Fe(NO 3 ) 3 .9H 2 O / Fe(HSO 4 ) 3 : An efficient reagent system for the oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers in the absence of solvent

A mild and efficient method for the oxidative deprotection of trimethylsilyl and tetrahydropyran-yl ethers with Fe(NO 3 ) 3 .9H 2 O in the presence of Fe(HSO 4 ) 3 in the absence of solvent at room temperature is reported


Introduction
Trimethylsilylation and tetrahydropyranylation are important reactions widely used for the protection of alcoholic hydroxyl group during a multi-step organic synthesis. 1,2 irect oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers to their corresponding carbonyl compounds are of value to synthetic organic chemists and, in recent years, have attracted much attentions.The available methods have been extensively reviewed, 3 and some representative reagents are: Jones reagent, 4 NBS, 5 aqueous acid, 6 tetrabutylammonium fluoride, 7 wet alumina supported chromium (VI) oxide, 8 cobalt and manganese salts of p-aminobenzoic acid supported on silica gel, 9 benzyltriphenylphosphonium chlorate, 10 (NO 3 ) 3 CeBrO 3 , 11 [(NO 3 ) 3 Ce] 3 .H 2 IO 6 , 12 silica chromate, 13 SiF 4 -MeCN 14 and K 2 S 2 O 8 in the presence of [bmim]Br. 15However, the disadvantages, such as long reaction times, low yields of the products, the requirement for the acidic and aqueous conditions, unavailability of the reagents, tedious work-up and, in most cases, inapplicability in the oxidation of the both type of the above mentioned substrates, clearly identifies a need to introduce new methods for such functional group transformations.
In 1999, Heravi and coworkers 16 reported that montmorillonite supported Fe(NO 3 ) 3 .9H 2 O can be used for the oxidative deprotection of tetrahydropyranyl ethers under microwave irradiation.Although, the yields of the obtained carbonyl compounds using this method are relatively high, the need to proceed under microwave, and the use of equimolar amounts of the reagents to substrate and also 1 g of montmorillonite K-10 during the course of each reaction, can be regarded as limitations of this method.

Results and Discussion
In continuation of our ongoing research program directed towards the development of the applications of hydrogen sulfate salts in organic reactions, [17][18][19] we have found that Fe(HSO 4 ) 3 20 is efficiently able to promote the oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers with Fe(NO 3 ) 3 .9H 2 O in the absence of solvent at room temperature in good to high yields (Scheme 1).

Scheme 1
Yields and reaction times are tabulated in Table 1.Benzylic trimethylsilyl and tetrahydropyranyl ethers, including electron-donating and -withdrawing groups are oxidized to their corresponding aldehydes and ketones in high yields (Table 1).Substrates containing the ethereal linkages are efficiently converted to their corresponding carbonyl compounds without cleavage of carbon-oxygen bond (Table 1, entries 10-12).This method is also very effective for the oxidation of aliphatic trimethylsilyl and tetrahydropyranyl ethers (Table 1, entries 15-18).The method is not useful for the oxidation of allylic substrates (Table 1, entry 19).Overoxidation of the products to their carboxylic acids or esters was not observed using this method.
To illustrate the efficiency of the proposed method, we have compared some of the results with some of those reported in the literature (Table 2), [8][9][10] which demonstrates its significant superiority.
In conclusion, in this study we have developed a mild, efficient and high-yielding method for the oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers in the absence of solvent.In addition, the stability of the reagents, high reaction rates and easy and clean work-up are worthy advantages of the present method.

Table 2.
Comparison of some of the results obtained by our method (I), with some of those reported by benzyltriphenyl-phosphonium chlorate (II), 10 Co and Mn salts / O 2 system (III), 9 and wet alumina supported chromium (VI) oxide (IV)  General method.A mixture of the substrate (1 mmol) substrate, 0.101 g Fe(NO 3 ) 3 .9H 2 O (0.25 mmol) and 0.087 g Fe(HSO 4 ) 3 (0.25 mmol) was ground in a mortar with a pestle for the specified time (Table 1).The progress of the reaction was monitored by TLC or GC.After completion of the reaction, the mixture was diluted with CH 2 Cl 2 (10 mL) and filtered to remove the solids.The solid residue was washed with CH 2 Cl 2 (5 mL).Evaporation of the solvent followed by column chromatography on silica gel gave the corresponding carbonyl compounds in good to high yields. 24

a
Products were characterized by their physical constants, comparison with authentic samples and IR and NMR spectroscopy.b Yields are based on isolated products.c Mixture of unidentified products.

Table 1 .
Oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers in the absence of solvent a,b 8 Chemicals were purchased from Fluka, Merck and Aldrich Chemical Companies.Yields refer to isolated products.Products were characterized by their physical constants, comparison with authentic samples and IR and NMR spectroscopy.The purity determination of the substrates and reaction monitoring were accompanied by TLC on silica gel polygram SILG/ UV 254 plates.