Friedel-Crafts Acylation of Pyrroles and Indoles using 1,5- Diazabicyclo[4.3.0]non-5-ene (DBN) as a Nucleophilic Catalyst

Size: px
Start display at page:

Download "Friedel-Crafts Acylation of Pyrroles and Indoles using 1,5- Diazabicyclo[4.3.0]non-5-ene (DBN) as a Nucleophilic Catalyst"

Transcription

1 Friedel-Crafts Acylation of Pyrroles and Indoles using 1,5- Diazabicyclo[4.3.0]non-5-ene (DB) as a ucleophilic Catalyst James E. Taylor, Mathew D. Jones, Jonathan M. J. Williams, and Steven D. Bull * Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY Contents General Experimental Starting Material Compound Data rganocatalytic Acylation General Procedure rganocatalytic Acylation Compound Data Tolmetin Synthesis MR Spectra Mechanistic Studies Crystallographic Data References S2 S2 S7 S7 S15 S18 S64 S67 S68 S1

2 General Experimental All reactions were performed under a nitrogen atmosphere in oven-dried apparatus, unless otherwise stated. Anhydrous acetonitrile, toluene, and tetrahydrofuran were obtained from an Innovative Technology Inc. PS solvent purification system. Petrol refers to the fraction of petroleum ether boiling at C. Pyrrole and -methylpyrrole were distilled before use. All other commercially available compounds were used as obtained from the chemical suppliers. Analytical thin layer chromatography was performed using commercially available aluminium backed plates coated with Merck G/UV254 neutral silica. Plates were visualised under UV light (at 254 nm) or by staining with phosphomolybdic acid followed by heating. Flash chromatography was performed using chromatography grade, silica 60 Å particle size microns from Fisher Scientific. 1 H MR spectra were recorded at 300 MHz and 13 C{ 1 H} spectra were recorded at 75 MHz on a Brüker Avance 300 spectrometer. Chemical shifts, δ, are quoted in parts per million and are referenced to the residual solvent peak. The following abbreviations are used: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of triplets; m, multiplet; app., apparent and br, broad.. Coupling constants, J, are quoted to the nearest 0.1 Hz. High resolution mass spectra were recorded on a Brüker Daltonics microtf spectrometer with an electrospray source and external calibration. Masses were recorded in positive electrospray ionisation mode and were introduced by flow injection. Masses are accurate to 5 ppm and data was processed using DataAnalysis software from Brüker Daltonics. Infra red spectra were recorded on a Perkin Elmer Spectrum 100 FT-IR spectrometer, using a Universal ATR accessory for sampling, with only selected absorbances quoted as ν in cm -1. Starting Material Compound Data 1-Benzyl-1H-pyrrole Bn Based on a literature procedure, 1 sodium hydride (60% dispersion in mineral oil, 1.32 g, 33 mmol) was added to anhydrous DMF (30 ml) in a nitrogen purged two-neck round-bottom flask. The solution was cooled to 0 C and pyrrole (2.08 ml, 30 mmol) in anhydrous DMF (8 ml) was added dropwise. The solution was allowed to warm to room temperature and was stirred for 30 minutes before being cooled back to 0 C when benzyl bromide (3.57 ml, 30 mmol) was added dropwise. The solution was again allowed to warm to room temperature and was stirred for one hour. The solution was then added to H 2 and extracted with 1:1 hexane : Et 2. The combined organic layers were washed with H 2 before drying over MgS 4, filtering, and concentrating under reduced pressure. The crude product was purified by flash column chromatography (hexane : Et 2 (95:5), R f = 0.64), S2

3 yielding the title compound (3.60 g, 76%) as a yellow oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (3H, m, ArH), (2H, m, ArH), 6.72 (2H, app. t, J = 1.6 Hz, CH), 6.22 (2H, app. t, J = 1.6 Hz, CHCH), 5.09 (2H, s, CH 2 Ph); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 138.3, 128.8, 127.8, 127.1, 121.3, 108.6, t-butyl 1H-pyrrole-1-carboxylate Boc Based on a literature procedure, 2 DMAP (0.12 g, 1 mmol) and di-t-butyl dicarbonate (2.62 g, 12 mmol) were added to a solution of pyrrole (0.69 ml, 10 mmol) in acetonitrile (10 ml) and the solution was stirred at room temperature for 24 hours. The reaction mixture was diluted with Et 2 and washed with ahc 3 and then brine. The organic layer was then dried over MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol : EtAc (99:1), R f = 0.19), yielding the title compound (1.44 g, 86%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = 7.24 (2H, t, J = 2.3 Hz, CH), 6.22 (2H, t, J = 2.3 Hz, CHCH), 1.60 (9H, s, C(CH 3 ) 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 149.1, 120.1, 112.0, 83.7, (4-Methoxybenzyl)-1H-pyrrole PMB Based on a literature procedure, 3 2,5-dimethoxytetrahydrofuran (1.30 ml, 10 mmol), 4- methoxybenzylamine (1.30 ml, 10 mmol), and glacial acetic acid (5 ml) were added to a carousel tube and heated at 115 C for 1.5 hours. The reaction was allowed to cool before being diluted with EtAc and quenched with ahc 3. The resulting layers were separated and the organics washed with brine before being dried over MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol : EtAc (95:5), R f = 0.44), yielding the title compound (0.98 g, 52%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = 7.08 (2H, d, J = 8.5 Hz, ArH), 6.86 (2H, d, J = 8.6 Hz, ArH), 6.68 (2H, t, J = 1.9 Hz, CH), 6.18 (2H, t, J = 1.9 Hz, CHCH), 5.01 (2H, s, CH 2 ), 3.80 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 159.3, 130.3, 128.6, 121.1, 114.2, 108.5, 55.4, S3

4 1-(2,4-Dimethoxybenzyl)-1H-pyrrole Based on a literature procedure, 3 2,5-dimethoxytetrahydrofuran (0.26 ml, 2 mmol), 2,4- dimethoxybenzylamine (0.30 ml, 2 mmol), and glacial acetic acid (2 ml) were added to a carousel tube and heated at 115 C for 1.5 hours. The reaction was allowed to cool before being diluted with EtAc and quenched with ahc 3. The resulting layers were separated and the organics washed with brine before being dried over MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol : EtAc (95:5), R f = 0.38), yielding the title compound (0.21 g, 49%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = 6.81 (1H, d, J = 8.2 Hz, ArH), 6.71 (2H, t, J = 2.0 Hz, CH), 6.46 (1H, d, J = 2.4 Hz, ArH), 6.41 (1H, dd, J = 8.3, 2.4 Hz, ArH), 6.15 (2H, t, J = 2.0 Hz, CHCH), 5.00 (2H, s, CH 2 ), 3.83 (3H, s, CH 3 ), 3.79 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 160.7, 157.9, 129.5, 121.2, 119.3, 108.0, 104.2, 98.6, 55.6, 55.5, 48.0; IR (film, cm -1 ): ν max = 1613, 1589, 1508; HRMS: m/z (ES) , C 13 H 15 a 2 [M+a] + requires (1H-Pyrrol-1-yl)propanenitrile C Based on a literature procedure, 4 1,8-diazabicyclo[5.4.0]undec-7-ene (0.15 ml, 1 mmol) was added to a solution of pyrrole (1.39 ml, 20 mmol) and acrylonitrile (1.7 ml, 26 mmol) in a round-bottom flask. The solution was stirred at room temperature for 20 hours before being diluted with Et 2 and washed with H 4 Cl. The organics were dried with MgS 4, filtered, and concentrated under reduced pressure, to yield the title compound (2.15 g, 90%) as a pale yellow oil. 1 H MR (300 MHz; CDCl 3 ): δ H = 6.71 (2H, t, J = 2.0 Hz, CH), 6.20 (2H, t, J = 2.0 Hz, CHCH), 4.19 (2H, t, J = 6.8 Hz, CH 2 ), 2.76 (2H, t, J = 6.8 Hz, CH 2 C); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 120.5, 117.3, 109.7, 45.2, S4

5 1,2-Dimethyl-1H-pyrrole Based on a literature procedure, 5 -methylpyrrole (0.90 ml, 10 mmol) and THF (10 ml) were added to a nitrogen purged three-neck round-bottom flask and cooled to 78 C. nbuli (2.5 M in hexanes, 4 ml, 10 mmol) was added dropwise and the solution was stirred overnight, allowing to warm slowly to room temperature. The solution was again cooled to 78 C and methyl iodide (0.62 ml, 10 mmol) in THF (10 ml) was added in one portion. The reaction was stirred at 78 C for four hours and was then allowed to warm slowly for three hours. The reaction was quenched by adding H 2 (20 ml) and was then extracted with Et 2. The organics were dried with MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by Kugelrohr distillation (bp 140 C), yielding the title compound (0.57 g, 60%) as a yellow oil. 1 H MR (300 MHz; CDCl 3 ): δ H = 6.56 (1H, t, J = 2.0 Hz, CH), 6.05 (1H, t, J = 3.0 Hz, CHCH), (1H, m, CHC), 3.54 (3H, s, CH 3 ), 2.24 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 129.0, 121.0, 106.6, 106.5, 33.7, ,2-Dimethyl-1H-indole Based on a literature procedure, 6 sodium hydride (60% dispersion in mineral oil, 0.44 g, 11 mmol) was added portionwise to a solution of 2-methylindole (1.31 g, 10 mmol) in anhydrous DMF (16 ml). The solution was stirred at room temperature for 30 minutes before cooling to 0 C, when methyl iodide (0.68 ml, 11 mmol) was added. The reaction was stirred at 0 C for 30 minutes before warming to room temperature and stirring overnight. The reaction was quenched by adding H 2 and was extracted with 1:1 hexane : Et 2. The organics were washed with H 2, dried over MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol : EtAc (95:5), R f = 0.60) yielding the title compound (0.84 g, 58%) as a peach coloured solid. 1 H MR (300 MHz; CDCl 3 ): δ H = 7.54 (1H, d, J = 7.6 Hz, ArH), 7.27 (1H, d, J = 7.6 Hz, ArH), 7.17 (1H, td, J = 7.0, 1.3 Hz, ArH), 7.08 (1H, td, J = 7.8, 1.3 Hz, ArH), 6.27 (1H, t, J = 0.9 Hz, CHC(CH 3 )), 3.68 (3H, s, CH 3 ), 2.44 (3H, d, J = 0.9 Hz, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 137.5, 136.9, 128.1, 120.6, 119.7, 119.4, 108.8, 99.7, 29.5, S5

6 5-Methoxy-1-methyl-1H-indole Based on a literature procedure, 6 sodium hydride (60% dispersion in mineral oil, 0.29 g, 7.1 mmol) was added portionwise to a solution of 5-methoxyindole (0.7 g, 4.8 mmol) in anhydrous DMF (9.6 ml). The solution was stirred at room temperature for 30 minutes before cooling to 0 C, when methyl iodide (0.33 ml, 5.3 mmol) was added. The reaction was stirred at 0 C for 30 minutes before warming to room temperature and stirring overnight. The reaction was quenched by adding H 2 and was extracted with 1:1 hexane : Et 2. The organics were washed with H 2, dried over MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography (petrol : EtAc (90:10), R f = 0.65), yielding the title compound (0.59 g, 76%) as a white crystalline solid. 1 H MR (300 MHz; CDCl 3 ): δ H = 7.22 (1H, d, J = 8.8 Hz, ArH), 7.11 (1H, d, J = 2.3 Hz, ArH), 7.03 (1H, d, J = 3.0 Hz, CH), 6.90 (1H, dd, J = 8.8, 2.4 Hz, ArH), 6.41 (1H, dd, J = 3.0, 0.8 Hz, CHCH), 3.87 (3H, s, CH 3 ), 3.78 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 154.1, 132.2, 129.3, 128.9, 111.9, 110.0, 102.6, 100.4, 55.9, 32.9; IR (film, cm -1 ): ν max = 1607, 1577, 1494, 1419; HRMS: m/z (ES) , C 10 H 12 [M+H] + requires S6

7 rganocatalytic Acylation - General Procedure To a nitrogen purged Radleys carousel tube ( mm fitted with gas-tight threaded PTFE caps with a suba-seal, sidearm and inlet valve) was added the appropriate -protected pyrrole or indole (1 mmol), toluene (0.11 ml, 1 mmol), 1,5-diazabicyclo[4.3.0]non-5-ene (DB) (0.018 ml, 0.15 mmol), and the acyl chloride (1.2 mmol). The sealed carousel tube was then heated at 115 C for four hours, before cooling to room temperature. The resulting mixture was diluted with CH 2 Cl 2 and washed with 1M HCl followed by 1M ah, before being dried with MgS 4, filtered, and concentrated under reduced pressure. The crude product was purified by either column chromatography or recrystallization. Conversions were obtained from the crude 1 H MR spectra using an internal standard of 2,5-dimethylfuran. rganocatalytic Acylation Compound Data (1-Methyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 2, entry 1) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (90:10), R f = 0.69), yielding the title compound (0.14 g, 73%) as a colourless oil with spectroscopic data in accordance to the literature. 7 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (3H, m, ArH), 6.92 (1H, app. t, J = 2.0 Hz, CH), 6.74 (1H, dd, J = 4.1, 1.7 Hz, CCH), 6.16 (1H, dd, J = 4.1, 2.5 Hz, CHCH), 4.04 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.3, 140.0, 131.6, 131.5, 130.6, 129.3, 128.2, 123.0, 108.2, 37.5; IR (film, cm -1 ): ν max = 1622 (C=); HRMS: m/z (ES) , C 12 H 12 [M+H] + requires (1-Methyl-1H-pyrrol-2-yl)(4-nitrophenyl)methanone (Table 2, entry 2) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and 4-nitrobenzoyl chloride (0.22 g, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : EtAc (90:10), R f = 0.20), yielding the title compound (0.17 g, 74%) as yellow crystals with spectroscopic S7

8 data in accordance with the literature. 8 mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 8.31 (2H, d, J = 8.7 Hz, ArH), 7.92 (2H, d, J = 9.0 Hz, ArH), 6.99 (1H, app. t, J = 1.8 Hz, CH), 6.68 (1H, dd, J = 4.2, 1.6 Hz, CCH), 6.19 (1H, dd, J = 4.2, 2.5 Hz, CHCH), 4.06 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 183.8, 149.4, 145.5, 132.9, 130.0, 123.8, 123.5, 109.0, 37.7; IR (film, cm -1 ): ν max = 1623 (C=); HRMS: m/z (ES) , C 12 H [M+H] + requires (4-Methoxyphenyl)(1-methyl-1H-pyrrol-2-yl)methanone (Table 2, entry 3) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and 4-methoxybenzoyl chloride (0.16 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (90:10), R f = 0.09), yielding the title compound (0.14 g, 66%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (2H, m, ArH), 6.89 (1H, app. t, J = 2.0 Hz, CH), 6.72 (1H, dd, J = 4.0, 1.7 Hz, CCH), 6.15 (1H, dd, J = 4.0, 2.5 Hz, CHCH), 4.01 (3H, s, CH 3 ), 3.87 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 185.3, 162.6, 132.6, 131.6, 130.8, 122.0, 113.4, 108.0, 55.5, 37.3; IR (film, cm -1 ): ν max = 1623 (C=); HRMS: m/z (ES) , C 13 H 14 2 [M+H] + requires (1-Methyl-1H-pyrrol-2-yl)(m-tolyl)methanone (Table 2, entry 4) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and m-toluoyl chloride (0.16 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (90:10), R f = 0.25), yielding the title compound (0.12 g, 58%) as a yellow oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (2H, m, ArH), 6.91 (1H, app. t, J = 2.0 Hz, CH), 6.74 (1H, dd, J = 4.0, 1.7 Hz, CCH), 6.16 (1H, dd, J = 4.0, 2.5 Hz, CHCH), 4.04 (3H, s, CH 3 ), 2.42 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.5, 140.1, 137.9, 132.2, 131.5, 130.8, 129.8, 128.0, S8

9 126.5, 122.9, 108.1, 37.5, 21.5; IR (film, cm -1 ): ν max = 1623 (C=); HRMS: m/z (ES) , C 13 H 14 [M+H] + requires (1-Methyl-1H-pyrrol-2-yl)(o-tolyl)methanone (Table 2, entry 5) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and o-toluoyl chloride (0.16 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (95:5), R f = 0.19), yielding the title compound (0.13 g, 63%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (2H, m, ArH), 6.80 (1H, app. t, J = 2.0 Hz, CH), 6.39 (1H, dd, J = 4.1, 1.8 Hz, CCH), 6.00 (1H, dd, J = 4.1, 2.6 Hz, CHCH), 3.99 (3H, s, CH 3 ), 2.28 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 188.3, 140.3, 136.2, 131.9, 131.5, 130.8, 129.5, 128.2, 124.9, 123.7, 108.3, 37.6, 19.7; IR (film, cm -1 ): ν max = 1619 (C=); HRMS: m/z (ES) , C 13 H 14 [M+H] + requires (4-Bromophenyl)(1-methyl-1H-pyrrol-2-yl)methanone (Table 2, entry 6) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and 4-bromobenzoyl chloride (0.22 g, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (95:5), R f = 0.24), yielding the title compound (0.18 g, 70%) as a white solid. mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 7.67 (2H, dt, J = 8.6, 2.0 Hz, ArH), 7.58 (2H, dt, J = 8.6, 2.0 Hz, ArH), 6.93 (1H, app. t, J = 2.0 Hz, CH), 6.70 (1H, dd, J = 4.1, 1.7 Hz, CCH), 6.16 (1H, dd, J = 4.2, 2.5 Hz, CHCH), 4.02 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 184.9, 138.8, 131.9, 131.4, 130.8, 130.3, 126.2, 122.9, 108.4, 37.5; IR (film, cm -1 ): ν max = 1624 (C=); HRMS: m/z (ES) , C 12 H 11 Br [M+H] + requires S9

10 2,2-Dichloro-1-(1-methyl-1H-pyrrol-2-yl)ethanone (Table 2, entry 7) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and dichloroacetyl chloride (0.12 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. o purification was required and the title compound (0.15 g, 80%) was obtained as a yellow solid with spectroscopic data in accordance with the literature. 9 mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 7.14 (1H, dd, J = 4.3, 1.5 Hz, CCH), 6.98 (1H, app. t, J = 1.7 Hz, CH), 6.58 (1H, s, CHCl 2 ), 6.23 (1H, dd, J = 4.3, 2.4 Hz, CHCH), 3.98 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 176.7, 134.0, 125.3, 121.3, 109.4, 68.1, 38.0; IR (film, cm -1 ): ν max = 1654 (C=); HRMS: m/z (ES) , C 7 H 8 Cl 2 [M+H] + requires (1-Methyl-1H-pyrrol-2-yl)-3-phenylpropan-1-one (Table 2, entry 8) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and hydrocinnamoyl chloride (0.18 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (90:10), R f = 0.24), yielding the title compound (0.15 g, 70%) as a yellow oil with spectroscopic data in accordance with the literature H MR (300 MHz; CDCl 3 ): δ H = (5H, m, ArH), 6.86 (1H, dd, J = 4.1, 1.7 Hz, CCH), 6.71 (1H, app. t, J = 1.9 Hz, CH), 6.02 (1H, dd, J = 4.1, 2.5 Hz, CHCH), 3.86 (3H, s, CH 3 ), (2H, m, CH 2 Ph), (2H, m, CH 2 CH 2 Ph); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 190.3, 141.6, 131.1, 130.7, 128.6, 128.5, 126.1, 119.1, 108.0, 40.8, 37.8, 31.0; IR (film, cm -1 ): ν max = 1643 (C=); HRMS: m/z (ES) , C 14 H 16 [M+H] + requires (1-Methyl-1H-pyrrol-2-yl)heptan-1-one (Table 2, entry 9) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and heptanoyl chloride (0.19 ml, 1.2 mmol) were heated at 115 C for four hours according to the general S10

11 procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (90:10), R f = 0.38), yielding the title compound (0.16 g, 82%) as a yellow oil with spectroscopic data in accordance with the literature H MR (300 MHz; CDCl 3 ): δ H = 6.95 (1H, dd, J = 4.1, 1.7 Hz, CCH), 6.78 (1H, app. t, J = 2.0 Hz, CH), 6.11 (1H, dd, J = 4.1, 2.5 Hz, CHCH), 3.94 (3H, s, CH 3 ), 2.75 (2H, t, J = 7.5 Hz, CCH 2 ), 1.69 (2H, app. p, J = 7.5 Hz, CCH 2 CH 2 ), (6H, m, (CH 2 ) 3 CH 3 ), 0.89 (3H, t, J = 6.8 Hz, CH 2 CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 191.9, 130.9, 119.0, 107.9, 39.3, 37.8, 31.8, 29.3, 25.4, 22.7, 14.2; IR (film, cm -1 ): ν max = 1646 (C=); HRMS: m/z (ES) , C 12 H 19 a [M+a] + requires ,2-Dimethyl-1-(1-methyl-1H-pyrrol-2-yl)propan-1-one (Table 2, entry 10) -Methylpyrrole (0.09 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and trimethylacetyl chloride (0.15 ml, 1.2 mmol) were heated at 115 C for six hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (90:10), R f = 0.36), yielding the title compound (0.08 g, 49%) as a colourless oil with spectroscopic data in accordance with the literature H MR (300 MHz; CDCl 3 ): δ H = 7.03 (1H, dd, J = 4.2, 1.6 Hz, CCH), 6.74 (1H, t, J = 2.0 Hz, CH), 6.11 (1H, dd, J = 4.2, 2.5 Hz, CHCH), 3.90 (3H, s, CH 3 ), 1.36 (9H, s, C(CH 3 ) 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 198.0, 129.9, 128.7, 118.8, 107.2, 43.9, 38.7, 29.0; IR (film, cm -1 ): ν max = 1636 (C=); HRMS: m/z (ES) , C 10 H 16 [M+H] + requires (1-Benzyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 1) -Benzylpyrrole (0.15 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (hexane : Et 2 (95:5), R f = 0.20), yielding the title compound (0.15 g, 56%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (3H, m, ArH), (5H, m, ArH), 6.91 (1H, dd, J = 2.5, 1.8 Hz, CH), 6.68 (1H, dd, J = 4.1, 1.7 Hz, CCH), 6.11 (1H, dd, J = 4.1, 2.5 Hz, CHCH), 5.57 (2H, s, CH 2 Ph); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.3, 140.0, 138.4, 131.5, 131.0, 130.3, 129.3, S11

12 128.7, 128.1, 127.6, 127.3, 123.6, 108.8, 52.5; IR (film, cm -1 ): ν max = 1616 (C=); HRMS: m/z (ES) , C 18 H 16 [M+H] + requires (1-(4-Methoxybenzyl)-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 2) 1-(4-Methoxybenzyl)-1H-pyrrole (0.19 g, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (95:5), R f = 0.27), yielding the title compound (0.23 g, 79%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (3H, m, ArH), 7.18 (2H, d, J = 8.7 Hz, ArH), 7.01 (1H, app. t, J = 2.0 Hz, CH), 6.85 (2H, d, J = 8.7 Hz, ArH), 6.76 (1H, dd, J = 4.0, 1.7 Hz, CCH), 6.19 (1H, dd, J = 4.0, 2.6 Hz, CHCH), 5.60 (2H, s, CH 2 Ar), 3.78 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.3, 159.2, 140.1, 131.5, 130.7, 130.4, 130.2, 129.4, 129.0, 128.1, 123.7, 114.2, 108.7, 55.4, 52.0; IR (film, cm -1 ): ν max = 1624 (C=); HRMS: m/z (ES) , C 19 H 18 2 [M+H] + requires (1-(2,4-Dimethoxybenzyl)-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 3) 1-(2,4-Dimethoxybenzyl)-1H-pyrrole (0.12 g, 0.5 mmol), toluene (0.05 ml, 0.5 mmol), DB (0.009 ml, mmol), and benzoyl chloride (0.08 ml, 0.7 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (90:10), R f = 0.32), yielding the title compound (0.10 g, 62%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (3H, m, ArH), (2H, m, ArH, CH), 6.72 (1H, dd, J = 4.0, 1.7 Hz, CCH), 6.46 (1H, d, J = 2.4 Hz, ArH), 6.40 (1H, dd, J = 8.3, 2.4 Hz, ArH), 6.14 (1H, dd, J = 4.0, 2.5 Hz, CHCH), 5.62 (2H, s, CH 2 Ar), 3.82 (3H, s, CH 3 ), 3.78 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.4, 160.7, 158.3, 140.3, 133.9, 131.4, 131.3, 130.3, 130.1, 129.4, 128.6, 128.1, 123.5, 119.3, 108.2, 104.2, 98.5, 55.5, 55.4, 47.1; IR (film, cm -1 ): ν max = 1691 (C=); HRMS: m/z (ES) , C 20 H 20 3 [M+H] + requires S12

13 3-(2-Benzoyl-1H-pyrrol-1-yl)propanenitrile (Table 3, entry 4) Ph C 3-(1H-Pyrrol-1-yl)propanenitrile (0.12 g, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (80:20), R f = 0.32), yielding the title compound (0.16 g, 73%) as a colourless solid. mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (3H, m ArH), 7.11 (1H, dd, J = 2.4, 1.8 Hz, CH), 6.84 (1H, dd, J = 4.1, 1.7 Hz, CCH), 6.25 (1H, dd, J = 4.1, 2.6 Hz, CHCH), 4.62 (2H, t, J = 6.3 Hz, CH 2 ), 3.03 (2H, t, J = 6.3 Hz, CH 2 C); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.4, 139.6, 131.8, 131.6, 129.7, 129.3, 128.3, 124.5, 117.7, 109.5, 45.7, 20.6; IR (film, cm -1 ): ν max = 2253 (C), 1608 (C=); HRMS: m/z (ES) , C 14 H 13 2 [M+H] + requires (1,5-Dimethyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 5) 1,2-Dimethyl-1H-pyrrole (0.10 g, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (90:10), R f = 0.42), yielding the title compound (0.13 g, 63%) as a pale yellow oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (2H, m, ArH), (3H, m, ArH), 6.65 (1H, d, J = 4.0 Hz, C(CH 3 )CHCH), 5.96 (1H, dd, J = 4.0, 0.6 Hz), 3.94 (3H, s, CH 3 ), 2.30 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 185.6, 140.6, 139.6, 131.1, 130.6, 129.2, 128.0, 123.4, 108.4, 33.0, 12.7; IR (film, cm -1 ): ν max = 1615 (C=); HRMS: m/z (ES) , C 13 H 14 [M+H] + requires S13

14 (1-Methyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 6) Ph 1-Methyl-1H-indole (0.12 ml, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (dichloromethane (neat), R f = 0.21), yielding the title compound (0.13 g, 54%) as a colourless oil. 1 H MR (300 MHz; CDCl 3 ): δ H = (1H, m, Ph-H), 7.82 (2H, app. dt, J = 6.5, 1.7 Hz, indole- H 2 ), (4H, m, indole-h 2, Ph-H, CH), (3H, m, Ph-H 3 ), 3.85 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 190.9, 141.0, 138.0, 137.7, 131.2, 128.8, 128.4, 127.3, 123.8, 122.9, 122.8, 115.7, 109.7, 33.6; IR (film, cm -1 ): ν max = 1611 (C=); HRMS: m/z (ES) , C 16 H 14 [M+H] + requires (1,2-Dimethyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 7) Ph 1,2-Dimethyl-1H-indole (0.15 g, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (80:20), R f = 0.35), yielding the title compound (0.22 g, 88%) as a peach coloured solid. mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 7.76 (2H, dt, J = 6.9, 1.6 Hz, ArH), 7.55 (1H, tt, J = 7.3, 1.4 Hz, ArH), (2H, m, ArH), (2H, m, ArH), 7.22 (1H, td, J = 7.2, 1.2 Hz, ArH), 7.07 (1H, td, J = 7.2, 1.0 Hz, ArH), 3.74 (3H, s, CH 3 ), 2.59 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 193.0, 144.8, 141.6, 136.7, 131.6, 129.2, 128.4, 127.2, 122.2, 121.5, 121.1, 113.8, 109.3, 29.8, 12.7; IR (film, cm -1 ): ν max = 1608 (C=); HRMS: m/z (ES) , C 17 H 16 [M+H] + requires S14

15 (5-Methoxy-1-methyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 8) 5-Methoxy-1-methyl-1H-indole (0.16 g, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (80:20), R f = 0.26), yielding the title compound (0.10 g, 40%) as a pale yellow oil. 1 H MR (300 MHz; CDCl 3 ): δ H = 7.88 (1H, d, J = 2.4 Hz, ArH), 7.70 (2H, dt, J = 6.5, 1.5 Hz, ArH), (4H, m, ArH, CH), 7.14 (1H, d, J = 8.9 Hz, ArH), 6.88 (1H, dd, J = 8.9, 2.5 Hz, ArH), 3.82 (3H, s, CH 3 ), 3.68 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 191.0, 156.7, 141.1, 138.1, 132.6, 131.1, 128.7, 128.4, 128.1, 115.3, 114.3, 110.6, 104.0, 55.9, 33.8; IR (film, cm -1 ): ν max = 1612 (C=); HRMS: m/z (ES) , C 17 H 16 2 [M+H] + requires Tolmetin Synthesis 2-(1-Methyl-1H-pyrrol-2-yl)-2-oxoacetic acid Based on a literature procedure, 13 oxalyl chloride (4.30 ml, 50 mmol) and CH 2 Cl 2 (20 ml) were added to a three-neck round-bottom flask and cooled to -10 C under a nitrogen atmosphere. - Methylpyrrole (4.44 ml, 50 mmol) in CH 2 Cl 2 (40 ml) was added dropwise via a dropping funnel, maintaining the temperature below 0 C. The resulting solution was stirred at 0 C for one hour before sufficient 20% KH(aq) was added to make the solution ph 10. The solution was stirred for 30 minutes and then diluted with H 2. The two layers were separated and the aqueous layer extracted with CH 2 Cl 2. To the combined organic layers was added 20% H 2 S 4 (aq) until a white precipitate formed and the solution was stirred for 30 minutes. The solid was filtered, washing with cold H 2, before being dried under reduced pressure to yield the title compound (5.28 g, 69%) as a pale yellow solid. mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 8.05 (1H, dd, J = 4.4, 1.6 Hz, CCH), 7.10 (1H, app. t, J = 1.8 Hz, CH), 6.28 (1H, dd, J = 4.4, 2.4 Hz, CHCH), 3.99 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 170.5, 160.5, 136.7, 128.9, 126.7, 111.1, 38.3; IR (film, cm -1 ): ν max = 2739 (-H), 1718 (C=); HRMS: m/z (ES) , C 7 H 8 3 [M+H] + requires S15

16 2-(1-Methyl-1H-pyrrol-2-yl)acetic acid Based on a literature procedure, 13 2-(1-methyl-1H-pyrrol-2-yl)-2-oxoacetic acid (3.08 g, 20 mmol), hydrazine monohydrate (2.00 ml, 40 mmol), and 20% KH(aq) (40 ml) were added to a two-neck round-bottom flask fitted with a reflux condenser under a nitrogen atmosphere. The resulting solution was refluxed at 100 C for eight hours. After cooling to room temperature, 2M HCl was added to make the solution ph 2. The mixture was extracted with CH 2 Cl 2 and the organics were washed with H 2, before drying with MgS 4 and filtering. The solvent was removed under reduced pressure and the crude recrystallized from Et 2 and petrol to yield the title compound (1.88 g, 68%) as a yellow solid. mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 6.61 (1H, app. t, J = 2.3 Hz, CH), (2H, m, CHCH, CCH), 3.67 (2H, s, CH 2 C 2 H), 3.59 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 176.9, 124.1, 122.9, 109.3, 107.3, 34.0, 32.4; IR (film, cm -1 ): ν max = 2919 (-H), 1688 (C=); HRMS: m/z (ES) , C 7 H 10 2 [M+H] + requires Methyl 2-(1-methyl-1H-pyrrol-2-yl)acetate (11) 2-(1-Methyl-1H-pyrrol-2-yl)acetic acid (1.14 g, 8 mmol) and p-toluenesulfonic acid (0.47 g, 2 mmol) were added to a two-neck round-bottom flask fitted with a reflux condenser under a nitrogen atmosphere. MeH (20 ml) was added and the reaction refluxed at 70 C for eight hours. After cooling to room temperature, the methanol was removed under reduced pressure and the crude was diluted with CH 2 Cl 2 before being washed with brine. The organics were dried with MgS 4, filtered, and concentrated under reduced pressure. The crude was purified by flash column chromatography (petrol : EtAc (90:10), R f = 0.38), yielding the title compound 11 (0.98 g, 80%) as a colourless oil with spectroscopic data in accordance with the literature H MR (300 MHz; CDCl 3 ): δ H = 6.60 (1H, app. t, J = 2.1 Hz, CH), (2H, m, CCH, CHCH), 3.71 (3H, s, CH 3 ), 3.64 (2H, s, CH 2 C 2 Me), 3.58 (3H, s, CH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 171.1, 124.9, 122.7, 108.9, 107.1, 52.2, 34.0, 32.6; IR (film, cm -1 ): ν max = 1733 (C=); HRMS: m/z (ES) , C 8 H 12 2 [M+H] + requires S16

17 Methyl 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetate (12) Methyl 2-(1-methyl-1H-pyrrol-2-yl)acetate (11) (0.46 g, 3 mmol), toluene (0.33 ml, 3 mmol), DB (0.054 ml, 0.45 mmol), and p-toluoyl chloride (0.48 ml, 3.6 mmol) were heated at 115 C for four hours according to the general procedure. The crude product was purified by flash column chromatography (petrol : EtAc (80:20), R f = 0.38) yielding the title compound (12) (0.54 g, 66%) as a pale yellow solid with spectroscopic data in accordance with the literature. 13 mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 7.63 (2H, d, J = 8.1 Hz, ArH), 7.16 (2H, d, J = 7.9 Hz, ArH), 6.59 (1H, d, J = 4.0 Hz, CHCC), 6.02 (1H, d, J = 4.0 Hz, CHCCH 2 ), 3.86 (3H, s, CH 3 ), 3.66 (3H, s, CH 3 ), 3.64 (2H, s, CH 2 C 2 Me), 2.34 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.0, 169.9, 142.0, 137.4, 134.5, 131.6, 130.3, 129.5, 129.3, 128.8, 122.4, 109.6, 52.6, 33.3, 32.8,, 21.6; IR (film, cm -1 ): ν max = 1722 (C=), 1622 (C=); HRMS: m/z (ES) , C 16 H 18 3 [M+H] + requires (1-Methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetic acid, Tolmetin (13) Methyl 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetate (12) (0.40 g, 1.5 mmol), H 2 (4.2 ml), and 2.5 M ah(aq) (0.72 ml, 1.8 mmol) were added to a round-bottom flask and stirred at room temperature for 48 hours, until all the solid had dissolved. The solution was acidified with 2M HCl until a precipitate was formed. The mixture was diluted with CH 2 Cl 2 and the layers were separated, washing the organics with brine, before drying with MgS 4, filtering, and concentrating under reduced pressure. The crude was purified by stirring with Et 2 and filtering, yielding the title compound (13) (0.30 g, 78%) as a white solid with spectroscopic data in accordance with the literature. 13 mp: C; 1 H MR (300 MHz; CDCl 3 ): δ H = 7.70 (2H, d, J = 7.9 Hz, ArH), 7.23 (2H, d, J = 7.9 Hz, ArH), 6.67 (1H, d, J = 3.8 Hz, CHCC), 6.12 (1H, d, J = 3.7 Hz, CHCCH 2 ), 3.93 (3H, s, CH 3 ), 3.75 (2H, s, CH 2 C 2 H), 2.41 (3H, s, CCH 3 ); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 186.3, 175.1, 142.2, 137.2, 133.9, 131.7, 129.6, 128.9, 122.6, 109.9, 33.4, 32.7, 21.7; IR (film, cm -1 ): ν max = 3199 (-H), 1731 (C=), 1698 (C=); HRMS: m/z (ES) , C 15 H 16 3 [M+H] + requires S17

18 (1-methyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 2, entry 1) Ph 300 MHz, CDCl ppm S18

19 (1-methyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 2, entry 1) Ph 75 MHz, CDCl ppm S19

20 (1-methyl-1H-pyrrol-2-yl)(4-nitrophenyl)methanone (Table 2, entry 2) MHz, CDCl ppm S20

21 (1-methyl-1H-pyrrol-2-yl)(4-nitrophenyl)methanone (Table 2, entry 2) MHz, CDCl ppm S21

22 (4-methoxyphenyl)(1-methyl-1H-pyrrol-2-yl)methanone (Table 2, entry 3) Me 300 MHz, CDCl ppm S22

23 (4-methoxyphenyl)(1-methyl-1H-pyrrol-2-yl)methanone (Table 2, entry 3) Me 75 MHz, CDCl ppm S23

24 (1-methyl-1H-pyrrol-2-yl)(m-tolyl)methanone (Table 2, entry 4) MHz, CDCl ppm S24

25 (1-methyl-1H-pyrrol-2-yl)(m-tolyl)methanone (Table 2, entry 4) MHz, CDCl ppm S25

26 (1-methyl-1H-pyrrol-2-yl)(o-tolyl)methanone (Table 2, entry 5) MHz, CDCl ppm S26

27 (1-methyl-1H-pyrrol-2-yl)(o-tolyl)methanone (Table 2, entry 5) MHz, CDCl ppm S27

28 (4-bromophenyl)(1-methyl-1H-pyrrol-2-yl)methanone (Table 2, entry 6) Br 300 MHz, CDCl ppm S28

29 (4-bromophenyl)(1-methyl-1H-pyrrol-2-yl)methanone (Table 2, entry 6) Br MHz, CDCl ppm S29

30 2,2-dichloro-1-(1-methyl-1H-pyrrol-2-yl)ethanone (Table 2, entry 7) Cl Cl 300 MHz, CDCl ppm S30

31 2,2-dichloro-1-(1-methyl-1H-pyrrol-2-yl)ethanone (Table 2, entry 7) Cl Cl MHz, CDCl ppm S31

32 1-(1-methyl-1H-pyrrol-2-yl)-3-phenylpropan-1-one (Table 2, entry 8) Ph 300 MHz, CDCl ppm S32

33 1-(1-methyl-1H-pyrrol-2-yl)-3-phenylpropan-1-one (Table 2, entry 8) MHz, CDCl 3 Ph ppm S33

34 1-(1-methyl-1H-pyrrol-2-yl)heptan-1-one (Table 2, entry 9) MHz, CDCl ppm S34

35 1-(1-methyl-1H-pyrrol-2-yl)heptan-1-one (Table 2, entry 9) MHz, CDCl ppm S35

36 2,2-dimethyl-1-(1-methyl-1H-pyrrol-2-yl)propan-1-one (Table 2, entry 10) MHz, CDCl ppm S36

37 2,2-dimethyl-1-(1-methyl-1H-pyrrol-2-yl)propan-1-one (Table 2, entry 10) MHz, CDCl ppm S37

38 (1-benzyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 1) Ph Bn 300 MHz, CDCl ppm S38

39 (1-benzyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 1) Ph Bn 75 MHz, CDCl ppm S39

40 (1-(4-methoxybenzyl)-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 2) Ph PMB 300 MHz, CDCl ppm S40

41 (1-(4-methoxybenzyl)-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 2) Ph PMB 75 MHz, CDCl ppm S41

42 (1-(2,4-dimethoxybenzyl)-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 3) Ph DMB 300 MHz, CDCl ppm S42

43 (1-(2,4-dimethoxybenzyl)-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 3) Ph DMB 75 MHz, CDCl ppm S43

44 3-(2-benzoyl-1H-pyrrol-1-yl)propanenitrile (Table 3, entry 4) Ph C 300 MHz, CDCl ppm S44

45 3-(2-benzoyl-1H-pyrrol-1-yl)propanenitrile (Table 3, entry 4) Ph C 75 MHz, CDCl ppm S45

46 (1,5-dimethyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 5) Ph 300 MHz, CDCl ppm S46

47 (1,5-dimethyl-1H-pyrrol-2-yl)(phenyl)methanone (Table 3, entry 5) Ph 75 MHz, CDCl ppm S47

48 (1-methyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 6) Ph 300 MHz, CDCl ppm S48

49 (1-methyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 6) Ph 75 MHz, CDCl ppm S49

50 (1,2-dimethyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 7) ppm Ph 300 MHz, CDCl S50

51 (1,2-dimethyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 7) Ph 75 MHz, CDCl ppm S51

52 (5-methoxy-1-methyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 8) Me Ph 300 MHz, CDCl ppm S52

53 (5-methoxy-1-methyl-1H-indol-3-yl)(phenyl)methanone (Table 3, entry 8) Me Ph 75 MHz, CDCl ppm S53

54 2-(1-methyl-1H-pyrrol-2-yl)-2-oxoacetic acid C 2 H 300 MHz, CDCl ppm S54

55 2-(1-methyl-1H-pyrrol-2-yl)-2-oxoacetic acid C 2 H MHz, CDCl ppm S55

56 2-(1-methyl-1H-pyrrol-2-yl)acetic acid C 2 H 300 MHz, CDCl ppm S56

57 2-(1-methyl-1H-pyrrol-2-yl)acetic acid C 2 H MHz, CDCl ppm S57

58 methyl 2-(1-methyl-1H-pyrrol-2-yl)acetate (11) C 2 Me 300 MHz, CDCl ppm S58

59 methyl 2-(1-methyl-1H-pyrrol-2-yl)acetate (11) C 2 Me MHz, CDCl ppm S59

60 methyl 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetate (12) C 2 Me 300 MHz, CDCl ppm S60

61 methyl 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetate (12) MHz, CDCl 3 C 2 Me ppm S61

62 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetic acid, Tolmetin (13) C 2 H 300 MHz, CDCl ppm S62

63 2-(1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl)acetic acid, Tolmetin (13) MHz, CDCl 3 C 2 H ppm S63

64 Kinetic Experiments -Benzyl-D 4 -pyrrole Firstly, D 5 -pyrrole was synthesised in accordance to a literature procedure. 14 Pyrrole (2 ml, 29 mmol), acetic acid-d 1 (1.83 ml, 32 mmol), and D 2 (4 ml) were equilibrated at room temperature for eight hours in the absence of light. Anhydrous CH 2 Cl 2 was added and the solution neutralised with K 2 C 3. The layers were then separated and the organics dried over MgS 4, filtered, and the solvent was allowed to evaporate slowly. The procedure was then repeated. -Benzyl-D 4 -pyrrole was then synthesised based on the literature procedure used previously. 1 Sodium hydride (60% dispersion in mineral oil, 0.17 g, 4.13 mmol) was added to anhydrous DMF (3.75 ml) in a nitrogen purged two-neck round-bottom flask. The solution was cooled to 0 C before pyrrole-d 5 (0.27 g, 3.75 mmol) in anhydrous DMF (1 ml) was added dropwise. The solution was allowed to warm to room temperature and was stirred for 30 minutes before cooling back to 0 C and benzyl bromide (0.45 ml, 3.75 mmol) was added dropwise. The solution was again allowed to warm to room temperature and was stirred for one hour. The solution was then added to H 2 and extracted with 1:1 hexane : Et 2. The combined organic layers were washed with H 2 before drying over MgS 4, filtering, and concentrating under reduced pressure. The crude product was purified by flash column chromatography (petrol : ethyl acetate (95:5), R f = 0.65) yielding the title compound (0.50 g, 83%) as a colourless oil with 85% deuterium incorporation, as determined by analysis of the 1 H MR spectra. 1 H MR (300 MHz; CDCl 3 ): δ H = (3H, m, ArH), (2H, m, ArH), 5.09 (2H, s, CH 2 Ph); 13 C{ 1 H} MR (75 MHz, CDCl 3 ): δ C = 138.3, 128.8, 127.8, 127.1, Benzyl-D 4 -pyrrole (0.16 g, 1 mmol), toluene (0.11 ml, 1 mmol), DB (0.018 ml, 0.15 mmol), and benzoyl chloride (0.14 ml, 1.2 mmol) were heated at 115 C according to the general procedure. Aliquots of 0.01 ml were taken every hour up to 6 hours and analysed using 1 H MR. The procedure was then repeated with -benzylpyrrole (0.16 g, 1 mmol). Comparison of the data showed essentially no difference in the rate of acylation between the deuterated and non-deuterated pyrroles, suggesting that re-aromatisation is not the rate determining step. S64

65 Conversion / % t / m Benzylpyrrole Benzyl D4 pyrrole The kinetic experiment was again repeated for -benzylpyrrole, taking aliquots at shorter time intervals to investigate whether there is a change in mechanism during the reaction. The smooth curve obtained suggests that a single mechanism operates throughout the reaction Conversion / % t / m S65

66 Acyl-DB Intermediate Analysis Benzoyl chloride (1) Cl 1 H MR (500 MHz; CDCl 3 ): δ H = 8.13 (2H, dd, J = 8.4, 1.2 Hz, o-arh), 7.69 (1H, tt, J = 7.4, 1.2 Hz, p-arh), 7.52 (2H, dd, J = 8.3, 7.6 Hz, m-arh); 13 C{ 1 H} MR (125 MHz, CDCl 3 ): δ C = 168.6, 135.5, 133.4, 131.6, IR (film, cm -1 ): ν max = 1770 (C=), 1730, 1595, ,5-Diazabicyclo[4.3.0]non-5-ene (DB) H MR (500 MHz; CDCl 3 ): δ H = 3.27 (2H, t, J = 5.5 Hz, H 2 ), 3.21 (2H, t, J = 6.8 Hz, H 6 ), 3.12 (2H, t, J = 6.0 Hz, H 4 ), 2.38 (2H, t, J = 7.8 Hz, H 8 ), 1.86 (2H, p, J = 7.3 Hz, H 7 ), 1.72 (2H, p, J = 5.8 Hz, H 3 ); 13 C{ 1 H} MR (125 MHz, CDCl 3 ): δ C = (C 9 ), 51.5 (C 6 ), 44.1 (C 2 ), 43.2 (C 4 ), 31.5 (C 8 ), 20.9 (C 3 ), 19.7 (C 7 ). -Acyl-DB Cl Intermediate (8) Cl Ph Benzoyl chloride (0.12 ml, 1 mmol) was added dropwise to a solution of DB (0.12 ml, 1 mmol) in CDCl 3. The solution turns yellow upon the addition of benzoyl chloride; after stirring at room temperature for two hours the colour had dissipated and complex 8 was formed in quantative yield, as shown by 1 H MR spectroscopy. The solution can be concentrated under reduced pressure to give a hygroscopic pale yellow powder. 1 H MR (500 MHz; CDCl 3 ): δ H = (2H, m, o-arh), (1H, m, p-arh), (2H, m, m-arh), 3.96 (2H, t, J = 7.5 Hz, H 6 ), (2H, m, H 2 ), (2H, br. s, H 4 ), (2H, m, H 8 ), (2H, m, H 7 ), (2H, m, H 3 ); 13 C{ 1 H} MR (125 MHz, CDCl 3 ): δ C = 170.9, 167.9, 133.5, 131.2, 129.6, 128.9, 55.4, 46.4, 44.6, 34.3, 19.7, 18.6; IR S66

Supporting Information. Table of Contents. 1. General Notes Experimental Details 3-12

Supporting Information. Table of Contents. 1. General Notes Experimental Details 3-12 Supporting Information Table of Contents page 1. General Notes 2 2. Experimental Details 3-12 3. NMR Support for Timing of Claisen/Diels-Alder/Claisen 13 4. 1 H and 13 C NMR 14-37 General Notes All reagents

More information

Tetrahydrofuran (THF) was distilled from benzophenone ketyl radical under an argon

Tetrahydrofuran (THF) was distilled from benzophenone ketyl radical under an argon SUPPLEMENTARY METHODS Solvents, reagents and synthetic procedures All reactions were carried out under an argon atmosphere unless otherwise specified. Tetrahydrofuran (THF) was distilled from benzophenone

More information

Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801.

Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801. Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801. Alan L. Sewell a, Mathew V. J. Villa a, Mhairi Matheson a, William G. Whittingham b, Rodolfo Marquez a*. a) WestCHEM, School of Chemistry,

More information

The First Asymmetric Total Syntheses and. Determination of Absolute Configurations of. Xestodecalactones B and C

The First Asymmetric Total Syntheses and. Determination of Absolute Configurations of. Xestodecalactones B and C Supporting Information The First Asymmetric Total Syntheses and Determination of Absolute Configurations of Xestodecalactones B and C Qiren Liang, Jiyong Zhang, Weiguo Quan, Yongquan Sun, Xuegong She*,,

More information

Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition

Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition Synthesis of fluorophosphonylated acyclic nucleotide analogues via Copper (I)- catalyzed Huisgen 1-3 dipolar cycloaddition Sonia Amel Diab, Antje Hienzch, Cyril Lebargy, Stéphante Guillarme, Emmanuel fund

More information

Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2MgCl 2 2LiCl ** Stefan H. Wunderlich and Paul Knochel*

Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2MgCl 2 2LiCl ** Stefan H. Wunderlich and Paul Knochel* Efficient Mono- and Bis-Functionalization of 3,6-Dichloropyridazine using (tmp) 2 Zn 2Mg 2 2Li ** Stefan H. Wunderlich and Paul Knochel* Ludwig Maximilians-Universität München, Department Chemie & Biochemie

More information

Iron Catalyzed Cross Couplings of Azetidines: Application to an Improved Formal Synthesis of a Pharmacologically Active Molecule

Iron Catalyzed Cross Couplings of Azetidines: Application to an Improved Formal Synthesis of a Pharmacologically Active Molecule Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Iron Catalyzed Cross Couplings of Azetidines: Application to an Improved Formal Synthesis of a

More information

Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4)

Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4) Supplementary Note 1 : Chemical synthesis of (E/Z)-4,8-dimethylnona-2,7-dien-4-ol (4) A solution of propenyl magnesium bromide in THF (17.5 mmol) under nitrogen atmosphere was cooled in an ice bath and

More information

Curtius-Like Rearrangement of Iron-Nitrenoid Complex and. Application in Biomimetic Synthesis of Bisindolylmethanes

Curtius-Like Rearrangement of Iron-Nitrenoid Complex and. Application in Biomimetic Synthesis of Bisindolylmethanes Supporting Information Curtius-Like Rearrangement of Iron-itrenoid Complex and Application in Biomimetic Synthesis of Bisindolylmethanes Dashan Li,, Ting Wu,, Kangjiang Liang,, and Chengfeng Xia*,, State

More information

Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is The Royal Society of Chemistry 2012

Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications This journal is The Royal Society of Chemistry 2012 Supporting Information. Experimental Section: Summary scheme H 8 H H H 9 a H C 3 1 C 3 A H H b c C 3 2 3 C 3 H H d e C 3 4 5 C 3 H f g C 2 6 7 C 2 H a C 3 B H c C 3 General experimental details: All solvents

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2006 69451 Weinheim, Germany A Highly Enantioselective Brønsted Acid Catalyst for the Strecker Reaction Magnus Rueping, * Erli Sugiono and Cengiz Azap General: Unless otherwise

More information

Reactions. James C. Anderson,* Rachel H. Munday. School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK

Reactions. James C. Anderson,* Rachel H. Munday. School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK Vinyl-dimethylphenylsilanes as Safety Catch Silanols in Fluoride free Palladium Catalysed Cross Coupling Reactions. James C. Anderson,* Rachel H. Munday School of Chemistry, University of Nottingham, Nottingham,

More information

Supporting Material. 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials

Supporting Material. 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials Supporting Material 2-Oxo-tetrahydro-1,8-naphthyridine-Based Protein Farnesyltransferase Inhibitors as Antimalarials Srinivas Olepu a, Praveen Kumar Suryadevara a, Kasey Rivas b, Christophe L. M. J. Verlinde

More information

A Photocleavable Linker for the Chemoselective Functionalization of Biomaterials

A Photocleavable Linker for the Chemoselective Functionalization of Biomaterials Electronic Supplementary Information A otocleavable Linker for the Chemoselective Functionalization of Biomaterials Liz Donovan and Paul A. De Bank* Department of armacy and armacology and Centre for Regenerative

More information

Supporting Information

Supporting Information Supporting Information ACA: A Family of Fluorescent Probes that Bind and Stain Amyloid Plaques in Human Tissue Willy M. Chang, a Marianna Dakanali, a Christina C. Capule, a Christina J. Sigurdson, b Jerry

More information

Supporting Information

Supporting Information An Improved ynthesis of the Pyridine-Thiazole Cores of Thiopeptide Antibiotics Virender. Aulakh, Marco A. Ciufolini* Department of Chemistry, University of British Columbia 2036 Main Mall, Vancouver, BC

More information

Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed. Cascade Trifluoromethylation/Cyclization of. 2-(3-Arylpropioloyl)benzaldehydes

Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed. Cascade Trifluoromethylation/Cyclization of. 2-(3-Arylpropioloyl)benzaldehydes Supporting Information to Synthesis of Trifluoromethylated Naphthoquinones via Copper-Catalyzed Cascade Trifluoromethylation/Cyclization of 2-(3-Arylpropioloyl)benzaldehydes Yan Zhang*, Dongmei Guo, Shangyi

More information

Phil S. Baran*, Jeremy M. Richter and David W. Lin SUPPORTING INFORMATION

Phil S. Baran*, Jeremy M. Richter and David W. Lin SUPPORTING INFORMATION Direct Coupling of Pyrroles with Carbonyl Compounds: Short, Enantioselective Synthesis of (S)-Ketorolac Phil S. Baran*, Jeremy M. Richter and David W. Lin SUPPRTIG IFRMATI General Procedures. All reactions

More information

Supporting Information

Supporting Information Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2012 Subcellular Localization and Activity of Gambogic Acid Gianni Guizzunti,* [b] Ayse Batova, [a] Oraphin Chantarasriwong,

More information

Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions

Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions SUPPORTIG IFORMATIO Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions Alexey Volkov, a Fredrik Tinnis, a and Hans Adolfsson.* a a Department of Organic Chemistry,

More information

Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A

Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A Fuerst et al. Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers: Approaches to Diazonamide A S1 Supporting Information for Synthesis of C(3) Benzofuran Derived Bis-Aryl Quaternary Centers:

More information

Triazabicyclodecene: an Effective Isotope. Exchange Catalyst in CDCl 3

Triazabicyclodecene: an Effective Isotope. Exchange Catalyst in CDCl 3 Triazabicyclodecene: an Effective Isotope Exchange Catalyst in CDCl 3 Supporting Information Cyrille Sabot, Kanduluru Ananda Kumar, Cyril Antheaume, Charles Mioskowski*, Laboratoire de Synthèse Bio-rganique,

More information

SYNTHESIS OF A 3-THIOMANNOSIDE

SYNTHESIS OF A 3-THIOMANNOSIDE Supporting Information SYNTHESIS OF A 3-THIOMANNOSIDE María B Comba, Alejandra G Suárez, Ariel M Sarotti, María I Mangione* and Rolando A Spanevello and Enrique D V Giordano Instituto de Química Rosario,

More information

Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain

Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain rganic Lett. (Supporting Information) 1 Synthetic Studies on Norissolide; Enantioselective Synthesis of the Norrisane Side Chain Charles Kim, Richard Hoang and Emmanuel A. Theodorakis* Department of Chemistry

More information

Brønsted Base-Catalyzed Reductive Cyclization of Alkynyl. α-iminoesters through Auto-Tandem Catalysis

Brønsted Base-Catalyzed Reductive Cyclization of Alkynyl. α-iminoesters through Auto-Tandem Catalysis Supporting Information Brønsted Base-Catalyzed Reductive Cyclization of Alkynyl α-iminoesters through Auto-Tandem Catalysis Azusa Kondoh, b and Masahiro Terada* a a Department of Chemistry, Graduate School

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2006 69451 Weinheim, Germany rganocatalytic Conjugate Addition of Malonates to a,ß-unsaturated Aldehydes: Asymmetric Formal Synthesis of (-)-Paroxetine, Chiral Lactams

More information

Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol.

Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol. Tetrahedron Letters 1 Pergamon TETRAHEDRN LETTERS Supplementary Material for: Unexpected Decarbonylation during an Acid- Mediated Cyclization to Access the Carbocyclic Core of Zoanthenol. Jennifer L. Stockdill,

More information

Effect of Conjugation and Aromaticity of 3,6 Di-substituted Carbazole On Triplet Energy

Effect of Conjugation and Aromaticity of 3,6 Di-substituted Carbazole On Triplet Energy Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2018 Electronic Supporting Information (ESI) for Effect of Conjugation and Aromaticity of 3,6 Di-substituted

More information

Supporting Information. (1S,8aS)-octahydroindolizidin-1-ol.

Supporting Information. (1S,8aS)-octahydroindolizidin-1-ol. SI-1 Supporting Information Non-Racemic Bicyclic Lactam Lactones Via Regio- and cis-diastereocontrolled C H insertion. Asymmetric Synthesis of (8S,8aS)-octahydroindolizidin-8-ol and (1S,8aS)-octahydroindolizidin-1-ol.

More information

Supporting Information

Supporting Information Supporting Information Total Synthesis of (±)-Grandilodine B Chunyu Wang, Zhonglei Wang, Xiaoni Xie, Xiaotong Yao, Guang Li, and Liansuo Zu* School of Pharmaceutical Sciences, Tsinghua University, Beijing,

More information

Supporting Information

Supporting Information 1 A regiodivergent synthesis of ring A C-prenyl flavones Alberto Minassi, Anna Giana, Abdellah Ech-Chahad and Giovanni Appendino* Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche

More information

hydroxyanthraquinones related to proisocrinins

hydroxyanthraquinones related to proisocrinins Supporting Information for Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins Joyeeta Roy, Tanushree Mal, Supriti Jana and Dipakranjan Mal* Address: Department of Chemistry,

More information

Supporting Information

Supporting Information Supporting Information Silver-Mediated Oxidative Trifluoromethylation of Alcohols to Alkyl Trifluoromethyl Ethers Jian-Bo Liu, Xiu-Hua Xu, and Feng-Ling Qing Table of Contents 1. General Information --------------------------------------------------------------------------2

More information

for Brønsted Base-Mediated Aziridination of 2- Alkyl Substituted-1,3-Dicarbonyl Compounds and 2-Acyl-1,4-Dicarbonyl Compounds by Iminoiodanes

for Brønsted Base-Mediated Aziridination of 2- Alkyl Substituted-1,3-Dicarbonyl Compounds and 2-Acyl-1,4-Dicarbonyl Compounds by Iminoiodanes 10.1071/CH16580_AC CSIRO 2017 Australian Journal of Chemistry 2017, 70(4), 430-435 Supplementary Material for Brønsted Base-Mediated Aziridination of 2- Alkyl Substituted-1,3-Dicarbonyl Compounds and 2-Acyl-1,4-Dicarbonyl

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2012 69451 Weinheim, Germany Substitution of Two Fluorine Atoms in a Trifluoromethyl Group: Regioselective Synthesis of 3-Fluoropyrazoles** Kohei Fuchibe, Masaki Takahashi,

More information

Metal-free general procedure for oxidation of secondary amines to nitrones

Metal-free general procedure for oxidation of secondary amines to nitrones S1 Supporting information Metal-free general procedure for oxidation of secondary amines to nitrones Carolina Gella, Èric Ferrer, Ramon Alibés, Félix Busqué,* Pedro de March, Marta Figueredo,* and Josep

More information

Supporting Information

Supporting Information Supporting Information Construction of Highly Functional α-amino itriles via a ovel Multicomponent Tandem rganocatalytic Reaction: a Facile Access to α-methylene γ-lactams Feng Pan, Jian-Ming Chen, Zhe

More information

Supporting Information

Supporting Information Supporting Information Divergent Reactivity of gem-difluoro-enolates towards Nitrogen Electrophiles: Unorthodox Nitroso Aldol Reaction for Rapid Synthesis of -Ketoamides Mallu Kesava Reddy, Isai Ramakrishna,

More information

SUPPORTING INFORMATION

SUPPORTING INFORMATION UPPRTING INFRMATIN Application of a Rhodium-Catalyzed Addition/Cyclization equence Toward the ynthesis of Polycyclic eteroaromatics Nai-Wen Tseng and Mark Lautens* Davenport Laboratories, Chemistry Department,

More information

Supporting Information for

Supporting Information for Page of 0 0 0 0 Submitted to The Journal of Organic Chemistry S Supporting Information for Syntheses and Spectral Properties of Functionalized, Water-soluble BODIPY Derivatives Lingling Li, Junyan Han,

More information

Diaza [1,4] Wittig-type rearrangement of N-allylic-N- Boc-hydrazines into -amino-n-boc-enamines

Diaza [1,4] Wittig-type rearrangement of N-allylic-N- Boc-hydrazines into -amino-n-boc-enamines Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2016 Diaza [1,4] Wittig-type rearrangement of N-allylic-N- Boc-hydrazines into -amino-n-boc-enamines

More information

All solvents and reagents were used as obtained. 1H NMR spectra were recorded with a Varian

All solvents and reagents were used as obtained. 1H NMR spectra were recorded with a Varian SUPPLEMETARY OTE Chemistry All solvents and reagents were used as obtained. 1H MR spectra were recorded with a Varian Inova 600 MR spectrometer and referenced to dimethylsulfoxide. Chemical shifts are

More information

Supporting Information

Supporting Information Supporting Information Synthesis of H-Indazoles from Imidates and Nitrosobenzenes via Synergistic Rhodium/Copper Catalysis Qiang Wang and Xingwei Li* Dalian Institute of Chemical Physics, Chinese Academy

More information

Synthesis of borinic acids and borinate adducts using diisopropylaminoborane

Synthesis of borinic acids and borinate adducts using diisopropylaminoborane Synthesis of borinic acids and borinate adducts using diisopropylaminoborane Ludovic Marciasini, Bastien Cacciuttolo, Michel Vaultier and Mathieu Pucheault* Institut des Sciences Moléculaires, UMR 5255,

More information

Synthesis and Use of QCy7-derived Modular Probes for Detection and. Imaging of Biologically Relevant Analytes. Supplementary Methods

Synthesis and Use of QCy7-derived Modular Probes for Detection and. Imaging of Biologically Relevant Analytes. Supplementary Methods Synthesis and Use of QCy7-derived Modular Probes for Detection and Imaging of Biologically Relevant Analytes Supplementary Methods Orit Redy a, Einat Kisin-Finfer a, Shiran Ferber b Ronit Satchi-Fainaro

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Supporting Information Pd-Catalyzed C-H Activation/xidative Cyclization of Acetanilide with orbornene:

More information

Mild Decarboxylative Activation of Malonic Acid Derivatives by 1,1 - Carbonyldiimidazole. Danny Lafrance*, Paul Bowles, Kyle Leeman and Robert Rafka

Mild Decarboxylative Activation of Malonic Acid Derivatives by 1,1 - Carbonyldiimidazole. Danny Lafrance*, Paul Bowles, Kyle Leeman and Robert Rafka Mild Decarboxylative Activation of Malonic Acid Derivatives by 1,1 - Carbonyldiimidazole. Danny Lafrance*, Paul Bowles, Kyle Leeman and Robert Rafka Development Science and Technology, Pfizer Inc., Eastern

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 214 Supporting Information Rapid and sensitive detection of acrylic acid using a novel fluorescence

More information

dichloropyrimidine (1.5 g, 10.1 mmol) in THF (10 ml) added at -116 C under nitrogen atmosphere.

dichloropyrimidine (1.5 g, 10.1 mmol) in THF (10 ml) added at -116 C under nitrogen atmosphere. Supporting Information Experimental The presence of atropisomerism arising from diastereoisomerism is indicated in the 13 C spectra of the relevant compounds with the second isomer being indicated with

More information

SUPPORTING INFORMATION

SUPPORTING INFORMATION SUPPRTING INFRMATIN A Direct, ne-step Synthesis of Condensed Heterocycles: A Palladium-Catalyzed Coupling Approach Farnaz Jafarpour and Mark Lautens* Davenport Chemical Research Laboratories, Chemistry

More information

An Efficient Total Synthesis and Absolute Configuration. Determination of Varitriol

An Efficient Total Synthesis and Absolute Configuration. Determination of Varitriol An Efficient Total Synthesis and Absolute Configuration Determination of Varitriol Ryan T. Clemens and Michael P. Jennings * Department of Chemistry, University of Alabama, 500 Campus Dr. Tuscaloosa, AL

More information

Supporting Information. Efficient N-arylation and N-alkenylation of the five. DNA/RNA nucleobases

Supporting Information. Efficient N-arylation and N-alkenylation of the five. DNA/RNA nucleobases Supporting Information Efficient -arylation and -alkenylation of the five DA/RA nucleobases Mikkel F. Jacobsen, Martin M. Knudsen and Kurt V. Gothelf* Center for Catalysis and Interdisciplinary anoscience

More information

Parallel sheet structure in cyclopropane γ-peptides stabilized by C-H O hydrogen bonds

Parallel sheet structure in cyclopropane γ-peptides stabilized by C-H O hydrogen bonds Parallel sheet structure in cyclopropane γ-peptides stabilized by C- hydrogen bonds M. Khurram N. Qureshi and Martin D. Smith* Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge

More information

Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins

Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins S1 Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins Antonia Kouridaki, Tamsyn Montagnon, Maria Tofi and Georgios Vassilikogiannakis* Department of

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Material (ESI) for Dalton Transactions. This journal is The Royal Society of Chemistry 2016 Electronic Supplementary Information for uminum complexes containing salicylbenzoxazole

More information

Supporting Information for. A New Method for the Cleavage of Nitrobenzyl Amides and Ethers

Supporting Information for. A New Method for the Cleavage of Nitrobenzyl Amides and Ethers SI- 1 Supporting Information for A ew Method for the Cleavage of itrobenzyl Amides and Ethers Seo-Jung Han, Gabriel Fernando de Melo, and Brian M. Stoltz* The Warren and Katharine Schlinger Laboratory

More information

Supporting Information for: Tuning the Binding Properties of a New Heteroditopic Salt Receptor Through Embedding in a Polymeric System

Supporting Information for: Tuning the Binding Properties of a New Heteroditopic Salt Receptor Through Embedding in a Polymeric System Supporting Information for: Tuning the Binding Properties of a ew Heteroditopic Salt Receptor Through Embedding in a Polymeric System Jan Romanski* and Piotr Piątek* Department of Chemistry, University

More information

Suzuki-Miyaura Coupling of Heteroaryl Boronic Acids and Vinyl Chlorides

Suzuki-Miyaura Coupling of Heteroaryl Boronic Acids and Vinyl Chlorides Suzuki-Miyaura Coupling of Heteroaryl Boronic Acids and Vinyl Chlorides Ashish Thakur, Kainan Zhang, Janis Louie* SUPPORTING INFORMATION General Experimental: All reactions were conducted under an atmosphere

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2014 Electronic Supplementary Information Visible light-mediated dehydrogenative

More information

Block: Synthesis, Aggregation-Induced Emission, Two-Photon. Absorption, Light Refraction, and Explosive Detection

Block: Synthesis, Aggregation-Induced Emission, Two-Photon. Absorption, Light Refraction, and Explosive Detection Electronic Supplementary Information (ESI) Luminogenic Materials Constructed from Tetraphenylethene Building Block: Synthesis, Aggregation-Induced Emission, Two-Photon Absorption, Light Refraction, and

More information

Supporting Information For:

Supporting Information For: Supporting Information For: Peptidic α-ketocarboxylic Acids and Sulfonamides as Inhibitors of Protein Tyrosine Phosphatases Yen Ting Chen, Jian Xie, and Christopher T. Seto* Department of Chemistry, Brown

More information

Synthesis of Secondary and Tertiary Amine- Containing MOFs: C-N Bond Cleavage during MOF Synthesis

Synthesis of Secondary and Tertiary Amine- Containing MOFs: C-N Bond Cleavage during MOF Synthesis Electronic Supplementary Material (ESI) for CrystEngComm. This journal is The Royal Society of Chemistry 2015 Supporting Information Synthesis of Secondary and Tertiary Amine- Containing MFs: C-N Bond

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Supplementary Method Synthesis of 2-alkyl-MPT(R) General information (R) enantiomer of 2-alkyl (18:1) MPT (hereafter designated as 2-alkyl- MPT(R)), was synthesized as previously described 1, with some

More information

1G (bottom) with the phase-transition temperatures in C and associated enthalpy changes (in

1G (bottom) with the phase-transition temperatures in C and associated enthalpy changes (in Supplementary Figure 1. Optical properties of 1 in various solvents. UV/Vis (left axis) and fluorescence spectra (right axis, ex = 420 nm) of 1 in hexane (blue lines), toluene (green lines), THF (yellow

More information

How to build and race a fast nanocar Synthesis Information

How to build and race a fast nanocar Synthesis Information How to build and race a fast nanocar Synthesis Information Grant Simpson, Victor Garcia-Lopez, Phillip Petemeier, Leonhard Grill*, and James M. Tour*, Department of Physical Chemistry, University of Graz,

More information

Pyridine-Containing m-phenylene Ethynylene Oligomers Having Tunable Basicities

Pyridine-Containing m-phenylene Ethynylene Oligomers Having Tunable Basicities Supporting nformation Pyridine-Containing m-phenylene Ethynylene ligomers Having Tunable Basicities Jennifer M. Heemstra and Jeffrey S. Moore* Departments of Chemistry and Materials Science & Engineering,

More information

Bulletin of the Chemical Society of Japan

Bulletin of the Chemical Society of Japan Supporting Information Bulletin of the Chemical Society of Japan Enantioselective Copper-Catalyzed 1,4-Addition of Dialkylzincs to Enones Followed by Trapping with Allyl Iodide Derivatives Kenjiro Kawamura,

More information

Chia-Shing Wu, Huai-An Lu, Chiao-Pei Chen, Tzung-Fang Guo and Yun Chen*

Chia-Shing Wu, Huai-An Lu, Chiao-Pei Chen, Tzung-Fang Guo and Yun Chen* Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry Supporting Information Water/alcohol soluble electron injection material containing azacrown ether groups: Synthesis, characterization

More information

Supporting Information for

Supporting Information for Supporting Information for Room Temperature Palladium-Catalyzed Arylation of Indoles icholas R. Deprez, Dipannita Kalyani, Andrew Krause, and Melanie S. Sanford* University of Michigan Department of Chemistry,

More information

Supporting Information. A rapid and efficient synthetic route to terminal. arylacetylenes by tetrabutylammonium hydroxide- and

Supporting Information. A rapid and efficient synthetic route to terminal. arylacetylenes by tetrabutylammonium hydroxide- and Supporting Information for A rapid and efficient synthetic route to terminal arylacetylenes by tetrabutylammonium hydroxide- and methanol-catalyzed cleavage of 4-aryl-2-methyl-3- butyn-2-ols Jie Li and

More information

Poly(4-vinylimidazolium)s: A Highly Recyclable Organocatalyst Precursor for. Benzoin Condensation Reaction

Poly(4-vinylimidazolium)s: A Highly Recyclable Organocatalyst Precursor for. Benzoin Condensation Reaction Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 24 Supporting Information Poly(4-vinylimidazolium)s: A Highly Recyclable rganocatalyst Precursor

More information

Supplementary Material

Supplementary Material 10.1071/CH13324_AC CSIRO 2013 Australian Journal of Chemistry 2013, 66(12), 1570-1575 Supplementary Material A Mild and Convenient Synthesis of 1,2,3-Triiodoarenes via Consecutive Iodination/Diazotization/Iodination

More information

Supporting Information

Supporting Information Supporting Information (Tetrahedron. Lett.) Cavitands with Inwardly and Outwardly Directed Functional Groups Mao Kanaura a, Kouhei Ito a, Michael P. Schramm b, Dariush Ajami c, and Tetsuo Iwasawa a * a

More information

Tuning Porosity and Activity of Microporous Polymer Network Organocatalysts by Co-Polymerisation

Tuning Porosity and Activity of Microporous Polymer Network Organocatalysts by Co-Polymerisation Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Supporting Information Tuning Porosity and Activity of Microporous Polymer Network Organocatalysts

More information

Supporting Information

Supporting Information Supporting Information Precision Synthesis of Poly(-hexylpyrrole) and its Diblock Copolymer with Poly(p-phenylene) via Catalyst-Transfer Polycondensation Akihiro Yokoyama, Akira Kato, Ryo Miyakoshi, and

More information

Electronic Supplementary Information. An Ultrafast Surface-Bound Photo-active Molecular. Motor

Electronic Supplementary Information. An Ultrafast Surface-Bound Photo-active Molecular. Motor This journal is The Royal Society of Chemistry and wner Societies 2013 Electronic Supplementary Information An Ultrafast Surface-Bound Photo-active Molecular Motor Jérôme Vachon, [a] Gregory T. Carroll,

More information

Maksim A. Kolosov*, Olesia G. Kulyk, Elena G. Shvets, Valeriy D. Orlov

Maksim A. Kolosov*, Olesia G. Kulyk, Elena G. Shvets, Valeriy D. Orlov 1 Synthesis of 5-cinnamoyl-3,4-dihydropyrimidine-2(1H)-ones Supplementary Information Maksim A. Kolosov*, lesia G. Kulyk, Elena G. Shvets, Valeriy D. rlov Department of organic chemistry, V.N.Karazin Kharkiv

More information

Sequential dynamic structuralisation by in situ production of

Sequential dynamic structuralisation by in situ production of Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2017 Electronic Supplementary Information Sequential dynamic structuralisation by in situ production

More information

Synthesis of Glaucogenin D, a Structurally Unique. Disecopregnane Steroid with Potential Antiviral Activity

Synthesis of Glaucogenin D, a Structurally Unique. Disecopregnane Steroid with Potential Antiviral Activity Supporting Information for Synthesis of Glaucogenin D, a Structurally Unique Disecopregnane Steroid with Potential Antiviral Activity Jinghan Gui,* Hailong Tian, and Weisheng Tian* Key Laboratory of Synthetic

More information

An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters

An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters S1 An unusual dianion equivalent from acylsilanes for the synthesis of substituted β-keto esters Chris V. Galliford and Karl A. Scheidt* Department of Chemistry, Northwestern University, 2145 Sheridan

More information

Ring-Opening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols

Ring-Opening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols Ring-pening / Fragmentation of Dihydropyrones for the Synthesis of Homopropargyl Alcohols Jumreang Tummatorn, and Gregory B. Dudley, * Department of Chemistry and Biochemistry, Florida State University,

More information

Supporting Information for:

Supporting Information for: Supporting Information for: Photoenolization of 2-(2-Methyl Benzoyl) Benzoic Acid, Methyl Ester: The Effect of The Lifetime of the E Photoenol on the Photochemistry Armands Konosonoks, P. John Wright,

More information

Supplementary Materials

Supplementary Materials Supplementary Materials ORTHOGOALLY POSITIOED DIAMIO PYRROLE- AD IMIDAZOLE- COTAIIG POLYAMIDES: SYTHESIS OF 1-(3-SUBSTITUTED-PROPYL)-4- ITROPYRROLE-2-CARBOXYLIC ACID AD 1-(3-CHLOROPROPYL)-4- ITROIMIDAZOLE-2-CARBOXYLIC

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION doi:10.1038/nature22309 Chemistry All reagents and solvents were commercially available unless otherwise noted. Analytical LC-MS was carried out using a Shimadzu LCMS-2020 with UV detection monitored between

More information

Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-on Fluorescent Probe

Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-on Fluorescent Probe Supporting Information for Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-on Fluorescent Probe Ho Yu Au-Yeung, Jefferson Chan, Teera Chantarojsiri and Christopher J. Chang* Departments

More information

Regioselective Silylation of Pyranosides Using a Boronic Acid / Lewis Base Co-Catalyst System

Regioselective Silylation of Pyranosides Using a Boronic Acid / Lewis Base Co-Catalyst System Regioselective Silylation of Pyranosides Using a Boronic Acid / Lewis Base Co-Catalyst System Doris Lee and Mark S. Taylor* Department of Chemistry, Lash Miller Laboratories, University of Toronto 80 St.

More information

4023 Synthesis of cyclopentanone-2-carboxylic acid ethyl ester from adipic acid diethyl ester

4023 Synthesis of cyclopentanone-2-carboxylic acid ethyl ester from adipic acid diethyl ester NP 4023 Synthesis of cyclopentanone-2-carboxylic acid ethyl ester from adipic acid diethyl ester NaEt C 10 H 18 4 Na C 2 H 6 C 8 H 12 3 (202.2) (23.0) (46.1) (156.2) Classification Reaction types and substance

More information

Supporting Information

Supporting Information Meyer, Ferreira, and Stoltz: Diazoacetoacetic acid Supporting Information S1 2-Diazoacetoacetic Acid, an Efficient and Convenient Reagent for the Synthesis of Substituted -Diazo- -ketoesters Michael E.

More information

Supporting Information

Supporting Information Supporting Information Organocatalytic Enantioselective Formal Synthesis of Bromopyrrole Alkaloids via Aza-Michael Addition Su-Jeong Lee, Seok-Ho Youn and Chang-Woo Cho* Department of Chemistry, Kyungpook

More information

Experimental details

Experimental details Supporting Information for A scalable synthesis of the (S)-4-(tert-butyl)-2-(pyridin-2-yl)-4,5-dihydrooxazole ((S)-t-BuPyx) ligand Hideki Shimizu 1,2, Jeffrey C. Holder 1 and Brian M. Stoltz* 1 Address:

More information

Accessory Information

Accessory Information Accessory Information Synthesis of 5-phenyl 2-Functionalized Pyrroles by amino Heck and tandem amino Heck Carbonylation reactions Shazia Zaman, *A,B Mitsuru Kitamura B, C and Andrew D. Abell A *A Department

More information

Supporting Information: Regioselective esterification of vicinal diols on monosaccharide derivatives via

Supporting Information: Regioselective esterification of vicinal diols on monosaccharide derivatives via Supporting Information: Regioselective esterification of vicinal diols on monosaccharide derivatives via Mitsunobu reactions. Guijun Wang,*Jean Rene Ella-Menye, Michael St. Martin, Hao Yang, Kristopher

More information

Preparation of the reagent TMPMgCl LiCl [1] (1):

Preparation of the reagent TMPMgCl LiCl [1] (1): Regio- and Chemoselective Magnesiation of Protected Uracils and Thiouracils using TMPMgCl LiCl and TMP 2 Mg 2LiCl upporting nformation Marc Mosrin, adège Boudet and Paul Knochel Ludwig-Maximilians-Universität

More information

Supporting Information

Supporting Information Supporting Information Towards Singlet Oxygen Delivery at a Measured Rate: A Selfreporting Photosensitizer Sundus Erbas-Cakmak #, Engin U. Akkaya # * # UNAM-National Nanotechnology Research Center, Bilkent

More information

Supporting Information:

Supporting Information: Electronic Supplementary Material (ESI) for Green Chemistry. This journal is The Royal Society of Chemistry 2016 Supporting Information: A metal free reduction of aryl-n-nitrosamines to corresponding hydrazines

More information

Anion binding vs. sulfonamide deprotonation in functionalised ureas

Anion binding vs. sulfonamide deprotonation in functionalised ureas S Anion binding vs. sulfonamide deprotonation in functionalised ureas Claudia Caltagirone, Gareth W. Bates, Philip A. Gale* and Mark E. Light Supplementary information Experimental Section General remarks:

More information

J. Am. Chem. Soc. Supporting Information Page 1

J. Am. Chem. Soc. Supporting Information Page 1 J. Am. Chem. Soc. Supporting Information Page 1 Short Total Synthesis of (±)-Sceptrin Phil S. Baran*, Alexandros L. Zografos, and Daniel P. Malley Contribution from the Department of Chemistry, The Scripps

More information

Supplemental material for: Concise Total Syntheses of (±)-Mesembrane and (±)-Crinane. Table of Contents

Supplemental material for: Concise Total Syntheses of (±)-Mesembrane and (±)-Crinane. Table of Contents Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2015 Das, De, Shubhashish and Bisai Supporting Information 1 Supplemental material

More information

Figure S1 - Enzymatic titration of HNE and GS-HNE.

Figure S1 - Enzymatic titration of HNE and GS-HNE. Figure S1 - Enzymatic titration of HNE and GS-HNE. Solutions of HNE and GS-HNE were titrated through their reduction to the corresponding alchools catalyzed by AR, monitoring the decrease in absorbance

More information

Indium Triflate-Assisted Nucleophilic Aromatic Substitution Reactions of. Nitrosobezene-Derived Cycloadducts with Alcohols

Indium Triflate-Assisted Nucleophilic Aromatic Substitution Reactions of. Nitrosobezene-Derived Cycloadducts with Alcohols Supporting Information Indium Triflate-Assisted ucleophilic Aromatic Substitution Reactions of itrosobezene-derived Cycloadducts with Alcohols Baiyuan Yang and Marvin J. Miller* Department of Chemistry

More information