A DFT Study of the Stereoselectivity of Cu(OTf)2 Catalyzed [3+2]
Cycloaddition of Trifluoromethylated Nacylhydrazones and Isoprene: A
Concerted Asynchronous Mechanism
Abstract
Pyrazolidines are very important compounds that widely exist in many
natural products. Herein, we have employed high-level DFT calculations
to systematically investigate the underlying mechanism of Cu(OTf)2
catalyzed [3+2] cycloaddition reactions that synthesis
CF3substituted 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, IRC paths and the wavefunction analysis, we concluded that
the Cu(OTf)2 catalyzed [3+2] cycloaddition follow a concerted
asynchronous mechanism. The CN bond forms immediately after the
formation of the CC bond. Among all eight reaction paths, the energy
barrier for the [3+2] reaction that lead to the CF3substituted
synpyrazolidine is the lowest one, ca. 3.2 kcal/mol, which might result
in the diastereoselectivity that observed in experiment. We have also
investigated the reaction processes that without Cu(OTf)2 molecule. The
computational results indicate that the energy barriers that form the
diastereoisomers are much closer and also larger than the Cu(OTf)2
catalyzed one. Therefore, Cu(OTf)2 catalyst plays an important role for
the diastereoselectivity of the [3+2] cycloaddition reaction. Our
present work not only gives the detail 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.