Cadiot-Chodkiewicz reaction

It was found [99JCS(PI )3713] that, in all cases, the formation of the deiodinated products 38 and 39 was accompanied by formation of the diynes 40 which were isolated in 60-90% yield. The authors believed that the mechanism of deiodination may be represented as an interaction ofbis(triphenylphosphine)phenylethynyl-palladium(II) hydride with the 4-iodopyrazole, giving rise to the bisftriphenylphos-phine)phenylethynyl palladium(II) iodide complex which, due to the reductive elimination of 1 -iodoalkyne and subsequent addition of alk-1 -yne, converts into the initial palladium complex. Furthermore, the interaction of 1-iodoalkynes with the initial alkyne in the presence of Cul and EtsN (the Cadiot-Chodkiewicz reaction) results in the formation of the observed disubstituted butadiynes 40 (Scheme 51). 

The scope of the SH reaction encompasses sp-sp2 (alkenyl, aryl (29),143 heteroaryl) and sp-sp couplings (the modified Cadiot-Chodkiewicz reaction).142 Iodides are most frequently used as electrophilic coupling partners, though the use of bromides, triflates (30),144 or even some reactive chlorides (31)145 is also possible. Due to the low steric bulk of the acetylenic unit, as well as its exceptional ability in the transduction of electronic effects, the SH reaction is well suited for construction of new (e.g., star-like) molecular architectures through polysubstitution (32).146... 

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, for C-C bond formation, 11, 19 Cadmate complex, formation, 2, 465 Cadmium-carbon bond formation, overview, 2, 462 Cadmium reagents... 

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... 

Haloalken-l-yl)dialkylboranes, synthesis, 9, 195—196 Halo-alkyl compounds, with Ti(IV), 4, 349 Haloalkynes, in Cadiot-Chodkiewicz reaction, 11, 19 Haloarenes... 

Nonoxidative Heterocoupling of Terminal Alkynes with Haloalkynes Cadiot-Chodkiewicz Reaction... 

Scheme 6.23 Synthesis of SPM 13 by a Pd-catalyzed Cadiot-Chodkiewicz reaction [34],...

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. 

In order to prepare nonsymmetrical diynes, one can use the Cadiot-Chodkiewicz reaction. It involves a haloalkyne such as a iodoalkyne or a bromoalkyne. Combined with the Glaser dimerization, this reaction provides a powerful entry to oligoyne bridging ligands and has been used extensively by Gladysz (see Figure 10) [34]. 

Cl-symmetric zirconocene dichloride 323 C60H38 hydrocarbon 128 Cadiot-Chodkiewicz reaction 204 (+)-(-calcidiol 250,251... 

Although the yields tend to be modest, coupling of alkynyl, alkenyl, and allylic halides to terminal alkynes in the presence of a cuprous halide and an amine (e.g. Et N, pyridine) by the Cadiot-Chodkiewicz reaction provides a direct route to acetylenic derivatives that are of interest in the construction of vitamin A (1) and carotenoids. For example, heating the acetylenes 104, 95 or 105 with the bromides 106 and 107 in the presence of cuprous chloride and an amine in methanol provides a convenient route to the corresponding acetylenic retinoids 108, 109 and 110 [53,54]. Similarly, heating 3-bromobut-2-en-2-ol with the acetylene 105 gives 11,12-didehydrovitamin A (108) [53] (Scheme 26). 

B.iv. Pd-CatalyzedAlkynyl-Alkenyl Coupling Route to Conjugated Diynes as a Strictly Pair-Selective Alternative to the Cadiot-Chodkiewicz Reaction... 

Scheme 9.23 The Cadiot-Chodkiewicz reaction between terminal acetylenes and haloalkynes catalyzed by Cu(l) salt in the presence of an amine base [175].

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