An Unconventional Mechanistic Insight into SCF₃ Formation from Difluorocarbene: Preparation of ¹⁸F‐Labeled α‐SCF₃ Carbonyl Compounds

Abstract

We discovered trifluoromethylthiolation occurred through sulfuration of difluorocarbene with elemental sulfur for the first time, which overrides our putative and long-standing trifluoromethyl anion-based theory. This mechanistic elucidation not only allows the discovery of an unprecedented chemical process for the formation of thiocarbonyl fluoride, but also enables transition metal-mediated trifluoromethylthiolation and [18F]trifluoromethylthiolation of α-bromo carbonyl compounds with broad substrate scope and compatibility.

Chemistry for Positron Emission Tomography: Recent Advances in 11C‐, 18F‐, 13N‐, and 15O‐Labeling Reactions

“…The method was compatible with aliphatic substrates bearing electron‐withdrawing or electron‐donating groups in RCCs of 22–83 %. Subsequently, the authors found α‐bromocarbonyl compounds could also be converted into α‐[ 18 F]SCF 3 carbonyl derivatives (Scheme 32 B) . An unconventional reaction mechanism was discovered through the identification of a key intermediate, a thiocarbonyl fluoride, in the formation of alkyl‐SCF 3 compounds.…”

Chemie der Positronenemissionstomographie: Aktuelle Fortschritte bei 11C‐, 18F‐, 13N‐ und 15O‐Markierungsreaktionen

“…Die Methode war kompatibel mit aliphatischen Substraten, die elektronenziehende oder elektronenschiebende Gruppen enthalten, wobei RCC von 22–83 % erreicht werden konnten. Anschließend fanden die Autoren, dass auch α‐Bromcarbonyle in die α‐[ 18 F]SCF 3 ‐Carbonyle umgewandelt werden konnten (Schema 32 B) . Bei der Bildung von Alkyl‐SCF 3 ‐Verbindungen wurde anhand der Identifizierung des Schlüsselintermediats Thiocarbonylfluorid ein unkonventioneller Reaktionsmechanismus entdeckt.…”

Synthesis of Alpha‐trifluoromethylthio Carbonyl Compounds: A Survey of the Methods for the Direct Introduction of the SCF3 Group on to Organic Molecules

“…[25] Difluoromethylene phosphobetaine 2 (triphenylphosphoniodifluoroacetate, PDFA), in the presence of elemental sulfur,w as found to generate thiocarbonyl fluoride 3,t hat in turn, after interaction with CsF,p romotes the a-trifluoromethylthiolation of carbonyl compounds (Scheme 16). Trifluoromethylthiolation of a-halo ketones using [Ag(SCF 3 )I] À + K. Very recently,Xiao and Liang, reported useful mechanistic informationf or the formation of trifluoromethylthio anion from difluorocarbene, sulfur,a nd fluoride, and the subsequent interactions between the generated SCF 3 anion and transition metals.…”

“…Very recently,Xiao and Liang, reported useful mechanistic informationf or the formation of trifluoromethylthio anion from difluorocarbene, sulfur,a nd fluoride, and the subsequent interactions between the generated SCF 3 anion and transition metals. [25] Difluoromethylene phosphobetaine 2 (triphenylphosphoniodifluoroacetate, PDFA), in the presence of elemental sulfur,w as found to generate thiocarbonyl fluoride 3,t hat in turn, after interaction with CsF,p romotes the a-trifluoromethylthiolation of carbonyl compounds (Scheme 16).…”