Total Synthesis of Biselyngbyolide A Yurika Tanabe, Eisuke Sato, Naoya Nakajima, Akifumi Ohkubo, Osamu Ohno, and Kiyotake Suenaga
|
|
- Dorothy Hunter
- 5 years ago
- Views:
Transcription
1 Total Synthesis of Biselyngbyolide A Yurika Tanabe, Eisuke Sato, Naoya Nakajima, Akifumi Ohkubo, Osamu Ohno, and Kiyotake Suenaga Supporting Information Experimental details including spectral data S2 ~ S20 Determination of stereochemistry of alcohol 21 and epi-21 S21 1H NMR spectra of all new compounds S22 ~ S52 13C NMR spectra of all new compounds S53 ~ S80 S1
2 Experimental Procedures and Spectral Data for All New Compounds. General Methods. Chemicals and solvents were the best grade available and were used as received from commercial sources. Optical rotations were measured with a JASCO DIP-360 polarimeter. 1 H NMR spectra were recorded on a JEOL JNM-EX270 (270 MHz) a JEOL JNM-A400 (400 MHz), or a JEOL JNM-GX400 (400 MHz) instrument. Chemical shifts are reported values in parts per million relative to the residual solvent signal (CHD2OD: = 3.31 ppm; CHCl3: = 7.26 ppm; CHD5: = 7.16 ppm for 1 H) and coupling constants are in hertz (Hz). The following abbreviations are used for spin multiplicity: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, and br = broad. 13 C NMR spectra were recorded on a JEOL JNM-EX270 (67.8 MHz) a JEOL A-GX400 (100.4 MHz), or a JEOL JNM-GX400 (100.4 MHz) instrument using CD3OD and CDCl3 as a solvent, respectively. Chemical shifts are reported in parts per million from the solvent signal (CDCl3: = 77.2 ppm; CHD2OD: = 49.0 ppm). IR spectra were recorded on a JASCO FT/IR-410 instrument and are reported in wavenumbers (cm -1 ). ESI mass spectra were recorded on a LCT premier EX spectrometer (Waters). Both TLC analysis and preparative TLC were conducted on E. Merck precoated silical gel 60 F254. Fuji Silysia silica gel BW-820 MH and FL-60D were used for column chromatography unless otherwise noted. Organic solvents for moisture-sensitive reactions were distilled from the following drying agents: THF (Na-benzophenone ketyl), diethyl ether (Na-benzophenone ketyl), benzene (Na), toluene (Na), CH2Cl2 (P2O5), DMSO (calcium hydride). Anhydrous DMF was used as obtained from commercial supplies. All moisture-sensitive reactions were performed under an atmosphere of nitrogen, and the starting materials were azeotropically dried with benzene before use. Alcohol 25: To a stirred suspension of lithium acetylide ethylenediamine complex (2.78 g, 30.2 mmol) in DMSO (7.6 ml) was added a solution of (R)-(+)-trityl glycidyl ether (10) (3.79 g, 12.0 mmol) in THF (9.0 ml) at room temperature. After stirring for 1 h, the mixture was diluted with saturated aqueous NH4Cl at 0 C, and extracted with EtOAc (3 50 ml). The combined extracts were washed with brine (70 ml), dried (Na2SO4), filtered, and concentrated. Crude alcohol 25 (4.60 g) was used for the next reaction without further purification. S2
3 Sylil ether 26: To a stirred solution of crude alcohol 25 (4.60 g) in DMF (15 ml) were added imidazole (3.68 g, 54.0 mmol) and TBDPSCl (6.0 ml, 23.3 mmol) at room temperature. After stirring for 40 min, the mixture was diluted with cooled H2O (30 ml), and extracted with EtOAc (3 50 ml). The combined extracts were washed with brine (70 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (150 g, hexane-etoac 25:1) to give silyl ether 26 (4.54 g, 99% in 2 steps) as a yellow oil: [ ]D (c 1.26, CHCl3); IR (neat, cm -1 ) 3308, 3069, 2931, 2858, 1590, 1490, 1448, 1428, 1362, 1218, 1112, 998, 936, 822, 760, 700, 633; 1H NMR (400 MHz, CDCl3) 7.70 (m, 2H), 7.62 (m, 2H), (m, 21H), 4.01 (dtd, J = 6.4, 5.1, 4.9 Hz, 1H), 3.28 (d, J = 5.1 Hz, 2H), 2.57 (ddd, J =16.7, 6.4, 2.6 Hz, 1H), 2.46 (ddd, J =16.7, 4.9, 2.8 Hz, 1H), 1.88 (dd, J = 2.8, 2.6 Hz, 1H), 1.09 (s, 9H); 13 C NMR (100 MHz, CDCl3) 144.1, 136.1, 135.9, 133.9, 129.8, 129.7, 128.9, 127.8, 127.7, 127.7, 127.0, 86.7, 81.1, 71.1, 70.1, 66.1, 27.1, 24.4, 19.4; HRMS (ESI) m/z , calcd for C40H41O2Si [M+H] Alcohol 11: To a stirred solution of silyl ether 26 (5.59 g, 9.67 mmol) in CH2Cl2 (6 ml) and MeOH (6 ml) was added TsOH H2O (183 mg, mmol) at room temperature. After stirring for 2.5 h, the mixture was diluted with saturated aqueous NaHCO3 (30 ml), extracted with EtOAc (3 50 ml). The combined extracts were washed with brine (50 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (140 g, hexane-etoac 30:1 to 10:1) to give alcohol 11 (2.78 g, 85%) as a colorless oil: [ ]D (c 1.07, CHCl3); IR (neat, cm -1 ) 3429, 3307, 3072, 2932, 2858, 1473, 1428, 1363, 1240, 1104, 1045, 977, 937, 822, 739, 612; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 3.94 (ddt, J = 8.4, 4.6, 4.5 Hz, 1H), 3.67 (d, J =4.6 Hz, 2H), 2.45 (ddd, J = 16.7, 8.4, 2.6 Hz, 1H), 2.29 (ddd, J = 16.7, 4.5, 2.6 Hz, 1H), 1.93 (t, J = 2.6 Hz, 1H), 1.09 (s, 9H); 13 C NMR (100 MHz, CDCl3) 135.9, 135.7, 133.5, 133.4, 130.0, 127.9, 127.8, 80.5, 72.0, 70.5, 65.3, 27.0, 23.5, 19.4; HRMS (ESI) m/z , calcd for C21H27O2Si [M+H] S3
4 Aldehyde 27: To a stirred solution of alcohol 11 (2.78 g, 8.23 mmol) in CH2Cl2 (40 ml) was added Dess-Martin periodinane (3.86 g, 9.14 mmol) at room temperature. The mixture was stirred for 25 min, diluted with saturated aqueous Na2S2O3 (30 ml), and extracted with EtOAc (3 50 ml). The combined extracts were washed with saturated aqueous NaHCO3 (50 ml) and brine (50 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (75 g, hexane-etoac 20:1) to give aldehyde 27 (2.67 g, 96%) as a colorless oil: [ ]D (c 1.48, CHCl3); IR (neat, cm -1 ) 3302, 3073, 3049, 2956, 2931, 2859, 1738, 1470, 1427, 1112, 822, 740, 701, 612; 1 H NMR (400 MHz, CDCl3) 9.64 (d, J = 1.0 Hz, 1H), (m, 4H), (m, 6H), 4.11 (ddd, J = 6.3, 5.9, 1.0 Hz, 1H), 2.51 (ddd, J = 17.1, 6.3, 2.9 Hz, 1H), 2.48 (ddd, J =17.1, 5.9, 2.9 Hz, 1H) 1.99 (t, J = 2.9 Hz, 1H), 1.13 (s, 9H); 13 C NMR (100 MHz, CDCl3) 202.1, 135.9, 135.9, 132.8, 132.7, 130.3, 130.0, 128.1, 128.0, 78.9, 75.8, 71.2, 27.0, 23.2, 19.5; HRMS (ESI) m/z , calcd for C21H25O2Si [M+H] Conjugated ester 12: To a stirred solution of Ando s reagent (2.43 g, 6.71 mmol) in THF (4 ml) was added NaH (60% in oil, 300 mg, 7.50 mmol) at 0 C. After stirring for 30 min, a solution of aldehyde 27 (2.05 g, 6.09 mmol) in THF (6 ml) was added to the reaction mixture at -78 C. The mixture was warmed to 0 C and stirred for 2.5 h. The mixture was diluted with saturated aqueous NH4Cl (20 ml) and extracted with EtOAc (3 30 ml). The combined extracts were washed with H2O (10 ml) and brine (10 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (70 g, hexane-etoac 20:1) to give conjugated ester 12 (2.38 g, 93%) as a colorless oil: [ ]D (c 1.03, CHCl3); IR (neat, cm -1 ) 3308, 3072, 2961, 2932, 2858, 1713, 1427, 1206, 1112, 1075, 739, 701, 611; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 5.97 (dq, J = 8.3, 1.5 Hz, 1H), 5.20(dt, J = 8.3, 4.9 Hz, 1H), 3.94 (q, J = 6.4 Hz, 2H), 2.44 (dd, J = 4.9, 2.4 Hz, 2H), 1.95 (t, J = 2.4 Hz, 1H), 1.73 (d, J = 1.5 Hz, 3H), 1.55 (t, J =6.4 Hz, 3H), 1.07 (s, 9H); 13 C NMR (100 MHz, CDCl3) 167.0, 144.2, 136.0, 134.1, 133.9, 129.8, 129.7, 127.6, 127.6, 127.1, 81.1, 70.0, 68.8, 60.4, S4
5 27.7, 27.1, 20.3, 19.5, 14.1; HRMS (ESI) m/z , calcd for C26H33O3Si [M+H] Allylic alcohol 28: To a stirred solution of conjugated ester 12 (2.38 g, 5.66 mmol) in THF (10 ml) was added lithium alminium hydride (1.0 M solution in THF, 13.5 ml, 13.5 mmol) at -25 C. After stirring for 15 min at -25 C, the mixture was diluted with saturated aqueous Na/K tartrate (20 ml) and stirred for additional 4 h at room temperature. The reaction mixture was extracted with EtOAc (3 20 ml). The combined extracts were washed with brine (20 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (75 g, hexane-etoac 20:1) to give allylic alcohol 28 (1.91 g, 89%) as a colorless oil: [ ]D (c 1.06, CHCl3); IR (neat, cm -1 ) 3417, 3307, 3071, 3050, 2932, 2858, 1473, 1427, 1112, 1072, 1005, 937, 823, 740, 702, 614; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 5.27 (d, J = 8.9 Hz, 1H), 4.55 (ddd, J = 8.9, 8.3, 4.9 Hz, 1H), 3.53 (d, J = 5.9 Hz,2H), 2.52 (ddd, J = 16.6, 4.9, 2.9 Hz, 1H), 2.38 (ddd, J = 16.6, 8.3, 2.9 Hz, 1H), 1.94 (t, J = 2.9 Hz, 1H), 1.64 (s, 3H), 1.05 (s, 9H); 13 C NMR (100 MHz, CDCl3) 136.8, 136.1, 136.0, 134.0, 133.8, 130.0, 129.9, 129.6, 127.8, 127.6, 81.7, 70.1, 68.3, 61.5, 28.5, 27.0, 21.1, 19.4; HRMS (ESI)m/z , calcd for C24H31O2Si [M+H] Allylicbromide 13: To a stirred solution of allylic alcohol 28 (385 mg, 1.02 mmol) in CH2Cl2 (3.8 ml) were added triphenyl phosphine (401 mg, 1.53 mmol) and carbon tetrabromide (507 mg, 1.53 mmol) at 0 C. The mixture was stirred for 30 min, and concentrated. The residual mixture was purified by column chromatography on silica gel (15 g, hexane-etoac 20:1) to give allylic bromide 13 (449 mg, quant.) as a colorless oil: [ ]D (c 1.05, CHCl3); IR (neat, cm -1 ) 3306, 3071, 2932, 2858, 1473, 1427, 1207, 1112, 1072, 740, 701, 668, 644, 613; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 5.42 (dq, J = 9.3, 1.4 Hz, 1H), 4.53 (ddd, J = 9.3, 6.3, 4.9 Hz, 1H), 3.47 (d, J = 10.2 Hz, 1H), 3.36 (d, J = 10.2 Hz, 1H), 2.43 (ddd, J = 16.0, 4.9, 2.4 Hz, 1H), 2.39 S5
6 (ddd, J = 16.0, 6.3, 2.4 Hz, 1H), 1.95 (t, J = 2.4 Hz, 1H), 1.71 (d, J = 1.4 Hz, 3H), 1.05 (s, 9H); 13 C NMR (100 MHz, CDCl3) 136.1, 136.0, 133.8, 133.7, 133.0, 132.2, 130.0, 129.8, 127.8, 127.7, 80.8, 70.5, 68.3, 31.5, 28.1, 27.0, 22.0, 19.4; HRMS (ESI) m/z , calcd for C24H30BrOSi [M+H] Diene 14: To a stirred degassed solution of allylic bromide 13 in THF (537mg, 1.09 mmol) were added trans-1-propen-1-ylbornic acid (227 mg, 2.65 mmol), K3PO4 (554 mg, 2.61 mmol), Pd(dba)2 (58.3 mg, 0.10 mmol) at room temperature. After stirring for 1.5 h, the reaction mixture was diluted with H2O (10 ml) and Et2O (5 ml), and extracted with Et2O (3 10 ml). The combined extracts were washed with 0.5 M aqueous NaOH (10 ml) and brine (20 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (50 g, hexane-toluene 50:1 to 20:1 to 10:1) to give a geometric mixture of diene 14 (229 mg, 52%, 18E/18Z = ca 2:1) as a colorless oil: IR (neat, cm -1 ) 3310, 3071, 2962, 2932, 2857, 1472, 1428, 1112, 1069, 937, 823, 739, 701, 613; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 5.36 (m, 0.3H), 5.27 (m, 1H), 5.24 (m, 0.3H), 5.19 (m,0.7h), 5.02 (m, 0.7H), 4.55 (m, 1H), 2.49 (m, 0.6H), 2.45 (m, 0.3 H), 2.41 (m,0.3h), 2.35 (m, 1.4 H), 2.31 (dd, J = 14.6, 6.5 Hz, 0.7H), 2.16 (dd, J =14.6, 6.7 Hz, 0.7H), 1.92 (t, J =2.7 Hz, 0.7H), 1.90 (t, J =2.5 Hz, 0.3H), 1.65 (dd, J =6.1, 1.1 Hz, 2.1H), 1.54 (d, J =1.1 Hz, 0.9H), 1.53 (dd, J =8.8, 1.4 Hz, 0.9H), 1.14 (d, J = 1.1 Hz, 2.1H), 1.06 (s, 9H); 13 C NMR (100 MHz, CDCl3) 136.6, 136.1, 136.1, 134.4, 134.3, 134.2, 129.7, 129.7, 129.6, 129.5, 128.7, 128.3, 127.7, 127.6, 127.4, 127.2, 126.7, 126.2, 81.7, 81.6, 69.8, 69.6, 69.0, 68.5, 42.7, 35.6, 28.8, 28.5, 27.1, 23.2, 19.4, 18.0, 17.9, 16.6; HRMS (ESI) m/z , calcd for C27H35OSi [M+H] Vinyl stannane 15: To a stirred degassed solution of diene 14 (49.4 mg, mmol) in toluene (0.6 ml) were added tri-n-butyltin hydride (0.16 ml, mmol) and AIBN (6.4mg, 39.0 mol) at 80 C, and the reaction mixture was stirred at 80 C for 2 h. After cooled to room temperature, the mixture was concentrated. The residual oil was S6
7 purified by column chromatography on silica gel (15 g, hexane-toluene 100:1 to 50:1) to give vinyl stannane 15 (61.3 mg, 72%, 18E/18Z = ca 2:1) as a colorless oil: 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 5.87 (m, 1H), 5.19 (m, 1H), 5.18 (m, 1H), (m, 2H), 4.43 (m, 1H), (m, 6H), 2.45 (m, 1H), 2.11 (m, 1H), 1.52 (dd, J = 6.7, 1.1 Hz, 3H), (m, 6H), 1.48 (d, J =1.4 Hz, 3H), (m, 12H), 1.03 (s, 9H), 0.88 (t, J = 7.2 Hz, 9H); HRMS (ESI) m/z , calcd for C39H63OSiSn [M+H] Alcohol 4: To a stirred solution of vinyl stannane 15 (39.0 mg, 56.2 mol) in THF (0.1 ml) was added tetrabutylammonium fluoride (TBAF) (1.0 M solution in THF, 0.09 ml, 90 mol) at 60 C. After stirring for 5 h, the mixture was diluted with saturated aqueous NH4Cl (2 ml), and extracted with EtOAc (3 3 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (13 g, hexane-etoac 20:1) to give crude alcohol 4 (32.1 mg, mixture with TBDPSF) as a colorless oil. Dibromoolefine 29: To a stirred solution of triphenylphosphine (3.21 g, 12.2 mmol) and carbon tetrabromide (2.03 g, 6.12 mmol) in CH2Cl2 (8 ml) were added a solution of aldehyde 16 (588 mg, 3.06 mmol) in CH2Cl2 (2 ml) and 2,6-lutidine (0.76 ml, 6.56 mmol) at 0 C. After stirring for 1 h, the mixture was diluted with saturated aqueous NH4Cl (10 ml) and extracted with hexane (3 15 ml). The combined extracts were washed with saturated aqueous Na2S2O3 (10 ml) and brine (10 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (30 g, hexane-etoac 15:1) to give dibromoolefin 29 (1.03 g, 97%) as a colorless oil: [ ]D (c 1.05, CHCl3); IR (neat, cm -1 ) 2962, 2928, 2868, 1454, 1363, 1104, 766, 735, 697; 1 H NMR (400 MHz, CDCl3) (m, 5H), 6.21 (d, J = 9.3 Hz, 1H), 4.50 (s, 2H), 3.48 (m, 2H), 2.68 (m, 1H), 1.70 (m, 1H), 1.62 (m, 1H), 1.03 (d, J = 3.8 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 143.8, 138.5, 128.5, 127.8, 127.7, 87.9, 73.3, 68.2, 36.1, 35.7, S7
8 19.4; HRMS (ESI) m/z , calcd for C13H16OBr2Na [M+Na] Alkyne 17: To a stirred solution of dibromoolefin 29 (789 mg, 2.27 mmol) in THF (2.4 ml) were added n-buli (1.6 M solution in hexane, 3.1 ml, 4.96 mmol) and iodomethane (0.55 ml, 8.83 mmol) at -78 C, and the mixture was stirred at room temperature for 2 h. The mixture was diluted with H2O (5 ml) and extracted with EtOAc (3 10 ml). The combined extracts were washed with H2O (10 ml) and brine (10 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (12 g, hexane-etoac 15:1) to give alkyne 17 (442 mg, 96%) as a yellow oil: [ ]D (c 1.00, CHCl3); IR (neat, cm -1 ) 2966, 2918, 2859, 1454, 1364, 1103, 737, 698; 1 H NMR (400 MHz, CDCl3) (m, 5H), 4.52 (s, 2H), 3.60 (m, 2H), 2.60 (m, 2H), 1.77, (d, J = 2.4 Hz, 3H), 1.72 (m, 1H), 1.70 (m, 1H), 1.15 (d, J = 6.3 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 138.8, 128.5, 127.8, 127.6, 83.3, 76.0, 73.1, 68.5, 37.3, 23.0, 21.6, 3.6; HRMS (ESI) m/z , calcd for C14H19O [M+H] Vinyl iodide 6: To a suspension of Schwartz s reagent (513 mg, 1.99 mmol) in benzene (2 ml) was added a solution of alkyne 17 (201 mg, mmol) in benzene (0.7 ml) in the dark at 55 C. After stirring for 1.5 h at same temperature, iodine (600 mg, 2.36 mmol) was added to the reaction mixure, and the mixture was stirred for 1 h. The mixture was cooled to room temperature, diluted withh2o (2 ml) and extracted with EtOAc (3 5 ml). The combined extracts were washed with saturated aqueous Na2S2O3 (5 ml) and brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (13 g, hexane-etoac 20:1) to give vinyl iodide 6 (297 mg, 90%) as a colorless oil: [ ]D (c 1.08, CHCl3); IR (neat, cm -1 ) 2957, 2925, 2867, 1633, 1496, 1454, 1378, 1363, 1152, 1104, 1051, 1028, 735, 698; 1 H NMR (400 MHz, CDCl3) (m, 5H), 5.92 (dq, J = 10.2, 2.4 Hz, 1H), 4.47 (s, 2H), 3.44 (m, 2H), 2.64 (m, 1H), 2.37 (d, J = 2.4 Hz, 3H), 1.66 (m, 1H), 1.48 (m, 1H), 0.97 (d, J = 5.8 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 146.7, 138.6, 128.5, 127.8, 127.7, 93.4, 73.2, S8
9 68.3, 36.8, 32.6, 27.9, 20.6; HRMS (ESI) m/z , calcd for C14H20IO [M+H] PMB ether 30: To a stirred solution of freshly prepared 4-methoxybenzyl trichloroacetimidate (5.5 g, 19.6 mmol) in CH2Cl2 (18 ml) were added a solution of allyl alcohol 18 (4.75 g, 13.4 mmol) in CH2Cl2 (12 ml) and (±)-camphor-10-sulfonic acid (311 mg, 1.34 mmol) at room temperature. After stirring for 23 h, the mixture was diluted with saturated aqueous NaHCO3 (20 ml), and extracted with EtOAc (3 50 ml). The combined extracts were washed with brine (20 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (200 g, hexane-etoac 20:1) to give PMB ether 30 (4.71 g, 74%) as a colorless oil: [ ]D (c 1.03, CHCl3); IR (neat, cm -1 ) 2954, 2931, 2857, 1613, 1514, 1428, 1248, 1112, 1089, 823, 738, 703; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 7.20 (d, J = 8.8 Hz, 2H), 6.84 (d, J = 8.8 Hz, 2H), 5.84 (ddt, J = 18.0, 8.8, 7.0 Hz, 1H), 5.08 (d, J = 18.0 Hz), 5.06 (d, J = 8.8 Hz), 4.49 (d, J = 11.0 Hz, 1H), 4.38 (d, J = 11.0 Hz, 1H), 3.83 (m, 1H), 3.79 (s, 3H), 3.73 (m, 2H), 2.32 (dd, J = 7.0, 5.8 Hz, 2H), 1.77 (q, J = 6.3 Hz, 2H), 1.05 (s, 9H); 13 C NMR (100 MHz, CDCl3) 159.2, 135.7, 135.1, 134.1, 131.1, 129.7, 129.4, 127.8, 117.1, 113.9, 75.2, 71.0, 60.7, 55.4, 38.7, 37.1, 27.0, 19.3; HRMS (ESI) m/z , calcd for C30H39O3Si [M+H] Aldehyde 19: To a stirred solution of PMB ether 30 (4.50 g, 9.48 mmol) in acetone/h2o (3:1, v/v, 48 ml) were added NMO (3.33 g, 28.4 mmol) and OsO4 (0.5 M solution in THF, 0.8 ml, 0.4 mmol) at room temperature, and the resultant mixture was stirred at room temperature for 2 h. To the mixture was added NaIO4 (4.46 g, 20.9 mmol), and the reaction mixture was stirred at room temperature for 30 min. The mixture was diluted with saturated aqueous Na2S2O3 (10 ml), and extracted with EtOAc (3 20 ml). The combined extracts were washed with saturated aqueous Na2S2O3 (15mL), brine (15 ml), dried (Na2SO4), filtered, and concentrated. The residual S9
10 oil was purified by column chromatography on silica gel (90 g, hexane-etoac 10:1 to 4:1) to give aldehyde 19 (3.52 g, 78%) as a colorless oil: [ ]D (c 1.05, CHCl3); IR (neat, cm -1 ) 2956, 2932, 2857, 2727, 1724, 1513, 1249, 1112, 1036, 823, 703; 1 H NMR (400 MHz, CDCl3) 9.73 (dd, J = 2.5, 2.0 Hz, 1H), (m, 4H), (m, 6H), 7.18 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 4.44 (s, 2H), 4.18 (m, 1H), 3.83 (m, 1H), 3.79 (s, 3H), 3.75 (m, 1H), 2.64 (ddd, J = 16.4, 7.2, 2.5 Hz, 1H), 2.57 (ddd, J = 16.4, 4.9, 2.0 Hz, 1H), 1.91 (m, 1H), 1.78 (m, 1H), 1.06 (s, 9H); 13 C NMR (100 MHz, CDCl3) 201.8, 159.4, 135.7, 133.7, 130.4, 129.9, 129.6, 127.9, 114.0, 71.4, 71.3, 60.2, 55.4, 48.7, 37.3, 27.0, 19.3; HRMS (ESI) m/z , calcd for C29H36O4SiNa [M+Na] Alcohol 20: To a stirred solution of (+)-B-methoxy(diisopinocamphenyl)borane (2.30 g, 7.27 mmol) in Et2O (15 ml) was added allylmagnesium bromide (1.0 M solution in Et2O, 6.4 ml, 6.4 mmol)at 0 C dropwise over 10 min. After 5 min, the reaction mixture was allowed to stirr at room temperature for 75 min. The mixture was cooled to -78 C, and a solution of aldehyde 19 (1.90 g, 3.99 mmol) in Et2O (22 ml) was added dropwise over 1 h. The reaction mixture was sttired at -78 C for 2 h and then stirred at room temperature for 14 h. The reaction mixture was diluted with 30% aqueous H2O2 (4 ml) and 3 M aqueous NaOH (8 ml), stirred at room temperature for 4 h, and extracted with EtOAc (3 15 ml). The combined extracts were washed with brine (15 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (110 g, hexane-etoac 25:1 to 5:1) to give alcohol 20 (1.85 g, 89%) as a colorless oil: [ ]D (c 1.06, CHCl3); IR (neat, cm -1 ) 3476, 2931, 2858, 1513, 1248, 1112, 1088, 1036, 823, 738, 702; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 6H), 7.21 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 5.83 (ddt, J = 16.6, 10.6, 6.5 Hz, 1H), 5.10 (d, J = 16.6 Hz, 1H), 5.01 (d, J = 10.6 Hz, 1H), 4.52 (d, J = 11.0 Hz, 1H), 4.36 (d, J = 11.0 Hz, 1H), (m, 4H), 3.80 (s, 3H), 2.19 (q, J = 6.5 Hz, 2H), 1.96 (m, 1H), 1.77 (m, 1H), 1.64 (m, 2H), 1.08 (s, 9H); 13 C NMR (100 MHz, CDCl3) 159.4, 135.7, 135.1, 133.8, 130.1, 129.8, 129.7, 127.8, 117.4, 114.0, 71.0, 70.6, 60.4, 55.4, 42.2, 40.8, 36.7, 27.0, 19.3; HRMS (ESI) m/z , calcd for C32H42O4SiNa [M+Na] S10
11 PMP acetal 31: To a stirred solution of alcohol 20 (173 mg, mmol) in CH2Cl2 (1.4 ml) were added MS3A (183 mg) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (92.2 mg, mmol) at 0 C. After stirring for 20 min at room temperature, the reaction mixture was diluted with saturated aqueous NaHCO3 (5 ml) and EtOAc (5mL), and stirred for additional 20 min. The reaction mixture was extracted with EtOAc (3 10 ml). The combined extracts were washed with saturated aqueous Na2S2O3 (10 ml), brine (10 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (11 g, hexane-etoac 10:1) to give PMP acetal 31 (143 mg, 83%) as a colorless oil: [ ]D (c 1.00, CHCl3); IR (neat, cm -1 ) 2931, 2857, 1616, 1517, 1428, 1249, 1112, 1011, 739, 702; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 8H), 6.88 (d, J = 9.0 Hz, 2H), 5.89 (ddt, J = 17.1, 9.9, 6.5 Hz, 1H), 5.47 (s, 2H), 5.13 (d, J = 17.1 Hz, 1H), 5.09 (d, J = 9.9 Hz, 1H), 4.07 (m, 1H), 3.92 (m, 1H), 3.86 (m, 1H), 3.79 (s, 3H), 3.77 (m, 1H), 2.46 (dt, J = 14.1, 6.5 Hz, 1H), 2.28 (dt, J = 14.1, 6.5 Hz, 1H), 1.87 (m, 1H), 1.82 (m, 1H), 1.61 (dt, J = 13.0, 2.5 Hz, 1H), 1.40 (dt, J = 13.0, 11.2 Hz, 1H), 1.06 (s, 9H); 13 C NMR (100 MHz, CDCl3) 159.9, 135.7, 134.3, 134.0, 133.9, 131.6, 129.7, 129.7, 127.8, 127.5, 117.4, 113.6, 100.6, 76.4, 73.6, 59.8, 55.5, 40.5, 38.9, 36.7, 27.0, 19.4; HRMS (ESI) m/z , calcd for C32H41O4Si [M+H] Aldehyde 7: To a stirred solution of PMP acetal 31 (134 mg, mmol) in acetone/h2o (3:1, v/v, 4 ml) were added NMO (92 mg, mmol) and OsO4 (0.5 M solution in THF, 0.04 ml, 0.02 mmol) at room temperature, and the resultant mixture was stirred at room temperature for 2 h. To the mixture was added NaIO4 (163 mg, 0.76 S11
12 mmol), and the reaction mixture was stirred at room temperature for 30 min. The mixture was diluted with saturated aqueous Na2S2O3 (5 ml), and extracted with EtOAc (3 10 ml). The combined extracts were washed with saturated aqueous Na2S2O3 (10 ml), brine (10 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (13 g, hexane-etoac 5:1 to 3:1) to give aldehyde 7 (129 mg, 96%) as a colorless oil: [ ]D (c 1.05, CHCl3); IR (neat, cm -1 ) 2960, 2931, 2857, 2735, 1727, 1615, 1518, 1428, 1250, 1112, 1034, 826, 741, 703; 1 H NMR (400 MHz, CDCl3) 9.86 (dd, J = 2.0, 1.6 Hz, 1H), (m, 4H), (m, 8H), 6.88 (d, J = 8.8 Hz, 2H), 5.52 (s, 1H), 4.34 (m, 1H), 4.14 (m, 1H), 3.92 (m, 1H), 3.81 (s, 3H), 3.77 (m, 1H), 2.79 (ddd, J = 16.8, 7.2, 2.0 Hz, 1H), 2.58 (ddd, J = 16.8, 4.9, 1.6 Hz, 1H), 1.95 (m, 1H), 1.87 (m, 1H), 1.66 (dt, J = 13.0, 2.5 Hz, 1H), 1.48 (dt, J = 13.0, 11.2 Hz, 1H), 1.07 (s, 9H); 13 C NMR (100 MHz, CDCl3) 200.7, 160.0, 135.7, 133.9, 133.9, 131.0, 129.8, 129.7, 127.8, 127.8, 127.5, 113.7, 100.7, 73.4, 72.0, 59.6, 55.4, 49.5, 38.7, 36.9, 27.0, 19.4; HRMS (ESI) m/z , calcd for C31H38O5SiNa [M+Na] Allylic alcohol 21: To a stirreddegassed solution of aldehyde 7 (387 mg, mmol) and vinyl iodide 7 (669 mg, 2.03 mmol) in DMSO (4.4 ml) were added a mixture of CrCl2 (1.73 g, 14.1 mmol) and NiCl2 (22.2 mg, mmol) at room temperature, and the mixture was stirred for 16 h at room temperature. The reaction mixture was diluted with saturated aqueous NH4Cl (5 ml)and extracted with EtOAc (5 10 ml). The combined extracts were washed with saturated aqueous NaHCO3 (10 ml), brine (10 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (17 g, hexane-etoac 10:1 to 8:1) to give allyl alcohol 21 (196 mg, 36%) and a mixture of allylic alcohol 21 and epi-21 (247 mg, 21 : epi-21 = 3:5, 46%) as a colorless oil: [ ]D (c 1.04, CHCl3); IR (neat, cm -1 ) 3488, 2953, 2929, 2858, 1614, 1518, 1429, 1250, 1112, 1035, 1010, 825, 739, 702; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 13H), 6.88 (d, J = 8.5 Hz, 2H), 5.49 (s, 1H), 5.22 (d, J = 9.4 Hz, 1H), 4.47 (s, 2H), 4.29 (dd, J = 8.9, 3.1 Hz, 1H), 4.10 (m, 1H), 4.02 (m, 1H), 3.93 (m, 1H), 3.81 (s, 3H), 3.79 (m, 1H), 3.43 (m, 2H), 2.61 (m, 1H), (m, 2H), 1.82 (m, 1H), 1.68 (m, 1H), 1.64 (s, 3H), (m, 4H), 1.07 (s, 9H), 0.98 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 159.9, 138.7, 135.9, 135.7, 134.0, 133.9, 132.1, S12
13 131.1, 129.8, 129.7, 128.5, 127.8, 127.6, 127.4, 113.7, 100.6, 77.4, 76.6, 73.5, 73.1, 68.8, 59.7, 55.4, 41.5, 38.8, 37.4, 37.3, 28.9, 27.0, 21.2, 19.4, 11.9; HRMS (ESI)m/z , calcd for C45H58O6SiNa [M+Na] epi-21: Analytical sample of epi-21 could be purified by PLC (hexane-etoac 4:1). [ ]D (c 0.75, CHCl3); IR (neat, cm -1 ) 3484, 2954, 2929, 2858, 1614, 1517, 1428, 1250, 1171, 1112, 1035, 825, 738, 702; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 13H), 6.87 (d, J = 8.8 Hz, 2H), 5.45 (s, 1H), 5.22 (dq, J = 9.4, 0.9 Hz, 1H), 4.49 (d, J = 11.9 Hz, 1H), 4.45 (d, J = 11.9 Hz, 1H), 4.29 (dd, J = 7.2, 3.1 Hz, 1H), (m, 2H), 3.91 (m, 1H), 3.81 (s, 3H), 3.79 (m, 1H), 3.44 (m, 2H), 2.60 (m, 1H), (m, 2H), 1.76 (m, 2H), 1.69 (m, 1H), 1.62 (d, J = 0.9 Hz, 3H), (m, 3H), 1.05 (s, 9H), 0.94 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 159.9, 138.7, 136.4, 135.7, 134.0, 131.4, 131.4, 129.7, 128.5, 127.8, 127.8, 127.8, 127.7, 127.5, 113.7, 100.6, 77.5, 74.4, 73.5, 73.1, 68.7, 59.7, 55.5, 40.9, 38.9, 37.5, 37.1, 28.9, 27.0, 21.2, 19.4, 12.5; HRMS (ESI)m/z , calcd for C45H58O6SiNa [M+Na] Conjugated ketone 32: To a stirred solution of a mixture of allyl alcohol 21 and epi-21 (247mg, mmol) in CH2Cl2 (2 ml) was added Dess-Martin periodinane (290mg, mmol) at room temperature. The mixture was stirred for 1 h, diluted with saturated aqueous Na2S2O3 (2 ml), and extracted with EtOAc (3 5 ml). The combined extracts were washed with saturated aqueous NaHCO3 (5 ml) and brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (14 g, hexane-etoac 8:1) to give conjugated ketone 32 (250 mg, quant.) as a colorless oil: [ ]D (c 1.02, CHCl3); IR (neat, cm -1 ) 2959, 2930, 2858, 1666, 1618, 1518, 1428, 1249, 1171, 1112, 1034, 825, 739, 703; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 13H), 6.87 (d, J = 8.8 Hz, 2H), 6.44 (dq, J = 9.9, 1.1 Hz, 1H), 5.51 (s, 1H), 4.43 (s, 2H), 4.39 (m, 1H), 4.14 (m, 1H), 3.93 (m, 1H), 3.80 (m, 1H), 3.79 (s, 3H), 3.41 (m, 1H), 3.33 (m, 1H), 3.17 (dd, J = 16.2, 6.3 Hz, 1H), 2.84 (m, 1H), 2.72 (dd, J = 16.2, 6.3 Hz, 1H), (m, 2H), 1.83 (d, J = 1.1 Hz, 3H), 1.77 (m, 2H), 1.56 (m, 1H), 1.43 (q, J = 11.2 Hz, 1H), 1.08 (s, 9H), 1.05 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 199.7, 159.8, 148.8, 138.4, 136.8, 135.7, 134.0, 133.9, 131.4, 129.7, 129.7, 128.5, 127.8, 127.7, 127.5, 113.6, 100.6, 73.9, 73.3, 73.2, 68.2, 59.7, 55.4, 43.6, 38.8, S13
14 37.3, 36.8, 30.7, 27.0, 20.2, 19.3, 11.5; HRMS (ESI) m/z , calcd for C45H56O6SiNa [M+Na] Allylic alcohol 21: To a stirred solution of ketone 32 (183 mg, mmol) in toluene (0.5 ml) were added (R)-(+)-2-methyl-CBS-oxazaborolidine (22) (13 mg, 46.9 mol) and BH3 SMe2 (0.06 ml, 1.02 mmol) at -15 C. After stirring for 40 min, the reaction mixture was quenched with MeOH, and concentrated. The residual oil was purified by column chromatography on silica gel (25 g, hexane-etoac 8:1) to give allylic alcohol 21 (148 mg, 80%) as a colorless oil. Methyl ether 33: To a stirred solution of alcohol 21 (785 mg, 1.09 mmol) in CH2Cl2 (4 ml) were added proton-sponge (1.61 g, 7.51 mmol) and Me3O BF4 (1.40 g, 9.47 mmol) in the dark at room temperature. The mixture was stirred at room temperature for 3 h, diluted with saturated aqueous NaHCO3 (5 ml), and extracted withetoac (3 5 ml). The combined extracts were washed with saturated aqueous citric acid (5 ml) and brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (20 g, hexane-etoac 10:1) to give methyl ether 33 (672 mg, 84%) as a colorless oil: [ ]D (c 1.02, CHCl3); IR (neat, cm -1 ) 2952, 2929, 2859, 1617, 1517, 1428, 1249, 1104, 824, 739, 701; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 13 H), 6.87 (d, J = 7.9 Hz, 2H), 5.36 (s, 1H), 5.16 (d, J = 9.7 Hz, 1H), 4.45 (d, J = 11.9 Hz, 1H), 4.41 (d, J = 11.9 Hz, 1H), 4.00 (m, 1H), 3.90 (m, 1H), 3.80 (s, 3H), (m, 2H), 3.70 (t, J = 6.7 Hz, 1H), 3.42 (m, 2H), 3.15 (s, 3H), 2.67 (m, 1H), 2.01 (m, 1H), (m, 2H), 1.69 (m, 1H), (m, 2H), 1.57 (s, 3H), (m, 2H), 1.04 (s, 9H), 0.99 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 159.8, 138.5, 135.8, 135.6, 133.9, 133.8, 132.6, 131.6, 129.7, 129.6, 128.4, 127.7, 127.7, 127.7, 127.6, 127.3, 113.5, 100.4, 83.4, 73.9, 73.5, 73.1, 68.6, 59.8, 55.5, 55.3, 39.6, 38.8, S14
15 37.4, 37.1, 29.1, 26.9, 21.4, 19.3, 10.5; HRMS (ESI) m/z , calcd for C46H60O6SiNa [M+Na] Alcohol 34: 4,4 -Di-tert-butylbiphenyl (209 mg, mmol) was dissolved in THF (2 ml). Lithium wire (ca. 20 mg) was cut into small pieces, washed with hexane, methanol and ether, and then added to the above solution. The reaction mixture was sonicated at 0 C for 30 min to provide deep blue color, and stirred at 0 C for 3 h. To a stirred solution of methyl ether 33 (93 mg, mmol) in THF (1 ml) was added LiDBB solution at -78 C. The mixture was stirred at -78 C for 1 h, diluted with saturated aqueous NH4Cl, and extracted with EtOAc (3 5 ml). The combined extracts were washed with saturated aqueous NaHCO3 (5 ml) and brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (14 g, hexane-etoac 5:1 to 3:1) to give alcohol 34 (65.8 mg, 81%) as a colorless oil: [ ]D (c 1.00, CHCl3); IR (neat, cm -1 ) 3458, 2951, 2930, 2859, 1616, 1519, 1428, 1250, 1171, 1112, 1062, 1036, 1011, 825, 756, 702; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 8H), 6.90 (d, J = 8.8 Hz, 2H), 5.41 (s, 1H), 5.24 (d, J = 9.2 Hz, 1H), 4.07 (m, 1H), 3.94 (m, 1H), (m, 2H), 3.82 (s, 3H), 3.75 (t, J = 7.2 Hz, 1H), (m, 2H), 3.19 (s, 3H), 2.65 (m, 1H), 2.05 (m, 1H), (m, 2H), 1.62 (m, 1H), (m, 2H), 1.60 (s, 3H), 1.48 (m, 2H), 1.09 (s, 9H), 1.03 (d, J = 6.5 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 159.8, 135.8, 135.6, 133.9, 133.9, 132.7, 131.6, 129.7, 129.7, 127.7, 127.7, 127.4, 113.6, 100.4, 83.4, 74.0, 73.6, 61.2, 59.9, 55.6, 55.4, 40.3, 39.6, 38.9, 37.1, 29.0, 27.0, 21.3, 19.3, 10.6; HRMS (ESI) m/z , calcd for C39H54O6SiNa [M+Na] Aldehyde 35: To a stirred solution of alcohol 34 (158 mg, mmol) were added iodobenzen diacetate (102 mg, mmol) and TEMPO (11.4 mg, mmol) at room S15
16 temperature. The mixture was stirred at room temperature for 1 h, diluted with saturated aqueous Na2S2O3, and extracted with EtOAc (3 5 ml). The combined extracts were washed with saturated aqueous NaHCO3 (5 ml) and brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (14 g, hexane-etoac 10:1 to 5:1) to give aldehyde 35 (157 mg, quant.) as a colorless oil: [ ]D (c 1.03, CHCl3); IR (neat, cm -1 ) 2948, 2931, 2851, 2720, 1726, 1616, 1517, 1428, 1342, 1249, 1104, 1035, 825, 754, 703, 616; 1 H NMR (400 MHz, CDCl3) 9.69 (dd, J = 2.2, 2.0 Hz, 1H), (m, 4H), (m, 8H), 6.88 (d, J = 8.5 Hz, 2H), 5.38 (s, 1H), 5.23 (d, J = 9.4 Hz, 1H), 4.06 (m, 1H), 3.90 (m, 1H), 3.83 (s, 3H), (m, 2H), 3.72 (t, J = 7.2 Hz, 1H), 3.16 (s, 3H), 3.07 (m, 1H), 2.42 (ddd, J = 16.2, 6.1, 2.0 Hz, 1H), 2.34 (ddd, J = 16.2, 8.1, 2.2 Hz, 1H), 1.99 (m, 1H), (m, 2H), 1.61 (s, 3H), 1.60 (m, 1H), 1.58 (dt, J = 12.1, 2.5 Hz, 1H), 1.44 (dt, J = 12.1, 11.0 Hz, 1H), 1.08 (d, J = 6.7 Hz, 3H), 1.06 (s, 9H); 13 C NMR (100 MHz, CDCl3) 201.7, 159.8, 135.7, 134.0, 134.0, 133.8, 133.6, 131.8, 129.7, 129.7, 127.8, 127.4, 113.6, 100.3, 83.3, 73.7, 73.6, 59.9, 55.7, 55.4, 51.2, 39.5, 38.9, 37.2, 27.5, 27.0, 21.3, ; HRMS (ESI) m/z , calcd for C39H52O6SiNa [M+Na] Vinyl iodide 23: To a stirred solution of CrCl2 (161 mg, 1.31 mmol) in dioxane (0.6 ml) were added a solution of aldehyde 35 (59.7 mg, 89.5 mol) and iodoform (142 mg, mmol) in dioxane (0.4 ml) at 60 C. After stirring at 60 C for 1.5 h, the mixture was diluted with cooled H2O (3 ml) and Et2O (3mL), and extracted with Et2O (3 5 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (15 g, hexane-etoac 15:1 to 8:1) to give vinyl iodide 23 (39.9 mg, 58%) as a colorless oil: [ ]D (c 1.03, CHCl3); IR (neat, cm -1 ) 2952, 2929, 2857, 1739, 1616, 1517, 1429, 1341, 1249, 1112, 1036, 950, 823, 755, 702, 615; 1 H NMR (400 MHz, CDCl3) (m, 4H), (m, 8H), 6.89 (d, J = 8.5 Hz, 2H), 6.45 (dt, J = 14.4, 6.7 Hz, 1H), 5.97 (d, J = 14.4 Hz, 1H), 5.44 (s, 1H), 5.18 (d, J = 9.4 Hz, 1H), 4.14 (m, 1H), 3.92 (m, 1H), (m, 3H), 3.81 (s, 3H), 3.16 (s, 3H), 2.58 (m, 1H), 2.10 (m, 1H), (m, 2H), (m, 2H), 1.64 (m, 1H), 1.57 (m, 1H), 1.56 (s, 3H), 1.45 (dt, J = 12.3, 11.7 Hz, S16
17 1H), 1.05 (s, 9H), 1.00 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 159.8, 145.2, 135.7, 134.8, 134.0, 133.1, 131.7, 129.7, 129.7, 127.8, 127.4, 113.6, 100.3, 83.4, 75.7, 73.7, 73.5, 59.9, 55.7, 55.5, 43.6, 39.6, 39.0, 37.4, 32.1, 27.1, 21.0, 19.4, 10.6; HRMS (ESI) m/z , calcd for C40H53IO5SiNa [M+Na] Alcohol 36: To a stirred solution of vinyl iodide 23 (25.9 mg, 33.7 mol) in THF (0.4 ml) was added tetrabutylammonium fluoride (TBAF) (1.0 M solution in THF, 0.06 ml, 60 mol) at room temperature. After stirring for 3 h, the mixture was diluted with saturated aqueous NH4Cl (2 ml), and extracted with EtOAc (3 3 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (4 g, hexane-etoac 2:1) to give alcohol 36 (15.3 mg, 85%) as a colorless oil: [ ]D (c 1.38, CHCl3); IR (neat, cm -1 ) 3441, 2952, 2917, 2875, 1616, 1517, 1435, 1401, 1341, 1251, 1095, 1036, 949, 828, 755, 666; 1 H NMR (400 MHz, CDCl3) 7.39 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 6.45 (dt, J = 14.6, 7.4 Hz, 1H), 5.96 (d, J = 14.6 Hz, 1H), 5.47 (s, 1H), 5.17 (d, J = 9.4 Hz, 1H), 4.15 (m, 1H), (m, 3H), 3.80 (s, 3H), 3.72 (dd, J = 8.3, 6.3 Hz, 1H), 3.15 (s, 3H), 2.57 (m, 1H), 2.08 (m, 1H), (m, 3H), 1.83 (m, 1H), (m, 3H), 1.54 (s, 3H), 0.99 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl3) 159.9, 145.2, 134.9, 133.1, 131.3, 127.3, 113.7, 100.6, 83.3, 76.2, 75.6, 73.8, 60.6, 55.6, 55.4, 43.6, 39.3, 38.1, 36.9, 32.0, 21.0, 10.6; HRMS (ESI) m/z , calcd for C24H36IO5 [M+H] Aldehyde 37: To a stirred solution of alcohol 36 (15.3 mg, 28.8 mol) in CH2Cl2 (0.3 ml) were added iodobenzen diacetate (17.2 mg, 53.4 mol) and TEMPO (1.0 mg, 6.4 mol) at room temperature. The mixture was stirred at room temperature for 5 h, S17
18 diluted with saturated aqueous Na2S2O3 (3 ml), and extracted with EtOAc (3 5 ml). The combined extracts were washed with saturated aqueous NaHCO3 (3 ml) and brine (3 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (12 g, hexane-etoac 8:1 to 4:1) to give aldehyde 37 (13.2 mg, 87%) as a colorless oil: [ ]D (c 1.40, CHCl3) IR (neat, cm -1 ) 2953, 2925, 2727, 1725, 1615, 1518, 1341, 1249, 1171, 1096, 1060, 1034, 829; 1 H NMR (400 MHz, CDCl3) 9.85 (dd, J = 2.0, 1.8 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 6.45 (dt, J = 14.4, 7.4 Hz, 1H), 5.96 (dt, J = 14.4, 1.4 Hz, 1H), 5.50 (s, 1H), 5.17 (dq, J = 10.6, 1.1 Hz, 1H), 4.47 (m, 1H), 3.81 (m, 1H), 3.81 (s, 3H), 3.72 (dd, J = 8.5, 6.3 Hz, 1H), 3.15 (s, 3H), 2.79 (ddd, J = 16.8, 7.4, 2.0 Hz, 1H), 2.61 (ddd, J = 16.8, 5.2, 1.8 Hz, 1H), 2.56 (m, 1H), 2.09 (m, 1H), (m, 2H), 1.70 (ddd, J = 12.8, 2.5, 2.2 Hz, 1H), 1.65 (m, 1H), 1.55 (d, J =1.1 Hz, 3H), 1.52 (dt, J = 12.8, 11.0 Hz, 1H), 0.99 (d, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) 200.7, 160.0, 145.2, 135.0, 133.0, 131.0, 127.4, 113.7, 100.6, 83.3, 75.7, 73.6, 71.9, 55.7, 55.4, 49.5, 43.6, 39.3, 36.7, 32.0, 21.0, 10.6; HRMS (ESI) m/z , calcd for C24H34IO5 [M+H] Carboxylic acid 5: To a stirred solution of aldehyde 37 (45.2 mg, 85.5 mol) in t-buoh (0.8 ml) were added 2-methyl-2-butene (0.4 ml, 4.76mmol), NaClO2 (24.0 mg, mmol) and NaH2PO4 (0.1 M aqueous solution, 3.4 ml, 0.34 mmol) at room temperature. The reaction mixture was stirred at room temperature for 3 h, diluted with saturated aqueous NH4Cl (2 ml), and extracted with EtOAc (3 5 ml). The combined extracts were washed with saturated brine (5 ml), dried (Na2SO4), filtered, and concentrated to give carboxylic acid 5 (42.9 mg, 92%) as a colorless oil: [ ]D (c 1.23, CHCl3); IR (neat, cm -1 ) , 2954, 2924, 1714, 1616, 1518, 1436, 1401, 1342, 1303, 1249, 1172, 1092, 1035, 948, 828, 755; 1 H NMR (400 MHz, CDCl3) 7.40 (d, J = 8.8 Hz, 2H), 6.89 (d, J =8.8 Hz, 2H), 6.44 (dt, J = 14.4, 7.2 Hz, 1H), 5.96 (dt, J = 14.4, 1.1 Hz, 1H),5.49 (s, 1H), 5.18 (d, J = 9.4 Hz, 1H), 4.37 (m, 1H), 3.80 (m, 1H), 3.80 (s, 3H), 3.74 (dd, J = 8.5, 6.3 Hz, 1H), 3.16 (s, 3H), 2.76 (dd, J = 15.9, 7.0 Hz, 1H), 2.58 (m, 1H), 2.58 (dd, J = 15.9, 5.8 Hz, 1H), 2.09 (m, 1H), (m, 2H), 1.73 (ddd, J = 13.0, Hz, 1H), 1.66 (m, 1H), 1.55 (s, 3H), 1.52 (dt, J = 13.0, 11.2 Hz, 1H), 0.99 (d, J = 6.7 Hz, S18
19 3H); 13 C NMR (100 MHz, CDCl3) 175.9, 160.0, 145.2, 135.1, 132.9, 131.0, 127.4, 113.7, 100.6, 83.3, 75.7, 73.6, 72.8, 55.6, 55.4, 43.6, 40.8, 39.3, 36.5, 32.0, 21.0, 10.6; HRMS (ESI) m/z , calcd for C24H32IO6 [M-H] Crude ester 3: To a stirred solution of carboxylic acid 5 (24.3 mg, 44.6 mol) and crude alcohol 20 (32.1 mg) in CH2Cl2 (0.6 ml) were added DMAP (2.0 mg, 16.4 mol), MNBA (25.2 mg, 73.2 mol) and NEt3 (0.04 ml, mmol) at room temperature. The mixture was stirred at room temperature for 2 h, diluted with saturated aqueous NaHCO3 (2 ml), and extracted with EtOAc (3 3 ml). The combined extracts were washed with brine (3 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (10 g, hexane-etoac 20:1 to 8:1) to give crude ester 3 (32.9 mg) as a colorless oil. Macrolactone 24: To a stirred degassed solution of crude ester 3 (23.1 mg, 23.5 mol) in DMF (6 ml) were added lithium chloride (4.2 mg, 99.1 mol) and Pd2(dba)3 (2.2 mg, 2.4 mol) at room temperature. After stirring for 2 h, the mixture was diluted with H2O (5 ml) and Et2O (2 ml), and extracted with Et2O (3 5 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on silica gel (10 g, hexane-etoac 8:1 to 6:1) to give macrolactone 24 (9.4 mg, 53% in 2 steps) as a colorless oil: [ ]D (c 0.47, CHCl3); IR (neat, cm -1 ) 2955, 2924, 1741, 1616, 1518, 1436, 1377, 1346, 1302, 1250, 1136, 1098, 1035, 990, 826, 755; 1 H NMR (400 MHz, CDCl3) 7.40 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 6.11 (dd, J = 14.8, 10.3 Hz, 1H), 5.87 (dd, J = 14.8, 12.1 Hz, 1H), 5.55 (m, 1H), (m, 4H), 5.41 (s, 1H), 5.17 (d, J = 9.8 Hz, 1H), 5.09 (d, J = 9.7 S19
20 Hz, 1H), 4.21 (m, 1H), 3.85 (m, 1H), 3.82 (s, 3H), 3.60 (m, 1H), 3.17 (s, 3H), 3.01 (dd, J = 14.6, 6.5 Hz, 1H), 2.74(dd, J = 14.6, 5.8 Hz, 1H), (m, 2H), 2.44 (m, 2H), 2.35 (m, 1H), (m, 2H), (m, 4H), 1.68 (d, J = 1.4 Hz, 3H), 1.55 (s, 3H), 1.33 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl , 159.8, 139.2, 137.0, 133.8, 133.7, 132.0, 131.4, 131.1, 128.3, 127.6, 127.2, 126.6, 124.3, 113.7, 99.9, 84.3, 75.6, 74.4, 70.6, 55.8, 55.5, 42.4, 41.3, 39.8, 37.5, 36.7, 35.9, 33.1, 23.6, 22.7, 18.0, 9.8; HRMS (ESI) m/z , calcd for C35H48O6Na [M+Na] Biselyngbyolide A: To a stirred solution of macrolactone 24 (5.3 mg, 9.38 mol) in MeOH (2 ml) was added PPTS (24.0 mg, 95.5 mol) at room temperature. After stirring for 18 h, the reaction mixture was diluted with H2O (2 ml) and EtOAc (5 ml), and extracted with EtOAc (3 5 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by column chromatography on ODS (1 g, 100% MeOH) followed by HPLC [Nacalai Colester ( nm); flow rate 5 ml/min; detection, UV 215 nm; solvent 75% MeCN/H2O] to give biselyngbyolide A (1.7 mg, 41%, tr = 48 min) as a colorless oil: [ ]D (c 0.08, CHCl3); IR (neat, cm -1 ) , 3014, 2923, 1732, 1431, 1377, 1254, 1156, 1098, 986; 1H NMR (400 MHz, CD3OD) 5.99 (m, 2H), 5.57 (td, J = 9.0, 3.4 Hz, 1H), (m, 2H), (m, 2H), 5.18 (m, 2H), 4.08 (m, 1H), 3.75 (dd, J = 7.9, 6.5 Hz, 1H), 3.65 (m, 1H), 3.17 (s, 3H), 2.95 (dd, J = 14.4, 6.7 Hz, 1H), 2.73 (dd, J = 14.4, 6.5 Hz, 1H), 2.63 (m, 1H), (m, 5H), 1.92 (m, 1H), 1.69 (d, J = 1.7 Hz, 3H), 1.65 (m, 3H), 1.64 (m, 1H), 1.60 (m, 2H), 1.52 (d, J = 1.1 Hz, 3H), 1.43 (m, 1H), 1.03 (d, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CD3OD) 172.4, 140.3, 137.9, 133.5, 133.3, 132.1, 129.4, 128.5, 127.8, 127.4, 124.9, 87.8, 71.6, 69.4, 68.5, 55.8, 45.3, 44.4, 42.1, 41.2, 39.8, 39.7, 36.7, 34.1, 23.5, 22.4, 18.0, 10.2; HRMS (ESI) m/z , calcd for C27H42O5Na [M+Na] S20
21 (R)-MTPA ester: To a stirred solution of allylic alcohol epi-21 (2.7mg, 3.73 mol) in pyridine (0.02 ml) were added DMAP (1.0 mg, 8.19 mol) and (+)-MTPACl (0.01 ml, 52 mol) at room temperature. The mixture was stirred for 7 h, diluted with saturated aqueousaqueous NH4Cl (1 ml) and EtOAc (1 ml), and extracted with EtOAc (3 5 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by PLC (hexane-etoac 4:1) to give (R)-MTPA ester (2.5 mg, 71%) as a colorless oil. (S)-MTPA ester: To a stirred solution of allylic alcohol epi-21 (2.5mg, 3.46 mol) in pyridine (0.02 ml) were added DMAP (1.0 mg, 8.19 mol) and (-)-MTPACl (0.01 ml, 52 mol) at room temperature. The mixture was stirred for 8 h, diluted with saturated aqueousaqueous NH4Cl (1 ml) and EtOAc (1 ml), and extracted with EtOAc (3 5 ml). The combined extracts were washed with brine (5 ml), dried (Na2SO4), filtered, and concentrated. The residual oil was purified by PLC (hexane-etoac 4:1) to give (S)-MTPA ester (2.9 mg, 89%) as a colorless oil. S21
22 S22
23 S23
24 S24
25 S25
26 S26
27 S27
28 S28
29 S29
30 S30
31 S31
32 S32
33 S33
34 S34
35 S35
36 S36
37 S37
38 S38
39 S39
40 S40
41 S41
42 S42
43 S43
44 S44
45 S45
46 S46
47 S47
48 S48
49 S49
50 S50
51 S51
52 S52
53 S53
54 S54
55 S55
56 S56
57 S57
58 S58
59 S59
60 S60
61 S61
62 S62
63 S63
64 S64
65 S65
66 S66
67 S67
68 S68
69 S69
70 S70
71 S71
72 S72
73 S73
74 S74
75 S75
76 S76
77 S77
78 S78
79 S79
80 S80
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 informationSupporting 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 informationTetrahydrofuran (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 informationSupporting Information. for. Angew. Chem. Int. Ed. Z Wiley-VCH 2002
Supporting Information for Angew. Chem. Int. Ed. Z50016 Wiley-VCH 2002 69451 Weinheim, Germany Total Synthesis of (±)-Wortmannin Takashi Mizutani, Shinobu Honzawa, Shin-ya Tosaki, and Masakatsu Shibasaki*
More informationSYNTHESIS 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 informationSupporting 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 informationThe 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 informationSupporting 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 informationSupporting 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 informationSupporting 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 informationSUPPLEMENTARY 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 informationSynthesis 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 informationTotal Syntheses of Aflavazole and 14-Hydroxyaflavinine
Electronic Supporting Information Total Syntheses of Aflavazole and 14-Hydroxyaflavinine Hailong Li, Qifeng Chen, Zhaohong Lu, and Ang Li* State Key Laboratory of Bioorganic and Natural Products Chemistry,
More informationStereodivergent Synthesis and Relative Stereostructure of the C1 C13 Fragment of
Stereodivergent Synthesis and Relative Stereostructure of the C1 C13 Fragment of Symbiodinolide Hiroyoshi Takamura, *, Hiroko Wada, Mao Ogino, Takahiro Kikuchi, Isao Kadota, *, and Daisuke Uemura Department
More informationDivergent 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 informationFast and Flexible Synthesis of Pantothenic Acid and CJ-15,801.
Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801. Alan L. Sewell a, Mathew V. J. Villa a, Mhairi Matheson a, William G. Whittingham b, Rodolfo Marquez a*. a) WestCHEM, School of Chemistry,
More informationSupporting 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 informationSynthetic 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 informationSupporting Information 1/2
Supporting nformation 1/2 Combinatorial Synthesis of 1,5-Polyol System Based on Cross Metathesis: Structure Revision of Amphidinol 3 Tohru Oishi,* Mitsunori Kanemoto, Respati Swasono, Nobuaki Matsumori,
More informationNature-Inspired Total Synthesis of ( )- Fusarisetin A
Supporting Information Nature-Inspired Total Synthesis of ( )- Fusarisetin A Jing Xu, Eduardo J.E. Caro-Diaz, Lynnie Trzoss, and Emmanuel A. Theodorakis* Department of Chemistry and Biochemistry, University
More informationEnantioselective Synthesis of Fused Heterocycles with Contiguous Stereogenic Centers by Chiral Phosphoric Acid-Catalyzed Symmetry Breaking
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2015 Enantioselective Synthesis of Fused Heterocycles with Contiguous Stereogenic Centers by Chiral
More informationSupporting 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 informationSupporting 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 informationConcise and Stereocontrolled Synthesis of the Tetracyclic Core of Daphniglaucin C
Supporting information Concise and Stereocontrolled Synthesis of the Tetracyclic Core of Daphniglaucin C Stephen Hanessian,* Stéphane Dorich, Helge Menz Department of Chemistry, Université de Montréal,
More informationSupplementary 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 informationSupporting 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 informationSupporting 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 informationAn 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 informationSupporting Information
1 A regiodivergent synthesis of ring A C-prenyl flavones Alberto Minassi, Anna Giana, Abdellah Ech-Chahad and Giovanni Appendino* Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche
More informationSynthesis 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 informationSupporting 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 informationStudies toward the Total Synthesis of Caribbean Ciguatoxin C-CTX-1: Synthesis of the LMN-Ring Fragment through Reductive Olefin Cross-Coupling
S1 Studies toward the Total Synthesis of Caribbean Ciguatoxin C-CTX-1: Synthesis of the LMN-Ring Fragment through Reductive lefin Cross-Coupling Makoto Sasaki,* Kotaro Iwasaki, Keisuke Arai Graduate School
More informationHow 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 informationElectronic 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 informationSynthesis 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 informationguanidine bisurea bifunctional organocatalyst
Supporting Information for Asymmetric -amination of -keto esters using a guanidine bisurea bifunctional organocatalyst Minami Odagi* 1, Yoshiharu Yamamoto 1 and Kazuo Nagasawa* 1 Address: 1 Department
More informationhydroxyanthraquinones 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 informationSUPPLEMENTARY 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 informationSUPPORTING INFORMATION
SUPPORTING INFORMATION Asymmetric Vinylogous aza-darzens Approach to Vinyl Aziridines Isaac Chogii, Pradipta Das, Michael D. Delost, Mark N. Crawford and Jon T. Njardarson* Department of Chemistry and
More informationSupporting 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 informationCarbonylative 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 informationBulletin 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 informationSupplementary 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 informationSupporting Information. Enantioselective Organocatalyzed Henry Reaction with Fluoromethyl Ketones
Supporting Information Enantioselective Organocatalyzed Henry Reaction with Fluoromethyl Ketones Marco Bandini,* Riccardo Sinisi, Achille Umani-Ronchi* Dipartimento di Chimica Organica G. Ciamician, Università
More informationAziridine 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 informationSupporting 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 informationSupporting 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 informationSupporting Information
Supporting Information Wiley-VCH 2011 69451 Weinheim, Germany Enantioselective Total Synthesis of ( )-Jiadifenolide** Jing Xu, Lynnie Trzoss, Weng K. Chang, and Emmanuel A. Theodorakis* anie_201100313_sm_miscellaneous_information.pdf
More informationBrønsted 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 informationQile Wang, and Nan Zheng* Department of Chemistry and Biochemistry, University of Arkansas. Fayetteville, Arkansas,
Supporting Information A Photocatalyzed Synthesis of Naphthalenes by Using Aniline as a Traceless Directing Group in [4+2] Annulation of AminoBenzocyclobutenes with Alkynes Qile Wang, and Nan Zheng* Department
More informationElectronic 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 informationA Strategy Toward the Synthesis of C 13 -Oxidized Cembrenolides
A Strategy Toward the Synthesis of C 13 -xidized Cembrenolides Alec Saitman, Steven D. E. Sullivan and Emmanuel A. Theodorakis* Department of Chemistry and Biochemistry, University of California, San Diego,
More informationA Total Synthesis of Paeoveitol
A Total Synthesis of Paeoveitol Lun Xu, Fengyi Liu, Li-Wen Xu, Ziwei Gao, Yu-Ming Zhao* Key Laboratory of Applied Surface and Colloid Chemistry of MOE & School of Chemistry and Chemical Engineering, Shaanxi
More informationSupporting 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 informationSUPPORTING INFORMATION
Y. Yamane, K. Sunahara, K. Okano, and A. Mori SUPPORTING INFORMATION Magnesium Bisamide-Mediated Halogen Dance of omothiophenes Yoshiki Yamane, Kazuhiro Sunahara, Kentaro Okano,* and Atsunori Mori Department
More informationSupporting 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 informationSupplementary 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 informationSUPPLEMENTARY 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 informationSupporting Information
Supporting Information Wiley-VCH 2007 69451 Weinheim, Germany Diphenylprolinol Silyl Ether in Enantioselective, Catalytic Tandem Michael-Henry Reaction for the Control of Four Stereocenters Yujiro Hayashi*,
More informationSupporting 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 informationSupporting Information
Supporting Information Wiley-VC 2008 69451 Weinheim, Germany SI-1 A Concise Approach to Vinigrol Thomas J. Maimone, Ana-Florina Voica, and Phil S. Baran* Contribution from the Department of Chemistry,
More informationPhotooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins
S1 Photooxidations of 2-(γ,ε-dihydroxyalkyl) furans in Water: Synthesis of DE-Bicycles of the Pectenotoxins Antonia Kouridaki, Tamsyn Montagnon, Maria Tofi and Georgios Vassilikogiannakis* Department of
More informationSupporting 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 informationSupplementary Figure S1 X-ray crystallographic structure of (C)-(-)-6. (a) ORTEP drawing of (C)-(-)-6 at probability ellipsoids of 50%: tope view.
Supplementary Figure S1 X-ray crystallographic structure of (C)-(-)-6. (a) ORTEP drawing of (C)-(-)-6 at probability ellipsoids of 50%: tope view. (b) Side view. All hydrogen atoms are omitted for clarity.
More informationEnantioselective 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 informationSupporting 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 informationSupporting Information
Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 2014 Supporting Information Rh 2 (Ac) 4 -Catalyzed 2,3-Migration of -rrocenecarboxyl -Diazocarbonyl
More informationSupporting Information
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2017 Supporting Information Palladium-Catalyzed Oxidative Allylation of Bis[(pinacolato)boryl]methane:
More informationDiaza [1,4] Wittig-type rearrangement of N-allylic-N- Boc-hydrazines into -amino-n-boc-enamines
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2016 Diaza [1,4] Wittig-type rearrangement of N-allylic-N- Boc-hydrazines into -amino-n-boc-enamines
More informationSupporting 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 informationSupporting Information
Supporting Information Precision Synthesis of Poly(-hexylpyrrole) and its Diblock Copolymer with Poly(p-phenylene) via Catalyst-Transfer Polycondensation Akihiro Yokoyama, Akira Kato, Ryo Miyakoshi, and
More informationSupporting information. *Corresponding Author: Telephone number: , Fax number: ; address:
Supporting information Synthesis of indolizidine, pyrrolizidine and quinolizidine ring systems by proline-catalyzed sequential -amination and HWE olefination of an aldehyde Shruti Vandana Kauloorkar, a
More informationSupporting Information
Supporting Information Design and Enantioselective Synthesis of β-vinyl Tryptamine Building Blocks for Construction of Privileged Chiral Indole Scaffolds Tao-Yan Lin, Hai-Hong Wu, Jian-Jun Feng*, and Junliang
More informationSupporting Information
Supporting Information F Nucleophilic-Addition-Induced Allylic Alkylation Panpan Tian,,, Cheng-Qiang Wang,, Sai-Hu Cai,, Shengjin Song,, Lu Ye, Chao Feng, *, and Teck-Peng Loh *,, Institute of Advanced
More informationSupporting Information
Supporting Information Wiley-VCH 2012 69451 Weinheim, Germany Concise Syntheses of Insect Pheromones Using Z-Selective Cross Metathesis** Myles B. Herbert, Vanessa M. Marx, Richard L. Pederson, and Robert
More informationAsymmetric Total Synthesis of Cyclocitrinol
Electronic Supplementary Information Experimental Procedures and Characterization Data Asymmetric Total Synthesis of Cyclocitrinol Junyang Liu, Jianlei Wu, Jian-Hong Fan, Xin Yan, Guangjian Mei, and Chuang-Chuang
More informationSupporting Information
Supporting Information Wiley-VCH 2007 69451 Weinheim, Germany Total Syntheses of Amphidinolide H and G Alois Fürstner,* Laure C. Bouchez, Jacques-Alexis Funel, Vilnis Liepins, François-Hugues Porée, Ryan
More informationSuzuki-Miyaura Coupling of Heteroaryl Boronic Acids and Vinyl Chlorides
Suzuki-Miyaura Coupling of Heteroaryl Boronic Acids and Vinyl Chlorides Ashish Thakur, Kainan Zhang, Janis Louie* SUPPORTING INFORMATION General Experimental: All reactions were conducted under an atmosphere
More informationSupporting Information for Sonogashira Hagihara reactions of halogenated glycals. Experimental procedures, analytical data and NMR spectra
Supporting Information for Sonogashira Hagihara reactions of halogenated glycals Dennis C. Koester and Daniel B. Werz* Address: Institut für Organische und Biomolekulare Chemie, Georg-August-Universität
More informationRing-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 informationEfficient 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 informationOxidation of Allylic and Benzylic Alcohols to Aldehydes and Carboxylic Acids
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2014 Supporting Information Oxidation of Allylic and Benzylic Alcohols to Aldehydes and Carboxylic Acids
More informationEnhanced Radical-Scavenging Activity of Naturally-Oriented Artepillin C Derivatives
Supporting nformation Enhanced Radical-Scavenging Activity of Naturally-Oriented Artepillin C Derivatives Sushma Manda, a kuo Nakanishi,* a,b Kei Ohkubo, b Yoshihiro Uto, c Tomonori Kawashima, b Hitoshi
More informationHighly 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 informationDepartment of Chemistry and Biochemistry, California State University Northridge, Northridge, CA Experimental Procedures
Supporting Information Low Temperature n-butyllithium-induced [3,3]-Sigmatropic Rearrangement/Electrophile Trapping Reactions of Allyl-1,1- Dichlorovinyl Ethers. Synthesis of - - and -lactones. Aaron Christopher
More informationA Meldrum s Acid-Derived Thione Dienophile in a Convergent and Stereoselective Synthesis of a Tetracyclic Quassinoid Intermediate
A ldrum s Acid-Derived Thione Dienophile in a Convergent and Stereoselective Synthesis of a Tetracyclic Quassinoid Intermediate Stéphane Perreault and Claude Spino* Supporting Information Experimental
More informationFacile Synthesis of Flavonoid 7-O-Glycosides
Facile Synthesis of Flavonoid 7-O-Glycosides Ming Li, a Xiuwen Han, a Biao Yu b * a State Key Laboratory of Catalyst, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China
More informationPhil S. Baran*, Ryan A. Shenvi, Christos Mitsos SUPPORTING INFORMATION
A Remarkable Ring Contraction En Route to the Chartelline Alkaloids Phil S. Baran*, Ryan A. Shenvi, Christos Mitsos Contribution from the Department of Chemistry, The Scripps Research Institute, 10550
More informationSolvent-Controlled Pd(II)-Catalyzed Aerobic Chemoselective. Intermolecular 1,2-Aminooxygenation and 1,2-Oxyamination of
Supporting Information Solvent-Controlled Pd(II)-Catalyzed Aerobic Chemoselective Intermolecular 1,2-Aminooxygenation and 1,2-Oxyamination of Conjugated Dienes for the Synthesis of Functionalized 1,4-Benzoxazines
More informationStraightforward 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 informationSupplementary Table 1. Small molecule screening data
Supplementary Table 1. Small molecule screening data Category Parameter Description Assay Type of assay Cell-based Target Primary measurement Key reagents Assay protocol PS1/BACE1 interaction Detection
More informationSupplementary Material. A Facile Preparation of α-aryl Carboxylic Acid
10.1071/CH15342_AC CSIRO 2015 Australian Journal of Chemistry 2015, 68(11), 1657-1661 Supplementary Material A Facile Preparation of α-aryl Carboxylic Acid via One-Flow Arndt-Eistert Synthesis Shinichiro
More informationAccessory 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 informationElectronic Supplementary Information. An Ultrafast Surface-Bound Photo-active Molecular. Motor
This journal is The Royal Society of Chemistry and wner Societies 2013 Electronic Supplementary Information An Ultrafast Surface-Bound Photo-active Molecular Motor Jérôme Vachon, [a] Gregory T. Carroll,
More informationSupplementary 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 informationSynthesis 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 informationSupporting Information for: Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions
Supporting Information for: Direct Conversion of Haloarenes to Phenols under Mild, Transition-Metal-Free Conditions Patrick S. Fier* and Kevin M. Maloney* S1 General experimental details All reactions
More informationA 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 informationSUPPORTING INFORMATION. The "Aqueous" Prins Reaction
SUPPRTING INFRMATIN The "Aqueous" Prins Reaction Danielle L. Aubele, Christopher A. Lee, and Paul E. Floreancig Department of Chemistry University of Pittsburgh Pittsburgh, PA 15260 General Procedures.
More informationDomino reactions of 2-methyl chromones containing an electron withdrawing group with chromone-fused dienes
Domino reactions of 2-methyl chromones containing an electron withdrawing group with chromone-fused dienes Jian Gong, Fuchun Xie, Wenming Ren, Hong Chen and Youhong Hu* State Key Laboratory of Drug Research,
More information