A General Platform for <i>S</i> ‐Stereogenic α‐Fluoroalkyl S(IV/VI) Compounds via Enantioselective Radical Fluoroalkylation of Sulfenamides
Abstract
ABSTRACT α‐Fluoroalkyl‐substituted high‐valent sulfur motifs are important structural elements in fluorinated molecule design and exhibit broad application potential in diverse fields. However, access to S ‐stereogenic α‐fluoroalkyl S(IV/VI) compounds still relies largely on classical resolution, resulting in limited efficiency and selectivity. We herein report a copper‐catalyzed asymmetric radical C–S cross‐coupling that effectively tames highly reactive α‐fluoroalkyl radicals, enabled by a sequential stereodiscrimination–chirality transfer strategy, providing rapid access to S ‐chiral α‐fluoroalkyl sulfilimines. Integrated with downstream transformations, this reaction serves as a general and systematic platform for S ‐chiral α‐fluoroalkyl S(IV/VI) compounds. The synthetic utility of the method is demonstrated by gram‐scale synthesis and concise access to diverse chiral fluoroalkyl reagents and bioisosteres of sulfur‐containing drugs.
Article Details
Authors (9)
Yu‐Shuai Zhang
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China
Li‐Wen Fan
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China
Pei‐Jie Huang
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China
Fu Liu
New Cornerstone Science Laboratory, Shenzhen Grubbs Institute, Department of Chemistry, and Guangming Advanced Research Institute
Li Qin
Dai‐Lei Yuan
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China
Chen‐Yu Xiao
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China
Xin‐Yuan Liu
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China
Qiang‐Shuai Gu
New Cornerstone Science Laboratory Shenzhen Grubbs Institute Department of Chemistry and Guangming Advanced Research Institute Southern University of Science and Technology Shenzhen China