Trimethylsilyl ethers, deprotective oxidations

An economical, practical, and environmentally acceptable procedure was elaborated for oxidative deprotection of trimethylsilyl ethers to their corresponding carbonyl compounds. The reaction proceeded in a solventless system, within a short period of time, and yields were good. On irradiation in a conventional microwave for 30 s, trimethylsilyl ether of benzyl alcohol in the presence of mont-morilonite KIO and finely grounded Fe(N03)3 9H2O gave rise to benzaldehyde in 95% yield. The applicability of this method was tested with several aromatic, alicyclic, and aliphatic trimethylsilyl ethers. Duration did not exceed 1 min, and yields were not lower than 80% (Mojtahedi et al. 1999). 

Hajipour and coworkers prepared benzyltriphenylphosphonium peroxymonosulfate (BnPhsPHSOs) in a very high yield (95%) and purity (99%). This new oxidizing reagent was applied successfully in various deprotection reactions such as the conversion of oximes, phenylhydrazones, 2,4-dinitrophenylhydrazones and semicarbazones to the corresponding carbonyl compounds in the presence of bismuth chloride under nonaqueous conditions . Oxidative deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers and ethylene acetals with BnPh3PHS05 under microwave irradiation affords the corresponding carbonyl compounds in very high yields (equation 71). The same reaction also proceeds under nonaqueous conditions ". 

Deprotection of trimethylsilyl ether has also been accomplished (88-100%) on KIO clay [47] or oxidative cleavage (70-95%) in the presence of clay and iron(III) nitrate [48]. Another oxidative deprotection of trimethylsilyl ethers using supported potassium ferrate, K2pe04 and MW has been reported [49]. 

Dicarboxypyridinium chlorochromate (2,6-DCPCC)392 possesses an acidic character that allows the in situ deprotection and oxidation of alcohols, protected as tetrahydropyranyl and trimethylsilyl ethers. 2,2 -Bipyridinium chlorochromate (BPCC)393 contains a ligand that complexes efficiently with the reduced chromium species, generated during the oxidation of alcohols, allowing for a substantial simplification of the work-ups. For this reason, it enjoys a popularity among chlorochromates surpassed by only PCC. 

Keywords trimethylsilyl ether, microwave irradiation, oxidative deprotection, ketone, aldehyde... 

PDC with trimethylsilyl chloride is not only a rapid oxidizing agent for alcohols, but will also effect a deprotection-oxidation sequence for silyl ethers. Both trimethylsilyl and r-butyldimethylsilyl ethers, which are normally stable to PDC, can be transformed directly into the corresponding carbonyl compounds in good yield (Table 13). 

EtsN in CH2CI2 in the presence of 4-dimethylaminopyridine (Scheme 13.68). Dihydroxylations of the trimethylsilyl ethers of 217 and 218 generate the 4-amino-4-deoxy-heptono-1,4-lactam derivatives 219 and 220, respectively [121]. Lactam hydrolysis of 219 with LiOH, followed by the Malaprade diol cleavage with NaI04 and further oxidation and deprotection, allows the preparation of 4- p/-polyoxamic acid [122]. Lactam 217 and its enantiomer derived from (5 )-24 have been converted into all four stereomers of cw-l,2-dihydroxypyrrolizidine [123]. Compounds 217 and 218 have been used also to prepare the rm/i5 -2,3-c/5 -3,4-dihydroxyprolines [124,125]. 

The synthesis of lepimectin (Scheme 29.6.2) is described in the following, as it is published in the patent literature [42-44]. However, it may be assumed that this sequence will be modified in the actual industrial preparation. To introduce the required oxygen functionality at Cl3, milbemycin A3/A4 is first protected as 5-0-trimethylsilyl ether. Reaction with 3-chloroperbenzoic acid results in the ep-oxidation of the double bond between C14 and CIS. The epoxide is rearranged by treatment with a mild Lewis acid (trimethylsilyl triflate), and the product is deprotected. To suitably protect the sensitive allylic C5 hydroxy group, it is oxidized to the ketone. The Cl3 ester substituent is introduced by an acid-mediated... 

Finally, benzylic oxidation offers a third method for deprotection, as an alternative to hydrogenolysis or electrophilic activation. For example, ozone converts benzyl ethers into benzoate esters at around 0 °C (Figure 2.13) [23], and ruthenium tetraoxide generated in situ has been used for the same purpose the conditions are sufficiently mild that labile trimethylsilyl ethers remain intact (Figure 2.14) [24]. 

The potentiality of the present methodology is demonstrated by the synthesis of y-undecalactone, as shown in Scheme 18 [37,47], The treatment of the THP-protected cu-hydroxyalkyl iodide with the anion of methoxybis(trimethylsilyl) methane gave the corresponding alkylation product. Acidic deprotection of the hydroxyl group followed by Swern oxidation produced the aldehyde. The aldehyde was allowed to react with heptylmagnesium bromide, and the resulting alcohol was protected as tm-butyldimethylsilyl ether. The electrochemical oxidation in methanol followed by the treatment with fluoride ion afforded the y-undeealactone. 

The mixture of chromium trioxide with one equivalent of trimethylsilyl chloride, with no solvent added, results in the formation of an explosive red liquid that is soluble in dichloromethane or tetrachloromethane.428 It is suggested, with no spectroscopic evidence, that it consists of trimethylsilyl chlorochromate [Me3Si-0-Cr(0)2-Cl]. This compound, which can safely be used in organic solvents, is able to oxidize alcohols to aldehydes or ketones, and interacts with r-butyldimethylsilyl ethers producing deprotection, followed by oxidation of the liberated alcohol.138 Compounds analogue to trimethylsilyl chlorochromate are also able to oxidize alcohols, although they possess lesser reactivity. They can be prepared by reaction of chromium trioxide with dimethyldichlorosilane and diphenyldichlorosilane.428b... 

A very usefiil development of diis reaction is the demonstration that trimethylsilyl-protected primary and secondary alcohols can be directly oxidized without pritN deprotection, but r-buQrldimediylsilyl ethers do itot similarly react... 

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