Enantioselective Synthesis of (+)-Aphanorphine by Means of Samarium
Diiodide Promoted Reductive Carbon-Nitrogen Bond-Cleavage Reaction

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

References

• 1 Gulavita N. Hori A. Shimizu Y. Laszlo P. Clardy J. Tetrahedron Lett.  1988,  29:  4381 
• 2 Honda T. Yamamoto A. Cui Y. Tsubuki M. J. Chem. Soc., Perkin Trans. 1  1992,  531 
• 3 Hallinan KO. Honda T. Tetrahedron  1995,  51:  12211 
• 4a Takano S. Inomata K. Sato T. Takahashi M. Ogasawara K. J. Chem. Soc., Chem. Commun.  1990,  290 
• 4b Hulme AN. Henry SS. Meyers AI. J. Org. Chem.  1995,  60:  1265 
• 4c Meyers AI. Schmidt W. Santiago B. Heterocycles  1995,  40:  525 
• 4d Fadel A. Arzel P. Tetrahedron: Asymmetry  1995,  6:  893 
• 4e Node M. Imazato H. Kurosaki R. Kawano Y. Inoue T. Nishide K. Fuji K. Heterocycles  1996,  42:  811 
• 4f Shiotani S. Okada H. Nakamata K. Yamamoto T. Sekino F. Heterocycles  1996,  43:  1031 
• 4g Fadel A. Arzel P. Tetrahedron: Asymmetry  1997,  8:  371 
• 4h Shimizu M. Kamikubo T. Ogasawara K. Heterocycles  1997,  46:  21 
• 4i Tanaka K. Taniguchi T. Ogasawara K. Tetrahedron Lett.  2001,  42:  1049 
• 4j Tamura O. Yanagimachi T. Kobayashi T. Ishibashi H. Org. Lett.  2001,  3:  2427 
• 4k Fuchs JR. Funk RL. Org. Lett.  2001,  3:  3923 
• 4l ElAzab AS. Taniguchi T. Ogasawara K. Heterocycles  2002,  56:  39 
• 4m Taylor SK. Ivanovic M. Simons LJ. Davis MM. Tetrahedron: Asymmetry  2003,  14:  743 
• 4n Kita Y. Futamura J. Ohba Y. Sawama Y. Genesh JK. Fujioka H. J. Org. Chem.  2003,  68:  5917 
• 4o Zhai H. Luo S. Ye C. Ma Y. J. Org. Chem.  2003,  68:  8268 
• 4p Tamura O. Yanagimachi T. Ishibashi H. Tetrahedron: Asymmetry  2003,  14:  3033 
• 4q Synthesis of (+)-aphanorphine, see: Takano S. Inomata K. Sato T. Ogasawara K. J. Chem. Soc., Chem. Commun.  1989,  1591 
• 5 Honda T. Ishikawa F. Chem. Commun.  1999,  1065 
• 6a Honda T. Kimura M. Org. Lett.  2000,  2:  3925 
• 6b Katoh M. Matsune R. Nagase H. Honda T. Tetrahedron Lett.  2004,  45:  6221 
• 6c Honda T. Takahashi R. Namiki H. J. Org. Chem.  2005,  70:  499 
• 6d Katoh M. Mizutani H. Honda T. Tetrahedron Lett.  2005,  46:  5161 
• 7a Katritzky AR. Lan X. Yang JZ. Denisko OV. Chem. Rev.  1998,  98:  409 
• 7b Katritzky AR. Cobo-Domingo J. Yang B. Steel PJ. Tetrahedron: Asymmetry  1999,  10:  255 
• 7c Koepler O. Laschat S. Baro A. Fischer P. Miehlich B. Hotfilder M. le Viseur C. Eur. J. Org. Chem.  2004,  3611 
• 8 Jurczak J. Gryko D. Kobrzycka E. Gruza H. Prokopowicz P. Tetrahedron  1998,  54:  6051 

9

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.

10

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.