H. Leisch et al. / Tetrahedron Letters 48 (2007) 3979–3981
3981
5. (a) Freund, M.; Speyer, E.; Guttmann, E. Chem. Ber.
1920, 53, 2250; (b) Skita, A.; Nord, F. F.; Reichert, J.;
Stukart, P. Chem. Ber. 1921, 54, 1560; (c) Wieland, H.;
Kotake, M. Ann. 1925, 444, 69; (d) Schopf, C. Ann. 1927,
452, 211; (e) Stork, G. J. Am. Chem. Soc 1952, 73, 504; (f)
Birch, A. J. J. Chem. Soc. (C) 1966, 1894; (g) Grew, E. L.;
Robertson, A. A. US 1974/3812132.
ine 4 was obtained in 8% yield along with 10% of tetra-
hydrothebaine 7.
In conclusion, some level of regioselectivity in hydro-
genation of the C-8/C-14 olefin was demonstrated by
using catalysts capable of coordinating to the nitrogen
atom of thebaine. Further optimisation studies for this
conversion are ongoing.
6. Eppenberger, V.; Warren, H. E.; Rapoport, H. Helv.
Chim. Acta 1968, 51, 381.
7. (a) Crabtree, R. Acc. Chem. Res. 1979, 12, 331; (b)
Crabtree, R. H.; Felkin, H.; Morris, G. E. J. Organomet.
Chem. 1977, 141, 205; (c) Crabtree, R. H.; Demou, P. C.;
Eden, D.; Mihelcic, J. M.; Parnell, C. A.; Quirk, J. M.;
Morris, G. E. J. Am. Chem. 1982, 104, 6994.
Acknowledgements
8. Ratios were determined by 1H NMR in CDCl3 by
comparison of the intensities of H-5 protons of the
morphine alkaloids (thebaine 1, 5.29 ppm (s); 8,14-di-
hydrothebaine 4, 4.84 ppm (s); codeine methylether 6,
4.99 ppm (d, J = 5.8 Hz); tetrahydrothebaine 7, 4.68 ppm
(d, J = 5.0 Hz). Separation by HPLC was performed on a
Hitachi L-6000 HPLC using a Hitachi L-4000H UV
detector (254 nm) with a Phenomenex primespher 5 C18
HC 250 · 10 mm column; 2 ml/min flow; 5 mM KH2PO4,
0.1% NEt3, pH 2.8 adjusted with 2 N HCl:MeOH (75:25).
Retention times are as follows: thebaine 1, 44.7 min;
8,14-dihydrothebaine 4, 41.2 min; tetrahydrothebaine 7,
31.0 min.
9. (a) Anderson, M. P.; Pignolet, L. H. Inorg. Chem. 1981,
20, 4101; (b) Brown, J. M.; Chaloner, P. A.; Kent, A. G.;
Murrer, B. A.; Nicholson, P. N.; Parker, D.; Sidebottom,
P. J. J. Organomet. Chem. 1981, 216, 263.
10. Wang, P. X.; White, C. R. WO 2005/047291 A1.
11. Przybyl, A. K.; Flippen-Anderson, J. L.; Jacobson, A. E.;
Rice, K. C. J. Org. Chem. 2003, 68, 2010.
The authors are grateful to Noramco, Inc., TDC
Research, Inc. and the Natural Sciences and Engineer-
ing Research Council of Canada (NSERC) for financial
support of this work. We also thank Brian Bullen, Chem
Actives, Inc. and Tasmanian Alkaloids, Inc. for the
provision of thebaine.12
References and notes
1. (a) Lopez, D.; Quinoa, E.; Riguera, R. Tetrahedron Lett.
1994, 35, 5727; (b) Lopez, D.; Quinoa, E.; Riguera, R.
J.Org. Chem. 2000, 65, 4671.
2. (a) Krassnig, R.; Hederer, C.; Schmidhammer, H. Arch.
Pharm. 1996, 329, 325; (b) Francis, C. A.; Lin, Z.;
Kaldahl, C. A.; Antczak, K. G., Kumar, V. US 2005/
0038251 A1; (c) Casner, M. L.; Dung, J. S.; Keskeny, E.
M.; Luo, J. US 2006/111383.
12. The use of thebaine and other morphinans was carried out
in accordance with Health Canada guidelines and proce-
dures. [licence # 2006/7531].
3. Barber, R. B.; Rapoport, H. J. Med. Chem. 1976, 19, 1175.
4. Dauben, W. G.; Baskin, C. P.; Van Riel, H. C. H. A. J.
Org. Chem. 1979, 44, 1567.