Assessing the environmental benefit of palladium-based single-atom heterogeneous catalysts for Sonogashira coupling

The Pd–Cu catalysed Sonogashira coupling of terminal alkynes and aryl halides is a cornerstone synthetic strategy for C–C bond formation. Homogeneous organometallic systems conventionally applied are typically not reusable and require efficient downstream Pd removal steps for product purification, making it challenging to fully recover the precious metal. A holistic cradle-to-gate life cycle assessment (LCA) unveils that process footprint can be improved up to two orders of magnitude from repeated catalyst reuse. New classes of heterogeneous catalysts based on isolated metal atoms (single-atom catalysts, SACs) demonstrate promising potential to synergise the benefits of solid and molecular catalysts for efficient Pd utilisation. Here we show that using Pd atoms anchored on nitrogen-doped carbon permits full recovery of the metal and reuse of the catalyst over multiple cycles. A hybrid process using the Pd-SAC with a homogeneous CuI cocatalyst is more effective than a fully heterogeneous analogue based on a bimetallic Pd–Cu SAC, which deactivates severely due to copper leaching. In some scenarios, the LCA-based metrics demonstrate the footprint of the hybrid homogeneous–heterogeneous catalytic process is leaner than the purely homogeneous counterpart already upon single reuse. Combining LCA with experimental evaluation will be a useful guide to the implementation of solid, reusable catalysts for sustainable organic transformations.


Catalyst characterisation
Powder X-ray diffractograms were acquired in a PANalytical X'Pert PRO-MPD instrument (Bragg-Brentano geometry) using a Ni-filtered Cu Ka source. Data was collected at 2q in the range of 3-60° with a step size of 0.08° and a collection time of 162 s. Nitrogen sorption isotherms (77 K) were acquired using a Micromeritics TriStar instrument and argon sorption was conducted (77 K) with a Micromeritics TriFlex analyser over previously degassed specimens (8 h, 423 K, vacuum).
The composition of the carbon carriers (C, H, N, O) was determined using a LECO CHN-900 elemental analyser equipped with an infrared spectrometer. The analysis of the metal content with inductively coupled plasma optical emission spectroscopy was conducted in a Horiba Ultra 2 instrument (photomultiplier tube detector). Sample aliquots (15 mg) were loaded into polytetrafluoroethylene tubes, to which a mixture (3:1, 2 cm 3 ) of nitric acid (>65 wt.%, Sigma-Aldrich) and hydrogen peroxide (30 wt.%, Sigma-Aldrich) was slowly added. Alumina-containing samples were digested with a mixture of phosphoric, sulfuric, and hydrofluoric acids. The capped tubes were heated (473 K, 20 min) in a microwave reactor (Turbowave) under elevated nitrogen pressure (48 bar). Liquid organic samples were dried (338 K) and carbonised with the abovementioned hydrogen peroxide-nitric acid mixture with added sulfuric acid (1 cm 3 , >95%, Sigma-Aldrich). The obtained solutions were diluted with MilliQ water and solids were removed through PTFE syringe filters (0.25 µm pore size). Quantification was based on the emission intensity at 340.46 nm (Pd) and 324.75 nm (Cu) averaged over three measurements. X-ray photoelectron spectroscopy was conducted on a Physical Electronics Instruments Quantum 2000 instrument with monochromatic Al Ka radiation (15 kV, 32.3 W). The spectral acquisition occurred under ultrahigh vacuum conditions (5·10 −8 Pa residual pressure) with a pass energy of 46.95 eV. All XPS signals were referenced using the C1 s photoemission which was set at 284.8 eV. Peak fitting with reference spectra 3-7 was conducted using the CasaXPS software. 8 For scanning transmission electron microscopy (STEM) the samples were dusted onto standard carbonfilm copper and nickel grids (300 mesh). High-angle annular dark-field (HAADF) STEM and energy dispersive X-ray spectroscopy (EDX) was performed on a FEI Talos F200X microscope with a SuperX detector (200 kV acceleration potential). Image frames of 512 by 512 pixels were acquired under varying dwell times (35-74 µs). EDX elemental maps were averaged over 20 frames in the spectral range up to 20 keV, and post-processed (background subtraction and Gaussian blur).
Aberration corrected annular dark-field STEM (AC-ADF-STEM) images of as-prepared and used catalysts were acquired on a Hitachi HD-2700CS instrument operated at 200 kV. X-ray absorption spectroscopy (XAS) was conducted at the X10DA (SuperXAS) beamline of the Swiss Light Source. The X-ray beam from the 2.9 T superbend was collimated using a Pt-coated mirror, monochromatised using a Si(111) channel-cut monochromator, and focused to a spot size of 500×100 µm (horizontal×vertical) using a Pt-coated toroidal mirror. Data were acquired from pressed pellets at the Pd and Cu K-edge in transmission mode, using three 15 cm long Ar/N2-filled ionisation chambers. The samples were placed between the first and the second ionisation chamber.
For the absolute energy calibration, a metallic (Pd, Cu) foil was measured simultaneously between the second and third ionisation chambers. The resulting spectra were energy calibrated, background corrected and normalised using the Athena program from the Demeter software suite. 9 EXAFS fitting was performed using the parameters described in Table S4.

Catalyst evaluation
Chemicals. All chemicals were acquired from Chemie Brunschwig AG and Merck and used without further purification.

Note S2. Experimental procedure under standard conditions
A degassed solution of iodobenzene (30.0 mmol), phenylacetylene (33.4 mmol), triethylamine (66.4 mmol), 1,3,5-trimethylbenzene (7.61 mmol), and acetonitrile (60 cm 3 ) was added to a glass vial containing solid SAC (623 mg, 0.5 wt.% palladium content), copper(I) iodide (58.9 mg), and triphenylphosphine (80.9 mg), and vigorously stirred for 24 h at 353 K under a protective atmosphere (argon). After cooling to room temperature, the catalyst was separated by filtration, washed three times with acetonitrile (10 cm 3 ) and once with ethyl acetate (10 cm 3 ), and dried under reduced pressure. Volatile compounds were removed from the reaction solution filtrate under reduced pressure at elevated temperature (353 K), the residue was treated with ethyl acetate, washed three times with water, and dried over sodium sulphate. Finally, the solvent was removed under reduced pressure with subsequent purification of the obtained residue by flash column chromatography (Combiflash Rf+, heptane eluent) equipped with a UV detector and silica gel columns (RediSep Rf+, 35-70 µm average particle size). Diphenylacetylene was obtained as a colourless crystalline solid (3.16 g, 17.7 mmol, 59%). The yield determined through gas chromatography (GC) was 62% (representative chromatogram in Fig. S11).

Note S3. Product isolation
Volatile substances were removed from the reaction solution under reduced pressure, the residue was treated with ethyl acetate, washed three times with water and dried over sodium sulfate.
Finally, solvent removal under reduced pressure with subsequent purification of the residue by flash column chromatography using a Combiflash Rf+ equipped with a UV detector and RediSep Rf+ columns (silica gel 60, 230-400 mesh, 35-70 µm average particle size) yielded diphenylacetylene as colourless, crystalline solid. 1 H-NMR spectra were recorded with a Bruker 300 Ultrashield spectrometer and referenced against the chemical shift of the residual protic-solvent peak (CDCl3: 7.26 ppm); for 13 C-NMR spectra the deuterated solvent peak (CDCl3: 77 ppm) was used (see Fig. S12-S15).    Notably, the surface composition revealed a higher palladium content than in the bulk, likely owing to the preferred surface localisation using the presented synthesis method. Furthermore, for PdCu/NC the surface Cu:Pd molar ratio was different (around 2:1) than the bulk composition, which is associated with a distinct localisation of the copper precursor (e.g., in the micropores).        S5. N 1s X-ray photoelectron spectroscopy (XPS) spectra of the as-prepared Pd SACs based on NC and ECN with overlaid spectral fit. The high nitrogen content present in Pd/ECN could be mainly attributed to aromatic ring nitrogen (398.8 eV) and tertiary nitrogen (399.8 eV) present in the tris-triazine sub-units of the scaffold. A contribution of NHx-groups can be assigned to defects due to unpolymerised nitrile groups (400.7 eV). 11,12 Both Pd/NC and PdCu/NC displayed qualitatively similar spectra. They could be fitted through components assigned to pyridinic nitrogen (398.6 eV), pyrrolic nitrogen (399.8 eV), graphitic nitrogen (402.6 eV), and oxidised nitrogen (405.1 eV). 4 Fig. S6. Pd 3d XPS spectra and corresponding fits (dotted line) of the as-prepared Pd SACs. Shaded areas indicate spectral components corresponding to Pd 4+ , Pd 2+ , and Pd 0 (relative contributions shown inset). As expected, all SACs evidenced predominantly positively charged palladium species. The reduced signal intensity in Pd/Al2O3 coincided with its lower metal content. The presence of a minor contribution of neutrally charged palladium, predominant for Pd/ECN, could either stem from small clusters or arise as an artefact of the fitting procedure.   Fig. 5 in the main text). The activity decrease observed from the first and second catalytic run (Pd/AC and Pd/ECN) may be caused by metal leaching. Differences between PdCu/NC operated in the presence and absence of CuI are likely caused by the abundance of soluble copper species. e) The evolution of bulk palladium content (wB(Pd)) over consecutive catalytic tests (R0, as-prepared catalyst) confirmed a significant loss of metal during the first run for all of these carriers. f) Analysis of the used catalysts confirmed the presence of Cu (wB(Cu)), likely owing to the adsorption of Cu species from the reaction medium (values for PdCu/NC shown in Table S5). The color codes shown in the legend apply to all panels. Standard reaction conditions: 353 K, 0.1 mol% Pd, 1 mol% CuI, 1 mol% PPh3, 2 eq. NEt3, 24 h (d-f). Fig. S9. a) Pd 3p and b) Cu 2p5/2 XPS spectra of the Pd SACs after one catalytic run (-R1). Shaded areas indicate spectral components corresponding to Pd 4+ , Pd 2+ and Pd 0 (relative contributions shown inset). The share of Pd 4+ in PdCu/NC-R1 decreased significantly in favour of Pd 2+ . AC-and Al2O3-supported catalysts displayed low signal intensity of palladium, coinciding with the reduced bulk palladium content evidenced. Both, Pd/AC-R1 and Pd/Al2O3-R1 displayed negligible copper uptake. The Pd speciation in Pd/ECN-R1 was similar to the as-prepared catalyst. Pd/ECN-R1, Pd/NC-R1, and PdCu/NC-R1 evidenced a notable signal in the Cu 2p5/2 region related to Cu 2+ . 7   S11. Example gas chromatogram of the reaction aliquot after 24 h. Measurements were performed on a Thermo TRACE 1300 chromatograph equipped with a flame ionisation detector, and a ZB-5 column (5%-phenyl-95%-dimethylpolysiloxane, 30 m length, 0.25 mm inner diameter, 0.25 µm film thickness) and helium as carrier gas (split injection, flow: 0.8 cm 3 min −1 , split ratio: 125). Inlet and detector temperature were set to 573 K. The initial column temperature was set to 313 K and continuously increased to 320 K (heating rate 20 K min −1 , hold time 10 min).