Exploring effects of the trifluoromethyl substituent on the chemoselectivity and regioselectivity of [3+2] cycloadditions of thiocarbonyl S‐methanides with α, β‐unsaturated ketones

Abstract

AbstractA [3+2] cycloaddition (32CA) reaction between a thiocarbonyl ylide (TCY 2) and an electron‐deficient enone (TFB 3) in tetrahydrofuran (THF) was studied in the light of molecular electron density theory at the DFT‐B3LYP/6‐31G(d) computational level to probe energetics and selectivities. The reaction was investigated in four competitive reaction paths associated with the CC and CO chemoselectivities in TFB 3. An analysis of the density functional theory‐based reactivity indices shows that TCY 2 is a strong nucleophile, and TFB 3 is also a strong electrophile. Although both C4─C5 and C6─O7 double bonds of TFB 3 can potentially be involved in 32CA reaction toward TCY 2, computed relative Gibbs free energies obviously demonstrate that C6─O7 involvement in a quite regioselective manner is entirely preferred over the C4─C5 one in an excellent agreement with the chemoselectivity and regioselectivity observed experimentally. Interestingly, such a chemoselectivity could not be rationalized through assessment of the electrophilic Parr functions calculated at the C4, C5, C6, and O7 centers of TFB 3. The global electron density transfer value, 0.31 e, calculated at the most energetically preferred transition state structure TS 1 involved within the C6─O7 chemoselective reaction channel demonstrates that this pseudodiradical type (pdr‐type) 32CA reaction has a notable polar character.