Cadiot-Chodkiewicz coupling alkynes

The dimerization of terminal alkynes, known as the Glaser coupling, the Eglinton coupling, and the Cadiot-Chodkiewicz coupling, is one... 

Pd/Cu-catalyzed cross-coupling of organohalides with terminal alkynes. Cf. Cadiot-Chodkiewicz coupling and Castro-Stephens reaction. The Castro-Stephens coupling uses stoichiometric copper, whereas the Sonogashira variant uses catalytic palladium and copper. 

Gung and Dickson reported the synthesis of this molecule [54] using a three-component Cadiot-Chodkiewicz coupling reaction [55] as the pivotal step (Scheme 12.17). In this three-component reaction, diyne 112 was utilized as a bidirectional synthon and was coupled successively with bromo alkynes 111 and 113 under... 

Whereas Glaser-type oxidative coupling opens efficient synthetic pathways toward symmetrical diynes, its performance in heterocoupling is poor. The latter may be accomplished by Cadiot-Chodkiewicz coupling of terminal alkynes with 1-haloalkynes (usually 1-bromoalkynes). The reaction is conducted in the presence of an amine and catalytic amounts of a copper(I) salt. Because, in contrast with the Glaser-type reactions described above, it follows a nonoxidative reaction mechanism, oxygen is not necessary - but needs often not to be excluded (Scheme 4) [9]. 

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 copper(I)-catalyzed cross-coupling of a terminal alkyne and an alkynyl halide to yield diyne is known as the Cadiot-Chodkiewicz coupling. ... 

The coupling of a terminal alkyne with a 1-bromoalkyne in the presence of a copper(i) salt and an amine base (B), referred to as the Cadiot-Chodkiewicz coupling , is of particular synthetic importance because of the facile roiite it provides to unsymmetrical polyacetylenes with an even or odd number of triple bonds (equation 10). The reaction has been reviewed and these reviews should be... 

Heterocoupling may be accomplished via the Cadiot-Chodkiewicz coupling of terminal alkynes with haloalkynes, catalyzed by cuprous salts in the presence of aliphatic amines ... 

Although there are cases in which the use of a cuprous acetylide rather than a terminal acetylene is preferred, the use of a terminal acetylene is much easier and, as described later, more common. The reaction between a terminal alkyne and a haloalkyne using catalytic amounts of a Cu(I) salt in an amine base is known as the Cadiot-Chodkiewicz coupling (Scheme 9.23) [175]. 

For the synthesis of nonsymmetrically substituted 1,3-butadiynes the Cadiot-Chodkiewicz coupling is usually apphed [30, 31]. In this protocol a terminal alkyne is reacted with a terminal bromoalkyne derivative in the presence of a Cu(i) salt and an amine. As examples we show in Scheme 7.3 the synthesis of the l-azacydotetradeca-3,5,10,12-tetrayne derivatives 10(3)a to 10(3)f [32], 1-isopropyl-l-azacydopentadeca-3,5,ll,13-tetrayne (10(4)(c)) [33] and 1-isopropyl-l-azacydo-hexadeca-3,5,12,14-tetrayne (10(S)(c)) [33]. 

Recently, Marino et al. reported a Cadiot-Chodkiewicz cross-coupling reaction of bulky trialkylsilyl-protected alkynes with 1-bromoalkynes in aqueous amine to form a variety of unsymmetrical diynes in good yields (75 95%) (Eq. 4.23).44... 

The two reactions described above can be applied for the synthesis of symmetrical few-acetylenes only. Unsymmetrical bis-acetylenes can be prepared by using the Cadiot-Chodkiewicz reaction. For that method a terminal alkyne 1 is reacted with a bromoalkyne 8 in the presence of a copper catalyst, to yield an unsymmetrical coupling product 9 ... 

This side-reaction is most serious in the case of acetylenes RC=CH with a relatively low acidity aliphatic 1-alkynes, e.g. 1-octyne, and acetylenic alcohols HCaC(CH2)nOH with n > 2, give reduced yields (40-50%) in the coupling reaction. In many other reactions, yields are high. Since the bromoalkyne usually has the highest "added value", economical considerations prescribe the use of an excess of the free acetylene, especially when it is inexpensive, e.g. propargyl alcohol. The mechanism of the Cadiot-Chodkiewicz reaction has not been studied in detail, but is seems likely that a copper acetylide ROCCu is formed first it often appears as a yellowish suspension. 

Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 Cu-mediated reactions acetylenes, 10, 551 dienes, 10, 552... 

Cross-coupling reactions 5-alkenylboron boron compounds, 9, 208 with alkenylpalladium(II) complexes, 8, 280 5-alkylboron boron, 9, 206 in alkyne C-H activations, 10, 157 5-alkynylboron compounds, 9, 212 5-allylboron compounds, 9, 212 allystannanes, 3, 840 for aryl and alkenyl ethers via copper catalysts, 10, 650 via palladium catalysts, 10, 654 5-arylboron boron compounds, 9, 208 with bis(alkoxide)titanium alkyne complexes, 4, 276 carbonyls and imines, 11, 66 in catalytic C-F activation, 1, 737, 1, 748 for C-C bond formation Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 via Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 via Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 for C-H activation, 10, 116-117 for C-N bonds via amination, 10, 706 diborons, 9, 167... 

As already mentioned, there have been few mechanistic examinations of the copper-catalyzed Cadiot-Chodkiewicz heterocoupling reaction. Kinetic studies with the less reactive chloroalkynes [11a] have led to the assumption, shown in Scheme 7, that coupling between alkynes and haloalkynes proceeds through initial formation of copper(I) acetylides, probably formed by an acetylenic activation process similar to that described above for oxidative homocouplings. Subsequently, two reaction pathways may be reasonable ... 

Unsymmetrically substituted 1,3-diynes can be obtained via the Cadiot-Chodkiewicz copper(I)-catalyzed coupling of 1-alkynes with 1-halo-l-alkynes in the presence of hydroxylamine hydrochloride and an amine. ... 

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