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Synlett 2007(13): 2116-2120  
DOI: 10.1055/s-2007-984903
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Formation and Cleavage of Benzylidene Acetals by Sodium ­Hydrogen Sulfate Supported on Silica Gel

Youhong Niua,b, Ning Wanga, Xiaoping Caob, Xin-Shan Ye*a
a The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd 38, Beijing 100083, P. R. of China
Fax: +86(10)62014949; e-Mail: xinshan@bjmu.edu.cn;
b State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
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Publication History

Received 13 April 2007
Publication Date:
17 July 2007 (online)

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Abstract

NaHSO4·SiO2 was used as an efficient heterogeneous catalyst for both the formation and the cleavage of benzylidene ­acetals. This catalyst is compatible with many functional or protective groups. Under different solvent systems, either the formation or the cleavage of benzylidene acetals was carried out smoothly in ­excellent yields and with good chemoselectivity.

Key words

sodium hydrogen sulfate supported on silica gel - protection - deprotection - benzylidene acetals - carbohydrate

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General Procedure for the Formation of Benzylidene Acetals To a stirred solution of the glycoside substrate (100 mg) and benzaldehyde dimethyl acetal (1.5 mmol) in MeCN (10 mL) was added activated NaHSO4·SiO2 (200 mg, dried at 105 °C for 10 h prior to use) at r.t. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with Et3N (0.2 mL). The catalyst was filtered off through a plug of Celite, and the filtrate was removed under reduced pressure to yield the product. Although the product was pure enough, analytical samples were prepared by passing the crude reaction product through a short column of silica gel using PE-EtOAc as eluent.
Compound 16: colorless solids, mp 108-109 °C. 1H NMR (500 MHz, CDCl3): δ = 8.10-8.08 (m, 2 H), 7.61-7.57 (m, 1 H), 7.49-7.44 (m, 4 H), 7.37-7.33 (m, 3 H), 6.02-5.94 (m, 1 H), 5.53 (s, 1 H), 5.39-5.35 (m, 1 H), 5.26-5.23 (m, 1 H), 4.98 (dd, J = 3.5, 10.5 Hz, 1 H), 4.52-4.46 (m, 3 H), 4.38-4.35 (dd, J = 2.0, 12.5 Hz, 1 H), 4.22-4.17 (m, 1 H), 4.13-4.08 (m, 2 H), 3.55 (d, J = 1.0 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 166.0, 137.5, 133.50, 133.45, 130.0, 129.3, 128.9, 128.5, 128.1, 126.1, 117.9, 101.0, 100.7, 72.8, 72.7, 70.3, 68.9, 66.4, 60.6. LRMS-FAB: m/z calcd for C23H27N4O6 [M + NH4 +]: 455; found: 455. Anal. Calcd for C23H23N3O6: 63.15; H, 5.30; N, 9.61, Found: C, 62.80; H, 5.47; N, 9.57.

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General Procedure for the Cleavage of Benzylidene Acetals To a stirred solution of the 4,6-O-benzylidene-glycopyrano-side (100 mg) in a mixed solvent of CH2Cl2 and MeOH (or i-PrOH; v/v 4:1, 10 mL) was added activated NaHSO4·SiO2 (200 mg, dried at 105 °C for 10 h prior to use) at r.t. After completion of the reaction (monitored by TLC), the mixture was filtered through a Celite bed and the filtrate was con-centrated. The residue was purified by column chromatog-raphy on silica gel using PE-EtOAc as eluent to afford the pure product. If the acid-sensitive functional groups exist, it is necessary to quench the reaction with Et3N (0.2 mL) after completion of the reaction.
Compound 19: white solids, mp 135-136 °C. 1H NMR (300 MHz, CDCl3): δ = 7.45 (d, J = 8.1 Hz, 2 H), 7.35 (d, J = 8.7 Hz, 2 H), 7.27-7.24 (m, 2 H), 7.10 (d, J = 8.1 Hz, 2 H), 6.91-6.85 (m, 4 H), 4.76 (d, J = 10.2 Hz, 1 H), 4.65 (d, J = 12.6 Hz, 3 H), 4.56 (d, J = 12.9 Hz, 1 H), 3.99-3.93 (m, 2 H), 3.81 (s, 3 H), 3.80 (s, 3 H), 3.79-3.72 (m, 1 H), 3.67 (t, J = 9.3 Hz, 1 H), 3.54 (dd, J = 3.3, 9.3 Hz, 1 H), 3.46-3.44 (m, 1 H), 2.58 (br s, 1 H), 2.32 (s, 3 H), 2.01 (br s, 1 H). 13C NMR (75 MHz, CDCl3): δ = 137.8, 132.6, 130.3, 129.9, 129.7, 129.6, 113.9, 113.8, 87.8, 82.1, 77.9, 75.4, 72.0, 69.4, 67.4, 62.8, 55.3. 21.1. ESI-HRMS: m/z calcd for C29H35O7S [M + H+]: 527.2098; found: 527.2104.