Copper alkynylation

The ability of alkynyl groups to bridge two metals may be employed in the construction of heterometallic complexes in a controlled manner (Figure 4.20 Chapter 6). Many metals will react directly with terminal alkynes or acetylide salts under basic conditions however, use is often made of copper alkynyls as tr /i.v-alkynylating reagents [usually generated in situ with catalytic amounts of Cu(I) salts]. 

Alkynyl anions are more stable = 22) than the more saturated alkyl or alkenyl anions (p/Tj = 40-45). They may be obtained directly from terminal acetylenes by treatment with strong base, e.g. sodium amide (pA, of NH 35). Frequently magnesium acetylides are made in proton-metal exchange reactions with more reactive Grignard reagents. Copper and mercury acetylides are formed directly from the corresponding metal acetates and acetylenes under neutral conditions (G.E. Coates, 1977 R.P. Houghton, 1979). 

Terminal alkynes react with propargylic carbonates at room temperature to afford the alka-l, 2-dien-4-yne 14 (allenylalkyne) in good yield with catalysis by Pd(0) and Cul[5], The reaction can be explained by the transmetallation of the (7-allenylpailadium methoxide 4 with copper acetylides to form the allenyKalk-ynyl)palladium 13, which undergoes reductive elimination to form the allenyl alkyne 14. In addition to propargylic carbonates, propargylic chlorides and acetates (in the presence of ZnCb) also react with terminal alkynes to afford allenylalkynes[6], Allenylalkynes are prepared by the reaction of the alkynyl-oxiranes 15 with zinc acetylides[7]. 

Silver(I) Inflate and copper(I) triflate can be applied as catalysts A representative example is the preparation of alkynyl tosylates by the catalytic decomposition of alkynyl lodonium salts in the presence of these salts [727] (equation 67)... 

The acetylide anion 3 is likely to form an alkynyl-copper complex by reaction with the cupric salt. By electron transfer the copper-II ion is reduced, while the acetylenic ligands dimerize to yield the -acetylene 2 ... 

Palladium And/Or Copper-Mediated Cross-Coupling Reactions Between 1-Alkynes And Vinyl, Aryl, 1-Alkynyl, 1,2-Propadienyl, Propargyl And Allylic Halides Or Related Compounds. A Review, Rossi. R. Carpita, A. Beilina, F. Org. Prep. Proceed. Int., 1995, 27, 129... 

Syntheses and luminescence studies of mixed-metal gold(I)-copper(l) and -silver (I) alkynyl complexes. The tuming-on of emission upon d metal ion encapsulation. Dalton Transactions, 1830-1835. 

Recently, Pal et al. found that (.S )-prolinol could facilitate the coupling reaction of terminal alkynes with 3-iodoflavone under palladium-copper catalysis in aqueous DMF to give 3-alkynyl substituted flavones of potential biological interest (Eq. 4.17). The coupling of iodobenzene with terminal alkynes at room temperature in water without any cosolvent was completed within 30 minutes, affording the desired product in good yield.36... 

McLaughlin and co-workers have described a one-pot copper-free Sonogashira alkynylation and base-mediated indolization reaction to access 1,2-disubstituted indoles 125 and azaindoles from o-chloroanilines 123 <060L3307>. A ligand-, copper, and amine-free variant of the Sonogashira coupling was used by Srinivasan and co-workers to access 2-substituded indoles <06T5109>. 

The reaction of 38 with nucleophiles gave a dinuclear species 39 in which each copper center is bonded to three C=C units, in contrast with the usual two-alkynyl-based bridge observed in many dinuclear alkynylcoppers.18 This... 

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... 

The remaining alkenyl copper moiety in 50 can react intramolecularly with the carbon—carbon triple bond to give metallofulvene derivatives 53. However, the coupling of the intermediate with the second molecule of alkynyl halide would seem to be faster than the cyclization reaction. Therefore, the dienediyne is obtained as the major product. 

The coupling with alkynyl iodides in the presence of CuCl and DMPU proceeds quite differently from that with alkynyl bromides. Although the first step of the coupling is the same, the subsequent Cu/I exchange reaction of the intermediate is different. As the final product, iododienyne 54 is obtained in high yields, as shown in Eq. 2.37 [35]. In the case of alkynyl bromides, Cu/Br exchange does not proceed. Therefore, the alkenyl copper moiety couples with the second alkynyl bromide molecule. 

This system was described in one report and has been synthesized by a copper-assisted cycloisomerization of alkynyl imines. The authors proposed the following mechanism at first, 372 could undergo a base-induced propargyl-allenyl isomerization to form 373 next, coordination of copper to the terminal double bond of the allene (intermediate 374) would make it subjected to intramolecular nucleophilic attack to produce a zwitterion 375. The latter would isomerize into the more stable zwitterionic intermediate 376, which would be transformed to the thiazole 377 (Scheme 55) <2001JA2074>. 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

The alkynyl epoxide 73 undergoes a copper-catalyzed reductive metallation by wBuLi [81, 83]. The resultant allenyllithium compound 74 is a versatile intermediate and reacts with various electrophiles (Scheme 3.37). 

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