Copper metal alkynes

CuBr/QUINAP System The CuBr/QUlNAP system was initially used in the enan-tioselective synthesis of proparyl amines via the reaction of alkynes and enamines (Scheme 5.5). It was rationalized that the enamines reacted with protons in terminal alkynes in the presence of copper catalyst to form zwitterionic intermediates in which both the generated iminiums and alkyne anions coordinate to the copper metal center. After an intermolecular transfer of the alkyne moiety to the iminium ion, the desired products were released and the catalyst was regenerated. The combination of CuBr as catalyst and the chiral ligand QUEMAP is crucial for the good reactivities and enantioselectivities seen in the reaction. Another potential... 

The cyclopropanation of alkenes, alkynes, and aromatic compounds by carbenoids generated in the metal-catalyzed decomposition of diazo ketones has found widespread use as a method for carbon-carbon bond construction for many years, and intramolecular applications of these reactions have provided a useful cyclization strategy. Historically, copper metal, cuprous chloride, cupric sulfate, and other copper salts were used most commonly as catalysts for such reactions however, the superior catalytic activity of rhodium(ll) acetate dimer has recently become well-established.3 This commercially available rhodium salt exhibits high catalytic activity for the decomposition of diazo ketones even at very low catalyst substrate ratios (< 1%) and is less capricious than the old copper catalysts. We recommend the use of rhodium(ll) acetate dimer in preference to copper catalysts in all diazo ketone decomposition reactions. The present synthesis describes a typical cyclization procedure. 

The above-described method which employs copper powder to activate 1,3-dipolar cycloaddition reaction of azides and alkynes in ball mill is related to work by Mack et al. [11], Here, copper catalyst was replaced by Cu vial and Cu milling balls as a source of metal catalyst. The efficacy and simplicity of the method is clearly shown by reaction of phenylacetylene and benzylazide in Spex Certiprep 8000M mixer mill (Scheme 5.11). Minute amounts of copper peeled off the balls were sufficient to afford 1,2,3-triazole 38 in excellent yield, without the need for purification of product. The ICP-MS analysis determined very low level of copper metal present in product after isolation (4.61 mg/g of copper in the product). Multicomponent variant of this reaction includes the in situ preparation of... 

In contrast, Cu(I) catalysis makes possible the efficient synthesis of 3,5-disubsti-tuted isoxazoles 57 from aromatic or aliphatic aldehydes and alkynes. Stable nitrile oxides can be isolated and subsequently submitted to the reaction [21] in isolated form and submitted to the reaction in one-pot, three-step process [131]. Here, nitrile oxide intermediates 56 are generated in situ via the corresponding aldoxime and halogenation/deprotonation by Chloramine-T [132]. Capture of the intermediate nitrile oxide by copper(I) acetylides occurs presumably before dimerization. In this case, the Cu catalyst was obtained from copper metal and copper(II) sulfate, and the products were isolated by simple filtration or aqueous work-up. Trace amounts of toluenesulfonamide and unreacted acetylene are easily removed by recrystallization or by passing the product through a short plug of silica gel. 

When the reaction of zirconacyclopentadiene 4 with DMAD proceeded in the presence of CuCl at -78 °C, the linear triene 20 was obtained in 78% yield after hydrolysis. When this mixture was wanned to room temperature, benzene derivative 6 was formed as a single product. This clearly indicates that benzene formation involves the insertion reaction of the third alkyne (DMAD) into the metal-carbon bond (path B). As shown in Scheme 11.7, the alkenyl copper moiety added to the carbon-carbon triple bond of DMAD and elimination of Cu metal led to the benzene derivatives 6. Indeed, a copper mirror was observed on the wall of the reaction vessel. However, benzene derivatives were also obtained by using only a catalytic amount of CuCl. In this case, copper metal deposition was obviously not observed. This means that path A cannot be ruled out. 

The reaction pathway proposed for this copper(I)-catalyzed reaction involves the formation of copper acetylide A, which coordinates with the internal nitrogen atom of the azide to form intermediate B [9], The key bond-forming step takes place when B is converted to the unusual six-membered copper metallacycle C and further into copper-metallated triazole D. The high regioselectivity is controlled by the binding of both azide and alkyne to copper prior to C—N bond formation. Eventually, protonation of D releases triazole and thereby regenerates the copper(I) species (Scheme 16.5). 

A unique method to generate the pyridine ring employed a transition metal-mediated 6-endo-dig cyclization of A-propargylamine derivative 120. The reaction proceeds in 5-12 h with yields of 22-74%. Gold (HI) salts are required to catalyze the reaction, but copper salts are sufficient with reactive ketones. A proposed reaction mechanism involves activation of the alkyne by transition metal complexation. This lowers the activation energy for the enamine addition to the alkyne that generates 121. The transition metal also behaves as a Lewis acid and facilitates formation of 120 from 118 and 119. Subsequent aromatization of 121 affords pyridine 122. 

The diazonio group of arenediazonium salts can be replaced by alkenes and alkynes or, seen from the other reaction partner, alkenes and alkynes can be arylated with arenediazonium salts. The reactions are catalyzed by copper salts and, as found more recently, also by salts of palladium and other metals. 

The NHCs have been used as ligands of different metal catalysts (i.e. copper, nickel, gold, cobalt, palladium, rhodium) in a wide range of cycloaddition reactions such as [4-1-2] (see Section 5.6), [3h-2], [2h-2h-2] and others. These NHC-metal catalysts have allowed reactions to occur at lower temperature and pressure. Furthermore, some NHC-TM catalysts even promote previously unknown reactions. One of the most popular reactions to generate 1,2,3-triazoles is the 1,3-dipolar Huisgen cycloaddition (reaction between azides and alkynes) [8]. Lately, this [3h-2] cycloaddition reaction has been aided by different [Cu(NHC)JX complexes [9]. The reactions between electron-rich, electron-poor and/or hindered alkynes 16 and azides 17 in the presence of low NHC-copper 18-20 loadings (in some cases even ppm amounts were used) afforded the 1,2,3-triazoles 21 regioselectively (Scheme 5.5 Table 5.2). 

When acetylene and real alkynes are in contact with copper, silver and transition metals, they form acetylides and analogues that are explosive, from ambient temperature upwards for acetylides. For instance, acetylene that was accidentally in the presence of electrical wires whose copper was bare led to a detonation. 

Another type of mixed cyanocuprate has both methyl and alkenyl groups attached to copper. Interestingly, these reagents selectively transfer the alkenyl group in conjugate addition reactions.16 These reagents can be prepared from alkynes via hydrozirconation, followed by metal-metal exchange.17... 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

The copper-alkoxo unit, which is usually synthesized in situ, plays a significant role in metal-promoted transformations of organic substrates by copper(I). To determine the reaction form of the Cu-OPh unit, Floriani and co-workers structurally characterized four complexes (772) (pseudotetrahedral Cu-Cu 3.223 AT (773) (pseudotetrahedral), (774) ( anion linear coordination) and (775) (planar trigonal).57 Using 3,3,6,6-tetramethyl-l-thia-4-cycloheptyne as terminal ligand the structural characterization of a copper(I)-alkyne complex (776) (Cu-Cu 2.940 A) was reported.573... 

Ethyl diazopyruvate, under copper catalysis, reacts with alkynes to give furane-2-carboxylates rather than cyclopropenes u3) (Scheme 30). What looks like a [3 + 2] cycloaddition product of a ketocarbenoid, may actually have arisen from a primarily formed cyclopropene by subsequent copper-catalyzed ring enlargement. Such a sequence has been established for the reaction of diazoacetic esters with acetylenes in the presence of certain copper catalysts, but metallic copper, in these cases, was not able to bring about the ring enlargement14). Conversely, no cyclopropene derivative was detected in the diazopyruvate reaction. 

A number of stable heterobimetallic copper alkyne complexes have been reported, based on the strategy of using another metal bis(alkynyl) complex as a chelating ligand for copper. The 1,4-diyne [(r -CsFGSiMe Ti-(C=GSiMe3)2]180 (or related complex) was found to stabilize the copper units GuX, with X = alkyl,180,181 vinyl,180... 

Hashmi et al. investigated a number of different transition metals for their ability to catalyze reactions of terminal allenyl ketones of type 96. Whereas with Cu(I) [57, 58] the cycloisomerization known from Rh(I) and Ag(I) was observed (in fact the first observation that copper is also active for cycloisomerizations of allenes), with different sources of Pd(II) the dimer 97 was observed (Scheme 15.25). Under optimized conditions, 97 was the major product. Numerous substituents are tolerated, among them even groups that are known to react also in palladium-catalyzed reactions. Examples of these groups are aryl halides (including iodides ), terminal alkynes, 1,6-diynes, 1,6-enynes and other allenes such as allenylcarbinols. This che-moselectivity might be explained by the mild reaction conditions. 

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