Diphenylphoshinylhydroxylamine (DPPH) Affords Late-Stage S-Imination To Access Free-NH Sulfilimines and Sulfoximines

Sulfilimines, as potential aza-isosteres of sulfoxides, are valued as building blocks, auxiliaries, ligands, bioconjugation handles, and as precursors to versatile S(VI) scaffolds including sulfoximines and sulfondiimines. Here, we report a thioether imination methodology that exploits O-(diphenylph...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2024-01, p.e202314906
Main Authors: Gunasekera, Shanal, Pryyma, Alla, Jung, Jimin, Greenwood, Rebekah, Patrick, Brian O, Perrin, David
Format: Article
Language:English
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Summary:Sulfilimines, as potential aza-isosteres of sulfoxides, are valued as building blocks, auxiliaries, ligands, bioconjugation handles, and as precursors to versatile S(VI) scaffolds including sulfoximines and sulfondiimines. Here, we report a thioether imination methodology that exploits O-(diphenylphosphinyl)hydroxyl amine (DPPH). Under mild, metal-free, and biomolecule-compatible conditions, DPPH enables late-stage S-imination on peptides, natural products, and a clinically trialled drug, and shows both excellent chemoselectivity and broad functional group tolerance. This methodological report is extended to an efficient and high-yielding one-pot reaction for accessing free-NH sulfoximines with diverse substrates including ones of potential clinical importance. In the presence of a rhodium catalyst, sulfoxides are S-iminated in higher yields to afford free-NH sulfoximines. S-imination was validated on an oxidatively delicate amatoxin to give sulfilimine and sulfoximine congeners. Interestingly, these new sulfilimine and sulfoximine-amatoxins show cytotoxicity. This is further extended to create sulfilimine and sulfoximine-Fulvestrant and Buthionine analogues.
ISSN:1521-3773