Deuterated solvents

NMR spectroscopic measurements were performed in D₂O at 300 K on a Bruker Avance^III 700 MHz (equipped with an inverse 5 mm quadruple-resonance Z-grad cryoprobe). Deuterated solvents were purchased from Deutero GmbH (Kastellaun, Germany). Acetone was used as an external standard to calibrate ¹H (δ_H 2.225) and ¹³C (δ_C 30.89) NMR spectra. ³¹P NMR spectra (δ_P 0.0) were calibrated with 85% phosphoric acid in D₂O as an external standard. ¹H NMR assignments were confirmed by two-dimensional ¹H, ¹H COSY and TOCSY experiments, and ¹³C NMR assignments were indicated by two-dimensional ¹H, ¹³C HSQC, based on the ¹H NMR assignments. Interresidual connectivity and further evidence for ¹³C assignment were obtained from two-dimensional ¹H, ¹³C HMBC and ¹H, ¹³C HSQC-TOCSY experiments. Phosphate group connectivity was assigned by two-dimensional ¹H, ³¹P HMQC and ¹H, ³¹P HMQC-TOCSY. All data were acquired and processed using Bruker TOPSIN V 3.0 or higher.

Lactic acid solution (≥85%), 1-butyl-3-methylimidazolium chloride (≥99%), ethylene glycol (≥99%), polyethylene glycol 8000 (USP), 4-dodecylbenzenesulfonic acid (≥95%), acetic acid (≥99%), 3-methacryloxypropyltrimethoxysilane (>98%), and 1,8-diazabicyclo[5.4.0]undec-7-ene (≥99%) were purchased from Sigma Aldrich (St. Louis, MO, USA). Clevios^TM PH-1000 (PEDOT:PSS) was purchased from Heraeus (Hanau, Germany). Amberlyst^TM A-26 (OH-form) and analytical grade solvents were purchased from Fisher Scientific (Hampton, NH, USA). Deuterated solvents were purchased from Deutero (Kastellaun, Germany). The N-substituted eight membered cyclic carbonates: 6-methyl-1,3,6-dioxazocan-2-one (8MC) and 6,6′-(ethane-1,2-diyl)bis(1,3,6-dioxazocan-2-one) bis-8MC were synthesized using the previously reported procedures [19 (link),20 (link)]. ILs were prepared using Amberlyst^TM A-26 (OH-form) exchange resin following the procedure in the literature [21 (link)], ILs were stored inside a N₂ filled glovebox (H₂O and O₂ < 5 ppm). ¹H- and ¹³C-NMR spectra were recorded with a Bruker Avance DPX 300 spectrometer. The NMR chemical shifts were reported as δ in parts per million (ppm) relative to the traces of non-deuterated solvent. Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy was performed with a Bruker Alpha.

Deuterated solvents were purchased from Deutero GmbH (Kastellaun, Germany). NMR spectroscopic measurements were performed in D₂O at indicated temperatures on a Bruker Avance^III 700 MHz (equipped with an inverse 5 mm quadruple-resonance Z-grad cryoprobe). Acetone was used as an external standard for calibration of ¹H (δ_H = 2.225) and ¹³C (δ_C = 30.89) NMR spectra41 (link), 85% phosphoric acid was used as an external standard for calibration of ³¹P NMR spectra (δ_P = 0.0) at the respective temperatures. Analysis of 5 was performed in CD₃OD, spectra were calibrated using the residual solvent peak (δ_H = 3.31, δ_C = 49.0)41 (link). All data were acquired and processed using Bruker TOPSPIN V 3.0 or 3.1. ¹H NMR assignments were confirmed by 2D ¹H,¹H-COSY and -TOCSY experiments, ¹³C NMR assignments were indicated by 2D ¹H,¹³C-HSQC, based on the ¹H NMR assignments. Interresidue connectivity and further evidence for ¹³C assignment were obtained from 2D ¹H,¹³C-HMBC and ¹H,¹³C-HSQC-TOCSY. Connectivity of phosphate groups were assigned by 2D ¹H,³¹P-HMQC and ¹H,³¹P-HMQC-TOCSY.

Four different experimental setups were explored, namely, A, B, C and D. These four procedures were used for liquid and water-miscible nitriles (A), liquid hydrophobic nitriles (B) and solid nitriles (C and D), see Table 1. All setups have been optimized for keeping substrates in solution with as little amount of DMF as possible. For comparison purposes between the different setups, it should be taken into account that, in order to avoid experimental bias (due to the extremely small amount of catalysts it would have been necessary to weigh), a larger amount of catalysts has been used in for setup A-D (0.050 mmol and 0.075 mmol for PdCl₂ and As₂O₃, roughly 1:380 with respect to substrates). At variance, the amount of PdCl₂ and As₂O₃ has been decreased (ratio 1:6,500, see below) in the large-scale setup allowing the calculation of the TON. For the characterization of the obtained products, the NMR spectra were acquired on a JEOL 400 YH spectrometer (resonating frequencies: 400 and 100 MHz for ¹H and ¹³C, respectively). Spectra were recorded at room temperature (25°C ± 2°C) using solvents with a deuteration degree ≥99.8% and calibrated on solvent residual signals. Deuterated solvents were purchased from Deutero GmbH.

Clopidogrel hydrogen sulphate (CLP) was kindly provided from RD&C Research, Development & Consulting GmbH, Vienna, Austria. Peroxymonosulfate (PMS, Oxone ^®: 2KHSO₅·KHSO₄·K₂SO₄, MW = 614.74 g·mol⁻¹) was purchased from TCI Deutschland. NaCl, NaBr and NaI were purchased from Sigma Aldrich, Inc. and used directly without further purification. All deuterated solvents were purchased from Deutero GmbH, Kastellaun, Germany.

Deuterated solvents were purchased from Deutero GmbH (Kastellaun, Germany). Nuclear magnetic resonance (NMR) spectroscopic measurements were performed in deuterated 25 mM sodium phosphate buffer (pH 5.5; to suppress fast de-alanylation) at 300 K on a Bruker Avance^III 700 MHz (equipped with an inverse 5-mm quadruple-resonance Z-grad cryoprobe) as described (Gisch et al., 2018 (link)).

Benzotriazole, Dimethyl 2,6-pyridinedicarboxylate, 5,5ʹ-dithiobis(2-nitrobenzoic acid), Naphtalene-2-thiol and pyridine dicarboxylic acid were purchased from Sigma Aldrich Chemie GmbH (Schnelldorf, Germany). All lanthanide compounds were purchased from Merck Chemicals GmbH (Darmstadt, Germany). Deuterated solvents were purchased from Deutero GmbH (Kastellaun, Germany). All NMR measurements were recorded at 25 °C on a BRUKER DRX 400 spectrometer and were referenced internally to TMS. The measured RDCs were obtained from the ¹³C dimension of the 2D ¹H⁻¹³C–HSQC spectra recorded without carbon decoupling and with a digital resolution of 0.4 Hz/data point. Electron Ionization Mode (EI–HRMS) analysis was conducted on Thermo Fischer Scientific 8230 Finnigan MAT Double Focusing Mass spectrometer with BE Geometry and EI mode at 70 eV (Bremen, Germany).