Frontispiece: BIAN-NHC Ligands in Transition-Metal-Catalysis: A Perfect Union of Sterically Encumbered,Electronically Tunable N-Heterocyclic Carbenes?

The discovery of NHCs (NHC = N-heterocyclic carbenes) as ancillary ligands in transition-metal-catalysis ranks as one of the most important developments in synthesis and catalysis. It is now well-recognized that the strong σ-donating properties of NHCs along with the ease of scaffold modification and a steric shielding of the N-wingtip substituents around the metal center enable dramatic improvements in catalytic processes, including the discovery of reactions that are not possible using other ancillary ligands. In this context, although the classical NHCs based on imidazolylidene and imidazolinylidene ring systems are now well-established, recently tremendous progress has been made in the development and catalytic applications of BIAN-NHC (BIAN = bis(imino)acenaphthene) class of ligands. The enhanced reactivity of BIAN-NHCs is a direct result of the combination of electronic and steric properties that collectively allow for a major expansion of the scope of catalytic processes that can be accomplished using NHCs. BIAN-NHC ligands take advantage of (1) the stronger σ-donation, (2) lower lying LUMO orbitals, (3) the presence of an extended π-system, (4) the rigid backbone that pushes the N-wingtip substituents closer to the metal center by buttressing effect, thus resulting in a significantly improved control of the catalytic center and enhanced air-stability of BIAN-NHC-metal complexes at low oxidation state. Acenaphthoquinone as a precursor enables facile scaffold modification, including for the first time the high yielding synthesis of unsymmetrical NHCs with unique catalytic properties. Overall, this results in a highly attractive, easily accessible class of ligands that bring major advances and emerge as a leading practical alternative to classical NHCs in various aspects of catalysis, cross-coupling and C−H activation endeavors.     

The importance of four-membered NHCs in stabilizing Breslow intermediates on benzoin condensation pathway

N-heterocyclic carbenes (NHCs) have been established to be effective organocatalysts for facilitating the benzoin condensation and many other reactions. These reactions involve the formation of a Breslow intermediate (BI), which exhibits umpolung chemistry. To facilitate organocatalysis, several new cyclic carbenes are being introduced, four-membered NHCs are of special interest. Whether these NHCs can exhibit catalytic influence or not, can be evaluated by exploring the potential energy surface (PES) of the benzoin condensation reaction. Quantum chemical analysis has been carried out to compare the PES of these four-membered NHCs with that of standard five-membered NHCs to explore their catalytic ability. The barrier for the first step of the reaction for the formation of BI is comparable in all the cases. But the barrier for the second step of the reaction leading to the benzoin formation from BI is estimated to be very high for the four membered NHCs. These results indicate that the probability of identifying and isolating the BI is very high in comparison to the completion of benzoin condensation reaction in the case of the four-membered NHCs.     

Catalytic enantioselective Steglich rearrangements using chiral N-heterocyclic carbenes

The evaluation of a range of enantiomerically pure NHCs, prepared in situ from imidazolinium or triazolium salt precatalysts, to promote the catalytic enantioselective Steglich rearrangement of oxazolyl carbonates to their C-carboxyazlactones, is reported. Modest levels of enantioselectivity (up to 66% ee) are observed using oxazolidinone derived NHCs.     

N-heterocyclic carbenes: reagents, not just ligands!

The unique properties of N-heterocyclic carbenes (NHCs) have attracted much attention, mainly from theorists and organometallic chemists, the latter using them impressively as ligands for metals. Less well known, however, has been their suitability as excellent catalysts and nucleophilic reagents. Transesterification, nucleophilic aromatic substitution, and cycloaddition reactions are examples in which NHCs can play an important role. Asymmetric reactions using catalytic amounts of chiral NHCs are an efficient approach to optically active compounds. This minireview focuses on this aspect of the chemistry of NHCs.     

Amine‐Linked N‐Heterocyclic Carbenes: The Importance of an Pendant Free‐Amine Auxiliary in Assisting the Catalytic Reaction

We have successfully expanded the library of amino–NHCs with varying substituents on the amine group, leading to insight about the instability of NHCs arising from the intermolecular interaction of the dangling amine side‐arm. However, the pendant amine plays an important role with respect to the catalytic process, resuscitating the catalytic activity of unsaturated NHC’s through a synergistic effect invoked by the secondary amine. This proof of concept allows us to expand the spectrum of catalysis to C C, as well as C B bond formation.     

镍N-杂环卡宾配合物在均相催化偶联反应中的应用

 近十几年来, N-杂环卡宾的配位化学和金属有机化学发展迅速, 已成为均相催化反应中研究最为广泛的配体之一. 在许多过渡金属催化的有机合成反应中特别是偶联反应中, N-杂环卡宾与传统有机膦配体相比具有较高的反应性. 镍价格低廉, 在很多反应中有望替代贵金属钯催化剂. 本文总结了镍 N-杂环卡宾化合物在催化交叉偶联反应和还原偶联反应中的最新应用进展.     

Palladium–N-heterocyclic carbene complexes for the Mizoroki–Heck reaction: An appraisal

This article presents a review of the most significant developments with N-heterocyclic carbene (NHC)–palladium catalytic systems used for the Heck reaction. For more than the past two decades, a large number of new NHC–Pd complexes have been synthesized and characterized. These studies focused on NHCs as a phosphine analogue, but the current review highlights the differences with particular ligands so as to attain a suitable balance between the electronic and bulky environments around the metal. NHCs have gained wide recognition as these ligands act as excellent σ-donors that form stable metal–NHCs with strong metal–carbon bonds. For this reason, metal–NHCs are commonly used as they are highly reactive and can selectively serve as catalysts for various chemical transformations. The objective of our article is to highlight significant recent progress in NHC–Pd(II) complexes and provide an overview of their extensive interaction in the Mizoroki–Heck reaction.     

Synthesis of Carbene-Metal-Amido (CMA) Complexes and Their Use as Precatalysts for the Activator-Free,Gold-Catalyzed Addition of Carboxylic Acids to Alkynes

A straightforward synthetic protocol leading to carbene–metal–amido (CMA) complexes (metal=Au, Cu) using a mild base and an environmentally desirable solvent (EtOH) has been explored, with a focus on complexes bearing backbone-substituted N-heterocyclic carbene (NHC) ligands, including BIAN-NHCs (BIAN=bis(imino)acenaphthene). The novel CMAs were structurally characterized, and gold-based CMAs bearing diverse NHCs were screened as simple, Brønsted-basic precatalysts. The readily accessible complexes display high catalytic activity in the intermolecular and intramolecular hydrocarboxylation of internal alkynes and alkynoic acids respectively, while the screening reveals the ancillary ligand effect of NHCs in these catalytic systems.     

Recent advances in the synthesis,structural diversity,and applications of mesoionic 1,2,3-triazol-5-ylidene metal complexes

Beyond the classic N-heterocyclic carbenes (NHCs) there is a subclass of NHCs called mesoionic carbenes (MICs). This review focuses on recent advances in the area of 1,2,3-triazol-5-ylidenes as the most abundant class of MICs and their metal complexes. The study of mesoionic 1,2,4- and 1,3,4-trisubstituted 1,2,3-triazol-5-ylidene transition metal complexes is a research area with a history of just ～10 years. During this relatively short period, hundreds of these complexes have appeared in the literature, reflecting their high stability and simpler synthesis compared with NHCs. Specifically, this review is focused on advances in the synthesis of 1,2,3-triazol-5-ylidene metal complexes derived from palladium, silver, gold, ruthenium, iridium, rhodium, iron, molybdenum, cobalt, nickel, platinum, and osmium, together with their catalytic, medicinal, and photophysical applications.     

Sulfur-functionalized N-heterocyclic carbene complexes of Pd(II): syntheses, structures and catalytic activities

N-heterocyclic carbenes (NHCs) can be easily modified by introducing functional groups at the nitrogen atoms, which leads to versatile coordination chemistry as well as diverse catalytic applications of the resulting complexes. This article summarizes our contributions to the field of NHCs bearing different types of sulfur functions, i.e., thioether, sulfoxide, thiophene, and thiolato. The experimental evidence for the truly hemilabile coordination behavior of a Pd(II) thioether-NHC complex has been reported as well. In addition, complexes bearing rigid CSC-pincer ligands have been synthesized and the reasons for pincer versus pseudo-pincer formation investigated. Incorporation of the electron-rich thiolato function resulted in the isolation of structurally diverse complexes. The catalytic activities of selected complexes have been tested in Suzuki-Miyaura, Mizoroki-Heck and hydroamination reactions.     

Anionic tethered N-heterocyclic carbene chemistry

Since the discovery of a stable "bottleable" N-heterocyclic carbene (NHC), there has been a spectacular explosion of interest in this ligand class. This interest stems from a desire to understand the fundamentals of the structure and bonding of these systems, but also because of their numerous and emerging applications in small molecule activation, homogeneous catalysis and Lewis acid-catalysed reactions. In this Tutorial Review, we introduce the reader to NHCs, cover general synthetic methods to prepare anionic tethered NHCs and their metal complexes, and discuss emerging applications in reactivity and catalytic studies.     

Remote Electronic Tuning of Chiral N-Heterocyclic Carbenes

Our recent efforts to develop novel N-Heterocyclic carbene (NHC)-catalyzed asymmetric reactions are described. During our investigation for development of the acylation reactions via acylazoliums generated by the reactions of NHCs and α-oxidized aldehydes, we have observed significant effects of substitution at a remote site of the carbene carbon of NHCs. In addition, we also observed a significant enhancement of the enantioselectivity by the addition of carboxylate anions. From this observation, we proposed a novel working hypothesis involving a formation of a complex of the substrate and additive to reinforce the recognition of the catalyst for enhancement of the catalytic performance of the asymmetric N-heterocyclic carbene system. By applying this concept, we achieved the kinetic resolutions of both cyclic and acyclic alcohols in excellent enantioselectivities. The effects of the remote substitution were also observed in intramolecular Stetter reaction and intermolecular benzoin reaction. In these reactions, the comparison of the catalytic performance of the NHCs bearing variable remote substitutions provided insights into the reaction mechanism because the remote substitution tuned the electronic nature of NHCs without affecting the steric and electrostatic factors around the reaction site. We also developed an intramolecular benzoin condensation involving two aldehydes, which is challenging to realize. Using the substrates bearing proper protecting groups, we succeeded in the stereo divergent synthesis of a variety of inososes, which are important intermediates for the synthesis of biologically active cyclitols.     

N-heterocyclic carbene-catalyzed Michael additions of 1,3-dicarbonyl compounds

A study of the organocatalytic activity of N‐heterocyclic carbenes (NHCs) in the Michael addition of 1,3‐dicarbonyl compounds has allowed us to identify 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene (IPr) as an excellent catalyst for this transformation (up to 99 % yield with a 2.5 mol % catalyst loading), and the reaction was found to be of broad scope. Two early applications of this unprecedented catalytic activity of NHCs are described, that is, the domino carbocyclization reactions of simple cyclic 1,3‐dicarbonyl and malonic acid derivatives, which allow stereoselective access to bridged bicyclic compounds, and the stereoselective synthesis of cyclohexanols (or cyclohexene). Early mechanistic investigations are also reported.     

Stable Cyclic Carbenes and Related Species beyond Diaminocarbenes

The success of homogeneous catalysis can be attributed largely to the development of a diverse range of ligand frameworks that have been used to tune the behavior of various systems. Spectacular results in this area have been achieved using cyclic diaminocarbenes (NHCs) as a result of their strong σ‐donor properties. Although it is possible to cursorily tune the structure of NHCs, any diversity is still far from matching their phosphorus‐based counterparts, which is one of the great strengths of the latter. A variety of stable acyclic carbenes are known, but they are either reluctant to bind metals or they give rise to fragile metal complexes. During the last five years, new types of stable cyclic carbenes, as well as related carbon‐based ligands (which are not NHCs), and which feature even stronger σ‐donor properties have been developed. Their synthesis and characterization as well as the stability, electronic properties, coordination behavior, and catalytic activity of the ensuing complexes are discussed, and comparisons with their NHC cousins are made.     

N-heterocyclic carbene-catalyzed silyl enol ether formation

N-Heterocyclic carbenes (NHCs) were found to catalyze the silyl transfer from trialkylsilyl ketene acetals to ketones. In the presence of a catalytic amount of NHC 3 (IAd, 0.1 to 5 mol %), a series of enolizable ketones as well as cyclohexanecarboxaldehyde were efficiently converted into the corresponding silyl enol ethers at 23 degrees C in THF.     

N-杂环卡宾催化选择性有机反应的新进展

近年来,有关N-杂环卡宾(NHC)的合成、催化性能及其应用得到了快速发展,特别是在催化选择性有机反应领域,NHC类催化剂显示出催化效率高、选择性好及性能优异等特点,而引起人们极大的关注。 本文从区域选择性、顺反异构选择性及手性选择性等方面综述了NHC催化选择性有机反应的最新进展,并予以了展望。     

Palladacycles bearing COOH‐/ester‐functionalized N‐heterocyclic carbenes: Divergent syntheses and catalytic applications

Two new [C^N]‐type palladacyclic dinuclear complexes bearing carboxylate‐containing N‐heterocyclic carbenes (NHCs) were synthesized, and in both cases the carboxylato‐NHC ligand adopts a bridging mode. Both complexes proved to be suitable precursors, which can be used to divergently access palladacycles bearing ester‐ or COOH‐functionalized NHCs upon esterification or acidolysis. In the esterification reactions, alkyl halides are found to selectively react with the carboxylato moieties, and the palladacycle scaffold is retained even when excess haloalkane is employed. In the acidolysis reactions, the desired COOH‐tethered complexes can only be obtained when stoichiometric acid (with respect to Pd) is used, while excess acid destroys the metallacycle scaffold. Finally, a preliminary catalytic study reveals the good performances of all newly synthesized complexes in direct aromatic C─H functionalization reactions with alkynes. Poisoning experiments indicate that these hydroarylation reactions are likely to be homogeneously catalyzed.     

N‐Heterocyclic Carbene Catalyzed Enantioselective α‐Fluorination of Aliphatic Aldehydes and α‐Chloro Aldehydes: Synthesis of α‐Fluoro Esters,Amides, and Thioesters

The asymmetric fluorination of azolium enolates that are generated from readily available simple aliphatic aldehydes or α‐chloro aldehydes and N‐heterocyclic carbenes (NHCs) is described. The process significantly expands the synthetic utility of NHC‐catalyzed fluorination and provides facile access to a wide range of α‐fluoro esters, amides, and thioesters with excellent enantioselectivity. Pyrazole was identified as an excellent acyl transfer reagent for catalytic amide formation.     

NHC Effects on Reduction Dynamics in Iron-Catalyzed Organic Transformations**

The high abundance, low toxicity and rich redox chemistry of iron has resulted in a surge of iron-catalyzed organic transformations over the last two decades. Within this area, N-heterocyclic carbene (NHC) ligands have been widely utilized to achieve high yields across reactions including cross-coupling and C−H alkylation, amongst others. Central to the development of iron-NHC catalytic methods is the understanding of iron speciation and the propensity of these species to undergo reduction events, as low-valent iron species can be advantageous or undesirable from one system to the next. This study highlights the importance of the identity of the NHC on iron speciation upon reaction with EtMgBr, where reactions with SIMes and IMes NHCs were shown to undergo β-hydride elimination more readily than those with SIPr and IPr NHCs. This insight is vital to developing new iron-NHC catalyzed transformations as understanding how to control this reduction by simply changing the NHC is central to improving the reactivity in iron-NHC catalysis.     

Chiral N-heterocyclic carbene catalyzed staudinger reaction of ketenes with imines: highly enantioselective synthesis of N-Boc beta-lactams

N-heterocyclic carbenes (NHCs) were demonstrated to be efficient catalysts for the Staudinger reaction of ketenes with N-tosyl, N-benzyloxycarbonyl, or N-tert-butoxycarbonyl imines. Chiral NHC 8b, conveniently prepared from L-pyroglutamic acid, catalyzed the reactions of arylalkylketenes with a variety of N-tert-butoxycarbonyl arylimines to give the corresponding cis-beta-lactams in good yields with good diastereoselectivities and excellent enantioselectivities (up to 99% ee). Two possible catalytic pathways, initiated by the addition of NHC to ketenes or imines, were discussed.