Cyclic (amino)(barrelene)carbene Ru-complexes: synthesis and reactivity in olefin metathesis.

The synthesis of ruthenium-complexes with cyclic (amino)(barrelene)carbenes (namely CABCs) as ligands is reported. Isolated in moderate to good yields, these new complexes showed impressive thermal stability at 110 °C over several days. Good catalytic performances were demonstrated in various ring-closing metathesis (RCM), macrocyclic-RCM, ring-closing enyne metathesis (RCEYM), cross-metathesis (CM), and ring-opening cross metathesis (ROCM) reactions.

1H-1,2,3-Triazol-5-ylidenes as Catalytic Organic Single-Electron Reductants.

Most of the known single-electron reductants are either metal based reagents, used in a stoichiometric amount, or a combination of an organic species and a photocatalyst. Here we report that 1H-1,2,3-triazol-5-ylidenes act not only as stoichiometric one-electron donors but also as catalytic organic reducing agents, without the need of a photocatalyst. As a proof of concept, we studied the reduction of quinones, which are well-known electron conveyors that are involved in various biological and industrial processes. This work also provides experimental evidence for the formation of a bis(triazolium)carbonate adduct, which acts as the resting state of the catalytic cycle and as the carbene reservoir.

A crystalline doubly oxidized carbene.

The chemistry of carbon is governed by the octet rule, which refers to its tendency to have eight electrons in its valence shell. However, a few exceptions do exist, for example, the trityl radical (Ph3C∙) (ref. 1) and carbocation (Ph3C+) (ref. 2) with seven and six valence electrons, respectively, and carbenes (R2C:)-two-coordinate octet-defying species with formally six valence electrons3. Carbenes are now powerful tools in chemistry, and have even found applications in material and medicinal sciences4. Can we undress the carbene further by removing its non-bonding electrons? Here we describe the synthesis of a crystalline doubly oxidized carbene (R2C2+), through a two-electron oxidation/oxide-ion abstraction sequence from an electron-rich carbene5. Despite a cumulenic structure and strong delocalization of the positive charges, the dicoordinate carbon centre maintains significant electrophilicity, and possesses two accessible vacant orbitals. A two-electron reduction/deprotonation sequence regenerates the parent carbene, fully consistent with its description as a doubly oxidized carbene. This work demonstrates that the use of bulky strong electron-donor substituents can simultaneously impart electronic stabilization and steric protection to both vacant orbitals on the central carbon atom, paving the way for the isolation of a variety of doubly oxidized carbenes.

Reactivity of Yellow Arsenic towards Cyclic (Alkyl)(Amino) Carbenes (CAACs).

Different cyclic (alkyl)(amino)carbenes (CAACs) were reacted with yellow arsenic. Several products [(CAAC-n)2 (µ,η1:1 -As2 )] (n=1 (1), 4 (2)), [(CAAC-2)3 (µ3 ,η1:1:1 -As4 )] (3) and [(CAAC-3)4 (µ4 ,η1:1:1:1 - As8 )] (6) were isolated due to the differing steric properties of CAAC-1-4. The products contain As2 , As4 or As8 units and represent the first examples of CAACs-substituted products of yellow arsenic. The reactivity of As4 was compared with the reactivities of P4 and the interpnictogen compound AsP3 , which led to a series of phosphorus-containing derivatives such as ([(CAAC-3)3 (µ3 ,η1:1:1 -P4 )] (4) and [(CAAC-3)4 (µ4 ,η1:1:1:1 -P8 )] (7)) and [(CAAC-3)3 (µ3 ,η1:1:1 -AsP3 )] (5). The products were characterized by spectroscopic and crystallographic methods and DFT computations were performed to clarify their formation pathway.

An Air-Stable "Masked" Bis(imino)carbene: A Carbon-Based Dual Ambiphile.

Carbenes, once considered laboratory curiosities, now serve as powerful tools in the chemical and material sciences. To date, all stable singlet carbenes are single-site ambiphiles. Here we describe the synthesis of a carbene which is a carbon-based dual ambiphile (both single-site and dual-site). The key is to employ imino substituents derived from a cyclic (alkyl)(amino)carbene (CAAC), which imparts a 1,3-dipolar character to the carbene. Its dual ambiphilic nature is consistent with the ability to activate simple organic molecules in both 1,1- and 1,3-fashion. Furthermore, its 1,3-ambiphilicity facilitates an unprecedented reversible intramolecular dearomative [3 + 2] cycloaddition with a proximal arene substituent, giving the carbene the ability to "mask" itself as an air-stable cycloadduct. We perceive that the concept of dual ambiphilicity opens a new dimension for future carbene chemistry, expanding the repertoire of applications beyond that known for classical single-site ambiphilic carbenes.

How To Enhance the Efficiency of Breslow Intermediates for SET Catalysis.

Oxidative carbene organocatalysis, which proceeds via single electron transfer (SET) pathways, has been limited by the moderately reducing properties of deprotonated Breslow intermediates BI-s derived from thiazol-2-ylidene 1 and 1,2,4-triazolylidene 2. Using computational methods, we assess the redox potentials of BI-s based on ten different types of known stable carbenes and report our findings concerning the key parameters influencing the steps of the catalytic cycle. From the calculated values of the first oxidation potential of BI-s derived from carbenes 1 to 10, it appears that, apart from the diamidocarbene 7, all the others are more reducing than thiazol-2-ylidene 1 and the 1,2,4-triazolylidene 2. We observed that while the reducing power of BI-s significantly decreases with increasing solvent polarity, the redox potential of the oxidant can increase at a greater rate, thus facilitating the reaction. The cation, associated with the base, also plays an important role when a nonpolar solvent is used; large and weakly coordinating cations such as Cs+ are beneficial. The radical-radical coupling step is probably the most challenging step due to both electronic and steric constraints. Based on our results, we predict that mesoionic carbene 3 and abnormal NHC 4 are the most promising candidates for oxidative carbene organocatalysis.

Cyclic (amino)(barrelene)carbenes: an original family of CAACs through a novel synthetic pathway.

A novel family of cyclic (alkyl)(amino)carbenes, which we name cyclic (amino)(barrelene)carbenes (CABCs) is reported. The key synthetic step involves an intramolecular [4+2] cyclization of an anthracene derivative with an alkyne. This synthetic approach allows for the attachment of both aryl and alkyl groups on the nitrogen atom. When used as ligand, two of the barrelene hydrogens are in close contact with the metal, which could stabilize low valent catalytic intermediates.

Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents.

Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.

Silylated Ge9 Clusters as New Ligands for Cyclic (Alkyl)amino and Mesoionic Carbene Copper Complexes.

The coordination of Ge9 Zintl clusters at (carbene)CuI moieties is explored, and the complexes [(CAAC)Cu]2[η3-Ge9{Si(TMS)3}2] (1), (CAAC)Cu[η3-Ge9{Si(TMS)3}3] (2), and (MIC)Cu[η3-Ge9{Si(TMS)3}3] (3) are compared with their known N-heterocyclic carbene (NHC) derivatives (A and B), where CAAC = cyclic (alkyl)amino carbene, MIC = mesoionic carbene, and TMS = trimethylsilane. In analogy to the NHC derivatives, the synthesis of 1-3 proceeds by single-step reactions of (CAAC)CuCl or (MIC)CuCl with the [Ge9R2]2- and [Ge9R3]- [R = Si(TMS)3] cluster ligands, respectively, and yields complexes of (carbene)CuI (carbene = CAAC, MIC) moieties exhibiting η3-coordination modes of the Ge9 deltahedron to the Cu atom. In 1, [Ge9R2]2- acts as a η3-bridging unit for two (CAAC)CuI moieties, and 2 and 3 feature single (carbene)CuI (CAAC and MIC) fragments η3-connected to [Ge9R3]- units. Analysis of the bond lengths in comparison with known examples shows a bond expansion within the coordinated Ge3 triangular faces for all (carbene)CuIGe9 complexes (carbene = NHC, MIC, CAAC). All compounds are characterized by single-crystal X-ray diffractometry, NMR spectroscopy [1H, 13C{1H}, and 29Si{1H}], electrospray ionization mass spectometry, elemental analysis (C, H, and N), and for the first time also by IR and Raman investigations (for 2 and 3). The new complexes add to the known NHC derivatives and extend the exploration of Ge9 clusters with carbene ligands at CuI atoms.

Highly Ambiphilic Room Temperature Stable Six-Membered Cyclic (Alkyl)(amino)carbenes.

Cyclic (alkyl)(amino)carbenes with a six-membered backbone were prepared. Compared to their five-membered analogues, they feature increased % Vbur and enhanced donor and acceptor properties, as evidenced by the observed n → π* transition trailing into the visible region. The high ambiphilic character even allows for the intramolecular insertion of the carbene into an unactivated C(sp3)-H bond. When used as ligands, they outcompete the five-membered analogues in the palladium-mediated α-arylation of ketones with aryl chlorides.

Controlled Expansion of a Strong-Field Iron Nitride Cluster: Multi-Site Ligand Substitution as a Strategy for Activating Interstitial Nitride Nucleophilicity.

Multimetallic clusters have long been investigated as molecular surrogates for reactive sites on metal surfaces. In the case of the µ4 -nitrido cluster [Fe4 (µ4 -N)(CO)12 ]- , this analogy is limited owing to the electron-withdrawing effect of carbonyl ligands on the iron nitride core. Described here is the synthesis and reactivity of [Fe4 (µ4 -N)(CO)8 (CNArMes2 )4 ]- , an electron-rich analogue of [Fe4 (µ4 -N)(CO)12 ]- , where the interstitial nitride displays significant nucleophilicity. This characteristic enables rational expansion with main-group and transition-metal centers to yield unsaturated sites. The resulting clusters display surface-like reactivity through coordination-sphere-dependent atom rearrangement and metal-metal cooperativity.

Modular Approach to Kekulé Diradicaloids Derived from Cyclic (Alkyl)(amino)carbenes.

A modular approach for the synthesis of Kekulé diradicaloids is reported. The key step is the insertion of a carbene, namely, a cyclic (alkyl)(amino)carbene (CAAC), into the C-H bonds of two terminal alkynes linked by a spacer. Subsequent hydride abstraction, followed by two-electron reduction of the corresponding bis(iminium) salts, affords the desired diradicaloids. This synthetic route readily allows for the installation of communicating spacers, featuring different degrees of aromaticity and lengths, and gives the possibility of generating unsymmetrical compounds with two different CAACs. Electron paramagnetic resonance (EPR), NMR, UV-vis, and X-ray studies in combination with quantum-chemical calculations give insight into the electronic nature of the deeply colored Kekulé diradicaloids. They feature a singlet ground state with varying degrees of diradical character in combination with small singlet/triplet gaps. Upon lengthening of the spacer, the properties of the compounds approach those of monoradicals in which steric protection of the propargyl radical moiety is necessary to inhibit decomposition pathways. Most of these diradicaloids are stable at room temperature, both in solution and in the solid state, but are highly oxygen-sensitive. They represent the first diradicaloids derived from iminium salts.

Organic Mixed Valence Compounds Derived from Cyclic (Alkyl)(amino)carbenes.

Readily available room temperature stable organic mixed valence compounds are prepared by one-electron reduction of cyclic bis(iminium) salts [derived from cyclic (alkyl)(amino)carbenes] bridged by various spacers. These compounds show characteristic intervalence charge transfer (IV-CT) bands in the near-infrared (NIR). Cyclic voltammetry, EPR, IR, UV-vis, and X-ray studies, as well as DFT calculations, show that, depending on the nature of the spacer, these mixed valence compounds range from class III to class II.

Crystalline Monomeric Allenyl/Propargyl Radical.

Reduction of alkynyl iminium salts derived from cyclic (alkyl)(amino)carbenes (CAACs) affords propargyl/allenyl radicals. Depending on the nature of the CAAC and alkyne substituents, these radicals can irreversibly dimerize, exist as monomers in solution but dimerize in the solid state, or can even remain monomeric as solids. The first characterization of an allenyl radical by single crystal X-ray crystallography is reported.

Bicyclic (Alkyl)(amino)carbenes (BICAACs): Stable Carbenes More Ambiphilic than CAACs.

A straightforward strategy allows for the synthesis of storable bicyclic (alkyl)(amino)carbenes (BICAACs), which feature enhanced σ-donating and π-accepting properties compared to monocyclic (alkyl)(amino)carbenes (CAACs). Due to the bicyclo[2.2.2]octane skeleton, the steric environment around the carbene center is different from that of CAACs and similar to that observed in classical N-heterocyclic carbenes. The different electronic properties of BICAACs as compared to CAACs allow for ligand exchange reactions not only at a metal center, but also at main group elements.

Cyclic (Alkyl)(amino)carbenes (CAACs): Recent Developments.

Discovered in 2005, cyclic (alkyl)(amino)carbenes (CAACs) are among the most nucleophilic (σ donating) and also electrophilic (π-accepting) stable carbenes known to date. These properties allow them to activate a variety of small molecules and enthalpically strong bonds, to stabilize highly reactive main-group and transition-metal diamagnetic and paramagnetic species, and to bind strongly to metal centers, which gives rise to very robust catalysts. The most important results published up to the end of 2013 are briefly summarized, while the majority of this Review focuses on findings reported within the last three years.

NHC-CAAC Heterodimers with Three Stable Oxidation States.

The synthesis of N-heterocyclic carbene (NHC)-cyclic (alkyl)(amino) carbene (CAAC) heterodimers is presented. As the free carbenes do not react together in solution, the synthetic approach involves the addition of a free NHC to a cyclic iminium salt, which results in the formation of the protonated heterodimer. Subsequent deprotonation leads to the isolation of the corresponding mixed Wanzlick dimers. One- and two-electron oxidations of these triazaolefins result in the formation of stable cationic radicals and bis(cations), respectively, which have been isolated and fully characterized. Cyclic voltammetry, UV/Vis spectroscopy, spin density, and DFT calculations suggest that these heterodimers feature complementary electronic properties to tetrathiafulvalenes (TTFs).

Synthesis of Hemilabile Cyclic (Alkyl)(amino)carbenes (CAACs) and Applications in Organometallic Chemistry.

A versatile methodology, involving readily available starting materials, allows for the synthesis of stable hemilabile bidentate cyclic (alkyl)(amino)carbenes (CAACs) featuring alkene, ether, amine, imine, and phosphine functionalities. The stability of the free carbenes has been exploited for the synthesis of copper(I) and gold(I) complexes. It is shown that the pendant imine moiety stabilizes the gold(III) oxidation state and enables the C-C bond oxidative addition of biphenylene to the corresponding cationic gold(I) complex. The latter and the corresponding copper(I) complex show high catalytic activity for the hydroarylation of α-methylstyrene with N,N-dimethylaniline, and the copper(I) complex promotes the anti-Markovnikov hydrohydrazination of phenyl acetylene with high selectivity.

Generalization of the Copper to Late-Transition-Metal Transmetallation to Carbenes beyond N-Heterocyclic Carbenes.

Carbene transition-metal complexes have become a prevalent family of catalysts enabling numerous organic transformations. Their facile synthetic access is a matter of great importance. To this end, the Cu(I) -NHC transfer methodology has emerged as a powerful alternative presenting attractive advantages over other methods. Herein, we report the remarkable ability of copper to transfer not only NHCs but also other types of carbenes such as abnormal NHCs (aNHCs), cyclic (alkyl)(amino)carbenes (CAACs), and mesoionic carbenes (MICs) to various transition metal precursors.

Ancillary ligand-free copper catalysed hydrohydrazination of terminal alkynes with NH2NH2.

An efficient and selective Cu-catalysed hydrohydrazination of terminal alkynes with parent hydrazine is reported. The methodology tolerates a broad range of functional groups, allows for the synthesis of symmetrical and unsymmetrical azines, and can be extended to hydrazine derivatives and amines.