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

Size: px
Start display at page:

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

Transcription

1 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, University of Glasgow, G12 8QQ, UK. b) Syngenta, Jealott s Hill Research Station, Bracknell, Berkshire, RG42 6EY. r.marquez@chem.gla.ac.uk Supporting Information Experimental Details pg. 2 Spectra Data... pg.14 1

2 General Conditions. All reactions were performed in oven-dried glassware under an inert argon atmosphere unless otherwise stated. Tetrahydrofuran (THF), diethyl ether, and dichloromethane (DCM) were purified through a Pure Solv 400-5MD solvent purification system (Innovative Technology, Inc). All reagents were used as received, unless otherwise stated. Solvents were evaporated under reduced pressure at 40 C using a Buchi Rotavapor. IR spectra were recorded as thin films on NaCl plates using a JASCO FT/IR410 Fourier Transform spectrometer. Only diagnostic absorptions (ν max ) are reported in wavenumbers (cm -1 ). Proton magnetic resonance spectra ( 1 H NMR) and carbon magnetic resonance spectra ( 13 C NMR) were recorded at 400MHz and 100MHz or at 500MHz and 125MHz using either a Bruker DPX Avance400 instrument or a Bruker Avance III 500 instrument. Chemical shifts (δ) are reported in parts per million (ppm) and are referenced to the residual solvent peak. The order of citation in parentheses is (1) number of equivalent nuclei (by integration), (2) multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b = broad, dm = double multiplet), and (3) coupling constant (J) quoted in Hertz to the nearest 0.1 Hz. High resolution mass spectra were recorded on a JEOL JMS-700 spectrometer by electrospray and chemical ionisation mass spectrometer operating at a resolution of full widths at half height. Flash chromatography was performed using silica gel (Fluorochem Silica Gel 60, micron) as the stationary phase. TLC was performed on aluminium sheets pre-coated 2

3 with silica (Merck Silica Gel 60 F 254 ). The plates were visualised by the quenching of UV fluorescence (λ max 254nm) and/or by staining with anisaldehyde, potassium permanganate, iodine or cerium ammonium molybdate followed by heating. N-Formyl-(R)-2,2,5,5-tetramethyl-[1,3]dioxane-4-carboxylic acid amide, 9. A solution of the (D-) pantolactone derived amide 8 (591 mg) in anhydrous THF (10 ml) was cooled to 0 o C before being treated with n-buli (1.37 ml, 1.1 mmol, 1.6 M solution in hexanes). The reaction mixture was then stirred at 0 o C for 5 minutes before being treated with N-formylbenzotriazole (551 mg, 1.2 mmol). The resulting mixture was then allowed to warm up to room temperature and then stirred for a further 2 hours. The reaction mixture was diluted with t-butylmethyl ether (10 ml), and quenched with a satd. aq. NaHCO 3 solution (10 ml). The aqueous phase was then extracted with diethyl ether (3 x 20 ml) and the combined organic layers dried over Na 2 SO 4. The solvent was removed under vacuum to afford the crude product, which was then purified by flash column chromatography (silica gel, elution gradient 10% to 20% ethyl acetate in petroleum ether) to afford 431 mg (64%) of the desired N-formyl imide 9 as a white solid. 1 H NMR (400MHz, CDCl 3 ) δ: 9.08 (1H, d, J = 10.4 Hz), 8.80 (1H, bs), 4.12 (1H, s), 3.65 (1H, d, J = 11.8 Hz), 3.27 (1H, d, J = 11.8 Hz), 1.41 (3H, s), 1.39 (3H, s), 0.99 (3H, s), 0.98 (3H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 170.6, 161.4, 99.7, 77.0, 71.1, 33.3, 29.3, 21.7, 18.9, IR ν max (film)/cm , 3268, 2874, 1743, HRMS calcd for C 10 H 18 O 4 N (M+H + ): Found [α] D (c = 1.4, CHCl 3 ). 3

4 (R,E)-Benzyl-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 10E and (R,Z)-Benzyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 10Z. A solution of n-formyl imide 9 (2.16 g, 9.9 mmol) in benzene (100 ml) was treated with benzyltriphenylphosphoranylidene (12.30 g, 30 mmol) and the resulting mixture heated to 95 o C for 19 h. Upon reaction completion as indicated by TLC analysis, the solvent was removed under vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient 10% to 30% EtOAc in petroleum ether) to afford the desired enamides 10E and 10Z (2.99 g, 87%) as a mixture of E and Z isomers in a 3: 1 ratio (E: Z). 10E. 1 H NMR (500MHz, CDCl 3 ) δ: 8.44 (1H, bd, J = 12.1), 8.04 (1H, dd, J = 14.5, 12.1 Hz), 7.37 (5H, m), 5.68 (1H, d, J = 14.5 Hz), 5.22 (2H, s), 4.20 (1H, s), 3.72 (1H, d, J = 12.0 Hz), 3.32 (1H, d, J = 11.5 Hz), 1.52 (3H, s), 1.46 (3H, s), 1.06 (3H, s), 1.01 (3H, s). 13 C NMR (125MHz, CDCl 3 ) δ: 167.9, 166.9, 136.4, 136.2, 128.5, 128.2, 128.1, 102.7, 99.6, 77.2, 71.3, 66.0, 33.4, 29.5, 21.9, 18.8, IR ν max (film)/cm , 2992, 2959, 2872, 1716, 1637, HRMS calcd for C 19 H 26 O 5 N (M+H + ): Found [α] D (c = 1.1, CHCl 3 ). 10Z. 1 H NMR (500MHz, CDCl 3 ) δ: (1H, bd, J = 14.5 Hz), 7.39 (1H, dd, J = 14.5, 11.0 Hz), 7.31 (5H, m), 5.26 (1H, d, J = 11.5 Hz), 5.12 (2H, s), 4.15 (1H, s), 3.66 (1H, d, J = 15.0 Hz), 3.26 (1H, d, J = 14.5 Hz), 1.52 (3H, s), 1.40 (3H, s), 0.98 (3H, s), 0.97 (3H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 168.8, 168.1, 136.6, 135.9, 128.6, 128.3, 128.2, 99.3, 97.6, 77.3, 71.3, 65.9, 33.3, 29.3, 21.9, 19.0,

5 IR ν max (film)/cm , 2992, 2957, 2872, 1712, HRMS calcd for C 19 H 26 O 5 N (M+H + ): Found [α] D (c = 0.9, CHCl 3 ). (R)-3-(2,2,5,5-Tetramethyl-1,3-dioxane-4-carboxamido)propanoic acid, 11. A solution of (R,Z)-benzyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate 10Z (220 mg, 6.3 mmol) in MeOH (5 ml) was treated with Pd/C (10% wt/wt). The heterogenous mixture was then stirred under a H 2 atmosphere for 24 h. Upon reaction completion as indicated by TLC analysis, the solvent was removed under vacuum. The crude residue (126 mg) was found by NMR to be the clean, desired acetonide 11 (85% yield) which required no further purification. 1 H NMR (400MHz, CDCl 3 ) δ: 7.07 (1H, t, J = 6.0 Hz), 4.13 (1H, s), 3.71 (1H, d, J = 11.7 Hz), 3.56 (2H, m), 3.30 (1H, d, J = 11.7 Hz), 2.63 (2H, t, J = 6.2 Hz), 1.48 (3H, s), 1.45 (3H, s), 1.05 (3H, s), 0.99 (3H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 176.7, 170.2, 99.1, 77.1, 71.4, 34.1, 33.9, 32.9, 29.4, 22.0, 18.8, IR ν max (film)/cm , 2992, 1731, HRMS calcd for C 12 H 22 O 5 N (M+H + ): Found [α] D (c = 1.2, MeOH). (R,E)-Benzyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate, 12. A solution of enamide 10E (1.01 g, 2.9 mmol) in MeCN (40 ml) was treated with Bi(III)Cl 3 (92 mg, 0.29 mmol) and H 2 O (6 drops) and stirred at room temperature for 3 h. Upon completion by TLC analysis, the reaction was quenched with sat. aq. NaHCO 3 soln. (7 ml) and stirred for a further 20 min. After this time, the mixture was filtered over Celite, dried over Na 2 SO 4 filtered a second time, and then the solvent removed under 5

6 vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient 10% to 50% EtOAc in petroleum ether) to afford 760 mg (88%) of the desired diol 12 as a clear oil. 1 H NMR (500MHz, CDCl 3 ) δ: 8.87 (1H, bd, J = 12.0 Hz), 8.04 (1H, dd, J = 14.0, 12.0 Hz), 7.34 (5H, m), 5.63 (1H, d, J = 14.0 Hz), 5.19 (2H, s), 4.19 (2H, bs), 3.63 (1H, dd, J = 10.5, 4.5 Hz), 3.56 (1H, dd, J = 10.5, 4.5 Hz), 2.38 (1H, t, J = 5.0 Hz), 1.05 (3H, s), 0.98 (3H, s). 13 C NMR (125MHz, CDCl 3 ) δ: 170.7, 167.1, 136.7, 136.1, 128.5, 128.2, 128.1, 102.5, 78.4, 72.0, 66.0, 39.2, 20.9, IR ν max (film)/cm , 2962, 1698, HRMS calcd for C 16 H 22 O 5 N (M+H + ): Found [α] D (c = 1.8, CHCl 3 ). (R)-3-(2,4-Dihydroxy-3,3-dimethyl butanamido)propanoic acid [(R)-pantothenic acid], 1. A solution of (R,Z)-benzyl 3-(2,4-dihydroxy-3,3-dimethyl butanamido)acrylate 12 (218 mg, 0.7 mmol) in MeOH (5 ml) was treated with Pd/C (10% wt/wt). The heterogenous mixture was then stirred under a H 2 atmosphere for 24h. Upon reaction completion as indicated by TLC analysis, the solvent was removed under vacuum. The crude residue was found by NMR to be the desired pantothenic acid 1 in 83% yield (135 mg), which required no further purification. 1 H NMR (400MHz, MeOD) δ: 3.92 (1H, s), 3.46 (4H, m), 2.56 (2H, t, J = 6.4 Hz), 0.94 (6H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 176.1, 175.5, 77.3, 70.4, 40.4, 35.8, 34.8, 21.3,

7 IR ν max (film)/cm , 2948, 1721, HRMS calcd for C 9 H 17 O 5 N (M+ ): Found [α] D (c = 1.3, MeOH). (R,E)-Methyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 13E and (R,Z)-Methyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 13Z. A solution of N-formyl imide 9 (193 mg, 0.89 mmol) in benzene (10 ml) was treated with methyltriphenylphosphoranylidene acetate (888 mg, 2.7 mmol) and the resulting mixture heated to 95 o C for 19 h. Upon reaction completion as indicated by TLC analysis, the solvent was removed under vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient, 10% to 30% EtOAc in petroleum ether) to afford the desired enamide 13 (220 mg, 91%) as a mixture of E and Z isomers in a 2:1 E: Z ratio. 13E 1 H NMR (500MHz, CDCl 3 ) δ: 8.40 (1H, bd, J = 11.5 Hz), 8.99 (1H, dd, J = 14.5, 12.0 Hz), 5.61 (1H, d, J = 14.0 Hz), 4.20 (1H, s), 3.73 (3H, s), 3.71 (1H, d, J = 11.5 Hz), 3.32 (1H, d, J = 11.5 Hz), 1.52 (3H, s), 1.46 (3H, s), 1.06 (3H, s), 1.01 (3H, s). 13 C NMR (125MHz, CDCl 3 ) δ: 167.9, 167.6, 136.2, 102.5, 99.6, 77.2, 71.2, 51.4, 33.4, 29.5, 21.9, 18.8, IR ν max (film)/cm , 2992, 2954, 1720, HRMS calcd for C 13 H 22 O 5 N (M+H + ): Found [α] D (c = 1.0, CHCl 3 ). 13Z 1 H NMR (400MHz, CDCl 3 ) δ: (1H, bd, J = 11.7 Hz), 7.37 (1H, dd, J = 11.7, 9.0 Hz), 5.11 (1H, d, J = 8.9 Hz), 4.15 (1H, s), 3.67 (4H, m), 3.26 (1H, d, J = 11.7 Hz), 1.53 (3H, s), 1.41 (3H, s), 0.98 (3H, s), 0.97 (3H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 168.8, 168.6, 136.1, 99.3, 97.6, 77.3, 71.3, 51.3, 33.3, 29.4, 21.9, 19.0,

8 IR ν max (film)/cm , 2955, 1696, HRMS calcd for C 13 H 22 O 5 N (M+H + ): Found [α] D (c = 1.1, CHCl 3 ). (R,E)-Methyl 3-(2,4-dihydroxy-3,3-dimethyl butanamido)acrylate, 14E. A solution of enamide 13E (391 mg, 1.44 mmol) in MeCN (12 ml) was treated with Bi (III)Cl 3 (45 mg, 0.14 mmol) and H 2 O (4 drops) and stirred at room temperature for 3h. Upon completion by TLC analysis, the reaction was quenched with sat. NaHCO 3 (2 ml) and stirred for a further 20min. After this time, the mixture was filtered through Celite, dried over Na 2 SO 4, filtered a second time, and then the solvent removed under vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient 10% to 30% EtOAc in petroleum ether) to afford 73 mg of the desired diol 14E (50%) as a colourless oil. 1 H NMR (500MHz, MeOD) δ: 7.94 (1H, d, J = 14.0 Hz), 5.78 (1H, d, J = 14.5 Hz), 4.01 (1H, s), 3.70 (3H, s), 3.48 (1H, d, J = 11.0 Hz), 3.37 (1H, d, J = 11.0 Hz), 0.93 (3H, s), 0.92 (3H, s). 13 C NMR (125MHz, MeOD) δ: 175.0, 170.2, 138.9, 102.5, 77.1, 69.8, 51.8, 40.8, 21.5, IR ν max (film)/cm , 2992, 1721, 1670, HRMS calcd for C 10 H 18 O 5 N (M+H + ): Found [α] D (c = 1.4, CHCl 3 ). (R,E)-tert-Butyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 15E and (R,Z)-tert-Butyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 15Z. A solution of n-formyl imide 9 (500 mg, 2.3 mmol) in benzene (20 ml) was treated with t-butoxycarbonylmethylene triphenylphosphorane (2.59 g, 6.9 mmol) and the resulting 8

9 mixture heated to 95 o C for 19 h. Upon reaction completion as indicated by TLC analysis, the solvent was removed under vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient 10% to 30% EtOAc in petroleum ether) to afford the desired enamides 15E and 15Z (614 mg, 85%) as a mixture of E and Z isomers in a 4:1 E: Z ratio. 15E 1 H NMR (500MHz, CDCl 3 ) δ: 8.46 (1H, bd, J = 11.5 Hz), 7.86 (1H, dd, J = 14.5, 12.0 Hz), 5.52 (1H, d, J = 14.0 Hz), 4.19 (1H, s), 3.71 (1H, d, J = 12.0 Hz), 3.31 (1H, d, J = 11.5 Hz), 1.51 (3H, s), 1.48 (9H, s), 1.45 (3H, s), 1.05 (3H, s), 1.00 (3H, s). 13 C NMR (125MHz, CDCl 3 ) δ: 167.9, 166.4, 134.9, 105.1, 99.5, 80.2, 77.2, 71.2, 33.4, 29.4, 28.2, 21.9, 20.2, 18.8, IR ν max (film)/cm , 2976, 1709, 1638, HRMS calcd for C 16 H 28 O 5 N (M+H + ): Found [α] D (c = 1.5, CHCl 3 ). 15Z 1 H NMR (500MHz, CDCl 3 ) δ: (1H, bd, J = 15.0 Hz), 7.37 (1H, dd, J = 14.5, 11.5 Hz), 5.11 (1H, d, J = 11.0 Hz), 4.23 (1H, s), 3.75 (1H, d, J = 14.5 Hz), 3.32 (1H, d, J = 14.5 Hz), 1.61 (3H, s), 1.52 (9H, s), 1.50 (3H, s), 1.08 (6H, s). 13 C NMR (100MHz, CDCl 3 ) δ: , 167.8, 135.1, 99.9, 99.2, 80.5, 77.3, 71.4, 33.2, 29.3, 28.3 (2C), 21.9, 19.1, IR ν max (film)/cm , 2980, 2872, 1686, HRMS calcd for C 16 H 28 O 5 N (M+H + ): Found [α] D (c = 1.9, CHCl 3 ). (R,E)-3-(2,4-Dihydroxy-3,3-dimethyl-butyrylamino)-acrylic acid tert-butyl ester, 16E. 9

10 A solution of enamide 15E (280 mg, 0.89 mmol) in MeCN (6.0 ml) was treated with H 2 O (200 μl) and Bi(III)Cl 3 (28 mg, 0.09 mmol) and the resulting mixture was stirred at room temperature overnight. Upon completion by TLC analysis (20 h), the reaction was filtered over Celite and dried over Na 2 SO 4. The solvent was removed under vacuum and the crude residue was then purified by flash column chromatography (silica gel, elution gradient 10% to 50% EtOAc in petroleum ether) to afford 196 mg (80%) of the desired diol, 16E as a clear oil. 1 H NMR (500MHz, CDCl 3 ) δ: 8.76 (1H, bd, J = 11.5 Hz), 7.90 (1H, dd, J = 14.5, 12.0 Hz), 5.50 (1H, d, J = 14.5 Hz), 4.19 (1H, d, J = 4.0 Hz), 4.12 (1H, d, J = 3.5 Hz), 3.64 (1H, dd, J = 11.0, 5.0 Hz), 3.56 (1H, dd, J = 11.0, 5.0 Hz), 2.36 (1H, t, J = 5.0 Hz), 1.49 (9H, s), 1.06 (3H, s), 0.98 (3H, s). 13 C NMR (125MHz, CDCl 3 ) δ: 170.6, 166.5, 135.3, 104.9, 80.3, 78.3, 72.0, 39.3, 28.2, 20.8, IR ν max (film)/cm , 2976, 1709, 1638, HRMS calcd for C 13 H 24 O 5 N (M+H + ): , Found (E)-2-(Trimethylsilyl)ethyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4- carboxamido)acrylate, 17E and (Z)-2-(Trimethylsilyl)ethyl 3-(2,2,5,5-tetramethyl- 1,3-dioxane-4-carboxamido)acrylate, 17Z. A solution of N-formyl imide 9 (200 mg, 0.9 mmol) in benzene (7 ml) was treated with trimethylsilylethylphosphoranylidene acetate (950 mg, 2.25 mmol) and the resulting mixture heated to 80 o C for 19 h. Upon reaction completion as indicated by TLC analysis, the solvent was removed under vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient, 5% to 15% EtOAc in

11 petroleum ether) to afford 241 mg of the desired enamides 17E and 17Z (76%) as a 1.5:1 mixture of E: Z isomers. 17E 1 H NMR (400MHz, CDCl 3 ) δ: 8.31 (1H, d, J = 12.0 Hz), 7.90 (1H, m), 5.52 (1H, d, J = 14.3 Hz), 4.18 (2H, m), 4.14 (1H, s), 3.66 (1H, d, J = 12.0 Hz), 3.26 (1H, d, J = 12.3 Hz), 1.46 (3H, s), 1.40 (3H, s), 1.00 (3H, s), 0.96 (5H, m), 0.00 (9H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 169.4, 168.7, 137.2, 104.7, 101.0, 78.7, 72.7, 63.9, 34.9, 30.9, 23.3, 20.3, 20.1, 18.8, 0.0. IR ν max (film)/cm , 2955, 2878, 1670, 1628, 1188, HRMS calcd for C 17 H 32 O 5 NSi (M+H + ): Found Z 1 H NMR (CDCl 3, 400 MHz): (1H, d, J =10.8 Hz), 7.35 (1H, dd, J = 11.6, 8.9 Hz), 5.09 (1H, d, J = 11.0 Hz), 4.18 (3H, m), 3.66 (1H, d, J = 11.7 Hz), 3.27 (1H, d, J = 11.7 Hz), 1.54 (3H, s), 1.41 (3H, s), 0.99 (3H, s), 0.98 (3H, s), 0.96 (2H, m), 0.00 (9H, s). IR ν max (film)/cm , 2955, 2878, 1697, 1636, HRMS calcd for C 17 H 32 O 5 NSi (M+H + ): Found (E)-3-(2,2,5,5-Tetramethyl-1,3-dioxane-4-carboxamido)acrylic acid, 18E. A solution of enamide 17E (110mg, 0.31 mmol) was treated with a 1M solution of tetrabutylammoniumfluoride in THF (0.37ml, 0.37 mmol) and the resulting mixture left to stir at RT for 19 h. Upon reaction completion as indicated by TLC analysis, solvent was removed under vacuum and the crude residue was purified by flash column chromatography (silica gel, elution gradient 0% to 5% methanol in dichloromethane) to afford 15 mg of the desired acid 18E. 11

12 The combined impure factions were reduced under vacuum and dissolved in ethyl acetate. 1M sodium hydroxide solution was added, and the solution was left to stir for 0.5 h. The phases were separated and the organic layer was extracted with water (2 x 15 ml). The combined aqueous layers were acidified with 1M hydrochloric acid to ph 2 and the resulting solution was extracted with ethyl acetate (2 x 15 ml). The combined organic extracts were washed with brine, dried over Na 2 SO 4 and concentrated under vacuum to give 48 mg (63 mg total, 79%) of the desired acid 18E as a white solid. Mp o C. 1 H NMR (400MHz, CDCl 3 ) δ: 7.95 (1H, d, J = 14 Hz), 5.86 (1H, d, J = 14 Hz), 4.31 (1H, s), 3.80 (1H, d, J = 11.6 Hz), 3.32 (1H, d, J = 11.6 Hz), 2.10 (3H, s), 1.51 (3H, s), 1.03 (3H, s), 1.02 (3H, s). 13 C NMR (100MHz, CDCl 3 ) δ: 170.9, 138.5, 104.0, 100.8, 78.6, 72.2, 34.3, 29.5, 22.2, 19.3, IR ν max (film)/cm , 3140, 3094, 2963, 2878, 1720, 1670, 1636, 1474, (R,E)-3-(2,4-Dihydroxy-3,3-dimethylbutanamido)acrylic acid [CJ-15,801], 3. From Diol 16E. A solution of tert-butyl ester 16E (59 mg, 0.21 mmol) in formic acid (1 ml) was stirred at room temperature for 120 min. After this time, the excess formic acid was removed under vacuum to afford 38 mg (83%) of CJ-15,801 3 which was clean by 1H NMR with the exception of formic acid traces. Purification by flash column chromatography (elution gradient 0 to 10% MeOH in DCM) afforded a yellow oil which upon azeotroping with chloroform yielded 22 mg (48%) of CJ-15,801 3 as a fine white powder. From Acetonide 15E. 12

13 A solution of (R,E)-tert-butyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate 15E (195 mg, 0.62 mmol) in formic acid (7 ml) was stirred at room temperature for 90 min. After this time, the excess formic acid was removed under vacuum. The crude residue was then taken up into MeOH (7 ml) and p-toluenesulfonic acid added (11 mg, 62 μmol) and the resulting mixture stirred for 75 min. After this time, the solvent was removed under vacuum, and the crude residue purified by flash column chromatography (silica gel, 50% EtOAc in petroleum ether) to afford CJ-15,801 3 in 20% yield over the two steps. From Acetonide 18E. A solution of (E)-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylic acid 18E (60 mg, 0.23 mmol) in MeCN (1 ml) was treated with Bi(III)Cl 3 (7 mg, 23 μmol) and H 2 O (50 μl) and stirred at room temperature for 19 h. Upon completion by TLC analysis, the mixture was filtered over Celite, and dried over Na 2 SO 4. The solution was filtered a second time, and then the solvent removed under vacuum. The crude residue was then purified by flash column chromatography (silica gel, elution gradient 5% to 10% methanol in dichloromethane) to afford 28 mg (56%) of CJ-15,801 3 as a white solid. 1 H NMR (500MHz, MeOD) δ: 7.94 (1H, d, J = 14.2 Hz), 5.69 (1H, d, J = 14.2 Hz), 4.02 (1H, s), 3.50 (1H, d, J = 10.9 Hz), 3.38 (1H, d, J = 10.9 Hz), 0.94 (3H, s), 0.93 (3H, s). 13 C NMR (125MHz, MeOD) δ: 173.4, 170.4, 137.1, 102.1, 75.6, 68.2, 39.2, 19.9, IR ν max (film)/cm , 2952, 2841, 1774, HRMS calcd for C 9 H 15 O 5 N (M+H + ): Found [α] D (c = 0.6, MeOH). 13

14 (R,E)-Benzyl-3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 10E 14

15 (R,Z)-Benzyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 10Z. 15

16 (R,E)-Benzyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate,

17 (R,E)-Methyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 13E 17

18 (R,Z)-Methyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 13Z. 18

19 (R,E)-Methyl 3-(2,4-dihydroxy-3,3-dimethyl butanamido)acrylate, 14E. 19

20 (R,E)-tert-Butyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 15E 20

21 (R,Z)-tert-Butyl 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido)acrylate, 15Z. 21

22 (R,E)-3-(2,4-Dihydroxy-3,3-dimethyl-butyrylamino)-acrylic acid tert-butyl ester, 16E. 22

23 (E)-2-(Trimethylsilyl)ethyl3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido) acrylate, 17E 23

24 (Z)-2-(Trimethylsilyl)ethyl acrylate, 17Z. 3-(2,2,5,5-tetramethyl-1,3-dioxane-4-carboxamido) 24

25 (E)-3-(2,2,5,5-Tetramethyl-1,3-dioxane-4-carboxamido)acrylic acid, 18E. 25

26 (R,E)-3-(2,4-Dihydroxy-3,3-dimethylbutanamido)acrylic acid [CJ-15,801], 3. 26

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

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

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

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

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

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

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

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

Supplementary Table S1: Response evaluation of FDA- approved drugs

Supplementary Table S1: Response evaluation of FDA- approved drugs SUPPLEMENTARY DATA, FIGURES AND TABLE BIOLOGICAL DATA Spheroids MARY-X size distribution, morphology and drug screening data Supplementary Figure S1: Spheroids MARY-X size distribution. Spheroid size was

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 Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2016 Supporting Information TEMPO-catalyzed Synthesis of 5-Substituted Isoxazoles from Propargylic

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

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

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

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

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

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

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 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

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

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

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

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

The all-photochemical Synthesis an. OGP (10-14) Precursor

The all-photochemical Synthesis an. OGP (10-14) Precursor SUPPORTING INFORMATION The all-photochemical Synthesis an OGP (10-14) Precursor Jean-Luc Débieux, Christian G. Bochet* Department of Chemistry, University of Fribourg, 9 Chemin du Musée, CH-1700 Fribourg,

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

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

Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis

Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis Scalable Synthesis of Fmoc-Protected GalNAc-Threonine Amino Acid and T N Antigen via Nickel Catalysis Fei Yu, Matthew S. McConnell, and Hien M. Nguyen* Department of Chemistry, University of Iowa, Iowa

More information

Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to. Vinyl Sulfone: An Organocatalytic Access to Chiral. 3-Fluoro-3-Substituted Oxindoles

Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to. Vinyl Sulfone: An Organocatalytic Access to Chiral. 3-Fluoro-3-Substituted Oxindoles Enantioselective Conjugate Addition of 3-Fluoro-Oxindoles to Vinyl Sulfone: An Organocatalytic Access to Chiral 3-Fluoro-3-Substituted Oxindoles Xiaowei Dou and Yixin Lu * Department of Chemistry & Medicinal

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

Supporting Information

Supporting Information Supporting Information Efficient Short Step Synthesis of Corey s Tamiflu Intermediate Nsiama Tienabe Kipassa, Hiroaki kamura, * Kengo Kina, Tetsuo Iwagawa, and Toshiyuki Hamada Department of Chemistry

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

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

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 SmI 2 -Mediated Carbon-Carbon Bond Fragmentation in α-aminomethyl Malonates Qiongfeng Xu,, Bin Cheng, $, Xinshan Ye,*, and Hongbin Zhai*,,,$ The State Key Laboratory of Natural and

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

Supporting Information

Supporting Information Intramolecular hydrogen-bonding activation in cysteines. New effective radical scavenging Luisa Haya, a Iñaki Osante, b Ana M. Mainar, a Carlos Cativiela, b Jose S. Urieta*,a a Group of Applied Thermodynamics

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION Synthetic chemistry ML5 and ML4 were identified as K P.(TREK-) activators using a combination of fluorescence-based thallium flux and automated patch-clamp assays. ML5, ML4, and ML5a were synthesized using

More information

Divergent Synthesis of CF 3 -Substituted Polycyclic Skeletons Based on Control of Activation Site of Acid Catalysts

Divergent Synthesis of CF 3 -Substituted Polycyclic Skeletons Based on Control of Activation Site of Acid Catalysts Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 Divergent Synthesis of CF 3 -Substituted Polycyclic Skeletons Based on Control of Activation Site

More information

Straightforward Synthesis of Enantiopure (R)- and (S)-trifluoroalaninol

Straightforward Synthesis of Enantiopure (R)- and (S)-trifluoroalaninol S1 Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is (c) The Royal Society of Chemistry 2010 Straightforward Synthesis of Enantiopure (R)- and (S)-trifluoroalaninol Julien

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

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

Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis

Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis Formal Total Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis Kazushi Watanabe, Yuto Suzuki, Kenta Aoki, Akira Sakakura, Kiyotake Suenaga, and Hideo Kigoshi* Department of Chemistry,

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

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

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

A Sumanene-based Aryne, Sumanyne

A Sumanene-based Aryne, Sumanyne A Sumanene-based Aryne, Sumanyne Niti Ngamsomprasert, Yumi Yakiyama, and Hidehiro Sakurai* Division of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871

More information

Simplified platensimycin analogues as antibacterial agents

Simplified platensimycin analogues as antibacterial agents Simplified platensimycin analogues as antibacterial agents Dragan Krsta, a Caron Ka, a Ian T. Crosby, a Ben Capuano a and David T. Manallack a * a Medicinal Chemistry and Drug Action, Monash Institute

More information

Highly stereocontrolled synthesis of trans-enediynes via

Highly stereocontrolled synthesis of trans-enediynes via Supporting Information for Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes Tsutomu Konno*, Misato Kishi, and Takashi Ishihara Address: Department of Chemistry

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

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

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

Supporting Information

Supporting Information Supporting Information Lewis acid-catalyzed intramolecular condensation of ynol ether-acetals. Synthesis of alkoxycycloalkene carboxylates Vincent Tran and Thomas G. Minehan * Department of Chemistry and

More information

Supporting Information for

Supporting Information for Electronic Supplementary Material (ESI) for New Journal of Chemistry. This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2017 Supporting Information for

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

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

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

Kinetics experiments were carried out at ambient temperature (24 o -26 o C) on a 250 MHz Bruker

Kinetics experiments were carried out at ambient temperature (24 o -26 o C) on a 250 MHz Bruker Experimental Materials and Methods. All 31 P NMR and 1 H NMR spectra were recorded on 250 MHz Bruker or DRX 500 MHz instruments. All 31 P NMR spectra were acquired using broadband gated decoupling. 31

More information

Electronic Supplementary Information for. A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective

Electronic Supplementary Information for. A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective Electronic Supplementary Information for A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H 2 S: Synthesis, Spectra and Bioimaging Changyu Zhang, 1 Runyu Wang,

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for Organic Chemistry Frontiers. This journal is the Partner Organisations 2016 Supporting Information Synthesis of Biaryl Sultams Using Visible-Light-Promoted Denitrogenative

More information

Supporting Information

Supporting Information Supporting Information Bioinspired Total Synthesis of Bussealin E David G. Twigg, Leonardo Baldassarre, Elizabeth C. Frye, Warren R. J. D. Galloway, David R. Spring* Department of Chemistry, University

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

Supporting Text Synthesis of (2 S ,3 S )-2,3-bis(3-bromophenoxy)butane (3). Synthesis of (2 S ,3 S

Supporting Text Synthesis of (2 S ,3 S )-2,3-bis(3-bromophenoxy)butane (3). Synthesis of (2 S ,3 S Supporting Text Synthesis of (2S,3S)-2,3-bis(3-bromophenoxy)butane (3). Under N 2 atmosphere and at room temperature, a mixture of 3-bromophenol (0.746 g, 4.3 mmol) and Cs 2 C 3 (2.81 g, 8.6 mmol) in DMS

More information

Total Synthesis of (±)-Vibsanin E. Brett D. Schwartz, Justin R. Denton, Huw M. L. Davies and Craig. M. Williams. Supporting Information

Total Synthesis of (±)-Vibsanin E. Brett D. Schwartz, Justin R. Denton, Huw M. L. Davies and Craig. M. Williams. Supporting Information Total Synthesis of (±)-Vibsanin E. Brett D. Schwartz, Justin R. Denton, Huw M. L. Davies and Craig M. Williams Supporting Information General Methods S-2 Experimental S-2 1 H and 13 C NMR Spectra S-7 Comparison:

More information

Hualong Ding, Songlin Bai, Ping Lu,* Yanguang Wang*

Hualong Ding, Songlin Bai, Ping Lu,* Yanguang Wang* Supporting Information for Preparation of 2-Amino-3-arylindoles via Pd-Catalyzed Coupling between 3-Diazoindolin-2-imines and Arylboronic Acids as well as Their Extension to 3-Aryl-3-fluoroindolin-2-imines

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

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

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

Protodecarboxylation of benzoic acids under radical conditions. Supporting Information

Protodecarboxylation of benzoic acids under radical conditions. Supporting Information Protodecarboxylation of benzoic acids under radical conditions Sangwon Seo, a John B. Taylor b and Michael F. Greaney a * a School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL,UK

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

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: Enantioselective Synthesis of (-)-Codeine and (-)-Morphine Barry M. Trost* and Weiping Tang Department of Chemistry, Stanford University, Stanford, CA 94305-5080 1. Aldehyde 7. Supporting Information:

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

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 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

Carbonylative Coupling of Allylic Acetates with. Arylboronic Acids

Carbonylative Coupling of Allylic Acetates with. Arylboronic Acids Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2015 Carbonylative Coupling of Allylic Acetates with Arylboronic Acids Wei Ma, a Ting Yu, Dong Xue,*

More information

Aziridine in Polymers: A Strategy to Functionalize Polymers by Ring- Opening Reaction of Aziridine

Aziridine in Polymers: A Strategy to Functionalize Polymers by Ring- Opening Reaction of Aziridine Electronic Supplementary Material (ESI) for Polymer Chemistry. This journal is The Royal Society of Chemistry 2015 Electronic Supplementary Information (ESI) Aziridine in Polymers: A Strategy to Functionalize

More information

A Concise Route to the Macrocyclic Core of the Rakicidins

A Concise Route to the Macrocyclic Core of the Rakicidins A Concise Route to the Macrocyclic Core of the Rakicidins Thomas B. Poulsen* Department of Chemistry, Aarhus University, Langelandsgade 140, 8000 Aarhus C, Denmark e-mail: thpou@chem.au.dk Supporting Information

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

Supporting Information

Supporting Information Supporting Information Calix[4, 5]tetrolarenes: A New Family of Macrocycles Yossi Zafrani* and Yoram Cohen* School of Chemistry, The Sackler Faculty of Exact Sciences, Tel Aviv University, Ramat Aviv 69978,

More information

Supplementary Information

Supplementary Information Supplementary Information C aryl -C alkyl bond formation from Cu(ClO 4 ) 2 -mediated oxidative cross coupling reaction between arenes and alkyllithium reagents through structurally well-defined Ar-Cu(III)

More information

Supporting Information

Supporting Information J. Am. Chem. Soc. Supporting Information S 1 The First Suzuki Cross-Coupling of Aryltrimethylammonium Salts. Simon B. Blakey and David W. C. MacMillan* Division of Chemistry and Chemical Engineering, California

More information

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

Electronic Supplementary Material (ESI) for Chemical Communications This journal is The Royal Society of Chemistry 2012 Ring Expansion of Alkynyl Cyclopropanes to Highly substituted Cyclobutenes via a N-Sulfonyl-1,2,3-Triazole Intermediate Renhe Liu, Min Zhang, Gabrielle Winston-Mcerson, and Weiping Tang* School of armacy,

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

SUPPORTING INFORMATION. Fathi Elwrfalli, Yannick J. Esvan, Craig M. Robertson and Christophe Aïssa

SUPPORTING INFORMATION. Fathi Elwrfalli, Yannick J. Esvan, Craig M. Robertson and Christophe Aïssa Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 SUPPORTING INFORMATION S1 Fathi Elwrfalli, Yannick J. Esvan, Craig M. Robertson and Christophe

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

Photolysis for Vitamin D Formation. Supporting Information

Photolysis for Vitamin D Formation. Supporting Information S1 Synthesis of 1α-Hydroxyvitamin D 5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation Supporting Information Robert M. Moriarty and Dragos Albinescu Spectra 1. 13 C: 3β-Acetoxy-stigmasta-5,7-diene

More information

Supporting Information

Supporting Information Supporting Information for Synthesis of a novel analogue of DPP-4 inhibitor Alogliptin: Introduction of a spirocyclic moiety on the piperidine ring Arumugam Kodimuthali 1,2, Padala Lakshmi Prasunamba 2,

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

A Facile and General Approach to 3-((Trifluoromethyl)thio)- 4H-chromen-4-one

A Facile and General Approach to 3-((Trifluoromethyl)thio)- 4H-chromen-4-one A Facile and General Approach to 3-((Trifluoromethyl)thio)- 4H-chromen-4-one Haoyue Xiang and Chunhao Yang* State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy

More information

Supporting Information

Supporting Information Supporting Information Catalytic Site-selective Acylation of Carbohydrates Directed by Cation-n Interaction Guozhi Xiao, 1 Gabriel A. Cintron-Rosado, 2 Daniel A. Glazier, 1,3 Bao-min Xi, 1, Can Liu, 1

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

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

1. Reagents: All commercial materials were used as received unless otherwise noted. The following solvents were obtained from a JC Meyer solvent dispe

1. Reagents: All commercial materials were used as received unless otherwise noted. The following solvents were obtained from a JC Meyer solvent dispe Supporting Information Pd-catalyzed Mono-selective ortho-c H Alkylation of N-Quinolyl Benzamides: Evidence for Stereo-retentive Coupling of Secondary Alkyl Iodides Shu-Yu Zhang, Qiong Li, Gang He, William

More information

SUPPLEMENTARY INFORMATION

SUPPLEMENTARY INFORMATION DOI: 10.1038/NCHEM.1989 Cooperative activation of cyclobutanones and olefins leads to bridged ring systems by a catalytic [4+2] coupling Haye Min Ko and Guangbin Dong* Department of chemistry and biochemistry,

More information

Flaws in foldamers: screw- sense fidelity and signal decay in achiral helical peptide oligomers

Flaws in foldamers: screw- sense fidelity and signal decay in achiral helical peptide oligomers Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 2015 Flaws in foldamers: screw- sense fidelity and signal decay in achiral helical peptide oligomers

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

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

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 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

Amide Directed Cross-Coupling between Alkenes and Alkynes: A Regio- and Stereoselective Approach to Substituted (2Z,4Z)-Dienamides

Amide Directed Cross-Coupling between Alkenes and Alkynes: A Regio- and Stereoselective Approach to Substituted (2Z,4Z)-Dienamides Supporting Information For the article entitled Amide Directed Cross-Coupling between Alkenes and Alkynes: A Regio- and Stereoselective Approach to Substituted (2Z,4Z)-Dienamides Keke Meng, Jian Zhang,*

More information