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

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. (C) 2015 Elsevier B.V. All rights reserved.