title: Metal-Free Synthesis of Fluorinated Indoles Enabled by Oxidative Dearomatization.
abstract: Nitrogen heterocycles are found in a majority of approved small-molecule pharmaceuticals, and the number of approved fluorinated drugs is increasing each decade. Therefore, new approaches for accessing fluorinated nitrogen heterocycles are of great significance. A novel, scalable, and metal-free method for accessing a wide range of fluorinated indoles is described. This oxidative-dearomatization-enabled approach assembles 2-trifluoromethyl NH-indole products from simple commercially available anilines with hexafluoroacetylacetone in the presence of an organic oxidant. The nature of the aniline N-capping group is critical for the success of this new reaction. Furthermore, the indole products contain a 3-trifluoroacetyl group, which can be exploited to access a plethora of useful functional groups.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 E. University Blvd., Tucson, AZ, 85721, USA.
authors.forename: Edon
authors.initials: E
authors.lastname: Vitaku
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 E. University Blvd., Tucson, AZ, 85721, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 E. University Blvd., Tucson, AZ, 85721, USA. njardars@email.arizona.edu.
authors.forename: Jon T
authors.initials: JT
authors.lastname: Njardarson
keywords: dearomatization; fluorine; indoles; nitrogen heterocycle; synthetic methods