Palladium catalyzed radical relay for the oxidative cross-coupling of quinolines

Abstract

Traditional approaches for transition-metal catalyzed oxidative cross-coupling reactions rely on sp²-hybridized starting materials, such as aryl halides, and more specifically, homogeneous catalysts. We report a heterogeneous Pd-catalyzed radical relay method for the conversion of a heteroarene C(sp³)-H bond into ethers. Pd nanoparticles are supported on an ordered mesoporous composite which, when compared with microporous activated carbons, greatly increases the Pd d charge because of their strong interaction with N-doped anatase nanocrystals. Mechanistic studies provide evidence that electron-deficient Pd with Pd-O/N coordinations efficiently catalyzes the radical relay reaction to release diffusible methoxyl radicals, and highlight the difference between this surface reaction and C-H oxidation mediated by homogeneous catalysts that operate with cyclopalladated intermediates. The reactions proceed efficiently with a turn-over frequency of 84 h^-1 and high selectivity toward ethers of >99%. Negligible Pd leaching and activity loss are observed after 7 catalytic runs.

Fig. 1. Structure of Pd nanocatalysts.

a, b Representative HAADF-STEM images for Pd/(N)TiO₂-OMC and c the corresponding Pd, N and Ti elemental maps. The inset in a is the Pd particle size distribution which was determined from at least 200 nanoparticles. d HRTEM image of Pd/(N)TiO₂-OMC. e Enlarged view of the white square in d. The top-right and bottom-right insets correspond to Pd and TiO₂ unit cells, respectively. f Selected-area FFT patterns of Pd and TiO₂ from the area in the blue circle in e.

Fig. 2. Electronic properties.

a, b XANES spectra of the a Pd K-edge and b Pd L₃-edge, c k²-weighted and FT-EXAFS spectra of the Pd K-edge, and d XPS spectra of the 3d level of Pd for Pd/TiO₂-OMC and Pd/(N)TiO₂-OMC catalysts. The reference samples include a Pd foil, PdO, and Pd/SBA-15. The Fourier transforms in c were not corrected for phase shifts. The Pd binding energies in d were fitted by peak fitting programs. Pd/(N)TiO₂-OMC-R7 is the catalyst after being used in seven runs.

Fig. 3. Kinetics study and substrate scope.

a Conversion plots for the Pd-catalyzed direct methoxylation of 8-MeQ with reaction time. b Comparison of the conversion of 8-MeQ with and without the addition of a solid SH-SBA-15 trapping agent over the various Pd catalysts (S:Pd = 35 in molar ratio). c Substrate scope of the C(sp³)–H direct oxidative functionalization of quinolines catalyzed by Pd/(N)TiO₂-OMC. d Relationship between the d-charge depletion at Pd sites and activation energy (E_a, blue bar), TOF (red sphere), and the activation entropy (ΔS^0*, orange bar) for the direct methoxylation of 8-MeQ over the Pd catalysts supported on TiO₂-OMC and (N)TiO₂-OMC carriers. Reaction conditions: 0.2 mmol of 8-MeQ; 0.22 mmol of PhI(OAc)₂; 1 mol% Pd catalyst; 2 mL of MeOH; 100°C; 800 rpm; atmospheric pressure; in air.

Fig. 4. Reaction mechanism.

a Intermolecular competition experiments between substituted quinolines showing the effects of electron-withdrawing or donating substituents on the Pd catalyzed direct methoxylation of quinolines. b Kinetic isotope effects measured using deuterated substrates under (i) intermolecular competition and (ii) independent experiments. c Radical trapping experiments and EPR spectra. (i) TEMPO, BQ and BHT were used as radical scavengers to quench the reaction. (ii) Excluding the complete poisoning effect of the radical scavenger of TEMPO on the Pd nanocatalyst in a reaction which is apparently not a radical-involving reaction (hydrogenation of 2-methyl-3-butyn-2-ol). (iii–v) EPR spectra of radical anions when the radical spin trapping reagent DMPO was added to (iii) the reaction system, (iv) in the absence of methanol, and (v) in the absence of PhI(OAc)₂. d DFT calculations. (i) Generation of methoxyl radicals by Pd-catalyzed radical relay reaction over an electron-deficient Pd(111) surface. (ii) Reaction paths and energy landscape of the direct methoxylation of 8-MeQ over Pd(111) and an electron-deficient Pd(111) surface.