biostudies-literatureZhang SLeverhulme TrustCAPES-PrInt/UFPele202511703https://www.ebi.ac.uk/biostudies/studies/S-EPMC12416468biostudies-literatureUnknown64(37)Arylacetamides are important structural motifs found in many bioactive compound classes. Given their significance, the selective decoration of arylacetamides by transition metal-catalyzed C─H activation has attracted considerable attention. Here, we report a two-step transition metal-free formal C─H/C─H coupling of arylacetamides with sulfoxides that proceeds via the formation and rearrangement of little-known α-amido sulfonium salts; the amide motif "catches" the sulfoxide partner prior to its delivery to the ortho-position of the aromatic ring by rearrangement of a sulfur ylide intermediate. The approach delivers alkylated arylacetamides bearing sulfide functional handles that can be exploited in downstream manipulations. This protocol has allowed the synthesis of a dopamine D1 receptor Angewandte Chemie (International ed. in English)Transition Metal-Free Formal C─H/C─H Coupling of Arylacetamides and Sulfoxides: An Interrupted Pummerer/[2,3]-sigmatropic Rearrangement Sequence.PMC12416468RPG‐2023‐156RPG-2023-156Joynson BWLarroza AProcter DJRomano CZhang SLou YXfalseTransition Metal-Free Formal C─H/C─H Coupling of Arylacetamides and Sulfoxides: An Interrupted Pummerer/[2,3]-sigmatropic Rearrangement Sequence.Arylacetamides are important structural motifs found in many bioactive compound classes. Given their significance, the selective decoration of arylacetamides by transition metal-catalyzed C─H activation has attracted considerable attention. Here, we report a two-step transition metal-free formal C─H/C─H coupling of arylacetamides with sulfoxides that proceeds via the formation and rearrangement of little-known α-amido sulfonium salts; the amide motif "catches" the sulfoxide partner prior to its delivery to the ortho-position of the aromatic ring by rearrangement of a sulfur ylide intermediate. The approach delivers alkylated arylacetamides bearing sulfide functional handles that can be exploited in downstream manipulations. This protocol has allowed the synthesis of a dopamine D1 receptor 2025-01-01T00:00:00Z2025 Sep2026-06-02T02:25:09.624Z2026-04-13T03:11:42.054ZS-EPMC124164684073426010.1002/anie.202511703