Newsletter Issue 14 Apr-Jun 2010

From Carboxylic Acids to the Trifluoromethyl Group Using BrF3

This paper by Rozen (Tel-Aviv University, Israel) shows a new method for transforming a carboxylic acid into a CF3 group, a useful bioisostere. Typical methods for introducing this moiety include the Prakash–Rupert’s reagent (CF3SiMe3), fluoroform (CF3H), trifluoromethyl halides (i.e., CF3I), and electrophilic trifluoromethylations. Carboxylic acids can be turned into CF3 by sulfur tetrafluoride (SF4). This new protocol uses also carboxylic acids as starting materials, which are in first transformed into dithioesters by sequential reaction of a starting acid chloride with ethanethiol, followed by the use of Lawesson's reagent. The dithioester is then solved in CFCl3, cooled to 0 °C and reacted with BrF3 (commercially available) for only 2-3 minutes. Yields are usually very good (around 70%) and the method can be applied both to aryl and alkylcarboxylic acids. No data is given on the use of heteroarylcarboxylic acids. The method can be long and smelly, but compared to other methods for the introduction of CF3 we have used... looks wonderful !

Tetrahedron 2010, Volume 66, Issue 20, Pages 3579-3582. See: 10.1016/j.tetlet.2010.03.045

GalChimia, S.L. Cebreiro s/n, 15823 O Pino (A Coruña) -  Spain Tel: +34 981 814 506 Fax: +34 981 814 507  www.galchimia.com