Supporting Information. Total Synthesis of Grandisine D. Haruaki Kurasaki, Iwao Okamoto, Nobuyoshi Morita, and Osamu Tamura*

Size: px
Start display at page:

Download "Supporting Information. Total Synthesis of Grandisine D. Haruaki Kurasaki, Iwao Okamoto, Nobuyoshi Morita, and Osamu Tamura*"

Transcription

1 Supporting Information Total Synthesis of Grandisine D Haruaki Kurasaki, Iwao Okamoto, Nobuyoshi Morita, and Osamu Tamura* Discovery Research Laboratories, Kyorin Pharmaceutical Co. Ltd , Nogi, Nogi-Machi, Shimotsuga-Gun, Tochigi , Japan, and Showa Pharmaceutical University, Higashi-tamagawagakuen, Machida, Tokyo , Japan tamura@ac.shoyaku.ac.jp Contents I. Experimental Section 1 II. 1 H and 13 C NMR Spectra 13 Experimental Section General. Melting points were determined with a Yanagimoto micro melting point apparatus and are uncorrected. Optical rotations were measured with a JASCO P-1020 auto digital polarimeter. Infrared spectra (IR) were recorded with PerkinElmer spectrum 100. Proton nuclear magnetic resonance ( 1 H NMR) spectra were recorded on a JEOL JNM-AL300 spectrometer. The chemical shifts are expressed in ppm downfield from tetramethylsilane (δ = 0) as an internal standard (CDCl 3 solution). Splitting patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad peak. Measurements of mass spectra (MS) and high resolution MS (HRMS) were performed with a JEOL JMS SX-102A or a JEOL JMS-T100LP mass spectrometer. HPLC analyses were conducted using a JASCO 880-PU with HITACHI 655A UV detection. Column chromatography was carried out on silica gel [silica gel µm neutral, Kanto Chemical Co., Inc. or Chromatorex NH DM2035 ( mesh Fuji Silysia Chemical, Ltd.)]. Merck precoated thin layer chromatography (TLC) plates (silica gel 60 F 254, 0.25 mm, Art 5715) were used for the TLC analysis. After extractive workup, organic layers were dried over anhydrous sodium sulfate or anhydrous magunesium sulfate and the solvent was removed by rotary evaporation under reduced pressure. (3S)-3-Acetoxy-1-(3-buten-1-yl)pyrrolidine-2,5-dione (12) A solution of L-malic acid (12.2 g, 91.1 mmol) in acetyl chloride (150 ml) was heated at reflux for 2 h. After evaporation of acetyl chloride, the residue was dissolved in CH 2 Cl 2 (70 ml). To the resulting solution was added dropwise a mixture of 4-amino-1-butene hydrochloride (22.1 g, 205 mmol) and triethylamine (28.5 ml, 205 mmol) in CH 2 Cl 2 (80 ml) at 0 o C and the mixture was 1

2 stirred at room temperature for 5 h. After evaporation of solvent, to the residue was added acetyl chloride (150 ml) and the mixture was heated at reflux for 1.5 h. After evaporation of acetyl chloride, the residue was dissolved in mixture of CH 2 Cl 2 (50 ml), water (50 ml), and a saturated aqueous NaHCO 3 (400 ml). The whole was extracted with CH 2 Cl 2 (50 ml x 2), washed with brine (50 ml), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane-acoet, 1:1) to afford imide 12 as a colorless solid (17.4 g, 90%). mp o C (hexane-acoet); [α] 24 D 19.0 (c 0.50, CHCl 3 ); IR (ATR) 2949, 1743, 1699 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ (m, 1H), 5.43 (dd, J = 8.8, 4.8 Hz, 1H), (m, 2H), 3.64 (t, J = 7.2 Hz, 2H), 3.15 (dd, J = 18.3, 8.6 Hz, 1H), 2.65 (dd, J = 18.3, 5.0 Hz, 1H), 2.38 (br q, J = 7.1 Hz, 2H), 2.17 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 173.3, 173.1, 169.8, 134.0, 117.8, 67.3, 38.2, 35.7, 31.7, 20.5; MS (CI+) m/z 212 (MH + ); HRMS calcd for C 10 H 14 NO , found The optical purity of 12 was measured to be 99.3% ee by chiral HPLC analysis (CHIRALPAK IA; 260 nm, 0.5 ml/min; hexane:etoh = 6:4; t R = min, t S = min) The corresponding enantiomer was prepared from D-malic acid by using the same procedure described above. (2R,3S)-1-Butenyl-2-ethoxy-5-oxopyrrolidin-3-yl acetate (trans-13) and (2S,3S)-1-Butenyl-2-ethoxy-5-oxopyrrolidin-3-yl acetate (cis-13) To a solution of imide 12 (10.0 g, 47.3 mmol) in EtOH (470 ml) was added NaBH 4 (8.96 g, 237 mmol) at -15 o C. After stirring for 15 min at -5 o C, the mixture was cooled to -52 o C, and then a 1M solution of H 2 SO 4 in EtOH (215 ml) was added over 55 min. The mixture was allowed to warm to room temperature, and stirring was continued for 13 h. The mixture was poured into a saturated aqueous NaHCO 3 (1.5 L), and the whole was extracted with CH 2 Cl 2 (200 ml x 4), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (hexane-acoet, 1:1) to afford trans-13 as a colorless oil (9.60 g, 84%) and cis-13 as a colorless oil (1.11 g, 10%). trans-13: [α] 24 D 26.5 (c 0.50, CHCl 3 ); IR (ATR) 2977, 2934, 1742, 1702 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 5.78 (ddt, J = 17.1, 10.2, 6.9 Hz, 1H), (m, 3H), 4.73 (s, 1H), 3.74 (dq, J = 9.6, 7.1 Hz, 1H), (m, 2H), 3.17 (br dt, J = 13.8, 7.2 Hz, 1H), 2.88 (ddd, J = 17.9, 6.5, 0.8 Hz, 1H), (m, 3H), 2.07 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H); 13 C NMR (75 MHz, CDCl 3,) δ 172.5, 170.3, 135.0, 116.9, 93.0, 70.5, 63.6, 39.7, 35.6, 32.2, 20.9, 15.2; MS (CI+) m/z 242 (MH + ); HRMS calcd for C 12 H 20 NO , found, cis-13: [α] 24 D 57.7 (c 0.49, CHCl 3 ); IR (ATR) 2978, 2935, 1739, 1702 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 5.76 (ddt, J = 17.1, 10.5, 7.2 Hz, 1H), (m, 4H), (m, 3H), 3.13 (ddd, J = 2

3 14.1, 7.8, 6.3 Hz, 1H), 2.66 (dd, J = 16.8, 7.8 Hz, 1H), 2.60 (dd, J = 16.8, 7.8 Hz, 1H), (m, 2H), 2.13 (s, 3H), 1.21 (t, J = 7.0 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 170.9, 170.7, 134.9, 117.2, 88.2, 67.7, 65.4, 39.9, 34.5, 32.1, 20.7, 15.5; MS (CI+) m/z 242 (MH + ); HRMS calcd for C 12 H 20 NO , found (2R,3S)-2-Ethoxy-5-oxo-1-[(3E)-5-oxo-3-pentenyl]pyrrolidinyl acetate (11) A solution of trans-13 (4.43 g, 18.4 mmol), acrolein (3.68 ml, 55.1 mmol), and Grubbs-Hoveyda catalyst (1.15 g, 1.84 mmol) in CH 2 Cl 2 (50 ml) was stirred at room temperature for 2 h. After concentration, the crude product was purified by column chromatography on silica gel (hexane-acoet, 1:2) to afford aldehyde 11 as a brown oil (4.14 g, 84%). [α] 24 D 24.8 (c 0.47, CHCl 3 ); IR (ATR) 2978, 1741, 1684 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 9.51 (d, J = 7.9 Hz, 1H), 6.81 (dt, J = 15.6, 7.0 Hz, 1H), 6.13 (ddt, J = 15.6, 7.9, 1.5 Hz, 1H), 5.07 (d, J = 6.1 Hz, 1H), 4.67 (s, 1H), 3.76 (dq, J = 9.3, 6.9 Hz, 1H), (m, 2H), 3.44 (br dt, J = 13.8, 6.6 Hz, 1H), 2.88 (dd, J = 17.8, 6.1 Hz, 1H), (m, 2H), 2.32 (d, J = 17.8 Hz, 1H), 2.07 (s, 3H), 1.25 (t, J = 7.0 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 193.6, 172.7, 170.3, 154.0, 134.6, 93.4, 70.2, 63.7, 39.1, 35.5, 31.4, 20.9, 15.2; MS (CI+) m/z 270 (MH + ); HRMS calcd for C 13 H 20 NO , found (1S,8aR)-8-Formyl-3-oxo-1,2,3,5,6,8a-hexahydroindolizin-1-yl acetate (trans-14) and (1S,8aS)-8-Formyl-3-oxo-1,2,3,5,6,8a-hexahydroindolizin-1-yl acetate (cis-14) To a solution of aldehyde 11 (4.00 g, 14.9 mmol) in CH 3 CN (75 ml) was added Me 2 S (1.64 ml, 22.3 mmol) and TfOH (3.29 ml, 37.1 mmol) at -35 o C. The resulting mixture was allowed to warm to room temperature and stirring was continued for 2 h. The reaction was quenched with a saturated aqueous NaHCO 3 (70 ml). After evaporation of CH 3 CN, the whole was extracted with CH 2 Cl 2 (30 ml x 3), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (MeOH-AcOEt, 1:20) to afford an inseparable mixture of trans-14 and cis-14 as a colorless solid (2.22 g, 67%, trans:cis = 96:4). IR (ATR) 2930, 2820, 1730, 1675 cm -1 ; MS (CI+) m/z 224 (MH + ); HRMS calcd for C 11 H 14 NO , found trans-14: 1 H NMR (300 MHz, CDCl 3 ) δ 9.43 (s, 1H), (m, 1H), 5.27 (ddd, J = 10.0, 5.0, 3.7 Hz, 1H), (m, 1H), 4.39 (br dd, J = 13.3, 6.7 Hz, 1H), 2.86 (dd, J = 17.4, 8.4 Hz, 1H), (m, 1H), 2.53 (ddd, J = 17.4, 6.3, 1.5 Hz, 1H), (m, 2H), 2.16 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 191.3, 170.4, 170.3, 149.7, 140.2, 69.7, 58.8, 38.3, 35.2, 25.5, cis-14: 1 H NMR (300 MHz, CDCl 3 ) δ 9.45 (s, 1H), (m, 1H), 5.69 (t, J = 5.0 Hz, 1H), (m, 1H), 4.38 (br, dd, J = 12.8, 5.7 Hz, 1H), (m, 2H), (m, 2H), 2.45 (d, J = 17.8 Hz, 1H), 1.91 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 191.0, 170.7, 169.6, 149.0, 137.5, 68.7, 3

4 56.9, 39.3, 35.0, 25.5, The spectral data of trans-14 and cis-14 were measured after deprotection of the acetal of trans-15 and cis-15 obtained below by acid hydrolysis, respectively. (1S,8aR)-8-[1,3-Dioxolan-2-yl]-3-oxo-1,2,3,5,6,8a-hexahydroindolizin-1-yl acetate (trans-15) and (1S,8aS)-8-[1,3-Dioxolan-2-yl]-3-oxo-1,2,3,5,6,8a-hexahydroindolizin-1-yl acetate (cis-15) A solution of indolizidine 14 (350 mg, 1.57 mmol) (mixture of trans-14 and cis-14), ethylene glycol (393 µl, 7.06 mmol), and PTSA (3 mg, mmol) in benzene (20 ml) was heated at reflux for 13 h. The reaction mixture was poured into a saturated aqueous NaHCO 3 (150 ml). The whole was extracted with CH 2 Cl 2 (200 ml x 4), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (AcOEt) to afford trans-15 as colorless crystals (347 mg, 88%) and cis-15 as a colorless oil (30.2 mg, 8%). trans-15: mp o C (hexane-acoet); [α] 25 D 88.5 (c 0.50, CHCl 3 ); IR (ATR) 2937, 2883, 1738, 1674 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.15 (br d, J = 6.0 Hz, 1H), 5.46 (br dt, J = 9.2, 4.1 Hz, 1H), 5.23 (s, 1H), (m, 1H), 4.27 (br dd, J = 13.2, 6.6 Hz, 1H), (m, 4H), 2.92 (dd, J = 17.6, 8.2 Hz, 1H), (m, 1H), 2.41 (ddd, J =17.6, 5.5, 1.5 Hz, 1H), (m, 1H), (m, 4H); 13 C NMR (75 MHz, CDCl 3 ) δ 170.6, 169.9, 132.6, 128.8, 103.8, 70.2, 64.9, 64.8, 60.0, 38.2, 36.0, 23.8, 20.9; MS (CI+) m/z 268 (MH + ); HRMS calcd for C 13 H 18 NO , found cis-15: [α] 25 D +194 (c 0.45, CHCl 3 ); IR (ATR) 2887, 1735, 1686 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.24 (d, J = 6.2 Hz, 1H), 5.49 (t, J = 4.5 Hz, 1H), 5.17 (s, 1H), (m, 1H), 4.26 (br dd, J = 12.9, 6.0 Hz, 1H), (m, 4H), (m, 2H), (m, 3H), 1.98 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 170.8, 170.4, 130.6, 129.7, 104.4, 69.4, 65.0, 64.9, 57.6, 39.8, 35.7, 24.2, 21.0; MS (ESI+) m/z 268 (MH + ); HRMS calcd for C 13 H 18 NO , found (1S,7aR)-7-Formyl-3-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizidin-1-yl acetate (trans-18) and (1S,7aS)-7-Formyl-3-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizidin-1-yl acetate (cis-18) An inseparable 91:9 mixture (58.7 mg, 36%, colorless oil) of trans-18 and cis-18 was obtained from aldehyde 16 (200 mg, mmol) prepared from L-malic acid 1) by using procedure similar to that for 14. trans-18: 1 H NMR (300 MHz, CDCl 3 ) δ 9.80 (s, 1H), 6.94 (apparent q, J = 1.8 Hz, 1H), 5.35 (ddd, J = 9.3, 8.4, 6.6 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 2.86 (dd, J = 16.5, 8.4 Hz, 1H), 2.75 (ddd, J = 16.2, 9.3, 0.9 Hz, 1H), 2.18 (s, 3H). cis-18: 1 H NMR (300 MHz, CDCl 3 ) δ 9.80 (s, 1H), 6.97 (apparent q, J = 2.1 Hz, 1H), 5.67 (t, J = 4.8 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 3.03 (dd, J = 17.4, 4.8 Hz, 1H), 2.41 (d, J = 17.1 Hz, 1H), 1.92 (s, 3H). 4

5 These spectral data of trans-18 and cis-18 are identical with those reported. 1) For the preparation of trans-19 and cis-19 (3S)-3-Acetoxy-1-(4-penten-1-yl)pyrrolidine-2,5-dione This compound (3.89 g, 83%, colorless oil) was obtained from L-malic acid (2.80 g, 20.9 mmol) and 5-amino-1-pentene (4.00 g, 47.0 mmol) prepared from 3-butene-1-ol in three steps 2) by using procedure similar to that for 12. [α] 22 D 17.2 (c 0.50, CHCl 3 ); IR (ATR) 2944, 1749, 1705 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 5.79 (ddt, J = 17.1, 10.2, 6.6 Hz, 1H), 5.41 (dd, J = 8.8, 4.8 Hz, 1H), (m, 2H), 3.57 (br t, J = 7.3 Hz, 2H), 3.15 (dd, J = 18.3, 8.8 Hz, 1H), 2.66 (dd, J = 18.3, 5.0 Hz, 1H), 2.17 (s, 3H), (m, 2H), 1.71 (br quin, J = 7.3 Hz, 2H); 13 C NMR (75 MHz, CDCl 3 ) δ 173.4, 173.2, 169.9, 137.1, 115.5, 67.5, 38.7, 35.7, 30.9, 26.5, 20.5; MS (CI+) m/z 226 (MH + ); HRMS calcd for C 11 H 16 NO , found (2R,3S)-1-(4-Pentenyl)-2-ethoxy-5-oxopyrrolidin-3-yl acetate (trans) and (2S,3S)-1-(4-Pentenyl)-2-ethoxy-5-oxopyrrolidin-3-yl acetate (cis) A trans-isomer as a colorless oil (2.07 g, 61%) and a cis-isomer as a colorless oil (607 mg, 18%) were obtained from imide (3.00 g, 13.3 mmol) prepared above by using procedure similar to that for 13. trans-isomer: [α] 23 D 33.5 (c 0.51, CHCl 3 ); IR (ATR) 2960, 2933, 1742, 1705 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 5.81 (ddt, J = 17.1, 10.2, 6.6 Hz, 1H), (m, 3H), 4.69 (s, 1H), 3.74 (dq, J = 9.3, 7.0 Hz, 1H) 3.60 (dq, J = 9.3, 7.0 Hz, 1H) (m, 1H) 3.15 (ddd, J = 13.5, 8.1, 5.4 Hz, 1H), 2.89 (ddd, J = 17.9, 6.5, 0.7 Hz, 1H), 2.32 (d, J = 18.0 Hz, 1H), (m, 2H), 2.09 (s, 3H), (m, 2H), 1.24 (t, J = 7.0 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 172.5, 170.3, 137.6, 115.2, 93.1, 70.6, 63.7, 40.1, 35.7, 30.9, 26.8, 21.0, 15.2; MS (CI+) m/z 256 (MH + ); HRMS calcd for C 13 H 22 NO , found cis-isomer: [α] 23 D 51.3 (c 0.50, CHCl 3 ); IR (ATR) 2990, 2933, 1740, 1702 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 5.80 (ddt, J = 16.8, 10.5, 6.6 Hz, 1H), 5.17 (td, J = 8.3, 5.3 Hz, 1H), (m, 2H), 5.04 (d, J = 5.3 Hz, 1H), (m, 3H), 3.10 (ddd, J = 18.8, 8.4, 5.4 Hz, 1H), 2.67 (dd, J = 18.6, 8.1 Hz, 1H), 2.61 (dd, J = 18.3, 8.1 Hz, 1H), (m, 2H), 2.13 (s, 3H), (m, 2H), 1.20 (t, J = 6.9 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 170.9, 170.7, 137.4, 115.3, 88.1, 67.8, 65.5, 40.3, 34.5, 31.0, 26.8, 20.7, 15.5; MS (CI+) m/z 256 (MH + ); HRMS calcd for C 13 H 22 NO , found (2R,3S)-2-Ethoxy-5-oxo-1-[(4E)-6-oxo-4-hexenyl]pyrrolidin-3-yl acetate (17) This compound (1.36 g, 82%, brown oil) was obtained from trans-aminal (1.50 g, 5.88 mmol) 5

6 prepared above by using procedure similar to that for 11. [α] 22 D 39.1 (c 0.50, CHCl 3 ); IR (ATR) 2990, 2934, 1741, 1685 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 9.52 (d, J = 7.7 Hz, 1H), 6.86 (dt, J = 15.6, 6.7 Hz, 1H), 6.14 (ddt, J = 15.6, 7.9, 1.5 Hz, 1H), 5.08 (d, J = 6.1 Hz, 1H), 4.68 (s, 1H), 3.75 (dq, J = 9.3, 7.1 Hz, 1H), 3.59 (dq, J = 9.3, 7.1 Hz, 1H), 3.47 (br dt, J = 13.8, 7.5 Hz, 1H), 3.30 (br ddd, J = 13.8, 7.5, 6.3 Hz, 1H), 2.90 (dd, J = 18.1, 6.5 Hz, 1H), (m, 3H), 2.09 (s, 3H), (m, 2H), 1.24 (t, J = 7.1 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 193.9, 172.7, 170.2, 157.1, 133.3, 93.4, 70.4, 64.0, 40.3, 35.7, 29.9, 26.2, 21.0, 15.2; MS (EI+) m/z 283 (M + ); HRMS calcd for C 14 H 21 NO , found (1S,9aR)-9-Formyl-3-oxo-2,3,5,6,7,9a-hexahydro-1H-pyrrolo[1,2-a]azepin-1-yl acetate (trans-19) and (1S,9aS)-9-Formyl-3-oxo-2,3,5,6,7,9a-hexahydro-1H-pyrrolo[1,2-a]azepin-1-yl acetate (cis-19) An inseparable 66:34 mixture (107 mg, 64%, colorless oil) of trans-19 and cis-19 was obtained from aldehyde (200 mg, mmol) prepared above by using procedure similar to that for 14. IR (ATR) 2943, 1739, 1677 cm -1 ; MS (CI+) m/z 238 (MH + ); HRMS calcd for C 12 H 16 NO , found trans-19: 1 H NMR (300 MHz, CDCl 3 ) δ 9.40 (s, 1H), 6.98 (br ddd, J = 8.1, 5.7, 1.2 Hz, 1H), 5.35 (dt, J = 6.9, 2.7 Hz, 1H), 4.63 (s, 1H), 4.25 (ddd, J = 13.8, 8.1, 6.3 Hz, 1H), 2.97 (br dt, J = 14.1, 6.9 Hz, 1H), 2.74 (dd, J = 17.8, 7.0 Hz, 1H), (m, 3H), (m, 1H), 2.10 (s, 3H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 192.9, 172.1, 170.2, 156.0, 142.1, 70.7, 64.4, 39.2, 37.2, 24.6, 24.2, cis-19: 1 H NMR (300 MHz, CDCl 3 ) δ 9.36 (s, 1H), 7.02 (dd, J = 8.3, 5.9 Hz, 1H), 5.54 (apparent t, J = 5.0 Hz, 1H), 4.90 (dd, J = 4.8, 1.5 Hz, 1H), 4.17 (ddd, J = 14.4, 7.8, 1.5 Hz, 1H), (m, 3H), 2.49 (d, J = 17.6 Hz, 1H), (m, 1H), (m, 1H), 1.96 (s, 3H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 192.3, 172.0, 169.5, 154.1, 139.5, 69.4, 62.4, 38.2, 38.1, 23.5, 23.5, The spectral data of trans-19 and cis-19 were measured after deprotection of the acetal of trans-20 and cis-20 obtained below by acid hydrolysis, respectively. (1S,9aR)-9-(1,3-Dioxolan-2-yl)-3-oxo-2,3,5,6,7,9a-hexahydro-1H-pyrrolo[1,2-a]azepin-1-yl acetate (trans-20) and (1S,9aS)-9-(1,3-Dioxolan-2-yl)-3-oxo-2,3,5,6,7,9a-hexahydro-1H-pyrrolo[1,2-a]azepin-1-yl acetate (cis-20) Trans-20 as colorless crystals (98.3 mg, 52%) and cis-20 as an orange oil (50.1 mg, 27%) were obtained from aldehyde (160 mg, mmol) (mixture of trans-19 and cis-19) prepared above by using procedure similar to that for 15. 6

7 trans-20: mp o C (hexane-acoet); [α] 24 D (c 0.50, CHCl 3 ); IR (ATR) 2930, 2892, 1728, 1691 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.15 (br dd, J = 8.4, 6.9 Hz, 1H), 5.62 (dt, J = 6.5, 1.9 Hz, 1H), 5.19 (s, 1H), 4.38 (br s, 1H), 4.14 (ddd, J = 14.1, 8.1, 6.0 Hz, 1H), (m, 2H), (m, 2H), 3.00 (br dt, J = 13.8, 6.9 Hz, 1H), 2.83 (dd, J = 17.6, 6.6 Hz, 1H), 2.35 (dd, J =17.7, 1.4 Hz, 1H), (m, 3H), 2.06 (s, 3H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 172.4, 170.1, 135.0, 134.5, 105.6, 71.1, 66.0, 65.1, 64.9, 39.9, 37.3, 24.9, 23.2, 21.1; MS (ESI+) m/z 282 (MH + ); HRMS calcd for C 14 H 20 NO , found cis-20: [α] 24 D (c 0.50, CHCl 3 ); IR (ATR) 2944, 2874, 1738, 1681 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.20 (dd, J = 8.9, 6.1 Hz, 1H), 5.43 (t, J = 5.0 Hz, 1H), 5.11 (s, 1H), 4.52 (dd, J = 4.3, 1.0 Hz, 1H), (m, 5H), 2.99 (ddd, J = 13.8, 10.8, 7.5 Hz, 1H), 2.75 (ddd, J = 17.4, 5.5, 0.7 Hz, 1H), (m, 1H), 2.42 (d, J = 17.6 Hz, 1H), (m, 2H), 2.00 (s, 3H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 171.9, 169.9, 133.8, 132.5, 105.8, 70.5, 65.2, 65.1, 63.3, 38.9, 37.9, 23.2, 21.4, 21.1; MS (ESI+) m/z 282 (MH + ); HRMS calcd for C 14 H 20 NO , found (1S,8aR)-8-(1,3-Dioxolan-2-yl)-1-hydroxy-1,5,6,8a-tetrahydro-2H-indolizin-3-one (21) To a solution of trans-15 (2.50 g, 9.95 mmol) in EtOH (6.5 ml) was added NaOEt (37.9 mg, mmol) in EtOH (6.5 ml) at 4 o C, then the mixture was stirred at room temperature. After 1 h, a solution of NaOEt (37.9 mg, mmol) in EtOH (2 ml) was added twice every 1 h. The mixture was poured into a saturated aqueous NH 4 Cl (100 ml), and the whole was extracted with CH 2 Cl 2 (40 ml x 2), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (MeOH-AcOEt, 1:20) to afford 21 as colorless crystals (1.57 g, 70%). mp o C (hexane-acoet); [α] 25 D 126 (c 0.50, CHCl 3 ); IR (ATR) 3292, 2864, 1654 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.20 (d, J = 5.7 Hz, 1H), 5.29 (s, 1H), (m, 7H), 3.82 (d, J = 2.4 Hz, 1H), (m, 3H), (m, 2H); 13 C NMR (75 MHz, CDCl 3 ) δ 170.3, 133.1, 128.5, 104.3, 72.3, 65.2, 64.5, 61.8, 39.4, 35.0, 24.6; MS (EI+) m/z 225 (MH + ); HRMS calcd for C 11 H 15 NO , found (1S,8aR)-8-(1,3-Dioxolan-2-yl)-3-oxo-1,2,3,5,6,8a-hexahydro-indolizin-1-yl phenoxythiocarbonate A solution of 21 (1.55 g, 6.88 mmol), DMAP (1.26 g, 10.3 mmol), and phenyl chlorothionoformate (1.40 ml, 10.3 mmol) in CH 2 Cl 2 (44 ml) was heated at reflux for 24 h. After concentration, the crude product was purified by column chromatography on silica gel (hexane-acoet, 1:2) to afford the title compound as colorless crystals (2.48 g, quant.). mp o C (hexane-acoet); [α] 25 D 30.0 (c 0.50, CHCl 3 ); IR (ATR) 2952, 2902, 2851, 1689 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ (m, 2H), (m, 1H), (m, 2H), 7

8 6.19 (br d, J = 6.1 Hz, 1H), 5.83 (ddd, J = 8.2, 5.9, 4.8 Hz, 1H), 5.27 (s, 1H), (m, 1H), 4.32 (br dd, J = 13.2, 6.6 Hz, 1H), (m, 2H), (m, 2H), 3.16 (dd, J = 17.5, 8.3 Hz, 1H), 2.88 (br td, J = 11.4, 4.8 Hz, 1H), 2.62 (ddd, J = 17.6, 5.9, 1.4 Hz, 1H), (m, 1H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 222.4, 198.3, 181.8, 161.0, 158.6, 158.1, 155.3, 150.3, 133.3, 108.1, 93.6, 93.5, 87.4, 66.2, 64.5, 52.5; MS (ESI+) m/z 362 (MH + ); HRMS calcd for C 18 H 20 NO 5 S , found (8aS)-8-(1,3-Dioxolan-2-yl)-1,5,6,8a-tetrahydro-2H-indolizin-3-one (22) A solution of phenoxythiocarbonate derivative prepared above (2.45 g, 6.78 mmol), n Bu 3 SnH (5.39 ml, 20.3 mmol), and AIBN (55.7 mg, mmol) in benzene (34 ml) was heated at reflux for 30 min. After concentration, the crude product was purified by column chromatography on silica gel containing 10%w/w KF 3) (MeOH-AcOEt, 1:20) to afford 22 as colorless crystals (1.33 g, 94%). mp o C (hexane-acoet); [α] 25 D 212 (c 0.50, CHCl 3 ); IR (ATR) 3475, 2849, 1660 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.06 (br d, J = 5.7 Hz, 1H), 5.23 (s, 1H), (m, 1H), 4.23 (dd, J = 12.6, 6.0 Hz, 1H), (m, 4H), 2.76 (br td, J = 11.7, 4.8 Hz, 1H), (m, 5H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 173.2, 135.3, 126.4, 104.3, 65.1, 64.7, 54.5, 35.8, 31.9, 26.4, 24.4; MS (EI+) m/z 209 (M + ); HRMS calcd for C 11 H 15 NO , found (8aS)-3-Oxo-1,2,3,5,6,8a-hexahydroindolizine-8-carbaldehyde (10) A solution of 22 (1.30 g, 6.21 mmol) and PTSA (1.18 g, 6.21 mmol) in acetone (62 ml) containing H 2 O (1.6 ml) was heated at reflux for 15 min. After concentration, the crude product was purified by column chromatography on silica gel (MeOH-AcOEt, 1:20) to afford 10 as a colorless oil (997 mg, 97%). [α] 25 D 424 (c 0.25, CHCl 3 ); IR (ATR) 3450, 2935, 2834, 1671 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 9.44 (s, 1H), (m, 1H), (m, 2H), (m, 2H), (m, 4H), (m, 1H); 13 C NMR (75 MHz, CDCl 3 ) δ 191.7, 173.3, 147.7, 142.6, 53.6, 35.1, 31.5, 26.0, 25.9; MS (EI+) m/z 165 (M + ); HRMS calcd for C 9 H 11 NO , found (8aS, 1 S, 6 S)-8-[(R)-Hydroxy(6-methyl-2 -oxo-cyclohex-3 -en-1-yl) methyl]-1,5,6,8atetrahydro-2h-indolizin-3-one (23) To a solution of (S)-5-methylcyclohexenone (9) 4) (500 mg, 4.54 mmol) in CH 2 Cl 2 (20 ml) was added dropwise successively i Pr 2 NEt (791 µl, 6.81 mmol), and n Bu 2 BOTf (1.0 M, 4.54 ml, 6.81 mmol) at -78 o C. After stirring at the same temperature for 1 h, a solution of aldehyde 10 (500 mg, 3.03 mmol) in CH 2 Cl 2 (10 ml) was added slowly at -78 o C. The mixute was allowed to warm to room temperature and stirring was continued for 1 h. The reaction was quenched by addition of MeOH (1.4 ml) and 30% H 2 O 2 (1.4 ml) at 4 o C, and then the mixture was poured into a saturated 8

9 aqueous NaHCO 3 (30 ml). The whole was extracted with CH 2 Cl 2 (20 ml x 2), washed with brine (20 ml), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (MeOH-AcOEt, 1:10) to afford 23 as colorless crystals (830 mg, quant.). mp o C (hexane-etoh); [α] 22 D 100 (c 0.50, CHCl 3 ); IR (ATR) 3404, 2918, 1648 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 6.91 (dt, J = 10.1, 4.1 Hz, 1H), 6.05 (dt, J = 10.1, 1.9 Hz, 1H), 5.78 (d, J = 5.5 Hz, 1H), (m, 3H), 2.73 (td, J = 12.1, 4.7 Hz, 1H), (m, 10H), (m, 1H), 1.14 (d, J = 7.0 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 201.1, 173.1, 148.4, 138.6, 128.6, 123.9, 73.0, 56.1, 55.3, 35.7, 31.9, 31.0, 30.7, 27.3, 24.7, 19.9; MS (ESI+) m/z 276 (MH + ); HRMS calcd for C 16 H 22 NO , found Determination of Stereochemistry at C-10 of 23 Stereochemistry of 23 was determined by modified Mosher s method. Derivatization of 23 to the corresponding (R)- or (S)-MTPA esters was conducted according to a usual method, and 1 H NMR data are as follows. (R)-MTPA ester of 23: 1 H NMR (300 MHz, CDCl 3 ) δ (m, 5H), (m, 1H), 6.17 (d, J = 5.9 Hz, 1H), 5.97 (dd, J = 10.3, 2.9 Hz, 1H), 5.85 (d, J = 10.6 Hz, 1H), 4.24 (dd, J = 13.0, 6.4 Hz, 1H), (m, 1H), 3.40 (d, J = 0.7 Hz, 3H), (m, 3H), (m, 7H), (m, 1H), 1.10 (d, J = 7.2 Hz, 3H). (S)-MTPA ester of 23: 1 H NMR (300 MHz, CDCl 3 ) δ (m, 5H), (m, 1H), 6.13 (d, J = 5.5 Hz, 1H), 6.00 (dd, J = 10.3, 2.8 Hz, 1H), 5.81 (d, J = 11.4 Hz, 1H), 4.16 (dd, J = 12.7, 5.4 Hz, 1H), (m, 1H), 3.58 (d, J = 1.7 Hz, 3H), (m, 3H), (m, 7H), 1.10 (d, J = 7.2 Hz, 3H), (m, 1H). MTPA O O H C O N H Fig. 1 Modified Mosher s method: differences of the chemical shifts ( δ = (δ S -δ R ), CDCl 3 ) between (R)- and (S)-MTPA esters of 23. (8aS,1 R,6 S)-8-[6 -Methyl-2 -oxo-cyclohex-3 -enecarbonyl]-1,5,6,8a-tetrahydro-2h-indolizin-3 -one (8) To a solution of 23 (500 mg, 1.82 mmol) in CH 2 Cl 2 (18 ml) was added a solution of Dess-Martin periodinane (15%w/w, 7.76 ml, 3.63 mmol) in CH 2 Cl 2 at 4 o C, and then the mixute was allowed to 9

10 warm to room temperature and stirring was continued for 3 h. The mixture was poured into a saturated aqueous NaHCO 3 (30 ml) and the whole was extracted with CH 2 Cl 2 (20 ml x 3), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (MeOH-AcOEt, 1:20) to afford 8 as a colorless syrup (436 mg, 88%). [α] 24 D 57.6 (c 0.50, CHCl 3 ); IR (ATR) 2906, 1685, 1671, 1642, 1625 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ 7.02 (ddd, J = 10.2, 5.7, 2.7 Hz, 1H), (m, 1H), 6.07 (dd, J = 10.1, 2.7, 1.3 Hz, 1H), (m, 1H), 4.29 (br dd, J = 12.0, 6.0 Hz, 1H), 3.81 (d, J = 11.2 Hz, 1H), (m, 3H), (m, 5H), 2.17 (ddt, J = 19.1, 10.3, 2.8 Hz, 1H), (m, 1H), 0.98 (d, J = 6.6 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 197.7, 196.3, 173.2, 150.0, 142.8, 140.0, 129.3, 60.5, 54.6, 34.8, 33.2, 33.0, 31.5, 26.7, 25.6, 19.9; MS (ESI+) m/z 274 (MH + ); HRMS calcd for C 16 H 20 NO , found (8aS,1 R,2 S,3 S)-8-[2 -Methyl-6 -oxo-4 -phenylsulfanyl-cyclohexanecarbonyl]-1,5,6,8a-tetrahy dro-2h-indolizin-3-one (24) To a solution of 8 (100 mg, mmol) and PhSH (112 µl, 1.10 mmol) in MeOH (5 ml) was added 60% HClO 4 (36.8 µl, mmol) at room temperature, and stirring was continued at the same temperature for 2 h. After concentration in vacuo, the crude product was purified by column chromatography on silica gel (MeOH-AcOEt, 1:20) to afford sulfide 24 as a colorless syrup (132 mg, 94% yield). [α] 22 D -185 (c 0.30, CHCl 3 ); IR (ATR) 2930, 1709, 1655 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), 6.85 (br d, J = 5.3 Hz, 1H), (m, 1H), 4.29 (dd, J = 13.0, 6.4 Hz, 1H), (m, 1H), 3.70 (d, J = 8.3 Hz, 1H), (m, 9H), 2.17 (dt, J = 14.4, 4.8 Hz, 1H), 1.91 (ddd, J = 14.4, 9.6, 3.9 Hz, 1H), (m, 1H), 0.96 (d, J = 6.8 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 205.3, 195.8, 173.5, 141.4, 139.2, 133.1, 132.9, 129.1, 127.8, 63.9, 54.6, 45.9, 43.9, 36.0, 34.9, 32.2, 31.5, 26.6, 25.4, 20.3; MS (ESI+) m/z 384 (MH + ); HRMS calcd for C 22 H 26 N 2 O 3 S , found (8aS,1 R,3 S,5 S)-(3-Methyl-5-phenylsulfanyl)-2-(3-thioxo-1,2,3,5,6,8a-hexahydro-indolizine-8- carbonyl)-cyclohexanone (25) A mixture of 24 (110 mg, mmol) and Lawesson s reagent (63.7 mg, mmol) in toluene-ch 2 Cl 2 (2:1, 6 ml) was stirred at 65 o C for 15 min. After concentration, the crude product was purified by column chromatography on silica gel (hexane-acoet, 1:1) to afford thioamide 25 as a colorless syrup (92.6 mg, 81%). [α] 23 D -263 (c 0.30, CHCl 3 ); IR (ATR) 2929, 1709, 1663 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ (m, 2H), (m, 3H), 6.90 (br d, J = 4.2 Hz, 1H), 5.07 (dd, J = 12.8, 5.7 Hz, 1H), (m, 1H), (m, 1H), 3.69 (d, J = 8.8 Hz, 1H), (m, 9H), (m, 10

11 1H), 1.91 (ddd, J = 14.1, 9.6, 3.9 Hz, 1H), (m, 1H), 0.95 (d, J = 6.6 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 205.1, 200.0, 195.6, 140.8, 138.9, 133.1, 133.0, 129.1, 127.9, 64.2, 61.9, 45.8, 44.3, 43.9, 39.9, 36.0, 32.1, 28.3, 25.1, 20.3; MS (ESI+) m/z 400 (MH + ); HRMS calcd for C 22 H 26 NO 2 S , found Grandisine D trifluoroacetic acid salt (5 TFA) To a solution of 25 (50.0 mg, mmol) in CH 3 CN (1.2 ml) was added Me 3 OBF 4 (55.5 mg, mmol) at 4 o C and then the mixture was stirred at room temperature for 1 h. After concentration, the residue (50.0 mg, mmol) was dissolved in MeOH (1.2 ml), and NaBH 3 CN (15.7 mg, mmol) was added to the solution. The mixture was stirred at room temperature for 1 h, and then was poured into a saturated aqueous NaHCO 3 (5 ml), and extracted with CH 2 Cl 2 (5 ml x 3), dried (Na 2 SO 4 ), and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (28% NH 3 -MeOH-AcOEt, 1:10:50) to afford 5 as a colorless oil (20.6 mg, 63% yield). A solution of 5 in CH 2 Cl 2 (1 ml) at 4 o C was added TFA (6.0 µl, mmol) and then the resulting mixture was allowed to warm to room temperature and stirring was continued for 1 h and concentrated in vacuo to afford 5 TFA. [α] 23 D (c 0.09, MeOH); IR (ATR) 2955, 2926, 2873, 2795, 1675, 1655 cm -1 ; 1 H NMR (300 MHz, CDCl 3 ) δ (br s, 1H), 7.34 (apparent t, J = 3.8 Hz, 1H), (m, 1H), 5.96 (dd, J = 10.0, 2.1 Hz, 1H), (m, 1H), 4.32 (d, J = 11.6 Hz, 1H), (m, 1H), (m, 2H), (m, 1H), (m, 2H), (m, 3H), (m, 1H), (m, 2H), (m, 1H), 0.85 (d, J = 6.2 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ 198.4, 196.8, 151.8, 140.2, 137.3, 128.4, 59.3, 58.0, 53.0, 43.1, 33.0, 32.7, 28.1, 23.0, 20.3, 19.2; MS (ESI+) m/z 260 (MH + ); HRMS calcd for C 16 H 22 NO , found We attribute the difference in the optical rotation data [found, [α] 23 D (c 0.09, MeOH), previously reported, [α] 23 D (c 0.09, MeOH)] to the synthetic 5 having a much higher level of purity. 11

12 O 9 16 H H N O Grandisine D 5 O H H N O Synthetic (5) 1 H-NMR (DMSO-d 6 ) (, multiplicity, J (Hz)) Reported 5) (600 MHz) Observed (Synthetic) (300 MHz) 1α 1.62 dddd (8.4, 9.6, 9.6, 9.6) 1.64 m 1β 2.40 dddd (8.4, 9.6, 9.6, 9.6) 2α 2.00 t (7.8) 2.01 m 2β 2.00 t (7.8) 2.01 m 3α 3.28 m 3.34 m 3β 3.48 ddd (10.8, 10.8, 10.8) 3.55 m bs bs 5α 3.28 m 3.34 m 5β 3.09 ddd (6.6, 6.6, 12.6) 3.11 m 6α 2.60 m 6β 2.60 m bdd (4.0, 4.0) 7.34 dd (3.8, 3.8) dd (8.4, 8.4) 4.39 bs d (11.4) 4.32 d (11.6) d (9.6) 5.96 dd (10.0, 2.1) ddd (5.4, 9.6, 9.6) 7.15 m 15α 2.20 dd (11.4, 19.8) 2.20 m 15β 2.45 m ddq (6.6, 6.6, 11.4) d (6.6) 0.85 d (6.2) 13 C-NMR (DMSO-d 6 ) (, multiplicity) Reported 5) (125 MHz) Observed (Synthetic) (75.5 MHz) , CH , CH , CH , CH , CH , CH , CH , CH , CH , CH , CH 140.2, CH , qc 137.3, qc , CH 58.0, CH , qc 198.4, qc , CH 59.3, CH , qc 196.8, qc , CH 128.4, CH , CH CH , CH , CH , CH 33.0, CH , CH , CH 3 References 1) Myers, E. L.; De Vries, J. G.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2007, 46, ) Zabawa, T. P.; Chemler, S. R. Org. Lett. 2007, 9, ) Harrowven, D. C.; Guy, I. L. Chem. Commun. 2004, ) (a) Katsuhara, J. J. Org. Chem. 1967, 32, (b) Mutti, S.; Daubié, C.; Decalogne, F.; Fournier, R.; Rossi, P. Tetrahedron Lett. 1996, 37, (c) Caine, D.; Procter, K.; Cassell, R. A. J. Org. Chem. 1984, 49, (d) Oppolzer, W.; Petrzilka, M. Helv. Chim. Acta 1978, 61, ) Katavic, P. L.; Venables, D. A.; Forster, P. I.; Guymer, G.; Carroll, A. R. J. Nat. Prod. 2006, 69,

13 13

14 14

15 15

16 16

17 17

18 18

19 19

20 20

21 21

22 22

23 23

24 24

25 25

26 26

27 27

28 28

29 29

30 30

31 31

32 32

33 33

34 34

35 35

36 36

37 37

38 38

39 39

40 40

41 41

42 42

43 43

44 44

45 45

46 46

47 47

48 48

49 49

50 50

51 51

52 52

53 53

54 54

55 55

56 56

57 57

58 58

59 59

60 60

61 61

62 62

63 63

64 64

65 65

Supporting information

Supporting information Supporting information Diversity Oriented Asymmetric Catalysis (DOAC): Stereochemically Divergent Synthesis of Thiochromanes Using an Imidazoline-aminophenol aminophenol (IAP)-Ni Catalyzed Michael/Henry

More information

Preparation of Stable Aziridinium Ions and Their Ring Openings

Preparation of Stable Aziridinium Ions and Their Ring Openings Supplementary Information Preparation of Stable Aziridinium Ions and Their Ring Openings Yongeun Kim a Hyun-Joon Ha*, a Sae Young Yun b and Won Koo Lee,*,b a Department of Chemistry and Protein Research

More information

Masatoshi Shibuya,Takahisa Sato, Masaki Tomizawa, and Yoshiharu Iwabuchi* Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences,

Masatoshi Shibuya,Takahisa Sato, Masaki Tomizawa, and Yoshiharu Iwabuchi* Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Oxoammonium ion/naclo 2 : An Expedient, Catalytic System for One-pot Oxidation of Primary Alcohols to Carboxylic Acid with Broad Substrate Applicability Masatoshi Shibuya,Takahisa Sato, Masaki Tomizawa,

More information

Rameshwar Prasad Pandit and Yong Rok Lee * School of Chemical Engineering, Yeungnam University, Gyeongsan , Korea

Rameshwar Prasad Pandit and Yong Rok Lee * School of Chemical Engineering, Yeungnam University, Gyeongsan , Korea Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2014 Novel ne-pot Synthesis of Diverse γ,δ-unsaturated β-ketoesters by Thermal

More information

p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of

p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of Supporting Information for: p-toluenesulfonic Acid-Mediated 1,3-Dipolar Cycloaddition of Nitroolefins with NaN 3 for Synthesis of 4-Aryl-NH-1,2,3-triazoles Xue-Jing Quan, Zhi-Hui Ren, Yao-Yu Wang, and

More information

Electronic Supplementary Information. Quinine/Selectfluor Combination Induced Asymmetric Semipinacol Rearrangement of

Electronic Supplementary Information. Quinine/Selectfluor Combination Induced Asymmetric Semipinacol Rearrangement of Electronic Supplementary Information Quinine/Selectfluor Combination Induced Asymmetric Semipinacol Rearrangement of Allylic Alcohols: An Effective and Enantioselective Approach to α Quaternary β Fluoro

More information

Supporting Information. Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base

Supporting Information. Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base Supporting Information Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base Feng Wang, a Haijun Yang, b Hua Fu, b,c * and Zhichao Pei a * a College

More information

Lewis acid-catalyzed regioselective synthesis of chiral α-fluoroalkyl amines via asymmetric addition of silyl dienolates to fluorinated sulfinylimines

Lewis acid-catalyzed regioselective synthesis of chiral α-fluoroalkyl amines via asymmetric addition of silyl dienolates to fluorinated sulfinylimines Supporting Information for Lewis acid-catalyzed regioselective synthesis of chiral α-fluoroalkyl amines via asymmetric addition of silyl dienolates to fluorinated sulfinylimines Yingle Liu a, Jiawang Liu

More information

Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature

Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature Supplementary Information Manganese powder promoted highly efficient and selective synthesis of fullerene mono- and biscycloadducts at room temperature Weili Si 1, Xuan Zhang 1, Shirong Lu 1, Takeshi Yasuda

More information

Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins

Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins Electronic Supplementary Information (ESI) Schwartz s reagent-mediated regiospecific synthesis of 2,3-disubstituted indoles from isatins A. Ulikowski and B. Furman* Institute of Organic Chemistry, Polish

More information

Synthesis and Blastocyst Implantation Inhibition Potential of Lupeol Derivatives in Female Mice

Synthesis and Blastocyst Implantation Inhibition Potential of Lupeol Derivatives in Female Mice Supporting Information Rec. Nat. Prod. 9:4 (2015) 561-566 Synthesis and Blastocyst Implantation Inhibition Potential of Lupeol Derivatives in Female Mice Anita Mahapatra 1*, Purvi Shah 1, Mehul Jivrajani

More information

Supporting Information

Supporting Information J. Am. Chem. Soc. Supporting Information S 1 Enantioselective rganocatalytic Indole Alkylations. Design of a New and Highly Effective Chiral Amine for Iminium Catalysis. Joel F. Austin and David W. C.

More information

Zinc Chloride Promoted Formal Oxidative Coupling of Aromatic Aldehydes and Isocyanides to α- Ketoamides

Zinc Chloride Promoted Formal Oxidative Coupling of Aromatic Aldehydes and Isocyanides to α- Ketoamides Supporting information for Zinc Chloride Promoted Formal xidative Coupling of Aromatic Aldehydes and Isocyanides to α- Ketoamides Marinus Bouma, Géraldine Masson* and Jieping Zhu* Institut de Chimie des

More information

Copyright Wiley-VCH Verlag GmbH, D Weinheim, Angew. Chem

Copyright Wiley-VCH Verlag GmbH, D Weinheim, Angew. Chem Copyright Wiley-VCH Verlag GmbH, D-69451 Weinheim, 2000. Angew. Chem. 2000. Supporting Information for Salen as Chiral Activator : Anti vs Syn Switchable Diastereoselection in the Enantioselective Addition

More information

Supporting Information. An Efficient Synthesis of Optically Active Physostigmine from Tryptophan via Alkylative Cyclization

Supporting Information. An Efficient Synthesis of Optically Active Physostigmine from Tryptophan via Alkylative Cyclization Supporting Information An Efficient Synthesis of Optically Active Physostigmine from Tryptophan via Alkylative Cyclization Michiaki, Kawahara, Atsushi Nishida, Masako Nakagawa* Faculty of Pharmaceutical

More information

Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction

Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction Enantioselective synthesis of anti- and syn-β-hydroxy-α-phenyl carboxylates via boron-mediated asymmetric aldol reaction P. Veeraraghavan Ramachandran* and Prem B. Chanda Department of Chemistry, Purdue

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Supporting Information Enantioselective Cu-catalyzed 1,4-Addition of Various Grignard Reagents to Cyclohexenone using Taddol-derived Phosphine-Phosphite

More information

Stereoselective Aza-Darzens Reactions of Tert- Butanesulfinimines: Convenient Access to Chiral Aziridines

Stereoselective Aza-Darzens Reactions of Tert- Butanesulfinimines: Convenient Access to Chiral Aziridines Stereoselective Aza-Darzens Reactions of Tert- Butanesulfinimines: Convenient Access to Chiral Aziridines Toni Moragas Solá, a Ian Churcher, b William Lewis a and Robert A. Stockman* a Supplementary Information

More information

Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF

Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF Supporting information Preparation of Fluorinated Tetrahydropyrans and Piperidines using a New Nucleophilic Fluorination Reagent DMPU/HF Otome E. Okoromoba, a Gerald B. Hammond, a, * Bo Xu b, * a Department

More information

Regioective Halogenation of 2-Substituted-1,2,3-Triazole via sp 2 C-H Activation

Regioective Halogenation of 2-Substituted-1,2,3-Triazole via sp 2 C-H Activation Regioective Halogenation of 2-Substituted-1,2,3-Triazole via sp 2 C-H Activation Qingshan Tian, Xianmin Chen, Wei Liu, Zechao Wang, Suping Shi, Chunxiang Kuang,* Department of Chemistry, Tongji University,

More information

Supplemental Material

Supplemental Material Supplemental Material General Methods Unless otherwise indicated, all anhydrous solvents were commercially obtained and stored under nitrogen. Reactions were performed under an atmosphere of dry nitrogen

More information

Supporting Information

Supporting Information Supporting Information Unconventional Passerini Reaction towards α-aminoxyamides Ajay L. Chandgude, Alexander Dömling* Department of Drug Design, University of Groningen, Antonius Deusinglaan 1, 9713 AV

More information

Divergent Construction of Pyrazoles via Michael Addition of N-Aryl Hydrazones to 1,2-Diaza-1,3-dienes

Divergent Construction of Pyrazoles via Michael Addition of N-Aryl Hydrazones to 1,2-Diaza-1,3-dienes Divergent Construction of Pyrazoles via Michael Addition of N-Aryl Hydrazones to 1,2-Diaza-1,3-dienes Serena Mantenuto, Fabio Mantellini, Gianfranco Favi,* and Orazio A. Attanasi Department of Biomolecular

More information

One-pot Synthesis of 1-Alkyl-1H-indazoles. Supporting Information

One-pot Synthesis of 1-Alkyl-1H-indazoles. Supporting Information One-pot Synthesis of 1-Alkyl-1H-indazoles from 1,1-Dialkylhydrazones via Aryne Annulation ataliya A. Markina, Anton V. Dubrovskiy, and Richard C. Larock* Department of Chemistry, Iowa State University,

More information

Ethyl 2-hydroxy-4-methyl-1-((prop-2-yn-1-yloxy)methyl)cyclohex-3-enecarboxylate (16):

Ethyl 2-hydroxy-4-methyl-1-((prop-2-yn-1-yloxy)methyl)cyclohex-3-enecarboxylate (16): General methods: 1 H NMR and 13 C NMR spectra were recorded in CDCl 3 or CDCl3 and CCl 4 as solvent on 300 MHz or 500 MHz spectrometer at ambient temperature. The coupling constant J is given in Hz. The

More information

Supporting Information Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C C Bond Cleavage of 2-Arylin

Supporting Information Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C C Bond Cleavage of 2-Arylin Supporting Information Synthesis of 2-Aminobenzonitriles through Nitrosation Reaction and Sequential Iron(III)-Catalyzed C C Bond Cleavage of 2-Arylindoles Wei-Li Chen, Si-Yi Wu, Xue-Ling Mo, Liu-Xu Wei,

More information

Naoya Takahashi, Keiya Hirota and Yoshitaka Saga* Supplementary material

Naoya Takahashi, Keiya Hirota and Yoshitaka Saga* Supplementary material Supplementary material Facile transformation of the five-membered exocyclic E-ring in 13 2 -demethoxycarbonyl chlorophyll derivatives by molecular oxygen with titanium oxide in the dark Naoya Takahashi,

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2008 69451 Weinheim, Germany Enantioselective Rhodium-catalyzed Addition of Arylboronic Acids to α-ketoesters Hai-Feng Duan, Jian-Hua Xie, Xiang-Chen Qiao, Li-Xin Wang,

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for rganic Chemistry Frontiers. This journal is the Partner rganisations 2016 Supporting Information Fangyi Li, Changgui Zhao, and Jian Wang* Department of Pharmacology

More information

An Unusual Glycosylation Product from a Partially Protected Fucosyl Donor. under Silver Triflate activation conditions. Supporting information

An Unusual Glycosylation Product from a Partially Protected Fucosyl Donor. under Silver Triflate activation conditions. Supporting information An Unusual Glycosylation Product from a Partially Protected Fucosyl Donor under Silver Triflate activation conditions Robin Daly a and Eoin M. Scanlan* a e-mail: eoin.scanlan@tcd.ie a Trinity Biomedical

More information

Supporting Information for. Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of. 3,5-Disubstituted Pyridines: Mechanistic Studies

Supporting Information for. Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of. 3,5-Disubstituted Pyridines: Mechanistic Studies Supporting Information for Use of the Curtius Rearrangement of Acryloyl Azides in the Synthesis of 3,5-Disubstituted Pyridines: Mechanistic Studies Ta-Hsien Chuang* a, Yu-Chi Chen b and Someshwar Pola

More information

Direct Aerobic Carbonylation of C(sp 2 )-H and C(sp 3 )-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source

Direct Aerobic Carbonylation of C(sp 2 )-H and C(sp 3 )-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source Direct Aerobic Carbonylation of C(sp 2 )-H and C(sp 3 )-H Bonds through Ni/Cu Synergistic Catalysis with DMF as the Carbonyl Source Xuesong Wu, Yan Zhao, and Haibo Ge* Table of Contents General Information...

More information

THE JOURNAL OF ANTIBIOTICS. Polyketomycin, a New Antibiotic from Streptomyces sp. MK277-AF1. II. Structure Determination

THE JOURNAL OF ANTIBIOTICS. Polyketomycin, a New Antibiotic from Streptomyces sp. MK277-AF1. II. Structure Determination THE JOURNAL OF ANTIBIOTICS Polyketomycin, a New Antibiotic from Streptomyces sp. MK277-AF1 II. Structure Determination ISAO MOMOSE, WEI CHEN, HIKARU NAKAMURA, HIROSHI NAGANAWA, HIRONOBU IINUMA and TOMIO

More information

Supporting Information. Recyclable hypervalent-iodine-mediated solid-phase peptide

Supporting Information. Recyclable hypervalent-iodine-mediated solid-phase peptide Supporting Information Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis Dan Liu, Ya-Li Guo, Jin Qu and Chi Zhang* for Address: State Key Laboratory of Elemento-Organic

More information

Palladium(II)-Catalyzed Cross-Coupling of Simple Alkenes with Acrylates: A Direct Approach to 1,3-Dienes through C H Activation

Palladium(II)-Catalyzed Cross-Coupling of Simple Alkenes with Acrylates: A Direct Approach to 1,3-Dienes through C H Activation 1 Palladium(II)-Catalyzed Cross-Coupling of Simple Alkenes with Acrylates: A Direct Approach to 1,3-Dienes through C H Activation Zhen-Kang Wen, Yun-He Xu* and Teck-Peng Loh* Division of Chemistry and

More information

Supporting Information

Supporting Information Supporting Information Synthesis of N-Heteropolycyclic Compounds Including Quinazolinone Skeletons by Using Friedel-Crafts Alkylation Bu Keun Oh, Eun Bi Ko, Jin Wook Han* and Chang Ho Oh* Department of

More information

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2007 Supporting Information General. NMR spectra for identification of intermediates and final compoundswere recorded

More information

NHC-catalyzed cleavage of vicinal diketones and. triketones followed by insertion of enones and

NHC-catalyzed cleavage of vicinal diketones and. triketones followed by insertion of enones and Supporting Information for NHC-catalyzed cleavage of vicinal diketones and triketones followed by insertion of enones and ynones Ken Takaki*, Makoto Hino, Akira Ohno, Kimihiro Komeyama, Hiroto Yoshida

More information

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2007 Organocatalytic Asymmetric Sulfa-Michael Addition to α,β- Unsaturated Ketones Paolo Ricci, Armando Carlone, Giuseppe

More information

Supporting Information. for. Access to pyrrolo-pyridines by gold-catalyzed. hydroarylation of pyrroles tethered to terminal alkynes

Supporting Information. for. Access to pyrrolo-pyridines by gold-catalyzed. hydroarylation of pyrroles tethered to terminal alkynes Supporting Information for Access to pyrrolo-pyridines by gold-catalyzed hydroarylation of pyrroles tethered to terminal alkynes Elena Borsini 1, Gianluigi Broggini* 1, Andrea Fasana 1, Chiara Baldassarri

More information

Supporting Information

Supporting Information Zinc-Mediated Addition of Diethyl Bromomalonate to Alkynes for the Cascade Reaction towards Polysubstituted Pyranones and Tetracarbonyl Derivatives Anne Miersch, Klaus Harms, and Gerhard Hilt* Fachbereich

More information

Supporting Information. Radical fluorination powered expedient synthesis of 3 fluorobicyclo[1.1.1]pentan 1 amine

Supporting Information. Radical fluorination powered expedient synthesis of 3 fluorobicyclo[1.1.1]pentan 1 amine Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2015 Supporting Information Radical fluorination powered expedient synthesis

More information

Preparation, isolation and characterization of N α -Fmoc-peptide isocyanates: Solution synthesis of oligo-α-peptidyl ureas

Preparation, isolation and characterization of N α -Fmoc-peptide isocyanates: Solution synthesis of oligo-α-peptidyl ureas SUPPORTING INFORMATION Preparation, isolation and characterization of N α -Fmoc-peptide isocyanates: Solution synthesis of oligo-α-peptidyl ureas Vommina V. Suresh Babu*, Basanagoud S. Patil, and Rao Venkataramanarao

More information

PREPARATION OF OPTICALLY ACTIVE 2,2-DISUBSTITUTED 5-HYDROXYCHROMENES BY ENZYMATIC RESOLUTION OF RACEMIC ESTERS

PREPARATION OF OPTICALLY ACTIVE 2,2-DISUBSTITUTED 5-HYDROXYCHROMENES BY ENZYMATIC RESOLUTION OF RACEMIC ESTERS 604 HETEROCYCLES, Vol. 97, No. 1, 2018 HETEROCYCLES, Vol. 97, No. 1, 2018, pp. 604-611. 2018 The Japan Institute of Heterocyclic Chemistry Received, 13th February, 2018, Accepted, 8th May, 2018, Published

More information

mm C3a. 1 mm C3a Time (s) C5a. C3a. Blank. 10 mm Time (s) Time (s)

mm C3a. 1 mm C3a Time (s) C5a. C3a. Blank. 10 mm Time (s) Time (s) 125 I-C5a (cpm) Fluorescnece Em 520nm a 4000 3000 2000 1000 c 0 5000 4000 3000 2000 Blank C5a C3a 6 0.3 mm C3a 7 9 10 11 12 13 15 16 0.3 mm C5a 0 300 600 900 1200 Time (s) 17 Fluorescnece Em 520nm Fluorescnece

More information

Catalytic decarboxylative alkylation of β-keto acids with sulfonamides via the cleavage of carbon nitrogen and carbon carbon bonds

Catalytic decarboxylative alkylation of β-keto acids with sulfonamides via the cleavage of carbon nitrogen and carbon carbon bonds Catalytic decarboxylative alkylation of β-keto acids with sulfonamides via the cleavage of carbon nitrogen and carbon carbon bonds Cui-Feng Yang, Jian-Yong Wang and Shi-Kai Tian* Joint Laboratory of Green

More information

Supporting Information. Asymmetric Formation of tert-alkylamines from Serinols by a Dual Function Catalyst

Supporting Information. Asymmetric Formation of tert-alkylamines from Serinols by a Dual Function Catalyst Supporting Information Asymmetric Formation of tert-alkylamines from Serinols by a Dual Function Catalyst Young Suk You, Tae Woo Kim and Sung Ho Kang* Molecular-Level Interface Research Center (MIRC),

More information

Structure and conserved function of iso-branched sphingoid bases from the nematode Caenorhabditis elegans

Structure and conserved function of iso-branched sphingoid bases from the nematode Caenorhabditis elegans Electronic Supplementary Material (ESI) for Chemical Science. This journal is The Royal Society of Chemistry 207 Structure and conserved function of iso-branched sphingoid bases from the nematode Caenorhabditis

More information

SUPPORTING INFORMATION FOR. Regioselective Ring-opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride

SUPPORTING INFORMATION FOR. Regioselective Ring-opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride S1 SUPPORTING INFORMATION FOR Regioselective Ring-opening and Isomerization Reactions of 3,4-Epoxyesters Catalyzed by Boron Trifluoride Javier Izquierdo, Santiago Rodríguez and Florenci V. González* Departament

More information

SUPPORTING INFORMATION

SUPPORTING INFORMATION SUPPORTING INFORMATION Exploiting the Ring Strain in Bicyclo[2.2.1]heptane Systems for the Stereoselective Preparation of Highly Functionalized Cyclopentene, Dihydrofuran, Pyrroline and Pyrrolidine Scaffolds

More information

Supporting Information. for. Synthesis of dye/fluorescent functionalized. dendrons based on cyclotriphosphazene

Supporting Information. for. Synthesis of dye/fluorescent functionalized. dendrons based on cyclotriphosphazene Supporting Information for Synthesis of dye/fluorescent functionalized dendrons based on cyclotriphosphazene Aurélien Hameau 1,2, Sabine Fuchs 1,2, Régis Laurent 1,2, Jean-Pierre Majoral* 1,2 and Anne-Marie

More information

University of Groningen

University of Groningen University of Groningen Copper phosphoramidite-catalyzed enantioselective desymmetrization of meso-cyclic allylic bisdiethyl phosphates Piarulli, Umberto; Claverie, Christelle; Daubos, Philippe; Gennari,

More information

Ruthenium-Catalyzed C H Oxygenation on Aryl Weinreb Amides

Ruthenium-Catalyzed C H Oxygenation on Aryl Weinreb Amides Supporting Information Ruthenium-Catalyzed C H xygenation on Aryl Weinreb Amides Fanzhi Yang and Lutz Ackermann* Institut für rganische und Biomolekulare Chemie Georg-August-Universität Tammannstrasse

More information

Eur. J. Org. Chem WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007 ISSN X SUPPORTING INFORMATION

Eur. J. Org. Chem WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim, 2007 ISSN X SUPPORTING INFORMATION Eur. J. Org. Chem. 2007 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2007 ISSN 1434 193X SUPPORTING INFORMATION Title: Effect of Varying the Anionic Component of a Copper(I) Catalyst on Homologation

More information

Base-promoted acetal formation employing aryl salicylates

Base-promoted acetal formation employing aryl salicylates Base-promoted acetal formation employing aryl salicylates Pinmanee Boontheung, Patrick Perlmutter*, and Evaloni Puniani School of Chemistry, Monash University, PO Box 23, Victoria 3800 Australia E-mail:

More information

Fluorescent probes for detecting monoamine oxidase activity and cell imaging

Fluorescent probes for detecting monoamine oxidase activity and cell imaging Fluorescent probes for detecting monoamine oxidase activity and cell imaging Xuefeng Li, Huatang Zhang, Yusheng Xie, Yi Hu, Hongyan Sun *, Qing Zhu * Supporting Information Table of Contents 1. General

More information

Supporting Materials. Experimental Section. internal standard TMS (0 ppm). The peak patterns are indicated as follows: s, singlet; d,

Supporting Materials. Experimental Section. internal standard TMS (0 ppm). The peak patterns are indicated as follows: s, singlet; d, CuBr-Catalyzed Efficient Alkynylation of sp 3 C-H Bonds Adjacent to a itrogen Atom Zhiping Li and Chao-Jun Li* Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A

More information

Supporting Information. Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as

Supporting Information. Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as Supporting Information Palladium-Catalyzed Formylation of Aryl Iodides with HCOOH as CO Source Guanglong Sun,,, Xue Lv,,, Yinan Zhang, Min Lei,*,, and Lihong Hu*, Jiangsu Key Laboratory for Functional

More information

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2006

Supporting Information. Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2006 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2006 Gold Catalysis: The Phenol Synthesis in the Presence of Functional Groups A. Stephen K. Hashmi, Jan P. Weyrauch,

More information

ph Switchable and Fluorescent Ratiometric Squarylium Indocyanine Dyes as Extremely Alkaline Sensors

ph Switchable and Fluorescent Ratiometric Squarylium Indocyanine Dyes as Extremely Alkaline Sensors ph Switchable and Fluorescent Ratiometric Squarylium Indocyanine Dyes as Extremely Alkaline Sensors Jie Li, Chendong Ji, Wantai Yang, Meizhen Yin* State Key Laboratory of Chemical Resource Engineering,

More information

Supporting Information

Supporting Information Supporting Information B(C 6 F 5 ) 3 -catalyzed Regioselective Deuteration of Electronrich Aromatic and Heteroaromatic compounds Wu Li, Ming-Ming Wang, Yuya Hu and Thomas Werner* Leibniz-Institute of Catalysis

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Information ~ Experimental Procedures and Spectral/Analytical Data ~ Use of Dimethyl Carbonate as a Solvent Greatly Enhances the Biaryl Coupling of Aryl Iodides and Organoboron

More information

Synthesis and Assignment of the Absolute Configuration of an Indenotryptoline Bisindole Alkaloid, BE-54017

Synthesis and Assignment of the Absolute Configuration of an Indenotryptoline Bisindole Alkaloid, BE-54017 Supporting Information Synthesis and Assignment of the Absolute Configuration of an Indenotryptoline Bisindole Alkaloid, BE-54017 Tomoyuki Kimura, Shuhei Kanagaki, Yusuke Matsui, Masaya Imoto, Takumi Watanabe*,,

More information

Chiral Squaramide Derivatives are Excellent Hydrogen Bond Donor Catalysts. Jeremiah P. Malerich, Koji Hagihara, and Viresh H.

Chiral Squaramide Derivatives are Excellent Hydrogen Bond Donor Catalysts. Jeremiah P. Malerich, Koji Hagihara, and Viresh H. Chiral Squaramide Derivatives are Excellent ydrogen Bond Donor Catalysts Jeremiah P. Malerich, Koji agihara, and Viresh. Rawal* Department of Chemistry, University of Chicago, Chicago, Illinois 60637 E-mail:

More information

Cu-Catalyzed Direct C6-Arylation of Indoles

Cu-Catalyzed Direct C6-Arylation of Indoles Cu-Catalyzed Direct C6-Arylation of Indoles (Supporting Information) Youqing Yang, Ruirui Li, Yue Zhao, Dongbing Zhao, and Zhuangzhi Shi*, State Key Laboratory of Coordination Chemistry, Collaborative

More information

Supporting Information

Supporting Information Investigation of self-immolative linkers in the design of hydrogen peroxide metalloprotein inhibitors Jody L. Major Jourden, Kevin B. Daniel, and Seth M. Cohen* Department of Chemistry and Biochemistry,

More information

Supporting Information

Supporting Information Supporting Information Wiley-VCH 2010 69451 Weinheim, Germany Direct, One-pot Sequential Reductive Alkylation of Lactams/Amides with Grignard and Organolithium Reagents through Lactam/Amide Activation**

More information

Supporting Information for. Boronic Acid Functionalized Aza-Bodipy (azabdpba) based Fluorescence Optodes for the. analysis of Glucose in Whole Blood

Supporting Information for. Boronic Acid Functionalized Aza-Bodipy (azabdpba) based Fluorescence Optodes for the. analysis of Glucose in Whole Blood Supporting Information for Boronic Acid Functionalized Aza-Bodipy (azabdpba) based Fluorescence Optodes for the analysis of Glucose in Whole Blood Yueling Liu, Jingwei Zhu, Yanmei Xu, Yu Qin*, Dechen Jiang*

More information

Supporting Information

Supporting Information Supporting Information Asymmetric Catalysis of the Carbonyl-Amine Condensation: Kinetic Resolution of Primary Amines Sayantani Das, Nilanjana Majumdar, Chandra Kanta De, Dipti Sankar Kundu, Arno Döhring,

More information

Analysis of fatty acid metabolism using Click-Chemistry and HPLC-MS

Analysis of fatty acid metabolism using Click-Chemistry and HPLC-MS Analysis of fatty acid metabolism using Click-Chemistry and HPLC-MS Alexander J. Pérez and Helge B. Bode -Supporting Information- Contents Experimental section Supplementary figures NMR spectra Page S2

More information

Supporting Information for. A convenient Method for Epoxidation of Alkenes using Aqueous. Hydrogen Peroxide

Supporting Information for. A convenient Method for Epoxidation of Alkenes using Aqueous. Hydrogen Peroxide Supporting Information for A convenient Method for Epoxidation of Alkenes using Aqueous Hydrogen Peroxide Man Kin Tse, Markus Klawonn, Santosh Bhor, Christian Döbler, Gopinathan Anilkumar, and Matthias

More information

Supporting Information

Supporting Information Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 Supporting Information Facile Three-Step Synthesis and Photophysical Properties of [8]-, [9]-,

More information

Organic Letters. Synthesis of Oxygen-Free [2]Rotaxanes: Recognition of Diarylguanidinium Ions by Tetraazacyclophanes. and Sheng-Hsien Chiu*

Organic Letters. Synthesis of Oxygen-Free [2]Rotaxanes: Recognition of Diarylguanidinium Ions by Tetraazacyclophanes. and Sheng-Hsien Chiu* Organic Letters Synthesis of Oxygen-Free [2]Rotaxanes: Recognition of Diarylguanidinium Ions by Tetraazacyclophanes Yu-Hsuan Chang, Yong-Jay Lee, Chien-Chen Lai, Yi-Hung Liu, Shie-Ming Peng, and Sheng-Hsien

More information

An Orthogonal Array Optimization of Lipid-like Nanoparticles for. mrna Delivery in Vivo

An Orthogonal Array Optimization of Lipid-like Nanoparticles for. mrna Delivery in Vivo Supporting Information An rthogonal Array ptimization of Lipid-like Nanoparticles for mrna Delivery in Vivo Bin Li, Xiao Luo, Binbin Deng, Junfeng Wang, David W. McComb, Yimin Shi, Karin M.L. Gaensler,

More information

Supporting Information. Copper-catalyzed cascade synthesis of benzimidazoquinazoline derivatives under mild condition

Supporting Information. Copper-catalyzed cascade synthesis of benzimidazoquinazoline derivatives under mild condition Supporting Information Copper-catalyzed cascade synthesis of benzimidazoquinazoline derivatives under mild condition Shan Xu, Juyou Lu and Hua Fu* Key Laboratory of Bioorganic Phosphorus Chemistry and

More information

Supporting Information

Supporting Information Supporting Information A Regioselective Ring-Expansion of Isatins with In-situ Generated α-aryldiazomethanes; Direct Access to Viridicatin Alkaloids Yellaiah Tangella,, Kesari Lakshmi Manasa,, Namballa

More information

Nitro-Grela-type complexes containing iodides. robust and selective catalysts for olefin metathesis

Nitro-Grela-type complexes containing iodides. robust and selective catalysts for olefin metathesis Supporting Information for Nitro-Grela-type complexes containing iodides robust and selective catalysts for olefin metathesis under challenging conditions. Andrzej Tracz, 1,2 Mateusz Matczak, 1 Katarzyna

More information

Supplementary Material. Efficient Synthesis of an Indinavir Precursor from Biomass Derived (-)- Levoglucosenone

Supplementary Material. Efficient Synthesis of an Indinavir Precursor from Biomass Derived (-)- Levoglucosenone 1.171/CH17227_AC CSIRO 217 Australian Journal of Chemistry 217, 7(1), 1146-115 Supplementary Material Efficient Synthesis of an Indinavir Precursor from Biomass Derived (-)- Levoglucosenone Edward T. Ledingham,

More information

Supporting Information

Supporting Information HYDRAmers: Design, synthesis and characterization of different generation novel Hydra-like dendrons based on multifunctionalized adamantane Giuseppe Lamanna,* Julie Russier, Cécilia Ménard-Moyon, and Alberto

More information

Asymmetric organocatalytic diboration of alkenes

Asymmetric organocatalytic diboration of alkenes Asymmetric organocatalytic diboration of alkenes Amadeu Bonet, a Cristina Solé, Henrik Gulyás,* Elena Fernández* a Dept. Química Física i Inorgànica, University Rovira i Virgili, C/Marcel lí Domingo s/n,

More information

Supplementary Materials Contents

Supplementary Materials Contents Supplementary Materials Contents Supporting information... S1 1. General Information & Materials... S2 2. General Procedure for ptimization of Amidation of Aryl Bromides with Copper/,-Dimethylglycine Catalytic

More information

All chemicals were obtained from Aldrich, Acros, Fisher, or Fluka and were used without

All chemicals were obtained from Aldrich, Acros, Fisher, or Fluka and were used without Supplemental Data Alexander et al. Experimental Procedures General Methods for Inhibitor Synthesis All chemicals were obtained from Aldrich, Acros, Fisher, or Fluka and were used without further purification,

More information

Supporting Information

Supporting Information Supporting Information for Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5- tetrafluorocyclohexane Mohammed Salah Ayoup 1,2, David B. Cordes 1,

More information

Solid Phase Peptide Synthesis (SPPS) and Solid Phase. Fragment Coupling (SPFC) Mediated by Isonitriles

Solid Phase Peptide Synthesis (SPPS) and Solid Phase. Fragment Coupling (SPFC) Mediated by Isonitriles Solid Phase Peptide Synthesis (SPPS) and Solid Phase Fragment Coupling (SPFC) Mediated by Isonitriles Ting Wang a and Samuel J. Danishefsky a,b,* alaboratory for Bioorganic Chemistry, Sloan- Kettering

More information

Catalyst-free chemoselective N-tert-butyloxycarbonylation of amines in water

Catalyst-free chemoselective N-tert-butyloxycarbonylation of amines in water SUPPORTING INFORMATION Catalyst-free chemoselective N-tert-butyloxycarbonylation of amines in water Sunay V. Chankeshwara and Asit K. Chakraborti* National Institute of Pharmaceutical Education and Research

More information

1,5-Electrocyclization of conjugated azomethine ylides derived from 3-formyl chromene and N-alkyl amino acids/esters

1,5-Electrocyclization of conjugated azomethine ylides derived from 3-formyl chromene and N-alkyl amino acids/esters Electronic Supplementary Material (ESI) for rganic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 7 Supporting Information for,5-electrocyclization of conjugated azomethine ylides

More information

Development of a near-infrared fluorescent probe for monitoring hydrazine in serum and living cells

Development of a near-infrared fluorescent probe for monitoring hydrazine in serum and living cells Supporting Information for Development of a near-infrared fluorescent probe for monitoring hydrazine in serum and living cells Sasa Zhu, Weiying Lin,* Lin Yuan State Key Laboratory of Chemo/Biosensing

More information

Supporting Information

Supporting Information Supporting Information De Novo Synthesis of Polysubstituted Naphthols and Furans Using Photoredox Neutral Coupling of Alkynes with 2-Bromo-1,3-Dicarbonyl Compounds Heng Jiang, Yuanzheng Cheng, Yan Zhang,*

More information

Supporting Information. for. Synthesis of 2,1-benzisoxazole-3(1H)-ones by basemediated. photochemical N O bond-forming

Supporting Information. for. Synthesis of 2,1-benzisoxazole-3(1H)-ones by basemediated. photochemical N O bond-forming Supporting Information for Synthesis of 2,1-benzisoxazole-3(1H)-ones by basemediated photochemical N O bond-forming cyclization of 2-azidobenzoic acids Daria Yu. Dzhons and Andrei V. Budruev* Address:

More information

Supporting information D. A. Fort, T. J. Woltering, M. Nettekoven, H. Knust, T. Bach ELECTRONIC SUPPORTING INFORMATION BELONGING TO THE PAPER

Supporting information D. A. Fort, T. J. Woltering, M. Nettekoven, H. Knust, T. Bach ELECTRONIC SUPPORTING INFORMATION BELONGING TO THE PAPER S1 =========================================== ELECTRONIC SUPPORTING INFORMATION =========================================== BELONGING TO THE PAPER Conformationally restricted pyrrolidines by intramolecular

More information

Supporting Information. Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to

Supporting Information. Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to Supporting Information Nitrodibenzofuran: a One- and Two-Photon Sensitive Protecting Group that is Superior to Brominated Hydroxycoumarin for Thiol Caging in Peptides M. Mohsen Mahmoodi, Daniel Abate-Pella,

More information

Supporting Information. Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally. Bioavailable HIV-1 Integrase Inhibitors.

Supporting Information. Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally. Bioavailable HIV-1 Integrase Inhibitors. Supporting Information Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors. Ester Muraglia, * Olaf Kinzel, Cristina Gardelli, Benedetta Crescenzi,

More information

Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide as the Acetylene Source

Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide as the Acetylene Source Electronic Supplementary Material (ESI) for Green Chemistry. This journal is The Royal Society of Chemistry 2015 Supporting Information Efficient Metal-Free Pathway to Vinyl Thioesters with Calcium Carbide

More information

A bidirectional synthesis of spiroacetals via Rh(II)-catalysed C H insertion

A bidirectional synthesis of spiroacetals via Rh(II)-catalysed C H insertion Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2017 Supporting Information A bidirectional synthesis of spiroacetals via Rh(II)-catalysed C H insertion

More information

Thiol-Activated gem-dithiols: A New Class of Controllable. Hydrogen Sulfide (H 2 S) Donors

Thiol-Activated gem-dithiols: A New Class of Controllable. Hydrogen Sulfide (H 2 S) Donors Thiol-Activated gem-dithiols: A New Class of Controllable Hydrogen Sulfide (H 2 S) Donors Yu Zhao, Jianming Kang, Chung-Min Park, Powell E. Bagdon, Bo Peng, and Ming Xian * Department of Chemistry, Washington

More information

Improved Carbonylation of Heterocyclic Chlorides and Challenging Aryl Bromides

Improved Carbonylation of Heterocyclic Chlorides and Challenging Aryl Bromides Albaneze-Walker et al S-1 Improved Carbonylation of Heterocyclic Chlorides and Challenging Aryl Bromides Jennifer Albaneze-Walker*, Charles Bazaral, Tanya Leavey, Peter G. Dormer, and Jerry A. Murry Department

More information

Supporting Information

Supporting Information Supporting Information Bisebromoamide, a Potent Cytotoxic Peptide from the Marine Cyanobacterium Lyngbya sp.: Isolation, Stereostructure, and Biological Activity Toshiaki Teruya, Hiroaki Sasaki, Hidesuke

More information

Electronic Supplementary Information

Electronic Supplementary Information Electronic Supplementary Information A Novel and Facile Zn-mediated Intramolecular Five-membered Cyclization of β-tetraarylporphyrin Radicals from β-bromotetraarylporphyrins Dong-Mei Shen, Chao Liu, Qing-Yun

More information

Nature Chemical Biology: doi: /nchembio.1721

Nature Chemical Biology: doi: /nchembio.1721 Synthesis of β-lactone probes. General experimental. Tetrahydrofuran (THF) was dried using a solvent dispensing system (SDS) with a column of neutral alumina. Pyridine, toluene, dimethylformamide (DMF),

More information

Christophe Lincheneau, Bernard Jean-Denis and Thorfinnur Gunnlaugsson* Electronic Supplementary Information

Christophe Lincheneau, Bernard Jean-Denis and Thorfinnur Gunnlaugsson* Electronic Supplementary Information Self-assembly formation of mechanically interlocked [2]- and [3]catenanes using lanthanide ion [Eu(III)] templation and ring closing metathesis reactions Christophe Lincheneau, Bernard Jean-Denis and Thorfinnur

More information