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

Article abstract of DOI:10.3762/bjoc.9.9

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 CH ₃OH at room temperature. A variety of carbohydrate diol derivatives were prepared from their benzylidene derivatives in excellent yield.

Full text of DOI:10.3762/bjoc.9.9

Removal of benzylidene acetal and benzyl ether
in carbohydrate derivatives using
triethylsilane and Pd/C
Abhishek Santra, Tamashree Ghosh and Anup Kumar Misra*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 74–78.
Bose Institute, Division of Molecular Medicine, P-1/12, C.I.T. Scheme
VII-M, Kolkata-700054, India; FAX: 91-33-2355 3886
doi:10.3762/bjoc.9.9
Received: 12 October 2012
Accepted: 17 December 2012
Published: 14 January 2013
Email:
Anup Kumar Misra* - akmisra69@gmail.com
* Corresponding author
Associate Editor: M. Rueping
Keywords:
© 2013 Santra et al; licensee Beilstein-Institut.
License and terms: see end of document.
benzylidene; glycoside; Pd/C; transfer hydrogenation; triethylsilane
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.
Introduction
Functionalization of carbohydrate intermediates is essential for or EtSH [20] or Na/NH3 [21], etc. However, most of the above-
their assembly towards the synthesis of complex oligo- mentioned methodologies have several shortcomings, such as
saccharides [1-9]. Benzylidene acetal is a frequently used harsh conditions, formation of unwanted byproducts, longer
protecting group for the simultaneous protection of 1,2- and reaction time, incompatibility of functional groups, use of
1,3-diol derivatives [10,11]. It can be removed under acidic expensive reagents, fire hazard, etc. In this context, the develop-
hydrolysis as well as under neutral conditions (e.g., hydrogeno- ment of a mild, neutral reaction condition for the removal of
lysis). The benzylidene acetal can also be regioselectively benzylidene acetals would be useful in the derivatization of a
opened under reductive conditions to produce partially benzyl- carbohydrate framework. Mandal et al. reported the removal of
ated derivatives [12-14]. A number of methods have been benzyl esters/ethers and the reduction of alkenes/alkynes by
reported for the removal of benzylidene acetals by using strong catalytic transfer hydrogenation using a combination [22] of
protic and Lewis acids [10,11,15] as well as some heteroge- triethylsilane (Et3SiH) and 10% Pd/C. In our synthetic endeavor
neous acidic catalysts [16,17]. Removal of benzylidene acetal we sought to explore the catalytic potential of a combination of
under nonacidic conditions includes hydrogenolysis using Et3SiH and 10% Pd/C in the deprotection of a benzylidene
hydrogen gas over Pd/C [18], or treatment with hydrazine [19] group in the carbohydrate derivatives, without the formation of
74

Beilstein J. Org. Chem. 2013, 9, 74–78.
Scheme 1: Removal of benzylidene acetal and benzyl ether by using a combination of triethylsilane and 10% Pd/C.
unwanted byproducts. We report herein our findings on the benzylidene acetal was observed in all cases. The effect of
removal of benzylidene acetal using a combination of triethylsi- triethylsilane and 10% Pd/C on the removal of benzylidene
lane and 10% Pd/C (Scheme 1).
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
Results and Discussion
In a set of initial experiments, methyl 2,3-di-O-acetyl-4,6-O- of carbohydrates (e.g., acetyl, benzoyl, phthaloyl, 2-(tri-
benzylidene-α-D-glucopyranoside (1) was treated with a combi- methylsilyl)ethyl, 4-methoxyphenyl, etc.); (c) clean and high
nation of a varied quantity of triethylsilane (1.0–5.0 equiv of the yielding; (d) no unwanted byproduct formation; (e) can be
substrate) and 10% Pd/C (10–20 mg per 100 mg substrate) in carried out at room temperature; (f) no flammable gas is
CH3OH at room temperature. It was observed that the use of a required. The reaction conditions were equally effective for the
total 3.0 equiv of triethylsilane and 10% Pd/C (10 mg/100 mg removal of 4-methoxybenzylidene acetal (Table 1, entries
of substrate) in CH3OH at room temperature furnished the clean 13–15). Allyl ether was reduced and benzyl ethers were
removal of the benzylidene group in a 87% yield in 30 min. removed under the reaction conditions, as expected from the
Generalizing the reaction conditions, a series of benzylidene earlier report [22] (Table 1, entry 8 and entries 3, 4, 9, 10, 12).
acetal containing monosaccharide and disaccharide derivatives, Benzyl ethers and benzylidene acetal in a compound can be
with different functional groups present in them, were treated removed in one pot by using these reaction conditions (Table 1,
with the optimized reagent system, and clean removal of entries 3, 4, 9, 10, 12). All debenzylidenated products were
Table 1: Conversions of carbohydrate derivatives effected with Et3SiH and 10% Pd/C.
Entry
Substrate
Producta
Time (min) Yieldb (%)
Ref.c
[23]
1
30
30
60
87
85
1
3
5
2
4
6
2
3
[24]
[25]
90d
4
60
88d
–
7
8
75

Beilstein J. Org. Chem. 2013, 9, 74–78.
Table 1: Conversions of carbohydrate derivatives effected with Et3SiH and 10% Pd/C. (continued)
5
40
40
87
82
[26]
[27]
9
10
12
6
7
11
40
40
90
92
–
–
14
16
13
15
8
9
40
84d,e
–
18
17
10
11
120
77d
[28]
20
19
21
60
84
–
22
12
13
90
40
80d,e
–
23
25
24
2
88
[23]
76

Beilstein J. Org. Chem. 2013, 9, 74–78.
Table 1: Conversions of carbohydrate derivatives effected with Et3SiH and 10% Pd/C. (continued)
14
40
30
90
86
[16]
[29]
26
28
27
29
15
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.
characterized by NMR spectral analysis. Known compounds Acknowledgements
gave acceptable NMR spectra that matched the previously A. S. and T. G. thank CSIR, New Delhi for providing Senior
reported data.
and Junior Research Fellowships respectively. This work was
supported by CSIR, New Delhi [Project No. 02 (0038)/11/
EMR-II].
Conclusion
In summary, the efficient deprotection of carbohydrate deriva-
tives 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 opera-
tionally simple and high yielding, these reaction conditions will
certainly be accepted as a useful alternative to those currently
existing in this area.
References
1. Demchenko, A. V., Ed. Handbook of Chemical Glycosylation;
Wiley-VCH: Weinheim, Germany, 2008. doi:10.1002/9783527621644
2. Ernst, B.; Hart, G. W.; Sinay, P., Eds. Carbohydrates in Chemistry and
Biology; Wiley-VCH: Weinheim, Germany, 2000; Vol. 1.
3. Levy, D. E.; Fugedi, P., Eds. The Organic Chemistry of Sugars; CRC
Press: Boca Raton, U.S.A., 2006.
4. Osborn, H. M. I., Ed. Carbohydrates: Best Synthetic Methods;
Academic Press: New York, 2003.
5. Kovac, P., Ed. Carbohydrate Chemistry: Proven Synthetic Methods;
CRC Press: Boca Raton, U.S.A., 2011; Vol. 1.
6. Hanessian, S., Ed. Preparative Carbohydrate Chemistry; CRC Press:
Boca Raton, U.S.A., 1997.
Experimental
Typical experimental procedure
7. Guo, J.; Ye, X.-S. Molecules 2010, 15, 7235–7265.
doi:10.3390/molecules15107235
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%).
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
9. Boltje, T. J.; Li, C.; Boons, G.-J. Org. Lett. 2010, 12, 4636–4639.
doi:10.1021/ol101951u
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
11.Kocienski, P. J. Protecting Groups, 1st ed.; Georg Thieme Verlag:
Stuttgart, Germany, 1994; pp 137–155.
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.
13.Garegg, P. J. Pure Appl. Chem. 1984, 56, 845–858.
doi:10.1351/pac198456070845
Supporting Information
14.Ohlin, M.; Johnsson, R.; Ellervik, U. Carbohydr. Res. 2011, 346,
1358–1370. doi:10.1016/j.carres.2011.03.032
Supporting Information File 1
Analytical data of new compounds, 1H NMR and 13C NMR
spectra.
15.Jarowicki, K.; Kocienski, P. J. J. Chem. Soc., Perkin Trans. 1 2001,
2109–2135. doi:10.1039/B103282H
16.Agnihotri, G.; Misra, A. K. Tetrahedron Lett. 2006, 47, 3653–3658.
doi:10.1016/j.tetlet.2006.03.133
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-9-S1.pdf]
77

Beilstein J. Org. Chem. 2013, 9, 74–78.
17.Kumar, P. S.; Kumar, G. D. K.; Baskaran, S. Eur. J. Org. Chem. 2008,
6063–6067. doi:10.1002/ejoc.200800963
18.Hartung, W. H.; Simonoff, R. Org. React. 1953, 7, 263–326.
19.Bieg, T.; Szeja, W. Synthesis 1986, 317–318.
doi:10.1055/s-1986-31597
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
21.Nayak, U. G.; Brown, R. K. Can. J. Chem. 1966, 44, 591–602.
doi:10.1139/v66-080
22.Mandal, P. K.; McMurray, J. S. J. Org. Chem. 2007, 72, 6599–6601.
doi:10.1021/jo0706123
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
24.Hasegawa, A.; Ogawa, M.; Ishida, H.; Kiso, M. J. Carbohydr. Chem.
1990, 9, 393–414. doi:10.1080/07328309008543841
25.Akita, H.; Kawahara, E.; Kato, K. Tetrahedron: Asymmetry 2004, 15,
1623–1629. doi:10.1016/j.tetasy.2004.03.046
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
27.Wang, P.; Wang, J.; Guo, T. T.; Li, Y. Carbohydr. Res. 2010, 345,
607–620. doi:10.1016/j.carres.2010.01.002
28.Zhang, Z.; Magnusson, G. Carbohydr. Res. 1996, 295, 41–55.
doi:10.1016/S0008-6215(96)90118-4
29.Gu, G.; Fang, M.; Liu, J.; Gu, L. Carbohydr. Res. 2011, 346,
2406–2413. doi:10.1016/j.carres.2011.08.026
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