Cadiot-Chodkiewicz reaction, Castro-Stephens

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. 

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... 

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. 

Inclusive reviews P. Cadiot, W. Chodkiewicz, Couplings of Acetylenes in Chemistry of Acetylenes, H. G. Viehe, Ed. (Marcel Dekker, New York, 1969) pp 597-647 K. Sonogashira, Comp. Org. Syn. 3, 551-561 (1991). Cf Castro-Stephens Coupling Ullmann Reaction. 

The Castro-Stephens reaction is the cross coupling of a copper acetylide (1) and an aryl or vinyl halide (2) to give a disubstituted alkyne (3). The reaction, which shares some common elements with the Sonogashira, Cadiot-Chodkiewicz, Rosenmund-von Braun, Hay, and Glaser coupling reactions, was discovered by Stephens and Castro in the early 1960s and has found some applications in synthesis. " ... 

A possible mechanism for the conversion of aryl halides 38 to aryl nitriles 40 invokes a copper(III) intermediate 41, which is reminiscent of the postulated key complex 35 in the Cadiot-Chodkiewicz mechanism outlined above. Despite the gross similarities among these three transformations, there is no clear evidence that the oxidative addition/elimination pathway and copper(III) intermediates which define the Cadiot-Chodkiewicz and Rosenmund-von Braun reaction mechanisms are operant in the typical Castro-Stephens coupling. 

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. ... 

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