Cu-acetylide

Butadiene CH2=CHCH= H2 Cu Acetylide, Vinyl Acetylene Ethylene Air (Peroxides) > 300 114 Inhibitor — t-Butyl Catechol — 115ppm Activation 12.0 429 Self-polymerization above RT or press... 

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). 

Cu Acetylide <500, and Pb Nieratohypophosphite <500. Other expls fulfilling the energy requirements are Silver Azide, Basic Lead Pi-crate and Lead Nitre to phosphate. LA requir-... 

Mercurous Acetyltde [Quecksilbet(I)-acetyl-enid, in Ger], HgaC,. HaO. Grey ppt, mp-lost some water on heating and then decompd or detond. Can be prepd by treating with acetylene a cold aq suspn of mercurous acetate or by treating Cu acetylide with an aq soln of mercurous nitrate. Both operations should be carried out in the absence of light... 

The use of very fast ign agents involves, in most cases, considerable danger from the hazard of static elecy. It has been found that ign compds which have a negligible induction period(or so -called fast compds) are susceptible to initiation by static elecy. Particularly susceptible to static elecy is Cu acetylide Ref W.H.Aughey, L.A.Burrows W.E.Lawson,... 

CA 31, 6467(1937)(Elec blasting initiator contg Cu acetylide) 4)L.A.Burrows, USP 2086532... 

This reaction is believed to proceed via nucleophilic combination of in situ generated Cu-acetylide and iminium ion. Mechanistic studies indicate a strong positive non-linear effect based on which a catalytic cycle is proposed that involves a dimeric Cu/quinap complex as the active catalytic species. 

In addition to coupling via Cu acetylides generated in situ as mentioned above, the coupling of terminal alkynes has been carried out smoothly using actylides of Zn and other metals as an alternative method of arylation and alkenylation of alkynes [66]. Sn[67], Zn[68] and Mg[69] acetylides are used frequently as activated alkynes, rather than the alkynes themselves, and their reaction with halides proceeds without using Cul. 

Fig. 16.30. Pd(0)-catalyzed arytation of a copper acetytide at the beginning of a three-step synthesis of an ethynyt aromatic compound. Mechanistic details of the C,C coupling Step 1 formation of a 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 cr-bonded aryl moiety. Step 3 formation of a Cu-acetylide. Step 4 trans-metalation the alkynyl-Pd compound is formed from the alkynyl-Cu compound via ligand exchange. Step 5 reductive elimination to form the -complex of the arylated alkyne. Step 6 decomposition of the complex into the coupling product and the unsaturated Pd(0) species, which reenters the catalytic cycle anew with step 1.

The reactions of Cu-acetylides with configurationally homogenous cts-iodoalkenes (accessible via the procedure in Figure 13.12) or with stereopure frans-iodoalkenes (e.g., preparation according to Figure 3.11), respectively, result in 1,3-enynes with retention of the respective double bond geometry (Figure 13.24). 

More often such bromo- and iodoalkynes are employed with another synthetic goal in mind, namely, in the Cadiot-Chodkiewicz reaction for the formation of symmetric or asymmetric 1,3-diynes by reaction of the haloalkyne with a terminal alkyne (Figure 13.25). Additional reagents essential for the success of this reaction are one equivalent or more of an amine and a substoichiometric amount of Cul. As with the Cacchi and Stephens-Castro coupling reactions of Section 13.3.4, a Cu-acetylide is the reactive species in the Cadiot-Chodkiewicz coupling. It is formed in step 1 of the mechanism illustrated in Figure 13.25. 

The problem with this scenario is that alkynes are more acidic than most hydrocarbons (pK 25), but they are not sufficiently acidic to be deprotonated by amines (p/temperature required for the Sonogashira coupling from >100 °C to room temperature. The Cul may convert the alkyne (RC=CH) to a copper(I) acetylide (RC=C-Cu), a species that can undergo transmetallation with Pd(II). Of course, now the question is, How is RC=C-H converted to RC=C-Cu The alkyne may form a tt complex with Cu, and this complex may be deprotonated (E2-like elimination) to give the Cu acetylide, which can transmetallate with Pd. 

The amine base may not only provide basic conditions to deprotonate the alkyne (28) and facilitate the formation of the Cu acetylide, but may also act as a reducing agent for the Pd(II) salt added to the reaction mixture. The role of the copper is to enhance the nucleophilicity of the alkyne toward Ar-Pd-X (3) species (Scheme 4). However, R-Pd-OTf species (where R = imines or pyridines) are readily attacked by... 

The preparation of 5 -alkyl- and 5 aryl-oestra-l(10),4-dieno[3,26)]furans (96) by treatment of 2-iodo-oestrone (95) or oestradiol with the corresponding Cu acetylides in boiling pyridine has been reported. 

In another copper-catalyzed reaction, cross-coupling of alkynes with phosphi-ne-boranes was followed by surprising oxidation to yield ketones (Scheme 69) [122]. The active species was proposed to be a copper phosphido-borane complex, formed by proton transfer to a Cu-OH group. Formation of a Cu-acetylide followed by P-C reductive elimination would then yield a phosphino-alkyne, whose subsequent Cu-mediated air oxidation yields the ketone. 

Whatever the details of the interactions of Cu with alkyne during the CuAAC reaction, it is clear that Cu-acetylide species are easily formed and are productive components of the reaction mechanism. Early indications that azide activation was rate-determining came from the CuAAC reaction of diazide 15, shown in Scheme 10.5, which afforded ditriazole 17 as the predominant product, even when 15 was used in excess [113]. The same phenomenon was observed for 1,1-, and 1,2-diazides, but not for 1,4-, 1,5-, and conformationally flexible 1,3-diazide analogues. The dialkyne 18, in contrast to its diazide analogue 15, gave statistical mixtures of mono- and di-triazoles 19 and 20 under similar conditions. Independent kinetics measurements showed that the CuAAC reaction of 16 was slightly slower than that of 15, ruling out the intermediacy of 16 in the efficient production of 17. The Cu-triazolyl precursor 21 is, therefore, likely to be converted to 17 very rapidly. 

The initial computational treatment of the CuAAC focused on the possible reaction pathways available to mononuclear copper(l) acetylides and organic azides propyne and methyl azide were chosen for simplicity [23]. The key bond-making steps are shown in Scheme 10.6. Formation of Cu-acetylide 16 (step A) was calcu-... 

Direct introduction of sp carbon to alkynes by the reaction of Cu acetylides with aryl and alkenyl halides to form arylalkynes and alkenylalkynes is known as the Castro reaction [1]. Later it was found that coupling of terminal alkynes (1-alkynes) with halides proceeds more smoothly by using Pd catalysts. There are two methods of Pd-catalyzed coupling, hi 1975 direct coupling of 1-alkynes catalyzed by a phosphine-Pd(O) complex in the presence of amines was reported by Heck and Cassar as an extension of the Heck reaction to 1-alkynes [2,3]. In the same year, Sonogashira and Hagihara found that the addition of Cul as a co-catalyst gave better results, and the Pd(0)-CuI-catalyzed reaction is called the... 

The reaction is explained by the following mechanism. At first, Cul activates 1-alkynes 1 by forming the Cu acetylides 6, which undergo transmetallation with arylpalladium halides to form the alkynylarylpalladium species 7, and reductive elimination to give 2 is the final step. However, the coupling proceeds even in the absence of Cul under certain conditions, and it may be possible to form the alkynylarylpalladium species 7 directly from 1-alkynes. As another less likely possibility, carbopalladation of a triple bond with Ar-Pd-X (or insertion of the triple bond to Ar-Pd-X) generates the alkenylpalladium 8 which undergoes dehydropal-ladation to afford disubstituted alkynes 2. In this mechanism, Cul plays no role. The mechanism of -H elimination of alkenylpalladium to form alkynes is not clearly known. 

This method does not require the isolation of Cu-acetylides, and typically gives yields 5-10% better than the previous procedure (Synth. Meth. 19, 891) hydroxyl groups, esters and nitriles are tolerated. F.e.s. G.J.S. Doad et al., Tetrahedron Letters 30, 1597-8 (1989). 

---