Silyl ethers removal

Protection of alcohol groups as silyl ethers Removal of the protective group... 

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. 

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. 

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

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. ... 

This is followed by hydrolysi.s of the ester moieties with potassium carbonate and reesterification of the carboxy moiety with diazomethane to produce intermediate 65. The solitary free alcoholic hydroxyl at C-9 is oxidized with Collins reagent and the silyl ether groups are removed with acetic acid to give enprostil (63) [15]. 

Hydrogenation of the product 147 removes the benzyl protecting groups and at the same time reduces the triazine to its dihydro derivative 148. A roundabout scheme is required for dehydrogenation due to the sensitivity of the intermediates. The product is thus converted to its silyl ether 149 exposure to air results in oxidation and desilylation. There is thus obtained the antineoplastic agent fazarabine (150), also known as ara-A C. 

Blechert s synthesis of the piperidine alkaloid (-)-halosaline (387) by Ru-catalyzed RRM is outlined in Scheme 76 [160]. In the presence of 5 mol% of catalyst A, the ring rearrangement of metathesis precursor 385 proceeded cleanly with formation of both heterocyclic rings in 386. In situ deprotection of the cyclic silyl ether in 386, followed by selective reduction and removal of the to-syl group led to 387. 

In order to ameliorate the problem of solvolytic degradation, compound 109 was treated with TIPSOTf, to provide silyl ether 113 in 72% yield (Scheme 19). The acetonides were removed with PPTS in warm MeOH to provide a mixture of compounds in which the TBS groups were also partially removed. Exposure of this mixture to HF-pyridine successfully generated filipin III (114), in 39 % overall yield from 113. 

The synthesis of this derivative of KDG was accomplished following the sequence depicted in figure 6. Methylation of the intermediate 8 with methyl Inflate afforded compotmd 21. Subsequent removal of the enol benzoate group at C-2 and of the silyl ether at C-6 provided the target compound 23 in 11% overall yield based on 8. This low yield could be due to the unstability of compotmds 8, 21 and 22 in a basic medium. However 24 was obtained in quantity sufficient for testing. 

The benzyl group was removed selectively from a silyl ether of the following compound by 10% Pd/C and formic acid in EtOH (Scheme 4.56).259... 

Addition of a silyl substituent into a-position of the a-(benzotriazol-l-yl)alkyl ether brings additional possibilities. Thus, lithiation of silyl ether 770 followed by treatment with an aldehyde or ketone gives unstable P-hydroxy-a-silyl-a-(benzotriazol-l-yl)alkyl ether 771 that spontaneously eliminates silanol to give vinyl ether 772 (Scheme 121). Treatment with ZnBr2 followed by hydrolysis with a diluted acid removes both the benzotriazolyl and the methyl groups to furnish carboxylic acid 773. In this way, in a simple manner, aldehydes and ketones are converted to one-carbon homologated carboxylic acid <1996S1425>. 

Silyl protecting groups are the gold standard for the protection of alcohols.234 Novel photochemically removable protection groups for alcohols have been developed by Brook et a/.23S and Pirrung et al,236 For instance, cyclo-pentanol can be reacted with tris(trimethylsilyl)chlorosilane 53 in the presence of a mild base to yield the protected silyl ether 54. The protection group can be removed conveniently upon UV irradiation or by the use of Bu4NF (Scheme 12). 

The tosyl protecting group of 4a is removed with sodium naphthalide at -60 °C, and an intramolecular nucleophilic attack of the nitrogen lone pair to the epoxide takes place spontaneously to afford the pyrrolidine hydroxy ester as a labile reaction product, which is immediately protected as the corresponding silyl ether 3a in 68%... 

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