Deprotection trimethylsilyl ether

Aryl and alkyl trimethylsilyl ethers can often be cleaved by refluxing in aqueous methanol, an advantage for acid- or base-sensitive substrates. The ethers are stable to Grignard and Wittig reactions and to reduction with lithium aluminum hydride at —15°. Aryl -butyldimethylsilyl ethers and other sterically more demanding silyl ethers require acid- or fluoride ion-catalyzed hydrolysis for removal. Increased steric bulk also improves their stability to a much harsher set of conditions. An excellent review of the selective deprotection of alkyl silyl ethers and aryl silyl ethers has been published. ... 

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 ". 

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... 

Selective deprotection of trialkylsilyl ethers can also be accomplished by Nafion-H. Trimethylsilyl ethers are cleaved to the corresponding alcohols under mild conditions680 [Eq. (5.241)]. Nafion-H with Nal (1 equiv.) in methanol was shown to readily cleave ferf-butyldimethylsilyl ethers (room temperature, 4—25 h,... 

The simultaneous and selective protection of the two equatorial hydroxyl groups in methyl dihydroquinate [11L1, Scheme 3.111 j as the butane-2,3-diace-tal 111 2 was a key strategic feature in a synthesis of inhibitors of 3-dehydroqui-nate synthase.205 Later in the synthesis, deprotection of intermediate 111.4 required three steps (a) hydrolysis of the trimethylsilyl ether and the butane-2,3-diacetal with trifluoroacetic acid (b) cleavage of the isopropyl phosphonate with bromotrimethylsilane and (c) hydrolysis of the methyl ester with aqueous sodium hydroxide. Compound 111 1 has also been used in the synthesis of inhibitors 3-dehydroquinate dehydratase206 and influenza neuraminadase207-208 as well as shikimic add derivatives.209 210... 

Similar to the deprotonation of enol radical cations, silyl enol ether radical cations can undergo loss of trialkylsilyl cations (most likely not as ionic silicenium ions [190]). Based on photoinduced electron transfer (PET), Gass-man devised a strategy for the selective deprotection of trimethylsilyl enol ethers in the presence of trimethylsilyl ethers [191]. Using 1-cyanonapthalene (1-CN) ( = 1.84 V) in acetonitrile/methanol or acetonitrile/water trimethylsilyl enol ether 93 ( j = 1.29 V) readily afforded cyclohexanone 64 in 60%. Mechanistically it was proposed that the silyl enol ether radical cation 93 undergoes O-Si bond cleavage, most likely induced by added methanol [192-194], and that radical 66 abstracts a hydrogen from methanol. Alternatively, back electron transfer from 1-CN - to 66 would yield the enolate of cyclohexanone which should be readily protonated by the solvent. 

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 next step involves selectively deprotecting the trimethylsilyl ether to produce (17) by a method described by Bunce and Hertzler. Their method involves treating TMS ethers with sulfonic acid type exchange resins which will remove the TMS group and not the TBS group. ... 

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]. 

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]. 

Protection and deprotection of functional groups is an important strategy in organic S3Tithesis. Particularly, trimethylsilyl ether (TMS), methotymethyl acetal (MOM) and tert-butoty carbamate (Boc) are three frequently used effective reagents in the protection of alcohols, phenols, amines, carbotylic... 

Silyl ethers are widely used protective groups because they also have a convenient method of deprotection treatment with tetrabutylammonium fluoride (n-Bu4NF or TBAF, pronounced t-baff ).The reaction of an alcohol (ROH) with trimethylsUyl chloride (Me sSiCl or TMSCl) and base makes the protected trimethylsilyl ether (ROTMS). Variation of the alkyl groups on the silicon (e.g., triisopropylsUyl TIPS, or r-butyldimethylsilyl TBDMS/TBS) increases the silyl ether s stability, especially toward acidic conditions, and also allows for selective protection of less hindered alcohols. 

The Lewis acid-catalysed acetaladons of alkyl D-gluco- and D-galactopyranoside-4,6-diols and their 4,6-bis(trimethylsilyl) ethers with methyl 2,2-(diphenylthio)propanoate or methyl pyruvate, respectively, have been studied in detail. It was observed that these reactions are often accompanied by anomerization and by isomerization of the initial, kinetic acetal to the thermodynamically stable diastereomer with an axial COjMe group. An example is given in Scheme 2. The 4,6-0-methyl pyruvate-based acetal 14 has been synthesized from benzyl a-D-mannopyranoside via the 4,6-0-(1,1,3,3-tetraisopropyldisUoxane-l,3-diyl)-piotected derivative 13 this procedure requires fewer protection/deprotection steps than use of the more common 4,6-bis(trimethylsilyl) ether as intermediate. ... 

Silvl Ethers.- The reductive cleavage of silyl ethers employing NaH in HMPA or DMPU has been reported. Methyl 6-Q-tert-butyldimethylsilyl-a-D-glucopyranoside and the 4,6-di-Q-tert-butyldimethylsilyl ether of D-glucal were each deprotected in 90% yield under these conditions. The deprotonation of a silyl ether with base is mentioned in Chapter 13. The trimethylsilyl ethers of a number of D-glucose derivatives have been prepared and characterized by H-, c- and Si-n.m.r. spectroscopy and mass spectroscopy. 

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