresponding ammonium acetylide or copper complex thereof. The copper iodide serves to trap this species as a copper acetylide. The copper acetylide represents a substantially improved nucleophile in comparison to the free acetylene. Without the Cul addition, the acetylide content of the reaction mixture is so small that a reaction occurs only at higher temperatures. 

Fig. 13.22. Mechanism of the Pd(0)-catalyzed arylation of a copper acetylide. Step 1 formation of a 7T complex between the catalytically active Pd(0) complex and the arylating agent. Step 2 oxidative addition of the arylating agent and formation of a Pd(II) complex with a

Although the reaction of copper acetylides with transition metal halides has been successfully applied to the preparation of a variety of transition metal acetylides (64), the generation of copper-complexed derivatives is not unprecedented (65). A simpler and more general route to ruthenium acetylide complexes involves the deprotonation of ruthenium vinylidene complexes as described in Section VI,C. 

AUenynes. An attractive route to allenynes involves the reaction of allcnic bromides with 1-alkynes in the presence of catalytic amounts of this Pd(0) complex and Cul in diethylamine at 25° (equation 1). The synthesis presumably involves cross-coupling between an allenic palladium cr-compound and a copper acetylide. 

Mechanistically, this new insertion-CI-Diels-Alder hetero domino sequence can be rationalized as follows (Scheme 64) After the oxidative addition of the aryl halide 115 or 118 to the in situ generated Pd(0) species the arylpalladium halide 120 intramolecularly coordinates and inserts into the tethered triple bond via a syn-carbopaUadation to furnish cyclized vinylpalladium species 121 with a p-acceptor substitution in a stereospecific fashion. Transmetallation of the in situ generated copper acetylide 122 gives rise to the diorganylpalladium complex 123 that readily undergoes a reductive elimination and liberates the electron poor vinylpropargylallyl ether 124. The triethylamine catalyzed propargyl-allene isomerization furnishes the... 

Mechanism The Pd complex such as Pd(PPh3)4 activates the organic halides by oxidative addition into the carbon-halogen bond. The copper(I) halides react with the terminal alkyne and produce copper acetylide, which acts as an activated species for the coupling reactions. The oxidative addition step is followed by the transmetallation step. The proposed catalytic cycle is shown in Scheme 5.21. 

Several studies of the kinetics and effects of structure on reactivity lend support to a mechanism of oxidative coupling of the type first proposed by Bohlmann and coworkers The rate is second order with respect to Cu(ii) and alkyne, and varies inversely with [H+] . This is interpreted in terms of rapid steps involving displacement of a solvent molecule or other ligand from the coordination sphere of Cu(n) by an alkyne molecule, followed by acid dissociation of the coordinated alkyne to give an acetylide complex. In the rate-determining step, copper(ii) is reduced and simultaneously the alkynyl groups are coupled. These steps are summarized in equations (6), (7) and (8), where L represents a ligand—solvent, for... 

---