J. Am. Chem. Soc. 1999, 121, 3541-3542
3541
that the sole product obtained in this reaction, 5, is in fact a latent
2-deoxy-â-glycoside, we sought to generalize and broaden the
scope of this reaction.
A Highly Stereoselective Synthesis of
2-Deoxy-â-glycosides Using
2-Deoxy-2-iodo-glucopyranosyl Acetate Donors
William R. Roush*,1 and Chad E. Bennett
Department of Chemistry, UniVersity of Michigan
Ann Arbor, Michigan 48109
Department of Chemistry, Indiana UniVersity
Bloomington, Indiana 47405
ReceiVed December 18, 1998
2-Deoxy glycosides are important structural components of
many natural products.2 Although 2-deoxy-R-glycosides are
generally easily prepared from glycals or activated 2-deoxysugar
precursors,3-5 the synthesis of 2-deoxy-b-glycosides has proven
to be a much more challenging undertaking.4,6-8 There are
relatively few methods for the synthesis of this important
glycosidic linkage directly from 2-deoxy glycosyl precursors, and
those procedures that have been reported lack generality and often
do not proceed with high selectivity.9-13 The most extensively
developed strategy for synthesis of 2-deoxy-â-glycosides utilizes
donors with equatorial C(2) heteroatom substituents (e.g., -Br,14
-SR,7,8,15-20 -SePh,21 -OAc,22 -NHCHO,22 and 1,2-epoxy23) that
are removed reductively after the glycosylation event. However,
most of these methods also lack broad generality, and highly
specialized syntheses of the donors are often required.7,8,14
We report herein a new, highly stereoselective synthesis of
2-deoxy-â-glucosides that utilizes 2-deoxy-2-iodo-glucopyran-
osyl acetates as the glycosyl donors, as illustrated by eq 1. This
Results of glycosidation reactions of donors 6-11 with
monosaccharide acceptors 4 and 12-15 are summarized in Table
1. These reactions were performed in CH2Cl2, usually in the
presence of activated 4 Å molecular sieves, using either TMS-
OTf or TBS-OTf as the promoter. Typically 2 equiv. of the less
reactive donors 8-11 are employed, while the more reactive
donors 6 and 7 may be used as the limiting reagent.25 Remarkably,
these glycosylations are highly stereoselective, and provide the
2-deoxy-2-iodo-â-disaccharides 16-29 in 62-92% yield. The
only cases in which R-glycosides were observed were experiments
using primary alcohol 12 as the acceptor, and the least selective
example (7 + 12) still proceeds with a 9:1 preference favoring
the â-disaccharide. Given the high selectivity of these glycosi-
dations and the ease with which the 2-iodo substituent is reduced
with Bu3SnH,24 we anticipate that 2-iodo-glycosyl donors will
find widespread application in the synthesis of 2-deoxy-â-
glycosides.
methodology evolved from earlier studies on the synthesis of the
R-L-olivomycoside linkage present in the aureolic acid antitumor
antibiotics. During these studies we examined a single example
of the glycosidation reaction of the â-L-2-iodo-olivomycosyl
acetate 3 using glucopyranose 4 as the acceptor.24 Recognizing
(1) Correspondence to this author should be sent to the University of
Michigan address.
(2) Kirschning, A.; Bechtold, A. F.-W.; Rohr, J. Top. Curr. Chem. 1997,
188, 1.
(3) Thiem, J.; Klaffke, W. Top. Curr. Chem. 1990, 154, 285.
(4) Toshima, K.; Tatsuta, K. Chem. ReV. 1993, 93, 1503.
(5) Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996,
35, 1380.
(6) Roush, W. R.; Lin, X.-F. J. Am. Chem. Soc. 1995, 117, 2236.
(7) Roush, W. R.; Sebesta, D. P.; Bennett, C. E. Tetrahedron 1997, 53,
8825.
(8) Roush, W. R.; Sebesta, D. P.; James, R. A. Tetrahedron 1997, 53, 8837.
(9) Wiesner, K.; Tsai, T. Y. R.; Jin, H. HelV. Chim. Acta 1985, 68, 300.
(10) Crich, D.; Ritchie, T. J. Carbohydr. Res. 1989, 190, C3.
(11) Kahne, D.; Yang, D.; Lim, J. J.; Miller, R.; Paguaga, E. J. Am. Chem.
Soc. 1988, 110, 8716.
(12) Binkley, R. W.; Sivik, M. R. J. Carbohydr. Chem. 1991, 10, 399 and
references therein.
(13) Hashimoto, S.-i.; Sano, A.; Sakamoto, H.; Nakajima, M.; Yanagiya,
Y.; Ikegami, S. Synlett 1995, 1271.
(14) Thiem, J.; Gerken, M. J. Org. Chem. 1985, 50, 954 and references
therein.
(15) Nicolaou, K. C.; Ladduwahetty, T.; Randall, J. L.; Chucholowski, A.
J. Am. Chem. Soc. 1986, 108, 2466.
(16) Ito, Y.; Ogawa, T. Tetrahedron Lett. 1987, 28, 2723.
(17) Preuss, R.; Schmidt, R. R. Synthesis 1988, 694.
(18) Grewal, G.; Kaila, N.; Franck, R. W. J. Org. Chem. 1992, 57, 2084.
(19) Hashimoto, S.; Yanagiya, Y.; Honda, T.; Ikegami, S. Chem. Lett. 1992,
1511.
(20) Franck, R. W.; Marzabadi, C. H. J. Org. Chem. 1998, 63, 2197 and
references therein.
(21) Perez, M.; Beau, J.-M. Tetrahedron Lett. 1989, 30, 75.
(22) Trumtel, M.; Tavecchia, P.; Veyrie´res, A.; Sinay¨, P. Carbohydr. Res.
1989, 191, 29.
10.1021/ja984365j CCC: $18.00 © 1999 American Chemical Society
Published on Web 03/26/1999