Stabilized Carbon‐Centered Radical‐Mediated Carbosulfenylation of Styrenes: Modular Synthesis of Sulfur‐Containing Glycine and Peptide Derivatives

• Published in: Advanced science 2024-08, Vol.11 (29), p.e2402428-n/a
• Main Authors: Yang, Zihui, Liu, Jia, Xie, Lan‐Gui
• Format: Article
• Language: English
• Subjects: Amino acids; capto‐dative effect; Carbon; carbosulfenylation; Hydrogen; Investigations; Light emitting diodes; Peptides; Photocatalysis; radicals; Reagents; Solvents; Sulfur; sulfur‐containing amino acids
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202402428

Sulfur‐containing amino acids and peptides play critical roles in organisms. Thiol‐ene reactions between the thiol residues of L‐cysteine and the alkenyl fragments in the designed coupling partners serve as primary tools for constructing C─S bonds in the synthesis of unnatural sulfur‐containing amino acid derivatives. These reactions are favored due to the preference for hydrogen transfer from thiol to β‐sulfanyl carbon radical intermediates. In this paper, the study proposes utilizing carbon‐centered radicals stabilized by the capto‐dative effect, generated under photocatalytic conditions from N–aryl glycine derivatives. The aim is to compete with the thiol hydrogen, enabling radical C─C bond formation with β‐sulfanyl carbon radicals. This protocol is robust in the presence of air and water, offers significant potential as a modular and efficient platform for synthesizing sulfur‐containing amino acids and modifying peptides, particularly with abundant disulfides and styrenes. Visible light‐induced carbosulfenylation of styrenes with N‐aryl glycinates and disulfides is achieved. Using N‐aryl glycinate substrates as precursors of the capto‐dative effect‐stabilized carbon‐centered radicals, the protocol shows insensitivity to air and water and demonstrate great potential as a modular and straightforward platform for the synthesis of sulfur‐containing amino acids and peptide modification.