Smiles Rearrangement as a Tool for the Preparation of Dihydrodipyridopyrazines

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1 Supporting Information for Smiles Rearrangement as a Tool for the Preparation of Dihydrodipyridopyrazines Oana-Irina Patriciu,, Adriana-LuminiŃa Fînaru, Stéphane Massip, Jean-Michel Leger, Christian Jarry, and Gérald Guillaumet * Institut de Chimie Organique et Analytique (ICOA), Université d Orléans, UMR CRS 65, BP 6759, rue de Chartres, 4567 Orléans Cedex 2, France Laboratorul de Sinteză Organică şi Analiză Structurală, Universitatea din Bacău, 157, Calea Mărăşeşti, 6115 Bacău, România EA 4138, Pharmacochimie, Université Victor Segalen Bordeaux 2, 146, rue Leo Saignat, 3376 Bordeaux Cedex, France gerald.guillaumet@univ-orleans.fr Table of Contents General Information S2 Experimental Details and Spectroscopic Data S2 1 and 13 C MR Spectra of ew Compounds S9 X-ray data S2 S1

2 Experimental Section General Information All air-sensitive experiments were performed under argon. Dioxane was distilled from sodium benzophenone ketyl prior to use. DMF was purified by distillation over Ca 2 and stored under an inert atmosphere over 4 Å molecular sieves. Dichloromethane was distilled from calcium hydride under argon prior to use. Petroleum ether, where used, had a boiling range of 4 6 C. All commercially available reagents were used without further purification unless otherwise noted. Thin-layer chromatography (TLC) was carried out on aluminium sheets precoated with silica gel (Merck 6 F254). Flash column chromatography was carried out with Merck 4 7 nm (23 4 mesh) silica gel under nitrogen pressure. Melting points were determined on a Büchi 51 melting point apparatus in open capillaries and are uncorrected. 1 and 13 C MR spectra were recorded on a Bruker Avance DPX 25 spectrometer (at 25 Mz and 62.9 Mz, respectively) or on a Bruker Avance II 4 spectrometer (at 4 Mz and 1.6 Mz, respectively), with TMS as an internal standard. Chemical shifts (δ) are reported in parts per million (ppm) and the coupling constants (J) are reported in ertz (z). IR spectra were recorded on a Thermo-icolet AVATAR 32 AEK2713 spectrometer by the ATR technique (germanium crystal) and are reported in cm 1. Low-resolution mass spectra (MS) were recorded on a Perkin Elmer SCIEX AOI 3 spectrometer. igh-resolution mass spectra (ESI-TOF) were recorded on a Q-Tof micro waters spectrometer. X-ray analyses were carried out on a Bruker Enraf onius CAD4 instrument with a Cu sealed tube for compounds 5, 7 and 13. The Shelxs 1 and Shelx 2 programs were used for structures determination and refinement. X-ray Crystallography: CCDC (for 5), (for 7) and (for 13) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via Starting Materials Preparation of the Starting Materials: The halopyridines and aminopyridines were either commercially available (1, 4) or were easily prepared from commercially available materials by literature procedures (2, ). General Procedure for the Palladium-Catalyzed -Arylations: A round-bottomed flask flushed with nitrogen was charged with Xantphos (2 mol-%) and anhydrous 1,4-dioxane (.2 mmol ml 1 ). After degassing, Pd(OAc) 2 (1 mol-%) was introduced and the mixture was stirred under nitrogen for 1 minutes. In a second round-bottomed flask, the heteroaryl halide (1 equiv.), the amine (1.2 equiv.) and K 2 CO 3 (1.5 equiv.) were poured into anhydrous 1,4-dioxane (.5 mmol halide per ml). The Pd(OAc) 2 /Xantphos solution was transferred by cannula and the resulted mixture was subsequently heated at reflux under argon with vigorous stirring. The progress of the reaction was monitored by TLC. After cooling, the residue was filtered off through a Celite pad and washed with C 2 Cl 2 and MeO. The solvent was evaporated and the residue was purified by flash chromatography on silica gel to afford the desired,-dipyridinylamines. Method A: Pd(OAc) 2 (1 mol-%), Xantphos (2 mol-%), K 2 CO 3 (1.5 equiv.), 1,4-dioxane, halogenopyridine (1 equiv.), aminopyridine (1.2 equiv.). Method B: Pd(OAc) 2 (15 mol-%), Xantphos (3 mol-%), K 2 CO 3 (1.5 equiv.), 1,4-dioxane, halogenopyridine (1 equiv.), aminopyridine (1.2 equiv.). S2

3 Br O 2 -(3-Bromopyridin-2-yl)--(3-nitropyridin-2-yl)-amine (5): This compound was obtained by the General Procedure for the palladium-catalyzed -arylations Method A, with 2-chloro-3-nitropyridine (1, 1 g, 6.31 mmol) and 2-amino-3-bromopyridine (3, 1.39 g, 7.57 mmol). Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 8:2 6:4 5:5) afforded product 5 (1.55 g, 83% yield) as a green-yellow solid. Mp C; 1 MR (4 Mz, CDCl 3 ) δ 1.24 (br s, 1, ), 8.58 (dd, J = 4.5, 1.7 z, 1), 8.53 (dd, J = 8.3, 1.7 z, 1), 8.44 (dd, J = 4.7, 1.5 z, 1), 7.95 (dd, J = 7.9, 1.6 z, 1), (m, 2); 13 C MR (62.9 Mz, CDCl 3 ) δ 154.9, 149.5, 148.8, 147.3, 141.1, 135.2, 131., 121.1, 116.2, 113.3; IR (ATR) 3344, 1578, 1478, 1255, 748 cm -1 ; MS (m/z) 297. ([M+] +, 81 Br), 295. ([M+] +, 79 Br); RMS calculated for C O 2 79 Br [M+] , found Cl O 2 -(3-Chloropyridin-2-yl)--(3-nitropyridin-2-yl)-amine (6): This compound was obtained by the General Procedure for the palladium-catalyzed -arylations Method B, with 3-chloro-2-iodopyridine (2, 23 mg,.96 mmol) and 2-amino-3-nitropyridine (4, 16.4 mg, 1.15 mmol). Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 8:2 7:3 6:4) afforded product 6 (22 mg, 91% yield) as a yellow-brown solid. Mp 9-91 C; 1 MR (25 Mz, CDCl 3 ) δ 1.26 (br s, 1, ), 8.56 (dd, J = 4.4, 1.9 z, 1), 8.5 (dd, J = 8.2, 1.9 z, 1, ), 8.38 (dd, J = 4.7, 1.6 z, 1), 7.75 (dd, J = 7.5, 1.6 z, 1), 7.8 (dd, J = 7.8, 4.7 z, 1), 7. (dd, J = 8.2, 4.4 z, 1); 13 C MR (62.9 Mz, CDCl 3 ) δ 154.9, 148.7, 148.5, 146.7, 138.2, 135.2, 131., 123.3, 12.8, 116.2; IR (ATR): 3373, 164, 157, 1488, 1256, 755 cm -1 ; MS (m/z) ([M+] +, 37 Cl), ([M+] +, 35 Cl); RMS calculated for C O 2 35 Cl [M+] , found General Procedure for Reduction Method 1: A mixture of,-dipyridinylamines and SnCl O (5 equiv.) in absolute ethanol (.7 g ml 1 ) was stirred at room temperature or at reflux. After reduction, the starting material had disappeared and the solution was cooled down and then poured into ice. The p was made basic by addition of a potassium carbonate solution before extraction with ethyl acetate and washing with brine. The organic layer was dried with magnesium sulphate, concentrated under reduced pressure and purified by flash chromatography on silica gel. Method 2: Concentrated Cl (w = 37%, 35 equiv.) was added to a hot mixture of,-dipyridinylamines and Fe powder (8 equiv.) in absolute ethanol (.5 mmol ml 1 ). The reaction mixture was heated under reflux for 7 minutes and quenched with solid a 2 CO 3 and crushed ice. The reaction mixture was filtered through a Büchner funnel and the filtrate was poured into water (2 ml). After extractive workup with Et 2 O (3 x 2 ml), the combined organic phases were dried over MgSO 4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel. S3

4 Br 2 2 -(3-Bromopyridin-2-yl)pyridine-2,3-diamine (7): This compound was obtained by the General Procedure for reduction Method 2, with compound 5 (25 mg,.85 mmol), Fe powder (394 mg, 6.69 mmol, 8 equiv.) and concentrated Cl (99 µl, mmol, 35 equiv.) and in absolute ethanol (2 ml). Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 7:3 5:5) afforded product 7 (27 mg, 92% yield) as a brown powder. Mp C; 1 MR (25 Mz, CDCl 3 + few drops of TFA) δ 8.31 (dd, J = 5.3, 1.3 z, 1), 8.19 (dd, J = 8., 1.3 z, 1), 7.9 (d, J = 6. z, 1), 7.8 (d, J = 8. z, 1), 7.34 (dd, J = 8., 6. z, 1), 7.2 (dd, J = 8., 5.3 z, 1); 13 C MR (1.6 Mz, CDCl 3 + few drops of TFA) δ 148.6, 146.6, 145.5, 141.5, 14.5, 139.8, 121.1, 12.5, 119.9, 19.6; IR (ATR): 3178, 2926, 1431 cm -1 ; MS (m/z) 267. ([M+] +, 81 Br), 265. ([M+] +, 79 Br); RMS calculated for C Br [M+] , found Cl 2 2 -(3-Chloropyridin-2-yl)pyridine-2,3-diamine (8): This compound was obtained by the General Procedure for reduction Method 1, with compound 6 (5 mg,.2 mmol) and stannous chloride dihydrate (225 mg, 1. mmol, 5 equiv.) at reflux in absolute ethanol (5 ml) for 5 hours. Purification by flash chromatography on silica gel (C 2 Cl 2 /ethyl acetate 8:2 5:5) afforded product 8 (3 mg, 68% yield) as a brown solid. Mp C; 1 MR (25 Mz,CDCl 3 + few drops of TFA) δ 8.3 (dd, J = 5.2, 1.5 z, 1), 7.98 (dd, J = 8., 1.5 z, 1), 7.82 (dd, J = 6., 1.2 z, 1), 7.72 (dd, J = 8., 1.2 z, 1), (m, 2); 13 C MR (1.6 Mz, CDCl 3 + few drops of TFA) δ 148.6, 146.3, 143.5, 14.2, 133.4, 131.2, 127.4, 121.4, 12.7, 119.3; IR (ATR): 3188, 2917, 1453, 78 cm -1 ; MS (m/z) 223. ([M+] +, 37 Cl), 221. ([M+] +, 35 Cl); RMS calculated for C Cl [M+] , found General Procedure for Alkylations: The appropriate,-dipyridinylamine (1 equiv.) in DMF was added under argon at C to a suspension of sodium hydride (6%, 1.1 equiv.) in DMF. The mixture was stirred at room temperature for 2 minutes and cooled to 78 C, and the halo derivative (1.2 equiv.) was added dropwise. The reaction mixture was allowed to warm slowly to room temperature and stirred until the end of the reaction. The reaction was monitored by TLC for the disappearance of starting materials. The mixture was hydrolyzed, extracted with ethyl acetate and dried with MgSO 4, and the solvent was removed under reduced pressure to give the crude product, which was purified by flash chromatography on silica gel to afford the desired product. Br O 2 -(3-Bromopyridin-2-yl)--methyl--(3-nitropyridin-2-yl)-amine (9a): This compound was obtained by the General Procedure for alkylations, with compound 5 (6 mg, 2.3 mmol) and methyl iodide (152 µl, 2.44 mmol). Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 8:2) S4

5 afforded product 9a (477 mg, 76% yield) as yellow-green crystals. Mp C; 1 MR (25 Mz, CDCl 3,) δ 8.52 (dd, J = 4.6, 1.7 z, 1), 8.18 (dd, J = 4.7, 1.6 z, 1), 8.11 (dd, J = 8., 1.7 z, 1), 7.98 (dd, J = 7.9, 1.6 z, 1), (m, 2), 3.58 (s, 3, C 3 ); 13 C MR (62.9 Mz, CDCl 3 ) δ 156.5, 151.7, 15.7, 147.3, 143.7, 136.1, 134.6, 122.8, 116.6, 115.9, 38.6; IR (ATR): 151, 1415, 136 cm -1 ; MS (m/z) ([M+] +, 81 Br), 39.5 ([M+] +, 79 Br); RMS calculated for C O 2 79 Br [M+] , found Br O 2 -(3-Bromopyridin-2-yl)--butyl--(3-nitropyridin-2-yl)-amine (9b): This compound was obtained by the General Procedure for alkylations, with compound 5 (2 mg,.68 mmol) and butyl bromide (87.3 µl,.81 mmol). Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 9:1 6:4) afforded product 9b (13 mg, 55% yield) as a brown gum. 1 MR (25 Mz, CDCl 3 ) δ 8.51 (dd, J = 4.4, 1.9 z, 1), 8.22 (dd, J = 4.7, 1.6 z, 1), 8.6 (dd, J = 8.2, 1.9 z, 1), 7.94 (dd, J = 7.8, 1.6 z, 1), (m, 2), 4.15 (t, J = 7.8 z, 2, C 2 ), (m, 2, C 2 ), (m, 2, C 2 ),.91 (t, J = 7.2 z, 3, C 3 ); 13 C MR (62.9 Mz, CDCl 3 ) δ 155.6, 151.7, 15.4, 147.4, 143.6, 136.4, 134.6, 122.4, 116.3, 115.8, 5.7, 3.1, 2.4, 14.; IR (ATR): 1599, 1424 cm -1 ; MS (m/z) 353. ([M+] +, 81 Br), 351. ([M+] +, 79 Br); RMS calculated for C O 2 79 Br [M+] , found Cl O 2 -(3-Chloropyridin-2-yl)--methyl--(3-nitropyridin-2-yl)-amine (1):This compound was obtained by the General Procedure for alkylations, with compound 6 (6 mg,.24 mmol) and methyl iodide (18 µl,.29 mmol). Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 8:2) afforded product 1 (42 mg, 67% yield) as brown crystals. Mp C; 1 MR (25 Mz, CDCl 3 ) δ 8.52 (dd, J = 4.7, 1.9 z, 1), (m, 2), 7.79 (dd, J = 7.9, 1.6 z, 1), 7.8 (dd, J = 7.9, 4.4 z, 1), 6.99 (dd, J = 7.8, 4.7 z, 1), 3.57 (s, 3, C 3 ); 13 C MR (62.9 Mz, CDCl 3 ) δ 155.3, 151.7, 15.6, 146.6, 14.2, 136.1, 134.6, 126.5, 122.5, 116., 38.; IR (ATR): 1422, 82 cm -1 ; MS (m/z) 267. ([M+] +, 37 Cl), 265. ([M+] +, 35 Cl); RMS calculated for C O 2 35 Cl [M+] , found Br 3 -(3-Bromopyridin-2-yl)- 2 -methyl-pyridine-2,3-diamine (11a): This compound was obtained by the General Procedure for reduction Method 1, with 9a (2 mg,.647 mmol) and stannous chloride dihydrate (73 mg, 3.23 mmol, 5 equiv.) in absolute ethanol (25 ml) at room temperature for 24 hours. Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 8:2 5:5) afforded product 11a (154 mg, 85% yield) as a brown powder. Mp C; 1 MR (25 Mz, CDCl 3 ) δ (m, 2), 7.71 (dd, J = 7.8, 1.6 z, 1), 7.48 (dd, J = 7.5, 1.3 z, 1), (m, 2), 6.3 (s, 1, S5

6 ), 4.69 (br s, 1, ), 3. (s, 3, C 3 ); 13 C MR (62.9 Mz, CDCl 3 ) δ 155.6, 153.2, 147.2, 145.4, 14.5, 133., 121.1, 115.8, 112.6, 16.3, 28.8; IR (ATR): 3299, 1589, 149 cm -1 ; MS (m/z) ([M+] +, 81 Br), ([M+] +, 79 Br); RMS calculated for C Br [M+] , found Br 3 -(3-Bromopyridin-2-yl)- 2 -butyl-pyridine-2,3-diamine (11b): This compound was obtained by the General Procedure for reduction Method 1, with 9b (1 mg,.285 mmol) and stannous chloride dihydrate (312 mg, mmol, 5 equiv.) in absolute ethanol (1 ml) at room temperature for 24 hours. Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 9:1 7:3) afforded product 11b (7 mg, 77% yield) as a beige-brown powder. Mp C; 1 MR (25 Mz, CDCl 3 ) δ (m, 2), 7.7 (dd, J = 7.8, 1.6 z, 1), 7.46 (dd, J = 7.5, 1.3 z, 1), (m, 2), 6.31 (br s, 1, ), 4.6 (br s, 1, ), (m, 2, C 2 ), (m, 2, C 2 ), (m, 2, C 2 ),.89 (t, J = 7.2 z, 3, C 3 ); 13 C MR (62.9 Mz, CDCl 3 ) δ 155., 153.1, 147.1, 145.3, 14.5, 132.9, 12.9, 115.8, 112.4, 16.2, 41.5, 31.9, 2.3, 14.; IR (ATR): 338, 3354, 1588, 1514, 1488 cm -1 ; MS (m/z) 323. ([M+] +, 81 Br), 321. ([M+] +, 79 Br); RMS calculated for C Br [M+] , found Cl 3 -(3-Chloropyridin-2-yl)- 2 -methyl-pyridine-2,3-diamine (12): This compound was obtained by the General Procedure for reduction Method 1, with compound 1 (8 mg,.32 mmol) and stannous chloride dihydrate (314 mg, 1.51 mmol, 5 equiv.) in absolute ethanol (1 ml) at room temperature for 6.5 hours. Purification by flash chromatography on silica gel (C 2 Cl 2 /MeO 1: 98:2) afforded product 12 (56 mg, 79% yield) as a green powder. Mp C; 1 (25 Mz, CDCl 3 ) δ (m, 2), (m, 2), (m, 2), 6.27 (s, 1, ), 4.7 (br s, 1, ), 2.98 (s, 3, C 3 ); 13 C MR (62.9 Mz, CDCl 3 ) δ 155.6, 152.5, 146.4, 145.3, 137., 132.8, 12.9, 116.2, 115.3, 112.6, 28.7; IR (ATR): 3321, 159, 1491 cm -1 ; MS (m/z) 237. ([M+] +, 37 Cl), 235. ([M+] +, 35 Cl); RMS calculated for C Cl [M+] , found O Br -{3-[(3-Bromopyridin-2-yl)amino]pyridin-2-yl}--methylpivalamide (13): Triethylamine (44 µl,.31 mmol, 1.25 equiv.) was added under argon to a solution of compound 11a (7 mg,.251 mmol), in dichloromethane (7 ml). After the mixture has been stirred for 5 minutes at room temperature, pivaloyl S6

7 chloride (35 µl,.27 mmol, 1.1 equiv.) was added at C. After 36 hours of stirring at room temperature, the reaction medium was hydrolyzed, extracted with dichloromethane and dried with MgSO 4, and the solvent was removed under reduced pressure to give the crude product. This residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate 1: 9:1) and the desired product 13 (54 mg, 59% yield) was obtained as a white-beige solid. Mp C; 1 (25 Mz, CDCl 3 ) δ 9.3 (d, J = 7.7 z, 1), 8.21 (dd, J = 5., 1.5 z, 1), 8.11 (dd, J = 4.7, 1.7 z, 1), 7.8 (dd, J = 7.7, 1.5 z, 1), 7.63 (br s, 1, ), 7.31 (dd, J = 8.2, 4.7 z, 1), 6.75 (dd, J = 7.7, 5. z, 1), 3.21 (s, 3, C 3 ), 1.1 (s, 9, 3C 3 -Piv); 13 C MR (62.9 Mz, CDCl 3 ) δ 181., 151.2, (2C), 141., 14.6 (2C), 132.9, 124.3, 117., 17.6, 41.2, 37.3, 28.6 (3C 3 -Piv); IR (ATR): 3367, 1653, 1514, 1426 cm -1 ; MS (m/z) ([M+a] +, 81 Br), ([M+a] +, 79 Br), ([M+] +, 81 Br), ([M+] +, 79 Br); RMS calculated for C O 79 Br [M+] , found Methyl-5,1-dihydrodipyrido[2,3-b:2,3 -e]pyrazine (14a): This compound was obtained by the General Procedure for the palladium-catalysed -arylations Method B, with compound 11a (6 mg,.215 mmol). Product 14a (42 mg), a green solid, was used in the next step without further purification. Mp C (ref C). The spectroscopic data (IR and MR) were in accordance with the literature values. 5 5-Butyl-5,1-dihydrodipyrido[2,3-b:2,3 -e]pyrazine (14b): This compound was obtained by the General Procedure for the palladium-catalysed -arylations Method B, with compound 11b (5 mg,.155 mmol). Product 14b (37 mg), a green solid, was used in the next step without further purification. Mp C (ref C). The spectroscopic data (IR and MR) were in accordance with the literature values. 5 5,1-Dimethyl-5,1-dihydrodipyrido[2,3-b:2,3 -e]pyrazine (15a): This compound was obtained by the General Procedure for alkylation, with non-purified compound 14a (42 mg,.212 mmol) and methyl iodide (16 µl,.258 mmol). The solution was stirred overnight at room temperature. Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 7:3) afforded product 15a (15 mg, 33% yield S7

8 calculated over two steps) as a green solid. Mp C (ref C). The spectroscopic data (IR and MR) were in accordance with the literature values. 6 5-Butyl-1-methyl-5,1-dihydrodipyrido[2,3-b : 2,3 -e]pyrazine (15b): This compound was obtained by the General Procedure for alkylation, with non-purified compound 14b (37 mg,.154 mmol). The solution was stirred overnight at room temperature. Purification by flash chromatography on silica gel (petroleum ether/ethyl acetate 8:2) afforded product 15b (13 mg, 32% yield calculated over two steps) as a green solid. Mp C (ref C). The spectroscopic data (IR and MR) were in accordance with the literature values. 5 References: 1. Sheldrick, G. M. SELXS-97, Program for Crystal Structure Solution, University of Göttingen, Germany, Sheldrick, G. M. SELXL-97, Program for Crystal Structure Refinement, University of Göttingen, Germany, Choppin, S.; Gros, P.; Fort, Y. Eur. J. Org. Chem. 21, 3, Amino-3-bromopyridine was prepared via a modification of a literature described by Turner (Turner, J. A. J. Org. Chem. 1983, 48, 341), using 1, 2-dibromoethane as a brominating agent. 5. Patriciu, O.-I.; Fînaru, A.-L.; Massip, S.; Leger, J.-M.; Jarry, C.; Guillaumet, G. Eur. J. Org. Chem. 29, Blanchard, S.; Rodriguez, I.; Kuehm-Caubère, C.; Renard, P.; Pfeiffer, B.; Guillaumet, G.; Caubère, P. Tetrahedron 22, 58, S8

9 mrc Br O 2 5 Frequency (Mz): (f1) (f1) (f1) ZG umber of Scans: 32 Fri Apr 13 1:47:17 PM C.mrc 5 Br O 2 1 Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 615 Thu May 6 9:44:25 AM S9

10 mrc Cl O Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 16 Thu Feb 2 12:47:34 AM C.mrc 6 Cl O Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 256 Thu Feb 2 12:59:38 AM S1

11 mrc Br Frequency (Mz): (f1) (f1) 8192 (f1) (f1) (f1) ZG umber of Scans: 64 Wed Apr 25 1:3: PM CDCl3 l + few drops of TFA C.mrc Br 7 2 CDCl3 C l + few drops of TFA Frequency (Mz): (f1) (f1) (f1) ZGPG umber of Scans: 248 Thu Apr 26 1:55:2 AM S11

12 mrc Cl CDCl3 + few drops of TFA Frequency (Mz): (f1) (f1) 8192 (f1) (f1) (f1) ZG umber of Scans: 16 Wed Sep 5 1:14:52 PM C.mrc Cl 8 2 CDCl3 C + few drops of TFA 5 Frequency (Mz): (f1) (f1) (f1) ZGPG umber of Scans: 248 Wed Sep 5 5:58:38 PM 15 1 S12

13 mrc a Br O Frequency (Mz): (f1) (f1) (f1) ZG umber of Scans: 64 Wed Apr 18 11:35:3 PM C.mrc 9a Br O Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 372 Sat Jun 18 11:31:39 AM S13

14 mrc b Br O Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 64 Sun Jun 4 7:29:33 PM C.mrc 9b Br O Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 372 Sun Jun 4 9:45:33 PM S14

15 mrc Cl O Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 64 Sun Oct 8 5:42:48 PM C.mrc 1 Cl O Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 496 Sun Oct 8 8:43:52 PM S15

16 Br a mrc Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 16 Thu Jun 3 7::55 AM C.mrc Br 11a 1 Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 124 Thu Jun 3 7:46:54 AM S16

17 mrc Br 11b 1 Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 64 Sun Jun 11 1:28:6 PM C.mrc Br 11b Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 372 Sun Jun 11 3:44:6 PM S17

18 mrc Cl 12 1 Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 64 Mon Jun 5 7:47:2 AM C.mrc Cl Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 372 Mon Jun 5 1:3:23 AM S18

19 mrc O Br 4 3 Frequency (Mz): (f1) (f1) (f1) (f1) ZG3 3 umber of Scans: 64 Sun ov 5 2:7:33 PM C.mrc O Br Frequency (Mz): (f1) (f1) (f1) ZGPG3 3 umber of Scans: 6144 Sun ov 5 6:38:5 PM S19

20 ORTEP of 5 with 5% of level probability Crystal data and structure refinement for 5. Identification code po119 Empirical formula C O 2 Br Formula weight g.mol -1 Temperature 293(2) K Wavelength Å Crystal system, space group Orthorhombic, Pna2 1 Unit cell dimensions a = 1.595(2) Å b = 7.426(3) Å c = (2) Å Volume 196.6(5) Å 3 Z, Calculated density 4, Mg/m 3 Absorption coefficient 5.18 mm -1 F() 584 Crystal size.15 x.15 x.1 mm Theta range for data collection 6.35 to deg. Limiting indices <=h<=12, <=k<=8, <=l<=16 Reflections collected / unique 978 / 978 Completeness to theta = % Max. and min. transmission.6291 and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 978 / 1 / 155 Goodness-of-fit on F^2.999 Final R indices [I>2sigma(I)] R1 =.376, wr2 =.951 R indices (all data) R1 =.385, wr2 =.963 Largest diff. peak and hole.557 and e. Å -3 CCDC deposition number: ydrogen bonding geometry (Å, ) Br1 8. Br1 = 3.57(5) 8-8. Br1 = deg O17 8. O17 = 2.647(7) 8-8. O17 = deg = 2.943(7) = deg. S2

21 ORTEP of 7 with 5% of level probability Crystal data and structure refinement for 7. Identification code po184 Empirical formula C Br Formula weight g.mol -1 Temperature 293(2) K Wavelength Å Crystal system, space group Monoclinic, P 2 1 /n Unit cell dimensions a = 8.638(1) Å b = 6.38(1) Å β = 94.2(2) deg. c = (3) Å Volume 135.1(3) Å 3 Z, Calculated density 4, 1.71 Mg/m 3 Absorption coefficient mm -1 F() 528 Crystal size.16 x.14 x.1 mm Theta range for data collection 4.71 to deg. Limiting indices -1<=h<=1, <=k<=7, <=l<=22 Reflections collected / unique 1716 / 1716 Completeness to theta = % Max. and min. transmission.6255 and.4913 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 1716 / / 137 Goodness-of-fit on F^ Final R indices [I>2sigma(I)] R1 =.548, wr2 =.1562 R indices (all data) R1 =.556, wr2 =.1574 Largest diff. peak and hole.477 and -.49 e. Å -3 CCDC deposition number: ydrogen bonding geometry (Å, ) 7(I)-7.. 3(II) = 3.44(5) = (I)-15A.. 13(III) = 3.134(5) O8 = B = 2.77(4) 1-1. O8 = Symmetry codes: II(1-x, -y, -z) ; III(x, 1+y, z) S21

22 ORTEP of 13 with 3% of level probability Crystal data and structure refinement for 13. Identification code po355 Empirical formula C O Br Formula weight g.mol -1 Temperature 293(2) K Wavelength Å Crystal system, space group Triclinic, P -1 Unit cell dimensions a = 7.538(1) Å α = 98.91(1) deg. b = 1.542(2) Å β = 12.36(1) deg. c = 12.44(1) Å γ = 19.92(1) deg. Volume 851.5(2) Å 3 Z, Calculated density 2, Mg/m 3 Absorption coefficient mm -1 F() 372 Crystal size.15 x.14 x.11 mm Theta range for data collection 3.88 to deg. Limiting indices -8<=h<=8, -12<=k<=12, <=l<=14 Reflections collected / unique 2893 / 2893 Completeness to theta = % Max. and min. transmission.798 and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 2893 / / 2 Goodness-of-fit on F^2 1.8 Final R indices [I>2sigma(I)] R1 =.369, wr2 =.998 R indices (all data) R1 =.383, wr2 =.116 Largest diff. peak and hole.599 and e. Å -3 CCDC deposition number: ydrogen bonding geometry (Å, ) Br7 8. Br7 = 3.51(2) 8-8. Br7 = = 2.72(3) = S22

Supporting Information

Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2014 Supporting Information Rhodium-catalyzed olefination of aryl tetrazoles