Facile Multistep Synthesis of Isotruxene and Isotruxenone

Transcription

1 Facile Multistep Synthesis of Isotruxene and Isotruxenone Jye-Shane Yang*, Hsin-Hau Huang, and Shih-Hsun Lin Department of Chemistry, National Taiwan University, Taipei, Taiwan Supporting Information Available. Experimental procedures and characterization data for compounds 4a, 6, and 9-14, 1 H spectrum of 3, and 1 H and 13 C NMR spectra of 9 and Contents: S1 Table of Contents S2 Synthesis of Compounds 4a and 6 S3 Synthesis of Compound 9 S4 Synthesis of Compounds 10 and 11 S5 Synthesis of Compound 12 S6 Synthesis of Compounds 13 and 14 S7 References S8 1 H spectrum of 3 S9 1 H and 13 C NMR spectra of 9 S11 1 H and 13 C NMR spectra of 12 S13 1 H and 13 C NMR spectra of 13 S15 1 H and 13 C NMR spectra of 14 S1

2 HO 2 C HO 2 C CO 2 H Synthesis of Compound 4a Compound 6 (10.0 g, 28.6 mmol) in 200 ml of pyridine and 18 ml of water containing 28.0 g of KMnO 4 (177 mmol) was heated at reflux for 2 h. 30 ml of water and 14.0 g of KMnO 4 (88.5 mmol) were added four times every 30 min. The reaction mixture was further refluxed for 16 h. The hot solution (ca. 80 o C) was filtered to remove the MnO 2 solid and the solid was washed with boiling water. The filtrate was concentrated and the acid was recovered by addition of 1 M HCl. The precipitate was filtered and washed with water and dried in vacuum to afford the white solid of 4a with a yield of 90 %: mp: o C (lit.: o C) S1 ; 1 H NMR (400 MHz, DMSO) δ (m, 2H), (m, 8H), 7.46 (m, 5H); 13 C NMR (100 MHz, DMSO) δ 128.0, 128.1, 128.5, 128.7, 129.4, 129.5, 129.8, 130.3, 133.9, 134.4, 136.4, 136.9, 140.7, 143.8, 145.8, 161.7, 161.9, Synthesis of Compound 6 S2 A suspension of CoBr 2 (cy-diimine) (1.71 g, 3.90 mmol, 5.00 mol%), zinc dust (0.25 g, 3.90 mmol, 5 mol%), and anhydrous ZnI 2 (1.24 g, 3.90 mmol, 5.00 mol%) in anhydrous CH 3 CN (13 ml) under argon was boiled up and allowed to cool to room S2

3 temperature. After 15 min, 5 was added and the mixture was heated to reflux for 24 h. The solvent was then removed under reduced pressure, and the residue was then dissolved in CH 2 Cl 2 and passed through a layer of silica gel. The CH 2 Cl 2 was then removed under reduced pressure and the crude product was recrystallized from CHCl 3 /MeOH to afford the white solid of 6 with a yield of 86 %: mp: o C (lit.: o C) S3 ; 1 H NMR (400 MHz, CDCl 3 ) δ 1.73 (s, 3H), 2.06 (s, 6H), (m, 9H), (m, 2H), (m, 4H) ; 13 C NMR (100 MHz, CDCl 3 ) δ 18.2, 18.4, 19.6, 125.5, 125.6, 126.3, 127.1, 127.2, 128.3, 129.2, 130.1, 131.1, 131.7, 133.8, 139.0, 140.4, 141.2, 141.4, O CO 2 H O Synthesis of Compound 9 In a 250 ml round-bottom flask was added 100 ml of conc. H 2 SO 4 (17.7 M) and stirring. A batch of 10.0 g powder of compound 4a (22.8 mmol) was then added and the mixture was kept at 25 o C for 3 h. After cooling to room temperature, the solution was poured into ice. The mixture was extracted with CH 2 Cl 2. The organic layer was washed with water and brine, and the yellow precipitate was collected on a filter and the crude product was recrystallized from acetone/h 2 O to afford the yellow solid of 9 with a yield of 65 %: mp: o C; 1 H NMR (400 MHz, CDCl 3 ) δ 6.42 (d, J = 6.8 Hz, 1H), 7.23 (t, J = 7.2 Hz, 1H), 7.32 (t, J = 7.2 Hz, 1H), (m, 3H), (m, 3H), (m, 4H); 13 C NMR (100 MHz, CDCl 3 ) δ , , 127.8, 128.1, 128.8, , , 129.3, 130.4, 130.9, 132.7, 134.2, 134.5, 135.1, 135.8, 136.4, 140.4, 141.1, 150.6, 160.0, 160.4, 189.6; IR (KBr) 3053, 3027, S3

4 1842, 1774, 1724 cm -1 ; FAB-HRMS calcd for C 27 H 14 O , found O O O EtO OEt Synthesis of Compound 10 To a stirred solution of benzil (20.7 g, 98.4 mmol) and 1,3-acetonedicarboxylate (20.0 g, 98.9 mmol) in EtOH (300 ml), 80 ml of KOH (6.00 g, 106 mmol) in EtOH was added and the reaction mixture was stirred for 24 h at room temperature. The yellow precipitate which formed was collected on a filter and dry in vacuum. The precipitate was dissolved in acetic anhydride (70 ml) containing concentrated sulfuric acid (3 ml), the mixture was stirred for 3 h at room temperature. The solution was added to water (450 ml) with stirring. The precipitate was collected on a filter, washed with H 2 O, and dried in vacuum to afford the orange solid of 10 with a yield of 97 %: mp: o C (Lit: o C) S4 ; 1 H NMR (400 MHz, CDCl 3 ) δ 1.72 (t, J = 7.2 Hz, 6H), 4.19 (q, J = 7.2 Hz, 4H), 7.02 (d, J = 8 Hz, 4H), 7.25 (t, J = 8 Hz, 4H), 7.35 (t, J = 8 Hz, 2H) O Synthesis of Compound 11 S5 To a stirred solution of benzil (20.0 g, 95.1 mmol) and 3-pentanone (8.16 g, 94.7 mmol) in isopropanol (400 ml), 200 ml of KOH (4.80 g, 85.5 mmol) in isopropanol was added and the reaction mixture was stirred for 3 h at room temperature. The EtOH was removed under reduced pressure, and the residue was extracted with S4

5 EA/5% HCl (aq). The organic layer was washed with water and brine, and then the organic layer was dried over anhydrous MgSO 4 and the filtrate was concentrated under reduced pressure. 80 ml of acetic anhydride and 0.5 ml H 2 SO 4 acid were added to the flask and the mixture was stirred for 5 h at room temperature. The solution was added to water (450 ml) with stirring. The precipitate was collected on a filter, washed with H 2 O, and dried in vacuum to afford the dimer of 11 with a yield of 87 %. 1 H NMR (400 MHz, CDCl 3 ) δ 0.57 (s, 3H), 1.25 (s, 3H), 1.63 (s, 3H), 2.24 (s, 3H), 6.68 (d, J = 8.8 Hz, 2H), (m, 6H), (m, 3H), 7.24 (d, J = 8.4 Hz, 2H) EtO 2 C Synthesis of Compound 12 To a solution of 10 (10.0 g, 57.4 mmol) and 11 (14.8g, 57.0 mmol) in toluene was heated to reflux for 24 h. The toluene was removed under reduced pressure, and the residue was recrystallized from ether to afford the white solid of 12 with a yield of 82 %: mp: o C; 1 H NMR (400 MHz, CDCl 3 ) δ 0.94 (t, J = 7.8 Hz, 3H), 1.56 (s, 3H), 1.79 (s, 3H), 3.95 (q, J = 7.8 Hz, 2H), (m, 4H), (m, 6H), (m, 5H) ; 13 C NMR (100 MHz, CDCl 3 ) δ 13.8, 18.2, 19.0, 60.9, 125.9, 126.0, 127.1, 127.4, 127.9, 129.3, 129.4, 129.7, 129.9, 131.9, 134.3, 138.1, 139.6, 140.1, 140.6, 141.1, 142.8, 169.7; IR (KBr) 3056, 2977, 1719, 1236 cm -1 ; FAB-HRMS calcd for C 29 H 26 O , found ; anal. calcd for C 29 H 26 O 2 : C 85.68, H 6.54; found: C 85.71, H S5

6 O Synthesis of Compound 13 The compond 12 (10.0 g, 24.6 mmol) was suspended in polyphosphoric acid (200 g) and the mixture was heated at 140 o C for 48 h. After cooling to room temperature, the mixture was poured into H 2 O. The precipitate was collected on a filter, washed with H 2 O, and dried in vacuum to afford the yellow solid of 13 with a yield of 96 %: mp: o C; 1 H NMR (400 MHz, CDCl 3 ) δ 2.30 (s, 3H), 2.38 (s, 3H), (m, 4H), (m, 6H), 7.29 (t, J = 7.6 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 7.6 Hz, 2H) ; 13 C NMR (100 MHz, CDCl 3 ) δ 15.9, 18.4, 123.7, 124.1, 126.4, 126.6, 127.7, 127.8, 128.4, 129.8, 130.1, 130.2, 130.5, 134.4, 135.4, 135.8, 139.6, 140.1, 142.2, 144.1, 144.6, 148.6, 195.4; IR (KBr) 3020, 1710, 1603, 1494, 1378 cm -1 ; FAB-HRMS calcd for C 27 H 20 O , found ; anal. calcd for C 27 H 20 O: C 89.97, H 5.59; found: C 89.67, H 5.54 O HO 2 C CO 2 H Synthesis of Compound 14 Compound 13 (10.0 g, 27.7 mmol) in 200 ml of pyridine and 18 ml of water containing 17.4 g of KMnO 4 (110 mmol) was heated at reflux for 2 h. 30 ml of water and 8.70 g of KMnO 4 (55.0 mmol) were added five times every 30 min. The reaction S6

7 mixture was further refluxed for 16 h. The hot solution (ca. 80 o C) was filtered to remove the MnO 2 solid and the solid was washed with boiling water. The filtrate was concentrated and the acid was recovered by addition of 1 M HCl. The precipitate was filtered and washed by water and dried in vacuum to afford the white solid of 14 with a yield of 76 %: mp> 300 o C; 1 H NMR (400 MHz, acetone-d 6 ) δ (m, 10H), 7.50 (t, J = 7.2 Hz, 1H), 7.68 (t, J = 7.2 Hz, 1H), (m, 2H); 13 C NMR (100 MHz, acetone-d 6 ) δ 123.1, 124.9, 127.9, 128.0, 128.1, 128.2, 129.1, 130.6, 130.7, 130.9, 131.0, 131.1, 133.9, 134.7, 136.1, 137.4, 138.0, 139.1, 140.3, 142.4, 145.7, 166.9, 168.6, 190.7; IR (KBr) 3442, 2919, 2559, 1703, 1604, 1300, 1229 cm -1 ; FAB-HRMS calcd for C 27 H 16 O , found References: (S1) Hübel, W.; Hoogzand, C. Chem. Ber. 1960, 93, (S2) Hilt, G.; Vogler, T.; Hess, W.; Galbiati, F. Chem. Commun. 2005, (S3) Eisch,J.J.; Kaska,W.C. J. Am. Chem. Soc. 1966, 88, (S4) Harano, K.; Ban, T.; Yasuda, M.; Osawa, E.; Kanematsu, K. J. Am.Chem. Soc. 1981, 103, (S5) Allen, C. F. H.; VanAllan, J. A. J. Am. Chem. Soc. 1950, 72, S7

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