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

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.