Silyl Group Research Articles

Room Temperature Intermolecular Dearomatization of Arenes by an Acyclic Iminosilylene.

A novel nontransient acyclic iminosilylene (1), bearing a bulky super silyl group (-SitBu3) and N-heterocyclic imine ligand with a methylated backbone, was prepared and isolated. The methylated backbone is the feature of 1 that distinguishes it from the previously reported nonisolable iminosilylenes, as it prevents the intramolecular silylene center insertion into an aromatic C-C bond of an aryl substituent. Instead, 1 exhibits an intermolecular Büchner-ring-expansion-type reactivity; the silylene is capable of dearomatization of benzene and its derivatives, giving the corresponding silicon analogs of cycloheptatrienes, i.e. silepins, featuring seven-membered SiC6 rings with nearly planar geometry. The ring expansion reactions of 1 with benzene and 1,4-bis(trifluoromethyl)benzene are reversible. Similar reactions of 1 with N-heteroarenes (pyridine and DMAP) proceed more rapidly and irreversibly forming the corresponding azasilepins, also with nearly planar seven-membered SiNC5 rings. DFT calculations reveal an ambiphilic nature of 1 that allows the intermolecular aromatic C-C bond insertion to occur. Additional computational studies, which elucidate the inherent reactivity of 1, the role of the substituent effect, and reaction mechanisms behind the ring expansion transformations, are presented.

Super silyl-based stable protecting groups for both the C- and N-terminals of peptides: applied as effective hydrophobic tags in liquid-phase peptide synthesis.

Tag-assisted liquid-phase peptide synthesis (LPPS) is one of the important processes in peptide synthesis in pharmaceutical discovery. Simple silyl groups have positive effects when incorporated in the tags due to their hydrophobic properties. Super silyl groups contain several simple silyl groups and play an important role in modern aldol reactions. In view of the unique structural architecture and hydrophobic properties of the super silyl groups, herein, two new types of stable super silyl-based groups (tris(trihexylsilyl)silyl group and propargyl super silyl group) were developed as hydrophobic tags to increase the solubility in organic solvents and the reactivity of peptides during LPPS. The tris(trihexylsilyl)silyl group can be installed at the C-terminal of the peptides in ester form and N-terminal in carbamate form for peptide synthesis and it is compatible with hydrogenation conditions (Cbz chemistry) and Fmoc-deprotection conditions (Fmoc chemistry). The propargyl super silyl group is acid-resistant, which is compatible with Boc chemistry. Both tags are complementary to each other. The preparation of these tags requires less steps than previously reported tags. Nelipepimut-S was synthesized successfully with different strategies using these two types of super silyl tags.

Solid-state mechanochemical cross-coupling of insoluble substrates into insoluble products by removable solubilizing silyl groups: uniform synthesis of nonsubstituted linear oligothiophenes.

Conventional solution-based organic reactions that involve insoluble substrates are challenging and inefficient. Furthermore, even if the reaction is successful, the corresponding products are insoluble in most cases, making their isolation and subsequent transformations difficult. Hence, the conversion of insoluble compounds into insoluble products remains a challenge in practical synthetic chemistry. In this study, we showcase a potential solution to address these solubility issues by combining a mechanochemical cross-coupling approach with removable solubilizing silyl groups. Our strategy involves solid-state Suzuki-Miyaura cross-coupling reactions between organoboron nucleophiles bearing a silyl group with long alkyl chains and insoluble polyaromatic halides. The silyl group on the nucleophile can act as a solubilizing group that enables product isolation via silica gel column chromatography and can be easily removed by the addition of fluoride anions to form the desired insoluble coupling products with sufficient purity. Furthermore, we demonstrate that after aromatic electrophilic bromination of the desilylated products, sequential solid-state cross-coupling of the obtained insoluble brominated substrates, followed by desilylation, afforded further π-extended functional molecules. Using this conceptually new protocol, we achieved the first uniform synthesis of the longest nonsubstituted linear insoluble 9-mer oligothiophene.

Dual photoredox nickel-catalyzed silylation of aryl/heteroaryl bromides using hydrosilanes.

Dual Ni and Ir catalysis enables the preparation of arylsilanes having a (TMS)3Si substituent from the corresponding aryl bromides and (TMS)3SiH at 30 °C using visible-light irradiation. This protocol avoids strong bases, high temperature and air and moisture sensitive silyl reagents, providing the expected arylsilanes in moderate to good yields. The reaction was shown to proceed through a silyl radical, likely generated by hydrogen atom abstraction from (TMS)3SiH by a bromide radical.

Reversible C-H bond silylation with a neutral silicon Lewis acid.

The silicon-carbon bond is a valuable linchpin for synthetic transformations. However, installing Si-C functionalities requires metalated C-nucleophiles, activated silicon reagents (silylium ions, silyl radicals, and silyl anions), or transition metal catalysis, and it occurs irreversibly. In contrast, spontaneous C-H silylations with neutral silanes leading to anionic silicates, and their reversible deconstruction, are elusive. Herein, the CH-bond silylation of heterocycles or a terminal alkyne is achieved by reaction with bis(perfluoro(N-phenyl-ortho-amidophenolato))silane and 1,2,2,6,6-pentamethylpiperidine. Computational and experimental insights reveal a frustrated Lewis pair (FLP) mechanism. Adding a silaphilic donor to the ammonium silicate products induces the reformation of the C-H bond, thus complementing previously known irreversible C-H bond silylation protocols. Interestingly, the FLP "activated" N-methylpyrrole exhibits "deactivated" features against electrophiles, while a catalytic functionalization is found to be effective only in the absence of a base.

Organophotocatalytic silyl transfer of silylboranes enabled by methanol association: a versatile strategy for C–Si bond construction

A visible light-induced organophotocatalytic silyl transfer strategy of silylboranes for the construction of C–Si bonds has been demonstrated, where methanol association with boron atoms enables the photocatalytic generation of silyl radicals.

Metal-free reductive desulfurization of C-sp3-substituted thiols using phosphite catalysis.

Phosphines and phosphites are critical tools for non-metal desulfurative methodologies due to the strength of the P[double bond, length as m-dash]S bond. An overarching premise in these methods has been that stoichiometric (or excess) P(iii) reagent is required for reactivity. Despite decades of research, a desulfurative process that is catalytic in phosphine/phosphite has not been reported. Here, we report the successful merging of two thermal radical processes: the desulfurization of unactivated and activated alkyl thiols and the reduction of P(v) = S to P(iii) by reaction with a silyl radical species. We employ catalytic trimethyl phosphite, catalytic azo-bis(cyclohexyl)nitrile, and two equivalents of tris(trimethylsilyl)silane as the stoichiometric reductant and sulfur atom scavenger. This method is tolerant of common organic functional groups and affords products in good to excellent yields.

Visible-light-induced decarboxylation/defluorosilylation protocol for synthesis ofgem-difluoroalkenes

A catalytic defluorosilylation is disclosed that provides a concise route togem-difluoroallylsilanes with broad functional-group compatibility from trifluoromethylalkenes and silacarboxylic acids, stable silyl radical precursors.

Synthesis of propargyl silanes from terminal alkynes via a migratory Sonogashira reaction.

Herein we report a mild synthesis of propargyl silanes from terminal alkynes. We exploit a bromonaphthyl-substituted silane as a silylmethyl electrophile surrogate, which participates in a Sonogashira reaction after an aryl-to-alkyl Pd-migration. Twenty-seven propargyl silanes were obtained in up to 88% yield. The obtained products were versatile building blocks that can be used in addition to electrophiles, triple bond hydrogenation or silyl group cleavage with acid or fluoride sources.

New cationic coinage metal complexes featuring silyl group functionalized phosphine: syntheses, structures and catalytic studies in alkyne-azide cycloaddition reactions.

A series of coinage metal complexes bearing rarely explored ortho-silylated phosphine is reported. The treatment of diphenyl(2-(trimethylsilyl)phenyl)phosphine (1) with CuCl and [Cu(CH3CN)4]BF4 furnished the corresponding neutral [(1)CuCl]2 (2) and mono-cationic [(1)2Cu(CH3CN)]BF4 (3) complexes, respectively. The reactions of 1 with AgX (X = BF4-, NO3-) in 2 : 1 ratio furnished the corresponding mono cationic dicoordinate silver(I) complexes of the type [(1)2Ag]X (X = BF4- (4a), NO3- (4b)). The ortho-silylated phosphine ligand (1) was conveniently converted into the corresponding sulfide (5a) and selenide (5b) species, and their reactions with [Cu(CH3CN)4]BF4 yielded mono-cationic, homoleptic tris(silylphosphinochalcogenide)copper(I) complexes of the type [(5a/5b)3Cu]BF4 (6a/6b). The molecular structures of 2-4 and 6 were established by single-crystal X-ray diffraction analysis. The copper complexes 2, 3, and 6a were employed as catalysts in azide-alkyne cycloaddition reactions. Among these complexes, 3 was extensively used in the preparation of various mono- and bis-triazoles consisting of tolyl, benzyl, carbazolyl, and propargylic ether groups. Three sets of substituted triazole derivatives were achieved under mild conditions by employing copper(I) catalytic systems. The mechanistic studies indicated the formation of a heteroleptic copper(I) triazolide intermediate which was detected by high-resolution mass spectral analysis.

Five Triisopropylsilyl Substituents in Ara‐β‐(1→2)‐Ara Disaccharide Glycosyl Donor Make Unselective Glycosylation Reaction Stereoselective

AbstractFormation of 1,2‐trans‐arabinofuranoside linkage in arabinans fromMycobacterium tuberculosisusing differently protected Ara‐β‐(1→2)‐Ara disaccharide glycosyl donors in the absence of a participating group at O‐2 was studied. The influence of the nature of the protective and leaving groups in glycosyl donors on the efficiency and stereoselectivity of the 1,2‐trans‐arabinofuranosylation was investigated. The efficiency of Ara‐β‐(1→2)‐Arap‐tolyl thioglycoside containing five triisopropylsilyl groups in 1,2‐trans‐stereoselective synthesis of a protected tetrasaccharide corresponding to a fragment of theM. tuberculosisarabinan was shown for the first time. On the contrary, the use of glycosyl donors based on Ara‐β‐(1→2)‐Ara containing only benzoyl or both silyl and benzoyl groups led to the loss of stereocontrol.

Diphenylsilylsilanolates Enable the Transfer of a Wide Range of Silyl Groups.

Development of silylating reagents that can transfer a wide range of silyl groups has been a long-standing challenge. Herein we report sodium diphenylsilylsilanolates as new stable and handy silylating reagents that could be synthesized from chlorosilanes. The new reagents retain the ability of dimethylsilylsilanolates for the delivery of a variety of silyl groups in palladium-catalyzed silylation of aryl bromides irrespective of the steric and electronic properties of silyl groups to be transferred.

Synthesis of (S)-Nyasol through a Copper-Catalyzed Propargylic Substitution

Abstract(S)-Nyasol was selected as a target to demonstrate the efficiency of a copper-catalyzed substitution of secondary propargylic phosphates. The key phosphate (R)-TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)]OP(O)(OEt)2 was synthesized from TBDPSO(CH2)2CO2H in four steps. Substitution of the phosphate with 4-TBSOC6H4MgBr in the presence of CuBr·Me2S as a catalyst in THF–DME proceeded with both stereo- and regioselectivity at the propargylic position. All the silyl groups in the propargylic product, TBDPSO(CH2)2CH[C≡C(C6H4-4-OTBS)](C6H4-4-OTBS) were removed, and the acetylene bond was reduced by using active Zn to produce the cis-olefin. Finally, the HO(CH2)2 moiety was converted into CH2=CH, giving (S)-nyasol with 97% cis selectivity, 94.5% ee, and >99% enantiospecificity. Similarly, dihydronyasol was synthesized through hydrogenation of the substitution product, followed by construction of the terminal olefin.

Silicon Carbide Precursor: Structure Analysis and Thermal Behavior from Polymer Cross-Linking to Pyrolyzed Ceramics

The Silres H62C methyl-phenyl-vinyl-hydrogen polysiloxane is a promising candidate as a SiC precursor for 3D printing based on photopolymerization reaction. An in-depth nuclear magnetic resonance spectroscopy analysis allowed us to determine its structure and quantify its functional groups. The polysiloxane was found to have a highly branched ladder-like structure, with 21.9, 31.4 and 46.7% of mono-, di- and tri-functional silicon atoms. The polysiloxane cross-links from 180 °C using hydrosilylation between silyl groups (8.4% of the total functional groups) and vinyl groups (12.0%) and contains a non-negligible ethoxy content (2.4%), allowing cross-linking through a hydrolyze/condensation mechanism. After converting the polymer into ceramic and thus releasing mainly hydrogen and methane, the ceramic yield was 72.5%. An X-ray diffraction analysis on the cross-linked and pyrolyzed polysiloxane showed that the ceramic is amorphous at temperatures up to 1200 °C and starts to crystallize from 1200 °C, leading into 3C-SiC carbon-rich ceramic at 1700 °C in an argon atmosphere.

Regioselective Ni-Catalyzed reductive alkylsilylation of acrylonitrile with unactivated alkyl bromides and chlorosilanes

Transition-metal catalyzed carbosilylation of alkenes using carbon electrophiles and silylmetal (-B, -Zn) reagents as the nucleophiles offers a powerful strategy for synthesizing organosilicones, by incorporating carbon and silyl groups across on C-C double bonds in one step. However, to the best of our knowledge, the study of silylative alkenes difunctionalization based on carbon and silyl electrophiles remains underdeveloped. Herein, we present an example of silylative alkylation of activated olefins with unactivated alkyl bromides and chlorosilanes as electrophiles under nickel catalysis. The main feature of this protocol is employing more easily accessible substrates including primary, secondary and tertiary alkyl bromides, as well as various chlorosilanes without using pre-generated organometallics. A wide range of alkylsilanes with diverse structures can be efficiently assembled in a single step, highlighting the good functionality tolerance of this approach. Furthermore, successful functionalization of bioactive molecules and synthetic applications using this method demonstrate its practicability.

Visible-Light-Mediated Radical Silyl-Oximation of Activated Alkenes Using tert-Butyl Nitrite and Silanes.

A metal-free radical 1,2-difunctionalization of activated alkenes with various silanes and tert-butyl nitrite is reported. The radical cascade occurs by light-promoted homolytic O-NO bond cleavage of tert-butyl nitrite and subsequent hydrogen atom abstraction by the alkoxyl radical from the silane. Silyl radical addition to the alkene and highly selective cross-coupling of the NO radical with the Si-adduct C-radical provide the silyl-oximation product in moderate to good yields. The reaction features good functional group tolerance and is easily scaled up.

Sialylations reactions: Expanding the effect of silicon protecting groups at C-4

As a part of a general research goal into evaluating the effect of O-protecting groups in sialylation reactions, we compared the reactivities of phenylthio α- and β-sialyl donors protected at C-4 with tert-butyldimethyl silyl (TBDMS) and tri-isopropylsilyl (TIPS) groups in the coupling with primary and secondary galactosyl acceptors. The effect of the solvent and the donor's anomeric configuration were investigated and compared to previously published data. It is demonstrated that silicon groups at C-4 have a significant influence on sialylation reactions, and in general their overall performance is optimized with the use of acetonitrile.

On the role of β-silyloxy- and β-alkoxyaldehyde protecting groups in Mukaiyama aldol 1,3-diastereocontrol

Longstanding paradigmatic studies have noted anti-1,3-diastereocontrol in Mukaiyama aldol reactions with β-silyloxy- and β-alkoxyaldehydes. In our efforts to exploit this stereocontrol, we found that an aldehyde of this type that lacks branching at the γ-carbon led to eroded diastereoselectivity that was restored upon changing the β-protecting group. This suggested the hypothesis that 1,3-anti selectivity in these cases is inversely dependent on the size of the β-protecting group. In testing this hypothesis, Mukaiyama aldol reactions of several analogs of unbranched β-silyloxy- and β-alkoxyaldehydes, varying only the protecting group, showed improved selectivity with smaller silyl and alkyl groups. These results will aid synthetic design as well as provide experimental benchmarks for computational studies.

Development of a Library of Extremely Bulky Amide Ligands, and their use for the Stabilization of Germanium(I) and Germanium(II) Compounds

AbstractEleven new extremely bulky aryl/silyl substituted secondary amines, L1–11H, have been prepared. These incorporate a combination of one of the bulky aryl groups, C6H2{C(H)Ph2}2R‐2,6,4; R=Me (Ar*), Pri (Ar†); C6H2{C(H)(C6H3But2‐3,5)2}2Me‐2,6,4) (Ar#); or C6H2{C(H)(2‐naphthyl)2}2Me‐2,6,4 (Ar¥), and one of the silyl fragments, SiMe3, SiCy3 (Cy=cyclohexyl), SiPri3, Si(p‐C6H4But)3, or Si(OBor)3 (OBor=[(1S)‐endo]‐(−)‐borneoxy). Amines including the latter silyl group represent the first enantiopure examples of this ligand class. All amines are readily deprotonated with n‐butyllithium or KH. Reactions of five alkali metal amide complexes with GeCl2⋅dioxane have given monomeric amido‐germanium(II) chloride complexes, LxGeCl (x=1–4, 7). Treatment of two of these with KOBut afforded monomeric amido‐germanium(II) tert‐butoxide species, LxGeOBut (x=1 or 3). Reductions of two amido‐germanium(II) chloride systems with a dimagnesium(I) compound afforded amido‐digermyne species, LxGeGeLx (x=3 or 4), the X‐ray crystal structures of which show them to possess very short Ge−Ge bonds, with considerable implied multiple bond character.

Photocatalytic Generations of Secondary and Tertiary Silyl Radicals from Silylboranes Using an Alkoxide Cocatalyst.

Silyl radicals are valuable species to prepare diverse organosilicon compounds. However, unlike stable tertiary silyl radicals, the use of secondary silyl radicals has been problematic in silylation reactions due to their instability. Here, we present photocatalytic in situ generations of both secondary and tertiary silyl radicals by one-electron oxidation of ate complexes, formed from silylboranes and an alkoxide cocatalyst, achieving highly efficient hydrosilylation and deuterosilylation of electron-rich alkenes and dienes as well as electron-deficient alkenes. The theoretical studies show that anionic borate complexes activated with an alkoxide have lower oxidation potentials than neutral borate complexes, allowing the formation of secondary silyl radicals. The calculated reaction pathways reveal that anionic conditions using the conjugate acid-base pair of NaOEt (cocatalyst) and EtOH (solvent) are the key to expanding the scope of silyl radicals and alkenes.