Theoretical Studies On Cu-catalyzed Cross-coupling Of Diazo Compounds With Terminal Alkynes

Transition-metal-catalyzed carbene transformations and cross-coupling reactionsrepresent two major reaction types in organometallic chemistry and organic synthesis.Metal carbene is an important intermediate in many catalytic reactions. Generally, themost common precursors of metal carbenes are diazo compounds, including relativelystable α-diazocarbonyl compounds and the nonstabilized diazo compounds that areusually generated in situ from N-tosylhydrazones under basic conditions. Metalcarbene can undergo a migratory insertion process. In such a process, a ligandmigrates from the metal center to the carbenic carbon to generate a new metal species.The metal carbene migratory insertion process, which is merged with thecross-coupling process, leads to the development of an array of novel cross-couplingreactions. Recent stuies show that this kind of cross-coupling reaction can becatalyzed by Pd, Rh, Ni, Co, and Cu catalysts. Because of the low cost of Cu catalysts,Cu-catalyzed reactions have obvious advantages in some cases for large-scaleapplications. Among these reactions, Cu-catalyzed cross-coupling reactions of diazocompounds with terminal alkynes have been used as a new approach forcarbon-carbon bond formation.With the aid of density functional theory (DFT) calculations, the detailedreaction mechanism for the Cu(I)-catalyzed cross-coupling of (diazomethyl)benezenewith trimethylsilylethyne and tert-butylethyne was studied. For both reactions, twocatalytic cycles were considered. In one catalytic cycle, the active species reacts firstwith trimethylsilylethyne or tert-butylethyne, while in the other one, the active speciesreacts first with (diazomethyl)benezene. In both catalytic cycles, the copper acetylide formation, copper carbene migratory insertion, and protonation steps are involved.The calculation results show that the protonation step is crucial for the productselectivity. In the reaction of trimethylsilylethyne, the protonation prefers to occur atthe phenyl-substituted carbon giving the alkyne product, while in the reaction oftert-butylethyne, the protonation favors the tert-butyl-substituted carbon affording theallene product, consistent with the experimental results. In addition, the reactionsaffording the allene products can tolerate various functional groups on both diazocompounds and terminal alkynes. The protonation steps for the reaction ofdiazoethane with tert-butylethyne and the reaction of (diazomethyl)benezene withphenylacetylene were also considered theoretically.