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DOI: 10.1055/s-2003-43364
Synthesis of Tropinones by Cyclization of 1,3-Bis-Silyl Enol Ethers with Iminium Triflates
Publication History
Publication Date:
26 November 2003 (online)
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Abstract
Tropinone derivatives were prepared by cyclization of 1,3-bis-silyl enol ethers with iminium salts.
Key words
cyclizations - iminium salts - Lewis acids - silyl enol ethers - tropinones
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References
Synthesis of Methyl 2-(3-Methoxycarbonyl-2-oxo-propyl)-pyrrolidine-1-carboxylate (3a): To a CH2Cl2 solution (20 mL) of 2c (0.165 g, 1.04 mmol) was added TMSOTf (0.227 g, 1.25 mmol) at -78 °C. After stirring for 5 min, 1a (0.306 g, 1.25 mmol) was added and the solution was warmed to ambient temperature during 12 h. After stirring for 2 h, an aq solution of HCl acid (10%, 10 mL) was added. The organic and the aq layers were separated and the latter was extracted with Et2O (3 × 100 mL) and CH2Cl2 (100 mL). The combined organic layers were dried (MgSO4), filtered and concentrated. The residue was purified by chromatography (silica gel, Et2O) to give 3a as a colorless oil (0.152 g, 65%). 1H NMR (250 MHz, CDCl3): δ = 1.59-1.70 (m, 1 H, CH2), 1.79-1.93 (m, 3 H, CH2), 2.03-2.17 (m, 1 H, CH2), 2.53-2.63 (m, 1 H), 3.55-3.58 (m, 4 H, NCH2, CH 2CO2CH3), 3.65 (s, 3 H, NCO2CH3), 3.71 (s, 3 H, OCH3), 4.12-4.22 (m, 1 H, 2-H). 13C NMR (62.9 MHz, CDCl3): δ = 23.60, 30.96, 36.31, 46.32, 49.15 (CH2), 52.22, 52.29 (OCH3), 53.77 (CH), 155.22 (NCO2CH3), 167.52 (CO2CH3), 201.12 (CO). IR (neat): 2597 (s), 2880 (w), 1750 (s), 1695 (s), 1454 (s), 1383 (s), 1317 (s), 1260 (s), 1189 (s), 1118 (s)cm-1. MS (EI, 70 eV): m/z (%) = 243 (2) [M+], 212 (4), 200 (7), 184 (12), 168 (10), 128 (100). HRMS (EI, 70 eV): m/z [M+] calcd for C11H17NO5 = 243.1107 ± 2 mD. All new compounds gave satisfactory spectroscopic and analytical and/or HRMS data.
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Typical Procedure for the Preparation of Tropinones 5
: To a CH2Cl2 solution (15 mL) of 4a (0.567 g, 3.0 mmol) were added 1-methoxy-1,3-bis(trimethylsilyloxy)-1,3-butadiene (0.520 g, 2.0 mmol) and TMSOTf (0.130 g, 0.6 mmol) at
-78 °C. After warming to r.t. within 16 h, a sat. aq solution of NaHCO3 was added. The organic and the aqueous layers were separated and the latter was extracted with CH2Cl2 (3 × 50 mL). The combined organic layers were dried (Na2SO4), filtered and the solvent was removed in vacuo. The residue was purified by column chromatography (silica gel, hexane-Et2O = 4:1) to give 5a (185 mg, 38%) as a colorless oil. IR (KBr): 3247 (w), 3201 (w), 2956 (s), 1748 (s), 1706 (s), 1673 (s), 1615 (s), 1483 (m), 1448 (s) cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.62-1.69 (m, 1 H, CH2), 1.90 (m, 1 H, CH2), 1.97-2.05 (m, 1 H, CH2), 2.07-2.23 (m, 1 H, CH2), 2.90 (d, J = 19 Hz, 1 H, CH2), 3.30-3.38 (m, 1 H, CH2), 3.67-3.70 (2 × s, 3 H, keto-enol, OCH3), 3.70 (m, 1 H, CH, keto), 3.73-3.77 (2 × s, 3 H, keto-enol, OCH3), 4.42-4.51 (m, 1 H, CH), 4.97-5.01 (m, 1 H, CH), 10.81 (s, OH, enol). 13C NMR (75 MHz, CDCl3, keto/enol = 2:1): δ = 28.69, 28.70, 29.51, 29.52, 35.28, 36.39 (CH2), 51.09, 51.10 (OCH3), 51.49, 51.95 (CH), 52.54, 52.55 (OCH3), 54.16, 55.78 (CH), 62.92 (CH, keto), 107.86 (C, enol), 153.06, 154.03 (C), 167.72, 167.73 (CO), 173.02 (enol), 203.22 (CO, keto). MS (EI, 70 eV): m/z (%) = 241 (8) [M+], 226 (28), 182 (100). Anal. Calcd for C11H15NO5 (241.24): C, 54.77; H, 6.27; N, 5.80. Found: C, 54.52; H, 6.40; N, 5.66.