Science of Synthesis

Witulski, B.; Alayrac, C., Science of Synthesis, (2006) 24, 927.

The copper-catalyzed cross coupling of 1-bromoalk-1-ynes with terminal alkynes in methanol and in the presence of ethylamine and hydroxylamine hydrochloride gives unsymmetrical 1,4-disubstituted buta-1,3-diynes ‌59‌ in high yields (‌Scheme 29‌).[‌18‌,‌116‌] This is known as the Cadiot–Chodkiewicz coupling reaction, which finds broad application in oligoyne natural product synthesis. Examples of polymer-supported Cadiot–Chodkiewicz couplings are known, and these rely on the use of bromoalkynes attached to a Merrifield resin.[‌117‌] The general reaction conditions involve a catalytic quantity of copper(I) chloride or bromide. The hydroxylamine salt is necessary to reduce copper(II) ions, formed in situ, to copper(I) in order to prevent the oxidative dimerization of the terminal alkyne, and ethylamine is present to neutralize hydrogen bromide that is formed. The reaction mechanism involves copper acetylide intermediates. Bromoalkynes are much more reactive than chloroalkynes, whereas iodoalkynes are unsuitable because they undergo dimerization under the usual reaction conditions. However, there are some examples of efficient palladium-catalyzed cross couplings of 1-iodoalk-1-ynes with terminal alkynes in the presence of copper(I) iodide and diisopropylamine that afford 1,4-disubstituted buta-1,3-diynes ‌60‌ (‌Scheme 29‌).[‌118‌,‌119‌] The copper chloride promoted cross-coupling reactions of 2-aryl-1-chloroalk-1-ynes with (arylethynyl)trimethylsilanes proceed under neutral conditions in dimethylformamide at 80°C and give unsymmetrical buta-1,3-diynes in moderate to good yields.[‌120‌]

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References

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