Theoretical study of copper hydride complexes catalyzing terminal alkyne hydroalkylation for C(sp2)–C(sp3) bond formation

Abstract

This study applies Density Functional Theory (DFT) to theoretically investigate the reaction mechanism of a copper complex catalyst facilitating the reaction between a terminal alkyne and α-bromo amide, enabling the formation of E-alkenes through C(sp²)–C(sp³) coupling. Initially, the study explores the reaction mechanism, identifying the predominant reaction pathway and the rate-determining step. Next, we discuss the addition reaction mode of copper hydride with terminal alkynes, determining the causes of regional and stereoselectivity. Subsequently, the reaction mechanism between the alkenyl copper intermediate and α-bromo amide is examined, including the discussion of alkyl fragment activation and introduction methods. Furthermore, the role of NHC ligands in catalyzing the single electron transfer process for C–Br bond activation is investigated. Finally, we analyze and discuss the reasons for the high energy barrier of the non-radical pathway. These investigations not only deepen our understanding of the reaction mechanisms of terminal alkynes and α-bromo amide catalyzed by copper but also provide valuable guidance for the future design of more efficient catalysts and reaction conditions.