COMMUNICATIONS
M. A. Foley, M. D. Shair, S. L. Schreiber, J. Am. Chem. Soc. 1998, 120,
8565 ± 8566; for reviews of molecular diversity, see: j) Comb. Chem.
Mol. Diversity Drug Discovery (Eds.: E. M. Gordon, J. F. Kerwin, Jr.),
Wiley, New York, 1998, p. 516; R. E. Dolle, Mol. Diversity 1998, 3,
199 ± 233; R. E. Dolle, K. H. Nelson, Jr., J. Comb. Chem. 1999, 1, 235 ±
282; H. Fenniri, Curr. Med. Chem. 1996, 3, 343 ± 378.
[22] Prepared in two steps from ethyl l-lactate by TBS protection (TBSCl,
imidazole) and DIBAL reduction (toluene, À788C).
[23] J.-L. Luche, J. Am. Chem. Soc. 1978, 100, 2226 ± 2227.
[24] For selected syntheses of l-vancosamine and derivatives thereof, see:
a) T. T. Thang, F. Winternitz, J. Chem. Soc. Chem. Commun. 1979,
153 ± 154; b) I. Dyong, H. Friege, Chem. Ber. 1979, 112, 3273 ± 3281;
c) T. T. Thang, F. Winternitz, Tetrahedron Lett. 1980, 21, 4495 ± 4498;
d) H. I. Ahmad, J. S. Brimacombe, A. S. Mengech, L. C. N. Tucker,
Carbohydr. Res. 1981, 93, 288 ± 293; e) I. Dyong, H. Friege, H.
Luftmann, H. Merten, Chem. Ber. 1981, 114, 2669 ± 2680; f) G. Fronza,
C. Fuganti, P. Grasselli, G. Pedrocchi-Fantoni, Tetrahedron Lett. 1981,
22, 5073 ± 5076; g) J. S. Brimacombe, A. S. Mengech, K. M. M. Rah-
man, L. C. N. Tucker, Carbohydr. Res. 1982, 110, 207 ± 215; h) G.
Fronza, C. Fuganti, P. Grasselli, G. Pedrocchi-Fantoni, J. Carbohydr.
Chem. 1983, 2, 225 ± 248; i) Y. Hamada, A. Kawai, T. Shioiri,
Tetrahedron Lett. 1984, 25, 5413 ± 5414; j) F. M. Hauser, S. R. Ellen-
berger, J. Org. Chem. 1986, 51, 50 ± 57; k) I. Dyong, J. Weigand, J.
Thiem, Liebigs Ann. Chem. 1986, 577 ± 599; l) A. Klemer, H. Wilbers,
Liebigs Ann. Chem. 1987, 815 ± 823; m) Y. Hamada, A. Kawai, T.
Matsui, O. Hara, T. Shioiri, Tetrahedron 1990, 46, 4823 ± 4846; n) R.
Greven, P. Jutten, H.-D. Scharf, Carbohydr. Res. 1995, 275, 83 ± 93;
o) K. C. Nicolaou, H. J. Mitchell, F. L. van Delft, F. Rübsam, R. M.
Rodríguez, Angew. Chem. 1998, 110, 1972± 1974; Angew. Chem. Int.
Ed. 1998, 37, 1871 ± 1874.
[25] J. O. Hoberg, Carbohydr. Res. 1997, 300, 365 ± 367.
[26] Extensive mechanistic studies dealing with the interactions of period-
inanes with anilides will be reported in due course.
[27] Crystallographic data (excluding structure factors) for the structure
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-142005. Copies of the data can be obtained free of charge on
application to CCDC, 12Union Road, Cambridge CB21EZ, UK (fax:
(44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
[2] For a recent review, see: K. C. Nicolaou, D. Vourloumis, N. Wins-
singer, P. S. Baran, Angew. Chem. 2000, 112, 46 ± 12 6;Angew. Chem.
Int. Ed. 2000, 39, 44 ± 122.
[3] For a comprehensive discussion, see: The Practice of Medicinal
Chemistry (Ed.: C. G. Wermuth), Academic Press, London, 1996,
p. 968.
[4] For selected reviews, see: a) M. S. Lee, H. Nakanishi, M. Kahn, Curr.
Opin. Drug Discovery Dev. 1999, 2, 332± 341; b) P. J. Edwards, M.
Gardner, W. Klute, G. F. Smith, N. K. Terrett, Curr. Opin. Drug
Discovery Dev. 1999, 2, 321 ± 331; c) C. D. Floyd, C. Leblanc, M.
Whittaker, Prog. Med. Chem. 1999, 36, 91 ± 168; d) S. Wilson, A. W.
Czarnik, Combinatorial Chemistry: Synthesis and Application, Wiley,
New York, 1997, p. 314.
[5] For some recent examples, see: G. W. Plant, S. Woerly, A. R. Harvey,
Exp. Neurol. 1997, 143, 287 ± 299; M. Chatterjee, P. J. Smith, C. A.
Townsend, J. Am. Chem. Soc. 1996, 118, 1938 ± 1948; G. S. Jacob,
Front. Biomed. Biotechnol. 1993, 1, 74 ± 86.
[6] Anonymous in Carbohydr. Chem. Vol. 30, Royal Society of Chemistry,
London, 1998, pp. 123 ± 140; J. Jurczak, Prep. Carbohydr. Chem. 1997,
595 ± 614.
[7] For the first preparation of IBX, see: C. Hartman, V. Meyer, Chem.
Ber. 1893, 26, 1727; for a superior route to IBX, see: M. Frigerio, M.
Santagostino, S. Sputore J. Org. Chem. 1999, 64, 4537 ± 4538; for the
introduction of the acronym ªIBXº, see: A. R. Katritzky, B. L. Duell,
J. K. Gallos, Org. Magn. Reson. 1989, 27, 1007 ± 1011; for use as a
selective oxidant for alcohols, see: M. Frigerio, M. Santagostino,
Tetrahedron Lett. 1994, 35, 8019 ± 8022; E. J. Corey, A. Palani,
Tetrahedron Lett. 1995, 36, 7945 ± 7948.
[8] For an insightful review of this approach, see: S. Knapp, Chem. Soc.
Rev. 1999, 28, 61 ± 72.
[9] Although, with such a mode of reaction as that shown in Scheme 1,
one might expect cis delivery to the olefin, trans addition is also
conceivable in certain cases. In the absence of a definitive mechanistic
trend for this IBX-mediated reaction at the outset of this work, it was
left to empirical observation to provide the answer as to the
stereochemical outcome.
[10] The aryl moiety and nitrogen atom of the carbamate group are
intimately involved in this IBX reaction, see Ref. [1f] for more
details.[26]
[11] D. R. Kronenthal, C. Y. Han, M. K. Taylor, J. Org. Chem. 1982, 47,
2765 ± 2768; S. Knapp, P. J. Kukkola , S. Sharma, J. Org. Chem. 1990,
55, 5700 ± 5710.
[12] H. H. Baer, L. Siemsen, J. DaFaye, K. Burak, Carbohydr Res. 1984,
134, 49 ± 61. The a- and b-isomers of this pyranose were separated
after reaction with DBU and p-methoxyphenyl isocyanate (a-anomer
used in Scheme 3; b-anomer used in entry 5, Table 1).
Novel Reactions Initiated by Titanocene
Methylidenes: Deoxygenation of Sulfoxides,
N-Oxides, and Selenoxides**
K. C. Nicolaou,* Alexandros E. Koumbis,
Scott A. Snyder, and Klaus B. Simonsen
Over the course of the past several years, sulfoxides have
become an increasingly important functional group in organic
synthesis, particularly as chirons in asymmetric synthesis.[1] As
[*] Prof. Dr. K. C. Nicolaou, Dr. A. E. Koumbis, S. A. Snyder,
Dr. K. B. Simonsen
[13] Compounds
9 and 10 were derived from methyl-a-d-mannose
pyranoside and methyl-b-d-galactose pyranoside, unpublished results.
[14] Compounds 11 and 12 were derived from l-arabinose, unpublished
results..
[15] K. C. Nicolaou, C. K. Hwang, B. E. Marrow, S. A. DeFrees, E. A.
Couladouros, Y. Abe, P. J. Carrol, J. Snyder, J. Am. Chem. Soc. 1990,
112, 3040 ± 3054.
[16] M. Brakta, G. Massiot, G. D. Sinou, G. Daves, J. Org. Chem. 1993, 58,
2992 ± 2998.
[17] G. F. Bordwell, S. R. Mrozack, J. Org. Chem. 1982, 47, 3802± 3803.
[18] Compounds 18 and 19 were derived from ethyl l-lactate, unpublished
results.
Department of Chemistry and The Skaggs Institute for Chemical
Biology
The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Fax : (1)858-784-2469
and
Department of Chemistry and Biochemistry
University of California San Diego
9500 Gilman Drive, La Jolla, CA 92093 (USA)
[19] A. W. Johnson, R. M. Smith, R. D. Guthrie, J. Chem. Soc. Perkin
Trans. 1 1972, 17, 2153 ± 2159; W. D. Weringa, D. H. Williams, J. Feeny,
J. P. Brown, R. W. King, J. Chem. Soc. Perkin Trans. 1 1972, 3, 443 ±
446.
[20] a) K. Takai, K. Kimura, T. Kuroda, T. Hiyama, H. Nozaki, Tetrahedron
Lett. 1983, 24, 5281 ± 5284; b) H. Jin, J. Uenishi, W. J. Christ, Y. Kishi,
J. Am. Chem. Soc. 1986, 108, 5644 ± 5646.
[**] We thank Drs. D. H. Huang and G. Suizdak for NMR spectroscopic
and mass spectroscopic assistance, respectively. Financial support for
this work was provided by The Skaggs Institute for Chemical Biology,
the National Institutes of Health (USA), fellowships from the
National Science Foundation (S.A.S.) and the Alfred Benzons
Foundation (K.B.S.), and grants from Abbott, Amgen, Boehringer-
Ingelheim, GlaxoWellcome, Hoffmann-LaRoche, DuPont, Merck,
Novartis, Pfizer, and Schering Plough.
[21] X. Lu, G. Zhu, S. Ma, Chin. J. Chem. 1993, 11, 267 ± 271.
Angew. Chem. Int. Ed. 2000, 39, No. 14
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