title: Charge-transfer-directed radical substitution enables para-selective C-H functionalization.
abstract: Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.|Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Boursalian
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
authors.forename: Won Seok
authors.initials: WS
authors.lastname: Ham
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Mazzotti
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.|Max-Planck-Institut für Kohlenforschung, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ritter
mesh_terms: D002244:Carbon / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D004553:Electric Conductivity; D004583:Electrons; D005449:Fluorenes / Q000138:chemical synthesis / Q000737:chemistry*; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry
chemical_list: D005449:Fluorenes; D006841:Hydrocarbons, Aromatic; D002244:Carbon; D006859:Hydrogen