N-Heterocyclic carbenes, despite being isolated and characterized three decades ago, still capture scientists’ interest as versatile, modular and strongly coordinating moieties. In the last decade, driven by the increasingly refined fundamental understanding of their behaviour, the emergence of new carbene frameworks and cogent sustainability issues, N-heterocyclic carbenes have experienced a tremendous increase in utilization across several disparate fields. In this Review, a concise overview of N-heterocyclic carbenes encompassing their history, properties and applications in transition metal catalysis, on-surface chemistry, main group chemistry and organocatalysis is provided. Emphasis is placed on developments emerging in the last seven years and on envisaging future directions. N-Heterocyclic carbenes continue to mesmerize scientists and open up new research avenues for academia and industry. Here, we provide a concise and up-to-date overview of N-heterocyclic carbenes, encompassing their history, properties and applications in transition metal catalysis, main group chemistry, on-surface chemistry and organocatalysis.

Recent advances in the chemistry and applications of N-heterocyclic carbenes

Transition-metal-catalysed direct C(sp3)−H functionalization of primary aliphatic amines is an attractive – but elusive – process that could provide efficient access to biologically and pharmaceutically important compounds. Now, a palladium-catalysed γ-arylation of primary alkylamines is achieved using an inexpensive, catalytic and transient directing group.

Site-Selective C−H Arylation of Primary Aliphatic Amines Enabled by a Catalytic Transient Directing Group

Transition-metal-catalyzed decarbonylation via carbon-carbon bond cleavage is an essential synthetic methodology. Given the ubiquity of carbonyl compounds, the selective decarbonylative process offers a distinct synthetic strategy using carbonyl groups as "traceless handles". This reaction has been significantly developed in recent years in many respects, including catalytic system development, mechanistic understanding, substrate scope, and application in the synthesis of complex functional molecules. Therefore, this review aims to summarize the recent progress on transition-metal-catalyzed decarbonylative process, from the discovery of new transformations to the understanding of reaction mechanisms, to reveal the great achievements and potentials in this field. The contents of this review are categorized by the type of chemical bond cleavage in the decarbonylative process. The main challenges and opportunities of the decarbonylative process are also examined with the goal of expanding the application range of decarbonylation reactions.

Selective Decarbonylation via Transition-Metal-Catalyzed Carbon-Carbon Bond Cleavage.

Transition metal complexes bearing N-heterocyclic carbene ligands (NHCs) have gained a place of crucial importance in numerous areas of research such as medicinal chemistry, material sciences, and homogeneous/heterogeneous catalysis In the present review, an updated overview of the main synthetic routes used for the preparation of this broad class of compounds along with their main applications are reported Particular attention will be paid to the synthesis of late transition metal–NHC complexes using weak bases, eco-friendly solvents, and mild operating conditions This simple synthetic approach, also known as the ‘weak base route’, represents a recent development with yet unrealized potential

Synthetic Routes to Late Transition Metal–NHC Complexes

N-Heterocyclic carbenes (NHCs) are efficient Lewis basic catalysts for the umpolung of various polarized unsaturated compounds usually including aldehydes, imines, acyl chlorides and activated esters. NHC catalysis involving electron pair transfer steps has been extensively studied; however, NHC catalysis through single-electron transfer (SET) processes, despite having the potential to achieve chemical transformations of inert chemical bonds and using green reagents, has long been a challenging task in organic synthesis. In parallel, visible-light-induced photocatalysis and photoexcitation have been established as powerful tools to facilitate sustainable organic synthesis, as they enable the generation of various reactive radical intermediates under extremely mild conditions. Recently, a number of elegant visible-light-induced, NHC-catalyzed transformations were developed for accessing valuable organic compounds. As a result, this minireview will highlight the recent advances in this field.

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Light opens a new window for N-heterocyclic carbene catalysis

In this contribution, we provide a comprehensive overview of C-H activation methods promoted by NHC-transition metal complexes, covering the literature since 2002 (the year of the first report on metal-NHC-catalyzed C-H activation) through June 2019, focusing on both NHC ligands and C-H activation methods. This review covers C-H activation reactions catalyzed by group 8 to 11 NHC-metal complexes. Through discussing the role of NHC ligands in promoting challenging C-H activation methods, the reader is provided with an overview of this important area and its crucial role in forging carbon-carbon and carbon-heteroatom bonds by directly engaging ubiquitous C-H bonds.

N-Heterocyclic Carbene Complexes in C–H Activation Reactions

IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) represents the most important NHC (NHC = N-heterocyclic carbene) ligand throughout the field of homogeneous catalysis. Herein, we report the synthesis, catalytic activity, and full structural and electronic characterization of novel, sterically-bulky, easily-accessible NHC ligands based on the hash peralkylation concept, including IPr#, Np# and BIAN-IPr#. The new ligands have been commercialized in collaboration with Millipore Sigma: IPr#HCl, 915653; Np#HCl; 915912; BIAN-IPr#HCl, 916420, enabling broad access of the academic and industrial researchers to new ligands for reaction optimization and screening. In particular, the synthesis of IPr# hinges upon cost-effective, modular alkylation of aniline, an industrial chemical that is available in bulk. The generality of this approach in ligand design is demonstrated through facile synthesis of BIAN-IPr# and Np#, two ligands that differ in steric properties and N-wingtip arrangement. The broad activity in various cross-coupling reactions in an array of N-C, O-C, C-Cl, C-Br, C-S and C-H bond cross-couplings is demonstrated. The evaluation of steric, electron-donating and π-accepting properties as well as coordination chemistry to Au(i), Rh(i) and Pd(ii) is presented. Given the tremendous importance of NHC ligands in homogenous catalysis, we expect that this new class of NHCs will find rapid and widespread application.

/pdf/ipr-highly-hindered-broadly-applicable-n-heterocyclic-1g1356nsbl.pdf

IPr# - highly hindered, broadly applicable N-heterocyclic carbenes

Major progress has recently been made in the challenging redox-neutral decarbonylative cross-coupling of carboxylic acids. For example, the use of acid fluorides as effective cross-coupling partners has been found to enable control of the decarbonylation selectivity and facilitates challenging Pd0 -catalyzed nucleophilic trifluoromethylation and exogenous base-free Suzuki cross-coupling reactions. In another recent advance, the use of acid chlorides in room temperature difluoromethylation and direct decarbonylative cross-coupling of carboxylic acids allows these classical substrates to be used as aryl electrophiles in cross-coupling reactions. Further challenges that are yet to be addressed in redox-neutral decarbonylative cross-couplings are also briefly summarized.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cssc.201900408

Redox-Neutral Decarbonylative Cross-Couplings Coming of Age

Selective activation of neutral carbon–nitrogen bonds is of great synthetic importance, because amines are among the most prevalent motifs across organic and bioactive molecules. Herein, we report ...

Qun Zhao

Papers

N-Heterocyclic Carbene Complexes in C–H Activation Reactions

IPr# - highly hindered, broadly applicable N-heterocyclic carbenes

Redox-Neutral Decarbonylative Cross-Couplings Coming of Age

Ruthenium(0)-Catalyzed Cross-Coupling of Anilineswith Organoboranes by Selective Carbon–Nitrogen Cleavage

Ruthenium(0)-sequential catalysis for the synthesis of sterically hindered amines by C-H arylation/hydrosilylation.