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DOI: 10.1055/s-2005-918925
Enantioselective Synthesis of (+)-Aphanorphine by Means of Samarium
Diiodide Promoted Reductive Carbon-Nitrogen Bond-Cleavage Reaction
Publication History
Publication Date:
10 October 2005 (online)
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Abstract
An enantioselective synthesis of (+)-aphanorphine has been achieved by application of a samarium diiodide promoted reductive carbon-nitrogen bond-cleavage reaction to a 1-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline providing a benzazepinone derivative as a key step.
Key words
samarium diiodide - benzazepinone - 1,2,3,4-tetrahydroisoquinoline - carbon-nitrogen bond cleavage reaction - aphanorphine
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References
Preparation and Spectroscopic Data of Compound 9.
To a stirred solution of 8 (1.00 g, 2.74 mmol) in THF (15 mL) was added a solution of SmI2 (0.2 M in THF, 68.5 mL, 13.7 mmol) containing HMPA (2.38 mL, 13.7 mmol) and MeOH (0.28 mL, 6.85 mmol) at 0 °C. The solution was gradually warmed up to r.t., and stirred overnight. To this solution were added excess of sat. NaHCO3 solution, Et2O and Celite. After removal of insoluble materials by filtration through Celite pad, the filtrate was extracted with EtOAc. The extract was washed with brine and dried over Na2SO4. Evaporation of the solvent gave a residue, which was subjected to column chromatography on silica gel. Elution with EtOAc-hexane (1:2) gave 9 (541 mg, 59%) as a colorless solid; mp 97-99 °C; [α]D
28 -11.7 (c 0.45, CHCl3). 1H NMR (270 MHz, CDCl3): δ = 7.05 (d, J = 8.9 Hz, 1 H), 6.72-6.78 (m, 2 H), 5.90 (br s, 1 H), 3.83 (d, J = 15.3 Hz, 1 H), 3.78 (s, 3 H), 3.72 (d, J = 15.3 Hz, 1 H), 3.55-3.67 (m, 2 H), 3.41-3.55 (m, 1 H), 2.99 (dd, J = 8.9, 15.1 Hz, 1 H), 2.90 (dd, J = 4.5, 15.1 Hz, 1 H), 0.90 (s, 9 H), 0.07 (s, 6 H). 13C NMR (68 MHz, CDCl3): δ = -5.4, 18.1, 25.7, 33.1, 42.7, 55.2, 55.3, 66.3, 112.7, 114.7, 128.1, 129.9, 134.5, 158.6, 170.8. IR (KBr): 3220, 2950, 2930, 2855, 1666, 1565, 1260, 1110, 840, 780 cm-1. MS (EI): m/z = 335 [M+]. Anal. Calcd for C18H29NO3Si: C, 64.44; H, 8.71; N, 4.17. Found: C, 64.53; H, 8.78; N, 4.16.
Compound 13: mp 144-145 °C; [α]D 25 +21.9 (c 0.71, CHCl3). 1H NMR (270 MHz, CDCl3): δ = 6.99 (d, J = 8.4 Hz, 1 H), 6.84 (d, J = 2.6 Hz, 1 H), 6.73 (dd, J = 2.6, 8.4 Hz, 1 H), 3.84 (dt, J = 2.5, 5.3 Hz, 1 H), 3.78 (s, 3 H), 2.91-2.97 (m, 2 H), 2.83 (s, 3 H), 2.18 (ddd, J = 0.9, 5.3, 10.7 Hz, 1 H), 2.02 (d, J = 10.7 Hz, 1 H), 1.55 (s, 3 H). 13C NMR (68 MHz, CDCl3): δ = 17.4, 27.5, 29.9, 40.7, 45.1, 54.9, 55.2, 110.0, 112.7, 124.4, 130.6, 141.4, 158.1, 177.0. IR (KBr): 2960, 1686, 1490, 1431, 1286, 1042 cm-1. MS (EI): m/z = 231 [M+]. Anal. Calcd for C14H17NO2: C, 72.70; H, 7.41; N, 6.06. Found: C, 72.79; H, 7.53; N, 6.08.