IPr**-Highly Hindered, Ring Extended N-Heterocyclic Carbenes.

There is a strong demand for the development of sterically-hindered N-heterocyclic carbenes due to their potential to stabilize reactive organometallic species. IPr* (IPr* = 1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazo-2-ylidene) is a highly-hindered and sterically-flexible ligands, which has found broad utilization in coordination chemistry. Herein, we report the synthesis, structural and electronic characterization of IPr** - a class of novel, sterically-bulky and easily-accessible N-heterocyclic carbene ligands that bearing biphenyl wingtips.

Cationic and Homoleptic Copper(I)-Thiazol-2-ylidenes: Highly Reactive Thiazole N-Heterocyclic Carbenes σ-Lewis Acid Catalysts.

Air- and moisture-stable cationic homoleptic Cu(I) thiazol-2-ylidene complexes are developed as highly efficient σ-Lewis acid catalysts, outperforming imidazol-2-ylidenes in the alkynylation of ketones without requiring stoichiometric Cu-acetylides. These complexes exhibit exceptional operational simplicity and robustness, enabling key C-C bond formation. Structural insights and DFT studies highlight their enhanced reactivity and stability.

Diversification of Pharmaceuticals via Late-Stage Hydrazination.

Developments in organic synthesis over the past century have greatly enabled the discovery of life-saving medicines. In this context, over the past two decades, palladium-catalyzed cross-coupling reactions have transformed the exploration of emerging therapeutics. However, the cross-coupling between aryl halides and hydrazine, NHNH, the smallest bis-nitrogen nucleophile, has been a long-standing challenge due to the reducing capacity of hydrazine and the presence of multiple N-H bonds.

IPaul - spatially-defined, wingtip-flexible, N,C-chelating oxazole and thiazole donor N-heterocyclic carbene ligands.

N-Heterocyclic carbenes (NHCs) are among the most versatile ligands in transition metal catalysis with their steric and electronic properties playing a critical role in governing reactivity and selectivity. In this area, the wingtip unsymmetrical IPaul ligand introduced by Nelson and co-workers offers a unique balance of steric bulk and flexibility characterized by spatially-defined steric features. Herein, we report a new class of IPaul-based ligands bearing benzoxazole and benzothiazole donor wingtips.

Gold(I) Complexes of ImPyDippDipp and ImPyMesMes: Biaryl L‑Shaped N‑Heterocyclic Carbene Analogues of IPr and IMes.

Imidazol-2-ylidenes, IPr and IMes, represent by far the most important and widely utilized N-heterocyclic carbenes in organic synthesis and catalysis. Herein, we report the synthesis, catalytic activity, and structural and electronic characterization of ImPyDippDipp and ImPyMesMes, sterically bulky and easily accessible biaryl L-shaped N-heterocyclic carbene analogues of IPr and IMes. These ligands exploit the rigid imidazo-[1,5-]-pyridin-3-ylidene architecture to merge the properties of the biaryl scaffold with the electron-rich characteristics of the carbene center.

IBzH (IBenzhydryl): Sterically-Flexible -Aliphatic -Heterocyclic Carbenes (NHCs) for Iron-Catalyzed C(sp)-C(sp) Cross-Coupling of Unactivated Haloalkanes.

Iron-catalyzed cross-coupling has emerged as a pivotal concept for the synthesis of valuable products across various facets of chemical research, including pharmaceuticals, organic materials and biological probes. In this respect, the use of -heterocyclic carbenes (NHCs) as ancillary ligands to iron has been particularly powerful. However, the major limitation is that the successful iron-catalytic systems have been almost exclusively limited to -aryl--heterocyclic carbenes, which significantly restricts future developments of this commanding catalysis platform.

IPr*: Sterically Adaptable Dinuclear N-Heterocyclic Carbenes.

N-Heterocyclic carbenes (NHCs) have been established as the predominant ligand class in inorganic and organometallic chemistry. Simultaneously, there has been a major interest in dinuclear ligands, where cooperative effects between the metal centers have been widely exploited across numerous research avenues. Herein, we report the synthesis of dinuclear sterically hindered and adaptable N-heterocyclic ligands based on the modular IPr* framework.

Pd-Catalyzed Decarbonylative Suzuki-Miyaura Cross-Coupling of Pyramidalized N-Mesyl Amides by a Tandem N-C(O)/C-C Bond Activation.

The Suzuki-Miyaura biaryl cross-coupling is the pivotal technology for carbon-carbon coupling in pharmaceutical, polymer, and agrochemical fields. A long-standing challenge has been the development of efficient precursors for the decarbonylative cross-coupling of amide bonds. Herein, we report a highly chemoselective palladium-catalyzed Suzuki-Miyaura cross-coupling of -mesyl amides for the synthesis of biaryls by a tandem N-C(O)/C-C bond activation with high selectivity for decarbonylative cleavage.

IPr Complexes-Highly-Hindered, Sterically-Bulky Cu(I) and Ag(I) N-Heterocyclic Carbenes: Synthesis, Characterization, and Reactivity.

Metal-N-heterocyclic carbene (M-NHC) complexes are well-known as an important class of organometallic compounds widely used in transition-metal catalysis. Taking into account that the steric hindrance around the metal center is one of the major effects in M-NHC catalysis, the development of new, sterically hindered M-NHC complexes is an ongoing interest in this field of research. Herein, we report the synthesis and characterization of exceedingly sterically hindered, well-defined, air- and moisture-stable Cu(I) and Ag(I) complexes, [Cu(NHC)Cl] and [Ag(NHC)Cl], in the recently discovered IPr family of ligands that hinge upon modular peralkylation of anilines.

Gold-catalysed amine synthesis by reductive hydroamination of alkynes with nitroarenes.

Amines are the most pivotal class of organic motifs in pharmaceutical compounds. Here we provide a blueprint for a general synthesis of amines by catalyst differentiation enabled by triple Au-H/Au/Au-H relay catalysis. The parent catalyst is differentiated into a set of catalytically active species to enable triple cascade catalysis, where each catalytic species is specifically tuned for one catalytic cycle.

IPr* - Highly Hindered, Fluorinated N-Heterocyclic Carbenes.

The introduction of fluorine atom has attracted considerable interest in molecular design owing to the high electronegativity and the resulting polarization of carbon-fluorine bonds. Simultaneously, sterically-hindered N-heterocyclic carbenes (NHCs) have received major interest due to high stabilization of the reactive metal centers, which has paved the way for the synthesis of stable and reactive organometallic compounds with broad applications in main group chemistry, inorganic synthesis and transition-metal-catalysis. Herein, we report the first class of sterically-hindered, fluorinated N-heterocyclic carbenes.

IPr* - wingtip-flexible, sterically hindered, modular, N,C/S,C-chelating thiazole-donor N-heterocyclic carbene ligands.

N-Heterocyclic carbenes (NHCs) represent a pivotal class of ligands in coordination chemistry owing to their unique electronic properties. In particular, hemilabile N-heterocyclic carbenes have garnered significant attention over the past decade due to their capacity to transiently coordinate to metals and open coordination sites. However, hemilabile NHC ligands have been predominantly limited to N, O and P donors, while NHC ligands bearing versatile S-donors have been severely underdeveloped.

Comparative profiling of serum biomarkers and ATR-FTIR spectroscopy for differential diagnosis of patients with rheumatoid and psoriatic arthritis - a pilot study.

Background: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory diseases in which innate and adaptive responses of the immune system are induced. RA and PsA have complex signaling pathways. Despite the differences in their clinical presentation, there is a great demand for fast and accurate diagnosis of diseases to implement treatment and plan an individual therapeutic strategy quickly.

[Au(Np)Cl]: Highly Reactive and Broadly Applicable Au(I)─NHC Catalysts for Alkyne π-Activation Reactions.

Cationic Au(I)─NHC (NHC = N-heterocyclic carbene) complexes have become an important class of catalysts for alkyne π-activation reactions in organic synthesis. In particular, these complexes are characterized by high stability of catalytic species engendered by strong σ-donation and metal backbonding. Herein, we report the synthesis and characterization of well-defined [Au(NHC)Cl] complexes featuring recently discovered IPr family of ligands that hinge upon modular peralkylation of aniline.

Indazolin-3-ylidenes (Indy*): easily accessible, sterically-hindered indazole-derived N-heterocyclic carbenes and their application in gold catalysis.

Sterically-hindered N-heterocyclic carbenes (NHCs) with functionalized -wingtips are a pivotal class of ligands in organic synthesis. Herein, we report the first class of sterically-hindered N-heterocyclic carbenes based on the indazole framework. These ligands combine the strong σ-donation of the carbene center due to the carbene placement at the C3-indazole position with the sterically-hindered and flexible -substitution with the versatile 2,6-bis(diphenylmethyl)aryl moiety that extends beyond the metal centre for the first time in non-classical N-heterocyclic carbenes.

Wingtip-Flexible N-Heterocyclic Carbenes: Unsymmetrical Connection between IMes and IPr.

IMes (IMes=1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) and IPr (IPr=1,3- bis(2,6-diisopropylphenyl)imidazol-2-ylidene) represent by far the most frequently used N-heterocyclic carbene ligands in homogeneous catalysis, however, despite numerous advantages, these ligands are limited by the lack of steric flexibility of catalytic pockets. We report a new class of unique unsymmetrical N-heterocyclic carbene ligands that are characterized by freely-rotatable N-aromatic wingtips in the imidazol-2-ylidene architecture. The combination of rotatable N-CH Ar bond with conformationally-fixed N-Ar linkage results in a highly modular ligand topology, entering the range of geometries inaccessible to IMes and IPr.

Well-Defined, Air- and Moisture-Stable Palladium-Imidazo[1,5-]pyridin-3-ylidene Complexes: A Versatile Catalyst Platform for Cross-Coupling Reactions by L-Shaped NHC Ligands.

We describe the development of [(NHC)Pd(cinnamyl)Cl] complexes of ImPy (ImPy = imidazo[1,5-]pyridin-3-ylidene) as a versatile class of precatalysts for cross-coupling reactions. These precatalysts feature fast activation to monoligated Pd(0) with 1:1 Pd to ligand ratio in a rigid imidazo[1,5-]pyridin-3-ylidene template. Steric matching of the C5-substituent and N2-wingtip in the catalytic pocket of the catalyst framework led to the discovery of ImPyMesDipp as a highly reactive imidazo[1,5-]pyridin-3-ylidene ligand for Pd-catalyzed cross-coupling of nitroarenes by challenging C-NO activation.

Application of vibrational and fluorescence spectroscopy to the compositional analysis of colored-flesh potatoes.

Background: Determination of composition and physicochemical parameters of natural products requires dedicated, often laborious and expensive, analytical protocols. Different spectroscopic techniques, in conjunction with chemometrics, seem to have a considerable potential in direct analysis of raw plant material and foods, without any chemical treatment.

Results: Fluorescence spectroscopy and three vibrational spectroscopy techniques were applied to determine total polyphenol content, antioxidant activity and macronutrient levels in red- and purple-fleshed potato varieties.

IPr* - a new class of sterically-hindered, wingtip-flexible N,C-chelating oxazole-donor N-heterocyclic carbene ligands.

N-heterocyclic carbenes (NHCs) have emerged as a major direction in ancillary ligand development for stabilization of reactive metal centers in inorganic and organometallic chemistry. In particular, wingtip-flexible NHCs have attracted significant attention due to their unique ability to provide a sterically-demanding environment for transition metals in various oxidation states. Herein, we report a new class of sterically-hindered, wingtip-flexible NHC ligands that feature N,C-chelating oxazole donors.

[IPr-PEPPSI]: A Well-Defined, Highly Hindered and Broadly Applicable Pd(II)-NHC (NHC = N-Heterocyclic Carbene) Precatalyst for Cross-Coupling Reactions.

In this Special Issue, "Featured Papers in Organometallic Chemistry", we report on the synthesis and characterization of [IPr-PEPPSI], a new, well-defined, highly hindered Pd(II)-NHC precatalyst for cross-coupling reactions. This catalyst was commercialized in collaboration with MilliporeSigma, Burlington, ON, Canada (no. 925489) to provide academic and industrial researchers with broad access to reaction screening and optimization.

IOct (IOctyl) - pushing the limits of IBu: highly hindered electron-rich N-aliphatic N-heterocyclic carbenes.

IBu (IBu = 1,3-di--butylimidazol-2-ylidene) represents the most important and most versatile -alkyl N-heterocyclic carbene available in organic synthesis and catalysis. Herein, we report the synthesis, structural characterization and catalytic activity of IOct (IOctyl), -symmetric, higher homologues of IBu. The new ligand class, including saturated imidazolin-2-ylidene analogues has been commercialized in collaboration with MilliporeSigma: IOct, 929 298; SIOct, 929 492 to enable broad access of the academic and industrial researchers within the field of organic and inorganic synthesis.

Thiazol-2-ylidenes as N-Heterocyclic carbene ligands with enhanced electrophilicity for transition metal catalysis.

Over the last 20 years, N-heterocyclic carbenes (NHCs) have emerged as a dominant direction in ligand development in transition metal catalysis. In particular, strong σ-donation in combination with tunable steric environment make NHCs to be among the most common ligands used for C-C and C-heteroatom bond formation. Herein, we report the study on steric and electronic properties of thiazol-2-ylidenes.

L-Shaped Heterobidentate Imidazo[1,5-a]pyridin-3-ylidene (N,C)-Ligands for Oxidant-Free Au /Au Catalysis.

In the last decade, major advances have been made in homogeneous gold catalysis. However, Au /Au catalytic cycle remains much less explored due to the reluctance of Au to undergo oxidative addition and the stability of the Au intermediate. Herein, we report activation of aryl halides at gold(I) enabled by NHC (NHC=N-heterocyclic carbene) ligands through the development of a new class of L-shaped heterobidentate ImPy (ImPy=imidazo[1,5-a]pyridin-3-ylidene) N,C ligands that feature hemilabile character of the amino group in combination with strong σ-donation of the carbene center in a rigid conformation, imposed by the ligand architecture.

Quantitative Determination of Diosmin in Tablets by Infrared and Raman Spectroscopy.

Diosmin is widely used in the treatment of chronic venous diseases and hemorrhoids. Based on Raman and infrared reflection spectra of powdered tablets in the mid- and near-infrared regions and results of reference high-performance liquid chromatographic analysis, partial least squares models that enable fast and reliable quantification of the studied active ingredient in tablets, without the need for extraction, were elaborated. Eight commercial preparations containing diosmin in the 66-92% (/) range were analyzed.

CAAC-IPr*: easily accessible, highly sterically-hindered cyclic (alkyl)(amino)carbenes.

IPr* (IPr* = 1,3-bis(2,6-bis(diphenylmethyl)-4-methylphenyl)imidazol-2-ylidene) has emerged as a powerful highly hindered and sterically-flexible ligand platform for transition-metal catalysis. CAACs (CAAC = cyclic (al-kyl)(amino)carbenes) have gained major attention as strongly electron-rich carbon analogues of NHCs (NHC = N-heterocyclic carbene) with broad applications in both industry and academia. Herein, we report a merger of CAAC ligands with highly-hindered IPr*.