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

• Published in: International journal of quantum chemistry 2020-07, Vol.120 (14), p.n/a
• Main Authors: Tang, Jing, Xu, Dong‐Hui, Wang, Xin, Li, Laicai, Liu, Xiang‐Yang, Su, Xin‐Tong, Guo, Jianmin, Zhai, Bin
• Format: Article
• Language: English
• Subjects: [3+2] cycloaddition; CF3‐substituted pyrazolidine; Chemical reactions; Chemical synthesis; Chemistry; concerted asynchronous mechanism; Cycloaddition; Density functional theory; Isoprene; Physical chemistry; Quantum physics; Stereoselectivity; Substitutes; Wave functions
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/qua.26236

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 CF3‐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 CF3‐substituted syn‐pyrazolidine 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. The concerted asynchronous mechanism and origin of diastereoselectivity of Cu(OTf)2‐catalyzed [3+2] cycloaddition of trifluoromethylated N‐acylhydrazones and isoprene in the synthesis of pyrazolidines are revealed by density functional theory calculations for the first time.