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S. Wendeborn et al. / Tetrahedron Letters 43 (2002) 5461–5464
In full agreement with our analysis, the use of
ATPH13,14 as Lewis acids led to formation 16b and 16a
in a ratio 45:1; even more impressive results were
obtained with MAD,13,15 which led to exclusive forma-
tion of the desired 16b. Interestingly, catalytic amounts
of MAD led to formation of 16 with only slightly
diminished b-selectivity.
2. (a) Becker, H.; Soler, M. A.; Sharpless, K. B. Tetrahedron
1995, 51, 1345; (b) Allevi, P.; Tarocco, G.; Longo, A.;
Anastasia, M.; Cajone, F. Tetrahedron: Asymmetry 1997,
8, 1315.
3. Krapcho, P. Synthesis 1982, 805.
4. Mulzer, J.; Kappert, M.; Huttner, G.; Jibril, I. Angew.
Chem., Int. Ed. Engl. 1984, 23, 704.
5. (a) Wessel, H.-P.; Iverson, T.; Bundle, D. R. J. Chem.
Soc., Perkin Trans. I 1985, 2247; (b) Nakajima, N.;
Horita, K.; Abe, R.; Yonemitsu, O. Tetrahedron Lett.
1988, 29, 4139 The resulting trichloroacetamide was best
removed from the crude product by Kugelrohr destilla-
tion, since it co-eluted on silica gel together with 10.
6. Examples for selective reductions of lactols in the pres-
ence of esters can be found: (a) Binch, H.; Stangier, K.;
Thiem, J. Carbohydrate Res. 1998, 306, 409; (b) Kohn, P.;
Samaritano, R. H.; Lerner, L. M. J. Am. Chem. Soc.
1965, 87, 5475; (c) Tse, A.; Mansour, T. Tetrahedron
Lett. 1995, 36, 7807.
7. ee’s were determined by chiral HPLC; hydrolysis of the
enantiomer of 10 (prepared from 4 by the same route but
using b-AD-mix) with NaOH gave enantiomer of 12,
allowing unambiguous determination of enantiomeric
excess by chiral HPLC.
When these conditions were applied to 13, compound
19 was obtained as a single diastereomer in 61% yield
(Scheme 6).
In conclusion, we have developed a highly stereoselec-
tive synthesis of 5%-(S)-methyl-3%-carboxymethylene-3%-
deoxythymidine. The stereochemistry at C(4%) and C(5%)
has been controlled by asymmetric Sharpless bishydroxy-
lation, while the C(3%)-stereochemistry could be
efficiently controlled during cyclization of the C(3%)-
pro-chiral diester 7 to the lactone 2. Enantiomeric
excess was increased to 100% through enantioselective
enzymatic hydrolysis of ester 10. In a final key step
thymine introduction was accomplished with exclusive
b-face selectivity through the novel use of Yamamoto’s
bulky aluminum based Lewis acid ‘MAD’ in a modified
Vorbru¨ggen-type nucleosidation reaction. We expect
that this methodology may be applied to the synthesis
of related nucleoside and C-nucleoside analogs.
8. See Ref. 1b.
9. Side group participation was reported to be successful in
a related Vorbru¨ggen reaction when the thionoester was
employed: Lavalle´e, J.-F.; Just, G. Tetrahedron Lett.
1991, 32, 3472.
10. For side group participation of methylenephosphonoth-
ioate in a related Vorbru¨ggen reaction see: Yokomatsu,
T.; Sada, T.; Shimizu, T.; Shibuya, S. Tetrahedron Lett.
1998, 39, 6299.
The use of 19 in the synthesis of novel oligonucleotide
backbone modifications will be reported elsewhere.
Acknowledgements
11. While our studies were in progress a similar approach for
the synthesis of C-glycosides from bicyclic lactones has
been reported: Gaertzen, O.; Misske, A. M.; Wolbers, P.;
Hoffmann, H. M. R. Synlett 1999, 1041.
We thank Mr. Hans-Rudolf Baumgartner for perform-
ing chiral HPLC analysis and Dr. Tammo Winkler for
superb NMR support.
12. Niedballa, U.; Vorbru¨ggen, H. J. Org. Chem. 1974, 39,
3654.
References
13. (a) Maruoka, K.; Imoto, H.; Yamamoto, H. Synlett
1994, 6, 441; (b) Maruoka, K.; Imoto, H.; Saito, S.;
Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 4131; (c)
Maruoka, K.; Shimada, I.; Imoto, H.; Yamamoto, H.
Synlett 1994, 7, 519; (d) Maruako, K.; Concepcion, B.;
Murase, N.; Oishi, M.; Hirayama, N.; Yamamoto, H. J.
Am. Chem. Soc. 1993, 115, 3943; (e) Saito, S.; Shiozawa,
M.; Yamamoto, H. Angew. Chem., Int. Ed. 1999, 38,
1769; (f) Saito, S.; Yamamoto, H. J. Chem. Soc., Chem.
Commun. 1997, 1585.
1. (a) Lebreton, J.; De Mesmaeker, A.; Waldner, A.;
Fritsch, V.; Wolf, R. M.; Freier, S. M. Tetrahedron Lett.
1993, 34, 6383; (b) De Mesmaeker, A.; Waldner, A.;
Lebreton, J.; Hoffmann, P.; Fritsch, V.; Wolf, R. M.;
Freier, S. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 226;
(c) Idziak, I.; Just, G.; Damha, M. J.; Giannaris, P. A.
Tetrahedron Lett. 1993, 34, 5417; (d) Wendeborn, S.;
Wolf, R. M.; De Mesmaeker, A. Tetrahedron Lett. 1995,
36, 6879; (e) De Mesmaeker, A.; Haener, R.; Martin, P.;
Moser, H. E. Acc. Chem. Res. 1995, 28, 366; (f) De
Mesmaeker, A.; Altmann, K.-H.; Waldner, A.; Wen-
deborn, S. Curr. Opin. Struct. Biol. 1995, 5, 343.
14. ATPH=aluminum tris(2,6-diphenylphenoxide).
15. MAD=methylaluminum bis(2,6-di-tert-butyl-4-methyl-
phenoxide).