Cyclopropenium Research Articles

Photocatalytic Decarboxylative Functionalization of Cyclopropenes via Cyclopropenium Cation Intermediates

AbstractA photocatalytic decarboxylative functionalization of cyclopropenes is reported. Starting from a broad range of redox‐active ester‐substituted cyclopropenes, cyclopropenylphthalimides can be synthesized in the absence of a nucleophile. Alternatively, different carbon and heteroatom nucleophiles can be introduced. The transformation proceeds most probably through the formation of an aromatic cyclopropenium cation, followed by trapping with the nucleophiles.

Photocatalytic Decarboxylative Functionalization of Cyclopropenes via Cyclopropenium Cation Intermediates.

A photocatalytic decarboxylative functionalization of cyclopropenes is reported. Starting from a broad range of redox-active ester-substituted cyclopropenes, cyclopropenylphthalimides can be synthesized in the absence of a nucleophile. Alternatively, different carbon and heteroatom nucleophiles can be introduced. The transformation proceeds most probably through the formation of an aromatic cyclopropenium cation, followed by trapping with the nucleophiles.

Gilding σ-type cyclopropenium cations

Gilding σ-type cyclopropenium cations

Accessing elusive σ-type cyclopropenium cation equivalents through redox gold catalysis

Cyclopropenes are the smallest unsaturated carbocycles. Removing one substituent from cyclopropenes leads to cyclopropenium cations (C3+ systems, CPCs). Stable aromatic π-type CPCs were discovered by Breslow in 1957 by removing a substituent on the aliphatic position. In contrast, σ-type CPCs—formally accessed by removing one substituent on the alkene—are unstable and relatively unexplored. Here we introduce electrophilic cyclopropenyl-gold(III) species as equivalents of σ-type CPCs, which can then react with terminal alkynes and vinylboronic acids. With catalyst loadings as low as 2 mol%, the synthesis of highly functionalized alkynyl- or alkenyl-cyclopropenes proceeded under mild conditions. A class of hypervalent iodine reagents—the cyclopropenyl benziodoxoles (CpBXs)—enabled the direct oxidation of gold(I) to gold(III) with concomitant transfer of a cyclopropenyl group. This protocol was general, tolerant to numerous functional groups and could be used for the late-stage modification of complex natural products, bioactive molecules and pharmaceuticals.

Development of high-voltage and high-energy membrane-free nonaqueous lithium-based organic redox flow batteries

Lithium-based nonaqueous redox flow batteries (LRFBs) are alternative systems to conventional aqueous redox flow batteries because of their higher operating voltage and theoretical energy density. However, the use of ion-selective membranes limits the large-scale applicability of LRFBs. Here, we report high-voltage membrane-free LRFBs based on an all-organic biphasic system that uses Li metal anode and 2,4,6-tri-(1-cyclohexyloxy-4-imino-2,2,6,6-tetramethylpiperidine)-1,3,5-triazine (Tri-TEMPO), N-propyl phenothiazine (C3-PTZ), and tris(dialkylamino)cyclopropenium (CP) cathodes. Under static conditions, the Li||Tri-TEMPO, Li||C3-PTZ, and Li||CP batteries with 0.5 M redox-active material deliver capacity retentions of 98%, 98%, and 92%, respectively, for 100 cycles over ~55 days at the current density of 1 mA/cm2 and a temperature of 27 °C. Moreover, the Li||Tri-TEMPO (0.5 M) flow battery delivers an initial average cell discharge voltage of 3.45 V and an energy density of ~33 Wh/L. This flow battery also demonstrates 81% of capacity for 100 cycles over ~45 days with average Coulombic efficiency of 96% and energy efficiency of 82% at the current density of 1.5 mA/cm2 and at a temperature of 27 °C.

Late‐Stage Aryl C−H Bond Cyclopropenylation with Cyclopropenium Cations

AbstractHerein, we disclose the first regio‐, site‐ and chemoselective late‐stage (hetero)aryl C−H bond cyclopropenylation with cyclopropenium cations (CPCs). The process is fast, operationally simple and shows an excellent functional group tolerance in densely‐functionalized drug molecules, natural products, agrochemicals and fluorescent dyes. Moreover, we discovered that the installation of the cyclopropene ring in drug molecules could not only be used to shield against metabolic instability but also as a synthetic tool to reach medicinally‐relevant sp3‐rich scaffolds exploiting the highly‐strained nature of the cyclopropene ring with known transformations.

Late-Stage Aryl C-H Bond Cyclopropenylation with Cyclopropenium Cations.

Herein, we disclose the first regio-, site- and chemoselective late-stage (hetero)aryl C-H bond cyclopropenylation with cyclopropenium cations (CPCs). The process is fast, operationally simple and shows an excellent functional group tolerance in densely-functionalized drug molecules, natural products, agrochemicals and fluorescent dyes. Moreover, we discovered that the installation of the cyclopropene ring in drug molecules could not only be used to shield against metabolic instability but also as a synthetic tool to reach medicinally-relevant sp3 -rich scaffolds exploiting the highly-strained nature of the cyclopropene ring with known transformations.

Borane-Catalyzed C-F Bond Functionalization of gem-Difluorocyclopropenes Enables the Synthesis of Orphaned Cyclopropanes.

Herein, we disclose an approach to synthesize tert-alkyl cyclopropanes by leveraging C-F bond functionalization of gem-difluorocyclopropenes using tris(pentafluorophenyl)borane catalysis. The reaction proceeds through the intermediacy of a fluorocyclopropenium ion, which was confirmed by the isolation of [Ph2(C6D5)C3]+[(C6F5)3BF]-. We found that silylketene acetal nucleophiles were optimal reaction partners with fluorocyclopropenium ion intermediates yielding fully substituted cyclopropenes functionalized with two α-tert-alkyl centers (63-93% yield). The regioselectivity of the addition to cyclopropenium ions is controlled by their steric and electronic properties and enables access to 3,3-bis(difluoromethyl)cyclopropenes in short order. The resulting cyclopropene products are readily reduced to the corresponding orphaned cyclopropanes under hydrogenation conditions. Quantum chemical calculations reveal the nature of the C-F bond cleavage steps and provide evidence for catalysis by boron and not silylated oxonium ions, though Si-F bond formation is the enthalpic driving force for the reaction.

Reactions of Acetonitrile with Trapped, Translationally Cold Acetylene Cations.

The reaction of the acetylene cation (C2H2+) with acetonitrile (CH3CN) is measured in a linear Paul ion trap coupled to a time-of-flight mass spectrometer. C2H2+ and CH3CN are both noted for their astrochemical abundance and predicted relevance for understanding prebiotic chemistry. The observed primary products are c-C3H3+, C3H4+, and C2NH3+. The latter two products react with excess CH3CN to form the secondary product C2NH4+, protonated acetonitrile. The molecular formula of these ionic products can be verified with the aid of isotope substitution via deuteration of the reactants. Primary product reaction pathways and thermodynamics are investigated with quantum chemical calculations and demonstrate exothermic pathways to two isomers of C2NH3+, two isomers of C3H4+, and the cyclopropenyl cation c-C3H3+. This study deepens our understanding of the dynamics and products of a pertinent ion-molecule reaction between two astrochemically abundant molecules in conditions that mimic those of the interstellar medium.

Cross-assembly confined bifunctional catalysis via non-covalent interactions for asymmetric halogenation

•Assembling bifunctional catalysts via non-covalent interactions •Enantioselectivity is largely optimized by changing the achiral catalytic species •Asymmetric halogenation to give various valuable building blocks •Access to the advanced intermediates of drugs and natural products Bifunctional catalysis plays a key role in the synthesis of useful compounds. By offering a sterically confined environment, chiral bifunctional catalysts can achieve highly enantioselective reactions. However, introducing suitable substituents to create a confined microenvironment for asymmetric catalysis on many occasions involves tedious procedures, leading to inefficient reaction optimization. Herein, we report a proof-of-concept study on formulating confined bifunctional catalysts by linking catalytic species via non-covalent interactions (NCIs). Chiral phosphate and achiral cyclopropenium cations cross-assembled to give a confined bifunctional system for asymmetric bromo-semipinacol rearrangement. By changing the achiral catalyst to aminopyridine, the system can be applied to asymmetric bromocycloetherification. These reactions are largely optimized by simply changing the achiral catalyst. A computational study revealed that the strength of the NCI donor is crucial in creating tighter catalytic pockets to amplify the effect of enantiofacial discrimination of substrates. Bifunctional catalysis plays a key role in the synthesis of useful compounds. By offering a sterically confined environment, chiral bifunctional catalysts can achieve highly enantioselective reactions. However, introducing suitable substituents to create a confined microenvironment for asymmetric catalysis on many occasions involves tedious procedures, leading to inefficient reaction optimization. Herein, we report a proof-of-concept study on formulating confined bifunctional catalysts by linking catalytic species via non-covalent interactions (NCIs). Chiral phosphate and achiral cyclopropenium cations cross-assembled to give a confined bifunctional system for asymmetric bromo-semipinacol rearrangement. By changing the achiral catalyst to aminopyridine, the system can be applied to asymmetric bromocycloetherification. These reactions are largely optimized by simply changing the achiral catalyst. A computational study revealed that the strength of the NCI donor is crucial in creating tighter catalytic pockets to amplify the effect of enantiofacial discrimination of substrates.

Ionic liquid Keggin polyoxometallates with the tris(dihexylamino)cyclopropenium cation

Five new Keggin polyoxometalate (POM) salts were prepared with the tris(dihexylamino)cyclopropenium cation [C3(NHex2)3]+ in an effort to investigate and understand the impact of combining triaminocyclopropenium (TAC) cations with POMs on their thermochemical and thermophysical properties. The tri-anions [PM12O40]3– (M = Mo, W) have high melting salts (Tm = 140 and 129 °C, respectively), whereas the tetra-anions [PVMo11O40]4– and [HPV2M10O40]4– (M = Mo, W), despite the increased electrostatic charge, have lower and very similar melting points (Tm ∼ 82 °C). The solid-state structures are all very similar, however, the tetra-anionic salts have a double layer of cations (compared to a single layer for the tri-anionic salts) and the electrostatic repulsion between these layers is likely responsible for the lower and similar melting points, as well as their increased solubility in non-polar solvents. The salts were also characterised by TGA, DSC, solubility studies, X-ray crystallography, NMR and infrared spectroscopy.

Tris(dialkylamino)cyclopropenium dialkylphosphate ionic liquids as lubricants.

Six new tris(dialkylamino)cyclopropenium dialkylphosphate ionic liquids (ILs), [C3(NR2)3]BEHP (NR2 = NEt2, NBuMe, NPr2, NBu2, NHex2, NDec2; BEHP = bis(2-ethylhexyl)phosphate), were prepared and characterised as potential lubricants. Thermophysical and thermochemical properties of these ILs were investigated, namely: viscosity, density, conductivity, miscibility, thermal stability and phase transitions. Miscibility studies indicated that [C3(NEt2)3]BEHP would not be suitable due to its water solubility and hexane immiscibility. [C3(NDec2)3]BEHP was not investigated as a lubricant due to its low purity (the chloride salt of this cation is also hexane miscible). Of the other four, [C3(NHex2)3]BEHP was found to exhibit significantly less wear for pin-on-disk test conditions than the standard phosphonium [P6,6,6,14]BEHP IL. The amount of wear was found to generally decrease with increasing molecular weight.

Electron-deficient cyclopropenium cations as Lewis acids in FLP chemistry.

Cyclopropenium cations incorporating electron deficient substituents are Lewis acidic despite the presence of π-electrons. The chloride and electron affinities are examined computationally and experimentally, respectively. These cations form classic Lewis acid-base adducts with PPh3, while sterically demanding phosphines yield frustrated Lewis pairs (FLPs) which participate in FLP additions. Depending on the basicity of the phosphine used, addition to alkynes or alkyne deprotonation is observed. In either case, new C-C bonds are formed, thus extending the utility of the concept of FLP chemistry to these delocalized π-cations.

High-resolution rovibrational and rotational spectroscopy of the singly deuterated cyclopropenyl cation, c-C3H2D.

Applying a novel action spectroscopic technique in a 4 K cryogenic ion-trap instrument, the molecule c-C3H2D+ has been investigated by high-resolution rovibrational and pure rotational spectroscopy for the first time. In total, 126 rovibrational transitions within the fundamental band of the ν1 symmetric C-H stretch were measured with a band origin centred at 3168.565 cm-1, which were used to predict pure rotational transition frequencies in the ground vibrational state. Based on these predictions, 16 rotational transitions were observed between 90 and 230 GHz by using a double-resonance scheme. These new measurements will enable the first radio-astronomical search for c-C3H2D+.

Accessing Cyclopropenium Cations via a Rh-Catalyzed Oxidative [2+1] Reaction

Key words rhodium catalysis - cyclopropenes - carbynoids - aromaticity

Cyclopropenium Ions in Catalysis.

Cyclopropenium ions are the smallest class of aromatic compounds, satisfying Hückel's rules of aromaticity with two π electrons within a three-membered ring. First prepared by Breslow in 1957, cyclopropenium ions have been found to possess extraordinary stability despite being both cationic and highly strained. In the 65 years since their first preparation, cyclopropenium ions have been the subject of innumerable studies concerning their synthesis, physical properties, and reactivity. However, prior to our work, the reactivity of these unique carbocations had not been exploited for reaction promotion or catalysis.Over the past 13 years, we have been exploring aromatic ions as unique and versatile building blocks for the development of catalysts for organic chemistry. A major portion of this work has been focused on leveraging the remarkable properties of the smallest of the aromatic ions─cyclopropeniums─as a design element in the invention of highly reactive catalysts. Indeed, because of its unique profile of hydrolytic stability, compact geometry, and relatively easy oxidizability, the cyclopropenium ring has proven to be a highly advantageous construction module for catalyst invention.In this Account, we describe some of our work using cyclopropenium ions as a key element in the design of novel catalysts. First, we discuss our early work aimed at promoting dehydrative reactions, starting with Appel-type chlorodehydrations of alcohols and carboxylic acids, cyclic ether formations, and Beckmann rearrangements and culminating in the realization of catalytic chlorodehydrations of alcohols and a catalytic Mitsunobu-type reaction. Next, we describe the development of cyclopropenimines as strong, neutral organic Brønsted bases and, in particular, the use of chiral cyclopropenimines for enantioselective Brønsted catalysis. We also describe the development of higher-order cyclopropenimine superbases. The use of tris(amino)cyclopropenium (TAC) ions as a novel class of phase-transfer catalysts is discussed for the reaction of epoxides with carbon dioxide. Next, we describe the formation of a cyclopropenone radical cation that has a portion of its spin density on the oxygen atom, leading to some peculiar metal ligand behavior. Finally, we discuss recent work that employs TAC electrophotocatalysts for oxidation reactions. The key intermediate for this chemistry is a TAC radical dication, which as an open-shell photocatalyst has remarkably strong excited-state oxidizing power. We describe the application of this strategy to transformations ranging from the oxidative functionalization of unactivated arenes to the regioselective derivatization of ethers, C-H aminations, vicinal C-H diaminations, and finally aryl olefin dioxygenations. Collectively, these catalytic platforms demonstrate the utility of charged aromatic rings, and cyclopropenium ions in particular, to enable unique advances in catalysis.

Catalytic Synthesis of Cyclopropenium Cations with Rh-Carbynoids.

Herein, we report the first catalytic one-step synthesis of cyclopropenium cations (CPCs) with readily available alkynes and hypervalent iodine reagents as carbyne sources. Key to the process is the catalytic generation of a novel Rh-carbynoid that formally transfers monovalent cationic carbynes (:+C-R) to alkynes via an oxidative [2+1] cycloaddition. Our process is able to synthesize a new type of CPC substituted with an ester group that underpins the regioselective attack of a broad range of carbon and heteroatomic nucleophiles, thus providing a new platform for the synthesis of valuable cyclopropenes difficult or not possible to make by current methodologies.

NBO technique as a descriptor of aromaticity

A Natural Bond Orbital (NBO) technique has been used as a descriptor of single or double aromaticity in cyclopropenyl, 1,3,5-dehydrophenyl and hexakis (phenylselenyl) benzene cations and their neutral species. A Density Functional Theory (DFT) exchange-correlation (B3LYP) and long-range-corrected (CAM-B3LYP) functionals with different basis sets have been applied. The regularities of the structural and electronic markers have been adopted as aromaticity indicators. The orderly Wiberg Bond Indices (WBIs) of neighbouring atoms and Harmonic Oscillator Model for Aromaticity (HOMA) indices complement these findings. The degree of delocalization, as an influential source of stability, together with steric and electrostatic factors are monitored for the confirmation of aromaticity.

Planar Networks of Boron Triangles: Analogies to Benzene and Other Planar Aromatic Hydrocarbons.

The lowest energy structures for Bn species (n = 6 to 23 except for 20) observed experimentally in the gas phase with a mass spectrometer are planar networks of boron triangles. Such networks are considered to consist of trigonal planar sp2-hybridized boron atoms having perpendicular p orbitals similar to the carbon atoms in benzene and other planar aromatic hydrocarbons. Electron bookkeeping for reasonable chemical bonding topologies of wheel-like structures such as B@Bn-1 (n = 6-9) leads to two π-electrons for B6 and B7+ similar to the cyclopropenyl cation and six π-electrons for B82- and B9- similar to benzene. Related chemical bonding topology analyses for low-energy oval B10 and B11- structures as well as for larger planar boron triangle networks with 12, 13, and 14 boron atoms suggest six π-electrons in such structures. Planar networks of boron triangles having 16-19 boron atoms are shown to be systems with 10 π-electrons similar to naphthalene. Similarly, low-energy planar B22 and B23- structures are shown to be 4 π-electron systems 1analogous to linear anthracene and angular phenanthrene, respectively. Intermediate B15- and B21- systems are shown to be systems with 4k rather than 4k + 2 π-electrons with 8 and 12 π-electrons, respectively. Structures based on planar networks of boron triangles are strongly energetically disfavored for B20 relative to a nonplanar decagonal antiprism structure with ideal D10d symmetry.

PKa Scale for Cyclopropenium Ions with Applications in CO2 Capture.

Molecular acid-base properties are core to understanding chemical systems and the prediction of reactivity. This axiom holds for cyclopropenium ions in terms of their broad use as (organo)catalysts, ligands, redox-flow batteries, and applications in materials sciences. In view of this significant status, and with it, the critical importance of acidity, we disclose in this report the first comprehensive computational study of the pKa values of cyclopropenium ions employing a subset of 70 structurally diverse cyclopropenium derivatives, density functional computations, and Hammett linear free-energy relationships. Capitalizing upon these computed findings, and with an eye toward greenhouse gas trapping, we further document the timely use of a cyclopropenium-cyclopropenylidene coupled platform for CO2 capture and light-triggered release.