Silyl-ether

Silyl ethers are renowned, and used, for their highly selective deprotection with fluoride sources (Method 14) as mentioned above, but selecting between different silyl ethers under these conditions is not always reliable unless the silyl alkyl substituents are sufficiently different. However, deprotection of silyl ethers of 1 -alcohols, in the presence of similarly protected 2°-alcohols, is routinely possible under either acidic or basic conditions [45]. 

Silyl Ethers.- The selective tert-butyldiphenylsilylatlon of sucrose has been examined. Monomolar silylation (BSph2SiCl- py-DMAP) gave the 6 -0-monoether yield, without chromatography), 

2 - and 3 -Mono-, as well as 2. 1 -bis-0-(tert-butyldlmethyl-sllyl)-rlbonucleosldes have been synthesized from corresponding 5 -0-(4-methoxytrityl)-derivatives by partial or complete silylation 

Octa-0-(trimethylsilyl)sucrose is a stable crystalline material that could have potential value as an internal g.l.c. standard. The selective hydrolysis of octa-0-(trimethylsilyl)-aa-trehalose at one or both of the primary positions has been noted earlier.  

Thmethylsityt OMS) Triethytsilyl (TES) Triphenytsityl (TPS) Th- sopropytsityl (TIPS) Thexyldinf ethyts4l (TOS) 

Cunico and BedelP measured the half lives of the more robust silyl ethers under a variety of conditions with the results shown in Tables 1 and 2 and a related study incorporating a large range of silyl ethers has appeared.  

THmethylsilyl ethers are widely used to derivatise polar and non-volatile compounds for gas chromatography or mass spectrometry but their use in synthesis is limited by their lability to hydrolysis and column chromatography. 

TMS ethers of primary alcohols and most secondary alcohols do not survive even the simplest synthetic manipulations — especially if protic solvents are involved. For example, Swem oxidation or Collins oxidation conditions will cleave a primary TMS ether and perform the oxidation in the presence of a secondary TMS ether. Owing to the sensitivity of TMS ethers, deprotection can usually be achieved under very mild conditions (e.g., acetic acid or potassium carbonate in methanol). The rate of hydrolysis depends on both steric and electronic effects with hindered environments decreasing the rate and electron-withdrawing substituents on the hydroxyl function increasing the rate. In a synthesis of Zaragozic Acid A. the 

However, reaction of substituted silylated phenols with phosgene does not always give the chloroformate product, owing to the faster reaction represented below [1102]  

Cyclic silyl ethers undergo ring opening with phosgene to produce chloroformates 

The dioxane derivative, illustrated below, reacts vigorously with phosgene to give high yields of chloroformate [1102]  

However, the related phenylene derivative reacts with phosgene only when the ring is opened on heating to 120-140 C in the presence of gaseous HCl [1102]  

The inertness of phosgene towards compounds containing the Si-O-aryl linkage is a general observation, and is extended to the compound (10.28) for which no reaction occurs with HCl/COClj mixtures at temperatures as high as 200 C for prolonged periods [1102], 

TBDMS and TBDPS triflate are very powerful silylating agents that have been used for the protection of sterically hindered hydroxyls.27 

Silyl ethers are cleaved under basic and acidic conditions as well as by nucleophilic attack by fluoride ions. The driving force of the latter 

The stabilities of silyl ethers are closely related to the electronic and steric effect of the substituents on the silicon atom and are generally proportional to the steric hindrance provided by the substituents. Moreover, electron-withdrawing substituents on the silicon atom increase the stability of the silyl groups toward acid but decrease their stability toward base. Consequently, their stability in acid follows the order TMS TES TBS TIPS TBDPS, whereas in base TMS TES TBS-TBDPS TIPS [1,112,113], Selective deprotection among these groups can thus be achieved 

Typical methods for silyl ether formation and cleavage. 

Reaction of t-butyldimethylchlorosilane with ribonucleosides and their 5 -ethers gave access to mono-, di-, and triethers, and optimal conditions for each were developed. Selectivity can be high, so that, for example, 65% of the 2, 5 -diether of uridine can be obtained. The use of these products in oligonucleotide synthesis was discussed.  

Both 1 1 and 1 2 complexes of BU4NF and BF3.0Et2 have been assessed for their unique properties for the selective removal of different silyl ethers. The Tips silyl group can be removed with KIO clay in aqueous methanol.  

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The distillate was dissolved in a mixture of 350 ml of dry diethyl ether and 45 g of dry triethylamine (dried over powdered KQH). Trimethylchlorosilane (45 g) was added in 20 min with cooling at about 10°C. After standing for 1 h at room temperature the precipitate was sucked off on a dry sintered-glass funnel and rinsed with pentane. The filtrate was concentrated in a water-pump vacuum- The small amount of salt which precipitated during this operation was removed by a second suction filtration. Subsequent distillation afforded the trimethyl silyl ether, b.p. 100°C/15 mmHg, 1.4330, in 944 yield. 

Low molecular mass enol esters (e.g. acetates H.O. House, 1965) or enol ethers (e.g. silyl ethers H.O. House, 1969) of ketones can be synthesized regioselectively and/or separated by distillation. Treatment with lithium alkyls converts them into the corresponding lithi-... 

A useful catalyst for asymmetric aldol additions is prepared in situ from mono-0> 2,6-diisopropoxybenzoyl)tartaric acid and BH3 -THF complex in propionitrile solution at 0 C. Aldol reactions of ketone enol silyl ethers with aldehydes were promoted by 20 mol % of this catalyst solution. The relative stereochemistry of the major adducts was assigned as Fischer- /ir o, and predominant /i -face attack of enol ethers at the aldehyde carbonyl carbon atom was found with the (/ ,/ ) nantiomer of the tartaric acid catalyst (K. Furuta, 1991). 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

The oxidation of higher alkenes in organic solvents proceeds under almost neutral conditions, and hence many functional groups such as ester or lac-tone[26,56-59], sulfonate[60], aldehyde[61-63], acetal[60], MOM ether[64], car-bobenzoxy[65], /-allylic alcohol[66], bromide[67,68], tertiary amine[69], and phenylselenide[70] can be tolerated. Partial hydrolysis of THP ether[71] and silyl ethers under certain conditions was reported. Alcohols are oxidized with Pd(II)[72-74] but the oxidation is slower than the oxidation of terminal alkenes and gives no problem when alcohols are used as solvents[75,76]. 

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

Various bicyclic and polycyclic compounds are produced by intramolecular reactions] 127]. In the syntheses of the decalin systems 157 [38] and 158 [128], cis ring Junctions are selectively generated. In the formation of 158, allyhc silyl ether remains intact. A bridged bicyclo[3.3. l]nonane ring 159 was constructed... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

Synthesis of Silicone Monomers and Intermediates. Another important reaction for the formation of Si—C bonds, in addition to the direct process and the Grignard reaction, is hydrosdylation (eq. 3), which is used for the formation of monomers for producing a wide range of organomodified sihcones and for cross-linking sihcone polymers (8,52—58). Formation of ether and ester bonds at sihcon is important for the manufacture of curable sihcone materials. Alcoholysis of the Si—Cl bond (eq. 4) is a method for forming silyl ethers. HCl removal is typically accomphshed by the addition of tertiary amines or by using NaOR in place of R OH to form NaCl. 

Silyl Ethers. The preparation of per- O-trimethyl silyl ethers of sucrose is generally achieved by reaction with chi orotrimethyl sil ane and/or hexamethyldisila2ane in pyridine (25,26). However, this reaction is not selective and in general per-trimethyl silyl ethers are only used as derivatives for gas chromatographic studies. 

StericaHy hindered silyl ethers such as ferZ-hutyl dimethyl silyl, / fZ-butyldiphenylsilyl, and tricyclohexylsilyl have been proposed as alternatives to trityl ethers. Reaction of sucrose with 3.5 molar equivalents of ferZ-hutyl dimethyl silyl chloride produces the 6,1/6 -tri-O-silyl derivative in good yield (27). 

These hindered silyl ethers are generally more stable to acid hydrolysis than their trityl ether equivalents and can be removed using... 

Conversion of Silyl Ethers to Other Functional Groups ESTERS... 

Me3SiCH2CH=CH2i TsOH, CH3CN, 70-80°, 1-2 h, 90-95% yield. This silylating reagent is stable to moisture. Allylsilanes can be used to protect alcohols, phenols, and carboxylic acids there is no reaction with thiophenol except when CF3S03H is used as a catalyst. The method is also applicable to the formation of r-butyldimethylsilyl derivatives the silyl ether of cyclohexanol was prepared in 95% yield from allyl-/-butyldi-methylsilane. Iodine, bromine, trimethylsilyl bromide, and trimethylsilyl iodide have also been used as catalysts. Nafion-H has been shown to be an effective catalyst. 

The DTBS group is probably the most useful of the bifunctional silyl ethers. Di-methylsilyl and diisbpropylsilyl derivatives of diols are very susceptible to hydrolysis even in water and therefore are of limited use. 

Silyl-derived protective groups are also used to mask the thiol function. A complete compilation is not given here since silyl derivatives are described in the section on alcohol protection. The formation and cleavage of silyl thioethers proceed analogously to simple alcohols. The Si—S bond is weaker than the Si—O bond, and therefore sulfur derivatives are more susceptible to hydrolysis. For the most part silyl ethers are rarely used to protect the thiol function because of their instability. Silyl ethers have been used for in situ protection of the — SH group during amide formation. ... 

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