Supporting Information

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1 Supporting Information Photoredox/Brønsted Acid Co-Catalysis Enabling Decarboxylative Coupling of Amino Acid and Peptide Redox-Active Esters with N- Heteroarenes Wan-Min Cheng, Rui Shang,* and Yao Fu* Hefei National Laboratory for Physical Sciences at the Microscale, ichem, CAS Key Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of Biomass Clean Energy, Department of Chemistry, University of Science and Technology of China, Hefei , China. S1

2 Table of Contents 1. General Information S3 2. Preparation of Photocatalyst and Redox Active Esters S3-S4 3. Investigation of the Key Reaction Parameters S4-S6 4. Experimental Procedures and Spectral Data S7-S24 5. Gram-scale Reaction S24 6. References S25 7. NMR Spectra S26-S61 S2

3 1. General Information All reactions were carried out in oven-dried Schlenk tubes under argon atmosphere (purity %) unless otherwise mentioned. Commercial reagents were purchased from Adamas, TCI and Aldrich. Organic solutions were concentrated under reduced pressure on Buchi rotary evaporator. Flash column chromatographic purification of products was accomplished using forced-flow chromatography on Silica Gel ( mesh). 1 H-NMR and 13 C-NMR spectra were recorded on a Bruker Avance 400 spectrometer at ambient temperature. Data for 1 H-NMR are reported as follows: chemical shift (ppm, scale), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet and/or multiplet resonances, br = broad), coupling constant (Hz), and integration. Data for 13 C- NMR are reported in terms of chemical shift (ppm, scale), multiplicity, and coupling constant (Hz). HRMS analysis was performed on Finnigan LCQ advantage Max Series MS System. ESI-mass data were acquired using a Thermo LTQ Orbitrap XL Instrument equipped with an ESI source and controlled by Xcalibur software. 2. Preparation of Photocatalyst and Redox Active Esters 2.1 Preparation of photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 The photocatalyst was synthesized according to literature report. 1 (Reference: Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal, R. A.; Malliaras, G. G.; Bernhard, S. Chem. Mater. 2005, 17, ) The spectral Data of the photocatalyst is consistent with the literature data. The other photocatalysts (Eosin Y, Ru(bpy)3(PF6)2, Ir(ppy)3 and Mes-Acr) are commercially available. 2.2 Preparation of Redox Active Esters According to literature reports, 2 the redox active esters can be synthesized by the condensation of corresponding carboxylic acids with N-hydroxyphthalimide. S3

4 The corresponding alkyl carboxylic acid (12 mmol, 1.2 equiv.), N-hydroxyphthalimide (1.63 g, 10 mmol, 1.0 equiv.), and 4-dimethylaminopyridine (61mg, 0.5 mmol, 5 mol %) were mixed in a flask with a magnetic stirring bar. Dry THF or CH2Cl2 (40 ml) (according to the solubility of the carboxylic acids) was added. Then a solution of N,N dicyclohexylcarbodiimide (2.48 g, 12 mmol, 1.2 equiv.) in THF or CH2Cl2 (15 ml) was added slowly at room temperature. The reaction mixture was stirred at room temperature for 6 h. After N-hydroxyphthalimide was completely converted, the white precipitate was filtered off and the solution was concentrated under vacuum. Corresponding redox active esters were purified by column chromatography on silica gel (CH2Cl2 or petroleum ether/ethyl acetate as eluent). 3. Investigation of the Key Reaction Parameters Table S1: Screening of different solvents. a Entry Solvent Yield (%) b 1 DMA 85 2 DMF 75 3 CH 2Cl MeCN 59 5 THF 69 6 Toluene 60 a 0.2 mmol 4-phenylquinoline, 0.3 mmol redox active ester, 2 mol % Ir[dF(CF 3)ppy] 2(dtbbpy)PF 6, 10 mol % PA-1, 2 ml solvent, be irradiated by 36 W Blue LEDs for 3 h under Ar. b Isolated yield. S4

5 Table S2: Screening of photocatalysts. a Entry Photocatalyst Yield (%) b 1 Ir[dF(CF 3)ppy] 2(dtbbpy)PF Ir(ppy) Ru(bpy) 3(PF 6) 2 < 5 4 c Eosin Y < 5 5 Mes-Acr < 5 a 0.2 mmol 4-phenylquinoline, 0.3 mmol redox active ester, 2 mol % photocatalyst, 10 mol % PA-1, 2 ml DMA, be irradiated by 36 W Blue LEDs for 3 h under Ar. b Isolated yield. c Using green LEDs. S5

6 Table S3: Screening of different additives. a Entry Additive Yield (%) b 1 10 mol % PA mol % PA mol % PA mol % H 3PO mol % TFA mol % Al(OTf) mol % La(OTf) mol % B(C 6F 5) 3 58 a 0.2 mmol 4-phenylquinoline, 0.3 mmol redox active ester, 2 mol % Ir[dF(CF 3)ppy] 2(dtbbpy)PF 6, additive, 2 ml DMA, be irradiated by 36 W Blue LEDs for 3 h under Ar. b Isolated yield. Table S4: Control Experiments. a Entry Variations from conditions Yield (%) b 1 none 85 2 without photocatalyst N.D. 3 without PA without light < 5 a 0.2 mmol 4-phenylquinoline, 0.3 mmol redox active ester, 2 mol % Ir[dF(CF 3)ppy] 2(dtbbpy)PF 6, 10 mol % PA-1, 2 ml DMA, be irradiated by 36 W Blue LEDs for 3 h under Ar. b Isolated yield. S6

7 4. Experimental procedures and spectral data 4.1 Experimental procedures General Procedure A N-heteroarene (1.0 equiv., 0.2 mmol) (if solid), redox active ester (1.5 equiv., 0.3 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1.0 mol %, 2.2 mg) and 1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate (PA-1, 10 mol %, 7.0 mg) were placed in a transparent Schlenk tube equipped with a stirring bar. The tube was evacuated and filled with argon (three times). To these solids, N-heteroarene (1.0 equiv., 0.2 mmol) (if liquid) and anhydrous N,Ndimethylacetamide (DMA, 2.0 ml) was added via a gastight syringe under argon atmosphere. The reaction mixture was stirred under the irradiation of a 36 W Blue LEDs (distance app. 3.0 cm from the bulb) at room temperature for 3 h. After 3 h, the mixture was quenched with water and extracted with ethyl acetate (3 x 10 ml). The organic layers were combined and concentrated under vacuo. The product was purified by flash column chromatography on silica gel (ethyl acetate : petroleum ether=10:1~1:1). General Procedure B N-heteroarene (2.0 equiv., 0.4 mmol) (if solid), redox active ester (1.0 equiv., 0.2 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1.0 mol %, 2.2 mg) and 1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate (PA-1, 10 mol %, 7.0 mg) were placed in a transparent Schlenk tube equipped with a stirring bar. The tube was evacuated and filled with argon (three times). To these solids, N-heteroarene (2.0 equiv., 0.4 mmol) (if liquid) and anhydrous N,Ndimethylacetamide (DMA, 2.0 ml) was added via a gastight syringe under argon atmosphere. The reaction mixture was stirred under the irradiation of a 36 W Blue LEDs (distance app. 3.0 cm from the bulb) at room temperature for 3 h. After 3 h, the mixture was quenched with water and extracted with ethyl acetate (3 x 10 ml). The organic layers were combined and concentrated under vacuo. The product was purified by flash column chromatography on silica gel (ethyl acetate : petroleum ether=10:1~1:1). 4.2 Spectral Data S7

8 tert-butyl (2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)carbamate (1): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 84% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.3 Hz, 1H), (m, 1H), (m, 1H), (m, 4H), (m, 2H), (m, 3H), (m, 2H), 6.83 (s, 1H), 6.26 (d, J = 6.8 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 1.46 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 159.3, 155.4, 148.4, 148.0, 137.9, , 129.7, 129.5, 129.4, 128.5, 128.4, 128.3, 126.4, 126.3, 125.9, 125.8, 120.9, 79.4, 57.2, 43.1, (one carbon signal is overlapped) HRMS (ESI) Calcd for C28H29N2O2 + [M+H] + : , found: Benzyl (2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)carbamate (2): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 81% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.69 (t, J = 7.5 Hz, 1H), (m, 4H), (m, 7H), (m, 3H), (m, 2H), 6.82 (s, 1H), 6.58 (d, J = 7.4 Hz, 1H), (m, 1H), (m, 2H), 3.41 (dd, J = 13.2, 5.6 Hz, 1H), 3.14 (dd, J = 13.2, 7.9 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 158.8, 155.9, 148.4, 147.9, 137.9, 137.3, 136.7, 129.7, 129.5, 129.4, 128.5, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 126.5, 126.4, 125.9, 125.8, 120.8, 66.7, 57.6, HRMS (ESI) Calcd for C31H27N2O2 + [M+H] + : , found: S8

9 N-(2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)benzamide (3): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 83% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ (m, 1H), 8.15 (d, J = 8.5 Hz, 1H), (m, 3H), (m, 1H), (m, 7H), (m, 2H), (m, 3H), (m, 2H), 6.89 (s, 1H), (m, 1H), 3.58 (dd, J = 13.1, 5.1 Hz, 1H), 3.24 (dd, J = 13.1, 8.3 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 166.7, 158.5, 148.7, 147.6, 137.7, 137.2, 134.8, 131.5, 129.8, 129.6, 129.5, 129.3, 128.6, 128.6, 128.3, 127.2, 126.6, 126.0, 125.9, 121.2, 56.0, (two carbon signals are overlapped) HRMS (ESI) Calcd for C30H25N2O + [M+H] + : , found: tert-butyl ((4-phenylquinolin-2-yl)methyl)carbamate (4): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 80% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.3 Hz, 1H), 7.88 (dd, J = 8.4, 0.8 Hz, 1H), (m, 1H), (m, 6H), 7.30 (s, 1H), 6.01 (s, 1H), 4.67 (d, J = 4.9 Hz, 2H), 1.50 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 155.7, 155.1, 148.3, 146.8, 136.8, 128.6, 128.5, 128.1, 127.6, 127.5, 125.4, 124.9, 124.8, 118.9, 78.5, 45.1, HRMS (ESI) Calcd for C21H23N2O2 + [M+H] + : , found: tert-butyl (1-(4-phenylquinolin-2-yl)ethyl)carbamate (5): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml S9

10 DMA, obtained in 78% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.88 (dd, J = 8.4, 0.7 Hz, 1H), 7.71 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), (m, 6H), 7.28 (s, 1H), 6.27 (br, s, 1H), (m, 1H), 1.58 (d, J = 6.8 Hz, 3H), 1.48 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 161.1, 155.4, 149.3, 147.8, 138.0, 129.5, 129.5, 129.4, 128.6, 128.5, 126.3, 125.9, 125.7, 119.6, 79.3, 51.5, 28.5, HRMS (ESI) Calcd for C22H25N2O2 + [M+H] + : , found: tert-butyl 2-(4-phenylquinolin-2-yl)pyrrolidine-1-carboxylate (6): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 92% yield as a white solid. 1 H NMR (400 MHz, CDCl3) (70:30 mixture of rotamers, peaks corresponding to minor rotamer starred 3 ) δ 8.11 (d, J = 8.5 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), (m, 1H), (m, 6H), 7.25 (s, 1H), (m, 0.3H) *, (m, 0.7H), (m, 2H), (m, 1H), (m, 3H), 1.47 (s, 2.7H) *, 1.13 (s, 6.3H). 13 C NMR (101 MHz, CDCl3) δ 163.9, 154.6, 149.1, 147.9, 138.2, 129.6, 129.4, 129.2, 128.6, 128.4, 126.1, 125.7, 125.6, 117.9, 79.4, 63.7, 47.3, 34.7, 28.2, HRMS (ESI) Calcd for C24H27N2O2 + [M+H] + : , found: tert-butyl (3-phenyl-1-(4-phenylquinolin-2-yl)propyl)carbamate (7): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 79% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 7.88 (dd, J = 8.4, 0.8 Hz, 1H), 7.70 (ddd, J = 8.4, 6.9, 1.4 Hz, 1H), (m, 6H), (m, 3H), (m, 3H), 6.19 (d, J = 7.6 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), 1.48 (s, 9H). S10

11 13 C NMR (101 MHz, CDCl3) δ 160.1, 155.7, 149.2, 148.0, 141.8, 138.0, 129.6, 129.5, 129.5, 128.6, 128.5, 128.4, 128.4, 126.4, 125.9, 125.8, 120.3, 79.4, 55.6, 38.5, 32.0, (one carbon signal is overlapped) HRMS (ESI) Calcd for C29H31N2O2 + [M+H] + : , found: tert-butyl (2-(4-iodophenyl)-1-(4-phenylquinolin-2-yl)ethyl)carbamate (8): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 95% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.4 Hz, 1H), 7.87 (dd, J = 8.4, 0.8 Hz, 1H), 7.71 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), (m, 6H), 7.30 (d, J = 6.8 Hz, 2H), (m, 3H), 6.28 (d, J = 6.8 Hz, 1H), (m, 1H), 3.34 (dd, J = 12.9, 5.4 Hz, 1H), 3.06 (dd, J = 13.1, 8.1 Hz, 1H), 1.47 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 158.6, 155.3, 148.4, 147.9, 137.7, 137.6, 137.3, 131.8, 129.4, 128.6, 128.5, 126.9, 126.5, 125.9, 125.8, 120.8, 91.8, 79.5, 56.9, 42.5, (one carbon signal is overlapped) HRMS (ESI) Calcd for C28H28IN2O2 + [M+H] + : , found: tert-butyl ((2S)-1-(isoquinolin-1-yl)-2-methylbutyl)carbamate (9): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, be irradiated by 36 W Blue LEDs for 6 h, obtained in 80% (A : B= 40% : 40%, dr= 1:1) yield as white liquid. A 1 H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 5.7 Hz, 1H), 8.23 (d, J = 8.2 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 7.2 Hz, 1H), 7.62 (t, J = 7.2 Hz, 1H), 7.56 (d, J = 5.7 Hz, 1H), 6.16 (d, J = 8.8 Hz, 1H), 5.70 (dd, J = 9.1, 4.4 Hz, 1H), (m, 1H), (m, 1H), 1.45 (s, 9H), (m, 1H), 1.02 (t, J = 7.4 Hz, 3H), 0.81 (d, J = 6.8 Hz, 3H). S11

12 13 C NMR (101 MHz, CDCl3) δ 160.2, 156.2, 141.0, 136.4, 130.1, 127.4, 125.8, 124.7, 120.0, 79.0, 53.9, 41.4, 28.4, 27.4, 13.8, (one carbon signal is overlapped) B 1 H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 5.6 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H), 7.56 (d, J = 5.7 Hz, 1H), 6.00 (d, J = 9.0 Hz, 1H), 5.56 (dd, J = 8.9, 6.6 Hz, 1H), (m, 1H), (m, 1H), 1.43 (s, 9H), (m, 1H), 0.87 (d, J = 6.8 Hz, 3H), 0.83 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 160.6, 156.0, 141.3, 136.3, 130.1, 127.4, 127.3, 126.3, 124.9, 120.0, 79.1, 54.9, 41.3, 28.4, 24.2, 16.4, HRMS (ESI) Calcd for C19H27N2O2 + [M+H] + : , found: Di-tert-butyl (1-(isoquinolin-1-yl)pentane-1,5-diyl)dicarbamate (10): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 93% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 5.7 Hz, 1H), 8.20 (d, J = 8.3 Hz, 1H), 7.84 (d, J = 8.1 Hz, 1H), 7.70 (t, J = 7.4 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.57 (d, J = 5.7 Hz, 1H), 6.28 (d, J = 7.8 Hz, 1H), (m, 1H), 4.74 (s, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 22H). 13 C NMR (101 MHz, CDCl3) δ 160.0, 156.0, 155.9, 141.0, 136.4, 130.3, 127.7, 127.5, 125.4, 124.4, 120.3, 79.3, 78.9, 50.5, 40.4, 36.9, 29.5, 28.5, 28.4, HRMS (ESI) Calcd for C24H36N3O4 + [M+H] + : , found: tert-butyl (2-(1H-indol-3-yl)-1-(isoquinolin-1-yl)ethyl)carbamate (11): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 91% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 5.6 Hz, 1H), 8.05 (s, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.51 (d, J = 5.6 Hz, 1H), 7.40 (t, J S12

13 = 7.5 Hz, 1H), 7.19 (t, J = 9.1 Hz, 2H), 7.06 (t, J = 7.4 Hz, 1H), 6.93 (t, J = 7.3 Hz, 1H), 6.63 (s, 1H), 6.29 (d, J = 8.0 Hz, 1H), (m, 1H), (m, 2H), 1.43 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 159.7, 155.6, 141.0, 136.2, 135.9, 130.1, 128.0, 127.2, 127.2, 125.9, 124.5, 122.9, 121.6, 120.3, 119.2, 118.7, 111.3, 110.9, 79.3, 51.5, 32.4, HRMS (ESI) Calcd for C24H26N3O2 + [M+H] + : , found: Cyclohexyl 3-((tert-butoxycarbonyl)amino)-3-(isoquinolin-1-yl)propanoate (12): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 92% yield as a liquid. 1 H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 5.4 Hz, 1H), 8.38 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 7.7 Hz, 1H), (m, 2H), 7.57 (d, J = 5.6 Hz, 1H), (m, 1H), 5.93 (d, J = 7.8 Hz, 1H), (m, 1H), 3.08 (dd, J = 14.8, 6.6 Hz, 1H), 2.91 (dd, J = 14.9, 6.0 Hz, 1H), (m, 4H), 1.44 (s, 9H), (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 170.4, 158.7, 155.1, 141.2, 136.5, 130.2, 127.7, 127.3, 125.8, 124.8, 120.7, 79.6, 72.8, 48.3, 41.0, 31.3, 28.4, 25.3, HRMS (ESI) Calcd for C23H31N2O4 + [M+H] + : , found: Methyl 4-(((benzyloxy)carbonyl)amino)-4-(isoquinolin-1-yl)butanoate (13) : Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 90% yield as a liquid. 1 H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 5.5 Hz, 1H), 8.35 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H), (m, 2H), 7.56 (d, J = 5.6 Hz, 1H), (m, 5H), 6.74 (d, J = 7.9 Hz, 1H), (m, 1H), (m, 2H), 3.63 (s, 3H), (m, 1H), (m, 2H), (m, 1H). 13 C NMR (101 MHz, CDCl3) δ 173.7, 158.8, 156.4, 141.0, 136.6, 136.5, 130.4, 128.5, 128.1, 128.0, 127.8, 127.4, 125.3, 124.5, 120.6, 66.8, 51.6, 50.7, 31.9, S13

14 HRMS (ESI) Calcd for C22H23N2O4 + [M+H] + : , found: Benzyl (1-(isoquinolin-1-yl)-3-(methylthio)propyl)carbamate (14): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 92% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 5.7 Hz, 1H), 8.28 (d, J = 8.3 Hz, 1H), 7.83 (d, J = 7.7 Hz, 1H), (m, 2H), 7.57 (d, J = 5.6 Hz, 1H), (m, 5H), 6.61 (d, J = 8.1 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 1H), (m, 1H), (m, 4H). 13 C NMR (101 MHz, CDCl3) δ 159.0, 156.3, 140.9, 136.6, 136.5, 130.5, 128.5, 128.1, 128.1, 127.9, 127.5, 125.4, 124.4, 120.6, 66.8, 50.6, 36.5, 30.4, HRMS (ESI) Calcd for C21H23N2O2S + [M+H] + : , found: tert-butyl (2-(4-(tert-butoxy)phenyl)-1-(isoquinolin-1-yl)ethyl)carbamate (15): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 96% yield as a liquid. 1 H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 5.6 Hz, 1H), 7.95 (d, J = 8.5 Hz, 1H), 7.74 (d, J = 8.2 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.52 (d, J = 5.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 6.76 (d, J = 8.2 Hz, 2H), 6.69 (d, J = 8.3 Hz, 2H), 6.26 (d, J = 8.3 Hz, 1H), (m, 1H), (m, 2H), 1.43 (s, 9H), 1.22 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 159.4, 155.3, 153.7, 141.3, 136.1, 132.4, 129.9, 127.2, 127.1, 125.9, 124.5, 123.9, 120.2, 79.2, 78.1, 52.2, 42.7, 28.7, (one carbon signal is overlapped) HRMS (ESI) Calcd for C26H33N2O3 + [M+H] + : , found: S14

15 Benzyl (4-amino-1-(isoquinolin-1-yl)-4-oxobutyl)carbamate (16) : Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 82% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.41 (d, J = 4.6 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.84 (d, J = 7.4 Hz, 1H), (m, 2H), 7.60 (d, J = 5.2 Hz, 1H), (m, 5H), 6.94 (d, J = 5.4 Hz, 1H), 6.52 (br, s, 1H), (m, 1H), 5.48 (br, s, 1H), (m, 2H), (m, 2H), (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 175.1, 158.6, 157.1, 140.7, 136.5, 136.5, 130.6, 128.5, 128.2, 128.1, 127.5, 125.1, 124.3, 120.8, 67.0, 50.9, 33.8, (one carbon signal is overlapped) HRMS (ESI) Calcd for C21H22N3O3 + [M+H] + : , found: tert-butyl (2-(tert-butoxy)-1-(isoquinolin-1-yl)ethyl)carbamate (17): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 89% yield as a liquid. 1 H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 5.7 Hz, 1H), 8.33 (d, J = 8.2 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 7.4 Hz, 1H), (m, 2H), 6.17 (d, J = 5.9 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 1.45 (s, 9H), 0.95 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 158.8, 155.6, 141.2, 136.2, 130.0, 127.0, 126.9, 126.7, 125.6, 120.3, 79.2, 73.2, 65.8, 51.5, 28.4, HRMS (ESI) Calcd for C20H29N2O3 + [M+H] + : , found: tert-butyl (1-(6-bromoisoquinolin-1-yl)-2-phenylethyl)carbamate (18): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 S15

16 ml DMA, obtained in 90% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 5.6 Hz, 1H), 7.92 (s, 1H), 7.83 (d, J = 9.0 Hz, 1H), 7.52 (d, J = 8.9 Hz, 1H), 7.42 (d, J = 5.2 Hz, 1H), (m, 3H), (m, 2H), 6.15 (br, s, 1H), (m, 1H), (m, 2H), 1.42 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 158.5, 154.2, 141.4, 136.2, 136.0, 129.7, 128.5, 128.2, 127.0, 125.4, 125.2, 123.8, 123.3, 118.1, 78.3, 51.1, 41.9, HRMS (ESI) Calcd for C22H24BrN2O2 + [M+H] + : , found: tert-butyl (1-(4-chloroquinolin-2-yl)-2-phenylethyl)carbamate (19): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 51% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.2 Hz, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.75 (t, J = 7.1 Hz, 1H), 7.61 (t, J = 7.6 Hz, 1H), (m, 3H), 7.10 (s, 1H), (m, 2H), 5.98 (d, J = 5.7 Hz, 1H), (m, 1H), 3.29 (dd, J = 13.0, 5.6 Hz, 1H), 3.17 (dd, J = 13.2, 7.5 Hz, 1H), 1.44 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 160.1, 155.3, 148.2, 142.6, 137.0, 130.5, 129.6, 129.4, 128.3, 127.3, 126.6, 125.5, 124.1, 120.5, 79.6, 57.0, 42.5, HRMS (ESI) Calcd for C22H24ClN2O2 + [M+H] + : , found: tert-butyl (1-(4-methylquinolin-2-yl)-2-phenylethyl)carbamate (20): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 88% yield as a liquid. 1 H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.67 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), (m, 3H), (m, 2H), 6.80 (s, 1H), 6.17 (d, J = 7.1 Hz, 1H), (m, 1H), 3.29 (dd, J = 13.1, 5.6 Hz, 1H), 3.16 (dd, J = 13.2, 7.6 Hz, 1H), 2.55 (s, 3H), 1.44 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 159.4, 155.4, 147.3, 144.4, 137.6, 129.7, 129.6, 129.2, S16

17 128.2, 127.4, 126.4, 126.1, 123.8, 121.3, 79.3, 57.0, 42.7, 28.5, HRMS (ESI) Calcd for C23H27N2O2 + [M+H] + : , found: tert-butyl (1-(3-chloroquinoxalin-2-yl)-2-phenylethyl)carbamate (21): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 53% yield as a liquid. 1 H NMR (400 MHz, CDCl3) δ (m, 2H), (m, 2H), (m, 3H), (m, 2H), (m, 2H), (m, 1H), (m, 1H), 1.41 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 155.0, 153.7, 146.0, 141.3, 140.4, 136.3, 130.8, 130.4, 129.6, 128.7, 128.3, 126.7, 79.7, 53.3, 41.2, (one carbon signal is overlapped) HRMS (ESI) Calcd for C21H23ClN3O2 + [M+H] + : , found: Di-tert-butyl (1-(phthalazin-1-yl)pentane-1,5-diyl)dicarbamate (22): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 58% yield as a yellow liquid. 1 H NMR (400 MHz, CDCl3) δ 9.46 (s, 1H), 8.22 (d, J = 7.7 Hz, 1H), (m, 3H), 6.25 (d, J = 7.5 Hz, 1H), (m, 1H), 4.66 (d, J = 6.8 Hz, 1H), (m, 2H), (m, 2H), (m, 22H). 13 C NMR (101 MHz, CDCl3) δ 159.3, 156.0, 155.9, 151.1, 133.2, 132.6, 127.3, 126.7, 124.4, 123.4, 79.6, 79.0, 49.9, 40.3, 36.6, 29.6, 28.4, 28.4, HRMS (ESI) Calcd for C23H35N4O4 + [M+H] + : , found: S17

18 tert-butyl (2-phenyl-1-(quinolin-4-yl)ethyl)carbamate (23): Following the general procedure B, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 74% yield as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 8.87 (d, J = 4.2 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 7.74 (t, J = 7.7 Hz, 1H), 7.60 (t, J = 7.7 Hz, 1H), (m, 4H), (m, 2H), 5.82 (br, s, 1H), (m, 1H), (m, 1H), (m, 1H), 1.37 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 154.9, 149.6, 149.5, 147.8, 136.3, 129.9, 129.6, 129.3, 128.6, 127.1, 127.0, 126.0, 122.8, 117.6, 80.2, 51.0, 41.8, HRMS (ESI) Calcd for C22H25N2O2 + [M+H] + : , found: tert-butyl (1-(phenanthridin-6-yl)ethyl)carbamate (24): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 89% yield as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 8.64 (d, J = 8.3 Hz, 1H), 8.54 (dd, J = 8.3, 1.1 Hz, 1H), 8.25 (d, J = 8.2 Hz, 1H), 8.15 (d, J = 7.9 Hz, 1H), (m, 1H), (m, 2H), 7.64 (ddd, J = 8.3, 7.1, 1.4 Hz, 1H), 6.74 (d, J = 6.2 Hz, 1H), (m, 1H), 1.63 (d, J = 6.6 Hz, 3H), 1.52 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 160.4, 155.4, 142.9, 133.2, 130.7, 129.8, 128.7, 127.5, 126.9, 125.4, 123.9, 123.3, 122.6, 122.0, 79.2, 47.6, 28.5, HRMS (ESI) Calcd for C20H23N2O2 + [M+H] + : , found: tert-butyl (1-(2-aminopyrimidin-4-yl)-2-(4-(tert-butoxy)phenyl)ethyl)carbamate (25): Following the general procedure B, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 56% yield as a yellow liquid. 1 H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 4.8 Hz, 1H), 6.92 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 8.1 Hz, 2H), 6.21 (d, J = 4.7 Hz, 1H), 5.58 (d, J = 7.2 Hz, 1H), 5.21 (s, 2H), 4.83 S18

19 4.70 (m, 1H), 3.07 (dd, J = 13.3, 5.9 Hz, 1H), 2.95 (dd, J = 13.1, 7.8 Hz, 1H), 1.42 (s, 9H), 1.31 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 169.6, 162.7, 157.7, 155.1, 154.0, 131.7, 129.8, 124.1, 109.7, 79.6, 78.3, 56.2, 41.3, 28.8, HRMS (ESI) Calcd for C21H31N4O3 + [M+H] + : , found: tert-butyl (2-phenyl-1-(quinazolin-4-yl)ethyl)carbamate (26): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 50% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 9.22 (s, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.86 (t, J = 7.6 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), (m, 3H), (m, 2H), 6.05 (d, J = 7.7 Hz, 1H), (m, 1H), (m, 2H), 1.42 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 168.7, 155.2, 154.0, 150.0, 136.4, 133.9, 129.5, 128.9, 128.2, 127.9, 126.7, 124.0, 122.5, 79.7, 52.0, 42.6, HRMS (ESI) Calcd for C21H24N3O2 + [M+H] + : , found: tert-butyl (1-(3,4,7,8-tetramethyl-1,10-phenanthrolin-2-yl)ethyl)carbamate (27): 0.2 mmol 3,4,7,8-Tetramethyl-1,10-phenanthroline, 0.4 mmol redox active ester, using 2.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 20 mol % PA-1, 2.0 ml DMA, be irradiated by 36 W Blue LEDs for 4 h, obtained in 72% yield as a white solid. 1 H NMR (400 MHz, CD2Cl2) δ 8.85 (s, 1H), (m, 2H), 7.35 (d, J = 7.4 Hz, 1H), (m, 1H), 2.66 (s, 3H), 2.64 (s, 3H), (m, 6H), (m, 12H). 13 C NMR (101 MHz, CD2Cl2) δ 159.8, 155.4, 150.8, 144.0, 143.1, 142.6, 142.1, 130.7, 127.4, 127.0, 126.0, 122.2, 121.5, 78.6, 48.6, 28.3, 22.2, 17.2, 14.8, 14.7, HRMS (ESI) Calcd for C23H30N3O2 + [M+H] + : , found: S19

20 Di-tert-butyl ((3,4,7,8-tetramethyl-1,10-phenanthroline-2,9-diyl)bis(ethane-1,1- diyl))dicarbamate: 0.2 mmol 3,4,7,8-Tetramethyl-1,10-phenanthroline, 0.4 mmol redox active ester, using 2.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 20 mol % PA-1, 2.0 ml DMA, be irradiated by 36 W Blue LEDs for 4 h, obtained in 10% yield as a white solid. 1 H NMR (400 MHz, CD2Cl2) δ 7.89 (s, 2H), 6.93 (d, J = 7.2 Hz, 2H), (m, 2H), 2.58 (br, s, 6H), 2.39 (br, s, 6H), 1.45 (d, J = 6.6 Hz, 6H), 1.39 (s, 18H). 13 C NMR (101 MHz, CD2Cl2) δ 158.9, 155.4, 142.7, 142.6, 127.5, 126.2, 121.8, 78.4, 48.6, 28.2, 21.7, 14.7, HRMS (ESI) Calcd for C30H43N4O4 + [M+H] + : , found: Di-tert-butyl (1-(5-((1,4-diazepan-1-yl)sulfonyl)isoquinolin-1-yl)pentane-1,5- diyl)dicarbamate (28): 0.2 mmol fasudil hydrochloride, 0.3 mmol redox active ester, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 2.0 ml DMA / H2O (10:1), be irradiated by 36 W Blue LEDs for 5 h, obtained in 91% yield as a yellow liquid. 1 H NMR (400 MHz, CDCl3) δ 8.60 (d, J = 6.0 Hz, 1H), 8.47 (d, J = 8.3 Hz, 1H), 8.38 (d, J = 6.0 Hz, 1H), 8.32 (d, J = 7.3 Hz, 1H), 7.71 (t, J = 8.0 Hz, 1H), 6.13 (d, J = 7.9 Hz, 1H), (m, 1H), 4.74 (br, s, 1H), (m, 4H), (m, 2H), (m, 6H), (m, 5H), (m, 20H). 13 C NMR (101 MHz, CDCl3) δ 161.2, 156.0, 155.8, 143.3, 135.3, 132.5, 132.3, 129.8, 126.2, 126.0, 116.9, 79.5, 79.0, 50.8, 50.4, 50.1, 47.3, 40.3, 36.7, 30.5, 29.7, 29.6, 28.4, (one carbon signal is overlapped) HRMS (ESI) Calcd for C29H46N5O6S + [M+H] + : , found: S20

21 Di-tert-butyl (1-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8- yl)pentane-1,5-diyl)dicarbamate (29): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 24% yield as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 5.24 (d, J = 6.6 Hz, 1H), (m, 1H), 4.59 (br, s, 1H), 4.02 (s, 3H), 3.56 (s, 3H), 3.40 (s, 3H), (m, 2H), (m, 1H), (m, 3H), (m, 2H), (m, 18H). 13 C NMR (101 MHz, CDCl3) δ 156.1, 155.5, 155.3, 153.6, 151.7, 147.7, 107.4, 80.3, 79.2, 46.3, 40.0, 34.2, 32.0, 29.9, 29.3, 28.4, 28.3, 27.9, HRMS (ESI) Calcd for C23H39N6O6 + [M+H] + : , found: (2-(2-amino-6-(2-(4-(tert-butoxy)phenyl)-1-((tert-butoxycarbonyl)amino)ethyl)- 9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate (30): 0.3 mmol famciclovir, 0.2 mmol redox active ester, using 1.0 mol% Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol% PA-1, 2.0 ml DMA, obtained in 62% yield as a colorless liquid. 1 H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H), 6.91 (d, J = 7.6 Hz, 2H), 6.79 (d, J = 7.7 Hz, 2H), 6.09 (d, J = 7.7 Hz, 1H), (m, 1H), 5.09 (s, 2H), (m, 6H), (m, 1H), (m, 1H), 2.07 (s, 6H), (m, 1H), (m, 2H), 1.40 (s, 9H), 1.28 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 170.9, 160.6, 159.2, 155.1, 153.7, 153.2, 141.2, 132.0, 130.0, 125.3, 123.8, 79.2, 78.1, 63.7, 53.6, 40.9, 40.7, 34.9, 28.9, 28.8, 28.4, HRMS (ESI) Calcd for C31H45N6O7 + [M+H] + : , found: S21

22 N-((2S)-1-((1-(isoquinolin-1-yl)ethyl)amino)-1-oxopropan-2-yl)benzamide (31): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 88% (A : B = dr = 1:1) yield as a white solid. 1 H NMR (400 MHz, CDCl3) (1:1 mixture of diastereomers) δ 8.42 (d, J = 5.7 Hz, 1H, A), 8.39 (d, J = 5.7 Hz, 1H, B), (m, 4H, A+B), (m, 6H, A+B), (m, 6H, A+B), (m, 6H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 12H, A+B). HRMS (ESI) Calcd for C21H22N3O2 + [M+H] + : , found: N-(2-((1-(isoquinolin-1-yl)-2-phenylethyl)amino)-2-oxoethyl)benzamide (32): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 94% yield as a white solid. 1 H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 5.7 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), (m, 4H), 7.66 (dd, J = 8.0, 7.0 Hz, 1H), (m, 3H), 7.42 (t, J = 7.6 Hz, 2H), 7.22 (d, J = 4.2 Hz, 1H), (m, 3H), (m, 2H), (m, 1H), 4.17 (d, J = 4.9 Hz, 2H), (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 168.0, 167.5, 158.1, 141.0, 136.7, 136.3, 133.9, 131.7, 130.3, 129.6, 128.5, 128.1, 127.6, 127.4, 127.2, 126.5, 125.7, 124.2, 120.6, 51.0, 43.5, HRMS (ESI) Calcd for C26H24N3O2 + [M+H] + : , found: Benzyl (2-((2-(1H-indol-3-yl)-1-(isoquinolin-1-yl)ethyl)amino)-2- S22

23 oxoethyl)carbamate (33): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 90% yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 5.5 Hz, 1H), 8.05 (d, J = 8.4 Hz, 1H), 7.97 (s, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.75 (d, J = 6.1 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.54 (d, J = 5.6 Hz, 1H), (m, 1H), (m, 5H), 7.21 (d, J = 8.1 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 8.1 Hz, 1H), 6.90 (t, J = 7.5 Hz, 1H), 6.60 (s, 1H), 6.28 (dd, J = 12.6, 6.4 Hz, 1H), 5.54 (s, 1H), 5.12 (s, 2H), 3.92 (d, J = 5.6 Hz, 2H), (m, 2H). 13 C NMR (101 MHz, CDCl3) δ 168.1, 158.5, 156.5, 140.6, 136.4, 136.3, 135.8, 130.3, 128.5, 128.1, 128.1, 127.9, 127.5, 127.3, 125.8, 124.4, 123.1, 121.7, 120.6, 119.3, 118.3, 111.0, 110.6, 67.0, 50.3, 44.5, HRMS (ESI) Calcd for C29H27N4O3 + [M+H] + : , found: tert-butyl ((2S)-1-((1-(5-((1,4-diazepan-1-yl)sulfonyl)isoquinolin-1-yl)-3- (methylthio)propyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (34): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 74% (A : B = dr = 1:1) yield as a viscous liquid. 1 H NMR (400 MHz, CDCl3) (1:1 mixture of diastereomers) δ (m, 4H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 6H, A+B), (m, 4H, A+B), 6.13 (br, s, 2H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 8H, A+B), (m, 16H, A+B), (m, 4H, A+B), 2.04 (s, 3H, A), 2.03 (s, 3H, B), (m, 6H, A+B), (m, 18H, A+B). HRMS (ESI) Calcd for C32H44N5O5S2 + [M+H] + : , found: S23

24 Benzyl (2-oxo-2-((2S)-2-((1-(phenanthridin-6-yl)ethyl)carbamoyl)pyrrolidin-1- yl)ethyl)carbamate (35): Following the general procedure A, using 1.0 mol % Ir[dF(CF3)ppy]2(dtbbpy)PF6, 10 mol % PA-1, 2.0 ml DMA, obtained in 84% (A : B = dr = 1:1) yield as a white solid. 1 H NMR (400 MHz, CDCl3) (1:1 mixture of diastereomers) δ (m, 2H, A+B), (m, 2H, A+B), 8.50 (d, J = 6.9 Hz, 1H, A), 8.36 (d, J = 7.1 Hz, 1H, B), (m, 2H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 6H, A+B), (m, 10H, A+B), (m, 2H, A+B), (m, 2H, A+B), (m, 4H, A+B), (m, 2H, A+B), (m, 4H, A+B), (m, 4H, A+B), (m, 8H, A+B), (m, 6H, A+B). HRMS (ESI) Calcd for C30H31N4O4 + [M+H] + : , found: Gram-scale reaction Redox active ester (2.25 g, 5 mmol), Ir[dF(CF3)ppy]2(dtbbpy)PF6 (1.0 mol %, 44 mg) and 1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate (PA-1, 10 mol%, 139 mg) were placed in a transparent Schlenk tube equipped with a stirring bar. The tube was evacuated and filled with argon (three times). To these solids, isoquinoline (517 mg, 4 mmol) and anhydrous N,N-dimethylacetamide (DMA, 30 ml) was added via a gastight syringe under argon atmosphere. The reaction mixture was stirred under the irradiation of a 36 W Blue LEDs (distance app. 3.0 cm from the bulb) at room temperature for 5 h. After 5 h, the mixture was diluted with ethyl acetate (120 ml) and washed with brine (3 x 50 ml). The organic layer was dried by Na2SO4 and concentrated under vacuo. After purification by flash column chromatography on silica gel, the product was obtained in 89%. S24

25 6. References 1. Lowry, M. S.; Goldsmith, J. I.; Slinker, J. D.; Rohl, R.; Pascal, R. A.; Malliaras, G. G.; Bernhard, S. Chem. Mater. 2005, 17, (a) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.; Pan, C.-M.; Gianatassio, R.; Schmidt, M. A.; Eastgate, M. D.; Baran, P. S. J. Am. Chem. Soc. 2016, 138, (b) Jin, Y.-H.; Jiang, M.; Wang, H.; Fu, H. Sci. Rep. 2016, 6, (c) Schwarz, J.; König, B. Green. Chem. 2016, 18, (d) Pratsch, G.; Lackner, G. L.; Overman, L. E. J. Org. Chem. 2015, 80, Spangler, J. E.; Kobayashi, Y.; Verma, P.; Wang, D.-H.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, S25

26 7. NMR Spectra 1 H NMR spectrum of tert-butyl (2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)carbamate S26

27 1 H NMR spectrum of benzyl (2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)carbamate 13 C NMR spectrum of benzyl (2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)carbamate S27

28 1 H NMR spectrum of N-(2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)benzamide 13 C NMR spectrum of N-(2-phenyl-1-(4-phenylquinolin-2-yl)ethyl)benzamide S28

29 1 H NMR spectrum of tert-butyl ((4-phenylquinolin-2-yl)methyl)carbamate 13 C NMR spectrum of tert-butyl ((4-phenylquinolin-2-yl)methyl)carbamate S29

30 1 H NMR spectrum of tert-butyl (1-(4-phenylquinolin-2-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(4-phenylquinolin-2-yl)ethyl)carbamate S30

31 1 H NMR spectrum of tert-butyl 2-(4-phenylquinolin-2-yl)pyrrolidine-1-carboxylate 13 C NMR spectrum of tert-butyl 2-(4-phenylquinolin-2-yl)pyrrolidine-1-carboxylate S31

32 1 H NMR spectrum of tert-butyl (3-phenyl-1-(4-phenylquinolin-2-yl)propyl)carbamate 13 C NMR spectrum of tert-butyl (3-phenyl-1-(4-phenylquinolin-2-yl)propyl)carbamate S32

33 1 H NMR spectrum of tert-butyl (2-(4-iodophenyl)-1-(4-phenylquinolin-2-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-(4-iodophenyl)-1-(4-phenylquinolin-2-yl)ethyl)carbamate S33

34 1 H NMR spectrum of tert-butyl ((2S)-1-(isoquinolin-1-yl)-2-methylbutyl)carbamate (9-A) 13 C NMR spectrum of tert-butyl ((2S)-1-(isoquinolin-1-yl)-2-methylbutyl)carbamate (9-A) S34

35 1 H NMR spectrum of tert-butyl ((2S)-1-(isoquinolin-1-yl)-2-methylbutyl)carbamate (9-B) 13 C NMR spectrum of tert-butyl ((2S)-1-(isoquinolin-1-yl)-2-methylbutyl)carbamate (9-B) S35

36 1 H NMR spectrum of di-tert-butyl (1-(isoquinolin-1-yl)pentane-1,5-diyl)dicarbamate 13 C NMR spectrum of di-tert-butyl (1-(isoquinolin-1-yl)pentane-1,5-diyl)dicarbamate S36

37 1 H NMR spectrum of tert-butyl (2-(1H-indol-3-yl)-1-(isoquinolin-1-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-(1H-indol-3-yl)-1-(isoquinolin-1-yl)ethyl)carbamate S37

38 1 H NMR spectrum of cyclohexyl 3-((tert-butoxycarbonyl)amino)-3-(isoquinolin-1-yl)propanoate 13 C NMR spectrum of cyclohexyl 3-((tert-butoxycarbonyl)amino)-3-(isoquinolin-1-yl)propanoate S38

39 1 H NMR spectrum of methyl 4-(((benzyloxy)carbonyl)amino)-4-(isoquinolin-1-yl)butanoate 13 C NMR spectrum of methyl 4-(((benzyloxy)carbonyl)amino)-4-(isoquinolin-1-yl)butanoate S39

40 1 H NMR spectrum of benzyl (1-(isoquinolin-1-yl)-3-(methylthio)propyl)carbamate 13 C NMR spectrum of benzyl (1-(isoquinolin-1-yl)-3-(methylthio)propyl)carbamate S40

41 1 H NMR spectrum of tert-butyl (2-(4-(tert-butoxy)phenyl)-1-(isoquinolin-1-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-(4-(tert-butoxy)phenyl)-1-(isoquinolin-1-yl)ethyl)carbamate S41

42 1 H NMR spectrum of benzyl (4-amino-1-(isoquinolin-1-yl)-4-oxobutyl)carbamate 13 C NMR spectrum of benzyl (4-amino-1-(isoquinolin-1-yl)-4-oxobutyl)carbamate S42

43 1 H NMR spectrum of tert-butyl (2-(tert-butoxy)-1-(isoquinolin-1-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-(tert-butoxy)-1-(isoquinolin-1-yl)ethyl)carbamate S43

44 1 H NMR spectrum of tert-butyl (1-(6-bromoisoquinolin-1-yl)-2-phenylethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(6-bromoisoquinolin-1-yl)-2-phenylethyl)carbamate S44

45 1 H NMR spectrum of tert-butyl (1-(4-chloroquinolin-2-yl)-2-phenylethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(4-chloroquinolin-2-yl)-2-phenylethyl)carbamate S45

46 1 H NMR spectrum of tert-butyl (1-(4-methylquinolin-2-yl)-2-phenylethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(4-methylquinolin-2-yl)-2-phenylethyl)carbamate S46

47 1 H NMR spectrum of tert-butyl (1-(3-chloroquinoxalin-2-yl)-2-phenylethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(3-chloroquinoxalin-2-yl)-2-phenylethyl)carbamate S47

48 1 H NMR spectrum of di-tert-butyl (1-(phthalazin-1-yl)pentane-1,5-diyl)dicarbamate 13 C NMR spectrum of di-tert-butyl (1-(phthalazin-1-yl)pentane-1,5-diyl)dicarbamate S48

49 1 H NMR spectrum of tert-butyl (2-phenyl-1-(quinolin-4-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-phenyl-1-(quinolin-4-yl)ethyl)carbamate S49

50 1 H NMR spectrum of tert-butyl (1-(phenanthridin-6-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(phenanthridin-6-yl)ethyl)carbamate S50

51 1 H NMR spectrum of tert-butyl (1-(2-aminopyrimidin-4-yl)-2-(4-(tertbutoxy)phenyl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(2-aminopyrimidin-4-yl)-2-(4-(tertbutoxy)phenyl)ethyl)carbamate S51

52 1 H NMR spectrum of tert-butyl (2-phenyl-1-(quinazolin-4-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (2-phenyl-1-(quinazolin-4-yl)ethyl)carbamate S52

53 1 H NMR spectrum of tert-butyl (1-(3,4,7,8-tetramethyl-1,10-phenanthrolin-2-yl)ethyl)carbamate 13 C NMR spectrum of tert-butyl (1-(3,4,7,8-tetramethyl-1,10-phenanthrolin-2-yl)ethyl)carbamate S53

54 1 H NMR spectrum of di-tert-butyl ((3,4,7,8-tetramethyl-1,10-phenanthroline-2,9-diyl)bis(ethane- 1,1-diyl))dicarbamate 13 C NMR spectrum of di-tert-butyl ((3,4,7,8-tetramethyl-1,10-phenanthroline-2,9-diyl)bis(ethane- 1,1-diyl))dicarbamate S54

55 1 H NMR spectrum of di-tert-butyl (1-(5-((1,4-diazepan-1-yl)sulfonyl)isoquinolin-1-yl)pentane- 1,5-diyl)dicarbamate 13 C NMR spectrum of di-tert-butyl (1-(5-((1,4-diazepan-1-yl)sulfonyl)isoquinolin-1-yl)pentane- 1,5-diyl)dicarbamate S55

56 1 H NMR spectrum of di-tert-butyl (1-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8- yl)pentane-1,5-diyl)dicarbamate 13 C NMR spectrum of di-tert-butyl (1-(1,3,7-trimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8- yl)pentane-1,5-diyl)dicarbamate S56

57 1 H NMR spectrum of 2-(2-(2-amino-6-(2-(4-(tert-butoxy)phenyl)-1-((tertbutoxycarbonyl)amino)ethyl)-9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate 13 C NMR spectrum of 2-(2-(2-amino-6-(2-(4-(tert-butoxy)phenyl)-1-((tertbutoxycarbonyl)amino)ethyl)-9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate S57

58 1 H NMR spectrum of N-((2S)-1-((1-(isoquinolin-1-yl)ethyl)amino)-1-oxopropan-2-yl)benzamide (1:1 mixture of diastereomers) 1 H NMR spectrum of N-(2-((1-(isoquinolin-1-yl)-2-phenylethyl)amino)-2-oxoethyl)benzamide S58

59 13 C NMR spectrum of N-(2-((1-(isoquinolin-1-yl)-2-phenylethyl)amino)-2-oxoethyl)benzamide 1 H NMR spectrum of benzyl (2-((2-(1H-indol-3-yl)-1-(isoquinolin-1-yl)ethyl)amino)-2- oxoethyl)carbamate S59

60 13 C NMR spectrum of benzyl (2-((2-(1H-indol-3-yl)-1-(isoquinolin-1-yl)ethyl)amino)-2- oxoethyl)carbamate 1 H NMR spectrum of tert-butyl ((2S)-1-((1-(5-((1,4-diazepan-1-yl)sulfonyl)isoquinolin-1-yl)-3- (methylthio)propyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (1:1 mixture of diastereomers) S60

61 1 H NMR spectrum of benzyl (2-oxo-2-((2S)-2-((1-(phenanthridin-6- yl)ethyl)carbamoyl)pyrrolidin-1-yl)ethyl)carbamate (1:1 mixture of diastereomers) S61