[Synthesis]
The general procedure for the synthesis of tert-butyl 2-oxa-3-azabicyclo[2.2.1]hept-5-ene-3-carboxylate from tert-butyl N-hydroxycarbamate and cyclopentadiene was carried out as follows: firstly, water (5 cm3) and sodium carbonate (23.9 g, 0.23 mol) were added to a suspension of hydroxylamine hydrochloride (24.0 g, 0.35 mol) in ether (150 cm3). The suspension was stirred at room temperature for 1 hour and subsequently cooled to 0°C. Next, a solution of di-tert-butyl dicarbonate (50.2 g, 0.23 mol) in ether (50 cm3) was added slowly and dropwise over 30 minutes. The reaction mixture was gradually warmed to room temperature and stirring was continued for 3 hours. After completion of the reaction, the mixture was filtered and the filter cake was washed with ether (2 x 100 cm3). The filtrate was concentrated to dryness to give a colorless oily product. Upon addition of cyclohexane, compound 1 precipitated as colorless needle-like crystals (27.2 g, 0.20 mol, 89% yield, after two crystallizations).
Subsequently, tetrabutylammonium periodate (2.0 g, 4.67 mmol) was added to a solution of freshly cleaved cyclopentadiene (0.46 g, 6.97 mmol) in dichloromethane (15 cm3). Tert-butyl-N-hydroxycarbamate 1 (0.62 g, 4.67 mmol, 1 eq.) was added over 5 min and the reaction mixture was stirred for 1 h at room temperature. Upon completion of the reaction, the organic phase was washed sequentially with 10% aqueous sodium thiosulfate solution (2 x 50 cm3) and saturated aqueous sodium bicarbonate solution (80 cm3), followed by drying with anhydrous sodium sulfate. After filtration and concentration, a crude black oil was obtained. Purification by fast column chromatography (silica gel, petroleum ether solution of 20% ethyl acetate) afforded bicyclo adduct 2 (0.73 g, 3.71 mmol, 79% yield) as a yellow oil, which solidified after being placed in a refrigerator.
The NMR hydrogen spectrum (400 MHz, CDCl?) data of the product were as follows: δ 6.41 (2H, m, CH=CH), 5.20 (1H, m, CHNBoc), 4.98 (1H, m, CHON), 1.98 (1H, dt, J=8.5, 1.9 Hz, CHH), 1.73 (1H, m, CHH), 1.46 (9H , s, CO?C(CH?)?) . The NMR carbon spectrum (100 MHz, CDCl?) data were as follows: δ 158.6 (s), 134.1 (d), 132.9 (d), 83.5 (d), 81.8 (s), 65.0 (d), 48.1 (t), 28.2 (q). |
[References]
[1] Synlett, 2012, vol. 23, # 12, p. 1801 - 1804
[2] Tetrahedron Letters, 1996, vol. 37, # 22, p. 3799 - 3802
[3] Tetrahedron, 2004, vol. 60, # 11, p. 2559 - 2567
[4] Patent: WO2004/13077, 2004, A2. Location in patent: Page 39
[5] Tetrahedron, 2011, vol. 67, # 5, p. 825 - 829 |