Synthesis of Cyclic Sulfilimines and Sulfoximines via Copper Mediated C(sp2)–H Sulfanylation of Benzylamines with a Catalytic Transient Directing Group

06 May 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

C–H Functionalization presents opportunities to streamline the synthesis of valuable molecular structures. This study details the development of a copper mediated, transient C(sp²)–H sulfanylation of benzylamines with a transient directing group (TDG). Subsequent oxidative cyclization forms novel cyclic sulfilimines and sulfoximines, emerging heterocyclic scaffolds with attractive properties for drug discovery. Crucially, sulfenamides were identified as effective sulfanylating reagents for the C–H sulfanylation with catalytic 2-hydroxynicotinaldehyde as the TDG. Unconventionally, sulfenamides provided a slow release of the essential sulfanyl radicals through a thermally induced homolytic cleavage of the N–S bond, supported by mechanistic studies including EPR spectroscopy and radical quenching experiments. The sulfide products were then readily diversified at sulfur and nitrogen including through cyclisation.

Keywords

C–H Functionalization
Transient directing group
Copper
Sulfanylation
Sulfenamide

Supplementary materials

Title
Description
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Title
Supporting Information
Description
Supporting Information – Reaction Optimization Data, Processed EPR data, Experimental Procedures, 1H and 13C NMR Spectra, X-Ray data
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