Difluorocarbene-Derived Trifluoromethylthiolation and [18F]Trifluoromethylthiolation of Aliphatic Electrophiles

• Published in: Angewandte Chemie International Edition 2015-11, Vol.54 (45), p.13236-13240
• Main Authors: Zheng, Jian, Wang, Lu, Lin, Jin-Hong, Xiao, Ji-Chang, Liang, Steven H.
• Format: Article
• Language: English
• Subjects: Aliphatic compounds; carbenes; Compatibility; Fluorides; fluorine; Fluorine - chemistry; Fluorine Radioisotopes - chemistry; Functional groups; Hydrocarbons, Fluorinated - chemical synthesis; Hydrocarbons, Fluorinated - chemistry; Ions - chemistry; isotopic labeling; Molecular Structure; positron emission tomography; Radiochemistry; Reaction time; Strategy; Sulfhydryl Compounds - chemical synthesis; Sulfhydryl Compounds - chemistry; Sulfur; Sulfur - chemistry; Tolerances; Transformations
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201505446

The first trifluoromethylthiolation and [18F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition‐metal‐free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous‐fluoride‐mediated transformation enables unprecedented syntheses of [18F]CF3S‐labeled molecules from most commonly used [18F]fluoride ions. The rapid radiochemical reaction time (≤1 min) and high functional‐group tolerance allow access to a variety of aliphatic [18F]CF3S compounds in high yields. [18F] label: An efficient, fast, and transition‐metal‐free protocol for trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external fluoride ions is described. This strategy was applied to [18F]trifluoromethylthiolation of alkyl electrophiles, which represents the first example of this type. Ts=4‐toluenesulfonyl.