/ Singlet oxygen-mediated transformation of furans into aromatic nitrogen-containing polycycles in water
Issue in Honor of Prof. Michael Orfanopoulos ARKIVOC 2015 (iii) 154-166 General procedure. Substituted furans (0.9 mmol for 1a-c, 1e, 1f) were dissolved in water (22.5 mL, 40 mM final concentration), or, in the case of 1d a mixture of H2O/CH3CN (9:1 v/v, 30 mL, 30 mM final concentration) was used. In the case of compounds 1a, 1c and 1d, the mixture was subjected to ultrasonic vibration until complete dissolution was achieved. Catalytic amounts of rose Bengal (10-4 M) were added to the solutions which were then cooled in an ice bath. Oxygen was gently bubbled through the solutions while they were irradiated with a xenon Variac Eimac Cermax 300 W lamp. The reactions were monitored by tlc (for compounds 1a, 1d-f) or by NMR (for compounds 1b & 1c). After completion of the photooxidation (20 min for 1a-c & 1e-f, 40 min for 1d) the solutions were warmed to rt and the appropriate amine (0.9 mmol of benzylamine for 1a, or tryptamine for 1a, 1d, 1f, or 0.54 mmol of tryptamine for 1b, or 0.63 mmol of tryptamine for 1c, or 1.08 mmol of tryptamine for 1e) was added. In case of 1e, before the addition of the amine, it was necessary to add Me2S (0.9 mmol) and leave the mixture to stir at rt for 30 min (vide supra and Scheme 3). The reaction mixtures were then stirred at room temperature for the formation (observed by TLC) of the intermediate pyrrolidinone of type 2a or 3 (30 min for 1a-d, 1f or 60 min for 1e). To verify its formation the pyrrolidinone 2a was isolated and characterized. The mixture was extracted with EtOAc (2 × 20 mL), the combined organic layers were then concentrated in vacuo and the residue purified by flash column chromatography (silica gel neutralized with triethylamine, petroleum ether/EtOAc, 5:1). In all the other cases the intermediate pyrrolidinones (3a-f) were treated in situ with the appropriate acid (0.9 mmol of TFA for 1a, or 0.63 mmol of TFA for 1b,c, or 1.08 mmol of TFA for 1d, or 0.9 mmol of PTSA for 1e,f). For the preparation of the spiro-adduct 7, TFA (0.27 mmol) was added. The reaction mixtures were stirred at rt for 30 min (or 60 min in case of compounds 1d,e). After the completion of the reactions, NaCl (300 mg) was added and the mixtures were extracted with EtOAc (2 × 20 mL). The combined organic phases were concentrated in vacuo and the products were purified by flash column chromatography (silica gel, petroleum ether/EtOAc, 2:1 for 4a and 4d; 1:1 for 4b, 4c, 7 and 8; 1:3 for 4e). To verify our mechanistic hypothesis, intermediate 1aD (starting furan 1a, Scheme 2) was isolated after photooxidation by extracting the mixture with EtOAc (2 × 20 mL). The combined organic layers were concentrated in vacuo and the residue was purified by flash column chromatography (silica gel, petroleum ether/EtOAc, 1:1). Ethyl 3-(3,6-dihydroxy-3,6-dihydro-1,2-dioxin-3-yl)propanoate (1aD). Isolated yield 36%. The isolated yield is low because this fragile intermediate was not highly stable to column chromatography. 1H NMR (500 MHz, CDCl3): δH 1.27 (3H, t, J 7.2 Hz), 2.05-2.09 (1H, m), 2.17-2.23 (1H, m), 2.40-2.49 (2H, m), 4.11-4.19 (2H, m), 5.30 (1H, d, J 3.9 Hz), 5.97 (1H, dd, J 0.8, 10.0 Hz), 6.11 (1H, dd, J 3.9, 10.0 Hz). 13C NMR (125 MHz, CDCl3): δC 14.0, 29.2, 32.1, 61.2, 90.8, 96.4, 126.7, 129.0, 174.1. HRMS (TOF ESI): calcd for C9H13O6: 217.0717 [M-H]-; found: 217.0716. Ethyl 3-(1-benzyl-5-oxo-4,5-dihydro-1H-pyrrol-2-yl)propanoate (2a). Isolated yield 54%. 1H NMR (500 MHz, CDCl3): δH 1.23 (3H, t, J 7.1 Hz), 2.47 (4H, s), 3.09 (2H, d, J 2.5 Hz), 4.11 Page 161 © ARKAT-USA, Inc.
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