title: Synthesis of Redshifted Azobenzene Photoswitches by Late-Stage Functionalization.
abstract: Azobenzenes are versatile photoswitches that can be cycled between their trans- and cis-configuration with light. The wavelengths required for this isomerization are substantially shifted from the UV to the visible range through tetra-ortho-chlorination. These halogenated azobenzenes display unique photoswitching characteristics, but their syntheses remain limited and inefficient. A new general method for the synthesis of tetra-ortho-chloro azobenzenes has been developed, which relies on direct palladium(II)-catalyzed C-H activation of pre-existing standard azobenzenes. This late-stage functionalization has a broad substrate scope and can be used to create a variety of useful building blocks for the construction of more elaborate redshifted photopharmaceuticals. This method is used to prepare red-AzCA-4, a photoswitchable vanilloid that enables optical control of the cation channel TRPV1 with visible light.
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: David B
authors.initials: DB
authors.lastname: Konrad
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: James A
authors.initials: JA
authors.lastname: Frank
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany. dirk.trauner@lmu.de.
authors.forename: Dirk
authors.identifier: http://orcid.org/0000-0002-6782-6056
authors.initials: D
authors.lastname: Trauner
mesh_terms: D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D054879:Halogenation; D006860:Hydrogen Bonding; D007536:Isomerism; D008027:Light; D055668:Photochemical Processes; D050916:TRPV Cation Channels / Q000737:chemistry*
chemical_list: D001391:Azo Compounds; D050916:TRPV Cation Channels; C009850:azobenzene
keywords: C−H activation; azobenzene; halogenation; ion channels; photopharmacology