title: Enhanced Structural Variety of Nonplanar N-Oxyl Radical Catalysts and Their Application to the Aerobic Oxidation of Benzylic C-H Bonds.
abstract: The design and synthesis of structurally variable, nonplanar N-oxyl radical catalysts and their application to the aerobic oxidation, etherification, and acetoamidation of benzylic C-H bonds are described. The catalytic oxidation of C-H bonds represents a powerful tool to synthesize oxygenated functional molecules from simple hydrocarbons in a straightforward way. Electron-deficient N-oxyl radical catalysts, such as phthalimidoyl N-oxyl (PINO) radical, generated from N-hydroxyphthalimide (1), have attracted much attention because of their applications in the oxidation of C-H bonds with high bond dissociation energy (BDE). However, a few sites in 1 are available for structural modifications and improvements of the catalytic performance. By replacing one carbonyl group in 1 with a trifluoromethyl (CF3)-substituted sp(3)-carbon, we generated an additional tunable site and a nonplanar backbone, while retaining the desirable electron-withdrawing properties and increasing the lipophilicity with respect to 1. We synthesized a variety of N-hydroxy precatalysts containing such a CF3 moiety, and investigated their utility in the aerobic oxidation of benzylic C-H bonds. Precatalysts with electron-withdrawing substituents, such as trifluoroethoxy and the acetophenone moieties, afforded higher yields than a corresponding methoxy-substituted analogue. The introduction of substituents at the aromatic ring was also effective, as evident from the performance of 7-CF3 and 4,5,6,7-tetrafluoro precatalysts. Especially the combination of trifluoroethoxy- and 4,5,6,7-tetrafluoro substitution afforded a superior performance. These catalyst systems exhibited high functional group tolerance during the aerobic oxidation of C-H bonds, and benzylic etherification and Ritter-type reactions could be carried out at room temperature when a selected precatalyst and N-bromosuccinimide (NBS) were used.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kadoh
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Oisaki
authors.forename: Motomu
authors.initials: M
authors.lastname: Kanai
mesh_terms: D000332:Aerobiosis; D001593:Benzyl Compounds / Q000737:chemistry*; D002384:Catalysis; D005609:Free Radicals / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010797:Phthalimides / Q000737:chemistry*
chemical_list: D001593:Benzyl Compounds; D005609:Free Radicals; D010797:Phthalimides