Triethylsilyl silyl ethers

Benzil is reductively triethylsilylated to the bis(silyl) ether in 83% yield.411 The combination of Et3SiH/ZnCl2 reductively triethylsilylates ketones in good yield.382 Excellent yields of triethylsilyl ethers from ketones are accomplished with the use of triethylsilane and catalyst 73 or 74.412 tert-liutyIditnelliyIsily 1 ethers can be synthesized by the reaction of TBSH/TBSOTf with a ketone (Eq. 240).392... 

Doyle and co-workers have employed Rh2(pfb)4 as a highly selective catalyst for the room temperature synthesis of silyl ethers from alcohols and triethylsilane.159 The selectivity of the catalyst is demonstrated by reactions of olefinic alcohols, in which hydrosilylation is not competitive with silane alcoholysis when equimolar amounts of silane and alcohol are employed. High yields (>85%) of triethylsilyl ethers are obtained from reactions of alcohols such as benzyl alcohol, 1-octanol, 3-buten-l-ol, cholesterol, and phenol. Tertiary alcohols are not active in this system. 

Oxidation of alkyl trimethyl- and triethylsilyl ethers, ROSi(CH3)3 or ROSi-(C2H5)3.1 Silyl ethers of this type can be oxidized directly to carbonyl compounds by the Swern reagent. This oxidation provides an efficient route to the Corey aldehyde (2). 

Silyl ethers, such as TMS, triethylsilyl (TES), triisopropylsilyl (TIPS), lerl-butyldi-methylsilyl (TBS), and terl-butyldiphenylsilyl (TBDPS) ethers (Scheme 2.6), are frequently used in carbohydrate chemistry due to their unique reactivity and steric effect (see Section 2.4.1) [1, 2], These groups are typically introduced onto the molecule by treatment with the corresponding silyl halide or triflate (OTf) and a base, such as Et3N, pyridine, 2,6-lutidine, or imidazole. 

Mukaiyama aldol reactions using a catalytic amount of a Lewis acidic metal salt afford silylated aldols (silyl ethers) as major products, but not free aldols (alcohols). Three mechanistic pathways which account for the formation of the silylated aldols are illustrated in Scheme 10.14. In a metal-catalyzed process the Lewis acidic metal catalyst is regenerated on silylation of the metal aldolate by intramolecular or intermolecular silicon transfer (paths a and b, respectively). If aldolate silylation is slow, a silicon-catalyzed process (path c) might effectively compete with the metal-catalyzed process. Carreira and Bosnich have concluded that some metal triflates serve as precursors of silyl triflates, which promote the aldol reaction as the actual catalysts, as shown in path c [46, 47]. Three similar pathways are possible in the triarylcarbenium ion-catalyzed reaction. According to Denmark et al. triarylcarbenium ions are the actual catalysts (path b) [48], whereas Bosnich has insisted that hydrolysis of the salts by a trace amount of water generates the silicon-based Lewis acids working as the actual catalysts (path c) [47]. Otera et al. have reported that 10-methylacridinium perchlorate is an efficient catalyst of the aldol reaction of ketene triethylsilyl acetals [49]. In this reaction, the perchlorate reacts smoothly with the acetals to produce the actual catalyst, triethylsilyl perchlorate. 

Silyl enol ethers. The reagent (1) reacts with enolizable ketones in refluxing xylene (7 hr.) to give triethylsilyl enol ethers (2) ... 

As above described, Bu-P4 base was found to catalyse the coupling reaction of aryl fluorides with silyl ethers. The use of silyl ether was required for these reactions, and direct arylation of unsilylated alcohols using superbase catalysed coupling reactions has been a challenge. Therefore, the combination of triethylsilyl hydride (Et3SiH) and catalytic Bu-P4 is considered to represent an attractive hydride generating system with which to carry out sequential deprotonation and Sj-jAr reaction [55] (Figure 5.5). 

Other compounds with sufficiently acidic C-H protons can serve as pronucleophiles in Michael additions to a,p-unsaturated aldehydes. Li, Wang and coworkers showed that arylmethanes bearing electron-withdrawing substituents underwent Michael addition to various enals mediated hy prolinol silyl ethers. Catalyst screening revealed that triethylsilyl catalyst Clb was the most efficient one (Scheme 8.10). Independently, Jorgensen and coworkers have also described benzylation of unsaturated aldehydes with toluenes. ... 

Swern conditions have been applied in the selective oxidation of primary silyl ethers, intermediates in the synthesis of natural products [1322], Thus, primary trimethylsilyl or triethylsilyl ethers 1868, in the presence of secondary trime-thylsilyl or triethylsilyl ethers, are selectively oxidized to the corresponding aldehydes 1869 under Swern conditions. A short synthesis of key intermediates towards various natural products, e.g. leukotrienes, has been achieved. 

Another common method for alcohol protection is reaction with RjSiCl to give a silyl ether. Reaction conditions usually involve RjSiCl, with 4-dimethylaminopyridine (DMAP) as the base. Both the ease of preparation of the silyl ether and the stability of the protected species depend on the nature of the R groups. Trimethylsilyl ethers (ROTMS) are very labile and readily removed with water and dilute acid. The triethylsilyl group (ROTES) is a little more robust but may be removed with fluoride ion (the use of fluoride to cleave silyl groups reflects the strength of the Si-F bond). r-BuMejSiCl (TBDMSCl) reacts selectively with... 

More recent studies of the utility of the complexed cations in synthesis have paid particular attention to stereoselectivity in their reaction with silyl enolates and enol borates, e.g. eq 52 in this case the same products result, but with only 2.5 1 stereoselection when using the triethylsilyl enol ether and Boron Trijluoride Etherate catalysis. 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

Excellent yields of silyl enol have also been obtained from enones using B(C6F5)3 as a catalyst.40 f-Butyldimethylsilyl, triethylsilyl, and other silyl enol ethers can also be made under these conditions. 

In addition, trimethylsilyl ether 197a and triethylsilyl ether 197b have conformations different from those of compounds 198a and 198b247, which bear a bulky PhsSi or a (z -Pr) vSi group, respectively. The change of conformation is due to the steric hindrance from these two bulky silyl groups. 

The final step in a recent synthesis of the antifungal agent Papulacandin D involved deprotection of five O-silyl groups including a di-ferr-butylsilylene group, a triethylsilyl ether and two phenolic tri-isopropylsilyl ethers [Scheme 3.115],215 Acid conditions were precluded by the add lability of the side chain. Use of TBAF was complicated by problems in separating the product from tetrabuty-Lammonium salts. The desired global deprotection was accomplished with tris-(dime thy iamino)sulfoni urn difluorotrimethylsilicate (TAS-F). 

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