Facile Method for the Preparation of Triarylsulfonium Bromides Using Grignard Reagents and Chlorotrimethylsilane as an Activator.

Imazeki, Shigeaki; Sumino, Motoshige; Fukasawa, Kazuhito; Ishihara, Mariko; Akiyama, Toru

doi:10.1002/chin.200445099

Cited by 1 publication

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our case, employment of a ketone building block ( cf. Figure 1 ) precluded the use of organometallic reagents 17 18 19 , and attempted reaction of the thioether 1a with diaryliodonium triflate under copper(II) catalysis 20 failed to provide the desired sulfonium salt 1b ( Figure 2 ). As aliphatic amines coordinate strongly with copper(II) ions, and the resulting complexes can undergo an intramolecular redox reaction to give copper(I) 21 , we attempted to mask the piperidine moiety by protonation with trifluoromethanesulfonic acid (TFSA).…”

Section: Resultsmentioning

confidence: 99%

Sulfonium Salts as Leaving Groups for Aromatic Labelling of Drug-like Small Molecules with Fluorine-18

Sander

Gendron

Yiannaki

et al. 2015

Sci Rep

View full text Add to dashboard Cite

Positron emission tomography (PET) is unique in that it allows quantification of biochemical processes in vivo, but difficulties with preparing suitably labelled radiotracers limit its scientific and diagnostic applications. Aromatic [18F]fluorination of drug-like small molecules is particularly challenging as their functional group compositions often impair the labelling efficiency. Herein, we report a new strategy for incorporation of 18F into highly functionalized aromatic compounds using sulfonium salts as leaving groups. The method is compatible with pharmacologically relevant functional groups, including aliphatic amines and basic heterocycles. Activated substrates react with [18F]fluoride at room temperature, and with heating the reaction proceeds in the presence of hydrogen bond donors. Furthermore, the use of electron rich spectator ligands allows efficient and regioselective [18F]fluorination of non-activated aromatic moieties. The method provides a broadly applicable route for 18F labelling of biologically active small molecules, and offers immediate practical benefits for drug discovery and imaging with PET.

show abstract