A. J. Walker, N. C. Bruce / Tetrahedron 60 (2004) 561–568
567
containing18 mgbis(acetylacetonato)cobalt(II).Phenylsilane
(70 mg, 2 neopinone equiv.) was added and the reaction was
stirred under an oxygen atmosphere for 12 h, being monitored
by TLC. At the conclusion of this period, the volatiles were
removed in vacuo, the solid residue was resuspended in 15 mL
chloroform and washed three times with 10 mL portions of
dilute aqueous potassium carbonate. The organic fraction was
dried over magnesium sulfate, filtered and chromatographed
onsilicagel toyield90 mg(29% basedontotalketonecontent,
92% based on neopinone alone) 14b-hydroxydihydrocodei-
none (oxycodone, 1).
neopinone to (þ/2)-codeine and (þ/2)-neopine was
observed. This was attributed to the poor solubility of
oxygen in ionic liquids preventing sufficient silylperoxide
formation and consequent reduction by the phenylsilane.
The repetition of reactions (a) and (b) above with the
addition of 5% v/v water to the solution had a profound
effect upon yields. As the enolisation of codeinone was
facilitated, so a greater proportion of the total ketone content
was found to undergo hydration, giving total yields of 68%
(THF) and 55% (14) from the total ketone content.
1H NMR [400 MHz, CDCl3, d (ppm)]: 1.55 (1H, m, 12,
15a-H), 1.63 (1H, d, 12, 8a-H), 1.83 (1H, d, 12, 8b-H), 2.15
(1H, t, 12, 15b-H), 2.26 (2H, m, 7a -Hþ16a-H), 2.37–2.41
(4H, sþm, 16a-HþN–CH3), 2.42 (1H, m, 16b-H), 2.57
(1H, dd, 16, 10a-H), 2.83 (1H, d, 4, 9-H), 2.98 (1H, t, 12,
7b-H), 3.12 (1H, d, 16, 10b-H), 3.88 (3H, s, 3-O–CH3),
4.64 (1H, s, 5-H), 5.05 (1H, br, OH), 6.61 (1H, d, 8, 2-H),
6.67 (1H, d, 8, 1-H).
Hence, if the entire reaction sequence were performed in
95:5 14/H2O, 6 could be converted to 1 in 14% yield.
Acknowledgements
The generous donation of codeine, codeinone, oxycodone
and thebaine by Macfarlan Smith Ltd, Edinburgh, UK is
gratefully acknowledged. The authors are indebted to Dr
Amrik Basran for the provision of purified MDH and to the
BBSRC and EPSRC for funding.
FT-IR (KBr disc, cm21): 1722, 1501, 1446, 1260, 1036,
2936, 1346, 1165, 1145, 1018.
The balance of the material was almost entirely composed
of codeinone; no neopinone could be detected in the
codeinone fraction by NMR and no quantifiable amounts of
7- or 8-hydroxylated products were found.
References and notes
When the above reaction was repeated with 200 mg pure
neopinone, oxycodone (205 mg, 97%) was recovered as the
sole product. When 200 mg pure codeinone was used, no
oxycodone was detected and the balance of the starting
material was recovered.
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(b) In ionic liquid. An equilibrium mixture of codeinone and
neopinone (as above) was dissolved in 5 mL dry 1-(3-
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