E. A. Voight et al. / Tetrahedron Letters 42 (2001) 8747–8749
8749
cat. RuCl3•3H2O
NaIO4, RT
CCl4/CH3CN/H2O;
tion; Gottschalk, A., Ed. The structure of sialic acids and
their quantitation; Elsevier: Amsterdam, 1972; p. 403.
For chemical syntheses not yet reviewed, see: (d) Li,
L.-S.; Wu, Y.-L.; Wu, Y. Org. Lett. 2000, 2, 891–894; (e)
Kang, S. H.; Choi, H.-w.; Kim, J. S.; Youn, J.-H. Chem.
Commun. 2000, 227–228; (f) Banwell, M.; Savi, C. D.;
Watson, K. J. Chem. Soc., Perkin Trans. 1 1998, 2251–
2252; (g) Takahashi, T.; Tsukamoto, H.; Kurosaki, M.;
Yamada, H. Synlett 1997, 1065–1066.
OAc
OMe
OMe
AcO
AcO
AcO
OMe
OMe
O
N3
AcO
TMSCHN2
PhH/MeOH, RT
66 %
OAc
12
OAc
H2, Pd/C, MeOH;
Ac2O, Et3N,
O
CO2Me
N3
AcO
OAc
DMAP, CH2Cl2
69 %
6. (a) For a recent example, see: Schmidt, B. J. Chem. Soc.,
Perkin Trans. 1 1999, 2627–2637; (b) For a review, see:
Parker, R. E.; Isaacs, N. S. Chem. Rev. 1959, 59, 737.
7. For recent reviews, see: (a) Fu¨rstner, A. Angew. Chem.,
Int. Ed. 2000, 39, 3012–3043; (b) Schrock, R. R. Tetra-
hedron 1999, 55, 8141–8153; (c) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413–4450; (d) Armstrong, S. K. J.
Chem. Soc., Perkin Trans. 1 1998, 371–388; (e) Schuster,
M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36,
2036–2056.
13
OAc
OMe
O
CO2Me
AcHN
AcO
OAc
14
Scheme 3. Completion of the formal synthesis of Neu5Ac.
8. (a) Paulsen, H.; Heitmann, A. C. Liebigs Ann. Chem.
1988, 11, 1061–1071; (b) Zbiral, E.; Schmid, W. Monatsh.
Chem. 1985, 116, 253–262.
9. Takatori, K.; Kajiwara, M. Synlett 1995, 3, 280–282.
10. Surprisingly, attempted epoxidation using Mitsunobu
conditions gave almost exclusively the undesired b-epox-
ide despite close precedent suggesting that 10 should be
the major product: Thomson, R.; von Itzstein, M. Carbo-
hydr. Res. 1995, 274, 29–44.
verted to Neu5Ac 1 using 1N aq. sodium hydroxide
followed by acidification with aq. HCl (70%).13a,d The
1H NMR, TLC Rf, IR, MS, and optical rotation data
for 14 matched those reported in the literature.13,14 The
formal total synthesis of Neu5Ac has thus been
achieved in 9.3% overall yield from diene diol 6
employing our convergent ketalization/ring-closing
metathesis strategy and exploiting the resulting rigid
6,8-dioxabicyclo[3.2.1]octane template. The develop-
ment and application of this strategy to other natural
products and ring systems is currently being explored.
11. Monneret, C.; Risse, S.; Ardouin, P.; Gouyette, A. Eur.
J. Med. Chem. Chim. Ther. 2000, 35, 137–146.
12. (a) Baker, R.; Boyes, H. O.; Broom, M. P.; O’Mahony,
M. J.; Swain, C. J. J. Chem. Soc., Perkin Trans. 1 1987,
1613–1621; (b) Ka˜le´, V. N.; Clive, D. L. J. J. Org. Chem.
1984, 49, 1554–1563.
Acknowledgements
13. (a) Julina, R.; Mu¨ller, I.; Vasella, A. Carbohyd. Res.
1987, 164, 415–432; (b) Okamoto, K.; Kondo, T.; Goto,
T. Bull. Chem. Soc. Jpn. 1987, 60, 631–636; (c) Ogura, H.;
Furuhata, K. Carbohyd. Res. 1986, 158, 37–51; (d) Zbiral,
E.; Brandstetter, H. H. Monatsh. Chem. 1985, 116, 87–98;
(e) Ponpipom, M. M.; Buglianesi, R. L.; Shen, T. Y. Can.
J. Chem. 1980, 58, 214–220.
We thank the NIH [Grant CA74394 (SDB) and CBI
Training Grant 5 T32 GM08505 (EAV)] for generous
support of this research. The NIH (1 S10 RR0 8389-01)
and NSF (CHE-9208463) are acknowledged for their
support of the NMR facilities of the University of
Wisconsin-Madison Department of Chemistry.
1
14. Data for 14: H NMR (CDCl3) l 5.41 (dd, J=4, 2 Hz,
1H), 5.31 (d, J=10 Hz, 1H), 5.25 (ddd, J=11.5, 10.5, 5
Hz, 1H), 5.23 (ddd, J=7.5, 2.5, 2 Hz, 1H), 4.81 (dd,
J=12.5, 2.5 Hz, 1H), 4.13 (ddd, J=10.5, 10.5, 10 Hz,
1H), 4.12 (dd, J=12.5, 7.5 Hz, 1H), 3.93 (dd, J=10.5, 2.5
Hz, 1H), 3.82 (s, 3H), 3.27 (s, 3H), 2.44 (dd, J=13, 5 Hz,
1H), 2.15 (s, 3H), 2.09 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H),
1.89 (s, 3H), 1.89 (dd, J=13, 11.5 Hz, 1H); 13C NMR
(CDCl3) l 171.0 (C), 170.7 (C), 170.6 (C), 170.2 (C),
170.1 (C), 167.3 (C), 98.9 (C), 72.0 (CH), 71.7 (CH), 68.8
(CH), 68.4 (CH), 62.4 (CH2), 52.7 (CH3), 51.3 (CH3),
49.3 (CH), 37.3 (CH2), 23.2 (CH3), 21.0 (CH3), 20.9
(CH3), 20.8 (CH3×2); IR (thin film) 1745, 1664, 1541,
1371, 1225, 1038 cm−1; [h]D22 −12° (c=0.67, CHCl3); mp
131–133°C; HRMS (ESI) calcd. for C21H31O13NaN (M+
Na+) 528.1693, found 528.1675.
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