Mechanistic Insights Into Silver(?)-Mediated Terminal Alkynes

Silver salts possess the high catalytic activity, lewis acid characteristic, low price, and can effectively avoid other transition-metals catalyzed terminal alkynes coupling reaction occuring. Therefore, silver-catalyzed terminal-alkynes reactions are developing to be a hot field of organic synthesis in recent years. Theoretical and computational chemistry plays an important role in clarifying reactions, especially organic reaction mechanisms. Thus it has become an indispensable means to explore the reaction mechanism. In this work, we focused on computational investigations on the effect of reaction conditions ?substrates, catalyst, ligand, solvent, and water? on the mechanism to disclose the unique catalytic nature and high catalytic activity of silver?I?. The main contents are shown as following:A combined Density functional theory ?DFT? and experimental study was performed to reveal the mechanism of isocyanide-alkyne cycloaddition. Our results indicate that the mechanism of this valuable reaction is an unexpected multi-catalyzed radical process, including the formation of isocyanide radical, the cycloaddition of isocyanide radical and silver-acetylide, protonation, and H-shift processes. The rate-determining step is the second C2-C4 bond formation with a free-energy barrier ???G++? of 10.2 kcal/mol. Ag₂CO₃ exposes double roles as base and initiator to form the initial isocyanide radical. Substrate ?isocyanide? and solvent ?dioxane? serve as radical shuttle to complete the protonation of silver-containing five-membered intermediate, simultaneously regenerating the isocyanide radical. Furthermore, dioxane serves as proton shuttle and hydrogen donor/accepctor to decrease the activation barrier of the last H shift process, increasing the reactivity dramatically. These findings may open new insights for the mechanistic understanding of silver-catalyzed isocyanides or alkynes reactions, which in turn may provide guidelines for further optimization of the reaction conditions experimentally.Density functional theory investigations have elucidated the mechanism of water-assisted silver???-mediated hydroazidation of terminal alkynes to vinyl azides. The reaction mechanism mainly involves four processes:Ag₂CO₃ coordinates with TMS-N₃ to assist water as hydrogen source and proton-shuttle in facilicating HN₃ formation, water assistes the deprotonation of terminal alkyne by Ag₂CO₃ to access silver-acetylide, the regioselective addition of HN₃, and the protonation of terminal carbon by AgHCO3. Ag₂CO₃-participated C-N bond formation is the rate-determining step. It is note worthy that the mediated mode of Ag₂CO₃ to substrates includes Ag₂CO₃-coordinated, Ag₂CO₃-participated, and the exchange with each other. The reaction regioselectivity follows Markovnikov'rule, which explains the experimental observations well. These results provide a universal mechanism for silver?I?-mediated hydroazidation of terminal alkynes and guidance for experimental researchers.