<i>N</i> ‐(Acyldithio)Saccharin: Design, Synthesis and Applications in Catalytic Enantioselective Disulfuration/Amination of Alkenes

Y Yu‐Xuan Huo (State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China) R Ren‐Fei Cao (State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China) J Jie Huang (Department of Chemistry) Z Ze‐Long Li (State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China) Z Zheng‐Wei Wei (State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China) D Deng Zhu Z Zhi‐Min Chen (State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China)

Abstract

Abstract We have designed and successfully synthesized N ‐(acyldithio)saccharin, which is a highly electrophilic, bench‐stable, and user‐friendly disulfurating reagent. This reagent can undergo reactions with diverse N‐, S‐, and C‐nucleophiles at room temperature. In most cases, no additional catalyst is required, and the desired disulfides were readily obtained in moderate to excellent yields. With this reagent, late‐stage disulfuration of pharmaceuticals and biomolecules was readily accomplished. For the first time, catalytic enantioselective disulfuration/amination of unactivated alkenes was achieved using this reagent. A series of chiral disulfides were obtained with high enantioselectivities and yields. The chiral disulfide products can be readily further transformed into chiral sulfonyl fluoride, chiral thiol, and structurally diverse disulfide products. Furthermore, we have evaluated the electrophilic reactivity of a series of disulfurating reagents based on density functional theory calculations, verifying the high reactivity of N ‐(acyldithio)saccharin both experimentally and theoretically.

Article Details

Volume / Issue Vol. 64, Issue 24
Published June 10, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (7)

Y

Yu‐Xuan Huo

State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China

R

Ren‐Fei Cao

State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China

J

Jie Huang

Department of Chemistry

Z

Ze‐Long Li

State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China

Z

Zheng‐Wei Wei

State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China

D

Deng Zhu

Z

Zhi‐Min Chen

State Key Laboratory of Synergistic Chem‐Bio Synthesis School of Chemistry and Chemical Engineering Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs Shanghai Jiao Tong University Shanghai 200240 P.R. China