Hydroalkylation of Alkynes: Functionalization of the Alkenyl Copper Intermediate through Single Electron Transfer Chemistry

We have developed a method for the stereoselective coupling of terminal alkynes and alpha-bromo carbonyls to generate functionalized E-alkenes. The coupling is accomplished by merging the closed-shell hydrocupration of alkynes with the open-shell single electron transfer (SET) chemistry of the resulting alkenyl copper intermediate. We demonstrate that the reaction is compatible with various functional groups and can be performed in the presence of aryl bromides, alkyl chlorides, alkyl bromides, esters, nitriles, amides, and a wide range of nitrogen-containing heterocyclic compounds. Mechanistic studies provide evidence for SET oxidation of the alkenyl copper intermediate by an alpha-bromo ester as the key step that enables the cross coupling.

Automated summary

The developed method allows for the stereoselective coupling of terminal alkynes and alpha-bromo carbonyls to generate functionalized E-alkenes. The key step for the cross coupling is identified as the SET oxidation of the alkenyl copper intermediate by an alpha-bromo ester.