Trityl Cation Research Articles

Video Documented Upscaled Synthesis of Salts of the Parent Carbaborate Ion [CB11H12]−, its Undecafluorinated Form [CHB11F11]− and Useful Starting Materials for its Introduction

AbstractIn this work, we present our improved protocols for the single batch syntheses of approximately 32 g of [NHMe3][CB11H12] and 10 g of Na[CHB11F11] as well as salt metathesis reactions, granting access to useful starting materials to introduce the [CHB11F11]− anion. This includes the trityl cation [Ph3C]+ and the bis‐1,2‐difluorobenzene‐silver(I)‐complex [Ag(odfb)2]+, as well as some applications of the shown compounds. The described methodology allows the synthesis of large amounts of both the [CB11H12]− and the [CHB11F11]− anion and therefore making them accessible for further reactions. To facilitate the reproducibility, we present video tutorials of the synthetic steps towards Na[CHB11F11].

(Invited) Spironanographenes: Chemospecific Scholl Reaction, Unexpected Formation of Bilayers and Donor-Acceptor Behavior

Bottom-up benchtop synthesis of nanometric fragments of graphene, molecular nanographenes (NGs), allows the design and monodisperse preparation of molecules with structures, and thus properties, at will. The most commonly employed methodology has mainly consisted in the π-extension of a central scaffold followed by a graphitization step, in which the honeycomb pattern of the final molecular nanographene is formed. The vast majority of syntheses involving molecular nanographenes, employ the Scholl reaction as graphitization step. This dehydrogenative C–C coupling, first described by Roland Scholl in 1910, has now become one of the most powerful reactions in NGs synthesis, although its mechanism pathway is still under debate.In this connection, in early 2023, we reported a chemospecific Scholl reaction depending on the electronic nature of the central scaffold. The formation of stabilized trityl cations using anthracene as central scaffold, led to the formation of spirocycles under Scholl reaction conditions, without interrupting the graphitization process, for the first time (Figure a).1 In contrast, the destabilization of the trityl cation by including fluorine atoms afforded helically arranged NGs (Figure b).2 Furthermore, in order to study the electronic communication in spironanographenes, recently we have extended the π-system of spirobifluorene yielding to two-fold chiral spironanographenes (Figure c). Surprinsingly, the π-π interactions of the graphitic moieties avoid their orthogonal disposition yielding a bilayer that could lead to important electronic features due to the overlap of the two fragments (Figure d).3 [1] P. Izquierdo-García, J. M. Fernández-García, J. Perles, I. Fernández, N. Martín. Angew. Chem. Int. Ed. 2023, 62, e202215655[2] P. Izquierdo-García, J. M. Fernández-García, I. Fernández, J. Perles, N. Martín. J. Am. Chem. Soc. 2021, 143, 11864–11870.[3] P. Izquierdo-Garcia, J. M. Fernandez-Garcia, S. Medina Rivero, M. Samal, J. Rybacek, L. Bednarova, S. Ramirez-Barroso, F. J. Ramirez, R. Rodriguez, J. Perles, D. Garcia-Fresnadillo, J. Crassous, J. Casado, I. G. Stara, N. Martin, J. Am. Chem. Soc. 2023, 145, 11599. Figure 1

An expanded framework toward improving the detritylation reaction in solid-phase oligonucleotide syntheses – filling the gap

A few interactions should be considered during the detritylation reaction of solid-phase oligonucleotide synthesis (SPOS): (i) interaction of solvent with acid; (ii) interaction (or reaction) of solvent with trityl cation, and (iii) interaction of scavenger with acid, with the last one as the focus of this work. Using a stopped-flow setup, commonly used trityl cation scavengers (methanol, thioanisole, 1-dodecanethiol, triisopropylsilane, triethylsilane, and trihexylsilane) were evaluated for their reactivity toward tritylium hexafluorophosphate. Among the scavengers screened, methanol and thioanisole were found to be the most and least reactive, respectively; however, methanol does interact and react with trichloroacetic acid, thus it should not be pre-mixed and stored with acid as deblock solutions. Overall, all aspects of interactions must be taken into consideration while optimizing the detritylation reaction, especially for large scale SPOS.

Dehydrative Alkylation of Phenols with Alcohols via Formation of Triflate.

An efficient synergistic trityl cation ([Ph3C][B(C6F5)4])/triflic anhydride (Tf2O) catalyzed alkylation of phenols with alcohols is reported. Benefiting from the formation of the triflate in situ, cheap and readily available active alcohols can be used as the alkylating reagents, and the reaction proceeds under mild reaction conditions with a broad substrate scope. This protocol enables the synthesis of ortho-selective phenols and 2,4,6-trisubstitued phenols containing three different alkyl groups. tert-Amyl triflate was synthesized, and mechanistic studies support a triflate-mediated alkylation process.

Pushing vs Pulling: The Unique Geometry of Mechanophore Activation in a Rotaxane Force Actuator.

Mechanophores (mechanosensitive molecules) are usually activated by pulling them with covalently attached polymers. A rotaxane actuator offers a new geometry of activation as the macrocycle pushes against a stoppering mechanophore. Here we compare both pulling and pushing activations and show that pushing is more efficient and selective than pulling. We found that the pulling activation of a bulky furan/maleimide adduct occurs via two competing dissociation pathways: retrocycloaddition and heterolytic cleavage (generating a trityl cation in the process), while the same adduct only cleaves by retrocycloaddition during pushing activation. These results further demonstrate the efficacy and versatility of rotaxane actuators.

Revisiting Textbook Azide-Clock Reactions: A "Propeller-Crawling" Mechanism Explains Differences in Rates.

An ongoing challenge to chemists is the analysis of pathways and kinetics for chemical reactions in solution, including transient structures between the reactants and products that are difficult to resolve using laboratory experiments. Here, we enabled direct molecular dynamics simulations of a textbook series of chemical reactions on the hundreds of ns to μs time scale using the weighted ensemble (WE) path sampling strategy with hybrid quantum mechanical/molecular mechanical (QM/MM) models. We focused on azide-clock reactions involving addition of an azide anion to each of three long-lived trityl cations in an acetonitrile-water solvent mixture. Results reveal a two-step mechanism: (1) diffusional collision of reactants to form an ion-pair intermediate; (2) "activation" or rearrangement of the intermediate to the product. Our simulations yield not only reaction rates that are within error of experiment but also rates for individual steps, indicating the activation step as rate-limiting for all three cations. Further, the trend in reaction rates is due to dynamical effects, i.e., differing extents of the azide anion "crawling" along the cation's phenyl-ring "propellers" during the activation step. Our study demonstrates the power of analyzing pathways and kinetics to gain insights on reaction mechanisms, underscoring the value of including WE and other related path sampling strategies in the modern toolbox for chemists.

Preparation and evaluation of in situ photocleavable mass tags with facile mass variation for matrix-free laser desorption ionization mass spectrometry.

Mass tags have been used for the precise identification, quantification, and characterization of macrobiomolecules and small organic molecules. Existing research has not yet demonstrated the preparation of a series of trityl-based photocleavable mass tags (PMTs) with similar structures but different molecular weights and mass variability. Herein, we introduce the design and synthesis of trityl-based in situ PMTs that generate heterolytic photocleavable cationic species upon laser irradiation. Mass variation of the PMTs was achieved via a simple conjugation reaction in the final step of synthesis. We prepared a series of PMTs with similar structures but different molecular weights and performed organic matrix-free laser desorption/ionization mass spectrometry (LDI MS) analysis. The practical applicability of the PMTs was evaluated by conjugating PMTs to oligonucleotides and utilizing them for detecting specific oligonucleotide targets combined with a mass signal amplification strategy. Quantitative aspects were also evaluated to verify the capability of the mass tags for multiplexed detection and the quantification of targets. The LDI MS analysis clearly demonstrated in situ heterolytic photocleavage that formed trityl cation peaks with high S/N ratios and high sensitivity. We strongly believe that the developed mass tags and LDI MS are useful alternatives to conventional signal transduction methods used for biosensors, such as surface plasmon resonance, electrochemical redox, and fluorescence.

(Invited) Conducting the Scholl Reaction: Spironanographenes Vs Helically Arranged Nanographenes

The stepwise synthesis of graphene molecular fragments, molecular nanographenes (NGs), allows the design and monodisperse preparation of sophisticated molecules with perfectly defined shapes and properties.1 The introduction of defects to the honeycomb pattern allows the preparation of nanographenes with finely tunable characteristics, as chirality. Helicenes and non-hexagonal rings are the most usual motifs to this end, as they generate axial chirality by diverting the structures from the 2D plane.In 2021 we reported a new family of molecular nanographenes in which the axial chirality results from the helical arrangement of the graphitized moieties covalently connected through a tetrafluorobenzene core 1.2 Although two enantiomers were confirmed by x-ray diffraction and chiral HPLC, racemization was observed.3 The isomerization process was evaluated, and the isomerization barrier resulted of ∆G≠= 24.6 kcal/mol at 40 ºC, which corresponds to a half-life time of t½ = 107 min.In order to modulate both optoelectronic and chiroptical properties we decided to increase the rigidity of the structure by introducing a 9,10-anthracene as central core. However, unexpected spironanographene 2 was obtained during the key step in the synthesis of nanographenes, the Scholl reaction. Under different reaction conditions we were able to obtain spirocompounds with different graphitization degree. Herein we reported the first spirocycles formation under Scholl reaction conditions without interrupting the graphitization process.4 To further understand the formation of the unexpected nanographenes, theoretical calculations were carried out and revealed the formation of a trityl cation that is involved in the formation of the spirocycles.Furthermore, in order to conduct the reaction towards the formation of the expected rigid helically arranged nanographene, an electron deficient core was designed. The substitution of the central anthracene with eight electron withdrawing fluorine atoms destabilizes the trityl cation and the expected helically arranged nanographene 3 was obtained.4 [1] Y. Gu, K. Müllen. J. Am. Chem. Soc. 2022 , 144, 11499–11524.[2] P. Izquierdo-García, J. M. Fernández-García, I. Fernández, J. Perles, N. Martín. J. Am. Chem. Soc. 2021, 143, 11864–11870.[3] J. M. Fernández-García, P. Izquierdo-García, M. Buendía, S. Filippone and N. Martín. Chem. Commun. 2022, 58, 2634-2645.[4] P. Izquierdo-García, J. M. Fernández-García, J. Perles, I. Fernández, N. Martín. Manuscript in preparation. Figure 1

Metal-Ligand Proton Tautomerism, Electron Transfer, and C(sp3)-H Activation by a 4-Pyridinyl-Pincer Iridium Hydride Complex.

The para-N-pyridyl-based PCP pincer proligand 3,5-bis(di-tert-butylphosphinomethyl)-2,6-dimethylpyridine (pN-tBuPCP-H) was synthesized and metalated to give the iridium complex (pN-tBuPCP)IrHCl (2-H). In marked contrast with its phenyl-based congeners, e.g., (tBuPCP)IrHCl and derivatives, 2-H is highly air-sensitive and reacts with oxidants such as ferrocenium, trityl cation, and benzoquinone. These oxidations ultimately lead to intramolecular activation of a phosphino-t-butyl C(sp3)-H bond and cyclometalation. Considering the greater electronegativity of N than C, 2-H is expected to be less easily oxidized than simple PCP derivatives; cyclic voltammetry and DFT calculations support this expectation. However, 2-H is calculated to undergo metal-ligand-proton tautomerism (MLPT) to give an N-protonated complex that can be described with resonance forms representing a zwitterionic complex (with a negative charge on Ir) and a p-N-pyridylidene (a remote N-heterocyclic carbene) Ir(I) complex. One-electron oxidation of this tautomer is calculated to be dramatically more favorable than direct oxidation of 2-H (ΔΔG° = -31.3 kcal/mol). The resulting Ir(II) oxidation product is easily deprotonated to give metalloradical 2• which is observed by NMR spectroscopy. 2• can be further oxidized to give cationic Ir(III) complex, 2+, which can oxidatively add a phosphino-t-butyl C-H bond and undergo deprotonation to give the observed cyclometalated product. DFT calculations indicate that less sterically hindered analogues of 2+ would preferentially undergo intermolecular addition of C(sp3)-H bonds, for example, of n-alkanes. The resulting iridium alkyl complexes could undergo facile β-H elimination to afford olefin, thereby completing a catalytic cycle for alkane dehydrogenation driven by one-electron oxidation and deprotonation, enabled by MLPT.

New photoacids in microarray synthesis of oligonucleotides

Photochemical activity of thiophene oxime esters and of sulfonium salt tris[4-(4-acetylphenyl)sulfanylphenyl]sulfonium tetrakis(2,3,4,5,6-pentafluorophenyl)boranuide (photoacid generator 290 [PAG 290]) was investigated in a reaction forming a trityl cation. Quantum yields of photoacid phototransformation reactions and of photodetritylation of 5′-O-(4,4′-dimethoxytrityl)thymidine were determined. Then, [(Z)-[(3Z)-3-[cyano(o-tolyl)methylene]-2-thienylidene]amino] 2,4,6-triisopropylbenzenesulfonate (H 365) and PAG 290 were used as detritylation photoactivators in a procedure of oligonucleotide synthesis on a microchip synthesizer prototype, and several oligonucleotides were synthesized. At the stage of oligonucleotide chain extension, the yield was 94–96%. The tested photoacids can be successfully applied to microchip synthesis of oligonucleotides.

A Guide to Tris(4-Substituted)-triphenylmethyl Radicals.

Triphenylmethyl (trityl, Ph3C•) radicals have been considered the prototypical carbon-centered radical since their discovery in 1900. Tris(4-substituted)-trityls [(4-R-Ph)3C•] have since been used in many ways due to their stability, persistence, and spectroscopic activity. Despite their widespread use, existing synthetic routes toward tris(4-substituted)-trityl radicals are not reproducible and often lead to impure materials. We report here robust syntheses of six electronically varied (4-RPh)3C•, where R = NMe2, OCH3, tBu, Ph, Cl, and CF3. The characterization reported for the radicals and related compounds includes five X-ray crystal structures, electrochemical potentials, and optical spectra. Each radical is best accessed using a stepwise approach from the trityl halide, (RPh)3CCl or (RPh)3CBr, by controllably removing the halide with subsequent 1e- reduction of the trityl cation, (RPh)3C+. These syntheses afford consistently crystalline trityl radicals of high purity for further studies.

Discrimination of the Enantiotopic Faces of Structurally Unbiased Carbenium Ions Employing a Cyclohexadiene-Based Chiral Hydride Source.

An enantioselective reduction of simple carbenium ions with cyclohexadienes containing a hydridic C-H bond at an asymmetrically substituted carbon atom is disclosed. The net reaction is a transfer hydrogenation of alkenes (styrenes) only employing chiral cyclohexadienes as dihydrogen surrogates. The trityl cation is used to initiate a Brønsted acid-promoted process, in which a delicate intermolecular capture of a carbenium-ion intermediate by the aforementioned chiral hydride source is enantioselectivity determining. Exclusively non-covalent interactions are rendering one of the transition states energetically more favored, giving the reduction products in good enantiomeric ratios. The computed reaction mechanism supports the present findings as well as previous results obtained from studies on other transfer-hydrogenation methods involving the cyclohexadiene platform.

Unterscheidung der enantiotopen Seiten von strukturell unvoreingenommenen Carbeniumionen unter Verwendung einer cyclohexadienbasierten, chiralen Hydridquelle

AbstractEs wird eine enantioselektive Reduktion von einfachen Carbeniumionen mit Cyclohexadienen, die eine hydridische C‐H‐Bindung an einem asymmetrisch substituierten Kohlenstoffatom tragen, vorgestellt. Die grundlegende Reaktion ist eine Transferhydrierung von Alkenen (Styrolen), bei der ausschließlich chirale Cyclohexadiene als Diwasserstoffsurrogate Anwendung finden. Das Tritylkation wird als Initiator dieses Brønsted‐Säure‐katalysierten Verfahrens eingesetzt, bei dem ein schwieriges intermolekulares Abfangen einer Carbeniumionenzwischenstufe durch die bereits erwähnte Hydridquelle enantioselektivitätsbestimmend ist. Lediglich nichtkovalente Wechselwirkungen begünstigen einen der Übergangszustände energetisch, was zu guten Enantiomerenverhältnissen der Hydrierungsprodukte führt. Der berechnete Reaktionsmechanismus sowie frühere Erkenntnisse aus Studien zu anderen Transferhydrierungsmethoden auf der Grundlage der Cyclohexadienplattform stützen die vorliegenden Ergebnisse.

Mechanochemical Synthesis and Reactivity of a Stable Nickel Borohydride

AbstractWe report the solvent‐assisted mechanochemically synthesised mononuclear Ni(II) borohydride complex supported by a macrocyclic tetradentate ligand. It was characterised as stable high‐spin [(LMe)Ni(η2‐BH4)]+ cation in solid‐state and in solution by various physicochemical methods and capable of transferring hydride. The stoichiometric reactivity of [(LMe)Ni(η2‐BH4)]+ cation was examined with trityl cation, alkyl halide, disulphide, thiol, carboxylic acid and enol at room temperature.

C-F Transformations of Benzotrifluorides by the Activation of Ortho-Hydrosilyl Group.

Single C-F transformations of aromatic trifluoromethyl compounds are challenging issues due to the strong C-F bond. We have recently developed selective methods for single C-F transformations such as allylation of o-hydrosilyl-substituted benzotrifluorides through the hydride abstraction with trityl cations. Single C-F thiolation and azidation of o-(hydrosilyl)benzotrifluorides were achieved using trityl sulfides and trityl azide catalyzed by Yb(OTf)3 . Treatment of o-(hydrosilyl)benzotrifluorides with trityl chloride resulted in single C-F chlorination. The resulting fluorosilyl group served in further transformations including protonation, halogenation, and Hiyama cross-coupling with C-Si cleavage. We also synthesized benzyl fluorides by LiAlH4 -reduction of the resulting fluorosilanes and further C-F transformations. These methods enabled us to prepare a broad range of organofluorines from simple benzotrifluorides through C-F and C-Si transformations.

Revealing the Electrophilic-Attack Doping Mechanism for Efficient and Universal p-Doping of Organic Semiconductors.

Doping is of great importance to tailor the electrical properties of semiconductors. However, the present doping methodologies for organic semiconductors (OSCs) are either inefficient or can only apply to some OSCs conditionally, seriously limiting their general applications. Herein, a novel p-doping mechanism is revealed by investigating the interactions between the dopant trityl tetrakis(pentafluorophenyl) borate (TrTPFB) and poly(3-hexylthiophene) (P3HT). It is found that electrophilic attack of the trityl cations on thiophenes results in the formation of tritylated thiophenium ions, which subsequently induce electron transfer from neighboring P3HT chains to realize p-doping. This unique p-doping mechanism enables TrTPFB to p-dope various OSCs including those with high ionization energy (IE≈5.8eV). Moreover, this doping mechanism endows TrTPFB with strong doping capability, leading to doping efficiency of over 80% in P3HT. The discovery and elucidation of this novel doping mechanism not only points out that strong electrophiles are a class of efficient p-dopants for OSCs, but also provides new opportunities toward highly efficient doping of various OSCs.

Trityl Cation-Catalyzed Hosomi-Sakurai Reaction of Allylsilane with β,γ-Unsaturated α-Ketoester to Form γ,γ-Disubstituted α-Ketoesters.

(Ph3C)[BPh(F)4]-catalyzed Hosomi-Sakurai allylation of allylsilanes with β,γ-unsaturated α-ketoesters has been developed to give γ,γ-disubstituted α-ketoesters in high yields with excellent chemoselectivity. Preliminary mechanistic studies suggest that trityl cation dominates the catalysis, while the silyl cation plays a minor role.

Recent advance in carbocation-catalyzed reactions

Carbocations such as tropylium and trityl cation, can be stable enough to be isolated and used without inert conditions. They can act as Lewis acids to lower the LUMO of electrophile, thus promoting reactions with nucleophiles. Additionally, the interaction between carbocations and alcohols can form Brønsted acids with enhanced acidity. Furthermore, electrophoto activation of TAC+ (trisaminocyclopropenium ion) delivers the excited radical dication TAC•2+*, which is a strong oxidant and capable of oxidizing a range of challenging substrates. Moreover, nPr-DMQA+ is disclosed as a versatile photoredox catalyst as its excited state can be quenched through both oxidation and reduction. This review summarizes recent advance in carbocation-catalyzed reactions. These developed methods provide an environmentally friendly pathway for the synthesis of valuable compounds and will inspire chemists to discover more interesting transformations promoted by carbocations.

Electronic Modification of a Sterically Demanding Anionic Pyridine Ligand

AbstractThe sterically demanding anionic pyridine ligand [4‐(Ph3B)‐2,6‐Mes2py]−([1]−) was used in salt metathesis reactions in order to obtain main group and transition metal complexes. Instead, reduction reactions were observed and identified as single electron transfer processes from [1]−to the respective Lewis acidic cations. The electron transfer was confirmed by reduction of the trityl cation. In order to reduce the reductive power of [1]−the borate function of the ligand was substituted with strongly electron withdrawing 3,5‐bis(trifluoromethyl)phenyl groups to give [1F]−. The redox potential was shifted from +0.56 V to +1.32 V and hence, [1F]−cannot reduce the trityl cation in contrast to [1]−. Consequently, the measured pKavalue of1F‐H (16.44) was lowered by two pKaunits compared with1‐H. Unfortunately, [1F]−still undergoes single electron transfer processes when used in salt metathesis reactions. We synthesized the anionic borane adduct [Li(THF)4][1F‐BH3] which demonstrates that [1F]−can be used as a ligand in main group chemistry. The determination of the crystal structures of [Li(THF)4][1F] and [Li(THF)4][1F‐BH3] revealed separated ion pairs while their analogs with the more electron rich [1]−are contact ion pairs.

The Tris(pentafluorophenyl)methylium Cation: Isolation and Reactivity.

Herein, we present two different routes for the synthesis of the perfluorinated trityl cation, which allowed the handling of the free, uncoordinated species in organic solvents for the first time. The usage of the weakly coordinating anion [Al(OTeF5)4]− and its derivatives allows the characterization of this species by NMR spectroscopy and most importantly by single‐crystal X‐ray diffraction. The high hydride ion affinity of the cation is shown by hydrogen abstraction from isobutane. Furthermore, cyclic voltammetry reveals its oxidative potential which is supported by the reaction with tris(4‐bromophenyl)amine, giving rise to the formation of the ammoniumyl radical cation, also known as “magic blue”.