title: Innate C-H trifluoromethylation of heterocycles.
abstract: Direct methods for the trifluoromethylation of heteroaromatic systems are in extremely high demand in nearly every sector of chemical industry. Here we report the discovery of a general procedure using a benchtop stable trifluoromethyl radical source that functions broadly on a variety of electron deficient and rich heteroaromatic systems and demonstrates high functional group tolerance. This C-H trifluoromethylation protocol is operationally simple (avoids gaseous CF(3)I), scalable, proceeds at ambient temperature, can be used directly on unprotected molecules, and is demonstrated to proceed at the innately reactive positions of the substrate. The unique and orthogonal reactivity of the trifluoromethyl radical relative to aryl radicals has also been investigated on both a complex natural product and a pharmaceutical agent. Finally, preliminary data suggest that the regioselectivity of C-H trifluoromethylation can be fine-tuned simply by judicious solvent choice.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Yining
authors.initials: Y
authors.lastname: Ji
authors.forename: Tobias
authors.initials: T
authors.lastname: Brueckl
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Baxter
authors.forename: Yuta
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Ian B
authors.initials: IB
authors.lastname: Seiple
authors.forename: Shun
authors.initials: S
authors.lastname: Su
authors.forename: Donna G
authors.initials: DG
authors.lastname: Blackmond
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D002244:Carbon / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D008745:Methylation
chemical_list: D006571:Heterocyclic Compounds; D006845:Hydrocarbons, Fluorinated; D002244:Carbon; D006859:Hydrogen