A density functional theory study of the stereoselectivity of Cu(OTf)₂‐catalyzed [3+2] cycloaddition of trifluoromethylated N‐acylhydrazones and isoprene: A concerted asynchronous mechanism

Abstract

Here we employ density functional theory calculations to systematically investigate the underlying mechanism of Cu(OTf) 2 -catalyzed [3+2] cycloaddition reactions in the synthesis of CF 3 -substituted pyrazolidines. About eight possible initial configurations of the [3+2] reaction is considered, and all relevant reactants, transition states, and products are optimized. Based on these structures, internal reaction coordinate paths, and wavefunction analysis results, we conclude that the Cu(OTf) 2 -catalyzed [3+2] cycloaddition follows a concerted asynchronous mechanism. The C N bond forms immediately after the formation of the C C bond. Among the eight reaction paths, the energy barrier for the [3+2] reaction that leads to the CF 3 -substituted synpyrazolidine is the lowest, $5.4 kcal/mol, which might result in the diastereoselectivity that is observed in the experiment. This work not only gives the detailed mechanism of the Cu(OTf) 2 -catalyzed [3+2] cycloaddition but can also be helpful for the future designation of Cu(OTf) 2 -based cycloaddition processes.

[3 + 2] Cycloadditions and Retrocycloadditions of Niobium Imido Complexes: An Experimental and Computational Mechanistic Study

“…The asynchronous nature of this reaction pathway is made apparent by the appearance of a "shoulder" in each of the reaction path diagrams. 33,58−60 While others have reported computational studies of asynchronous 58,59 and even "highly asynchronous" cycloadditions, 60 we could find no other reports of bond formation disrupting the two bond formation/cleavage events.…”

“…Overall, the individual cycloaddition and retrocycloaddition processes in this reaction pathway are predicted to occur via an asynchronous concerted reaction mechanism: Nb–N1 and N3–N4 bond cleavage/formation occur at distinct points along the reaction coordinate and are separated by the formation of an Nb–N3 bond, while no stable intermediates are formed along the reaction path. The asynchronous nature of this reaction pathway is made apparent by the appearance of a “shoulder” in each of the reaction path diagrams. ,− While others have reported computational studies of asynchronous , and even “highly asynchronous” cycloadditions, we could find no other reports of bond formation disrupting the two bond formation/cleavage events.…”