Tert-butyldimethylsilyl Ethers Research Articles

Aryl Silyl Ethers Enable Preferential Ar-O bond Cleavage in Reductive Generation of Aryllithium Species.

Two-electron transfer to haloarenes constitutes one of the most reliable synthetic methodologies for the generation of aryllithiums. In addition to the conventional halides, readily available aryl ethers can function as potent substrates. However, it is known that the reductive cleavage of alkoxides is plagued by insufficient selectivity concerning the cleaving bond adjacent to the ether oxygen, resulting in decreased reliability of these alkoxyarene substrates. In the present study, we discovered that naphthalenes bearing readily installable tert-butyldimethylsilyl ethers undergo two-electron reduction with lithium metal, resulting in lithiation at the position of the original siloxy group. DFT calculations elucidated the rationale for the change in selectivity upon incorporation of the siloxy group. Our results underscore the practical utility of a siloxy group as a leaving group for reductive transformations involving electron transfer.

Conjugated Polymers with Self-Immolative Sidechain Linkers for Carbon Nanotube Dispersion.

Single-walled carbon nanotubes (SWNTs) are promising materials for generating high-performance electronic devices. However, these applications are greatly restricted by their lack of purity and solubility. Commercially available SWNTs are a mixture of semi-conducting (sc-) and metallic (m-) SWNTs and are insoluble in common solvents. Conjugated polymers can selectively disperse either sc- or m-SWNTs and increase their solubility; however, the conductivity of conjugated polymer-wrapped SWNTs is largely affected by the polymer side chains. Here, a poly(fluorene-co-phenylene) polymer that contains a self-immolative linker as part of its sidechains is reported. The self-immolative linker is stabilized with a tert-butyldimethylsilyl ether group that, upon treatment with tetra-n-butylammonium fluoride (TBAF), undergoes a 1,6-elimination reaction to release the sidechain. Sonication of this polymer with SWNTs in tetrahydrofuran (THF) results in concentrated dispersions that are used to prepare polymer-SWNT thin films. Treatment with TBAF caused side-chain cleavage into carbon dioxide and the corresponding diol, which can be easily removed by washing with solvent. This process is characterized by a combination of absorption and Raman spectroscopy, as well as four-point probe measurements. The conductance of the SWNT thin films increased ≈60-fold upon simple TBAF treatment, opening new possibilities for producing high-conductivity SWNT materials for numerous applications.

Synthesis of methyl 3,4-anhydro-6-bromo-2-o-tert-butyldimethylsilyl-6-deoxy-α-d-allopyranoside from α-d-glucose

Some of simple carbohydrates and their derivatives are used clinically for the treatment of various diseases. Epoxide derivatives, which can be obtained by the intramolecular elimination of water from two vicinal hydroxyl groups, are stable, but sufficiently reactive compounds very often used as intermediaries in various syntheses. Synthesis of epoxide derivative, methyl 3,4-anhydro-6- bromo-2-O-tert-butyldimethylsilyl-6-deoxy-?-D-allopyranoside from ?-D-glucose was achieved in high yields in the minimal number of synthetic steps. Anhydrous glucose was used as a starting material which was transformed into methyl ?-D-glucopyranoside using dry, gaseous hydrogen chloride. Thus obtained derivative was treated with benzaldehyde in the presence of zinc chloride as Lewis acid giving methyl (R)-4,6-O-benzylidene-?-D-glucopyranoside. Obtained compound was treated with NBS (N-bromosuccinimide) in dichloromethane in the presence of barium carbonate giving methyl 4-O-benzoyl-6-bromo-6-deoxy-?-D-glucopyranoside. In the next step obtained compound was treated with TBDMSCl (tert-butyldimethylsilyl chloride) in pyridine, and methyl 4-O-benzoyl-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-?-D-glucopyranoside was further mesylated, and obtained methyl 4-O-benzoyl-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-3- O-mesyl-?-D-glucopyranoside was treated at the end with KOH to give methyl 3,4-anhydro-6-bromo-2-O-tert-butyldimethylsilyl-6-deoxy-?-D-allopyranoside (yield 78 %).

Power of Portieria hornemannii: influence on zebrafish antioxidant system-inflammatory cascade by combatting copper-induced inflammation

Portieria hornemannii, a marine red alga, has attracted considerable attention due to its possible therapeutic characteristics. NFκB, a crucial transcription factor involved in regulating immune and inflammatory responses, plays a central role in controlling the expression of various genes associated with inflammation, such as MMP 9. This study employed an aqueous extract of Portieria hornemannii (Ph) and subjected it to UV-Visible, FTIR spectroscopy, and GC-MS analysis to identify its phytochemical composition. The presence of Vanillin, tert-butyldimethylsilyl ether, Dodecane, 1-fluoro-, and Pentanoic acid, 5-hydroxy-2,4-di-t-butylphenyl esters in Ph indicates their potential anti-inflammatory properties, suggesting their potential application in inflammation treatment. In summary, Ph exhibited anti-inflammatory properties by modulating the expressions of NFκB-associated MMP 9 in zebrafish embryos, potentially reducing the risk of inflammatory diseases.

Access to Enantiomerically Pure P-Chiral 1-Phosphanorbornane Silyl Ethers.

Sulfur-protected enantiopure P-chiral 1-phosphanorbornane silyl ethers 5a,b are obtained in high yields via the reaction of the hydroxy group of P-chiral 1-phosphanorbornane alcohol 4 with tert-butyldimethylsilyl chloride (TBDMSCl) and triphenylsilyl chloride (TPSCl). The corresponding optically pure silyl ethers 5a,b are purified via crystallization and fully structurally characterized. Desulfurization with excess Raney nickel gives access to bulky monodentate enantiopure phosphorus(III) 1-phosphanorbornane silyl ethers 6a,b which are subsequently applied as ligands in iridium-catalyzed asymmetric hydrogenation of a prochiral ketone and enamide. Better activity and selectivity were observed in the latter case.

A Greener Technique for Microwave-Assisted O-Silylation and Silyl Ether Deprotection of Uridine and Other Substrates

A single clean, good-yielding, environment-friendly microwave-assisted procedure for O-silylation of uridine with tert-butyldimethylsilyl chloride (TBDMSCl), 1,8-Diazabicyclo(5.4.0)undec-7-ene (DBU) and potassium nitrate as catalyst under solvent-free conditions is reported. Subsequent silyl ether deprotection is accomplished with a reusable acidic resin via microwave irradiation. Both the silylation and desilylation protocols have been applied to a panel of alcohols of pharmaceutical interest.

Development of Silicon Carbide-Supported Palladium Catalysts and Their Application as Semihydrogenation Catalysts for Alkynes under Batch- and Continuous-Flow Conditions

Silicon carbide (SiC)-supported palladium (Pd) catalysts [3% Pd/SiC and a 3% Pd-diethylenetriamine (DETA)/SiC complex] for chemoselective hydrogenation under batch- and continuous-flow conditions were developed. The alkyne, alkene, azide, nitro, and benzyloxycarbonyl-protected aromatic amine (N-Cbz) functionalities were chemoselectively reduced in the presence of 3% Pd/SiC. By contrast, benzyl ether, alkyl N-Cbz, epoxide, aromatic chloride, aromatic ketone, and tert-butyldimethylsilyl ether were tolerant to the 3% Pd/SiC-catalyzed hydrogenation. The combined use of 3% Pd/SiC and DETA demonstrated excellent chemoselectivity toward the semihydrogenation of various mono- and disubstituted alkynes under batch- and continuous-flow conditions. Furthermore, compared with the separate use of 3% Pd/SiC and DETA, the newly developed 3% Pd(DETA)/SiC-packed in a cartridge showed higher chemoselectivity toward the continuous-flow semihydrogenation of alkyne over 24 h.

Facile synthesis of per(6-O-tert-butyldimethylsilyl)-α-, β-, and γ-cyclodextrin as protected intermediates for the functionalization of the secondary face of the macrocycles.

Per(6-O-tert-butyldimethylsilyl)-α-, β- and γ-cyclodextrin derivatives are well-known as synthetic intermediates that enable the selective mono-, partial, or perfunctionalization of the secondary face of the macrocycles. Although silylation of the primary rim is readily achieved by treatment with tert-butyldimethylsilyl chloride in the presence of pyridine (either alone or mixed with a co-solvent), the reaction typically results in a mixture containing both under- and oversilylated byproducts that are difficult to remove. To address this challenge in preparing a pure product in high yield, we describe an approach that centers on the addition of a controlled excess of silylating agent to avoid the presence of undersilylated species, followed by the removal of oversilylated species by column chromatography elution with carefully designed solvent mixtures. This methodology works well for 6-, 7-, and 8-member rings (α-, β-, and γ-cyclodextrins, respectively) and has enabled us to repeatedly prepare up to ⁓35 g of ≥98% pure product (as determined by HPLC) in 3 d. We also provide procedures for lower-scale reactions, as well as an example of how the β-cyclodextrin derivative can be used for functionalization of the secondary face of the molecule.

Multifunctional polyimides by direct silyl ether reaction of pendant hydroxy groups: Toward low dielectric constant, high optical transparency and fluorescence

Unsatisfied overall properties and high-cost production are major obstacles for the commercialization of polyimide (PI) films. This work aims to develop a convenient way with low cost to prepare multifunctional PI films with excellent combined properties of low dielectric constant (k), high transparence and fluorescence by the direct structural modification on easily available PIs containing active groups. Thus, a series of fluorene-based PIs with tert-butyldimethylsiloxy (TBS) side groups (PI-TBSs) were successfully synthesized by a direct silyl ether reaction of hydroxyl-containing PIs (PI-OHs) with tert-butyldimethylsilyl chloride (TBSCl). The resulted PI-TBSs with high yield are readily soluble in many common solvents, even in low-boiling-point solvents at room temperature. Due to the presence of the cardo-type fluorene structure, PI-TBS films still possess the excellent thermal properties with a glass transition temperature (Tg) of 311.2–338.9 °C and a 5% weight loss temperature (T5%) of 469.5–506.4 °C in N2 and the good mechanical properties with a tensile strength (TS) of 57.7–79.1 MPa. In addition, PI-TBS films exhibit the light color with the high optical transparence (over 80% at 450 nm), the low dielectric constant (as low as 2.44 at 1 MHz for PI-TBS-2F) and the bright fluorescence because of the reduced charge transfer (CT) interaction in PI chains chemically bonded by bulky non-polar TBS groups. As the result, this work provides a convenient way to prepare multifunctional PI films with the excellent overall properties, which show high potential applications of these PI films in microelectronic, electric and photonics industries.

MASS SPECTROMETRIC FRAGMENTATION OF TRIMETHYLSILYL AND RELATED ALKYLSILYL DERIVATIVES.

This review describes the mass spectral fragmentation of trimethylsilyl (TMS) and related alkylsilyl derivatives used for preparing samples for analysis, mainly by combined gas chromatography and mass spectrometry (GC/MS). The review is divided into three sections. The first section is concerned with the TMS derivatives themselves and describes fragmentation of derivatized alcohols, thiols, amines, ketones, carboxylic acids and bifunctional compounds such as hydroxy- and amino-acids, halo acids and hydroxy ethers. More complex compounds such as glycerides, sphingolipids, carbohydrates, organic phosphates, phosphonates, steroids, vitamin D, cannabinoids, and prostaglandins are discussed next. The second section describes intermolecular reactions of siliconium ions such as the TMS cation and the third section discusses other alkylsilyl derivatives. Among these latter compounds are di- and trialkyl-silyl derivatives, various substituted-alkyldimethylsilyl derivatives such as the tert-butyldimethylsilyl ethers, cyclic silyl derivatives, alkoxysilyl derivatives, and 3-pyridylmethyldimethylsilyl esters used for double bond location in fatty acid spectra. © 2019 Wiley Periodicals, Inc. Mass Spec Rev 0000:1-107, 2019.

Diastereoconvergent synthesis of chiral sulfoxides containing vicinal amino alcohol framework

A highly diastereoconvergent synthesis of chiral sulfoxides containing vicinal amino alcohol framework has been achieved in moderate to good yield with up to 99:1 dr. Different from the previous work, the stereochemistry of the new chiral center was determined solely by the configuration of benzyl tert-butyl sulfoxide, while both the chiral sulfinyl group and the tert-butyldimethylsilyl ether (α-OTBS) group at the α-position of imine were not involved in the stereo induction. This approach also provides an efficient synthesis of chiral building blocks of pyrrolidinones.

A tunable synthesis of either benzaldehyde or benzoic acid through blue-violet LED irradiation using TBATB

In this paper, a highly efficient, metal-free, and homogeneous method for the selective aerobic photooxidation of alcohols and photooxidative-desilylation of tert-butyldimethylsilyl ethers (TBDMS) in the presence of tetrabutylammonium tribromide (TBATB) under irradiation of visible light was reported. The light source: blue (460 nm) and violet (400 nm) LED, can control selective oxidation to aldehyde or carboxylic acid.

Silica-coated Fe3O4 magnetic nanoparticles-supported sulfonic acid as a highly active and reusable catalyst in chemoselective deprotection of tert-butyldimethylsilyl (TBDMS) ethers

Anchored propyl sulfonic acid on the surface of silica-coated magnetic nanoparticles (Fe3O4@SiO2@PrSO3H) was successfully employed in the deprotection of TBDMS ethers. The prepared magnetically separable nanocatalyst exhibited efficient catalytic activity with high conversion and selectivity in cleavage of TBDMS ethers. TBDMS ethers are efficiently cleaved to the corresponding hydroxyl compounds in methanol solution containing 2 mol% magnetic nano-catalysts. Good to excellent yields of products, simple work-up and product separation, selective cleavage of TBDMS ethers in the presence of TBDPS ethers, easy recycling of the catalyst with external magnet with no loss in its activity (7 reaction cycles) are important features of this new protocol.

Efficient Heterodifunctional Unimolecular Ring‐Closure Method for Cyclic Polymers by Combining RAFT and SuFEx Click Reactions

A novel ring-closure strategy for cyclic polymers by combining reversible addition-fragmentation chain transfer polymerization (RAFT) and the sulfur(VI)-fluoride exchange (SuFEx) click reaction is presented. Herein, a new heterodifunctional trithiocarbonate RAFT agent, 2-((tert-butyldimethylsilyl)oxy)ethyl (4-(fluorosulfonyl)benzyl) carbonotrithioate (TBDMS-FSBCT), containing both tert-butyldimethylsilyl ether and sulfonyl fluoride moieties, is developed. The polymerization behavior of TBDMS-FSBCT is first demonstrated by a standard RAFT polymerization procedure for two types of vinyl monomers, N-isopropylacrylamide (NIPAAm) (conjugated vinyl monomer) and N-vinylpyrrolidone (NVP) (unconjugated vinyl monomer). The tert-butyldimethylsilyl ether and sulfonyl fluoride groups at the α and ω positions of the obtained linear polymer precursors (L-PNIPAAm and L-PVP) are verified by 1 H, 13 C, and 19 F NMR spectra. Subsequent intramolecular SuFEx click cyclization of the α,ω-heterofunctionalized linear precursors in air at room temperature conveniently yields the corresponding cyclic polymers (C-PNIPAAm and C-PVP). Overall, this is the first report on the preparation of cyclic polymers based on the SuFEx reaction under ambient conditions. It is envisioned that the approach may open an avenue for the formation of cyclic polymers.

Catalytic removal of tert-butyldimethylsilyl (TBS) ether by PVP-I

A mild, efficient and rapid protocol the deprotection of alcoholic TBDMS ethers using PVP-1 as catalyst in methanol, the procedure of deprotection of various TBDMS ethers were found to be very convenient, easy work-up, high yielding.

Selective Protection of Secondary Alcohols by Using Formic Acid as a Mild and Efficient Deprotection Reagent for Primary tert-Butyldimethylsilyl Ethers

A mild, efficient, and environmentally friendly method for the selective protection of secondary hydroxyl groups is described. The method involves the protection of both primary and secondary hydroxyl groups as tert-butyldimethylsilyl (TBDMS) ethers and selective deprotection of the primary TBDMS group with formic acid in acetonitrile/water. The rates of desilylation of primary and secondary TBDMS ethers by different concentrations of formic acid are determined. Formic acid of 5–20% concentration is found to selectively deprotect primary TBDMS ethers while keeping more than 95% of their secondary counterparts intact.

Base and Catalyst-Free Preparation of Silyl Ethers in the Choline Chloride/Urea Deep Eutectic Solvent (DES)

An efficient, fast, green, and mild procedure is reported for preparation of silyl ethers from aliphatic, benzylic, allylic, propargylic alcohols, phenols, naphthols, and some phenolic drugs. In this method, choline chloride/urea (ChCl/urea) deep eutectic solvent (DES) is used as an environmentally benign reaction medium. Silylation was accomplished by employing trimethylsilylchloride (TMSCl), triethylsilylchloride (TESCl), and t-butyldimethylsilylchloride (TDSCl) as the silylating agents. The significant advantages offered by this green protocol are high yields, operational simplicity, short reaction time, and also avoiding the use of any environmentally hazardous solvents, bases, and catalysts. This procedure can also be utilized in large scale silylation for industrial applications.

Total Synthesis of (±)-Prostratin

Summary Prostratin, a highly complex diterpene natural product, is a pre-clinical candidate in developing a cure for HIV-1 infection and also a potent and selective inhibitor of several tumors. Despite nearly 40 years of progress, prostratin and related natural products still present formidable challenges for synthetic chemists. Here, we report a total synthesis of (±)-prostratin that proceeds in 23 steps from cyclopentadiene. The synthetic strategy includes rapid assembly of the tricyclic core and highly controlled establishment of the densely functionalized C ring, featuring an array of stereoselective transformations including alkoxide-guided 1,4-additions and cyclopropane formation. This work should enable further explorations of chemical and biological spaces based on prostratin and related natural products.

Hafnium Triflate as a Highly Potent Catalyst for Regio- and Chemoselective­ Deprotection of Silyl Ethers

As a Group IVB transition metal Lewis acid, hafnium triflate [Hf(OTf)4] exhibited exceptionally high potency in desilylations. Since the amounts of Hf(OTf)4 required for the deprotection of 1°, 2°, 3° alkyl and aryl tert-butyldimethylsilyl (TBS) ethers are significantly different, ranging from 0.05 mol% to 3 mol%, regioselective deprotection of TBS could be easily implemented. Moreover, chemoselective cleavage of different silyl ethers or removal of TBS in the presence of most hydroxyl protecting groups was also accomplished. NMR analyses of silyl products from TBS deprotection indicated that Hf(OTf)4-catalyzed desilylation may proceed via different mechanisms, depending on the solvent used.

Substituent Effects in the Silylation of Secondary Alcohols: A Mechanistic Study.

Relative rates for the silylation of C4-substituted 1-(naphthalen-1-yl)ethanol substrates with tert-butyldimethylsilyl chloride (TBSCl) in CDCl3 catalyzed by 9-azajulolidine (TCAP) have been measured. Hammett plot analysis of the resulting selectivity data yields two intersecting linear correlations. A small positive slope of ρ=+0.09 is observed for donor-substituted alcohols, while silylation rates for acceptor-substituted alcohols correlate best with a slightly larger negative slope (ρ=-0.48). The reaction of methanol with TBSCl catalyzed by 4-(N,N-dimethylamino)pyridine (DMAP) has been studied at several different theoretical levels in chloroform solution. Silyl-group transfer between silylated DMAP and methanol occur over an exceedingly flat surface with barely defined minima and transition states. Reaction pathway calculations for the Lewis base and general base catalyzed mechanisms for reaction of TBSCl with C4-substituted 1-(naphthalen-1-yl)ethanol compounds predict a close competition of both pathways.