Exploration of Vitamin B6-Based Redox-Active Pyridinium Salts Towards the Application in Aqueous Organic Flow Batteries.

Pyridoxal hydrochloride, a vitamin B6 vitamer, was synthetically converted to a series of diverse redox-active benzoyl pyridinium salts. Cyclic voltammetry studies demonstrated redox reversibility under basic conditions, and two of the most promising salts were subjected to laboratory-scale flow battery tests involving galvanostatic cycling at 10 mM in 0.1 M NaOH. In these tests, the battery was charged completely, corresponding to the transfer of two electrons to the electrolyte, but no discharge was observed. Both CV analysis and electrochemical simulations confirmed that the redox wave observed in the experimental voltammograms corresponds to a two-electron process. To explain the irreversibility in the battery tests, we conducted bulk electrolysis with the benzoyl pyridinium salts, affording the corresponding benzylic secondary alcohols. Computational studies suggest that the reduction proceeds in three consecutive steps: first electron transfer (ET), then proton-coupled electron transfer (PCET) and finally proton transfer (PT) to give the secondary alcohol. 1H NMR deuterium exchange studies indicated that the last PT step is not reversible in 0.1 M NaOH, rendering the entire redox process irreversible. The apparent reversibility observed in CV at the basic media likely arises from the slow rate of the PT step at the timescale of the measurement.

"Inverted" Cyclic(Alkyl)(Amino)Carbene (CAAC) Ruthenium Complex Catalyzed Isomerization Metathesis (ISOMET) of Long Chain Olefins to Propylene at Low Ethylene Pressure.

Isomerization Metathesis (ISOMET) reaction is an emerging tool for "open loop" chemical recycling of polyethylene to propylene. Novel, latent N-Alkyl substituted Cyclic(Alkyl)(Amino)Carbene (CAAC)-ruthenium catalysts (5a-Ru, 3b-Ru - 6c-Ru) are developed rendering "inverted" chemical structure while showing enhanced ISOMET activity in combination with (RuHCl)(CO)(PPh3)3 (RuH) double bond isomerization co-catalyst. Systematic investigations reveal that the steric hindrance of the substituents on nitrogen and carbon atom adjacent to carbene moiety in the CAAC ligand have significantly improved the catalytic activity and robustness. In contrast to the NHC-Ru and CAAC-Ru catalyst systems known so far, these systems show higher isomerization metathesis (ISOMET) activity (TON: 7400) on the model compound 1-octadecene at as low as 3.0 bar optimized pressure, using technical grade (3.0) ethylene. The propylene content formed in the gas phase can reach up to 20% by volume.

Activation of H2 using ansa-aminoboranes: solvent effects, dynamics, and spin hyperpolarization.

Spin hyperpolarization generated upon activation of parahydrogen, the spin-0 isomer of H2, by ansa-aminoboranes (AABs) constitutes a rare but interesting example of applied metal-free catalysis in parahydrogen-induced polarization (PHIP). AAB molecular moieties made of light elements would be useful in important areas of NMR, such as chemosensing and the production of hyperpolarized substances, or generally in NMR sensitivity enhancement. At the same time, little is known about the detailed mechanistic aspects of underlying chemical processes. Herein, we present a joint experimental-computational study of the kinetic and thermodynamic aspects of H2 activation by AABs, for the first time providing molecular-level details and results of PHIP experiments with AABs in various solvents. Specifically, a large number of kinetic and thermodynamic parameters are measured experimentally for H2 activation by 2-aminophenylboranes of variable steric bulkiness of the boryl site. A clear correlation between the experimental and DFT-predicted thermochemical parameters is observed. PHIP effects in toluene, dichloromethane, and acetonitrile are characterized and rationalized based on the use of the kinetic and nuclear spin relaxation parameters. Altogether, the obtained results provide valuable information for the further rational design of efficient AAB catalysts for metal-free PHIP based on frustrated Lewis pair (FLP) chemistry.

N-Alkylated Pyridoxal Derivatives as Negative Electrolyte Materials for Aqueous Organic Flow Batteries: Computational Screening.

N-functionalized pyridinium frameworks derived from the three major vitamers of vitamin B6, pyridoxal, pyridoxamine and pyridoxine, have been screened computationally for consideration as negative electrode materials in aqueous organic flow batteries. A molecular database including the structure and the one-electron standard reduction potential of related pyridinium derivatives has been generated using a computational protocol that combines semiempirical and DFT quantum chemical methods. The predicted reduction potentials span a broad range for the investigated pyridinium frameworks, but pyridoxal derivatives, particularly those involving electron withdrawing substituents, have potentials compatible with the electrochemical stability window of aqueous electrolytes. The stability of radicals formed upon one-electron reduction has been analyzed by a new computational tool proposed recently for large-scale computational screening.

Late-Stage Formal Double C-H Oxidation of Prenylated Molecules to Alkylidene Oxetanes and Azetidines by Strain-Enabled Cross-Metathesis.

Prenylation is a ubiquitous late-stage modification in nature that often confers significantly improved bioactivity for secondary metabolites. While this lipophilic modification renders enhanced potency, the lipophilic tag(s) can diminish bioavailability and adversely alter drug transportation and metabolism. Thus, a functional-group-tolerant, mild, and selective late-stage C-H functionalization of prenyl tags would present a great potential in drug discovery programs but could also impact other fields, such as agrochemistry and chemical biology. Herein we report an exocyclic-strain-driven cross-metathesis reaction of prenyl tags, a formal double C-H oxidation protocol, that can be used for the selective late-stage derivatization of prenylated compounds and natural products. This methodology avoids the need for prefunctionalization of target molecules and affords ready access to an unprecedented library of oxo- and aza-prenylated complex molecules. Thus, in a broader context, this methodology extends late-stage functionalization beyond that available to nature.

Carboxylate Catalyzed Isomerization of ß,γ-Unsaturated N-Acetylcysteamine Thioesters.

We demonstrate herein the capacity of simple carboxylate salts - tetrametylammonium and tetramethylguanidinium pivalate - to act as catalysts in the isomerization of ß,γ-unsaturated thioesters to α,ß-unsaturated thioesters. The carboxylate catalysts gave reaction rates comparable to those obtained with DBU, but with fewer side reactions. The reaction exhibits a normal secondary kinetic isotope effect (k1H /k1D =1.065±0.026) with a ß,γ-deuterated substrate. Computational analysis of the mechanism provides a similar value (k1H /k1D =1.05) with a mechanism where γ-reprotonation of the enolate intermediate is rate determining.

Are bis(pyridine)iodine(I) complexes applicable for asymmetric halogenation?

Enantiopure halogenated molecules are of tremendous importance as synthetic intermediates in the construction of pharmaceuticals, fragrances, flavours, natural products, pesticides, and functional materials. Enantioselective halofunctionalizations remain poorly understood and generally applicable procedures are lacking. The applicability of chiral trans-chelating bis(pyridine)iodine(I) complexes in the development of substrate independent, catalytic enantioselective halofunctionalization has been explored herein. Six novel chiral bidentate pyridine donor ligands have been designed, routes for their synthesis developed and their [N-I-N]+-type halogen bond complexes studied by 15N NMR and DFT. The chiral complexes encompassing a halogen bond stabilized iodenium ion are shown to be capable of efficient iodenium transfer to alkenes; however, without enantioselectivity. The lack of stereoselectivity is shown to originate from the availability of multiple ligand conformations of comparable energies and an insufficient steric influence by the chiral ligand. Substrate preorganization by the chiral catalyst appears a necessity for enantioselective halofunctionalization.

The Influence of Secondary Interactions on the [N-I-N]+ Halogen Bond.

[Bis(pyridine)iodine(I)]+ complexes offer controlled access to halonium ions under mild conditions. The reactivity of such stabilized halonium ions is primarily determined by their three-center, four-electron [N-I-N]+ halogen bond. We studied the importance of chelation, strain, steric hindrance and electrostatic interaction for the structure and reactivity of halogen bonded halonium ions by acquiring their 15 N NMR coordination shifts and measuring their iodenium release rates, and interpreted the data with the support of DFT computations. A bidentate ligand stabilizes the [N-I-N]+ halogen bond, decreasing the halenium transfer rate. Strain weakens the bond and accordingly increases the release rate. Remote modifications in the backbone do not influence the stability as long as the effect is entirely steric. Incorporating an electron-rich moiety close by the [N-I-N]+ motif increases the iodenium release rate. The analysis of the iodine(I) transfer mechanism highlights the impact of secondary interactions, and may provide a handle on the induction of stereoselectivity in electrophilic halogenations.

Synthesis of azahelicenes through Mallory reaction of imine precursors: corannulene substrates provide an exception to the rule in oxidative photocyclizations of diarylethenes.

Typically, the synthesis of phenanthrene-based polycyclic aromatic hydrocarbons relies on the Mallory reaction. In this approach, stilbene (PhCH[double bond, length as m-dash]CHPh)-based precursors undergo an oxidative photocyclization reaction to join the two adjacent aromatic rings into an extended aromatic structure. However, if one C[double bond, length as m-dash]C carbon atom is replaced by a nitrogen atom (C[double bond, length as m-dash]N), the synthesis becomes practically infeasible. Here, we show the very first examples of a successful Mallory reaction on stilbene-like imine precursors involving the molecularly curved corannulene nucleus. The isolated yields exceed 90% and the resulting single and double aza[4]helicenes exhibit adjustable high affinity for electrons.

Air-stable 18-electron adducts of Schrock catalysts with tuned stability constants for spontaneous release of the active species.

Schrock alkylidenes are highly versatile, very active olefin metathesis catalysts, but their pronounced sensitivity to air still hinders their applications. Converting them into more robust but inactive 18-electron adducts was suggested previously to facilitate their handling. Generating the active species from the inactive adducts, however, required a high-temperature Lewis acid treatment and resulted in an insoluble by-product, limiting the practicality of the methodology. Herein, we introduce an approach to circumvent the inconvenient, costly, and environmentally taxing activation process. We show that 18-electron adducts of W- and Mo-based Schrock catalysts with finite stability constants (typically K = 200-15,000 M-1) can readily be prepared and isolated in excellent yields. The adducts display enhanced air-stability in the solid state, and in solution they dissociate spontaneously, hence liberating the active alkylidenes without chemical assistance.

Establishing the Role of Triflate Anions in H2 Activation by a Cationic Triorganotin(IV) Lewis Acid.

Cationic Lewis acids (LAs) are gaining interest as targets for frustrated Lewis pair (FLP)-mediated catalysis. Unlike neutral boranes, which are the most prevalent LAs for FLP hydrogenations, the Lewis acidity of cations can be tuned through modulation of the counteranion; however, detailed studies on such anion effects are currently lacking in the literature. Herein, we present experimental and computational studies which probe the mechanism of H2 activation using iPr3SnOTf (1-OTf) in conjunction with a coordinating (quinuclidine; qui) and noncoordinating (2,4,6-collidine; col) base and compare its reactivity with {iPr3Sn·base}{Al[OC(CF3)3]4} (base = qui/col) systems which lack a coordinating anion to investigate the active species responsible for H2 activation and hence resolve any mechanistic roles for OTf- in the iPr3SnOTf-mediated pathway.

Mechanochemical Synthesis of Corannulene-Based Curved Nanographenes.

It is shown that corannulene-based strained π-surfaces can be obtained through the use of mechanochemical Suzuki and Scholl reactions. Besides being solvent-free, the mechanochemical synthesis is high-yielding, fast, and scalable. Therefore, gram-scale preparation can be carried out in a facile and sustainable manner. The synthesized nanographene structure carries positive (bowl-like) and negative (saddle-like) Gaussian curvatures and adopts an overall quasi-monkey saddle-type of geometry. In terms of properties, the non-planar surface exhibits a high electron affinity that was measured by cyclic voltammetry, with electrolysis and in situ UV/vis spectroscopy experiments indicating that the one-electron reduced state displays a long lifetime in solution. Overall, these results indicate the future potential of mechanochemistry in accessing synthetically challenging and functional curved π-systems.

O-I-O halogen bond of halonium ions.

The reactivity of halonium ions is conveniently modulated by three-center, four-electron halogen bonds. Such stabilized halonium complexes are valuable reagents for oxidations and halofunctionalization reactions. We report the first example of the stabilization of a halenium ion in a three-center, four-electron halogen bond with two oxygen ligands. The influence of electron density and solvent on the stability of the complexes is assessed. O-I-O halogen bond complexes are applicable as synthetic reagents and as supramolecular synthons.

Metal-Free C-H Borylation of N-Heteroarenes by Boron Trifluoride.

Organoboron compounds are essential reagents in modern C-C coupling reactions. Their synthesis via catalytic C-H borylation by main group elements is emerging as a powerful tool alternative to transition metal based catalysis. Herein, a straightforward metal-free synthesis of aryldifluoroboranes from BF3 and heteroarenes is reported. The reaction is assisted by sterically hindered amines and catalytic amounts of thioureas. According to computational studies the reaction proceeds via frustrated Lewis pair (FLP) mechanism. The obtained aryldifluoroboranes are further stabilized against destructive protodeborylation by converting them to the corresponding air stable tetramethylammonium organotrifluoroborates.

Enantioselective Acetalization by Dynamic Kinetic Resolution for the Synthesis of γ-Alkoxybutenolides by Thiourea/Quaternary Ammonium Salt Catalysts: Application to Strigolactones.

Although acetalization is a fundamental transformation in organic synthesis, intermolecular asymmetric acetalization remains an unsolved problem. In this study, a thiourea-ammonium hybrid catalyst was shown to promote the O-alkylation of enols with a racemic γ-chlorobutenolide through dynamic kinetic resolution to give chiral acetals with good enantioselectivity. The catalyst simultaneously activates both the nucleophile and electrophile in a multifunctional manner. This method was applied to the asymmetric synthesis of several strigolactones. DFT calculations suggest that hydrogen-bonding interactions between the chlorine atom of the γ-chlorobutenolide and the tosylamide hydrogen atom of the catalyst, as well as other types of noncovalent catalyst-substrate interactions, are crucial for achieving high stereoselectivity.

Conformationally Locked Pyramidality Explains the Diastereoselectivity in the Methylation of trans-Fused Butyrolactones.

A stereoselectivity model inspired by the total synthesis of stemona alkaloids is developed to explain why enolate-derived 3,4-fused butyrolactones are methylated with a preference for syn alkylation. The model shows how conformational locking present in nonplanar enolate structures favors syn over anti methylation, due to less significant structural distortions in the syn pathway. The developed model was also successfully used to rationalize selectivities of previously documented methylation reactions.

Catalytic Activity of trans-Bis(pyridine)gold Complexes.

Gold catalysis has become one of the fastest growing fields in chemistry, providing new organic transformations and offering excellent chemoselectivities under mild reaction conditions. Methodological developments have been driven by wide applicability in the synthesis of complex structures, whereas the mechanistic understanding of Au(III)-mediated processes remains scanty and have become the Achilles' heel of methodology development. Herein, the systematic investigation of the reactivity of bis(pyridine)-ligated Au(III) complexes is presented, based on NMR spectroscopic, X-ray crystallographic, and DFT data. The electron density of pyridines modulates the catalytic activity of Au(III) complexes in propargyl ester cyclopropanation of styrene. To avoid strain induced by a ligand with a nonoptimal nitrogen-nitrogen distance, bidentate bis(pyridine)-Au(III) complexes convert into dimers. For the first time, bis(pyridine)Au(I) complexes are shown to be catalytically active, with their reactivity being modulated by strain.

Mechanism of Au(III)-Mediated Alkoxycyclization of a 1,6-Enyne.

Gold-mediated homogeneous catalysis is a powerful tool for construction of valuable molecules and has lately received growing attention. Whereas Au(I)-catalyzed processes have become well established, those mediated by Au(III) have so far barely been explored, and their mechanistic understanding remains basic. Herein, we disclose the combined NMR spectroscopic, single-crystal X-ray crystallographic, and computational (DFT) investigation of the Au(III)-mediated alkoxycyclization of a 1,6-enyne in the presence of a bidentate pyridine-oxazoline ligand. The roles of the counterion, the solvent, and the type of Au(III) complex have been assessed. Au(III) is demonstrated to be the active catalyst in alkoxycyclization. Alkyne coordination to Au(III) involves decoordination of the pyridine nitrogen and is the rate-limiting step.

Dynamic Refolding of Ion-Pair Catalysts in Response to Different Anions.

Four distinct folding patterns are identified in two foldamer-type urea-thiourea catalysts bearing a basic dimethylamino unit by a combination of X-ray crystallography, solution NMR studies, and computational studies (DFT). These patterns are characterized by different intramolecular hydrogen bonding schemes that arise largely from different thiourea conformers. The free base forms of the catalysts are characterized by folds where the intramolecular hydrogen bonds between the urea and the thiourea units remain intact. In contrast, the catalytically relevant salt forms of the catalyst, where the catalyst forms an ion pair with the substrate or substrate analogues, appear in two entirely different folding patterns. With larger anions that mimic the dialkyl malonate substrates, the catalysts maintain their native fold both in the solid state and in solution, but with smaller halide anions (fluoride, chloride, and bromide), the catalysts fold around the halide anion (anion receptor fold), and the intramolecular hydrogen bonds are disrupted. Titration of catalyst hexafluoroacetylacetonate salt with tetra-n-butylammonium chloride results in dynamic refolding of the catalyst from the native fold to the anion receptor fold.

Halogen Bonding Helicates Encompassing Iodonium Cations.

The first halonium-ion-based helices were designed and synthesized using oligo-aryl/pyridylene-ethynylene backbones that fold around reactive iodonium ions. Halogen bonding interactions stabilize the iodonium ions within the helices. Remarkably, the distance between two iodonium ions within a helix is shorter than the sum of their van der Waals radii. The helical conformations were characterized by X-ray crystallography in the solid state, by NMR spectroscopy in solution and corroborated by DFT calculations. The helical complexes possess potential synthetic utility, as demonstrated by their ability to induce iodocyclization of 4-penten-1-ol.