Synergistic photoredox and copper catalysis by diode-like coordination polymer with twisted and polar copper–dye conjugation

Synergistic photoredox and copper catalysis confers new synthetic possibilities in the pharmaceutical field, but is seriously affected by the consumptive fluorescence quenching of Cu(II). By decorating bulky auxiliaries into a photoreductive triphenylamine-based ligand to twist the conjugation between the triphenylamine-based ligand and the polar Cu(II)–carboxylate node in the coordination polymer, we report a heterogeneous approach to directly confront this inherent problem. The twisted and polar Cu(II)–dye conjunction endows the coordination polymer with diode-like photoelectronic behaviours, which hampers the inter- and intramolecular photoinduced electron transfer from the triphenylamine-moiety to the Cu(II) site and permits reversed-directional ground-state electronic conductivity, rectifying the productive loop circuit for synergising photoredox and copper catalysis in pharmaceutically valuable decarboxylative C(sp3)–heteroatom couplings. The well-retained Cu(II) sites during photoirradiation exhibit unique inner-spheric modulation effects, which endow the couplings with adaptability to different types of nucleophiles and radical precursors under concise reaction conditions, and distinguish the multi-olefinic moieties of biointeresting steride derivatives in their late-stage trifluoromethylation-chloration difunctionalisation.

Solid state cyclic voltammograms (CV) and electrochemical impedance spectroscopy (EIS) were measured on ZAHNER ENNIUM Electrochemical Workstation with a typical threeelectrode system. The sample electrode separately served as the working electrode, a platinumwire and Ag/AgCl electrode served as the counter electrode and reference electrode, respectively. For CV measurements, an acetonitrile solution of ammonium hexafluorophosphate (0.1 M) served as the electrolyte, and for EIS measurements, aqueous KCl (0.1 M) solution was used as the electrolyte.
Photoelectrochemical measurements were performed on a CHI 660E electrochemical workstation using a standard three-electrode system with tetrabutylammonium hexafluorophosphate acetonitrile solution (0.05 M) as the electrolyte. Ag/AgCl and platinum flake were used as reference electrode and counter electrode, respectively. The sample electrode separately served as the working electrode. The photocurrent responses were measured in the prescence of O2 (1 atom) at room temperature under the irradiation of a 300 W Xenon lamp with a 400 nm cut-off filter.

Tri(4'-carboxybiphenyl)amine (H3L-Planar)
Tri(4'-carboxybiphenyl)amine was synthesized according to the literature methods 6 and characterized by 1 H NMR. 1 7 To a solution of triphenylamine (10.0 g, 40.8 mmol) in DMF (120 mL) at 0 o C, NBS (25.1 g, 134.6 mmol) in DMF (60 mL) was added dropwise. The mixture was then stirred at room temperature for 12h. Then DCM was added and the resulting mixture was washed with a large amount of water, the organic phase was washed with saturated NaCl(aq.) and dried over anhydrous Na2SO4. Ice methanol was poured into the DCM phase to produce the product as a white solid (16.7 g, 85%). 1 8 Tris(4-bromophenyl)amine (3.86 g, 8.0 mmol), bis(pinacolato)diborane (7.6 g, 30.0 mmol), KOAc (13.7 g, 140.0 mmol), and dioxane (120 mL) were mixed together in a 250 mL flask. After degassing, [Pd(dppf)Cl2] (1.0 g, dppf = 1,1'-bis(diphenylphosphanyl) ferrocene) was added. The reaction mixture was kept at 85 o C overnight before it was cooled to room temperature. The organic solvent was removed under vacuum, and the residual was dissolved in DCM and washed with water. After drying the organic layer with MgSO4, the solvent was removed. The crude product was purified by flash chromatography to give the product as a white solid (3.5 g, 70%). 1 9 To a cooled solution of 2-bromo-4-nitrobenzoic acid (12.3 g, 50.0 mmol) in dry ethanol (80 mL) SOCl2 (13.1 mL, 180 mmol) was added slowly at 0 o C over a period of 30 minutes, the reaction mixture was first warmed to room temperature and then heated to reflux for 6h. The reaction mixture was then cooled to room temperature and organic solvent was evaporated under vacuum, the crude product was purified by column chromatography on silica gel to give the product as a yellow oil (13.0 g, 95%). 1

Powder X-ray Crystallography of Cu-Twisted
Powder X-ray diffraction data were collected using a Rigaku D/Max-2400 X-ray diffractometer in parallel beam geometry employing Cu Kα line focused radiation at 9000W (45 kV, 200 mA) power and equipped with a position sensitive detector with at 10.0 mm radiation entrance slit. Samples were mounted on zero background air-tight sample holders during the data acquisition. The best counting statistics were achieved by collecting samples using a 0.01° 2θ step scan from 2° to 50° with exposure time of 30 s per step.
Due to the large void space of Cu-Twisted, the single crystal X-ray diffraction measurement cannot offer sufficient reflection data in high-angle regions for exact structure resolution, Crystal structure of Cu-Twisted was therefore resolved by using powder X-ray diffraction measurement in conjunction with Le Bail refinement and structural simulation based on density functional theory calculation. The crystalline structure of Cu-Twisted was built by Materials Studio 10 . The initial lattice was created by starting with the space group P23. Structural simulation of Cu-Twisted was performed based on the reticular chemistry of non-interwoven of pto-net and single-crystal structures of MOF-143 11 and Cu-TCA 12 . The lattice parameters were obtained by Le Bail refinements of experimental powder XRD pattern. The constructed model was optimized using the CASTEP module, and the calculated PXRD pattern was generated with the Reflex Plus module in the Materials Studio package.

Single-crystal X-ray Crystallography of Cu-Planar
Single crystal of Cu-Planar with suitable dimensions was placed into a glass tube filled with mother liquid for data collection. The intensity data for crystal was collected at 200 K on Bruker SMART APEX diffractometer equipped with a CCD area detector and a graphite monochromated Mo-Kα (λ = 0.71073 Å) radiation source. The data integration and reduction were processed using the SMART and SAINT software 13,14 . The structure was solved by direct methods using SHELXTL and refined on F 2 by the full-matrix least-squares method using the program SHELXL-2017 15 . All the non-hydrogen atoms were refined with anisotropic thermal displacement coefficients. Except for the coordinated water molecules, hydrogen atoms were fixed geometrically at calculated positions and allowed to ride on the parent non-hydrogen atoms. The lattice solvent molecules as well as the hydrogen atoms of the coordinated water molecules could S10 not be located from difference Fourier map due to disorder in the highly symmetric space group. The influence of disordered solvent molecules on the reliability factors was eliminated by applying the SQUEEZE procedure 16 , implemented in PLATON program 17 . To enhance the stability of the refinement, the benzene rings beside nitrogen atoms were disordered and splitted into two parts. Several constraints, including fixing the bond distances of these disordered atoms, were used. The geometrical constraints of idealized regular polygons were used for the benzene rings. The X-ray crystallographic coordinates for structures of Cu-Planar has been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 1870816. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Dye Uptake Experiments.
Crystals of Cu-Twisted (13.3 mg) were soaked in a methanol solution of Brilliant Blue R (24 mM, 2 mL) overnight. The resulting blue crystals were rinsed until the washings became colourless. Then, the samples were destroyed by HCl, the resultant clear solution was diluted to 250 mL and the pH of the solution was adjusted to 1.7. The concentration of Brilliant Blue R was determined by comparing the UV-vis absorption with a standard curve. The amount of Brilliant Blue R uptaken by Cu-Twisted was calculated to be 54% (wt%) of the framework weight.

General procedure for the synthesis of Hypervalent Iodine Reagents (GP1)
Hypervalent iodine reagents were synthesized as reported 1 . A 500 mL round-bottom flask was charged with iodomesitylene diacetate (10 mmol), carboxylic acid (20.5~21 mmol), and 200 mL toluene. The flask was attached to a rotary evaporator with the water bath heated to 55 o C and the solvent (and the generated acetic acid) was removed over a time period of about 10 min. A second 150 mL aliquot of toluene was added to the flask and the evaporation step was repeated. Repeat the evaporation step for two more times with 100 mL toluene each time. After further removal of residual toluene under high vacuum, the result product was used directly without purification.

General procedure for the synthesis of NHPI esters (GP2)
NHPI esters were synthesized as reported 2 . A round-bottom flask was charged with carboxylic acid (if solid, 5 mmol), N-hydroxyphthalimide (5 mmol) and DMAP (0.5 mmol). Dichloromethane was added (25 mL), and the mixture was stirred vigorously. Carboxylic acid (if liquid, 5 mmol) was added via syringe, DIC (5.5 mmol) was then added dropwise via syringe. And the mixture was allowed to stir under N2 overnight. After reaction, the mixture was filtered over Celite and rinsed with DCM. The solvent was removed under reduced pressure, and purified via column chromatography to afford the corresponding activated esters.

General procedure for the synthesis of olefin substrates (GP3)
The synthesis method was revised from the literature 5 . To a solution of the corresponding alcohol/phenol or amine (10.0 mmol) and 4-dimethylaminopyridine (2.0 mmol) in dry DCM (20 mL) at 0 o C was added trimethylamine (12.0 mmol) and a solution of acryloyl/methacryloyl chloride (12.0 mmol) in dichloromethane (20 mL) dropwise subsequently. The reaction mixture was warmed up to room temperature and stirred for 12 h before it was diluted with distilled water and extracted twice with DCM. The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography to give the desired product.

Substrate Ingress and Product Egress Experiments
For substrate ingress experiment, crystals of Cu(II)-dye coordination polymers (0.0625 mmol) was soaked into a solution of substrate 2a in dioxane (0.05 M), then the mixture was shaken by vortex reactor. The uptake amount of 2a was monitored by time-course sampling of supernatant and gas chromatography (GC). For product egress experiment, crystals of Cu(II)-dye coordination polymers (0.0625 mmol) was immersed into a concentrated solution of product 3a in dioxane for 24h, then the crystals were taken out of the solution and washed with a small quantity of dioxane quickly to remove the product absorbed on the surface. Then these crystals were immersed into fresh dioxane (1 mL) and shaken by a vortex reactor. The release amount of 3a was time-course monitored by GC analysis.

17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl 2chloro-4,4,4-trifluoro-2-methylbutanoate (8p) DFT Computational Analysis
We optimized the molecular geometries of the model complexes with DFT calculations using the Becke's nonlocal three-parameter exchange and correlation functional with the Lee-Yang-Parr correlation functional (B3LYP) [28][29][30][31] . And for the basis set, we chose the effective core potentials of Hay and Wadt with double-ξ valence basis sets (LanL2DZ) 32,33 to describe Cu; while the 6-31G(d) basis set 34,35 were used for all other atoms(C H O F Cl). Frequency calculations were carried out at the same level of theory to identify all of the stationary points include minima who has zero imaginary frequencies and saddle point has only one imaginary frequencies. Frequency calculation can also provide free energies at 298 K, which include entropic contributions by taking into account the vibrational, rotational, and translational motions of the species under consideration. All calculations were performed with the Gaussian 09 software package 36 . Relative free energies (kcal mol -1 ) are presented in calculations of all the figures that contain potential energy profiles. Table 7. The calculated free energy data for the adsorption of substrate 7l and product 8l on the node of Cu-Twisted, respectively Both the adsorption of substrate 7l and product 8l are thermodynamically feasible pathways. Moreover, the adsorption of substrate 7l should be more favoured than that of product 8l (-12.4391 < -11.0335 kcal mol -1 ), implying that the generated product may be crowded out from copper centre by the competitive coordination of substrate to trigger the new round of photocatalysis.

Geometrical coordinates of 7l and Cu-Twisted fragment and transition states for electronic structure calculations.
Organic molecule 7l