Ceric Ammonium Nitrate/Pyridine: A Mild Reagent for the Selective Deprotection of Cyclic Acetals and Ketals in the Presence of Acid Labile Protecting Groups

Abstract

The reagent system ceric ammonium nitrate/pyridine can perform the cleavage of primary and (in some cases) secondary acetonides, benzylidenes and tetrahydropyranyl ethers. The mild acididity of the reaction system (pH 4.4) allows deprotections to be performed in the presence of several acid labile protecting groups.

Key words

ceric ammonium nitrate - lanthanides - hydroxyl-protecting groups - hydrolysis - carbohydrates

References

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31

General Procedure for Removal of Acetal (Ketal) Protecting Groups with CAN/Pyridine. An aqueous solution of CAN at pH = 4.4 is prepared dissolving 105 mg of CAN (purchased from Fluka) (0.19 mmol) in 19 mL of water and adding 60 µL of pyridine. An aliquot of this solution (1 mL, 0.01 mmol) is added to a solution of substrate (0.33 mmol) in acetone (1 mL). The mixture is kept at 68 °C and every 2 h another aliquot of CAN solution is added until completion of the reaction (see Table [1] for the amounts of catalyst added). The reaction is quenched with pyridine and the mixture is then concentrated under vacuum and product is extracted in chloroform or ethyl acetate and then purified by silica gel chromatography (eluent chloroform:methanol mixtures). The upscaling of the process (to a 3 mmolar scale) was performed in the deprotection of entry o with a comparable yield of 13b. In this case an equal volume of acetone was added after every addition of the aqueous solution of CAN/pyridine to prevent the precipitation of the starting compound and the mixture was extracted with ethyl acetate after neutralization without concentrating the reaction solvent under vacuum. GLC analysis was performed after peracetylation of the crude reaction mixture.
Spectroscopic data of isolated saccharidic products.
1b: ¹H NMR (200 MHz): δ = 7.20-7.50 (aromatic protons), 4.82 (1 H, d, J _1,2 = 3.6 Hz, H-1), 4.05 (1 H, m, H-4), 3.74-3.90 (3 H, m, H-2, H-3, H-5), 3.43 (3 H, s, -OCH₃), 3.36-3.48 (2 H, m, 6-CH₂). ¹³C NMR: δ = 143.7, 128.6, 127.8 and 127.0 (aromatic carbons), 99.4 (C-1), 86.8 (non aromatic trityl carbon), 71.0, 69.7, 69.5, 69.1, 63.2 (C-2, C-3, C-4,
C-5, and C-6), 55.2 (-OCH₃).
8b: ¹H NMR (200 MHz): δ = 7.30-6.90 (aromatic protons), 5.90 (1 H, d, J _1,2 = 3.8 Hz, H-1), 4.58 (1 H, d, H-2), 4.54 (2 H, AB, J _gem = 11.6 Hz, -O-CH ₂Ar), 3.92-4.14 (3 H, m, H-3, H-4 and H-5), 3.78 (OCH₃), 1.46 and 1.30 (6 H, 2 × s, acetonide CH₃). ¹³C NMR: δ = 129.6, 129.2, 114.1 (aromatic carbons), 111.7 (acetonide quaternary carbon), 105.1 (C-1), 82.1, 81.5, 79.8, 71,7, 69.2 and 64.3 (C-2, C-3, C-4 and C-5, C-6 and -OCH₂Ar), 55.2 (-OCH₃), 26.7 and 26.2 (acetonide CH₃).
11b: ¹H NMR (200 MHz): δ = 7.30-6.90 (aromatic protons), 5.75 (1 H, d, J _1,2 = 3.8 Hz, H-1), 4.74 (2 H, AB, J _gem = 13.1 Hz, -OCH ₂SCH₃), 4.70 (1 H, dd, J _2,3 = 8.7 Hz, H-2), 4.18 (1 H, dd, J _3,4 = 3.4 Hz, H-3), 3.95-4.10 (2 H, m, H-4 and H-5), 3.69 (2 H, m, 6-CH₂), 2.18 (3 H, s, -OCH₂SCH ₃), 1.55 and 1.32 (6 H, 2 × s, acetonide CH₃). ¹³C NMR: δ = 113.1 (acetonide quaternary carbon), 104.0 (C-1), 78.5, 77.6, 75.0, 74,7, 71.2 and 63.0 (C-2, C-3, C-4 and C-5, C-6 and
-OCH₂SCH₃), 26.7 and 26.4 (acetonide CH₃), 14.5
(-OCH₂SCH₃).
13b: ¹H NMR (200 Mhz, CDCl₃): δ = 5.30 (1 H, t, J _2,3 =
J _3,4 = 9.8 Hz, H-3), 4.91 (1 H, d, J _1,2 = 3.8 Hz, H-1), 4.83
(1 H, dd, H-2), 3.65-3.90 (3 H, m, H-4, H-5, H-6), 3.40 (3 H, s, 1-OCH₃), 2.08 and 2.10 (6 H, 2 × s, 2 × -COCH₃).
¹³C NMR (50 Mhz, CDCl₃): δ = 171.2 and 170.4 (COCH₃), 96.6 (C-1), 72.6, 71.1, 70.8 and 68.6 (C-2, C-3, C-4 and
C-5), 61.2 (C-6), 55.0 (1-OCH₃), 20.7 and 20.6 (COCH₃).