Efficient Synthesis of Trifluoromethyl Amines through a Formal Umpolung Strategy from the Bench-Stable Precursor (Me4N)SCF3

• Published in: Angewandte Chemie Vol. 129; no. 1; pp. 227 - 230
• Main Authors: Scattolin, Thomas, Deckers, Kristina, Schoenebeck, Franziska
• Format: Journal Article
• Language: English; German
• Published: Weinheim Wiley Subscription Services, Inc 02-01-2017
• Subjects: Amines; Chemistry; Fluorides; Functional groups; Intermediates; Reagents; Room temperature; Synthesis
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201609480

Reported herein is the one-pot synthesis of trifluoromethylated amines at room temperature using the bench-stable (Me4N)SCF3 reagent and AgF. The method is rapid, operationally simple and highly selective. It proceeds via a formal umpolung reaction of the SCF3 with the amine, giving quantitative formation of thiocarbamoyl fluoride intermediates within minutes that can readily be transformed to N-CF3. The mildness and high functional group tolerance render the method highly attractive for the late-stage introduction of trifluoromethyl groups on amines, as demonstrated herein for a range of pharmaceutically relevant drug molecules.