Selective, Nickel-Catalyzed Hydrogenolysis of Aryl Ethers

www.sciencemag.org/cgi/content/full/332/6028/439/dc1 Supporting nline Material for Selective, Nickel-Catalyzed Hydrogenolysis of Aryl Ethers Alexey G. Sergeev and John F. Hartwig* *To whom correspondence should be addressed. E-mail: jhartwig@illinois.edu This PDF file includes: Published 22 April 2011, Science 332, 439 (2010) DI: 10.1126/science.1200437 Materials and Methods SM Text Figs. S1 to S3 Tables S1 to S6 References

Supporting nline Material Selective, Nickel-Catalyzed Hydrogenolysis of Aryl Ethers Alexey G. Sergeev and John F. Hartwig * Department of Chemistry, University of Illinois, 600 South Matthews Avenue, Urbana, Illinois 61801 Table of Contents: 1. Full References from the Main Text 3 2. General Experimental Details 3 3. Preparation of Aryl and Benzyl Ethers 5 4. Stability of the Ni(CD) 2 /PCy 3 Catalyst Under the Conditions of Reductive Cleavage of Aromatic C- bonds 15 Figure S1. Attempted Hydrogenolysis of Diphenyl Ether Catalyzed by Ni(CD) 2 /PCy 3 15 Figure S2. Attempted Reductive Cleavage of Anisole with Triethylsilane Catalyzed by Ni(CD) 2 /PCy 3 16 5. Nickel-NHC Catalyzed Reductive Cleavage of Aryl and Benzyl Ethers with Hydride Donors 18 Discussion 19 Table S1. Selected Results on the Effect of Ligand, Nickel and Hydride Source and Base Amount on the Reductive Cleavage of Diphenyl Ether 21 Figure S3. Carbene Ligands Used in the Study 21 Table S2. Reductive Cleavage of Aryl and Benzyl Ethers with Hydride Donors 22 6. Nickel-NHC Catalyzed Selective Hydrogenolysis of Aryl and Benzyl Ethers 29 Competition Experiments 43 * To whom correspondence should be addressed. E-mail: jhartwig@illinois.edu

Supporting nline Material. Mercury Poisioning Experiments 45 Table S3. Selected Results on Effect of Ligand, Temperature and Amount of Base on Hydrogenolysis of Diphenyl Ether 47 Table S4. Effect of Ligand, Nickel Source, Temperature, Amount of Base and AlMe 3 on Hydrogenolysis of 2-Methoxynaphthalene 47 Table S5. Control Experiments for Hydrogenolyisis of 2-Methoxynaphthalene 48 Table S6. Catalyst Stability Estimation in Hydrogenolysis of Methyl Aryl Ethers 48 7. NMR spectra 49 8. References 67 2

Supporting nline Material. 1. Full References from the Main Text Ref. 20: B. T. Guan, S. K. Xiang, T. Wu, Z. P. Sun, B. Q. Wang, K. Q. Zhao, Z. J. Shi, Chem. Comm., 1437 (2008). Ref. 35: B. A. Ellsworth, W. Meng, M. Patel, R. N. Girotra, G. Wu, P. M. Sher, D. L. Hagan, M. T. bermeier, W. G. Humphreys, J. G. Robertson, A.Wang, S. Han, T. L.Waldron, N. N. Morgan, J. M. Whaley, W. N. Washburn, Bioorg. Med. Chem. Lett. 18, 4770 (2008). 2. General Experimental Details Equipment and methods All air-sensitive manipulations were conducted under an inert atmosphere in a nitrogenfilled Innovative Technology glovebox or by standard Schlenk technique under argon. All glassware was heated in an oven and cooled in an inert atmosphere prior to use. GC analyses were obtained on an Agilent 6890 Gas Chromatograph equipped with an HP- 5 25 m x 0.20 mm ID x 0.33 µm capillary column (Agilent) and an FID detector. The following GC oven temperature programs were used: A) 100 C hold for 3 min, ramp 40 C/min to a final temperature of 300 C, and hold for 2.5 min; B) 80 C, ramp 110 C/min to a final temperature of 300 C, and hold for 3.2 min; C) 35 C hold for 2 min, ramp 45 C/min to a final temperature of 300 C, and hold for 2 min. Helium was used as a carrier gas, with a constant column flow of 5.6 ml/min (program A and B) or 6.6 ml/min (program C). The injector temperature was held at 250 C (program A) or 300 C (program B and C). GC-MS analyses were obtained on an Agilent 6890-N Gas Chromatograph equipped with an HP-5 30 m 0.25 mm 0.25 µm capillary column (Agilent). The GC was directly interfaced to an Agilent 5973 mass selective detector (EI, 70 ev). The following GC oven temperature programs were used: A) 50 C hold for 2 min, ramp 40 C/min to a final temperature of 300 C, and hold for 2 min; B) 100 C hold for 3 min, ramp 40 C/min to 3

Supporting nline Material. a final temperature of 300 C, and hold for 2.5 min. Helium was used as a carrier gas, with a constant column flow of 1 ml/min. The injector temperature was held constant at 250 C. NMR spectra were acquired on a 400 MHz Varian Unity instrument or on 500 MHz Varian Unity or Inova instruments at the University of Illinois VICE NMR facility. Chemical shifts are reported in ppm relative to a peak of a residual protiated solvent (CDCl 3, δ 7.26 ppm for 1 H and 77 ppm for 13 C). Flash column chromatography was performed on a Teledyne Isco CombiFlash Rf automated chromatography system with RediSep Rf Gold normal-phase silica columns (40 and 80 g). Analytical thin-layer chromatography (TLC) was performed using glass plates pre-coated with silica gel (0.25 mm, 60 Å pore size) impregnated with a fluorescent indicator (254 nm). TLC plates were visualized by exposure to ultraviolet light (UV) and/or submersion in aqueous potassium permanganate solution (KMn 4 ), followed by brief heating. Elemental analyses were performed by the University of Illinois at Urbana-Champaign Microanalysis Laboratory and by Robertson Microlit Laboratories, Inc. (Madison, NJ). Solvents and reagents Benzene, toluene, and tetrahydrofuran (THF) were degassed by purging with nitrogen for 45 min and purified using an Innovative Technology Pure Solv PS-400-6 solvent purification system equipped with 1 m column with activated alumina. Anhydrous dioxane, m-xylene and dimethylsulfoxide (DMS) where purchased from Aldrich and used as received. All the solvents were stored under nitrogen atmosphere in glovebox. Methylene chloride, diethyl ether, acetone, ethyl acetate and hexanes were purchased from Fisher Scientific and used as received. Nickel acetylacetonate (Ni(acac) 2 ) and nickel cyclooctadiene (Ni(CD) 2 ) were purchased from Aldrich or Aldrich and Strem respectively. Tricyclohexylphosphine was purchased from Strem. 1,3-Bis(2,6-di-isopropylphenyl)imidazolinium tetrafluoroborate (SIPr HBF 4 ) was purchased from Aldrich, 1,3-Bis(2,6-di-isopropylphenyl)imidazolinium chloride (SIPr HCl) (S1) and 4,5-dimethyl- 4

Supporting nline Material. 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr Me HCl) (S2) were prepared according to the literature procedures. m-bis(m-phenoxyphenyl)benzene (Santovac 5P Ultra) was purchased from Scientific Instrument Services, Inc. 4-methoxybiphenyl, and phenyl 4-trifluoromethylphenyl ether were purchased from Alfa-Aesar. Diphenyl ether, di-4-methylphenyl ether, 4-tert-butylanisole, anisole, dibenzofuran, 1- and 2- methoxynaphthalene, sodium tert-butoxide were purchased from Aldrich and used as received. Triethylsilane, diisobutylaluminum hydride (1M solution in hexanes), trimethylaluminum (2M solution in toluene) were purchased from Aldrich. N-methy-N- (trimethylsilyl) trifluoroacetamide (MSTFA) was ordered from Acros. Anhydrous copper iodide, pyridine-2-carboxylic acid (picolinic acid), anhydrous K 3 P 4, phenols and aryl iodides (if not otherwise mentioned) were purchased from Aldrich. ther solvents and reagents were ordered from Aldrich and used as received. Hydrogen (>99%) was purchased from Linde Gas North America LLC and used as received. 3. Preparation of Diaryl and Benzyl Ethers General procedure for the preparation of diarylethers (modified literature procedure) (S3) I H R 1 R 2 10 mol% CuI, 20 mol% L K 3 P 4, DMS, 100 o C, 20h R 1 R 2 L = N C 2 H In a glovebox, a 50 ml round bottom flask was charged with copper (I) iodide (152 mg, 0.798 mmol), picolinic acid (pyridine-2-carboxylic acid, 197 mg, 1.60 mmol), aryl iodide (8.00 mmol), phenol (9.60 mmol), potassium phosphate (16.0 mmol, 3.40 g), a magnetic stir bar and DMS (16 ml). The reaction flask was sealed with a septum, removed from the box, and the reaction mixture was stirred at 100 C for 20 h. The reaction mixture was cooled and diluted with a 1:1 mixture of saturated aqueous solution of ammonium chloride (100 ml) and water (100 ml). The crude product was extracted with methylene chloride (3 100 ml). The combined organic extracts were successively washed with a 5% aqueous solution of potassium hydroxide (100 ml), brine (100 ml) and dried over 5

Supporting nline Material. anhydrous sodium sulfate. The crude product was preadsorbed on silicagel (3-4 g) and purified by flash column chromatography. Di-2-methoxyphenyl ether (a model of the 5--5 lignin ether linkage) (S4) Prepared according to the general procedure using 2-iodoanisole (0.963 g, 4.11 mmol), guaiacol (2-methoxyphenol, 0.597 g, 4.81 mmol), potassium phosphate (1.89 g, 8.90 mmol), copper (I) iodide (78 mg, 0.41 mmol), pyridine-2- carboxylic acid (100 mg, 0.812 mmol) and DMS (8 ml). The crude product was purified by flash column chromatography (eluent: hexanes to hexanes-ethyl acetate, 10:1) to give di-2-methoxyphenyl ether as a white solid (0.425 g, 1.84 mmol) in 45% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.04-7.10 (m, 2H), 6.98 (dd, J = 1.5, 8.0 Hz, 2H), 6.80-6.90 (m, 4H), 3.86 (s, 6H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 150.5 (C), 146.0 (C), 123.7 (CH), 120.8 (CH), 118.8 (CH), 112.6 (CH), 55.9 (CH 3 ). 2-Methoxyphenyl phenyl ether (a model of the 5--5 lignin ether linkage) (S5) Prepared according to the general procedure using iodobenzene (0.760 g, 3.16 mmol), guaiacol (2-methoxyphenol, 0.654 g, 5.26 mmol), potassium phosphate (1.78 g, 8.34 mmol), copper (I) iodide (80 mg, 0.42 mmol), pyridine-2-carboxylic acid (103 mg, 0.836 mmol) and DMS (8 ml). The crude product was purified by flash column chromatography (eluent: hexanes to hexanes-ethyl acetate, 10:1) to give 2-methoxyphenyl phenyl ether as a white solid (0.455 g, 2.27 mmol) in 72% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.27-7.34 (m, 2H), 7.10-7.17 (m, 1H), 6.89-7.08 (m, 6H), 3.85 (s, 3H). Di-3-methoxyphenyl ether (S5, S6) Me Prepared according to the general procedure using 3-iodoanisole (0.717 g, 3.06 mmol), 3-methoxyphenol (0.469 g, 3.77 mmol), potassium phosphate (1.66 g, 7.82 mmol), copper (I) iodide (60 mg, 0.32 mmol), pyridine-2-carboxylic acid (83 mg, 0.67 mmol) and DMS (6 ml). The crude product was purified by flash column chromatography (eluent: hexanes-ethyl acetate, from 20:1 to 10:1) to give di-3-methoxyphenyl ether as a colorless oil (0.486 g, 2.11 mmol) in 69% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.23 (apparent t, J = 8.0 Hz, 2H), 6.64-6.69 (m, 2H), 6

Supporting nline Material. 6.58-6.63 (m, 4H), 3.78 (s, 6H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 160.9 (C), 158.2 (C), 130.0 (CH), 111.1 (CH), 109.0 (CH), 105.0 (CH), 55.3 (CH 3 ). Di-4-tert-butylphenyl ether (S4, S7) Prepared according to the general procedure using 4-iodo-tert- t Bu t Bu butylbenzene (1.18 g, 4.54 mmol), 4-tert-butylphenol (0.817 g, 5.43 mmol), potassium phosphate (1.63 g, 7.67 mmol), copper (I) iodide (74 mg, 0.39 mmol), pyridine-2-carboxylic acid (103 mg, 0.852 mmol) and DMS (10 ml). The crude product was purified by flash column chromatography (eluent: hexanes) to give di-4-tertbutylphenyl ether as a white solid (1.01 g, 3.58 mmol) in 78% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.36 (apparent d, J = 9 Hz), 6.97 (apparent d, J = 9 Hz), 1.35 (s, 18H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) δ 155.1 (C), 145.8 (C), 126.4 (CH), 118.2 (CH), 34.3 (C), 31.5 (CH 3 ). Di-3-methylphenyl ether (S8, S9) Me Me Prepared according to the general procedure using 3-iodotoluene (0.889 g, 4.03 mmol), 3-methylphenol (0.535 g, 4.95 mmol), potassium phosphate (1.69 g, 7.96 mmol), copper (I) iodide (77 mg, 0.40 mmol), pyridine-2-carboxylic acid (100 mg, 0.812 mmol) and DMS (8 ml). The crude product was purified by flash column chromatography (eluent: hexanes) to give di-3- methylphenyl ether as an colorless oil (0.655 g, 3.30 mmol) in 82% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.23 (t, J = 8 Hz, 2H), 6.93 (apparent d, J = 7.5 Hz, 2H), 6.84-6.86 (apparent br s, 2H), 6.81-6.84 (m, J = 8.0, 2 Hz, 2H), 2.35 (s, 6H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) δ 157.3 (C), 139.8 (C), 129.4 (CH), 119.5 (CH), 115.9 (CH), 21.4 (CH 3 ). 4-Methoxyphenyl 4-trifluoromethylphenyl ether (S10) F 3 C Prepared according to the general procedure using 4-iodotrifluoromethylbenzene (0.853 g, 3.14 mmol), 4-methoxyphenol (0.474 g, 3.82 mmol), potassium phosphate (1.97 g, 9.28 mmol), copper (I) iodide (58 mg, 0.30 mmol), pyridine-2-carboxylic acid (75 mg, 0.61 mmol) and DMS (6 ml). The crude product was purified by flash column chromatography (eluent: hexanes to hexanes- 7

Supporting nline Material. ethyl acetate, 40:1) to give 4-methoxyphenyl 4-trifluoromethylphenyl ether as a white solid (0.706 g, 2.63 mmol) in 84% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.54 (d, J = 9 Hz, 2H), 7.01 (apparent d, J = 9 Hz, 2H), 6.98 (d, J = 8.5 Hz, 2H), 6.93 (apparent d, J = 9 Hz, 2H), 3.83 (s, 3H). 19 F { 1 H} NMR (470 MHz, CDCl 3 ) δ -62.1. 13 C { 1 H} NMR (470 MHz, CDCl 3 ). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) δ 161.5 (C), 156.7 (C), 148.8 (C), 127.0 (q, J CF = 3.5 Hz, CH), 124.2 (q, J CF = 272 Hz, CF 3 ), 124.3 (q, J CF = 32 Hz, C), 121.5 (CH), 116.9 (CH), 115.2 (CH), 55.7 (CH 3 ). 4-Methoxyphenyl phenyl ether (S11) Prepared according to the general procedure using iodobenzene (0.836 g, 4.09 mmol), 4-methoxyphenol (0.654 g, 5.26 mmol), potassium phosphate (1.73 g, 8.14 mmol), copper (I) iodide (79 mg, 0.42 mmol), pyridine-2- carboxylic acid (119 mg, 0.967 mmol) and DMS (8 ml). The crude product was purified by flash column chromatography (eluent: hexanes to hexanes-ethyl acetate, 20:1) to give 4-methoxyphenyl phenyl ether as a colorless oil (0.651 g, 3.24 mmol) in 79% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.35 (apparent t, J = 8 Hz, 2H), 7.09 (apparent t, J = 7.5 Hz, 1H), 7.04 (apparent d, J = 9.0 Hz, 2H), 7.01 (apparent t, J = 8 Hz, 2H), 6.93 (apparent d, J = 9.0 Hz, 2H), 3.84 (s, 3H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 158.5 (C), 155.8 (C), 150.0 (C), 129.5 (CH), 122.3 (CH), 120.7 (CH), 117.5 (CH), 114.8 (CH), 55.5 (CH 3 ). Di-2-methylphenyl ether (S11) Me Me Prepared according to the general procedure using 2-iodomethylbenzene (0.899 g, 4.12 mmol), 2-methylphenol (0.492 g, 4.54 mmol), potassium phosphate (1.84 g, 8.67 mmol), copper (I) iodide (81 mg, 0.43 mmol), pyridine-2-carboxylic acid (99 mg, 0.80 mmol) and DMS (8 ml). The crude product was purified by flash column chromatography (eluent: hexanes) to give di-2- methylphenyl ether as a colorless oil (0.692 g, 3.49 mmol) in 85% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.32 (d, J = 7.5 Hz, 2H), 7.19 (apparent t, J = 8 Hz, 2H), 7.08 (apparent t, J = 7.5 Hz, 2H), 6.81 (d, J = 8 Hz, 2H), 2.37 (s, 6H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 155.2 (C), 131.3 (CH), 128.8 (C), 127.0 (CH), 123.0 (CH), 117.6 (CH), 16.1 (CH 3 ). 8

Supporting nline Material. 2-(Hexyloxy)naphthalene (S12). A 25 ml Schlenk flask equipped with a Teflon stopcock and a magnetic stir bar was charged with anhydrous potassium carbonate (1.05 g, 7.60 mmol), evacuated and filled with argon. 2-Naphthol (0.721 g, 5.00 mmol), acetone (7.5 ml) and 1-iodohexane (1.64 g, 7.73 mmol) were added. The flask was sealed and the reaction mixture was stirred at 70 C for 14 h. The mixture was cooled to room temperature, evaporated and the residue was partitioned between ether (150 ml) and water (50 ml). rganic layer was separated, washed with 5% aqueous potassium hydroxide solution (50 ml), brine (50 ml), and dried over anhydrous sodium sulfate. The solution was evaporated on silica gel (3.2 g) and the crude product was purified by flash column chromatography (eluent: hexanes) to give 2- (hexyloxy)naphthalene as a colorless oil (1.05 g, 4.60 mmol) in 92% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.77-7.78 (m, 3H), 7.47-7.54 (m, 1H), 7.37-7.43 (m, 1H), 7.17-7.27 (m, 2H), 7.32 (t, J = 6.5 Hz, 2H), 1.86-1.97 (2H), 1.52-1.63 (m, 2H), 1.38-1.51 (m, 4H), 0.97-1.07 (m, 3H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 157.1 (C), 134.6 (C), 129.24 (CH), 128.8 (C), 127.6 (CH), 126.6 (CH), 126.2 (CH), 123.4(CH), 119.0 (CH), 106.5 (CH), 67.9 (CH 2 ), 31.6 (CH 2 ), 29.2 (CH 2 ), 25.8 (CH 2 ), 22.6 (CH 2 ), 14.0 (CH 3 ). 4-(Hexyloxy)biphenyl (S13) Prepared in a similar manner to 2-(hexyloxy)naphthalene using 4-hydroxybiphenyl (0.853 g, 5.01 mmol), 1-iodohexane (1.65 g, 7.78 mmol), potassium carbonate (1.05 g, 7.60 mmol) and acetone (7.5 ml). The crude product was purified by flash column chromatography (eluent: hexanes) to give 4-(hexyloxy)biphenyl as white crystals (0.977 mg, 3.84 mmol) in 76% yield. The product was further purified via recrystallization from methanol. 1 H NMR (400 MHz, CDCl 3 ) δ 7.60 (apparent d, J = 7.5 Hz, 2H), 7.56 (apparent d, J = 8.5 Hz, 2H), 7.46 (apparent t, J = 7.5 Hz, 2H), 7.34 (apparent t, J = 8.5 Hz, 1H), 7.01 (apparent d, J = 7.5 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 1.85 (m, 2H), 1.47-1.59 (m, 2H), 1.34-1.59 (m, 4H), 0.91-1.04 (m, 3H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 158.7 (C), 9

Supporting nline Material. 140.8 (C), 133.5 (C), 128.7 (CH), 128.0 (CH), 126.7 (CH), 126.5 (CH), 114.7 (CH), 68.0 (CH 2 ), 31.6 (CH 2 ), 29.3 (CH 2 ), 25.7 (CH 2 ), 22.6 (CH 2 ), 14.0 (CH 3 ). General procedure for preparation of benzyl aryl ethers H Br R 1 R 2 K 2 C 3, acetone, reflux, 3 h A 100 ml flask equipped with a reflux condenser, argon inlet and magnetic stir bar, was charged with anhydrous potassium carbonate (1.66 g, 12 mmol), evacuated and filled with argon. A phenol (12 mmol), acetone (24 ml), and a benzyl bromide (10 mmol) were then added and the reaction mixture was refluxed for 3 h. The mixture was cooled down, and filtered. The filtrate was evaporated and dissolved in methylene chloride (100 ml). The resulting solution was washed with 5% aqueous solution of potassium hydroxide (50 ml), brine (50 ml) and dried over anhydrous sodium sulfate. The solution was evaporated and the crude product was either purified by flash column chromatography (liquids) or by recrystallization (solids). R 1 R 2 4-tert-Butylbenzyl phenyl ether. Prepared according to the general procedure using 4-tert-butylbenzyl t Bu bromide (2.47 g, 10.9 mmol), phenol (1.20 g, 12.8 mmol), potassium carbonate (2.12 g, 15.3 mmol), and acetone (25 ml). The crude product was recrystallyzed from hexanes (10 ml) to give 4-tert-butylbenzyl phenyl ether as white crystals (2.23 g, 9.28 mmol) in 85% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.47 (apparent d, J = 8.5 Hz, 2H), 7.42 (apparent d, J = 8.5 Hz, 2H), 7.34 (apparent t, J = 8.0 Hz, 2H), 6.98-7.07 (m, 3H), 1.39 (s, 9H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 158.9 (C), 151.0 (C), 134.0 (C), 129.4 (CH), 127.4 (CH), 125.5 (CH), 120.8 (CH), 114.8 (CH), 69.8 (CH 2 ), 34.6 (C), 31.4 (CH 3 ). Anal. Calcd for C17H20: C, 84.96; H, 8.39; Found: C, 85.05; H, 8.55. 10

Supporting nline Material. 3,4-Dimethoxybenzyl 2-methoxyphenyl ether (a model of the α--4 lignin ether linkage) (S14) Me Me Prepared according to the general procedure using 3,4- dimethoxybenzyl bromide (6.49 g, 28.1 mmol) (15), 2- methoxyphenol (4.85 g, 39.1 mmol), potassium carbonate (4.82 g, 34.9 mmol), and acetone (60 ml). The crude product was recrystallized from hexanes (ca 300 ml) to give 3,4-dimethoxybenzyl 2-methoxyphenyl ether as white crystals (6.05 g, 22.1 mmol) in 78% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 6.81-7.03 (m, 7H), 5.08 (s, 2H), 3.88 (s, 6H), 3.87 (s, 3H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) δ 149.8 (C), 149.1 (C), 148.7 (C), 129.8 (C), 148.2 (C), 121.5 (CH), 120.7 (CH), 120.0 (CH), 111.9 (CH), 111.0 (CH), 110.8 (CH), 71.2 (CH 2 ), 55.9 (CH 3 ), 55.8 (CH 3 ). 1-Methoxy-1-phenylpropane (S16) A 100 ml two neck flask equipped with reflux condenser and argon inlet and magnetic stir bar was evacuated, filled with argon and charged with NaH (60% suspension in mineral oil, 1.40 g, 57.5 mmol) and THF (20 ml). 1-Phenyl-1- propanol (3.97 g, 29.2 mmol) was added by a syringe and the reaction mixture was stirred at room temperature for 5 min. Methyl iodide (8.17 g, 57.6 mmol) was added by a syringe over 2 min and the reaction mixture was refluxed for 2 h, then cooled to room temperature and carefully quenched with water (40 ml) to give a two-layer mixture. THF was evaporated, and the crude product was extracted from the resulting aqueous mixture with dichloromethane (3 25 ml). The combined organic layers were dried over anhydrous magnesium sulfate and evaporated. The oily residue was distilled in vacuum (bp. 75-77 C/18-20 mm) to give 1-methoxy-1-phenylpropane (3.04 g, 20.2 mmol) as a colorless oil in 69% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 7.30-7.37 (m, 2H), 7.27 (apparent d, J = 7.0 Hz, 3H), 4.01 (t, J = 6.5 Hz, 1H), 3.21 (s, 3H), 1.75-1.89 (m, 1H), 1.59-1.73 (m, 1H), 0.87 (t, J = 7.5 Hz, 3H). 13 C { 1 H} NMR (100 MHz, CDCl 3 ) δ 142.2 (C), 128.2 (CH), 127.4 (CH), 126.7 (CH), 85.5 (CH), 56.6 (CH 3 ), 30.9 (CH 2 ), 10.1 (CH 3 ). 11

Supporting nline Material. Methyl 4-tert-butylbenzyl ether (S17) t Bu Under argon, a 100 ml Schlenk flask was charged with sodium methoxide (0.680 g, 12.6 mmol), methanol (20 ml), magnetic stir bar and sealed with a septum. To the resulting solution 4-tert-butylbenzyl bromide (2.37 g, 10.4 mmol) was added by a syringe at room temperature for 2 min. The reaction mixture was stirred for 48 h, then solvent was evaporated and the residue was treated with water (100 ml). The crude product was extracted with ether (3 50 ml), the combined organic extracts were washed with brine (50 ml), and dried over anhydrous sodium sulfate. The product was purified by flash column chromatography (eluent: ethyl acetate-hexanes 1:40) to give methyl 4-tert-butylbenzyl ether as a colorless oil (1.21 g, 6.79 mmol) in 65% yield. 1 H NMR (500 MHz, CDCl 3 ) δ 7.43 (apparent d, J = 8.4 Hz, 2H), 7.33 (apparent d, J = 8.4 Hz, 2H), 4.48 (s, 2H), 3.43 (s, 3H), 1.38 (s, 9H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) δ 150.9 (C), 133.5 (C), 127.9 (CH), 125.5 (CH), 74.8 (CH 3 ), 58.3 (CH 2 ), 34.8 (C), 31.6 (CH 3 ). Preparation of 1-(3,4-Dimethoxyphenyl)-2-(2-methoxyphenoxy)-l,3-propanediol (S18- S20) (a model of the β--4 lignin ether linkage; modified literature procedure for an analogous compound) (S21-S23) H H A. Methyl 2-(2-methoxyphenoxy)acetate (S24) H Br K 2 C 3, acetone, reflux, 2.5 h A 250 ml two-neck flask equipped with a reflux condenser, argon inlet, and magnetic stir bar was charged with potassium carbonate (10.40 g, 75.24 mmol), evacuated, and filled with argon. Acetone (80 ml), methyl bromoacetate (11.59 g, 75.76 mmol), and guaiacol (6.20 g, 49.9 mmol) were added to the flask via syringe and the reaction mixture was 12

Supporting nline Material. refluxed for 2.5 h, then cooled to room temperature and filtered. The filtrate was evaporated, to give a pale yellow oil, which was dissolved in methanol and placed in a fridge (ca -5 C) overnight. The resulting colorless crystals were filtered, and washed with cold methanol to give methyl 2-(2-methoxyphenoxy)acetate (8.40 g, 42.8 mmol) in 85% yield. 1 H NMR (400 MHz, CDCl 3 ) δ 6.94-7.00 (m, 1H), 6.80-6.92 (m, 3H), 4.68 (s, 2H), 3.86 (s, 3H), 3.77 (s, 3H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) δ 169.4 (C), 150.0 (C), 147.2 (C), 122.6 (CH), 120.7 (CH), 114.6 (CH), 112.2 (CH), 66.5 (CH 2 ), 55.8 (CH 3 ), 55.0 (CH 3 ). B. Methyl 3-(3,4-dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propanoate LDA THF 0 o C, 30 min C 2 Me Li Me CH THF, -78 o C, 2 h H Me A 250 ml Schlenk flask equipped with a magnetic stir bar and septum cap, was evacuated and filled with argon. THF (30 ml) and diisopropylamine (3.1 ml, 22 mmol) were added by a syringe. The resulting solution was cooled to 0 C and a 1.6 M solution of n- butyllithium in hexanes (13.75 ml, 22.00 mmol) was added by a syringe for 3 min. The reaction mixture was stirred for 30 min, then cooled to -78 C and a solution of methyl 2- (2-methoxyphenoxy)acetate (3.92 g, 20.0 mmol) in THF (40 ml) was added dropwise for 15 min to give a pale yellow solution. The solution was stirred for 15 min and a solution of 3,4-dimethoxybenzaldehyde (3.32 g, 20.0 mmol) in THF (20 ml) was added dropwise for 5 min. The reaction mixture was stirred for 2 h, then quenched at -78 C with a saturated solution of ammonium chloride (75 ml), and warmed up to room temperature to give a two-layer mixture. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 50 ml). The combined organic layers were washed with brine (50 ml), and dried over anhydrous sodium sulfate. The crude product was purified by flash column chromatography (eluent: ethyl acetate-hexanes from 1:2 to 1:1) to give methyl 3-(3,4-dimethoxyphenyl)-3-hydroxy-2-(2-methoxyphenoxy)propanoate (3.59 g, 9.91 mmol) as a white solid in 49% yield. 1 H NMR (500 MHz, CDCl 3 ), major isomer δ 6.78-7.06 (m, 7H), 5.13 (t, J = 5.5 Hz, 1H), 4.73 (d, J = 5.0 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 13

Supporting nline Material. 3H), 3.84 (s, 3H), 3.71 (d, J = 6.0 Hz, 1H), 3.68 (s, 3H); minor isomer δ 6.78-7.06 (m, 7H), 5.07 (dd, J = 7.0, 3.5 Hz, 1H), 4.50 (d, J = 7.0 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 3.85 (s, 3H), 3.60 (s, 3H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) major minor δ 169.9, 169.8, 150.5, 150.3, 149.0, 148.9, 148.8, 148.7, 147.2, 147.1, 131.7, 130.6, 123.9, 121.1, 121.0, 119.4, 119.2, 118.8, 118.1, 112.3, 110.7, 110.0, 109.8, 85.3, 83.9, 74.7, 73.8, 55.8, 55.7, 52.1, 52.0. Ratio of diastereomers (major to minor): 4.5. Anal. Calcd for C19H227: C, 62.97; H, 6.12; Found: C, 62.68; H, 6.07. C. 1-(3,4-Dimethoxyphenyl)-2-(2-methoxyphenoxy)-l,3-propanediol (S18) H Me NaBH 4 THF/water (3:1), rt, 22 h A 250 ml Schlenk flask was charged with methyl 3-(3,4-dimethoxyphenyl)-3-hydroxy-2- (2-methoxyphenoxy)propanoate (3.15 g, 8.69 mmol), a magnetic stir bar and sealed with a septum. The flask was evacuated, filled with argon and a 3:1 mixture of THF/water (80 ml) was added. Sodium borohydride (43.6 mmol) was added to the solution in two portions (2 0.825 g) over about 1 h, and the stirring was continued for 22 h. The resulting mixture was evaporated to ca. 20 ml, diluted with 80 ml of water and the crude product was extracted with ethyl acetate (3 60 ml). The combined extracts were washed with brine (50 ml) and dried over anhydrous sodium sulfate. The product was purified by flash column chromatography (eluent: ethyl acetate-hexanes from 1:1 to 3:1) to give 1- (3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)-l,3-propanediol (2.32 g, 6.94 mmol) as a white solid in 80% yield. 1 H NMR (500 MHz, CDCl 3 ), major minor diastereoisomers δ 6.80-7.14 (m, 7H), 4.95-5.01 (m, 1H), 4.13-4.19 (m, 0.77 H, major diastereoisomer), 3.99 (m, 0.35 H, minor isomer), 3.82-3.95 (m, 10H), 3.44-3.74 (m, 2H), 2.69-2.82 (1H), 1.71-1.83 (m, 0.3H). 13 C { 1 H} NMR (125 MHz, CDCl 3 ) major minor diastereomers δ 151.6, 151.3, 149.1, 149.0, 148.9, 148.5, 147.6, 146.9, 132.5, 132.1, 124.2 (2C), 121.6 (2C), 121.0, 120.9, 119.6, 118.4, 112.2, 111.0, 109.9, 109.2, 89.4, 87.4, 73.9, 72.7, 61.0, 60.7, 55.9 (C). Ratio of diastereomers (major to minor): 2.2. MS (ESI) m/z: 357.3 [MNa]. H H 14

Supporting nline Material. 4. Stability of the Ni(CD) 2 /PCy 3 under the Conditions of Reductive Cleavage of Aromatic C- bonds Figure S1. Attempted hydrogenolysis of diphenyl ether catalyzed by Ni(CD) 2 /PCy 3. (1 equiv.) conversion: ca 1% Procedure: H 2 Ni(CD) 2 P 3 m-xylene, (1 bar) 120 o C, 16 h (0.2 equiv.) (0.4 equiv.) The yields were based on the amount of PCy 3, assuming that only one cyclohexyl group of the phosphine ligand is converted to the hydrocarbons. X H (traces, ~1%) 44% 7% products of the C-P bond cleavage in PCy 3 The reaction was conducted according to General Procedure A (p. 29) with Ni(CD) 2 (8.4 mg, 3.1 10-2 mmol), PCy 3 (16.7 mg, 5.95 10-2 mmol), diphenyl ether (25.4 mg, 0.155 mmol), dodecane (internal standard for GC, 25.8 mg) and m-xylene (0.8 ml) at 120 C for 16 h. After saturation of the reaction mixture with hydrogen at room temperature, the yellow color changed to dark red within 15 min; the final color of the reaction mixture after heating for 16 h was dark brown. GC and GC/MS analyses of the reaction mixture showed low conversion of diphenyl ether (~1%). Benzene was detected in only trace amounts (1%). Cyclohexane (m/z 84) and cyclohexene (m/z 82) from cleavage of the C-P bond in PCy 3 were observed in 44% and 7% yields, respectively. The yields were based on the amount of PCy 3, assuming that only one cyclohexyl group of the phosphine ligand is converted to the hydrocarbons. Cyclooctane (m/z 112) from hydrogenation of CD was also detected. Decomposition of PCy 3 under the Conditions of Hydrogenolysis Ni(CD) 2 (1 equiv.) P H 2 3 m-xylene, (1 bar) 120 o C, 16 h (2 equiv.) 55% 7% The reaction was conducted according to General Procedure A (p. 29) with Ni(CD) 2 (8.4 mg, 3.1 10-2 mmol), PCy 3 (18.0 mg, 6.42 10-2 mmol), dodecane (internal standard for GC, 24.4 mg) and m-xylene (0.8 ml) at 120 C for 16 h. The color changes were similar 15

Supporting nline Material. to those observed for the above procedure of the reaction with diphenyl ether. GC and GC/MS analyses of the reaction mixture showed the formation of cyclohexane (m/z 84) and cyclohexene (m/z 82) in 55% and 7% yields, respectively. The yields were based on the amount of PCy 3, assuming that only one cyclohexyl group of the phosphine ligand is converted to the hydrocarbons. Cyclooctane (m/z 112) from hydrogenation of CD was also detected. Figure S2. Attempted Reductive Cleavage of Anisole with Triethylsilane Catalyzed by the Combination of Ni(CD) 2 /PCy 3. X Et 3 SiH (1 equiv.) (25 equiv.) conversion ca 1% Ni(CD) 2 (0.2 equiv.) P 3 (0.4 equiv.) toluene, 140 o C, 16 h The yields were based on the amount of PCy 3, assuming that only one cyclohexyl group of the phosphine ligand is converted to the hydrocarbons. (traces, ~1%) 18% 41% products of the C-P bond cleavage in PCy 3 The reaction was conducted according to the General Procedure (p. 18) with Ni(CD) 2 (8.3 mg, 3.0 10-2 mmol), PCy 3 (16.7 mg, 5.95 10-2 mmol), anisole (16.0 mg, 0.148 mmol), triethylsilane (600 µl, 3.76 mmol), dodecane (internal standard for GC, 23.2 mg) and toluene (0.3 ml) at 140 C for 16 h. The starting reaction mixture was yellow; after heating at 140 C for 5 min, the color changed to dark red; the color after heating at 140 C for 16 h was dark brown, and nickel black was observed. GC and GC/MS analyses of the reaction mixture showed low conversion of anisole (ca 1%). Cyclohexane (m/z 84) and cyclohexene (m/z 82) from cleavage of the C-P bond in PCy 3 were observed in 18% and 41% yields, respectively. These yields were based on the amount of PCy 3, assuming that only one cyclohexyl group of the phosphine ligand is converted to the hydrocarbons. 16

Supporting nline Material. Decomposition of PCy 3 under the Conditions of Reductive Cleavage with Triethylsilane Ni(CD) 2 (1 equiv.) P 3 Et 3 SiH toluene, 140 o C, 16 h (2 equiv.) (125 equiv.) 8% 36% The reaction was conducted according to General Procedure (p. 18) with Ni(CD) 2 (8.5 mg, 3.1 10-2 mmol), PCy 3 (16.7 mg, 6.42 10-2 mmol), dodecane (internal standard for GC, 19.2 mg) and toluene (0.3 ml) at 140 C for 16 h. The color changes were similar to those for the above procedure containing anisole. GC and GC/MS analyses of the reaction mixture showed the formation of cyclohexane (m/z 84) and cyclohexene (m/z 82) in 8% and 36% yields, respectively. The yields were based on the amount of PCy 3, assuming that only one cyclohexyl group of the phosphine ligand is converted to the hydrocarbons. Cyclooctane (m/z 112) from hydrogenation of CD was also detected. 17

Supporting nline Material. 5. Nickel-NHC Catalyzed Reductive Cleavage of Aryl and Benzyl Ethers with Hydride Donors Reactions were conducted in 4 ml screw thread vials (15 mm 45 mm; supplied by Kimble Chase) equipped with Teflon-lined screw caps (13 mm diameter, 425 GPI thread; supplied by Qorpak) and Teflon-coated magnetic stir bars (3 mm 10 mm; supplied by Fisher Scientific). The vials were heated in an aluminum heating block; the reaction temperature was measured by a thermocouple immersed into a silicone oil in a separate 4 ml vial, placed in the same heating block. General procedure In a glovebox, a 4 ml vial was charged with Ni(CD) 2 (0.75 10-2 -3.0 10-2 mmol, 5-20 mol%), a carbene ligand salt (1.5 10-2 -6.0 10-2 mmol, 10-40 mol%), Na t Bu (0.375 mmol) and a magnetic stir bar. After 0.3 ml of 0.5 M solution of aryl or benzyl ether (0.15 mmol) in toluene and dodecane (internal standard for GC) were added, the mixture was stirred for 3 min and DIBAL (0.375 mmol, 1M solution in hexanes) or triethylsilane (0.375-1.50 mmol) was added by a syringe. Note, for reductions with Li(Al( t Bu) 3 H, the reductant was added in the beginning together with other solid reagents and the reaction mixture was diluted with additional 0.5 ml of toluene. The resulting dark brown mixture was stirred for 1 min. The reaction vial was sealed with a screw cap, removed from the glovebox and heated at 60-140 C for 16-96 h (see Table S2). After cooling to room temperature, dark brown to black reaction mixture was diluted with ether (1 ml) and carefully quenched at 0 C with 1 ml of 1.5 M aqueous HCl. The resulting mixture was stirred for 10 min for reactions with triethylsilane or 40 min when DIBAL or Li(Al( t Bu) 3 H were used. The organic layer was separated, the aqueous layer was extracted with ether (1 ml), and the combined organic layers were passed through a short pad of Celite and subjected to GC and GC/MS analyses. The products were all known compounds and were identified using GC/MS and GC by comparison of the mass spectra and retention times of the products with those of authentic compounds. 18

Supporting nline Material. Discussion We initially tested nickel-nhc catalysts for the reduction of the C- bond of diphenyl ether in the presence of the hydride donors, DIBALH (diisobutylaluminum hydride), LiAl( t Bu) 3 H, and Et 3 SiH in place of H 2, because of the convenience of evaluating catalysts for reactions with liquid and solid reagents. These reactions were conducted with the combination of a nickel(0) precursor, Ni(CD) 2 or Ni(acac) 2 (acac, acetylacetonate), and an NHC ligand formed in situ by deprotonation of the corresponding salt NHC HX with a base (Na t Bu) (Table S1). We found that the highest yields of the products from aromatic C- bond cleavage were obtained with Ni(CD) 2 as the source of nickel, with SIPr HCl (shown in Fig. S3) as ligand precursor, and the aluminium hydride donors DIBALH and LiAl( t Bu) 3 H (2.5 equiv.) in the presence of Na t Bu (2.5 equiv.) as a base in toluene (Table S1 and S2). Although the base was added initially to generate the free carbene from the salt form, the highest yields of the products were obtained with an excess of base (Table S1). Under these conditions, cleavage of diphenyl ether with DIBALH proceeded, even at 60 C, to give benzene and phenol in nearly quantitative yields in the presence of 20 mol% Ni(CD) 2 and 40 mol% of SIPr HCl (Table S2, Entry 1). Reaction with LiAl( t Bu) 3 H occurred with 10 mol% of the catalyst at 100 C to give the arene and phenol in 82% and 86% yields (Table S2, Entry 2). Cleavage with the milder reagent Et 3 SiH (10 equiv.) occurred with less catalyst (5%) but gave moderate yields of the products (Table S2, Entry 3). This class of catalyst, in tandem with either aluminum hydrides or silane reducing agents, was then tested for the reductive cleavage of a series of unactivated aryl and benzyl ethers. In addition to the cleavage of diphenyl ether, reduction of a cyclic diaryl ether, dibenzofuran, gave 2-hydroxybiphenyl in nearly quantitative yield (99%) with triethylsilane as hydride source at 120 C for 48 h (Table S2, Entry 4). 4- Methoxybiphenyl was cleaved with triethylsilane, DIBALH and LiAl( t Bu) 3 H to form excellent yields of biphenyl (89%-99%) in the presence of the Ni-SIPr catalyst (Table S2, Entries 5-7). The same system catalyzed reduction of the fully unactivated alkyl ether anisole with DIBALH and LiAl( t Bu) 3 H to give benzene in 87% and 62% yields, 19

Supporting nline Material. respectively, at 120 C (Table S2, Entries 8-9). Cleavage of the aromatic C- bond in anisole with the milder reductant triethylsilane was induced by Ni(CD) 2 in combination with the bulkier carbene ligand IPr Me (shown in Fig. S3) to give benzene in 77% yield at 140 C for 96 h (Table S2, Entry 10). Under the same conditions the reaction catalyzed by Ni(CD) 2 and PCy 3 failed to form products from cleavage of anisole, instead forming cyclohexane and cyclohexene from the phosphine ligand (Fig. S2). The Ni-SIPr system also catalyzed the reduction of unactivated benzyl ethers (Table S2, Entries 11-14). In this case, cleavage occurred at the benzylic C- bond. Reduction of this C- bond in an alkyl benzyl ether proceeded much more slowly than reduction of aryl benzyl ethers and required similar conditions to those for the cleavage of alkyl aryl ethers. Thus, reduction of α-ethylbenzyl methyl ether with aluminum hydrides occurred at 120 C for 16 h (Table S2, Entries 11, 12), whereas reduction of phenyl tertbutylbenzyl ether was complete at 80 C in 16 h (Table S2, Entries 13, 14). 20

Supporting nline Material. Table S1. Selected Results on the Effect of Ligand, Nickel and Hydride Source and Base Amount on the Reductive Cleavage of Diphenyl Ether. See General Procedure (p. 18). "H - " 5-10% Ni(CD) 2, 10-40% SIPr HCl Na t Bu, toluene, temp, 16 h H Entry Ligand Ni Ni, mol% H - H -, equiv. Base, equiv. T, C Conversion, % Yield of benzene, % Yield of phenol, % 1 SImBu HBF 4 Ni(CD) 2 10 Et 3 SiH 2.5 2.5 100 20 20 16 2 SIMes HBF 4 Ni(CD) 2 10 Et 3 SiH 2.5 2.5 100 46 44 44 3 IMes HCl Ni(CD) 2 10 Et 3 SiH 2.5 2.5 100 52 48 52 4 IPr HCl Ni(CD) 2 10 Et 3 SiH 2.5 2.5 100 58 38 54 5 SIPr HCl Ni(CD) 2 10 Et 3 SiH 2.5 2.5 100 65 42 65 6 SIPr HCl Ni(CD) 2 10 Et 3 SiH 2.5 0.5 100 29 9 21 7 SIPr HCl Ni(CD) 2 5 Et 3 SiH 10 2.5 100 70 56 70 8 IPr HCl Ni(CD) 2 5 Et 3 SiH 10 2.5 100 50 47 50 9 IPr HCl Ni(CD) 2 10 DIBALH 2.5 2.5 100 2 0 0 10 SIPr HCl Ni(CD) 2 10 DIBALH 2.5 2.5 100 41 41 37 11 IPr HCl Ni(CD) 2 10 LiAl( t Bu) 3 H 2.5 2.5 100 83 75 75 12 SIPr HCl Ni(CD) 2 10 LiAl( t Bu) 3 H 2.5 2.5 100 90 82 86 13 SIPr HCl Ni(CD) 2 20 DIBALH 2.5 2.5 60 100 99 99 14 SIPr HCl Ni(CD) 2 20 DIBALH 2.5 0.44 60 0 0 0 15 SIPr HCl Ni(acac) 2 20 DIBALH 2.5 2.5 60 35 37 10 16 IPr HCl Ni(CD) 2 20 DIBALH 2.5 2.5 60 87 87 60 17 - Ni(CD) 2 20 DIBALH 2.5 2.5 60 11 11 7 18 IPr HCl Ni(CD) 2 20 LiAl( t Bu) 3 H 2.5 2.5 60 1 0 0 19 SIPr HCl Ni(CD) 2 20 LiAl( t Bu) 3 H 2.5 2.5 60 0 0 0 Figure S3. Carbene Ligands Used in the Study N BF 4 N N BF 4 N N Cl N SImBu HBF 4 SIMes HBF 4 IMes HCl N Cl N N Cl N IPr HCl SIPr HCl 21

Supporting nline Material. Table S2. Reductive Cleavage of Aryl and Benzyl Ethers with Hydride Donors. See General Procedure (p. 18). 5-20% Ni(CD) 2, R 1 R 2 "H - 10-40% SIPr HCl " Na t Bu (2.5 equiv), (2.5 equiv) toluene R 1 H R 2 H R 1 = Aryl, Benzyl; R 2 = Aryl, Methyl "H - " = DIBALH, LiAl( t Bu) 3 H, Et 3 SiH Entry Aryl/Benzyl ether Hydride donor Ni, mol% T, C Time, h Conv, % R 1 H, % R 2 H, % 1 DIBAL 20 100 16 100 99 99 2 LiAl( t Bu) 3 H 10 100 16 90 82 86 3 Et 3 SiH* 5 100 16 70 56 70 4 Et 3 SiH 20 120 48 100 99 5 DIBALH 20 120 16 100 99 nd 6 LiAl( t Bu) 3 H 20 120 32 91 90 nd 7 Ph Et 3 SiH 20 120 56 91 89 nd 8 DIBALH 20 120 40 94 87 nd 9 LiAl( t Bu) 3 H 20 120 36 85 62 nd 10 Et Et 3 SiH,II 20 140 96 84 77 nd 11 DIBALH 20 120 16 100 94 nd 12 LiAl( t Bu) 3 H 20 120 56 92 91 nd 13 Ph DIBALH 20 80 16 100 79 55 # 14 LiAl( t t Bu) 3 H 20 80 16 100 82 99 Bu *10 equiv. of Et 3 SiH. Phenyltriethylsilane as a side product. Not determined. 25 equiv. of Et 3 SiH. II IPr Me HCl as a ligand. Benzene (15%) as a side product. # 4-tert-butylbenzyl alcohol (16%) as a side product. 22

Supporting nline Material. Reductive cleavage of diphenyl ether with DIBALH (Table S2, Entry 1) DIBALH 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 60 C, 16 h H 99% 99% The reaction was conducted according to the general procedure with Ni(CD) 2 (8.2 mg, 3.0 10-2 mmol), SIPr HCl (25.4 mg, 5.95 10-2 mmol), t BuNa (40.2 mg, 0.418 mmol), diphenyl ether (25.8 mg, 0.152 mmol), DIBALH (0.375 ml of 1M solution in hexanes, 0.375 mmol), dodecane (internal standard for GC, 6.3 mg) and toluene (0.3 ml) at 60 C for 16 h. GC and GC/MS analyses of the reaction mixture showed complete conversion of diphenyl ether and formation of benzene (78 m/z) and phenol (94 m/z) in 99% yields. Reductive cleavage of diphenyl ether with LiAl( t Bu) 3 H (Table S2, Entry 2) LiAl( t Bu) 3 H 10% Ni(CD) 2, 20% SIPr HCl Na t Bu, toluene, 100 C, 16 h H 82% 86% The reaction was conducted according to the general procedure with Ni(CD) 2 (4.1 mg, 1.5 10-2 mmol), SIPr HCl (14.0 mg, 3.28 10-2 mmol), Na t Bu (38.4 mg, 0.400 mmol), diphenyl ether (26.4 mg, 0.155 mmol), LiAl( t Bu) 3 H (96.4 mg, 0.379 mmol), dodecane (internal standard for GC, 6.4 mg) and toluene (0.8 ml) at 100 C for 16 h. GC and GC/MS analyses of the reaction mixture showed formation of benzene (78 m/z) and phenol (94 m/z) in 82% and 86% yields respectively at 90% conversion of diphenyl ether. Reductive cleavage of diphenyl ether with Et 3 SiH (Table S2, Entry 3) Et 3 SiH 5% Ni(CD) 2, 10% SIPr HCl Na t Bu, toluene, 100 C, 16 h H 56% 70% The reaction was conducted according to the general procedure with Ni(CD) 2 (2.3 mg, 8.0 10-3 mmol), SIPr HCl (7.0 mg, 1.6 10-2 mmol), Na t Bu (37.3 mg, 0.388 mmol), diphenyl ether (25.8 mg, 0.152 mmol), Et 3 SiH (240 µl, 174 mg, 1.50 mmol), dodecane (internal standard for GC, 6.3 mg) and toluene (0.3 ml) at 100 C for 16 h. GC and GC/MS analyses of the reaction mixture showed formation of benzene (m/z 78) and SiEt 3 23

Supporting nline Material. phenol (m/z 94) in 56% and 70% yields respectively at 70% conversion of diphenyl ether. Triethylphenylsilane (m/z 163, [M-Et] ) was detected as a main side product. Et 3 Si t Bu (m/z 173 [M-Et] ) was the major silicon product. Reductive cleavage of dibenzofuran with Et 3 SiH (Table S2, Entry 4) Et 3 SiH 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 120 C, 48 h H 99% The reaction was conducted according to the general procedure with Ni(CD) 2 (8.3 mg, 3.0 10-2 mmol), SIPr HCl (28.6 mg, 6.69 10-2 mmol), Na t Bu (41.8 mg, 0.435 mmol), dibenzofuran (25.2 mg, 0.150 mmol), Et 3 SiH (60 µl, 43.7 mg, 0.376 mmol), dodecane (internal standard for GC, 9.4 mg) and toluene (0.3 ml) at 120 C for 48 h. GC and GC/MS analyses of the reaction mixture showed formation of 2-hydroxybiphenyl (m/z 170) in 99% yield. Et 3 Si t Bu (m/z 173 [M-Et] ) was the major silicon product. Reductive cleavage of 4-methoxybiphenyl with DIBALH (Table S2, Entry 5) Ph DIBALH 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 120 C, 16 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.7 mg, 3.2 10-2 mmol), SIPr HCl (29.9 mg, 7.00 10-2 mmol), t BuNa (43.4 mg, 0.452 mmol), 4- methoxybiphenyl (28.1 mg, 0.151 mmol), DIBALH Ph 99% (0.375 ml of 1M solution in hexanes, 0.375 mmol), dodecane (internal standard for GC, 14 mg) and toluene (0.3 ml) at 120 C for 16 h. GC and GC/MS analyses of the reaction mixture showed complete consumption of 4-methoxybiphenyl and formation of biphenyl (m/z 154) in 99% yield. Reductive cleavage of 4-methoxybiphenyl with LiAl( t Bu) 3 H (Table S2, Entry 6) Ph LiAl( t Bu) 3 H 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 120 C, 32 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.5 mg, 3.1 10-2 mmol), SIPr HCl (25.8 mg, 6.04 10-2 mmol), Na t Bu (36.6 mg, 0.381 mmol), 4- methoxybiphenyl (25.5 mg, 0.149 mmol), LiAl( t Bu) 3 H (95.3 mg, 0.371 mmol), Ph 90% 24

Supporting nline Material. dodecane (internal standard for GC, 20 mg) and toluene (0.8 ml) at 120 C for 32 h. GC and GC/MS analyses of the reaction mixture showed formation of biphenyl (m/z 154) in 90% yield at 91% conversion of 4-methoxybiphenyl. Reductive cleavage of 4-methoxybiphenyl with Et 3 SiH (Table S2, Entry 7) Ph Et 3 SiH 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 140 C, 56 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.1 mg, 2.9 10-2 mmol), SIPr HCl (27.2 mg, 6.36 10-2 mmol), Na t Bu (36.9 mg, 0.384 mmol), 4- methoxybiphenyl (27.6 mg, 0.150 mmol), Et 3 SiH (600 µl, 437 mg, 3.76 mmol), dodecane (internal standard for GC, 12.8 mg) and toluene (0.3 ml) at 140 C for 56 h. GC and GC/MS analyses of the reaction mixture showed the formation of benzene (m/z 78) in 89% yield at 91% conversion of 4-methoxybiphenyl. Et 3 Si t Bu (m/z 173 [M-Et] ) was the major silicon product. Reductive cleavage of anisole with DIBALH (Table S2, Entry 8) DIBALH 20% Ni(CD) 2, 40% SIPr HBF 4 Na t Bu, toluene, 120 C, 40 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.4 mg, 3.1 10-2 mmol), SIPr HBF 4 (30.1 mg, 6.29 10-2 mmol), t BuNa (43.4 mg, 0.452 mmol), anisole (16.4 mg, 0.15 mmol), DIBALH (0.375 ml of 1M solution in hexanes, 0.375 mmol), dodecane (internal standard for GC, 10.9 mg) and toluene (0.3 ml) at 120 C for 40 h. GC and GC/MS analyses of the reaction mixture showed the formation of benzene (m/z 78) in 87% yield at 94% conversion of anisole. Ph 87% 89% 25

Supporting nline Material. Reductive cleavage of anisole with LiAl( t Bu) 3 H (Table S2, Entry 9) LiAl( t Bu) 3 H 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 120 C, 32 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.4 mg, 3.1 10-2 mmol), SIPr HCl (26.8 mg, 5.60 10-2 mmol), Na t Bu (39.0 mg, 0.406 mmol), anisole (16.4 mg, 0.151 mmol), LiAl( t Bu) 3 H (91.8 mg, 0.375 mmol), dodecane (internal standard for GC, 11.9 mg) and toluene (0.8 ml) at 120 C for 40 h. GC and GC/MS analyses of the reaction mixture showed the formation of benzene (m/z 78) in 62% yield at 85% conversion of anisole. Reductive cleavage of anisole with Et 3 SiH (Table S2, Entry 10) Et 3 SiH 20% Ni(CD) 2, 40% IPr Me HCl Na t Bu, toluene, 140 C, 96 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.0 mg, 3.0 10-2 mmol), SIPr HCl (27.2 mg, 6.36 10-2 mmol), Na t Bu (46.0 mg, 0.479 mmol), anisole (17.8 mg, 0.165 mmol), Et 3 SiH (600 µl, 437 mg, 3.76 mmol), dodecane (internal standard for GC, 12.8 mg) and toluene (0.3 ml) at 140 C for 96 h. GC and GC/MS analyses of the reaction mixture showed the formation of benzene (m/z 78) in 77% yield at 84% conversion of anisole. Et 3 Si t Bu (m/z 173 [M-Et] ) was the major silicon product. Reductive cleavage of 1-methoxy-1-phenylpropane with DIBALH (Table S2, Entry 11) DIBALH 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 120 C, 16 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.4 mg, 3.1 10-2 mmol), SIPr HCl (27.8 mg, 6.51 10-2 mmol), Na t Bu (38.3 mg, 0.499 mmol), 1- methoxy-1-phenylpropane (23.3 mg, 0.155 mmol), DIBALH (0.240 ml of 1M solution 77% 62% 94% 26

Supporting nline Material. in hexanes, 0.240 mmol), dodecane (internal standard for GC, 11.5 mg) and toluene (0.3 ml) at 120 C for 16 h. GC and GC/MS analyses of the reaction mixture showed complete consumption of 1-methoxy-1-phenylpropane and formation of 1-phenylpropane (m/z 120) in 94% yield. Reductive cleavage of 1-methoxy-1-phenylpropane with LiAl( t Bu) 3 H (Table S2, Entry 12) LiAl( t Bu) 3 H 20% Ni(CD) 2, 40% SIPr HCl Na t Bu, toluene, 120 C, 56 h The reaction was conducted according to the general procedure with Ni(CD) 2 (8.1 mg, 2.9 10-2 mmol), SIPr HCl (26.0 mg, 6.09 10-2 mmol), Na t Bu (36.3 mg, 0.378 mmol), 1- methoxy-1-phenylpropane (22.0 mg, 0.146 mmol), LiAl( t Bu) 3 H (95.7 mg, 0.376 mmol), dodecane (internal standard for GC, 8.8 mg) and toluene (0.8 ml) at 120 C for 56 h. GC and GC/MS analyses of the reaction mixture showed the formation of 1- phenylpropane (m/z 120) in 91% yield at 92% conversion of 1-methoxy-1- phenylpropane. Reductive cleavage of 4-tert-butylbenzyl phenyl ether with DIBALH (Table S2, Entry 13) 91% t Bu DIBALH 10% Ni(CD) 2, 20% SIPr HCl Na t Bu, toluene, 80 C, 16 h t Bu Me H 79% 15% H The reaction was conducted according to the general procedure with Ni(CD) 2 (8.3 mg, 3.0 10-2 mmol), SIPr HCl (27.2 mg, 6.37 10-2 mmol), Na t Bu (39.0 mg, 0.406 mmol), 4- tert-butylbenzyl phenyl ether (36.1 mg, 0.150 mmol), DIBALH t Bu 16% 55% (0.210 ml of 1M solution in hexanes, 0.210 mmol), dodecane (internal standard for GC, 12.6 mg) and toluene (0.3 ml) at 80 C for 16 h. GC and GC/MS analyses of the reaction mixture showed complete consumption of 4-tert-butylbenzyl phenyl ether and formation of 4- tert-butyltoluene (m/z 148), benzene (m/z 78), phenol (m/z 94), and 4-tert-butylbenzyl alcohol (m/z 164) in 79%, 15%, 16% and 55% yields respectively. 27

Supporting nline Material. Reductive cleavage of 4-tert-butylbenzyl phenyl ether with LiAl( t Bu) 3 H (Table S2, Entry 14) t Bu LiAl( t Bu) 3 H 10% Ni(CD) 2, 20% SIPr HCl Na t Bu, toluene, 80 C, 32 h t Bu Me H 82% 99% The reaction was conducted according to the general procedure with Ni(CD) 2 (8.4 mg, 3.1 10-2 mmol), SIPr HCl (26.9 mg, 6.29 10-2 mmol), Na t Bu (36.5 mg, 0.380 mmol), 4- tert-butylbenzyl phenyl ether (36.1 mg, 0.150 mmol), LiAl( t Bu) 3 H (92.2 mg, 0.363 mmol), dodecane (internal standard for GC, 36.9 mg) and toluene (0.3 ml) at 80 C for 32 h. GC and GC/MS analyses of the reaction mixture showed complete consumption of 4- tert-butylbenzyl phenyl ether and formation of 4-tert-butyltoluene (m/z 148), and phenol (m/z 94) in 82% and 99% yields respectively. 28

Supporting nline Material. 6. Nickel-NHC Catalyzed Selective Hydrogenolysis of Aryl and Benzyl Ethers Reactions were conducted in 15 ml Schlenk tubes (exact volume 14.8 ml, outer diameter of the tube 16 mm) equipped with Teflon-stopcocks and Teflon-coated magnetic stir bars (3 mm 10 mm; supplied by Fisher Scientific). The reported pressure of hydrogen refers to the readings from the gauge of the gas cylinder at room temperature. The reaction tubes were heated in an oil bath; the reaction temperature refers to the temperature of the oil bath. General Procedure A In a glovebox, a 15 ml Schlenk tube equipped with a Teflon-stopcock was charged with Ni(CD) 2 (0.75 10-2 -3.0 10-2 mmol, 5-20 mol%), SIPr HCl (1.5 10-2 - 6.0 10-2 mmol, 10-40 mol%), Na t Bu (0.375 mmol) and a magnetic stir bar. Then a solution of aryl or benzyl ether (0.15 mmol) and dodecane internal standard for GC) in m-xylene (0.8 ml) were added, and the mixture was stirred for 3 min. The Schlenk tube was sealed with the Teflon stopcock and removed form the glovebox. The reaction mixture was degassed via two cycles of freeze-pump-thaw and the tube was pressurized with 1 bar (15 psi) of hydrogen at room temperature; saturation with hydrogen leads to slightly noticeable change in color from dark brown to dark red brown. The tube was sealed with the Teflon stopcock and heated in an oil bath at 80, 100 or 120 C for 16-48 h. The resulting dark brown to black mixture was cooled to room temperature, diluted with ether (1 ml) and quenched with 1.5 M aqueous HCl (1 ml) followed by stirring for 15 min. The organic layer was separated and the aqueous layer was extracted with 1 ml of ether. The combined organic layers were passed through a short pad of Celite and subjected to GC and GC/MS analyses. The products were all known compounds and were identified using GC/MS and GC by comparison of the mass spectra and retention times of the products with those of commercially available authentic compounds. General Procedure B (Hydrogenolysis in the Presence of 1 equiv. of AlMe 3 ) The procedure is similar to General Procedure A, but includes addition of AlMe 3 (2 M in toluene, 75 µl, 0.15 mmol) after mixing of all reagents and stirring for 3 min. 29