Silylated ethers, deprotection

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. 

Completion of the synthesis was readily achieved. Diastereoselective reduction of the ketone was accomplished with (S)-BINOL/LiAlH4. Then, removal of the tether by acidic hydrolysis, which also effected silyl ether deprotection, afforded dihydroxy lactol 223 allowing introduction of the final side chain using a Wittig reaction (Scheme 10-71). 

When a solution of Et2Zn was treated with enantioenriched 225 (er, 76 24) in THF at 40°C for 24h, foUowed by acidic hydrolysis and silyl ether deprotection with tetra-n-butylammonium fluoride (TBAF), the corresponding cyclic alcohol... 

Poly(lactide-g-dextran) copolymers were synthesized by a three-step process partial silylation of the dextran hydroxyl groups, ROP of D,L-lactide initiated by the remaining hydroxyl groups of dextran, followed by silyl ether deprotection under mild conditions. The emulsifying properties of these glycopolymers depend on the PLA/dextran ratio [104]. PLA-g-dextran and PLA-g-silylated dextran adopt a core-shell conformation in various solvents [105]. Studies on encapsulation and release behavior of bovine serum albumin from PLA-g-dextran revealed a higher loading than in PLLA microspheres [106]. 

T. D. Nelson and R. D. Crouch, Selective Deprotection of Silyl Ethers, Synthesis, 1031 (1996). 

The oxidative deprotection of silyl ethers, such as the TBDMS ether, has been reviewed. " ... 

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. ... 

Under carefully controlled conditions, TBAF and aqueous HF selectively deprotect phenolic and alcoholic silyl ethers respectively. An excess of either reagent will, of course, ultimately result in complete deprotection. 

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. 

Silyl Ethers as Protective Groups for Alcohols. Oxidative Deprotection and Stability Under Alcohol Oxidation Conditions, Muzart. J. Synthesis. 1993, 11... 

Silyl-derived linker 36 was prepared in three steps from a silyl ether of serine and incorporated for Fmoc/tBu-based assembly of protected gly-copeptide blocks (Scheme 11) [42]. The a-carboxylic acid function of serine was protected as an allyl ester. Deprotection by a Pd(0) catalyst in the presence of dimedone liberated the carboxylic acid in order for subsequent... 

Our retrosynthesis of (—)-kinamycin F (6) is shown in Scheme 3.20 [45]. It was envisioned that (—)-kinamycin F (6) could be prepared from the protected diazofluorene 114 by conversion of the ketone function of 114 to a trans-], 2-diol, followed by deprotection of the acetonide and methoxymethyl ether protecting groups. The diazofluorene 114 was envisioned to arise from diazo transfer to the hydroxyfulvene 115. The cyclopentadiene substructure of 115 was deconstructed by a two-step annulation sequence, to provide the bromoquinone 116 and the p-trimethylsilylmethyl unsaturated ketone 117. The latter two intermediates were prepared from juglone (118) and the silyl ether 119, respectively. 

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

Deprotection of trimethyl silyl ether has also been accomplished (88-100%) on K 10 day [43] or oxidative deavage (70-95%) in presence of day and iron(III) nitrate [44]. 

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). 

Most of the more recently described allenic steroids bear an allene group at the 17-position, which was usually formed by an SN2 substitution [106] or reduction [86d] process of a suitable propargylic electrophile. Thus, reduction of the pro-pargylic ether 109 with lithium aluminum hydride followed by deprotection of the silyl ether resulted in the formation of the allenic steroid 110, which irreversibly inhibits the biosynthesis of the insect moulting hormone ecdysone (Scheme 18.35) [107]. 

It has been reported that (TMS)3SiCl can be used for the protection of primary and secondary alcohols [55]. Tris(trimethylsilyl)silyl ethers are stable to the usual conditions employed in organic synthesis for the deprotection of other silyl groups and can be deprotected using photolysis at 254 nm, in yields ranging from 62 to 95%. Combining this fact with the hydrosilylation of ketones and aldehydes, a radical pathway can be drawn, which is formally equivalent to the ionic reduction of carbonyl moieties to the corresponding alcohols. 

Protection of hydroxy groups as the THP and ferf-butyldimethyl silyl ethers and, conversely, deprotection of these derivatives to the original alcohols. 

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