Understanding the regioselectivity and molecular mechanism in the synthesis of isoxazoles containing pentafluorosulfanyl substitution via a [3+2] cycloaddition reaction: A DFT study

Abstract

Abstract A theoretical study was performed on the [3+2] cycloaddition (32CA) reaction of benzonitrile oxide, BNO 4, toward phenyl SF5-acetylene, PAC 5, in the presence of tetrahydrofuran (THF) at the DFT-B3LYP/6-31G* level. Calculated relative Gibbs free energies indicate that the studied 32CA reaction takes place via a complete C1 C4 regioselective channel passing through TS1 affording the unique formal [3+2] cycloadduct CA1 observed experimentally. While based on the calculated Parr functions on the interacting sites of reagents this cycloaddition should proceed via energetically unfavorable C1 C5 channel passing through TS2, a natural steric analysis evidently showed that destabilizing repulsion effects, rather than the electronic ones, are responsible for the complete C1 C4 regioselective fashion provided by the considered 32CA reaction. An ELF topological analysis of the bonding changes along this 32CA reaction supports a non-concerted two-stage one-step molecular mechanism in which the formation of second O3 C5 single bond takes place when the formation of first C1 C4 one is almost complete.