Removal of benzylidene acetal and benzyl ether in carbohydrate derivatives using triethylsilane and Pd/C

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Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme VII-M, Kolkata-700054, India; FAX: 91-33-2355 3886
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Associate Editor: M. Rueping
Beilstein J. Org. Chem. 2013, 9, 74–78. https://doi.org/10.3762/bjoc.9.9
Received 12 Oct 2012, Accepted 17 Dec 2012, Published 14 Jan 2013
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Abstract

Clean deprotection of carbohydrate derivatives containing benzylidene acetals and benzyl ethers was achieved under catalytic transfer hydrogenation conditions by using a combination of triethylsilane and 10% Pd/C in CH3OH at room temperature. A variety of carbohydrate diol derivatives were prepared from their benzylidene derivatives in excellent yield.

Keywords: benzylidene; glycoside; Pd/C; transfer hydrogenation; triethylsilane

Introduction

Functionalization of carbohydrate intermediates is essential for their assembly towards the synthesis of complex oligosaccharides [1-9]. Benzylidene acetal is a frequently used protecting group for the simultaneous protection of 1,2- and 1,3-diol derivatives [10,11]. It can be removed under acidic hydrolysis as well as under neutral conditions (e.g., hydrogenolysis). The benzylidene acetal can also be regioselectively opened under reductive conditions to produce partially benzylated derivatives [12-14]. A number of methods have been reported for the removal of benzylidene acetals by using strong protic and Lewis acids [10,11,15] as well as some heterogeneous acidic catalysts [16,17]. Removal of benzylidene acetal under nonacidic conditions includes hydrogenolysis using hydrogen gas over Pd/C [18], or treatment with hydrazine [19] or EtSH [20] or Na/NH3 [21], etc. However, most of the above-mentioned methodologies have several shortcomings, such as harsh conditions, formation of unwanted byproducts, longer reaction time, incompatibility of functional groups, use of expensive reagents, fire hazard, etc. In this context, the development of a mild, neutral reaction condition for the removal of benzylidene acetals would be useful in the derivatization of a carbohydrate framework. Mandal et al. reported the removal of benzyl esters/ethers and the reduction of alkenes/alkynes by catalytic transfer hydrogenation using a combination [22] of triethylsilane (Et3SiH) and 10% Pd/C. In our synthetic endeavor we sought to explore the catalytic potential of a combination of Et3SiH and 10% Pd/C in the deprotection of a benzylidene group in the carbohydrate derivatives, without the formation of unwanted byproducts. We report herein our findings on the removal of benzylidene acetal using a combination of triethylsilane and 10% Pd/C (Scheme 1).

[1860-5397-9-9-i1]

Scheme 1: Removal of benzylidene acetal and benzyl ether by using a combination of triethylsilane and 10% Pd/C.

Results and Discussion

In a set of initial experiments, methyl 2,3-di-O-acetyl-4,6-O-benzylidene-α-D-glucopyranoside (1) was treated with a combination of a varied quantity of triethylsilane (1.0–5.0 equiv of the substrate) and 10% Pd/C (10–20 mg per 100 mg substrate) in CH3OH at room temperature. It was observed that the use of a total 3.0 equiv of triethylsilane and 10% Pd/C (10 mg/100 mg of substrate) in CH3OH at room temperature furnished the clean removal of the benzylidene group in a 87% yield in 30 min. Generalizing the reaction conditions, a series of benzylidene acetal containing monosaccharide and disaccharide derivatives, with different functional groups present in them, were treated with the optimized reagent system, and clean removal of benzylidene acetal was observed in all cases. The effect of triethylsilane and 10% Pd/C on the removal of benzylidene acetal is presented in Table 1. The noteworthy features of the reaction condition are: (a) neutral conditions; (b) compatibility with a large number of functional groups used in the protection of carbohydrates (e.g., acetyl, benzoyl, phthaloyl, 2-(trimethylsilyl)ethyl, 4-methoxyphenyl, etc.); (c) clean and high yielding; (d) no unwanted byproduct formation; (e) can be carried out at room temperature; (f) no flammable gas is required. The reaction conditions were equally effective for the removal of 4-methoxybenzylidene acetal (Table 1, entries 13–15). Allyl ether was reduced and benzyl ethers were removed under the reaction conditions, as expected from the earlier report [22] (Table 1, entry 8 and entries 3, 4, 9, 10, 12). Benzyl ethers and benzylidene acetal in a compound can be removed in one pot by using these reaction conditions (Table 1, entries 3, 4, 9, 10, 12). All debenzylidenated products were characterized by NMR spectral analysis. Known compounds gave acceptable NMR spectra that matched the previously reported data.

Table 1: Conversions of carbohydrate derivatives effected with Et3SiH and 10% Pd/C.

Entry Substrate Producta Time (min) Yieldb (%) Ref.c
1 [Graphic 1]
1 		[Graphic 2]
2 		30 87 [23]
2 [Graphic 3]
3 		[Graphic 4]
4 		30 85 [24]
3 [Graphic 5]
5 		[Graphic 6]
6 		60 90d [25]
4 [Graphic 7]
7 		[Graphic 8]
8 		60 88d –
5 [Graphic 9]
9 		[Graphic 10]
10 		40 87 [26]
6 [Graphic 11]
11 		[Graphic 12]
12 		40 82 [27]
7 [Graphic 13]
13 		[Graphic 14]
14 		40 90 –
8 [Graphic 15]
15 		[Graphic 16]
16 		40 92 –
9 [Graphic 17]
17 		[Graphic 18]
18 		40 84d,e –
10 [Graphic 19]
19 		[Graphic 20]
20 		120 77d [28]
11 [Graphic 21]
21 		[Graphic 22]
22 		60 84 –
12 [Graphic 23]
23 		[Graphic 24]
24 		90 80d,e –
13 [Graphic 25]
25 		[Graphic 26]
2 		40 88 [23]
14 [Graphic 27]
26 		[Graphic 28]
27 		40 90 [16]
15 [Graphic 29]
28 		[Graphic 30]
29 		30 86 [29]

aAbbreviations used: PMP: 4-methoxyphenyl; Phth: phthaloyl. bAfter short-column chromatography; cPreparation reported earlier. dSpectra recorded after per-O-acetylation using acetic anhydride and pyridine (1:1; v/v). eAzide group reduced to amine.

Conclusion

In summary, the efficient deprotection of carbohydrate derivatives containing benzylidene acetal and O-benzyl groups under catalytic transfer hydrogenation conditions has been developed by using a combination of triethylsilane and 10% Pd/C. The efficacy of this methodology is comparable to the conventional hydrogenation involving hydrogen gas and Pd/C, whereas it does not require handling of a flammable gas. Being operationally simple and high yielding, these reaction conditions will certainly be accepted as a useful alternative to those currently existing in this area.

Experimental

Typical experimental procedure

To a solution of compound 1 (500 mg, 1.36 mmol) and 10% Pd(OH)2/C (50 mg) in CH3OH (5 mL) was added Et3SiH (650 μL, 4.07 mmol) portionwise, and the reaction mixture was stirred at room temperature for an appropriate time, given in Table 1. The reaction mixture was filtered through a Celite bed, and the filtering bed was washed with CH3OH. The combined filtrate was concentrated under reduced pressure to give the crude product, which was passed through a short pad of SiO2 with EtOAc as eluant to give pure compound 2 (330 mg, 87%).

Supporting Information

Supporting Information File 1: Analytical data of new compounds, 1H NMR and 13C NMR spectra.
Format: PDF Size: 1.9 MB Download

Acknowledgements

A. S. and T. G. thank CSIR, New Delhi for providing Senior and Junior Research Fellowships respectively. This work was supported by CSIR, New Delhi [Project No. 02 (0038)/11/EMR-II].

References

  1. Demchenko, A. V., Ed. Handbook of Chemical Glycosylation; Wiley-VCH: Weinheim, Germany, 2008. doi:10.1002/9783527621644
    Return to citation in text: [1]
  2. Ernst, B.; Hart, G. W.; Sinay, P., Eds. Carbohydrates in Chemistry and Biology; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1.
    Return to citation in text: [1]
  3. Levy, D. E.; Fugedi, P., Eds. The Organic Chemistry of Sugars; CRC Press: Boca Raton, U.S.A., 2006.
    Return to citation in text: [1]
  4. Osborn, H. M. I., Ed. Carbohydrates: Best Synthetic Methods; Academic Press: New York, 2003.
    Return to citation in text: [1]
  5. Kovac, P., Ed. Carbohydrate Chemistry: Proven Synthetic Methods; CRC Press: Boca Raton, U.S.A., 2011; Vol. 1.
    Return to citation in text: [1]
  6. Hanessian, S., Ed. Preparative Carbohydrate Chemistry; CRC Press: Boca Raton, U.S.A., 1997.
    Return to citation in text: [1]
  7. Guo, J.; Ye, X.-S. Molecules 2010, 15, 7235–7265. doi:10.3390/molecules15107235
    Return to citation in text: [1]
  8. Codée, J. D. C.; Ali, A.; Overkleeft, H. S.; van der Marel, G. A. C. R. Chim. 2011, 14, 178–193. doi:10.1016/j.crci.2010.05.010
    Return to citation in text: [1]
  9. Boltje, T. J.; Li, C.; Boons, G.-J. Org. Lett. 2010, 12, 4636–4639. doi:10.1021/ol101951u
    Return to citation in text: [1]
  10. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John Wiley and Sons: New York, 1999; pp 219–229. doi:10.1002/0471220574
    Return to citation in text: [1] [2]
  11. Kocienski, P. J. Protecting Groups, 1st ed.; Georg Thieme Verlag: Stuttgart, Germany, 1994; pp 137–155.
    Return to citation in text: [1] [2]
  12. Garegg, P. J. Regioselective Cleavage of O-Benzylidene Acetals to Benzyl Ethers. In Preparative Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel Dekker: New York, 1997; pp 53–67.
    Return to citation in text: [1]
  13. Garegg, P. J. Pure Appl. Chem. 1984, 56, 845–858. doi:10.1351/pac198456070845
    Return to citation in text: [1]
  14. Ohlin, M.; Johnsson, R.; Ellervik, U. Carbohydr. Res. 2011, 346, 1358–1370. doi:10.1016/j.carres.2011.03.032
    Return to citation in text: [1]
  15. Jarowicki, K.; Kocienski, P. J. J. Chem. Soc., Perkin Trans. 1 2001, 2109–2135. doi:10.1039/B103282H
    Return to citation in text: [1]
  16. Agnihotri, G.; Misra, A. K. Tetrahedron Lett. 2006, 47, 3653–3658. doi:10.1016/j.tetlet.2006.03.133
    Return to citation in text: [1] [2]
  17. Kumar, P. S.; Kumar, G. D. K.; Baskaran, S. Eur. J. Org. Chem. 2008, 6063–6067. doi:10.1002/ejoc.200800963
    Return to citation in text: [1]
  18. Hartung, W. H.; Simonoff, R. Org. React. 1953, 7, 263–326.
    Return to citation in text: [1]
  19. Bieg, T.; Szeja, W. Synthesis 1986, 317–318. doi:10.1055/s-1986-31597
    Return to citation in text: [1]
  20. Nicolaou, K. C.; Veale, C. A.; Hwang, C.-K.; Hutchinson, J.; Prasad, C. V. C.; Ogilvie, W. W. Angew. Chem., Int. Ed. Engl. 1991, 30, 299–303. doi:10.1002/anie.199102991
    Return to citation in text: [1]
  21. Nayak, U. G.; Brown, R. K. Can. J. Chem. 1966, 44, 591–602. doi:10.1139/v66-080
    Return to citation in text: [1]
  22. Mandal, P. K.; McMurray, J. S. J. Org. Chem. 2007, 72, 6599–6601. doi:10.1021/jo0706123
    Return to citation in text: [1] [2]
  23. Adinolfi, M.; De Napoli, L.; Di Fabio, G.; Iadonisi, A.; Montesarchio, D.; Piccialli, G. Tetrahedron 2002, 58, 6697–6704. doi:10.1016/S0040-4020(02)00684-1
    Return to citation in text: [1] [2]
  24. Hasegawa, A.; Ogawa, M.; Ishida, H.; Kiso, M. J. Carbohydr. Chem. 1990, 9, 393–414. doi:10.1080/07328309008543841
    Return to citation in text: [1]
  25. Akita, H.; Kawahara, E.; Kato, K. Tetrahedron: Asymmetry 2004, 15, 1623–1629. doi:10.1016/j.tetasy.2004.03.046
    Return to citation in text: [1]
  26. Kochetkov, N. K.; Byramova, N. E.; Tsvetkov, Yu. E.; Backinowsky, L. V. Tetrahedron 1985, 41, 3363–3375. doi:10.1016/S0040-4020(01)96688-8
    Return to citation in text: [1]
  27. Wang, P.; Wang, J.; Guo, T. T.; Li, Y. Carbohydr. Res. 2010, 345, 607–620. doi:10.1016/j.carres.2010.01.002
    Return to citation in text: [1]
  28. Zhang, Z.; Magnusson, G. Carbohydr. Res. 1996, 295, 41–55. doi:10.1016/S0008-6215(96)90118-4
    Return to citation in text: [1]
  29. Gu, G.; Fang, M.; Liu, J.; Gu, L. Carbohydr. Res. 2011, 346, 2406–2413. doi:10.1016/j.carres.2011.08.026
    Return to citation in text: [1]

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