Cadiot-Chodkiewicz procedure

The cyclization of thienyl-substituted diacetylenes with hydrogen sulfide or sodium sulfide is also a very successful method for the synthesis of oligothiophenes. The key point here is the synthesis of the precursor diynes. Symmetrical diacetylenes can be obtained by the oxidative coupling of acetylenes with copper(I) or copper(II) salts ( Glaser, Hay, or Eglington coupling ). The synthesis of unsymmetric diynes proceeds best via the Cadiot-Chodkiewicz procedure in which an acetylene is reacted with an acetylic halide in the presence of copper(I) salts [117]. Therefore, thienyl-substituted acetylenes and bromoacetylenes are important starting materials. 

Z,Z-C2H5SCH=CHCH=CHCaC-r-Bu (undistilled) is obtained from Z-C2HjS--CH CHC=CCsC-t-Bu by a similar procedure (1 h reflux). The starting compound is prepared by Cadiot-Chodkiewicz coupling of Z-CjHjSCf CHGsCH with BiO C-t-Bu... 

A coupling procedure particularly suited to the synthesis of unsymmetrical diacetylenes involves the reaction of a terminal acetylene with a 1-bromo-acetylene in the presence of a catalyst consisting of a solution of copper(i) chloride in a primary amine to which small quantities of hydroxylamine hydrochloride is added (the Cadiot-Chodkiewicz coupling). 

Although palladium-catalyzed processes have also achieved improvements in the field of acetylenic coupling [2], the Glaser-Hay and Cadiot-Chodkiewicz copper-mediated methods still remain the most used. Further mechanistic investigations seem to be necessary, to overcome the limitations of the existing procedures, mainly poor selectivity and predictability. 

General procedure for Cadiot-Chodkiewicz Couplings CH3OH, H, CuCl... 

Thus all four geometrical isomers of 1,4-disubstituted 1,3-dienes can be readily prepared starting from two terminal acetylene units. The Z,Z isomer is available via Cadiot-Chodkiewicz coupling (e.g. Figure 12) both the j3,J3 and 13,j3 isomers can be prepared via the procedure in Figure 17 and the JS.JL isomer can be isolated from the equilibration-crystallization procedure described above. 

General Procedure for the Cadiot-Chodkiewicz Coupling During the Syntheses of Azacyclotetraynes 10(n)... 

Compounds with a terminal acetylenic function, RCsCH, react with 1-bromoalkynes, R CsCBr in the presence of an aliphatic amine and a catalytic amount of a copper salt to give the coupling products RCsCCsCR. This useful reaction, discovered by Cadiot and Chodkiewicz [195], gives a ready access to a number of poly-unsaturated systems. The usual procedure involves dropwise addition of the bromoacetylene R GsCBr to a mixture of the acetylene RCsCH, ethylamine, ethanol or methanol, a catalytic amount of copper chloride or bromide and a small amount of hydroxylamine.HCl. This reducing agent prevents the oxidation to copper ). The reaction is usually very fast at temperatures in the region of 30 C. Since much heat is evolved, the reaction can be monitored easily by temperature observation. 

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