Copper acetylides synthesis

STEPHENS CASTRO Acetylene cycloptiane synthesis Polyacetylene cyclophane synthesis from an iodophenyl copper acetylide... 

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. 

Whereas the condensation of o-iodonitrobenzene with copper acetylides is accompanied by cyclization into isatogens, neither 4-iodo-3-nitro- nor 5-iodo-4-nitro-l,3-dimethylpyrazole gives cyclized products in conditions of acetylide synthesis. Moreover, nitropyrazolylphenylacetylene, as compared with o-nitrotolane, does not undergo thermal, catalytic, or photochemical isomerization to give the fused five-membered rings. 

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 ... 

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.

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. 

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. 

Copper acetylides have also been used, for the synthesis of 3-alkyl isocoumarins... 

Anodendroic acid 68 has been isolated from Anodendron affine Durce while euparin 69 and pterofuran 70 have been obtained from Eupatoriumpurpureum and Pterocarpus indicus respectively. The synthesis of (+) anodendroic acid 6< , euparin 69 and pterofuran 70 also involves use of copper acetylide. The dihydrobenzo-furan, intermediate 67 has been converted to (+) anodendroic acid 68... 

Replacing the Cul with ZnCl2 affords primarily isocoumarins [30]. The direct reaction of o-halobenzoic acids with copper acetylides also affords phthalides [22-24]. The reaction of (Z)-3-halopropenoic acid and terminal alkynes in the presence of a palladium catalyst and catalytic amounts of Cul provides a convenient synthesis of alkylidene butenolides (Eq. 8) [31,32]. 

In 2009, de Meijere s group reported on the formal cycloaddition of a-metallated methyl isocyanides onto the triple bond of electron-deficient acetylenes, giving oligosubstituted pyrroles. The reaction showed broad scope (24 examples, 25-97% yield). In addition, a related novel Cu(l)-mediated synthesis of 2,3-disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides was reported (11 examples, 5-88% yield) [99,100]. 

Over the past 5 years Cu(I)-catalyzed addition of terminal acetylenes to imines has been an intense area of research for the synthesis of chiral propargyl amines. Two mechanistic proposals have been put forth which utilize Cu(I) complexes as Lewis acids in these additions. Benaglia and coworkers reported a mechanism for reactions utilizing preformed imines (Scheme 17.37). The chiral Cu(I) salt (171) initially coordinates imine (172) to generate complex (173). Subsequent coordination of the terminal acetylene (174) affords complex (175). Formation of requisite copper acetylide results in the formation of complex (176), which facilitates intramolecular addition of the acetylide to the imine. Decomplexation of the resulting propargyl imine from (177) regenerates the catalytic Cu(I) species. 

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