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DOI: 10.1055/s-2007-970761
New Access to a Tricyclo[3.2.1.02,7]oct-3-ene Structure
Publication History
Publication Date:
08 March 2007 (online)
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Abstract
A thermally induced reaction cascade including an electrocyclic rearrangement, two Diels-Alder reactions and a 1,4-elimination from a simple cyclobutene carbonate can explain the synthesis of a complex tricyclo[3.2.1.02,7]oct-3-ene core structure.
Key words
1,4-elimination - Diels-Alder - electrocyclic reaction - polycycles - stereoselective synthesis
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References and Notes
Methyl 3-Phenylcyclobut-2-enyl Carbonate ( 5). To a solution of 3-phenylcyclobutenone (3, 2.1 g, 14.5 mmol) and CeCl3·7H2O (5.6 g, 22.7 mmol) in MeOH (50 mL) at r.t. was slowly added NaBH4 (580 mg, 15 mmol) over 15 min. The reaction mixture was stirred at that temperature for 5 min, hydrolyzed with brine (50 mL) and extracted with Et2O (3 × 50 mL). The organic layer was dried over MgSO4 and evaporated to give a residue (2.1 g) which was dissolved in CH2Cl2 (150 mL) in the presence of Et3N (8 mL, 57 mmol) and 4-dimethylamino pyridine (1 g, 8 mmol). Then, ClCO2Me (4.7 mL, 60 mmol) was slowly added and the reaction mixture was stirred for 75 min at r.t. After dilution in CH2Cl2 (50 mL), it was hydrolyzed with brine (100 mL) and extracted with Et2O (3 × 100 mL). The organic layer was dried over MgSO4, evaporated and the residue was purified by flash chromatography (pentane-CH2Cl2 = 70:30) to give the carbonate 5 as a yellow oil (1.83 g, 62%). 1H NMR (400 MHz, CDCl3): δ = 7.50-7.30 (m, 5 H), 6.34 (br s, 1 H), 5.40 (dt, J = 3.9, 1.0 Hz, 1 H), 3.81 (s, 3 H), 3.23 (ddd, J = 13.1, 3.9, 1.0 Hz, 1 H), 2.83 (dt, J = 13.1, 1.0 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3): δ = 155.4, 148.6, 133.0, 129.1, 128.4, 125.6, 125.0, 71.1, 54.6, 36.9 ppm. IR (CHCl3): ν = 3062-2850, 1743, 1444, 1259 cm-1. MS (EI): m/z = 146 [MNH4 + - MeOCO2H].
12
Compounds 6:
The carbonate 5 (300 mg, 1.5 mmol) in DMSO (1 mL) was heated at DMSO reflux for 1.5 h under argon. The crude reaction mixture was diluted with brine (15 mL) and extracted with EtOAc (3 × 10 mL). The organic layer was dried over MgSO4, evaporated and the residue was purified by flash chromatography (CH2Cl2-pentane = 1:2) to give the compound 6 as a white solid (84 mg, 33%). 1H NMR (300 MHz, CDCl3): δ = 7.50-7.20 (m, 10 H, arom.), 6.59 (dd, J = 6.2, 2.3 Hz, H3), 5.26 (dd, J = 4.7, 2.3 Hz, 1 H, H6), 3.71 (t, J = 3.9 Hz, 1 H, H5), 3.69 (s, 3 H, H10), 2.35 (dd, J = 6.8, 2.4 Hz, 1 H, H7), 2.23 (dd, J = 8.0, 6.2 Hz, 1 H, H2), 2.18 (dd, J = 11.7, 5.1 Hz, 1 H, H8
′), 1.57 (d, J = 11.7 Hz, 1 H, H8) ppm. 13C NMR (75 MHz, CDCl3): δ = 155.5 (C=O), 141.2 (Ph), 139.2 (C4), 135.9, 127.5, 126.7, 126.2, 126.0, 124.9 (Ph), 120.4 (C3), 75.5 (C6), 54.5 (methoxy), 38.3 (C5), 31.9 (C1), 31.2 (C8), 28.2 (C2), 27.2 (C7) ppm. Mp 117 °C. IR (KBr): 3031, 2922, 2856, 1742, 1440, 1292, 1265, 968, 755, 697 cm-1. Anal. Calcd for C22H20O3: C, 79.50; H, 6.06. Found: C, 79.50; H, 6.31.
The carbonate 5 (368 mg, 1.8 mmol) was heated at 140 °C (neat) for 30 min. The residue was purified by flash chromatography (pentane-Et2O = 95:5, followed by pentane-Et2O = 80:20) to afford successively the tricyclic compound 6 as a white solid (62 mg, 21%), a mixture of the diastereomers 8 (69 mg, 19%) and diene 7 (10 mg, 5%).
Diastereomers 8: 1H NMR (300 MHz, CDCl3): δ = 7.50-7.20 (m, 20 H, Ph), 6.95 (d, J = 12.6 Hz, 1 H, CHtrans), 6.91 (d, J = 12.7 Hz, 1 H, CHtrans), 6.32 (br d, J = 5.1 Hz, 1 H, CH), 6.29 (dt, J = 4.3, 1.6 Hz, 1 H, CH), 5.73 (d, J = 12.6 Hz, 1 H, CHtrans), 5.65 (d, J = 4.3 Hz, 1 H, CHO), 5.63 (d, J = 12.7 Hz, 1 H, CHtrans), 5.51 (d, J = 5.1 Hz, 1 H, CHO), 3.82 (s, 3 H, OMe), 3.81 (s, 3 H, OMe), 3.77 (s, 3 H, OMe), 3.55 (s, 3 H, OMe), 2.70-2.40 (m, 4 H, CH2), 2.40-2.10 (m, 4 H, CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 155.4, 155.0, 153.4, 153.3 (CO), 142.9, 142.2, 142.1, 142.0 (Cipso), 140.1, 140.0 (CQ), 138.9, 138.4 (CH), 128.4, 128.3, 128.2, 128.1, 127.9, 127.3, 126.9, 126.8, 126.7, 125.6, 125.5, 120.6, 119.5, 118.9, 118.7 (CH), 77.2, 75.7 (CH), 55.2, 55.1, 54.8, 54.6 (CH3), 44.4, 44.1 (CQ), 29.7, 27.7, 25.5, 25.1 (CH2) ppm. HRMS: m/z calcd for C24H28O6N [M + NH4]: 426.1917; found: 426.1915.
Diene 7: 1H NMR (300 MHz, CDCl3): δ = 7.09 (d, J = 12.4 Hz, 1 H), 6.32 (dd, J = 12.4, 0.8 Hz, 1 H), 5.27 (dd, J = 1.5, 0.6 Hz, 1 H), 5.15 (d, J = 1.5 Hz, 1 H), 3.84 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 153.3, 143.6, 140.3, 139.5, 128.4, 127.8, 117.2, 116.5, 55.3 ppm. MS (EI): m/z = 178 [MNH4
+ - CO2].