Vinyl Cation Research Articles

Carbon–Carbon Bond Forming Reactions of Vinyl Cations: A Personal Perspective

Carbon–Carbon Bond Forming Reactions of Vinyl Cations: A Personal Perspective

Copper‐Catalyzed Enantioselective Dehydro‐Diels–Alder Reaction: Atom‐Economical Synthesis of Axially Chiral Carbazoles

AbstractThe dehydro‐Diels–Alder (DDA) reaction is a powerful method for the construction of aromatic compounds. However, the enantioselective DDA reaction has been rarely developed, probably due to the competitive thermal reaction. Herein, we report a copper‐catalyzed enantioselective DDA reaction through vinyl cation pathway. The reaction leads to the atom‐economical synthesis of axially chiral phenyl and indolyl carbazoles in generally excellent yields with good to excellent atroposelectivities. This methodology represents the first example of non‐noble metal‐catalyzed enantioselective DDA reaction. Notably, new chiral ligand and organocatalyst derived from the constructed axially chiral carbazole are demonstrated to be useful in asymmetric catalysis.

Asymmetric Büchner reaction and arene cyclopropanation via copper-catalyzed controllable cyclization of diynes

The asymmetric Büchner reaction and related arene cyclopropanations represent one type of the powerful methods for enantioselective dearomatization. However, examples of asymmetric Büchner reactions via a non-diazo approach are quite scarce, and the related arene cyclopropanation based on alkynes has not been reported. Herein, we disclose an asymmetric Büchner reaction and the related arene cyclopropanation by copper-catalyzed controllable cyclization of N-propargyl ynamides via vinyl cation intermediates, leading to chiral tricycle-fused cycloheptatrienes and benzonorcaradienes in high yields and enantioselectivities. Importantly, this protocol represents an asymmetric arene cyclopropanation reaction of alkynes and an asymmetric Büchner reaction based on vinyl cations.

The concept of Gallium-controlled double C–H functionalization of aliphatic CH2-groups driven by Vinyl carbocations

The direct C–H activation of inert C(sp3)–H bonds in a hydrocarbon chain has been a very attractive target in organic synthesis for many decades. Among all the variety of processes, those driven by vinyl carbocations are quite scarce thus far, and it is hard to control for unstabilized vinyl cations. In this study, we designed a double C(sp3)–H functionalization of unactivated alkyl CH2 groups to produce a totally substituted quaternary carbon stereocenter via insertion of vinyl carbocations. These processes represent complicated reaction cascades with high molecular complexity controlled by the cooperative action of Ga(III) salts & GaHal4– anions and allow one-step deep poly-functionalization of simple CH substrates to be performed. In practice, this concept was initially implemented with simple starting compounds such as alkyl acetylenes and activated cyclopropanes, alkenes, or cyclobutanes to construct norbornane, cyclopentatetralin, and other important skeletons.

Copper-Catalyzed Enantioselective Dehydro-Diels-Alder Reaction: Atom-Economical Synthesis of Axially Chiral Carbazoles.

The dehydro-Diels-Alder (DDA) reaction is a powerful method for the construction of aromatic compounds. However, the enantioselective DDA reaction has been rarely developed, probably due to the competitive thermal reaction. Herein, we report a copper-catalyzed enantioselective DDA reaction through vinyl cation pathway. The reaction leads to the atom-economical synthesis of axially chiral phenyl and indolyl carbazoles in generally excellent yields with good to excellent atroposelectivities. This methodology represents the first example of non-noble metal-catalyzed enantioselective DDA reaction. Notably, new chiral ligand and organocatalyst derived from the constructed axially chiral carbazole are demonstrated to be useful in asymmetric catalysis.

Electrochemical Homo- and Crossannulation of Alkynes and Nitriles for the Regio- and Chemoselective Synthesis of 3,6-Diarylpyridines.

We disclose a mediated electrochemical [2+2+2] annulation of alkynes with nitriles, forming substituted pyridines in a single step from low-cost, readily available starting materials. The combination of electrochemistry and a triarylamine redox mediator obviates the requirements of transition metals and additional oxidants. Besides the formation of diarylpyridine moieties via the homocoupling of two identical alkynes, the heterocoupling of two different alkynes depending on their electronic nature is possible, highlighting the unprecedented control of chemoselectivity in this catalytic [2+2+2] process. Mechanistic investigations like cyclic voltammetry and crossover experiments combined with DFT calculations indicate the initial oxidation of an alkyne as the key step leading to the formation of a vinyl radical cation intermediate. The utilization of continuous flow technology proved instrumental for an efficient process scale-up. The utility of the products is exemplified by the synthesis of π-extended molecules, being relevant for material or drug synthesis.

Copper-catalyzed intermolecular formal [4 + 1] annulation of 1,5-diynes with benzocyclobutenones

The one-carbon ring expansion of benzocyclobutenones is an efficient methodology for the assembly of cyclic ketones. However, hazardous reagents or noble metal catalysts are frequently required. Herein, we disclose a copper-catalyzed intermolecular formal [4 + 1] annulation of 1,5-diynes with benzocyclobutenones, allowing the practical and atom-economical construction of diverse pyrryl 1-indanones in generally good yields under mild reaction conditions. This reaction represents an important advancement in the ring expansion of benzocyclobutenones via vinyl cation pathway.

1,2-Silyl Rearrangement in Gold Carbene Chemistry: Synthesis of Furyl-Decorated Tetrasubstituted Silylallene Derivatives.

The gold-catalyzed reaction of 2-en-4-ynones with alkynylsilanes provides fully substituted allene derivatives bearing furyl and silyl groups. This transformation would involve generation of a gold furyl carbene intermediate, which regioselectively undergoes a nucleophilic attack by the alkynylsilane at the electrophilic carbene carbon atom with the formation of a β-gold vinyl cation species. The subsequent release of the gold catalyst, accompanied by a 1,2-silyl shift, leads to the formation of tetrasubstituted allene products.

Synthesis of Seven- and Eight-Membered Rings by a Brønsted Acid Catalyzed Cationic Carbocyclization of Biphenyl Embedded Enynes.

A Brønsted acid catalyzed cyclization of o-alkenyl-o'-alkynylbiaryls for the synthesis of biologically relevant dibenzo-fused medium-sized rings has been developed. The outcome of the cyclization is determined by the nature of the substituent at the alkyne, with arenes favoring seven-membered rings and alkyl substituents producing eight-membered rings. These reactions proceed via a vinyl cation, which is captured by water and, notably, by C-nucleophiles, such as electron-rich (hetero)arenes.

Aluminum-Catalyzed Intramolecular Vinylation of Arenes by Vinyl Cations.

This study addresses the challenges associated with vinyl cation generation, a process that traditionally requires quite specific counterions. Described herein is a novel intramolecular vinylation of arenes catalyzed by aluminum(III) chloride, utilizing practical conditions and readily available vinyl triflates derived from 2-aceto-3-arylpropionates. Comprehensive experimental data support diverse carbocycle synthesis, exemplified by indenes and higher analogues. Control experiments verify the applicability of the vinylation protocol, and synthetic applications showcase a potent tubulin polymerization inhibitor with anticancer properties. Density functional theory computations reveal a Lewis-acid-driven mechanism involving triflate moiety abstraction to generate a reactive vinyl cation.

Enantioselective functionalization of unactivated C(sp3)–H bonds through copper-catalyzed diyne cyclization by kinetic resolution

Site- and stereoselective C–H functionalization is highly challenging in the synthetic chemistry community. Although the chemistry of vinyl cations has been vigorously studied in C(sp3)–H functionalization reactions, the catalytic enantioselective C(sp3)–H functionalization based on vinyl cations, especially for an unactivated C(sp3)–H bond, has scarcely explored. Here, we report an asymmetric copper-catalyzed tandem diyne cyclization/unactivated C(sp3)–H insertion reaction via a kinetic resolution, affording both chiral polycyclic pyrroles and diynes with generally excellent enantioselectivities and excellent selectivity factors (up to 750). Importantly, this reaction demonstrates a metal-catalyzed enantioselective unactivated C(sp3)–H functionalization via vinyl cation and constitutes a kinetic resolution reaction based on diyne cyclization. Theoretical calculations further support the mechanism of vinyl cation-involved C(sp3)–H insertion reaction and elucidate the origin of enantioselectivity.

Borataalkenes, boraalkenes, and the η2-B,C coordination mode in coordination chemistry and catalysis.

Borataalkenes and boraalkenes are the boron-containing isoelectronic analogues of alkenes and vinyl cations respectively. Compared with alkenes, the borataalkene and boraalkene ligand motifs in transition metal coordination chemistry are relatively underexplored. In this review, the synthesis of borataalkene and boraalkene complexes and other transition metal complexes featuring the η2-B,C coordination mode is described. The diversity of coordination modes and geometry in these complexes, and the spectroscopic and structural evidence supporting their assignments is disclosed as well as computational analysis of bonding. The applications of the borataalkene ligand motif in synthetic organic homogeneous catalysis, especially those involving geminal bis(pinacolatoboronates) and 1,4-azaborines, are discussed.

Lewis acid-mediated transformations of 5-acyl-N-fluoroalkyl-1,2,3-triazoles to cyclopentenones, indenones, or oxazoles.

We present a transition metal-free approach to 2-N-substituted indenones, cyclopentenones, and 4-carbonyl oxazoles, based on the reaction of 5-acylated N-fluoroalkyl substituted 1,2,3-triazoles (prepared by a three-component click reaction of copper acetylides, fluoroalkyl azides, and acyl chlorides) with Lewis acids aluminium trichloride or boron trifluoride etherate, proceeding via the generation and cyclization of vinyl cations.

Direct synthesis of phenanthrenyl triflates from 1-biphenylyl-2-diazo-2-aryl ketones and triflic anhydride.

A strategy for direct synthesis of phenanthrenyl triflates from 1-biphenylyl-2-diazo-2-aryl ketones and triflic anhydride is described. The reaction of 1-biphenylyl-2-diazo-2-aryl ketones with triflic anhydride proceeded smoothly in the presence of 2,6-di-tert-butylpyridine under mild conditions to produce phenanthrenyl triflates in high to excellent yields. The phenanthrenyl triflate products were demonstrated to be utilized as coupling partners in various coupling reactions. The proposed mechanism involves an intramolecular Friedel-Crafts reaction of a vinyl cation intermediate formed in situ.

Molecular Dynamics Simulations of Ammonium-Based Acrylate Polymerized Ionic Liquids

Polymerized ionic liquids (polyILs) are interesting materials that may find application as the electrolyte in electrochemical devices provided that they can be made with sufficiently high ion conductivities. The continuous optimization requires the understanding of the ion transport in available materials. In this work, a group of ammonium-based acrylate polyILs were examined as the candidates with engineered side chains containing long linker and various alkyl tails. Classical molecular dynamics simulations were performed to investigate the mechanism of ion transport. For all simulated systems, the diffusion coefficients were higher than previously investigated polyILs with imidazolium vinyl cations directly bonded to the backbones. Diffusivity was further improved when the tail length increased from methyl to propyl, but this trend did not persist for butyl and longer tails. The higher diffusion coefficient generally coexisted with less ion pair association, lower dynamical heterogeneity, and suppressed string-like cooperative motion. It was affirmed that only a few counterions were fast-moving for effective hopping, and the counterions exhibited smoother motion in acrylate polyILs than the imidazolium-based polyIL with a shorter side chain. For better ion transport, this work suggested that long linker and intermediate tails in the polymerized ions appeared to be the attractive candidates.

Synthesis of Cobalt-Tin and -Lead Tetrylidynes-Reactivity Study of the Triple Bond.

Tetrylidynes [TbbSn≡Co(PMe3 )3 ] (1 a) and [TbbPb≡Co(PMe3 )3 ] (2) (Tbb=2,6-[CH(SiMe3 )2 ]2 -4-(t-Bu)C6 H2 ) are accessed for the first time via a substitution reaction between [Na(OEt2 )][Co(PMe3 )4 ] and [Li(thf)2 ][TbbEBr2 ] (E=Sn, Pb). Following an alternative procedure the stannylidyne [Ar*Sn≡Co(PMe3 )3 ] (1 b) was synthesized by hydrogen atom abstraction using AIBN from the paramagnetic hydride complex [Ar*SnH=Co(PMe3 )3 ] (4) (AIBN=azobis(isobutyronitrile)). The stannylidyne 1 a adds two equivalents of water to yield the dihydroxide [TbbSn(OH)2 CoH2 (PMe3 )3 ] (5). In reaction of the stannylidyne 1 a with CO2 a product of a redox reaction [TbbSn(CO3 )Co(CO)(PMe3 )3 ] (6) was isolated. Protonation of the tetrylidynes occurs at the cobalt atom to give the metalla-stanna vinyl cation [TbbSn=CoH(PMe3 )3 ][BArF 4 ] (7 a) [ArF =C6 H3 -3,5-(CF3 )2 ]. The analogous germanium and tin cations [Ar*E=CoH(PMe3 )3 ][BArF 4 ] (E=Ge 9, Sn 7 b) (Ar*=C6 H3 (2,6-Trip)2 , Trip=2,4,6-C6 H2 iPr3 ) were also obtained by oxidation of the paramagnetic complexes [Ar*EH=Co(PMe3 )3 ] (E=Ge 3, Sn 4), which were synthesized by substitution of a PMe3 ligand of [Co(PMe3 )4 ] by a hydridoylene (Ar*EH) unit.

Gold(I)-Catalyzed Bis-Cyclization of Allenynes for the Synthesis of Strained and Planar Polycyclic Compounds.

A gold-catalyzed cascade cyclization of naphthalene-tethered allenynes gave strained fused phenanthrene derivatives. The reaction proceeds through the nucleophilic reaction of an alkyne with the activated allene to generate a vinyl cation intermediate, followed by arylation with a tethered naphthalene ring to form the 4H-cyclopenta[def]phenanthrene (CPP) scaffold. When using aryl-substituted substrates on the alkyne terminus, the gold-catalyzed reaction produced dibenzofluorene derivatives along with the CPP derivatives. Selective formation of CPP and dibenzofluorene derivatives depending on the reaction conditions is also presented.

Gold(I)‐Catalyzed Bis‐Cyclization of Allenynes for the Synthesis of Strained and Planar Polycyclic Compounds

Gold(I)‐Catalyzed Bis‐Cyclization of Allenynes for the Synthesis of Strained and Planar Polycyclic Compounds

Substitution of H Atoms in Unsaturated (Vinyl-Type) Carbocations by Cl or O Atoms.

Introduction of Cl and O atoms into C4-vinyl carbocations was studied by X-ray diffraction analysis and IR spectroscopy. Chlorine atoms are weak electron acceptors in ordinary molecules but, within vinyl carbocations, manifest themselves as strong electron donors that accept a positive charge. The attachment of a Cl atom directly to a C=C bond leads to an increase in the e-density on it, exceeding that of the common double bond. The positive charge should be concentrated on the Cl atom, and weak δ- may appear on the C=C bond. More distant attachment of the Cl atom, e.g., to a C atom adjacent to the C=C bond, has a weaker effect on it. If two Cl atoms are attached to the Cγ atom of the vinyl cation, as in Cl2CγCδHCαHCH3, then the cation switches to the allyl type with two practically equivalent and almost uncharged CγCδCα bonds. When such a strong nucleophile as the O atom is introduced into the carbocation, a protonated ester molecule with a C-O(H+)-C group and a C=C bond forms. Nonetheless, in the future, there is still a possibility of obtaining carbocations with a non-protonated C-O-C group.

When Does Hammond's Postulate Predict Stabilities of Carbocations?

AbstractHammond's postulate, which relates the rate of formation of an unstable intermediate to the energy of this intermediate, has widely been used to determine stabilities of carbocations. However, the rates of formation of highly stabilized carbocations R+ by ionization of R−X are only weakly or not at all correlated with their stabilities, because the corresponding activation energies are strongly affected by intrinsic barriers. In this article we will show that consideration of the rate of the reverse reaction allows one to define the range in which Hammond's postulate holds and when its predictive power fades as the role of intrinsic barriers is gaining importance. The ambiguity of the term “carbocation stability” is discussed. Kinetic data and quantum chemical calculations show that vinyl cations are not extraordinarily high energy intermediates, but that high intrinsic barriers account for their slow formation from vinyl halides and their rather slow reactions with nucleophiles.