Air Tolerant Cadiot–Chodkiewicz and Sonogashira Cross-Couplings

• Published in: Organic letters 2023-11, Vol.25 (45), p.8145-8149
• Main Authors: Fung, Alfred K. K., Sowden, Madison J., Coote, Michelle L., Sherburn, Michael S.
• Format: Article
• Language: English
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.3c03314

Cadiot–Chodkiewicz cross-couplings generate an unsymmetric buta-1,3-diyne by way of a Cu­(I)-catalyzed coupling between a terminal alkyne and a 1-haloalkyne. Despite their widespread use, Cadiot–Chodkiewicz reactions are plagued by the generation of symmetric buta-1,3-diyne side products, formed through competing: (a) formal reductive homo-coupling of the 1-haloalkyne and (b) oxidative (Glaser–Hay/Eglinton) homo-coupling of the terminal alkyne. To overcome this issue, a large excess of one of the two reacting alkynes is commonly deployed, and difficult separations of cross- and homo-coupled products are often encountered. Here, we demonstrate that the use of ascorbate as a reductant leads to a suppression of these unwanted side reactions, hence permitting excellent yields with a roughly stoichiometric ratio of reactants. The procedure also avoids an inert gas atmosphere and uses a sustainable solvent. A similar approach is effective for cross-couplings involving a Pd(0)/Pd­(II) catalytic cycle, with air tolerant Sonogashira couplings also established.