FLUORINE: THE KEY OF MEDICAL DEVELOPMENT

M. Calles

   Synthesising organic products with fluorine atoms has a huge interest in the world of organic chemistry because of the introduction of fluorine in order to develop small-molecule drugs^1-4. For this reason, there has been interest to produce pharmacologically fluoridated pyridines, since pyridines are part of the structure of a large number of pharmacologically significant compounds⁴. In this way, a study carried out for some researchers from Xiangtan University have developed a NH₄I- based reductive system in which the oxime N-O bond is cleaved.

Scheme 1. Transition-Metal-Free Reduction of Oximes for Fluorinated Pyridines

   Using O-acyl oximes allows to construct heterocycles in an easy way due to the in-situ imine formation by reducing O-acyl oximes, which avoid the use of anhydrous solvents⁵. In this case, the researchers have developed an iodine-based system to reduce N-O bond of oximes using trifluoromethylated carbonyl compounds that couple with O-acyl oximes.

Scheme 2. Formation of N-Containing Heterocycles through Oxime N−O Reduction

   Furthermore, this protocol is highly regio and chemoselective, with tolerance to the presence of other functional groups and high yields are obtained comparing with traditional condensation methods for pyridine assembly.

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[2] Kirk, K. L. J. Fluorine Chem. 2006, 127, 1013.

[3] Swain, C.; Rupniak, N. M. J. Annu. Rep. Med. Chem. 1999, 34, 51.

[4] Kiss, L. E.; Ferreira, H. S.; Learmonth, D. A. Org. Lett. 2008, 10, 1835.

[5] Kitamura, M.; Narasaka, K. Chem. Rec. 2002, 2, 268.