Investigation on the effect of trifluoromethyl group on the [3+2] cycloadditions of thiocarbonyl S-methanides with α, β-unsaturated ketones: A theoretical study using DFT

A [3+2] cycloaddition (32CA) reaction among a thiocarbonyl ylide (TCY 2) with (E)-4,4,4- trifluoro-4-phenylbut-3-en-2-one (TFB 4) as an electron-deficient enone in tetrahydrofuran (THF) were studied within the Molecular Electron Density Theory (MEDT), at the DFTB3LYP/6-31G(d) computational level to analysis energetics, selectivities, and mechanistic aspects. The reaction can progress in four competitive 32CA reaction paths. An analysis of the density functional theory (DFT)-based reactivity indices shows that TCY 2 is a strong nucleophile and TFB 4 is a strong electrophile. Parr function analysis at the reactive sites of reagents demonstrates that the C1-C6 attack should be the more favorable regioselective channel in 32CA reaction of TCY 2 toward TFB 4. An exploration of computed relative Gibbs free energies implies that the studied 32CA reaction leads to thiolanes 4 as the unique cycloadduct, in complete agreement with the experimental outcomes. The global electron density transfer (GEDT) value at the energetically most preferred transition state TS 1 reveals that this pseudoradical type (pdr-type) 32CA reactions exhibits a notable polar character.