Silyl Ethers Research Articles

Palladium‐Catalyzed Dehydrogenation Cross‐Coupling Reactions of Hydrosilanes: Facile Synthesis of Silanols and Silyl Ethers

AbstractA palladium‐catalyzed dehydrogenative cross‐coupling reactions between silanes and oxygen‐containing functional groups (water, alcohols, phenols) to generate the corresponding silanols, monosilane ethers, and disilane ethers directly in moderate to high yields. This strategy does not rely on any additional oxidizing agents or proton reductants. The possible mechanisms for this transformation are also proposed.

Chemical Synthesis of β‐(1,4)‐d‐Oligomannurarates with Purported Anti‐Alzheimer Activity

Sodium oligomannate, a sophisticated mixture of acidic linear β‐(1,4)‐d‐oligomannurarate ranging from dimers to decamers with an average molecular weight of 670∼880 Da, has gained conditional approval for the treatment of Alzheimer's disease. Herein, we develop an efficient approach to the chemical synthesis of well‐defined β‐(1,4)‐d‐mannurarate di‐, tetra‐, hexa‐ and octasaccharides (1‐4), utilizing N‐phenyl trifluoroacetimidate donors and thioglycoside acceptors for the stereoselective assembly of the desired β‐(1,4)‐d‐mannuronate linkages. This approach features a straightforward protecting group strategy with only two types of protecting groups: tert‐butyldimethylsilyl (TBS) for the 4‐OH at the non‐reducing end and benzyl (Bn) for free hydroxyl and carboxylic acid moieties, thereby ensuring the stereoselective formation of the β‐mannosyl bonds and facilitating sequential transformation into the target β‐(1,4)‐d‐mannurarate oligosaccharides. The scalability of the present synthesis of these oligosaccharides paves the way for in‐depth structure‐activity relationship studies and pharmacological investigations of sodium oligomannates.

Synthetic studies on fusicoccin A: Enantioselective synthesis of the C-ring fragment

The enantioselective synthesis of the C-ring fragment of fusicoccin A is described. The TBS ether of hydroxyketone prepared by baker’s yeast reduction was converted to the α-ethylidene ketone by aldol condensation with propionaldehyde, followed by Michael reaction with divinylcopper reagent and conversion to enol triflate to afford a single diastereomer. X-ray crystallographic analysis of the crystalline derivative of the single diastereomer showed that the asymmetric carbon formed by the Michael reaction was consistent with the configuration of the C15 asymmetric carbon of fusicoccin A. The vinyl group of the enol triflate was converted to a hydroxymethyl group by selective dihydroxylation with a bulky ligand, oxidative cleavage of the resultant 1,2-diol with lead tetraacetate, and DIBAL-H reduction. The hydroxymethyl group was subsequently converted to TBS ether, followed by the hydrogenolysis of the benzyl group and Dess–Martin oxidation, accomplishing the enantioselective synthesis of the desired C-ring fragment of fusicoccin A.

Shape memory, reprocessable and photothermal networks of polyurethane with silyl ether bonds and croconaine segments

Organic dyes were integrated into networks of polyurethane (PU) in the form of croconaine segments, in order to bestow photothermal properties on the materials. In addition, the PU networks were crosslinked with polysilsesquioxane (PSSQ) so that the materials can be reprocessed (or self-healing) via the metathesis of silyl ether bonds under catalysis. Toward this end, we synthesized a novel diol bearing croconaine moiety, which was used as one of chain extenders and a series of linear PU telechelics with dihydroxyl termini were synthesized. The α,ω-dihydroxyl PU telechelics were then allowed to react with 3-isocyanatopropyltriethoxysilane to gain α,ω-ditriethoxysilane PU telechelics. Through sol-gel process, α,ω-ditriethoxysilane PU telechelics readily underwent crosslinking with PSSQ as the crosslinkages. The crosslinking of PU was in marked contrast to traditional crosslinking of PU with multifunctional ols (or amines) as the crosslinkers. Owing to the crosslinking, shape memory properties were bestowed on the organic-inorganic PU networks. Thanks to the metathesis of silyl ether bonds under catalysis, the organic-inorganic PU networks were reprocessable (or recyclable). Benefiting from the built-in of dye segments, the PU networks significantly displayed excellent photothermal conversion properties. By leveraging the photothermal properties, the shape shifting of the PU networks can be triggered via the irradiation under infrared laser and in a non-contact fashion. In addition, the PU networks were capable of displaying the light-triggered self-healing properties. Thanks to these excellent properties, we demonstrated a successful application of the PU networks a soft robot.

Encasing Triaryltriazine with a Bulky Chiral Cap: Luminescent Chiral Crystalline Molecular Rotors with Modulation of Solid-State Chiroptical Properties Mediated by Molecular Rotation.

A novel structural motif for luminescent chiral crystalline molecular rotors with chiroptical properties correlated with the rotational motion in crystalline media is presented. This scaffold incorporates bulky chiral caps consisting of a homochiral binaphthyl moiety with a triisopropylsilyl (TIPS) group into triaryltriazine, as confirmed by single-crystal X-ray diffraction (XRD) analysis. Variable-temperature solid-state 2H NMR studies revealed a 4-fold rotation of the phenylenes occurred in the rotor crystal between 263 and 333 K, while a steric rotor analogue shows no rotational motion. Notably, a reduction in the dihedral angle of the binaphthyl moiety upon heating was observed in the chiral rotors, and a corresponding alteration of the circular dichroism (CD) signal was detected in the solid-state, while those of the steric rotors showed no alteration by the temperature change. We propose that the fast rotation of the phenyl rings affects the motion of neighboring isopropyl groups, leading to steric repulsion with the binaphthyl moieties and thereby inducing its conformational change. Furthermore, the chiral rotors exhibited circularly polarized phosphorescence in the solid-state at low temperature, originating from rotational displacement of the phenylene on triphenyltriazine during structural relaxation in the excited state. Meanwhile, the steric rotors showed significant circularly polarized fluorescence induced by the suppressed molecular motion via a sterically hindered lattice environment in the excited state. These results indicate that the bulky chiral cap introduced into the triaryltriazines, acting as a luminescent chiral crystalline molecular rotor, can be a useful scaffold for the modulation of solid-state chiroptical properties via molecular rotational motions.

Correlation between the Molecular Properties of Semiconducting Polymers of Intrinsic Microporosity and Their Photocatalytic Hydrogen Production.

Increasing the interface area between organic semiconductor photocatalysts and electrolyte by fabricating nanoparticles has proven to be an effective strategy to increase photocatalytic hydrogen production activity. However, it remains unclear if increasing the internal interface by the introduction of porosity has as clear benefits for activity. To better inform future photocatalyst design, a series of polymers of intrinsic microporosity (PIMs) with the same conjugated backbone were synthesized as a platform to independently modulate the variables of porosity and relative hydrophilicity through the use of hydrophilic alcohol moieties protected by silyl ether protecting groups. When tested in the presence of ascorbic acid and photodeposited Pt, a strong correlation between the wettable porosity and photocatalytic activity was found, with the more wettable analogue of two polymers of almost the same surface area delivering 7.3 times greater activity, while controlling for other variables. Transient absorption spectroscopic (TAS) investigation showed efficient intrinsic charge generation within 10 ps in two of the porous polymers, even without the presence of ascorbic acid or Pt. Detectable hole polarons were found to be immediately extracted by added ascorbic acid, suggesting the generation of reactive charges at regions readily accessible to electrolyte in the porous structures. This study directs organic semiconductor photocatalysts design toward more hydrophilic functionality for addressing exciton and charge recombination bottlenecks and clearly demonstrates the advantages of wettable porosity as a design principle.

Silyl Ethers as Latent Pronucleophiles in Enantioselective Lewis Base Catalyzed Synthesis of Allylic Ethers from Allylic Fluorides

Allylic ethers are a common occurrence in natural products and are often used as intermediates in target-oriented synthesis. Their synthesis often relies on the use of transition metal catalysts. Here we report an organocatalytic method for allylation of O-centered nucleophiles: Lewis base catalyzed allylation of silyl ethers with allylic fluorides. The method relies on the concept of latent pronucleophiles in Lewis base catalysis to overcome common limitations in substrate scope even allowing for allylation of sterically congested O-pronucleophiles. When chiral Lewis base catalysts are used, the allyl ethers are produced in enantioenriched form via a kinetic resolution of fluorides where streoselectivity is determined by the chiral catalyst.

Hydrogen Fluoride Imidazole: A Simple, Efficient, Mild, and Cost-Effective Silyl-Ether Deprotection Reagent.

Despite the availability of numerous -OH silyl protection and deprotection methods, the selective cleavage of silyl ethers in highly complex molecules can still be a challenge. In this article, we present results from a full investigation of a novel, efficient, and mild desilylation protocol using HF/imidazole. Imidazole significantly enhances the desilylation reaction efficiency of HF, allowing clean and complete deprotection of TBDPS ethers in substrates containing both acid and base sensitive groups. For example, four- and five-mer oligonucleotides were efficiently deprotected where all other conditions failed. HF/imidazole is also an effective reagent for the deprotection of TIPS and TBDMS ethers. The reagent prepared using commercially available HF and imidazole maintained the same reactivity even after 4 years of storage at 4 °C. Residual reagents and byproducts can be readily removed with a simple workup; consequently, deprotection of TBDPS was successfully implemented in a 2.5 kg scale synthesis of a five-mer oligonucleotide.

AgOTf-catalyzed three-component coupling for the synthesis of C-alkynyl iminosugars

A3 coupling of tosylribose, primary amine and alkyne has been accomplished for the synthesis of C-alkynyl iminosugars using a catalytic amount of AgOTf under extremely mild conditions. This method is compatible with acid sensitive acetonide and cyclohexylidene and also TBS and PMB ethers The reaction proceeds through a cyclic iminium ion, which is formed from tosylribose and a primary amine followed by the attack of alkyne resulting in the formation of C-alkynyl iminosugar, which is a key intermediate of many biologically important natural products.

GC-MS Profiling, Pharmacological Predictions, Molecular Docking, and ADME Studies of Different Parts of Thymus Linearis against Multiple Target Proteins in Wound Healing.

Thymus linearis from the Himalayan woodlands of Gilgit Baltistan, Pakistan, is a phytomedicine that has not been well-studied. Traditionally, it is recognized for its potential in treating conditions such as dermatitis, psoriasis, weight loss, and discomfort. The study investigates the wound-healing properties of methanolic extracts from the plant's stems, leaves, and roots. GC-MS disclosed cadaverine, dihydroxy-3,3-dimethyl-3-hydroxy-N-isopropylbutyramide, phthalic acid-di(2-propylpentyl)ester, and benzo[h]quinolone-2,4-dimethyl in stem along with betamethasone velerate, 17-pentatriacontene, 1,1-cyclobutanedicarboxmide, heptadecane-9-hexyl, cyclohexanol-2-methylene-3(1-methylethenyl) and pentacyclo[12.3.0.0(1,13).0(2,10).0(5,9)]hepatodecane-6-ol-15-one in leaf extracts and 2-myristynonyl pantetheine, 7,8-epoxylanostan-11-ol-3-acetoxy, heneicosane (1-(1-ethyl propyl)), 2-piperidinone-N-[4-bromobutyl] and 1-monolinoleoylglycerol trimethyl silyl ether in the root extract. The antioxidant activity was assessed using several assays including DPPH, bound iron %, ABTS, total flavonoid content, and total phenolic content. The methanolic stem extract (MSE) showed the highest antioxidant capacity compared to the leaf and root extracts. The stem extract demonstrated the highest wound-healing potential, followed by leaves and roots in albino mice. The findings were supported by computational analysis, which revealed that the binding interactions of phytochemicals from stem have more affinity than leaf and root with specific receptor sites. The in-silico analysis ascertains that dihydroxy-3,3-dimethyl-3-hydroxy-N-isopropylbutyramide from MSE is the most effective wound-healing agent. Moreover, ADME predictions demonstrated the drug-like properties of the hit compounds.

Effect of sensing material basicity on excited-state intramolecular proton transfer-based detection of G-series nerve agents

The use of G-series nerve agents represents a significant threat and there is a need for rapid and selective in-field identification. We report that sensing materials composed of ESIPT-based silyl ethers can be used to detect the hydrogen fluoride that is present in phosphonofluoridate agents such as sarin and its simulant di-iso-propyl fluorophosphate (DFP). We find that the ability of the sensing material to detect the hydrogen fluoride in DFP is dependent on the basicity of the nitrogen atom that forms part of the ESIPT moiety upon deprotection. When the pKa of the conjugate acid of the nitrogen atom was lower than that of hydrogen fluoride the ability of the sensing material to detect the acid and hence simulant was curtailed. However, when the pKa of the conjugate acid was 3 or higher, then hydrogen fluoride could be rapidly detected. The best performing sensing material could detect hydrogen fluoride concentrations as low as 3 ppb in DFP of 99 % purity in one minute. Based on sarin having the same purity level, we estimate that it would be detectable at a concentration of ≈40 ppb in one minute, which is lower than the Acute Exposure Guideline 3 (life-threatening effects) of 64 ppb for a 10-min exposure.

Dehydrosilylation of Alcohols Using Gold Nanoparticles Deposited on Citric Acid Modified Fibrillated Cellulose

AbstractThe development of an effective catalytic system for the dehydrogenative coupling of hydrosilanes with alcohols remains an ongoing challenge, particularly for alcohol protection applications. In this study, we report the development and optimization of a highly efficient gold catalyst supported on fibrillated cellulose modified with citric acid. The catalyst exhibited remarkable catalytic activity under mild conditions with 0.01–0.05 mol% of Au loading, facilitating the formation of silyl ethers with excellent yield. Notably, our catalytic system overcomes the need for excess alcohol, typically required in such reactions, making it highly practical for alcohol protection applications. This work represents a significant advancement in the field of dehydrosilylation catalysis, offering a sustainable, efficient, and environmentally friendly approach for the synthesis of functional silanol-based materials and alcohol protection applications. The scope of substrates and the utility of the catalyst have been thoroughly studied.

Stereocontrolled 1,2-trans-arabinofuranosylation in the absence of 2-O-acyl group in glycosyl donor

Stereocontrolled 1,2-trans-α-arabinofuranosylation using polysilylated mono- and disaccharide glycosyl donors was investigated. A complete α-stereoselectivity of 1,2-trans-arabinofuranosylation was found for Ara-β-(1 → 2)-Ara disaccharide glycosyl donors containing five triisopropylsilyl (TIPS) groups with arylthiol (1) (as shown in our previous publications) or N-phenyltrifluoroacetimidoyl (2) (this work) leaving groups. Conversely, in case of monosaccharide thioglycosides polysilylated with acyclic silyl groups (TIPS, TBDPS), stereoselectivity of glycosylation was lower (α:β = 7–8:1), although the desired α-isomer still dominated. Disaccharide glycosyl donor 2 was successfully used in the synthesis of linear α-(1 → 5)-, β-(1 → 2)-linked hexaarabinofuranoside useful for further preparation of conjugates thereof as antigens valuable for the diagnosis of mycobacterioses.

Synthesis of 2-Amino-2-deoxy Sugars via Boron-Catalyzed Coupling of Glycosyl Fluorides and Silyl Ether Acceptors.

Although aminosugars are important components in a variety of bioactive molecules, their stereoselective formation is made challenging by the Lewis basic nature of amino substituents. Additionally, the use of N-acyl protecting groups is often problematic due to the competing formation of oxazolines during the glycosylation of 2-aminosugar derivatives. Herein, we report a boron-catalyzed strategy utilizing silyl ether glycosyl acceptors and 2-aminosugar donors that employs the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group for the C2 amino functionality in glycosyl fluorides. This modification allows for operationally simple room-temperature glycosylations and features a rapid reaction profile that addresses some of the limitations in the synthesis of 2-amino-2-deoxy sugar-containing glycosides. Tailoring the order of reactivity of the silyl acceptors enables one-pot iterative glycosylations, thus streamlining the synthesis of complex oligosaccharides while allowing fewer intermediates and purification steps.

Effect of Silyl Ether Bulk on Excited-State Intramolecular Proton Transfer-Based Sensing of Extant Hydrogen Fluoride for G-Series Nerve Agent Detection.

Luminescence-based sensing provides a method for the rapid detection of nerve agents. Previous approaches have generally focused on sensing materials containing a nucleophilic group that can react with the electrophilic phosphorus atom found in nerve agents. Herein we report an alternative approach for the detection of phosphonofluoridate-based G-series nerve agents that utilizes the fact they contain hydrogen fluoride. We have developed silylated sensing materials based on an excited-state intramolecular proton transfer (ESIPT) reporter compound, 2-[benzo[d]thiazol-2-yl]phenol. Thin films of differently silylated 2-[benzo[d]thiazol-2-yl]phenol were found to react with the hydrogen fluoride found in di-iso-propyl fluorophosphate (DFP), a simulant of sarin (G-series nerve agent), and turn on the ESIPT emission of the reporter compound. The use of the ESIPT emission reduced the impact of background fluorescence and improved the sensitivity of the detection. The effectiveness of the approach was dependent on the stability of the silyl protecting group used, with the least sterically hindered (trimethylsilyl) found to be too unstable to the ambient environment while the most sterically hindered, e.g., tri-iso-propylsilyl and tert-butyldiphenylsilyl were found to be insufficiently reactive to be useful in a real detection scenario. The sensing material composed of the tert-butyl dimethylsilyl protected 2-[benzo[d]thiazol-2-yl]phenol was found to have the best balance between stability under ambient conditions, and reactivity and selectivity to hydrogen fluoride. In a 3s exposure, it could detect hydrogen fluoride down to a concentration of around 23 ppm in DFP with 99% purity.

Intermolecular Formal [2π + 2σ] Cycloaddition of Enol Silyl Ethers with Bicyclo[1.1.0]butanes Promoted by Lewis Acids.

Silyl enol ethers react with bicyclo[1.1.0]butanes (BCBs) through Yb(OTf)3-promoted formal [2π + 2σ] cycloaddition reactions to furnish bicyclo[2.1.1]hexanes (BCHs). This new reaction tolerated a wide range of enol silyl ethers and BCBs. Furthermore, the amplification experiments and synthetic transformations of the cycloaddition compounds further highlighted their practicality.

Asymmetric Synthesis of α-Arylcyclohexenones Catalyzed by Diphenylprolinol Silyl Ether.

A general methodology for the asymmetric synthesis of α-arylcyclohexeneones from arylacetones and α,β-unsaturated aldehydes catalyzed by diphenylprolinol silyl ether followed by p-TSA-mediated cyclization is developed. A variety of arylacetones and α,β-unsaturated aldehydes were successfully converted to α-arylcyclohexeneones in 34-67% yield, 10:1-100:0 dr, and 81-99% ee. The scalability of this methodology by a gram-scale synthesis and their utility by converting the product to the corresponding epoxide, alcohol, and diol are demonstrated.

A comprehensive gas chromatography electron ionization high resolution mass spectrometry study of a new steroidal selective androgen receptor modulator (SARM) compound S42.

The synthetic 20-keto-steroid S42 (1) demonstrated selective androgen receptor modulator (SARM) properties in preclinical studies and, consequently, received growing attention also in the context of sports drug testing programs. Fundamental understanding of the behavior of S42 (1) and of relevant derivatives in gas chromatography-electron ionization MS experiments at high resolution (GC-EI-HRMS) is indispensable to develop a reliable qualitative and quantitative doping control method for S42 (1) and its metabolites in body fluid matrices. We present important fundamental mechanistic data on the EI fragmentation behavior of S42 (1) and of silyl ether derivatives as well as of stable isotope-labelled reference material.

Ring Rearrangement Reactions of 4-Alkenylisocoumarins and Photophysical Evaluation of Multi-Substituted Anthracene Products.

Herein we report that readily available 4-alkenylisocoumarins can be regarded as potent dienolate equivalents. For example, lactol silyl ethers derived from 4-alkenylisocoumarins were selectively converted to the corresponding benzo-homophthalates through a fluoride-induced ring opening step that was followed by a ring closure through a vinylogous intramolecular aldol condensation. Likewise, nucleophilic activation of 4-alkenylisocoumarins directly yields diversely poly-substituted naphthalenes and anthracenes without formation of any regioisomer. Photophysical evaluation of a set of thus obtained 1,3-di- and 1,3,4-trisubstituted anthracenes reveals their distinct intramolecular charge transfer (ICT) character during light absorption in polar solutions and excimer emission from the solid state when a face-to-face π-stacked molecular assembly is present in the crystal packing.

Unveiling the Reactivity of Part Per Million Levels of Cobalt-Salen Complexes in Hydrosilylation of Ketones.

A series of air-stable cobalt(III)salen complexes Co-1 to Co-4 have been synthesized and employed in the hydrosilylation of ketones. Notably, the most intricately tailored Co-3 pre-catalyst exhibited exceptional catalytic activity under mild reaction conditions. The developed catalytic hydrosilylation protocol proceeded with an unusual ppm level (5 ppm) catalyst loading of Co-3 and achieved a maximum turnover number (TON) of 200,000. A wide variety of aromatic, aliphatic, and heterocyclic ketones encompassing both electron-donating and electron-withdrawing substituents were successfully transformed into the desired silyl ethers or secondary alcohols in moderate to excellent yields.