A novel and efficient deprotection of the allyl group at the anomeric oxygen of carbohydrates

Article abstract of DOI:10.1055/s-1998-1579

Perfluoroalkylation with perfluoroalkyl iodide under sodium dithionite and sodium bicarbonate in acetonitrile/water followed by elimination in the presence of zinc powder and ammonium chloride in ethanol was disclosed to be an extremely mild and efficient procedure for deprotection of the anomeric allyl group of carbohydrates.

Full text of DOI:10.1055/s-1998-1579

January 1998
SYNLETT
29
A Novel and Efficient Deprotection of the Allyl Group at the Anomeric Oxygen of
Carbohydrates
Biao Yu,* Jianbo Zhang, Shoufu Lu, Yongzheng Hui*
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
Fax: 21 64166128; E-mail: byusioc@fudan.ac.cn
Received 14 October 1997
Abstract: Perfluoroalkylation with perfluoroalkyl iodide under sodium
dithionite and sodium bicarbonate in acetonitrile/water followed by
elimination in the presence of zinc powder and ammonium chloride in
ethanol was disclosed to be an extremely mild and efficient procedure
for deprotection of the anomeric allyl group of carbohydrates.
Synthetic oligosaccharides and glycoconjugates are indispensable
probes for life science and promising drug candidates for the
1
pharmaceutical industry. In the course of synthesizing an
oligosaccharide or a glycoconjugate, the manipulation of the anomeric
2
hydroxyl of a carbohydrate plays a pivotal role. The anomeric hydroxyl
has to be protected then a carbohydrate can be converted into a
glycosylation acceptor; and the anomeric hydroxyl protection has to be
released, if it can not directly serve as a leaving group as that in
3
4
5
6
thioglycosides, glycals, 4-pentenyl glycosides, and vinyl glycosides,
7
etc., then a carbohydrate can be used as or functionalized into a variety
of glycosyl donors, such as glycosyl imidates,
2b
2a
halides, and
8
phosphites, etc. Therefore, the protective group for the anomeric
hydroxyl not only should stay intact under the conditions for the
manipulation of other protective groups and for glycosylation, but also
should be selectively removed afterwards without affecting other
protective groups. Although, many protective groups have been
successfully employed for the anomeric hydroxyl protection in the
block synthesis of oligosaccharides and glycoconjugates, such as tert-
butyldimethylsilyl,
methoxylphenyl, and allyl, etc., there are none generally applicable.
Allyl is one of the most commonly used protective group in
Scheme
9
10
11
2-trimethylsilylethyl,
benzyl,
4-
12
13
14
carbohydrate chemistry, which is compatible with fairly strong acidic
or basic conditions, and could be removed under many procedures.
14-18
The most useful conditions for deallylation in carbohydrate chemistry
16
17
18
involved the utilization of palladium, rhodium, or iridium species.
It seems ideal to use allyl as the protective group for the anomeric
hydroxyl of a carbohydrate building block, ignoring the expensiveness
of these metal species. However, deblocking the allyl protection at the
anomeric hydroxyl of
a carbohydrate was found to be very
16c,19
capricious,
the results were subtly dependent on the substrates.
Herein we disclosed an extremely mild and efficient procedure to
remove the anomeric allyl protection. The results are listed in the
scheme and table.
Employing the well documented and widely applicable
perfluoroalkylation of the terminal carbon carbon double bond with
perfluoroalkyl iodide under sodium dithionite/sodium bicarbonate in
22
acetonitrile/water, allyl glycosides (1a-9a) were perfluoroalkylated
under almost neutral conditions at rt. After an easy work up, the
anomeric anchor of 1b-9b was eliminated efficiently in the presence of
zinc powder and ammonium chloride in ethanol (reflux, 5 min). Both
steps were found to be very clean on the TLC, after purification by a
silica gel column chromatography, good yields of the corresponding
carbohydrates with a free hemiacetal (1c-9c) were obtained. The most
commonly used protective groups, including benzyl, benzoyl, acetyl,
benzylidene (either dioxolane-type or dioxane-type), tert-
butyldimethylsilyl, and N-phthalimide, were all intact. In comparison,
some unsuccessful palladium species involving deallylation of the allyl
glycosides were listed in the table (entry 10-14).
It is worthy noting that the finally removed perfluoroalkane moiety
could not only be a ballast but a useful anchor for further purpose, such
23
as for the “fluorous synthesis” of carbohydrates, that is also our
current interest.

30
LETTERS
SYNLETT
Acknowledgments. This work is supported by the State Science and
Technology Committee of China. B. Yu thank Chinese Academy of
Sciences and the National Education Committee of China for partial
financial support, thank Prof. Long Lü for his helpful discussion.
34, 6929. (c) Nakayama, K.; Uoto, K.; Higashi, K.; Soga, T.;
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References and Notes:
1.
(a) Synthetic Oligosaccharides, Indispensable Probes for the Life
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17. (a) Corey, E. J.; Suggs, J. W. J. Org. Chem. 1973, 38, 3223. (b)
Boons, G.-J. J. Chem. Soc., Chem. Common. 1996, 141.
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Common. 1978, 694. (b) Oltvoort, J. J.; Van Boechel, C. A. A.; de
Koning, J. H.; Van Boom, J. H. Synthesis, 1981, 305.
2.
(a) Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
(b) Schmidt, R. R. ibid. 1986, 25, 212. (c) Toshima, K.; Tatsuta,
K. Chem. Rev. 1993, 93, 1503. (d) Ogawa, T. Chem. Soc. Rev.
1994, 397. (e) Boons, G.-J. Comtemporary Organic Synthesis
1995, 173.
19. (a) Lüning, J.; Möller, U.; Debski, N.; Welzel, P. Tetrahedron
Lett. 1993, 34, 5871. (b) Mostowicz, D.; Chmielewski, M. Polish.
J. Chem. 1993, 67, 1235.
20. Herein, I(CF ) Cl (n = 2, 6) were gifts from Prof. L. Lü. When
3.
4.
5.
6.
7.
8.
9.
for an example see: Cheng, M. K.; Douglas, N. L.; Hinzen, B.;
Ley, S. V.; Pannecoucke, X. Synlett 1997, 257
2 n
perfluoroalkylated with I(CF ) Cl, the corresponding products
2 2
have the same R as that of the starting allyl glycosides, therefore
f
Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl.
1996, 35, 1380.
the reaction can not be monitored by TLC. Several other
perfluoroalkyl iodides are available in Aldrich catalog.
Fraser-Reid, B.; Wu, Z.; Andrews, C. W.; Skowronski, E.;
Browen, J. P. J. Am. Chem. Soc. 1991, 113, 1434.
21. Typical procedure: To a stirred solution of 1a (200 mg, 0.39
mmol) and I(CF ) Cl (180 mg, 1.0equiv) in CH CN (12 mL), was
2 6
3
Boons, G.-J.; Heskamp, B.; Hout, F. Angew. Chem., Int. Ed. Engl.
1996, 35, 2845.
added H O (3 mL) at rt, the mixture turned to be an emulsion, to
2
which a mixture of Na S O (335 mg, 5.0 equiv) and NaHCO
3
2
2
4
Garcia, B. A.; Poole, J. L.; Gin, D. Y. J. Am. Chem. Soc. 1997,
119, 7597 and the references cited therein.
(162 mg, 5.0 equiv) was added. After being stirred at rt for 30
min, the mixture was diluted with EtOAc (50 mL), the organic
layer separated was washed with brine twice, dried over
Kondo, H.; Aoki, S.; Ichikawa, Y.; Halcomb, R. L.; Ritzen, H.;
Wong, C. H. J. Org. Chem. 1994, 59, 864.
anhydrous Na SO and concentrated. The residue was
2
4
chromatoghaphed on a silica gel column to give 1b (96%) or
For an example see: Windmüller, R.; Schmidt, R. R. Tetrahedron
Lett. 1994, 35, 7927.
directly treated with Zn powder (125 mg, 5.0 equiv) and NH Cl
4
(40 mg, 2.0 equiv) in absolute EtOH, after being refluxed for 5
min, the mixture was cooled to rt, filtered and concentrated. Flash
10. For an example see: Tietze, L. F.; Keim, H. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1615.
chromatography of the residue on a silica gel column afforded 1c
11. For an example see: Sugimoto, M.; Fujikura, K.; Nunomura, S.;
1
(85%, based on 1a). 1b: H NMR (300 MHz, CDCl ): δ 8.05 (m,
3
Ito, Y.; Ogawa, T. Tetrahedron Lett. 1990, 31, 1435.
4H, Ar), 7.50 (m, 4H, Ar), 7.38 (m, 7H, Ar), 6.20 and 6.14 (2(t,
1H, J = 9.7, H-3’), 5.64 and 5.62 (2 x s, 1H, PhCH), 5.36(m, 1H,
12. Goto, F.; Ogawa, T. Pure Appl. Chem. 1993, 65, 793.
13. For an example see: Yamada, H.; Harada, T.; Takahashi, T. J. Am.
Chem. Soc. 1994, 116, 7917.
H-2’), 4.46-3.70 (m, 8H), 3.05 and 2.75 (2 x m, 2H, H-3) ppm;
19
F NMR (TFA as a standard): δ 68.8 (s, 2F, ClCF ), 112.8 (s, 2F,
2
+
CH CF ), 119.2-121.4 (m, 8F) ppm; EIMS (m/z): 978 (M ), 930,
830, 696, 506, 105 (100%). 1c: H NMR (CDCl ): δ 8.00 and 7.40
14. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1991; p42.
2
2
1
3
(m, 15H, Ar), 6.13 (t, 0.75H, J = 9.8, H-3α), 5.85 (t, 0.25H, J =
9.7, H-3β), 5.68 (d, 0.75H, J = 3.4, H-1α), 5.56 (s, 0.75H,
PhCHα), 5.53 (s, 0.25H, PhCHβ), 5.30 (m, 1.25H, H-2, H-1β),
4.35 (m, 2H), 3.90 (m, 2H) ppm; EIMS (m/z): 476 (M ), 459, 353,
327, 105 (100%).
15. Recent examples on the deallylation see: (a) Thomas, R. M.;
Mohan, G. H.; Iyengar, D. S. Tetrahedron Lett. 1997, 38, 4721.
(b) Lee, J.; Cha, J. K. ibid. 1996, 37, 3663. (c) Yadav, J. S.;
Chandrasekhar, S.; Sumithra, Sumithre, G; Kacke, R. ibid. 1996,
37, 6603. (d) Diaz, R. R.; Melagatejo, C. R.; Espinosa, M. T. P.
L.; Cubero, I. I. J. Org. Chem. 1994, 59, 7928. (e) Ito, H.;
Taguchi, T.; Hanzawa, Y. ibid. 1993, 58, 774.
+
22. Huang, W. Y. J. Fluoro. Chem. 1992, 58, 1.
23. Studer, A.; Hadida, S.; Ferritto, R.; Kim, S.-Y.; Jegar, P.; Wipf,
P.; Curran, D. P. Science, 1997, 275, 823.
16. (a) Beugelmans, R.; Bourdet, S.; Bigot, A.; Zhu, J. Tetrahedron
Lett. 1994, 35, 4349. (b) Mereyala, H. B.; Guntha, S. ibid. 1993,