Anthraquinone-based covalent organic framework as a recyclable direct hydrogen atom transfer photocatalyst for C–H functionalization

Photocatalytic direct hydrogen atom transfer (d-HAT) is a synthetically important strategy to convert C–H bonds to useful C–X bonds. Herein we report the synthesis of an anthraquinone-based two-dimensional covalent organic framework, DAAQ-COF, as a recyclable d-HAT photocatalyst for C–H functionalization. Powder X-ray diffraction, N2 sorption isotherms, solid-state NMR spectra, infrared spectra, and thermogravimetric analysis characterized DAAQ-COF as a crystalline, porous COF with a stable ketoenamine linkage and strong absorption in the visible region. Under visible light irradiation, DAAQ-COF is photo-excited to cleave C(sp3)–H or C(sp2)–H bonds via HAT to generate reactive carbon radicals, which add to different radical acceptors to achieve C–N or C–C coupling reactions. DAAQ-COF is easily recovered from the reaction mixture via centrifugation or filtration and used in six consecutive reaction runs without any decrease in catalytic efficiency. The ease of catalyst separation allows sequential conversion of the C–N coupling intermediate to synthetically useful amide, ester, or thioester products. Photophysical and isotope labelling experiments support the d-HAT mechanism of DAAQ-COF-catalyzed C–H bond functionalization.


Introduction
0][11] A hydrogen atom is abstracted from the substrate by the photoexcited catalyst to generate a reactive carbon radical, which adds to a radical acceptor and then undergoes radical rebound to form the desired C-H functionalized product.In such d-HAT processes, C-H bonds can be functionalized into various C-X bonds (X = C, N, etc.) via judicious choices of coupling agents.The selectivity of HAT reactions is typically high as the hydrogen abstraction step is dictated by the strength of different C-H bonds.
Carbonyl compounds are an important class of photocatalysts for d-HAT. 12,13In the photoexcited state, the C]O group can abstract a hydrogen atom from a substrate to form a HO-Cc intermediate and a substrate radical to initiate the d-HAT cycle.5][16] However, carbonyl HAT catalysts can be deactivated under photocatalytic conditions via multimolecular pathways (such as dimerization), 17,18 and cannot be easily separated from reaction mixtures for reuse in additional catalytic cycles.
Covalent organic frameworks (COFs) are an emerging class of porous materials with an ordered arrangement of organic building blocks.0][21][22][23][24][25][26] Unlike traditional crosslinked organic polymers, ordered structures of crystalline COFs can be readily characterized by X-ray and electron diffraction to guide the rational design of functional COFs. 27,28For example, catalytic COFs have been designed using catalytically active units as the building units.  The gh porosity of COFs allows facile access of catalytically active sites to substrates and diffusion of products through COF channels.3][54][55] Heterogeneous COF-based catalysts can be easily recovered aer the reactions and reused in subsequent reaction cycles.These advantages of COFs have motivated us to explore the design of COF-based catalysts for C-N and C-C coupling reactions via d-HAT.

EDGE ARTICLE
Here we report the rst example of d-HAT catalyzed by a twodimensional (2D) COF, DAAQ-COF, based on 2,6-diaminoanthraquinone (DAAQ) building units.Under visible light irradiation, DAAQ-COF activates C(sp 3 )-H and C(sp 2 )-H bonds to generate carbon-based radicals for C-C or C-N coupling reactions.Unlike indirect HAT, no additional oxidant is required in DAAQ-COF-catalyzed coupling reactions.The DAAQ-COF catalyst is easily separated from the reaction mixture, allowing convenient downstream modications of the product to achieve C-H to C-N/C-S/C-O transformations.The ketoenamine linkage in DAAQ-COF endows high stability under photocatalytic conditions to allow for its recovery and use in six reaction cycles.

Results and discussion
Synthesis and characterization of DAAQ-COF DAAQ-COF was synthesized solvothermally by heating a mixture of DAAQ and 1,3,5-triformylphloroglucinol (TFP) at 120 °C in dimethylacetamide (DMA) and mesitylene with acetic acid (HOAc) as a modulator. 56,57DAAQ-COF was collected via centrifugation and washed with DMA, and then stirred in DMA at 80 °C for 20 hours to completely remove residual DAAQ and TFP monomers.DAAQ-COF appeared dark red with an absorption maximum around 450 nm, suggesting its potential as a photocatalyst under visible light.DAAQ-COF exhibited high crystallinity with a good agreement between the experimental and simulated powder X-ray diffraction patterns (Fig. 1b).Rietveld tting afforded a 2D network structure of DAAQ-COF with an interlayer distance of 3.3 Å.The PXRD pattern of DAAQ-COF did not match the simulated pattern based on the staggered (AB) stacking of 2D networks (Fig. S2 †).The AA stacking of 2D layers afforded more porous structures with large channels of 24 Å in dimension to facilitate substrate access to the catalytic sites.The high porosity of DAAQ-COF was characterized by N 2 sorption isotherms, affording a Brunauer-Emmett-Teller surface area of 1999 ± 55 m 2 g −1 (Fig. 1e).
Transmission electron microscopy (TEM) imaging showed that DAAQ-COF possessed a spherical morphology with a diameter of ∼100 nm and exhibited lattice fringes of ∼3 nm in spacing (Fig. 1c and d S7 †).This b-ketoenamine-based linkage is more stable than the imine linkage in many COFs, which is important for catalytic applications. 58,59Thermogravimetric analysis was conducted by ramping the temperature from 20 °C to 800 °C at a 1.5 °C min −1 in air, and the result showed that DAAQ-COF was stable up to 350 °C and lost 100% of its weight by 500 °C (Fig. S9 †).

Catalytic performance of DAAQ-COF
As anthraquinone (AQ) was reported as a d-HAT catalyst, we tested the HAT catalytic performance of DAAQ-COF.The formation of C-N bonds is an important organic transformation in the synthesis of pharmaceutical compounds. 60We selected the coupling between diethyl azodicarboxylate (DEAD) and tetrahydrofuran (THF) as the model reaction to test the ability of the photoexcited DAAQ-COF in homolytically breaking the C-H bond and abstracting a hydrogen atom from THF.With 1% loading of DAAQ-COF catalyst, the yellow color of DEAD solution faded in 24 hours under CFL light irradiation, and the C-N coupling product was obtained in 94% yield.Without DAAQ-COF, there was only 3% conversion of DEAD, excluding the possibility that DEAD could spontaneously react with THF under compact orescent light (CFL) irradiation.A control experiment without light gave only 2% yield of the coupling product, with most of the starting material remaining unreacted.The addition of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) as a radical scavenger completely shut down the reaction without any conversion of DEAD, indicating the involvement of radical species in this d-HAT reaction.Aer the photocatalytic coupling reaction between DEAD and THF, DAAQ-COF was collected by centrifugation and washed with THF to remove trapped organic compounds.The recycled DAAQ-COF was used as the catalyst in ve subsequent runs without any decrease of catalytic efficiency (Fig. 2b).The PXRD pattern of the recovered DAAQ-COF aer six reaction runs demonstrated the retention of its crystallinity aer d-HAT reactions.In contrast to homogeneous catalysts which are typically difficult to recover from reaction mixtures, DAAQ-COF was stable under photocatalytic conditions and retained its crystallinity aer the reactions (Fig. S13 †), allowing straightforward recovery from the reaction mixtures for reuse in subsequent reaction runs.Thus, DAAQ-COF shows great advantages over homogeneous d-HAT catalysts.
We also examined the substrate scope of DAAQ-COF-catalyzed C-N coupling reactions (Table 1).Both C(sp 3 )-H bonds and C(sp 2 )-H bonds were efficiently activated by DAAQ-COF via HAT to undergo C-N coupling with DEAD.Several activated C(sp 3 )-H bonds in THF (1a), dioxolane (1b), indane (1c), isochroman (1d) and various aldehydes (1e-1n) underwent d-HAT to afford C-N couple products in moderate to high yields.DAAQ-COF also showed high tolerance to different electronwithdrawing and electron-donating functional groups on aryl aldehyde substrates and exhibited great catalytic performance on aliphatic aldehydes as well.
As DAAQ-COF can be easily removed from reaction mixtures by centrifugation or ltration, we tested the feasibility of sequential synthesis via direct conversion of the generated hydrazine imide to other products. 61,62Aer the C-N coupling between benzaldehyde and DEAD under photocatalytic condition, DAAQ-COF was removed from the reaction mixture by ltration, followed by the addition of nucleophilic reactants to the hydrazine imide intermediate.Through reactions with allylamine, phenol, and thiophenol, the hydrazine imide was quantitatively converted to the synthetically useful amide, ester, or thioester, respectively (Fig. 2c).This sequential approach elaborated unfunctionalized C-H bonds to useful C-X bonds under a photocatalytic condition with a recyclable metal-free catalyst.
We next examined the HAT efficiency of DAAQ-COF in C-C coupling reactions.Aer transferring a hydrogen atom from C(sp 3 )-H bonds and C(sp 2 )-H bonds to the photoexcited DAAQ-COF catalyst, the generated carbon radicals reacted with activated pyridine to afford C-H pyridylation products with exclusive C4-selectivity (>98%). 63As shown in Table 1b, 2% loading of DAAQ-COF catalyzed C-C coupling between the activated pyridine and THF or dioxane to afford pyridyl furane 6a in 86% yield or pyridyl dioxane 6b in 53% yield, respectively.Aryl aldehydes with different substituents, including hydrogen, electronwithdrawing uorine, and electron-donating methoxy group were tolerated in the reactions to give products 6c-6e in 75-90% yields.Aliphatic aldehydes were also readily pyridylated to afford products 6f-6h in high yields.

Mechanistic study
Photophysical and kinetic isotope effect (KIE) experiments were conducted to elucidate the mechanism of DAAQ-COF-catalyzed d-HAT reactions.The diffuse reectance UV-vis spectrum of DAAQ-COF exhibited a broad absorption in the visible light region with the maxima at 440 to 480 nm (Fig. 3a).The optical band gap of DAAQ-COF was estimated to be 2.02 eV with the Tauc plot (Fig. 3b).DAAQ-COF exhibited emissions at 453 nm and 545 nm with 400 nm excitation (Fig. S16 †).These results show that DAAQ-COF can be irradiated by visible light to its excited state to initiate the catalytic cycle.No signicant quenching was observed between the excited DAAQ-COF and benzaldehyde, suggesting no rapid electron transfer or energy transfer between the photoexcited catalyst and the substrate (Fig. S17 †).The KIE experiment on DAAQ-COF-catalyzed C-N coupling reaction was conducted using DEAD and a 1 : 1 mixture of THF and d 8 -THF. 13,64The intermolecular KIE was determined to be 2.6 by calculating the product distribution from the NMR spectrum (Fig. 3c).As this value is a typical of primary KIEs, we believe that the cleavage of the C-H bond in the substrate is the rate-determining step in the d-HAT processes.Based on these ndings, we propose a catalytic cycle for the photocatalyzed C-N coupling reaction in Fig. 3d.Under visible light irradiation, the excited AQ moiety in DAAQ-COF homolytically cleaves the C-H bond in the substrate via abstracting a hydrogen atom.The resulting substrate radical is quenched by the radical acceptor DEAD to generate a N-based radical, which abstracts a hydrogen atom to the H-AQc species to form the C-N coupling product and regenerate the AQ catalyst.Similarly, in the C-C coupling reaction, the substrate radical can be quenched by 5 to realize pyridylation.The leaving amine radical undergoes reverse hydrogen atom transfer and converts the H-AQc species back to the AQ catalyst (Fig. S20 †).Light on/off experiment ruled out the involvement of a radical chain process in the C-C coupling reaction, as no product was generated aer the light was turned off (Fig. S19 †).

Conclusions
In this work, we synthesized an anthraquinone-based 2D COF as a d-HAT catalyst.Under visible light irradiation, DAAQ-COF cleaves the C-H bond of the substrate to generate a carbon radical, which further reacts with different radical acceptors such as DEAD or activated pyridine to realize C-N or C-C coupling reactions.As a heterogenous catalyst, DAAQ-COF is  easily separated from the mixture by ltration or centrifugation and reused in ve reaction runs without any decrease in catalytic performance.The C-N coupling product in the ltrate directly react with nucleophilic reagents to realize C-H bond functionalization.This work highlights the potential of designer COFs in catalytic C-H functionalization via d-HAT processes.
), which was consistent with the lattice parameter of DAAQ-COF.The lattice fringes correspond to the in-plane periodicity of the 2D COF.Solid-state NMR spectrum of DAAQ-COF supported the complete imine condensation of DAAQ and TFP monomers and tautomerization of the TFP units (Fig. S8 †) with C]O peaks at d = 183 and 180 ppm for the DAAQ and tautomerized TFP moieties, respectively.The C]C peaks for the tautomerized TFP moieties appeared at d = 142 and 108 ppm.The comparison of FT-IR spectra of the two monomers and DAAQ-COF revealed the disappearance of n(C-H) aldehyde at 2899 cm −1 due to the formation of enamine bonds (Fig.

Fig. 2
Fig. 2 (a) Control experiments of DAAQ-COF catalyzed C-N coupling between THF and DEAD.(b) Yields of the C-N coupling product between THF and DEAD in six consecutive reaction runs with the recovered DAAQ-COF as catalyst.(c) A sequential approach to convert the C-H bond in benzaldehyde to C-O, C-S and C-N bonds without rigorous isolation of the intermediates.

Table 1
DAAQ-COF-catalyzed C-N and C-C coupling reactions with DEAD a and the activated pyridine b a Reactions were performed at 0.2 mmol scale with 1 mol% DAAQ-COF for 24 h in the corresponding solvents (THF for 3a, dioxolane for 3b, acetone for 3c-n).b Reactions were performed at 0.2 mmol scale with 2 mol% loading of DAAQ-COF for 48 h in the corresponding solvents (THF for 6a, 1 : 1 dioxane/acetonitrile for 6b, acetonitrile for 6c-h).Isolated yields for all reactions.

Fig. 3
Fig. 3 (a) Diffuse reflectance UV-vis spectrum of DAAQ-COF.(b) Tauc plot from the diffuse reflectance UV-vis spectrum of DAAQ-COF.(c) Kinetic isotope experiment of DAAQ-COF-catalyzed C-N coupling reaction between DEAD and a mixture of THF and d 8 -THF in a one-pot reaction.(d) Proposed mechanism for DAAQ-COF-catalyzed C-N coupling with DEAD as the radical acceptor.