A combined experimental and computational study of ligand-controlled Chan-Lam coupling of sulfenamides.

Han, Kaiming; Liu, Hong; Rotella, Madeline E; Xu, Zeyu; Tao, Lizhi; Chen, Shufeng; Kozlowski, Marisa C; Jia, Tiezheng · Nat Commun · 2024

basic_science · Level V

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Abstract

The unique features of the sulfenamides' S(II)-N bond lead to interesting stereochemical properties and significant industrial functions. Here we present a chemoselective Chan-Lam coupling of sulfenamides to prepare N-arylated sulfenamides. A tridentate pybox ligand governs the chemoselectivity favoring C-N bond formation, and overrides the competitive C-S bond formation by preventing the S,N-bis-chelation of sulfenamides to copper center. The Cu(II)-derived resting state of catalyst is captured by UV-Vis spectra and EPR technique, and the key intermediate is confirmed by the EPR isotope response using <sup>15</sup>N-labeled sulfenamide. A computational mechanistic study reveals that N-arylation is both kinetically and thermodynamically favorable, with deprotonation of the sulfenamide nitrogen atom occurring prior to reductive elimination. The origin of ligand-controlled chemoselectivity is explored, with the interaction between the pybox ligand and the sulfenamide substrate controlling the energy of the S-arylation and the corresponding product distribution, in agreement with the EPR studies and kinetic results.