Catalytic difunctionalization of unactivated alkenes with unreactive hexamethyldisilane through regeneration of silylium ions

A metal‐free, intermolecular syn‐addition of hexamethyldisilane across simple alkenes is reported. The catalytic cycle is initiated and propagated by the transfer of a methyl group from the disilane to a silylium‐ion‐like intermediate, corresponding to the (re)generation of the silylium‐ion catalyst. The key feature of the reaction sequence is the cleavage of the Si−Si bond in a 1,3‐silyl shift from silicon to carbon. A central intermediate of the catalysis was structurally characterized by X‐ray diffraction, and the computed reaction mechanism is fully consistent with the experimental findings.TU Berlin, Open-Access-Mittel - 201

Catalytic dehydrogenative Si-N coupling of pyrroles, indoles, carbazoles as well as anilines with hydrosilanes without added base

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.A base-free, catalytic protocol for the dehydrogenative Si–N coupling of weakly nucleophilic N–H groups of heteroarenes or aryl-substituted amines with equimolar amounts of hydrosilanes is reported. Cooperative Si–H bond activation at a Ru–S bond generates a silicon electrophile that forms a Si–N bond prior to the N–H deprotonation by an intermediate Ru–H complex, only releasing H2.DFG, GRK 1143, Komplexe chemische Systeme: Design, Entwicklung und Anwendunge

Efficient Biocatalytic Synthesis of Dihalogenated Purine Nucleoside Analogues Applying Thermodynamic Calculations

The enzymatic synthesis of nucleoside analogues has been shown to be a sustainable and efficient alternative to chemical synthesis routes. In this study, dihalogenated nucleoside analogues were produced by thermostable nucleoside phosphorylases in transglycosylation reactions using uridine or thymidine as sugar donors. Prior to the enzymatic process, ideal maximum product yields were calculated after the determination of equilibrium constants through monitoring the equilibrium conversion in analytical-scale reactions. Equilibrium constants for dihalogenated nucleosides were comparable to known purine nucleosides, ranging between 0.071 and 0.081. To achieve 90% product yield in the enzymatic process, an approximately five-fold excess of sugar donor was needed. Nucleoside analogues were purified by semi-preparative HPLC, and yields of purified product were approximately 50% for all target compounds. To evaluate the impact of halogen atoms in positions 2 and 6 on the antiproliferative activity in leukemic cell lines, the cytotoxic potential of dihalogenated nucleoside analogues was studied in the leukemic cell line HL-60. Interestingly, the inhibition of HL-60 cells with dihalogenated nucleoside analogues was substantially lower than with monohalogenated cladribine, which is known to show high antiproliferative activity. Taken together, we demonstrate that thermodynamic calculations and small-scale experiments can be used to produce nucleoside analogues with high yields and purity on larger scales. The procedure can be used for the generation of new libraries of nucleoside analogues for screening experiments or to replace the chemical synthesis routes of marketed nucleoside drugs by enzymatic processes.DFG, 390540038, EXC 2008: UniSysCatDFG, 414044773, Open Access Publizieren 2019 - 2020 / Technische Universität Berli

Synthese eines gegenanionstabilisierten Bis(silylium)ions

Es wird über die Darstellung eines Moleküls mit zwei alkylverknüpften Silyliumionzentren ausgehend vom entsprechenden Bis(hydrosilan) mittels zweifacher Hydridabstraktion berichtet. Die Länge der konformativ flexiblen Alkylbrücke ist entscheidend, denn sonst bleibt die Hydridabstraktion auf der Stufe eines cyclischen bissilylierten Hydroniumions stehen. Für den Fall einer Ethylenbrücke ist die offene Form der Hydroniumionzwischenstufe energetisch zugänglich und geht eine weitere Hydridabstraktion ein. Das daraus hervorgehende Bis(silylium)ion wurde NMR‐spektroskopisch und strukturell charakterisiert. Verwandte Systeme auf der Grundlage von starren Naphthalen‐n,m‐diylplattformen können nur dann in die Dikationen überführt werden, wenn die positiv geladenen Silyliumioneinheiten voneinander entfernt sind (1,8 gegenüber 1,5 und 2,6).DFG, 390540038, EXC 2008: Unifying Systems in Catalysis "UniSysCat

Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study

We recently reported a new method for the direct dehydrogenative C–H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si–H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with (KOt-Bu)_4 as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C–Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H_2 gas. In situ NMR experiments with deuterated substrates show that H_2 is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a ^2H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates

Silylium-ion-promoted (5+1) cycloaddition of aryl-substituted vinylcyclopropanes and hydrosilanes involving aryl migration

A transition-metal-free (5+1) cycloaddition of aryl-substituted vinylcyclopropanes (VCPs) and hydrosilanes to afford silacyclohexanes is reported. Catalytic amounts of the trityl cation initiate the reaction by hydride abstraction from the hydrosilane, and further progress of the reaction is maintained by self-regeneration of the silylium ions. The new reaction involves a [1,2] migration of an aryl group, eventually furnishing 4- rather than 3-aryl-substituted silacyclohexane derivatives as major products. Various control experiments and quantum-chemical calculations support a mechanistic picture where a silylium ion intramolecularly stabilized by a cyclopropane ring can either undergo a kinetically favored concerted [1,2] aryl migration/ring expansion or engage in a cyclopropane-to-cyclopropane rearrangement.DFG, 390540038, EXC 2008: Unifying Systems in Catalysis "UniSysCat"TU Berlin, Open-Access-Mittel – 202

Two-Silicon Cycle for Carbonyl Hydrosilylation with Nikonov’s Cationic Ruthenium(II) Catalyst

An experimental analysis proves that Nikonov’s carbonyl hydrosilylation proceeds through a two-silicon cycle rather than the originally proposed one-silicon cycle. The intermediate ruthenium­(II) monohydride is not sufficiently hydridic to transfer its hydride onto the silylcarboxonium ion. However, that hydricity is enhanced by oxidative addition of another hydrosilane molecule to afford the corresponding ruthenium­(IV) silyl dihydride as the actual hydride donor. The present study also demonstrates that the acetonitrile ligands in Nikonov’s ruthenium­(II) catalyst are not innocent. That complex is able to hydrosilylate its own ligand(s), and the resulting <i>N</i>,<i>N</i>-disilylated amine base accounts for competing dehydrogenative silylation of enolizable carbonyl compounds, explaining the formation of a silyl enol ether in substantial quantities next to the expected silyl ether. Both findings lead to a revised mechanistic picture that provides the basis for the development of more efficient and chemoselective catalysts

C(sp³)–F Bond Activation of CF₃‑Substituted Anilines with Catalytically Generated Silicon Cations: Spectroscopic Evidence for a Hydride-Bridged Ru–S Dimer in the Catalytic Cycle

Heterolytic splitting of the Si–H bond mediated by a Ru–S bond forms a sulfur-stabilized silicon cation that is sufficiently electrophilic to abstract fluoride from CF₃ groups attached to selected anilines. The ability of the Ru–H complex, generated in the cooperative activation step, to intramolecularly transfer its hydride to the intermediate carbenium ion (stabilized in the form of a cationic thioether complex) is markedly dependent on the electronic nature of its phosphine ligand. An electron-deficient phosphine thwarts the reduction step but, based on the Ru-S catalyst, half of an equivalent of an added alkoxide not only facilitates but also accelerates the catalysis. The intriguing effect is rationalized by the formation of a hydride-bridged Ru–S dimer that was detected by ¹H NMR spectroscopy. A refined catalytic cycle is proposed

Brønsted Acid-Promoted Formation of Stabilized Silylium Ions for Catalytic Friedel–Crafts C–H Silylation

A counterintuitive approach to electrophilic aromatic substitution with silicon electrophiles is disclosed. A strong Brønsted acid that would usually promote the reverse reaction, i.e., protodesilylation, was found to initiate the C–H silylation of electron-rich (hetero)­arenes with hydrosilanes. Protonation of the hydrosilane followed by liberation of dihydrogen is key to success, fulfilling two purposes: to generate the stabilized silylium ion and to remove the proton released from the Wheland intermediate