X. Hong et al. / Tetrahedron Letters 47 (2006) 8387–8390
8389
Stull, P. D. J. Org. Chem. 1989, 54, 817; (g) Padwa, A.;
Sandanayaka, V. P.; Curtis, E. A. J. Am. Chem. Soc. 1994,
116, 2667; (h) Curtis, E. A.; Sandanayaka, V. P.; Padwa,
A. Tetrahedron Lett. 1995, 36, 1989.
MgI2
O
O
O
MeO
O
MeO
O
MeO2C
OH
20
3. (a) Padwa, A.; Precedo, L.; Semones, M. J. Org. Chem.
1999, 64, 4079; (b) Padwa, A.; Curtis, E. A.; Sandanayaka,
V. P. J. Org. Chem. 1997, 62, 1317.
O
MgI
O
MgI
21
22
4. (a) Kinder, F. R., Jr.; Bair, K. W. J. Org. Chem. 1994, 59,
6965; (b) Chen, B.; Ko, R. Y. Y.; Yuen, M. S. M.; Cheng,
K.-F.; Chiu, P. J. Org. Chem. 2003, 68, 4195; (c) Hodgson,
D. M.; Avery, T. D.; Donohue, A. C. Org. Lett. 2002, 4,
1809; (d) Dauben, W. G.; Dinges, J.; Smith, T. C. J. Org.
Chem. 1993, 58, 7635.
5. Padwa, A.; Brodney, M. A.; Marino, J. P., Jr.; Sheehan, S.
M. J. Org. Chem. 1997, 62, 78.
6. (a) Cox, E. D.; Cook, J. M. Chem. Rev. 1995, 5, 1797; (b)
Claret, P. A. In Comprehensive Organic Chemistry;
Barton, D., Ollis, W. D., Eds.; Pergamon: Oxford, 1979;
Vol. 4, p 209.
H+
H+
H2O
O
O
OMgI
H
MeO
H
HO
O
MeO
O
O
O
25
24
23
Scheme 4.
7. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin
Trans. 1 1975, 1574.
8. Oneto, J. M. M.; Padwa, A. Org. Lett. 2006, 8, 3275.
9. (a) Krapcho, A. P. Synthesis 1982, 805, 893; (b) McMurry,
J. Org. React. 1976, 101, 187; (c) Stevens, R. V.; Lee, A.
W. M. J. Am. Chem. Soc. 1979, 101, 7032.
is probably due to activation of the ester by chelation of
the Mg(II) cation with both carbonyl groups. Analo-
gous base-catalyzed rearrangements of a-hydroxy b-di-
ketones to a-keto esters have been reported by Davis
et al.14 and others.15–18 The pathway shown in Scheme
4 is supported by the isolation of carbonate 10 when
the reaction of 7 was carried out with Cs2CO3 in aceto-
nitrile at 81 °C for 1 h. Under these conditions, carbon-
ate 10 was obtained in 75% yield and could be readily
10. (a) Krapcho, A. P.; Glynn, G. A.; Grenon, B. J.
Tetrahedron Lett. 1967, 215; (b) Krapcho, A. P.;
Weimaster, J. F.; Eldridge, J. M.; Jahngen, E. G. E., Jr.;
Lovey, A. J.; Stephens, W. P. J. Org. Chem. 1978, 43, 138.
11. (a) Bunce, R. A.; Dowdy, E. D.; Jones, P. B.; Holt, E. M.
J. Org. Chem. 1993, 58, 7143; (b) Takei, S.; Kowano, Y.
Tetrahedron Lett. 1975, 16, 4389; (c) Belletire, J. L.;
Walley, D. R. Tetrahedron Lett. 1983, 24, 1475; (d)
Bo¨hrer, G.; Bo¨hrer, P.; Knorr, R. Chem. Ber. 1990, 123,
2167.
12. It should be noted that heating an authentic sample of the
carbonate derived from 12 in acetonitrile in the absence of
MgI2 resulted in the recovery of starting material. The
decarboalkoxylation of the carbonate was completely
suppressed when the reaction was carried out in the
presence of proton sponge. By executing the reaction of 11
in MgI2 in acetonitrile in the presence of acetic anhydride,
it was possible to isolate the corresponding acetate in 78%
yield.
hydrolyzed to
conditions.
9 when subjected to mild acidic
In summary, we have uncovered a novel Lewis acid-
promoted a-hydroxy b-dicarbonyl to a-ketol ester
rearrangement. This reaction can be used to give ready
access to carbonate 10 which corresponds to a key inter-
mediate en route to ( )-aspidophytine. Moreover, we
have investigated the decarboalkoxylation of a number
of related a-hydroxy carbomethoxy substituted cycloal-
kanones and have developed conditions for the chemo-
selective removal of either (or both) the hydroxyl and/
or carboalkoxy functionalities. Application of the meth-
od toward the synthesis of a number of aspidosperma
alkaloids is currently underway and will be described
in forthcoming publications.
13. A typical magnesium iodide decarbomethoxylation reaction.
To a 0.9 g (1.9 mmol) sample of 7 in acetonitrile (150 mL)
was added 1.1 g (4 mmol) of magnesium iodide and the
mixture was heated at reflux for 4 h. The solution was
allowed to cool to rt, concentrated under reduced pressure
and the residue was taken up in methylene chloride
(50 mL) and H2O (50 mL). This solution was added to a
saturated aqueous solution of NaHCO3 (200 mL). The
organic layer was separated and the aqueous layer was
extracted twice with methylene chloride, dried over
MgSO4, and concentrated under reduced pressure to give
0.6 g (75%) of 7 as a white solid: mp 210–212 °C; IR (neat)
Acknowledgements
We appreciate the financial support provided by the
National Institutes of Health (GM 059384) and the
National Science Foundation (CHE-0450779).
1794, 1720, 1609, 1494, 1263, and 1193 cmÀ1 1H NMR
;
(400 MHz, CDCl3) d 1.30–1.45 (m, 1H), 1.58–1.81 (m,
2H), 2.27 (d, 1H, J = 17.4 Hz), 2.34 (d, 1H, J = 17.4 Hz),
2.35–2.42 (m, 1H), 2.80 (d, 1H, J = 18.0 Hz), 2.93 (dt, 1H,
J = 14.0 and 6.7 Hz), 3.14 (s, 3H), 3.27 (dd, 1H, J = 18.0
and 0.8 Hz), 3.68 (d, 1H, J = 3.6 Hz), 3.69 (s, 3H), 3.83 (s,
3H), 3.85 (d, 1H, J = 3.6 Hz), 4.21–4.30 (m, 1H), 4.84 (t,
1H, J = 3.6 Hz), 6.48 (d, 1H, J = 8.6 Hz), and 6.89 (d, 1H,
J = 8.6 Hz); 13C NMR (100 MHz, CDCl3) d 20.4, 34.1,
37.3, 40.0, 41.4, 44.7, 51.7, 53.4, 56.2, 60.4, 78.0, 98.0,
105.1, 120.4, 122.9, 135.3, 146.5, 155.5, 170.4, 172.5, and
207.8; Anal. Calcd for C22H24N2O7: C, 61.67; H, 5.65; N,
6.54. Found: C, 61.18; H, 6.21; N, 5.94.
References and notes
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