LETTER
Synthesis of Enantiopure C-Glycosides and Pseudo C-Glycosides
(3) a) Discovery and structure elucidation: Searle, P. A.;
1043
glycosides under these conditions (entry c). However, em-
ploying acetonitrile as the solvent in case of lactone 3 led
to significant improvement (entry d). In general, by
changing the solvent from dichloromethane to acetoni-
trile, all reactions gave excellent chemical yields. Ni-
tromethane also served well in some cases, but provided
no major advantage over acetonitrile. Other Lewis acids,
such as BF3◊Et2O or ZnCl2, were used, but gave mainly
elimination products or decomposition under similar con-
ditions. In nearly all cases the 2,6-trans-C-glycoside ste-
reochemistry was established exclusively, which is a
result of the anomeric effect and shielding by the carbox-
ylate leaving group. Examples are reactions of lactones 3
to 6. Even lactones unsubstituted in 3-position gave exclu-
sively the 2,6-trans product. In contrast, steric hindrance
of the axial methyl group of lactone 7 furnished a mixture
of epimers where 2,6-cis configuration is favored when
bulky silyl ketene acetal was used (entry r). The less hin-
dered allylsilane gave only the 2,6-trans-C-glycoside (en-
try h). Considering lactone 4, the selectivity of silyl ketene
acetal addition is reduced, perhaps caused by conforma-
tional flexibility of the tetrahydropyran ring due to the
exocyclic double bond (entry o).
Molinski, T. F. J. Am. Chem. Soc. 1995, 117, 8126; Searle, P.
A.; Molinski, T. F.; Brzezinski, L. J.; Leahy, J. W. J. Am.
Chem. Soc. 1996, 118, 9422; Molinski, T. F. Tetrahedron Lett.
1996, 37, 7879; b) total synthesis: Forsyth, C. J.; Ahmed, F.;
Cink, R. D.; Lee, C. S. J. Am. Chem. Soc. 1998, 120, 5597, and
references cited therein; other synthetic efforts: c) Ye, T.;
Pattenden, G. Tetrahedron Lett. 1998, 39, 319; d) Pattenden,
G.; Plowright, A. T.; Tornos, J. A.; Ye, T. Tetrahedron Lett.
1998, 39, 6099; e) Paterson, I.; Arnott, E. A. Tetrahedron Lett.
1998, 39, 7185; f) Williams, D. R.; Brooks, D. A.; Meyer, K.
G.; Clark, M. P. Tetrahedron Lett. 1998, 39, 7251; g) Wolbers,
P.; Hoffmann, H. M. R. Tetrahedron 1999, 55, 1905;
h) Misske, A. M.; Hoffmann, H. M. R. Tetrahedron 1999, 55,
4315.
(4) a) Hosomi, A.; Sakata, Y.; Sakurai, H. Tetrahedron Lett.
1984, 25, 2383; b) Jégou, A.; Pacheco, C.; Veyrières, A.
Tetrahedron 1998, 54, 14779.
(5) a) Craig, D.; Munasinghe, V. R. N. Tetrahedron Lett. 1992,
33, 663; b) Craig, D.; Pennington, M. W.; Warner, P.
Tetrahedron Lett. 1995, 36, 5815.
(6) Brown, D. S.; Bruno, M.; Davenport, R. J.; Ley, S. V.
Tetrahedron 1989, 45, 4293.
(7) Fernandez-Megia, E.; Gourlaouen, N.; Ley, S. V.; Rowlands,
G. J. Synlett 1998, 991.
(8) a) Minehan, T. G.; Kishi, Y. Tetrahedron Lett. 1997, 38, 6815;
b) Ichikawa, Y.; Isobe, M.; Konobe, M.; Goto, T. Carbohydr.
Res. 1987, 171, 193.
(9) a) Buffet, M. F.; Dixon, D. J.; Ley, S. V.; Tate, E. W. Synlett
1998, 1091; b) Dixon, D. J.; Ley, S. V.; Tate, E. W. Synlett
1998, 1093; c) Dixon, D. J.; Ley, S. V.; Tate, E. W. J. Chem.
Soc. Perkin Trans. I 1998, 3125.
In summary, we have shown that 2,6-trans-C-glycosides
are easily and selectively prepared in high yield from ox-
abicyclic lactones. Thanks to Lewis acid the lactone moi-
ety serves as an efficient leaving group and the
stereochemistry of nucleophilic attack at the anomeric
centre is predetermined. In our opinion the methodology
is of high utility for the synthesis of carbon linked pyran
rings. The diversity of our anomeric oxabicyclic [3.3.1]
lactones provides high flexibility of this synthetic ap-
proach. The C-glycosides prepared are useful precursors
for the synthesis of a variety of biologically important nat-
ural products.3g
(10) Illustrative procedure for the preparation of lactones 2 and 3:
Acknowledgement
We thank the Fonds der Chemischen Industrie for a PhD fellowship
(A. M. M.), the Deutsche Forschungs-gemeinschaft for a PhD fel-
lowship (P. W., Graduiertenkolleg Chemische und technische
Grundlagen der Naturstofftransformation) and Ulrike Eggert and
Marc Schinner for their help and experimental contributions.
References and Notes
(1) Recent reviews on C-glycosides: a) Hosomi, A.; Sakata, Y.;
Sakurai, H. Carbohydr. Res. 1987, 171, 223; b) Jaramillo, C.;
Knapp, S. Synthesis 1994, 1; c) Postema, M. H. D. C-
Glycoside Synthesis, CRC Press Inc., Boca Raton, Fl 1995;
Postema, M. H. D. Tetrahedron 1992, 48, 8545; d) Levy, D.
E.; Tang, C. The Chemistry of C-Glycosides, Pergamon Press,
Tarrytown 1995; e) Bertozzi, C.; Bednarski, M. in Modern
Methods in Carbohydrate Synthesis, Khan, S. H.; O´Neill, R.
A. ed., Harwood Amsterdam 1996, 319.
(2) Discovery and structure elucidation: a) Uemura, M.; Ueda, K.;
Hirata, Y.; Naoki, H.; Iwashita, T. Tetrahedron Lett. 1981, 22,
2781; b) Moore, R. E.; Bartolini, G. J. Am. Chem. Soc. 1981,
103, 2491; total synthesis: Kishi, Y.; Suh, E. M. J. Am. Chem.
Soc. 1994, 116, 11205, and references cited therein.
Conditions: i) L-Selectride®, THF, -78ºC, 2 h; ii) NaH, THF,
BnBr, reflux, 16 h; iii) a) (-)-(Ipc)2BH, THF; b) NaOH, H2O2;
iv) PCC, NaOAc, 4Å molecular sieves, DCM, rt, 1 h; v) m-
CPBA, F3CCO2H, DCM, rt, 15 h; vi) m-CPBA, NaHCO3,
DCM, rt, 15 h.
For preparation of lactones 1, 4-8 see refs. 3h and 11.
(11) a) Lampe, T. F. J.; Hoffmann, H. M. R. J. Chem. Soc. Chem.
Commun. 1996, 1931; b) Weiss, J. M.; Hoffmann, H. M. R.
Tetrahedron: Asymmetry 1997, 8, 3913; c) Stark, C. B. W.;
Eggert, U.; Hoffmann, H. M. R. Angew. Chem. 1998, 110,
1337; Angew. Chem. Int. Ed. Engl. 1998, 37, 1266;
d) Schinner, M.; PhD thesis, Universität Hannover 1999; see
also: Wittenberg, J.; Beil, W.; Hoffmann, H. M. R.
Synlett 1999, No. 07, 1041–1044 ISSN 0936-5214 © Thieme Stuttgart · New York