Copper acetylides alkynylation

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]. 

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 ... 

The total of the reactions 2-5 results in reaction 1. The oxidative addition and formation of copper acetylide are well known. The intermetal transfer of the alkynyl group from copper acetylide (e.g., from Cu(I) to Pd(II) [8]) has been revealed by organometallic chemistry [8-11]. 

In the industrial manufacture of important starting compounds such as HteCCH2OH, HCaCCH(CHg)OH, and HOCH CsCCI OH, high pressure techniques are employed using alkali hydroxides or copper acetylide as catalyst. For extensive reviews on the alkynylation processes the reader is referred to the book [8] and review of Ziegenbein [6]. 

Alkynyl iodides and bromides react smoothly with various zinc-copper organometaUics at — 60 "C leading to polyfunctional aUcynes. lodoalkynes, such as 296, react at very low temperature, but lead in some cases to copper acetylides as by-products (1/Cu exchange reaction). 1-Bromoalkynes are the preferred substrates. Corey and Helel have prepared a key intennediate 297 of the side chain of Cicaprost by reacting the chiral zinc... 

As a last example of an uncatalyzed C,C coupling of a neutral organocopper compound Figure 16.9 depicts the alkynylation of a copper acetylide with a bromoalkyne which is easily accessible via bromination of a terminal alkyne ... 

Alternatively, copper acetylides can be alkynylated with iodoalkynes. Iodoalkynes can be prepared in the same way as bromoalkynes. 

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.

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

Alkynyl copper reagents are an exception and must be used as the copper(I) acetylides. 

The Pd-catalyzed coupling of o-haloanilines and terminal alkynes tends to produce either the 2-(l-alkynyl)aniline or mixtures of the alkynylanilines and the corresponding indoles [17,18]. However, iV-benzyl-2-iodoaniline has recently been cross-coupled with terminal alkynes to afford the corresponding ben-zylindoles using a Pd zeolite catalyst (Eq. 14) [39]. One can also employ stoichiometric amounts of copper acetylides to effect this transformation [22-24]. 

Alkynyl complexes contain metal-carbon bonds in which the metal is bound to the sp-hybridized carbon at the terminus of a metal-carbon triple bond. The materials properties of these complexes have been investigated extensively. The properties of these complexes include luminescence, optical nonlinearity, electrical conductivity, and liquid crystallinity. These properties derive largely from the extensive overlap of the metal orbitals with the ir-orbitals on the alkynyl ligand. The M-C bonds in alkynyl complexes appear to be considerably stronger than those in methyl, phenyl, or vinyl complexes. Alkynyl complexes are sometimes prepared from acetylide anions generated from terminal alkynes and lithium bases (e.g., method A in Equation 3.42), but the acidity of alkynyl C-H bonds, particularly after coordination of the alkyne to the transition metal, makes it possible to form alkynyl complexes from alkynes and relatively weak bases (e.g., method B in Equation 3.42). Alkynyl copper complexes are easily prepared and often used to make alkynylnickel, -palladium, or -platinum complexes by transmetallation (Equation 3.43). This reaction is a step in the preparation of Ni, Pd, or Pt alkynyl complexes from an alkyne, base, and a catalytic amoimt of Cul (Equation 3.44). This protocol for... 

Keywords Copper acetylides, secondary phosphine-boranes, 1,10-phenanthroline, oxygen atmosphere, toluene, room temperature, oxidative P-alkynylation, enantioselective alkynylphosphine-boranes... 

C(l)-Alkynylated tetrahydroquinolines (160) have been prepared from tettahydro-quinoline, an aldehyde (R -CHO) and an alkyne (R -C=C-H), using copper(I) iodide at 50 °C in toluene. The first two components are proposed to form an ejto-iminium ion in situ, which isomerizes to the n<7o-iminium, which then adds copper acetylide. 

So far, alkynyl ligands have been considered unreactive in copper-promoted conjugate additions and are often used as non-transferable groups in mixed lithium diorganocuprates. However, it is noteworthy that Nilsson and co-workers have demonstrated the conjugate addition of copper acetylides in THF together with iodotrimethylsilane to enones and to o, 8-unsaturated aldehydes (eq 7). ... 

This reaction process takes advantage of the ease with which a copper acetylide will oxidatively insert into an alkynyl halide bond. The postulated mechanism begins with and in situ base- and Cu(I)-induced formation of a copper acetylide (1) from a terminal alkyne (33). This intermediate undergoes oxidative addition into the activated C-X bond of an alkynyl halide (34) to afford the copper(III) species 35. Reductive elimination of the bis-alkyne 32 from complex 35 delivers the reaction product and regenerates the copper(l) halide 36 which may re-enter the catalytic cycle. 

The Cadiot-Chodkiewicz coupling typically proceeds under conditions which are considerably milder than Castro-Stephens reactions. Triethylsilylacetylene 74 rapidly undergoes Cadiot-Chodkiewicz coupling with alkynyl bromide 75 to generate the unsymmetrical bisalkyne 76 in nearly quantitative yield when those two reactants are treated with catalytic cuprous chloride and catalytic ammonium hydroxide in -butylamine solution. This coupling process affords one of the best entries into compounds such as 76 and is permissive of TES and larger silylated copper acetylide species because of the lower reaction temperature. ... 

More recently, we demonstrated the first alkynylation of benzylic C-H bonds not adjacent to a heteroatom with 1 mol% of a CuOTf-toluene complex in the presence of 1.5 equiv. of DDQ. Various allq nes were successfully coupled with diphenylmethane derivatives (Scheme 1.8). Aromatic allq nes were smoothly converted and the use of electron-rich derivatives resulted in a slightly improved jdeld, rationalized by the nucleophilicity of the substrates. However, aliphatic allq nes [i.e., n-heiq ne) did not give the corresponding CDC product under standard conditions. The mechanism was proposed to proceed via the generation of radical intermediates, which were converted into a benzylic cation in the presence of DDQ through two successive SET steps. The resulting hydroquinone subsequently then abstracted the acidic proton from the allq ne to form the copper acetylide, which added to the benzylic cation to afford the desired product. 

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). 

Oxidative addition of the copper(I) acetylide to the alkynyl halide with formation of a copper(III) intermediate (15), giving the corresponding diacetylene by reductive elimination [11a]. 

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]. 

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