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. 2018 Nov 2;20(21):6845-6849.
doi: 10.1021/acs.orglett.8b02975. Epub 2018 Oct 17.

Synthesis of 1,3-Diynes via Cadiot-Chodkiewicz Coupling of Volatile, in Situ Generated Bromoalkynes

Phil C Knutson  1 , Haleigh E Fredericks  1 , Eric M Ferreira  1
Affiliations

Synthesis of 1,3-Diynes via Cadiot-Chodkiewicz Coupling of Volatile, in Situ Generated Bromoalkynes

Phil C Knutson et al. Org Lett. .

Abstract

A convenient Cadiot-Chodkiewicz protocol that facilitates the use of low molecular weight alkyne coupling partners is described. The method entails an in situ elimination from a dibromoolefin precursor and immediate subjection to copper-catalyzed conditions, circumventing the hazards of volatile brominated alkynes. The scope of this method is described, and the internal 1,3-diyne products are preliminarily evaluated in ruthenium-catalyzed azide-alkyne cycloadditions.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
1,3-Diynes in natural product synthesis.
Figure 2.
Figure 2.
1,3-Diynes from volatile bromoalkynes - synthetic strategy.
Scheme 1.
Scheme 1.
Coupling of in situ-generated 1-bromopropyne. a CH2Cl2 was added to the coupling reaction to solubilize the reactants. b Coupling stirred 4 h at 0 °C and 2 h at 23 °C. c Gram scale.
Scheme 2.
Scheme 2.
Coupling of in situ-generated 1-bromobutyne.
Scheme 3.
Scheme 3.
1,3-Diynes in Azide-Alkyne Cycloadditions
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