The first N-heterocyclic carbene-based nickel catalyst for C-S coupling

We have developed the first N-heterocyclic carbene (NHC)-based transition metal catalysts for C-S coupling reactions. Ni-NHC catalysts showed good to excellent activities toward various aryl halides in C-S coupling reactions. The catalytic activities were greatly affected by the electronic and steric properties of the NHC ligands. The new catalysts were inexpensive, easy to synthesize, and environmentally friendly. They could be excellent candidates to replace Pd-organophosphanes for C-S coupling catalysis.     

N-heterocyclic carbene-catalyzed radical reactions

While N-heterocyclic carbene(NHC)catalyzed electron-pair-transfer processes have been developed into an important tool for synthetically important bond formations during the past decades,the corresponding radical reactions via NHC catalysis have only received growing attention in the past six years.Taking into account the advantages NHC-catalyzed radical reactions might bring,such as creating new activation modes that were previously unobtainable,it is worthwhile to provide a conceptual understanding of this emerging area.Therefore,herein we give an overview of NHC-catalyzed radical reactions via different synthetic techniques.     

N‐Heterocyclic Carbene/Copper Cooperative Catalysis for the Asymmetric Synthesis of Spirooxindoles

Highly enantioselective [3+3] and [3+4] annulations of isatin‐derived enals with ethynylethylene carbonates and ethynyl benzoxazinanones are enabled by NHC/cooper cooperative catalysis, leading to a big library of spirooxindole derivatives in high structural diversity and enantioselectivity (up to 99 % ee). Both reactions represent a nicely synergistic integration of NHC and copper catalysis, in which both catalysts activate the substrates and the chiral NHC perfectly controls the stereochemistry.     

Nickel and palladium <Emphasis Type="Italic">N</Emphasis>-heterocyclic carbene complexes. Synthesis and application in cross-coupling reactions

N-Heterocyclic carbenes (NHCs) are widely used as ligands in catalysis by transition metal complexes. The catalytic activity of transition metal NHC complexes is much higher than that of the transition metal complexes bearing the phosphine and nitrogen-containing ligands. They show excellent catalytic performance in different transformations of the organic compounds, especially in the carbon—carbon and carbon—element bond forming reactions. Palladium NHC complexes are very efficient catalysts for the cross-coupling reactions. On the other hand, nickel is less expensive and regarded as a promising alternative to palladium and, therefore, it attracts increasing attention from the researches. The present review is focused on the recent advances in the synthesis of N-heterocyclic carbene complexes of nickel and palladium and their application in catalysis of cross-coupling reactions of organic, organoelement and organometallic compounds with organic halides.     

Comparative investigation of ruthenium-based metathesis catalysts bearing N-heterocyclic carbene (NHC) ligands

Exchange of one PCy3 unit of the classical Grubbs catalyst 1 by N-heterocyclic carbene (NHC) ligands leads to "second-generation" metathesis catalysts of superior reactivity and increased stability. Several complexes of this type have been prepared and fully characterized, six of them by X-ray crystallography. These include the unique chelate complexes 13 and 14 in which the NHC- and the Ru-CR entities are tethered to form a metallacycle. A particularly favorable design feature is that the reactivity of such catalysts can be easily adjusted by changing the electronic and steric properties of the NHC ligands. The catalytic activity also strongly depends on the solvent used; NMR investigations provide a tentative explanation of this effect. Applications of the "second-generation" catalysts to ring closing alkene metathesis and intramolecular enyne cycloisomerization reactions provide insights into their catalytic performance. From these comparative studies it is deduced that no single catalyst is optimal for different types of applications. The search for the most reactive catalyst for a specific transformation is facilitated by IR thermography allowing a rapid and semi-quantitative ranking among a given set of catalysts.     

Recent advances in tertiary amine Lewis base-promoted cycloadditions of allenoates

Lewis base-catalyzed annulations of allenoates have been one of the most powerful synthetic strategies for the synthesis of various valuable cycles, especially in the preparation of biologically active natural products and pharmaceuticals. Generally, the effective Lewis bases mainly include tertiary phosphine,NHC and tertiary amine catalysts, among those catalysis, tertiary amine Lewis bases have proven to be effective catalysts for a range of synthetic transformations. In the past decades, trem...     

Recent advances in annulations enabled by nucleophilic Lewis base/metal dual catalysis

Metal/nucleophilic Lewis base dual catalysis has been recognized as a reliable and promising strategy for finishing ideal organic synthesis over the past decades. The new strategy can usually achieve some chemical reactions that cannot be realized by the traditionally mono-catalytic system, dramatically expanding the synthetic utility of chemical transformations by leveraging additional activation modes. Thus considerable progress has been made in the synthesis of a wide range of heterocyclic and biologically active compounds by using the combination of diversely metal/nucleophilic Lewis base dual catalysts, including metal/phosphine, metal/N-heterocyclic carbene (NHC) and metal/tertiary amine dual catalysis systems. In this review, we describe a comprehensive and updated advance of metal/nucleophilic Lewis base dual catalytic annualtion reactions, meanwhile, the related mechanism and the application of these annulation strategies in natural product total synthesis will be highlighted in detail.     

An Original L‐shape,Tunable N‐Heterocyclic Carbene Platform for Efficient Gold(I) Catalysis

The synthesis and characterization of original NHC ligands based on an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold functionalized with a flanking barbituric heterocycle is described as well as their use as tunable ligands for efficient gold‐catalyzed C?N, C?O, and C?C bond formations. High activity, regio‐, chemo‐, and stereoselectivities are obtained for hydroelementation and domino processes, underlining the excellent performance (TONs and TOFs) of these IPy‐based ligands in gold catalysis. The gold‐catalyzed domino reactions of 1,6‐enynes give rise to functionalized heterocycles in excellent isolated yields under mild conditions. The efficiency of the NHC gold 5^Me complex is remarkable and mostly arises from a combination of steric protection and stabilization of the cationic Au^I active species by ligand 1^Me .     

An Original L‐shape,Tunable N‐Heterocyclic Carbene Platform for Efficient Gold(I) Catalysis

The synthesis and characterization of original NHC ligands based on an imidazo[1,5‐a]pyridin‐3‐ylidene (IPy) scaffold functionalized with a flanking barbituric heterocycle is described as well as their use as tunable ligands for efficient gold‐catalyzed C?N, C?O, and C?C bond formations. High activity, regio‐, chemo‐, and stereoselectivities are obtained for hydroelementation and domino processes, underlining the excellent performance (TONs and TOFs) of these IPy‐based ligands in gold catalysis. The gold‐catalyzed domino reactions of 1,6‐enynes give rise to functionalized heterocycles in excellent isolated yields under mild conditions. The efficiency of the NHC gold 5^Me complex is remarkable and mostly arises from a combination of steric protection and stabilization of the cationic Au^I active species by ligand 1^Me .     

Chiral N-heterocyclic carbenes as stereodirecting ligands in asymmetric catalysis

In recent years, N-heterocyclic carbenes (NHC) have proved to be a versatile class of spectator ligands in homogeneous catalysis. Being robust anchoring functions for late transition metals, their ligand donor capacity and their molecular shape is readily modified by variation of the substituents at the N-atoms and the structure of the cyclic backbone. After the first attempts to use chiral NHC ligands in asymmetric catalysis in the late 1990's, which initially met with limited success, several novel structural concepts have emerged during the past two years which have led literally to an explosion of the field. With a significant number of highly selective chiral catalysts based on chiral NHCs having been reported very recently, several general trends in the design of new NHC-containing molecular catalysts for stereoselective transformations in organic synthesis emerge.     

Silver(I)-carbene complexes/ionic liquids: novel N-heterocyclic carbene delivery agents for organocatalytic transformations

[reaction: see text] N-Heterocyclic carbene (NHC) complexes with silver were investigated as sources of unsaturated NHC carbene catalysts via thermal decomposition. The NHC complex (1-ethyl-3-methylimidazol-2-ylidene)silver(I) chloride is an ionic liquid, and was found to catalyze the ring-opening polymerization of lactide at elevated temperatures to give narrowly dispersed polylactide of predictable molecular weight. Silver-carbene complexes can also be used for the catalysis of small molecule transesterification reactions. Thermolysis of the silver complexes in the presence of CS(2) yielded the zwitterionic CS(2) adducts of the carbene, implicating the intermediacy of the free carbene in these reactions.     

Chiral iridium(I) bis(NHC) complexes as catalysts for asymmetric transfer hydrogenation

The common use of NHC complexes in transition‐metal mediated C–C coupling and metathesis reactions in recent decades has established N‐heterocyclic carbenes as a new class of ligand for catalysis. The field of asymmetric catalysis with complexes bearing NHC‐containing chiral ligands is dominated by mixed carbene/oxazoline or carbene/phosphane chelating ligands. In contrast, applications of complexes with chiral, chelating bis(NHC) ligands are rare. In the present work new chiral iridium(I) bis(NHC) complexes and their application in the asymmetric transfer hydrogenation of ketones are described. A series of chiral bis(azolium) salts have been prepared following a synthetic pathway, starting from L ‐valinol and the modular buildup allows the structural variation of the ligand precursors. The iridium complexes were formed via a one‐pot transmetallation procedure. The prepared complexes were applied as catalysts in the asymmetric transfer hydrogenation of various prochiral ketones, affording the corresponding chiral alcohols in high yields and moderate to good enantioselectivities of up to 68%. The enantioselectivities of the catalysts were strongly affected by the various, terminal N‐substituents of the chelating bis(NHC) ligands. The results presented in this work indicate the potential of bis‐carbenes as stereodirecting ligands for asymmetric catalysis and are offering a base for further developments. Copyright © 2010 John Wiley & Sons, Ltd.     

Recyclable and eco-friendly Pd-complexed graphene oxide/N-heterocyclic carbene catalyst for various coupling reactions in aqueous phase

In this study, we report recyclable Pd-complexed graphene oxide (GO) catalysts with a bulky N-heterocyclic carbene (NHC) ligand (GO/NHC-Pd) for various cross-coupling reactions in the aqueous phase. To prepare GO/NHC-Pd, the NHC precursor and a trimethoxy-silane linker were combined on the GO surface via condensation, followed by the Pd chelation over GO/NHC. The GO-based catalysts were applied to three types of CC cross-coupling reactions including Suzuki, Heck and Sonogashira reactions in the aqueous phase, to evaluate their catalytic performance. The reusability of the catalysts was tested by performing five consequent cross-coupling reactions.     

Exploring Molecular Complexity by N-Heterocyclic Carbene Organocatalysis: New Activation and Reaction Diversity

The development of catalytic synthetic approaches towards molecular complexity from simple materials continues to be an ultimate goal in synthetic chemistry. Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has been extensively investigated to provide opportunities for a vast number of novel chemical transformations. Various activation modes and reactive intermediates enabled by NHC small-molecule catalysts, such as Breslow intermediates, (homo)enolates, acyl azoliums and their derived unsaturated azoliums exhibit great potential in the construction of complicated skeletons. This personal account will summarize our group's recent work in the exploration of new activation modes of NHC catalysis towards molecular complexity with a focus on the development and applications of NHC to achieve diversity and enantioselectivity in the preparation of functional molecules.     

Single-Electron Transfer Reactions Enabled by N-Heterocyclic Carbene Organocatalysis

Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has undergone a flourish of development on the basis of closed-shell reaction paths. By contrast, the emerging area of single-electron transfer (SET) reactions enabled by NHC catalysis still remain underdeveloped, but offer plenty of opportunities to develop new catalytic modes and useful synthetic methods. A number of interesting transformations were triggered by the SET process from the electron-rich Breslow intermediates to various single-electron acceptors. In additions, recent studies revealed that the Breslow radical cations could also be generated by single-electron reduction of the electron-deficient acyl azolium intermediates. These discoveries open a new avenue for NHC organocatalysis to harness radical reactions. The present review will focus on the exciting advancements in the dynamic area of radical NHC organocatalysis.     

Auto‐Tandem Catalysis: A Single Catalyst Activating Mechanistically Distinct Reactions in a Single Reactor

Domino reactions have received great attention as efficient synthetic methodologies for the construction of structurally complex molecules from simple materials in a single operation. Catalysts in domino reactions have also been well studied. In these reactions, a catalyst activates the substrate(s) only once, and the structure of the product is delineated at that time. Recently, the new concept of “tandem catalysis” in domino reactions, in which catalyst(s) sequentially activate more than two mechanistically distinct reactions, has been proposed. Tandem catalysis is categorized into three subclasses: orthogonal‐, auto‐, and assisted‐tandem catalyses. Auto‐tandem catalysis is defined as a process in which one catalyst promotes more than two fundamentally different reactions in a single reactor. An overview of recent and significant achievements in auto‐tandem catalysis is presented in this paper.     

Exploring Cooperative Effects in Oxidative NHC Catalysis: Regioselective Acylation of Carbohydrates

The utility of oxidative NHC catalysis for both the regioselective and chemoselective functionalization of carbohydrates is explored. Chiral NHCs allow for the highly regioselective oxidative esterification of various carbohydrates using aldehydes as acylation precursors. The transformation was also shown to be amenable to both cis/trans diol isomers, free amino groups, and selective for specific sugar epimers in competition experiments. Efficiency and regioselectivity of the acylation can be improved upon using two different NHC catalysts that act cooperatively. The potential of the method is documented by the regioselective acylation of an amino‐linked neodisaccharide.     

Nickel-Catalyzed Arylative Cyclizations of Alkyne- and Allene-Tethered Electrophiles using Arylboron Reagents

The use of arylboron reagents in metal-catalyzed domino addition–cyclization reactions is a well-established strategy for the preparation of diverse, highly functionalized carbo- and heterocyclic products. Although rhodium- and palladium-based catalysts have been commonly used for these reactions, more recent work has demonstrated nickel catalysis is also highly effective, in many cases offering unique reactivity and access to products that might otherwise not be readily available. This review gives an overview of nickel-catalyzed arylative cyclizations of alkyne- and allene-tethered electrophiles using arylboron reagents. The scope of the reactions is discussed in detail, and general mechanistic concepts underpinning the processes are described.     

Aerobic Oxidative N-Heterocyclic Carbene Catalysis

The ease with which simple starting materials can be transformed into highly functionalized products has made oxidative N-heterocyclic carbene (NHC) catalysis an area of significant interest. However, the use of stoichiometric amounts of high molecular weight oxidants in most reactions generates an undesired equivalent amount of waste. To address this issue, the use of oxygen as the terminal oxidant in NHC catalysis has been developed. Oxygen is attractive due to its low cost, low molecular weight, and ability to generate water as the sole by-product. However, molecular oxygen is challenging to use as a reagent in organic synthesis due to its unreactive ground state, which often requires reactions to be run at high temperatures and results in the formation of kinetic side-products. This review covers the development of aerobic oxidative carbene catalysis, including NHC-catalyzed reactions with oxygen, strategies for oxygen activation, and selectivity issues under aerobic conditions.     

Lessons from nature: biomimetic organocatalytic carbon-carbon bond formations

Nature utilizes simple C2 and C3 building blocks, such as dihydroxyacetone phosphate (DHAP), phosphoenolpyruvate (PEP), and the "active aldehyde" in various enzyme-catalyzed carbon-carbon bond formations to efficiently build up complex organic molecules. In this Perspective, we describe the transition from using enantiopure chemical synthetic equivalents of these building blocks, employing our SAMP/RAMP hydrazone methodology and metalated chiral alpha-amino nitriles, to the asymmetric organocatalytic versions developed in our laboratory. Following this biomimetic strategy, the DHAP equivalent 2,2-dimethyl-1,3-dioxan-5-one (dioxanone) has been used in the proline-catalyzed synthesis of carbohydrates, aminosugars, carbasugars, polyoxamic acid, and various sphingosines. Proline-catalyzed aldol reactions involving a PEP-like equivalent have also allowed for the asymmetric synthesis of ulosonic acid precursors. By mimicking the "active aldehyde" nucleophilic acylations in Nature catalyzed by the thiamine-dependent enzyme, transketolase, enantioselective N-heterocyclic carbene-catalyzed benzoin and Stetter reactions have been developed. Finally, based on Nature's use of domino reactions to convert simple building blocks into complex and highly functionalized molecules, we report on our development of biomimetic asymmetric multicomponent domino reactions which couple enamine and iminium catalysis.