Fluorine-activated and -directed allene cycloadditions with nitrile oxide: Exploration of selectivities, reactivities, energetic aspects, and molecular mechanism.

This work investigates theoretically the activation and directing effects in a fluorinated allenic system, 1-(5,5-difluoropenta-3,4-dienyl)benzene (FPB), during a Cu+-catalyzed cycloaddition reaction with phenyl nitrile oxide (NO). The FPB…Cu+ interactions were studied and it was found coordination of Cu+ ion to the central carbon atom of the allenic system and a cation-π interaction in the most stable complex. Four potential possible reaction paths were considered between FPB and NO and the computational results corroborated the experimental findings, indicating that the formation of CA-2 is favored in uncatalyzed reaction, whereas CA-3 formation is preferred in catalyzed one. The calculated energy difference between the most stable and unstable TS is about 32 kJ/mol for the uncatalyzed system, a value that increases to 192 kJ/mol under catalysis. Furthermore, the computed activation Gibbs free energy for TS-2 (the most favorable transition state in uncatalyzed reaction) is 101.03 kJ/mol and that for TS-3-cat (the most favorable TS in catalyzed reaction) is 92.02 kJ/mol. Consequently, the catalyst is shown to be effective not only in decreasing the activation barrier but also in controlling the regioselectivity of the reaction by increasing the difference between the energy surfaces of TSs. The regioselectivity was rationalized through Natural Bond Orbital NBO (based on Ei→j(2) values resulted from E(2) perturbation theory) and Independent Gradient Model based on Hirshfeld partition (IGMH) analyses. Finally, application of the Electron Localization Function (ELF) analysis revealed the molecular mechanism to be a two-stage one-step mechanism in both cases.