NMR and DFT Studies with a Doubly Labelled 15 N/ 6 Li S ‐Trifluoromethyl Sulfoximine Reveal Why a Directed ortho ‐Lithiation Requires an Excess of n ‐BuLi

Matthieu Hédouin (1) , Anne‐laure Barthelemy (2) , Nicolas Vanthuyne (3) , Hend Besrour (1) , Jacques Maddaluno (1) , Emmanuel Magnier (2) , Hassan Oulyadi (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 ILV - Institut Lavoisier de Versailles
3 ISM2 - Institut des Sciences Moléculaires de Marseille

This work shows why it is imperious to use an excess of butyllithium for a directed ortho-lithiation of a trifluoromethyl sulfoximine. The analysis of mixtures of n-BuLi and sulfoximine 1 in THF-d8 using {1H, 6Li, 13C, 15N, 19F} NMR experiments at low temperatures reveal that a first deprotonation occurs that leads to dimeric and tetrameric N-lithiated sulfoximine (93 : 7). Using an excess n-BuLi (5 equivalents), the second deprotonation on the ortho-position of the aromatic occurs. Six species were observed and characterized on the way. It includes three aggregates involving a sulfoximine: i) a [dilithiated sulfoximine/(n-BuLi)] dimer solvated by four molecules of THF (Agg2, 39 %); ii) a [dilithiated sulfoximine/(n-BuLi)3] tetramer solvated by six molecules of THF (Agg3, 39 %); iii) a [dilithiated sulfoximine/(n-BuOLi)3] tetramer solvated by four molecules of THF (Agg1, 22 %). A DFT study afforded optimized solvated structures for all these aggregates, fully consistent with the NMR data

Domaines: Chimie organique; Chimie théorique et/ou physique

Matthieu Hédouin, Anne‐laure Barthelemy, Nicolas Vanthuyne, Hend Besrour, Jacques Maddaluno, et al.. NMR and DFT Studies with a Doubly Labelled 15 N/ 6 Li S ‐Trifluoromethyl Sulfoximine Reveal Why a Directed ortho ‐Lithiation Requires an Excess of n ‐BuLi. Angewandte Chemie International Edition, 2023, 62 (5), pp.e202214106. ⟨10.1002/anie.202214106⟩. ⟨hal-03912827⟩