The 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 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. 

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]. 

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].

Pd cocatalysts, which have recently been implemented into the Cadiot-Chodkiewicz reaction, gave yield improvements and, more importantly, allowed for efficient heterocoupling of iodoalkynes and chloroalkynes (Table 9.15). Upon... 

Table 9.15 Examples of Pd cocatalysts in the Cadiot-Chodkiewicz reaction.

One of the reactions that has some mechanistic relationship to the Castro-Stephens coupling is the Cadiot-Chodkiewicz synthesis of unsymmetrical bis-alkynes (32). This coupling reaction finds occasional use in modem synthesis. Like the Castro-Stephens, this cross coupling is promoted by cuprous halides and proceeds through a putative copper aeetylide. The Cadiot-Chodkiewicz reaction requires a terminal alkyne (33), an alkynyl... 

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