Alkyl silyl ethers

Alkyl silyl ethers are cleaved by a variety of reagents Whether the silicon-oxygen or the carbon-oxygen bond is cleaved depends on the nature of the reagent used Treatment of alkoxysilanes with electrophilic reagents like antimony tri-fluonde, 40% hydrofluonc acid, or a boron tnfluonde-ether complex results in the cleavage of the silicon-oxygen bond to form mono-, di-, and tnfluorosiloxanes or silanes [19, 20, 21) (equations 18-20)... 

Benzyl and alkyl tnalkylsilyl ethers undergo clean fluonnation to give good yields of benzyl and alkyl fluorides, respectively, when reacted with a combination of d quaternary ammonium fluoride and methanesulfonyl orp- toluenesulfonyl fluoride. The reactions are applicable strictly to a primary carbon-oxygen bond, secondary and tertiary alkyl silyl ethers remain intact or, under forcing conditions, aie dehydrated to olefins [29] (equation 22)... 

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. ... 

The transition metal catalysed addition of a hydridosilane to a multiply-bonded system is known as hydrosilylation (1). Under such conditions, alkynes undergo clear cis-addition, so providing one of the most direct routes to vinylsilanes (Chapter 3). Hydridosilanes also add to the carbonyl group of saturated aldehydes and ketones, to produce alkyl silyl ethers. Fot example, under suitable conditions, 4-t-butylcyclohexanone (2) can be reduced with a high degree of stereoselectivity. 

Aldehydes, 43 a-Chiral, 112 a/MJnsaturated, 85,110 /3-Aldchydosi lanes, 22 Aldol reaction, directed, 139 Alkoxytrimethylsilanes, 122 Alkyl lithium. 67 Alkyl silyl ethers, 91-97,127 Alkylation, 33 of ethyl glycinate, 88-89 t-Alkylation, 111-135... 

The notion of enol silyl ethers (ESE) as electron donors was first provided by Gassman and Bottorff,34 who showed that selective (carbonyl) deprotection can be readily achieved in the presence of an alkyl silyl ether group via an electron-transfer activation (e.g., equation 9). 

The success of this transformation depends upon the oxidation potential of the ESE group (Eox 1.5 V), which is lower than that of the alkyl silyl ether group (Eax 2.5 V). Recently, Schmittel et al.35 showed (by product studies) that the enol derivatives of sterically hindered ketones (e.g., 2,2-dimesityl-1-phenyletha-none) can indeed be readily oxidized to the corresponding cation radicals, radicals and a-carbonyl cations either chemically with standard one-electron oxidants (such as tris(/>-bromophenyl)aminium hexachloroantimonate or ceric ammonium nitrate) or electrochemically (equation 10). 

It has been known for some time that the basicities of a heteroatom decrease upon a-silyl substitution [12], For example, alkyl silyl ethers (R3Si-0-R ) are less basic than dialkly ethers. Silylamines are weak bases compared to alkylam-ines. This electron-withdrawing effect of silyl groups has been explained in terms of the interaction between low lying vacant orbitals such as 3d orbitals of silicon or a orbitals with the nonbonding p orbitals (lone pairs) of the heteroatom (Fig. 4). This interaction decreases the HOMO level which in turn lowers the basicity of the heteroatom. Such effect may also cause the increase of the oxidation potentials, but little study has been reported on the electrochemical properties of this type of compounds. 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

Palladium catalysts, 230 of alkyl silyl ethers to alkanes Nickel boride, 197 of alkyl sulfonates to alkanes Lithium triethylborohydride, 153 of alkynes to cis-alkenes... 

Methyl ethers are stable to acidic and basic conditions, and oxidising or reducing reagents. Deprotection to regenerate the alcohol is difficult (see Section 9.6.10, p. 1254) a convenient mild procedure uses iodotrimethylsilane in chloroform solution at room temperature.768 The alkyl methyl ether under these conditions gives the alkyl silyl ether and methyl iodide the former on treatment with methanol gives the deprotected alcohol. 

Rather more conventional means were used to remove an alkyl silyl ether in the presence of an ary silyl ether in a synthesis of Dynemicin Here the task was simply accomplished with HF in acetonitrile [Scheme 4.56].92 Acidic conditions also prevailed in a synthesis of Doliculide wherein an alkyl tert-butyl ether, a tert-butyl ester and an N-fert-butoxycarbonyl group were cleaved simultaneously without challenge to the remaining aryl silyl ether [Scheme 4.57] ... 

During a synthesis of Hennoxazole, Wipf and Lim97 found that Lithium hydroxide at 90 3 C offered a convenient method for removing a TBS ether in the presence of a TIPS ether [Scheme 4.59], This is a rare example of the use of basic hydrolysis in selective alkyl silyl ether deprotection. 

The main applications of oxidation with chromium trioxide are transformations of primary alcohols into aldehydes [184, 537, 538, 543, 570, 571, 572, 573] or, rarely, into carboxylic acids [184, 574], and of secondary alcohols into ketones [406, 536, 542, 543, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584]. Jones reagent is especially successful for such oxidations. It is prepared by diluting with water a solution of 267 g of chromium trioxide in a mixture of 230 mL of concentrated sulfuric acid and 400 mL of water to 1 L to form an 8 N CrOj solution [565, 572, 579, 581, 585, 556]. Other oxidations with chromic oxide include the cleavage of carbon-carbon bonds to give carbonyl compounds or carboxylic acids [482, 566, 567, 569, 580, 587, 555], the conversion of sulfides into sulfoxides [541] and sulfones [559], and the transformation of alkyl silyl ethers into ketones or carboxylic acids [590]. 

Trityl ethers are cleaved by 12/MeOH when other protecting groups (e.g., acetates) are not affected. Discrimination of aryl and alkyl silyl ethers is possible by the same treatment (alkyl TBS ethers are selectively hydrolyzed). The A-(4-pentenoyl) group is removed from such amides by brief treatment with iodine in aqueous THF. ... 

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