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Exploring effects of the trifluoromethyl substituent on the chemoselectivity and regioselectivity of [3+2] cycloadditions of thiocarbonyl S‐methanides with α, β‐unsaturated ketones
Author(s) -
Hosseini Seyed J.
Publication year - 2020
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.201900360
Subject(s) - chemoselectivity , regioselectivity , chemistry , electrophile , cycloaddition , nucleophile , substituent , density functional theory , ylide , medicinal chemistry , transition state , reactivity (psychology) , stereochemistry , computational chemistry , organic chemistry , catalysis , medicine , alternative medicine , pathology
A [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 CC and CO 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.