J. D. More, M. G. Campbell / Tetrahedron Letters 50 (2009) 2617–2619
2619
14 gave the previously unknown acetonide 15 in 58% yield.17
Increasing the amount of AlMe3 to 7 equiv gave complete conver-
sion of starting material but increased decomposition; only 12% of
15 was isolated after chromatography (not shown).
In summary, we have discovered a novel and useful rearrange-
ment-addition reaction of AlMe3 with per-acetylated carbohy-
drates. This reaction allows for direct installation of the 1,2-
acetonide onto ribose, glucose, and arabinose, thereby enabling a
direct synthesis of these valuable building blocks. Our synthesis
7. Chan, K. L.; Coumbarides, G. S.; Islam, S.; Wyatt, P. B. Tetrahedron Lett. 2005, 46,
61–65.
8. Brown, D. S.; Bruno, M.; Davenport, R. J.; Ley, S. V. Tetrahedron 1989, 45, 4293–
4308.
9. (a) Puech, F.; Gosselin, G.; Imbac, J-L. Tetrahedron Lett. 1989, 30, 3171–3174; (b)
Ma, T.; Pai, B.; Zhu, Y. L.; Lin, J. S.; Shanmuganathan, K.; Du, J.; Wang, C.; Kim,
H.; Newton, M. G.; Cheng, Y. C.; Chu, C. K. J. Med. Chem. 1996, 39, 2835–2843;
(c) Choo, H.; Chen, X.; Yadav, V.; Wang, J.; Schinazi, R. F.; Chu, C. K. J. Med. Chem.
2006, 49, 1635–1647.
10. (a) Pàmies, O.; Net, G.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry 1999, 10,
2007–2014; (b) Lu, Y.; Just, G. Tetrahedron Lett. 2000, 41, 9223–9227; (c)
Guimet, E.; Diéguez, M.; Ruiz, A.; Claver, C. Tetrahedron: Asymmetry 2004, 15,
2247–2251.
11. He, D. Y.; Li, Z. J.; Li, Z. J.; Liu, Y. Q.; Qiu, D. X.; Cai, M. S. Synth. Commun. 1992,
22, 2653–2658.
12. (a) Tsutsumi, H.; Kawai, Y.; Ishido, Y. Carbohydr. Res. 1979, 73, 293–296; (b)
Kim, J.; Weledji, Y. N.; Greenberg, M. M. J. Org. Chem. 2004, 69, 6100–6104; (c)
Koth, D.; Fiedler, A.; Scholz, S.; Gottschaldt, M. J. Carbohydr. Res. 2007, 26, 267–
278.
of 1,2-O-isopropylidene-D-ribofuranose is high-yielding, operation-
ally simple,18 and easily scalable, giving improved access to this
valuable chiral synthon. Given the difficulty of preparing carbohy-
drate 1,2-acetonides, this reaction should be of general utility to
the synthetic organic chemistry community.
13. Xie, M.; Berges, D. A.; Robins, M. J. J. Org. Chem. 1996, 61, 5178–5179.
14. (a) Lemieux, R. U.; Detert, D. H. Can. J. Chem. 1968, 46, 1039–1040; (b) Dick, W.
E.; Weisleder, D.; Hodge, J. E. Carbohydr. Res. 1972, 23, 229–242.
15. Lohman, G. J. C.; Seeberger, P. H. J. Org. Chem. 2003, 68, 7541–7543.
16. Cano, F. H.; Foces-Foces, C.; Jiminez-Barbero, J.; Bernabe, M.; Martin-Lomas, M.
Carbohydr. Res. 1987, 170, 100–105.
Acknowledgments
The authors thank Loyola College for funding and Professor
George Greco for use of and help with the 400 MHz NMR spec-
trometer in the Goucher College Department of Chemistry.
17. Characterization data for 15: Rf = 0.49 (1:1 ethyl acetate/hexane). IR (cmÀ1
)
2962, 2919, 2849, 1745, 1371, 1261, 1224, 1163, 1096, 1020. 1H NMR
(400 MHz, CDCl3) d 5.93 (d, J = 4 Hz, 1H), 5.08 (s, 1H), 4.60 (d, J = 4 Hz, 1H),
4.26–4.31 (m, 3H), 2.09 (s, 6 H), 1.56 (s, 3H), 1.31 (s, 3H). 13C NMR (100 MHz,
CDCl3) d 170.6, 169.8, 113.1, 105.9, 84.3, 83.0, 77.3 (overlapping with solvent),
63.7, 26.7, 25.9, 20.8 (two carbons). HRMS (EI) m/z calculated for C11H15O7 (M–
CH3): 259.0818. Found: 259.0815.
Supplementary data
Supplementary data (copies of 1H NMR spectra for compounds
4, 11, and 15) associated with this article can be found, in the on-
18. Preparation of 4: A flame-dried 25 mL round-bottomed flask was charged with
2 (0.20 g, 0.63 mmol, 1 equiv) and 5.0 mL anhydrous dichloromethane. The
flask was placed under argon (balloon) and cooled to 0 °C.
Trimethylaluminum(2.0 M in hexane, 0.47 mL, 0.94 mmol, 1.5 equiv) was
added dropwise via syringe. The reaction was allowed to slowly warm to
room temperature and stirred for 15 h, at which point TLC analysis showed the
absence of 2 and the appearance of a new spot (Rf 0.49, 1:1 ethyl acetate/
hexane). The reaction was re-cooled to 0 °C and quenched by the dropwise
addition of 5 mL of saturated aqueous sodium-potassium tartrate (Rochelle’s
salt), diluted with 10 mL dichloromethane, and stirred for 2 h. The organic
layer was removed and the aqueous layer was extracted once with
dichloromethane. The combined organic layers were washed with water and
brine, dried over Na2SO4, and concentrated. Flash column chromatography on
silica gel (40% ethyl acetate in hexane) gave 4 (0.14 g, 79%) as a clear oil. 1H
NMR (400 MHz, CDCl3) d 5.82 (d, J = 4 Hz, 1H), 4.81 (t, J = 4 Hz, 1H), 4.66 (dd,
J = 5 Hz, 9 Hz, 1H), 4.35 (dd, J = 2 Hz, 12 Hz), 4.28–4.32 (m, 1H), 4.13 (dd,
J = 5 Hz, 12 Hz), 2.12 (s, 3H), 2.08 (s, 3H), 1.55 (s, 3H), 1.33 (s, 3H).
References and notes
1. Kocienski, P. G. Protecting Groups, 3rd Edition; Georg Thieme: Stuttgart, 2003.
2. Preparative Carbohydrate Chemistry; Hanessian, S., Ed.; CRC: New York, 1997.
3. (a) Demchenko, A. In Handbook of Chemical Glycosylation; Demchenko, A., Ed.;
Wiley-VCH: Weinheim, 2008; pp 5–6; (b) Hunig, S. Angew. Chem., Int. Ed. Engl.
1964, 3, 548–560.
4. Chittenden, G. J. F. Carbohydr. Res. 1972, 22, 491–493.
5. For
a review, see: (a) Kong, F. Carbohydr. Res. 2007, 342, 345–373; (b)
Kochetkov, N. K.; Khorlin, A. J.; Bochkov, A. F. Tetrahedron 1967, 23, 693–707.
6. (a) Betaneli, V. I.; Ovchinnikov, M. V.; Backinowsky, L. V.; Kochetkov, N. K.
Carbohydr. Res. 1979, 68, C11–C13; (b) Betaneli, V. I.; Ovchinnikov, M. V.;
Backinowsky, L. V.; Kochetkov, N. K. Carbohydr. Res. 1979, 76, 252–256.