713 results on '"Steven P. Nolan"'
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2. [Pd(NHC)(μ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products
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Tongliang Zhou, Siyue Ma, Fady Nahra, Alan M.C. Obled, Albert Poater, Luigi Cavallo, Catherine S.J. Cazin, Steven P. Nolan, and Michal Szostak
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Chemistry ,Inorganic Chemistry ,Catalysis ,Organic Synthesis ,Science - Abstract
Summary: The development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(μ-allyl)(μ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.
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- 2020
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3. Buchwald–Hartwig Amination and C–S/S–H Metathesis of Aryl Sulfides by Selective C–S Cleavage Mediated by Air- and Moisture-Stable [Pd(NHC)(μ-Cl)Cl]2 Precatalysts: Unified Mechanism for Activation of Inert C–S Bonds
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Shiyi Yang, Xiang Yu, Albert Poater, Luigi Cavallo, Catherine S. J. Cazin, Steven P. Nolan, and Michal Szostak
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Chemistry ,HETEROCYCLIC CARBENE COMPLEXES ,Organic Chemistry ,ESTERS ,CARBON-SULFUR ,Physical and Theoretical Chemistry ,COUPLINGS ,Biochemistry ,AMIDES - Abstract
We report a combined experimental and mechanistic study on the Buchwald-Hartwig amination and C-S/S-H metathesis of aryl sulfides by selective activation of C-S bonds mediated by well-defined, air-and moisture-stable Pd(II)-NHC precatalysts, [Pd(NHC)(mu-Cl)Cl]2. This class of Pd(II)-NHC precatalysts displays excellent activity in the cross coupling of aryl sulfides. Most crucially, we unravel the unified mechanism for activation of C-S bonds in the C-N cross-coupling and C-S metathesis manifolds, where the inert C-S bond serves as a precursor to valuable amine or thioether products.
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- 2022
4. Straightforward synthesis of [Cu(NHC)(alkynyl)] and [Cu(NHC)(thiolato)] complexes (NHC = N-heterocyclic carbene)
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Luigi Cavallo, Catherine S. J. Cazin, Nikolaos V. Tzouras, Lucia Caporaso, Ishfaq IbniHashim, Ida Ritacco, Steven P. Nolan, Thomas Scattolin, Laurens Bourda, and Kristof Van Hecke
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Steric effects ,Ligand ,ALKYNYLATION ,CATALYSTS ,Medicinal chemistry ,Inorganic Chemistry ,Chemistry ,chemistry.chemical_compound ,Monomer ,chemistry ,H BONDS ,ALKYNES ,Weak base ,Carbene ,Single crystal - Abstract
The synthetic access to monomeric copper-alkynyl and copper-thiolato complexes of the type [(NHC)Cu(R)] (R = alkynyl or thiolato) using a weak base approach is reported. All reported reactions proceed under mild conditions in air and in environmentally acceptable solvents. The novel complexes are fully characterized and single crystal X-ray analyses unambiguously establish the atom connectivity in these mononuclear complexes. The importance of the supporting NHC ligand steric properties in stabilizing mononuclear complexes is discussed.
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- 2022
5. A Simple Synthetic Route to [Rh(acac)(CO)(NHC)] Complexes: Ligand Property Diagnostic Tools and Precatalysts
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Gianmarco Pisanò, Bernd H. Müller, Johannes G. de Vries, Sébastien G. Guillet, Soumyadeep Chakrabortty, Catherine S. J. Cazin, Paul C. J. Kamer, and Steven P. Nolan
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Tolman Electronic structure ,PHOSPHORUS LIGANDS ,CATALYST ,PHOSPHINE ,Property (philosophy) ,BEARING ,NHC ,Ligand ,chemistry.chemical_element ,Diagnostic tools ,Combinatorial chemistry ,Rhodium ,ELECTRONIC-PROPERTIES ,Inorganic Chemistry ,Chemistry ,RUTHENIUM COMPLEXES ,N-HETEROCYCLIC CARBENE ,chemistry ,Simple (abstract algebra) ,NMR-SPECTROSCOPY ,HYDROGENATION ,Carbene ligands - Abstract
An operationally simple, user and eco-friendly synthetic protocol for the synthesis of [Rh(acac)(CO)(NHC)] complexes is described. Insights into the mechanism are provided using operando spectroscopy. The spectroscopic fingerprints of these complexes are correlated to NHCs reported electron-donating descriptor values, highlighting a new strategy to evaluate carbenes' electronic properties. An assessment of these complexes in catalytic applications is also reported, showing promising results in the catalytic hydrogenation of aromatic ketones.
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- 2021
6. Continuous Flow Synthesis of [Au(NHC)(Aryl)] (NHC=N‐Heterocyclic Carbene) Complexes
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Nikolaos V. Tzouras, Subhrajyoti Bhandary, Thibault Cauwenbergh, Andreas Simoens, Thomas Scattolin, Steven P. Nolan, Christian V. Stevens, and Kristof Van Hecke
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Chemistry ,Continuous flow ,Aryl ,Organic Chemistry ,General Chemistry ,Continuous manufacturing ,continuous-flow synthesis ,gold(I)-aryl ,N-heterocyclic carbenes ,sustainability ,weak-base routes ,Combinatorial chemistry ,REACTIVITY ,Catalysis ,chemistry.chemical_compound ,GOLD(I) ,ROUTES ,Reactivity (chemistry) ,TRANSMETALATION ,Carbene - Abstract
The use of weak and inexpensive bases has recently opened promising perspectives towards the simpler and more sustainable synthesis of Au(I)-aryl complexes with valuable applications in catalysis, medicinal chemistry, and materials science. In recent years, continuous manufacturing has shown to be a reliable partner in establishing sustainable and controlled process scalability. Herein, the first continuous flow synthesis of a range of Au(I)-aryl starting from widely available boronic acids and various [Au(NHC)Cl] (NHC=N-heterocyclic carbene) complexes in unprecedentedly short reaction times and high yields is reported. Successful synthesis of previously non- or poorly accessible complexes exposed fascinating reactivity patterns. Via a gram-scale synthesis, convenient process scalability of the developed protocol was showcased.
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- 2021
7. Silver N-heterocyclic carbenes: emerging powerful catalysts
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Nikolaos V. Tzouras, Xihe Bi, Zikun Wang, and Steven P. Nolan
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chemistry.chemical_classification ,Transmetalation ,chemistry.chemical_compound ,Biocompatibility ,Chemistry ,Organic synthesis ,General Chemistry ,Lewis acids and bases ,Combinatorial chemistry ,Catalysis ,Coordination complex - Abstract
Silver N-heterocyclic carbenes (Ag–NHCs) exhibit good biocompatibility and have found a wide range of applications in medicine and coordination chemistry. However, due to the strong σ donor nature of NHC, its coordination with silver can weaken the Lewis acidity of Ag(I), leading to slow development of Ag-NHCs in the field of catalysis. Here, we systematically review the application of Ag-NHCs as catalysts in organic synthesis and clearly elaborate the reasons for the slow development of Ag-NHCs in the field of catalysis along with future development opportunities for such complexes as catalysts.
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- 2021
8. Synthesis of γ,δ-Unsaturated Esters and Amides via Au(I)-Catalyzed Reactions of Aryl Ynol Ethers or Ynamides with Allylic Alcohols
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Yoshihiro Sato, Yoshihiro Oonishi, Steven P. Nolan, Souta Misawa, and Asaki Miyairi
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Allylic rearrangement ,Aryl ,Claisen rearrangement ,Organic Chemistry ,Regioselectivity ,Ether ,hydroalkoxylation ,Medicinal chemistry ,gold catalysis ,Catalysis ,amides ,chemistry.chemical_compound ,ynols ,esters ,chemistry ,Cascade reaction ,ynamides ,Ynol ,Hydroalkoxylation - Abstract
Polarized alkynes such as ynol ethers and ynamides have attracted much attention due to their inherent unique reactivity. Herein, we report Au(I)-catalyzed hydroalkoxylation/Claisen rearrangement cascade reactions of aryl ynol ethers and ynamides with allylic alcohols. At the first stage (hydroalkoxylation) of this cascade reaction, attack of allylic alcohols to aryl ynol ethers or ynamides occurs at the α-position of the polarized alkynes in a completely regioselective manner. Claisen rearrangement of the resulting adducts subsequently takes place to give γ,δ-unsaturated esters or amides, respectively. The [Au(IPr)NTf2] catalyst is most effective for this reaction, and the reaction proceeds under mild conditions (in the case of aryl ynol ether: in THF, 60 °C; in the case of ynamides: in toluene, 80 °C) in an atom-economical way.
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- 2021
9. Optimizing Catalyst and Reaction Conditions in Gold(I) Catalysis–Ligand Development
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David J. Nelson, Steven P. Nolan, and Alba Collado
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Reaction conditions ,TERMINAL ALKYNES ,Ligand ,NITROGEN ACYCLIC CARBENES ,General Chemistry ,CYCLIC (ALKYL)(AMINO)CARBENES CAACS ,NHC LIGANDS ,Combinatorial chemistry ,ONE-POT SYNTHESIS ,Catalysis ,ELECTRONIC-PROPERTIES ,Chemistry ,chemistry.chemical_compound ,ROOM-TEMPERATURE ,N-HETEROCYCLIC CARBENE ,chemistry ,WATER-SOLUBLE GOLD(I) ,QD ,Organic synthesis ,Carbene ,Phosphine ,PI-ACCEPTOR PROPERTIES - Abstract
This review considers phosphine and N-heterocyclic carbene complexes of gold(I) that are used as (pre)catalysts for a range of reactions in organic synthesis. These are divided according to the structure of the ligand, with the narrative focusing on studies that offer a quantitative comparison between the ligands and readily available or widely used existing systems.
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- 2021
10. Fluoroalkyl N-Triftosylhydrazones as Easily Decomposable Diazo Surrogates for Asymmetric [2 + 1] Cycloaddition: Synthesis of Chiral Fluoroalkyl Cyclopropenes and Cyclopropanes
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Xinyu Zhang, Zhanjing Wang, Paramasivam Sivaguru, Xihe Bi, Steven P. Nolan, and Chunqi Tian
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chemistry.chemical_compound ,chemistry ,Organic synthesis ,Diazo ,General Chemistry ,Cyclopropene ,Carbene ,Combinatorial chemistry ,Catalysis ,Cycloaddition ,Cyclopropane - Abstract
The development of asymmetric carbene transfer reactions using N-sulfonylhydrazones as the diazo surrogate is a long-term issue in organic synthesis since N-sulfonylhydrazones commonly require high...
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- 2021
11. The 'weak base route' leading to transition metal–N-heterocyclic carbene complexes
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Catherine S. J. Cazin, Nikolaos V. Tzouras, Steven P. Nolan, Gianmarco Pisanò, and Ekaterina A. Martynova
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STRUCTURAL-CHARACTERIZATION ,BISCARBENE COMPLEXES ,SUPPORTED PRECATALYSTS ,CATALYTIC-PROPERTIES ,Catalysis ,RUTHENIUM COMPLEXES ,chemistry.chemical_compound ,Transition metal ,Computational chemistry ,OXIDATIVE ADDITION ,PD-NHC NHC ,TRANSFER HYDROGENATION ,Materials Chemistry ,Organometallic chemistry ,Reaction conditions ,VERSATILE PRECATALYST ,Chemistry ,Metals and Alloys ,General Chemistry ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,ELECTRONIC-PROPERTIES ,Ceramics and Composites ,Weak base ,Carbene - Abstract
N-Heterocyclic carbenes (NHCs) are nowadays ubiquitous in organometallic chemistry and catalysis. Recently, a synthetic method which makes use of weak bases and desirable solvents has emerged as a simple, widely applicable and cost-effective pathway to well defined M-NHC complexes. Herein, recent studies devoted to the weak base approach are examined in detail, in order to showcase the simplicity, scope and variations of the method with regards to the azolium salts, bases and the metal sources, as well as the reaction conditions used. Mechanistic investigations are presented, illustrating the formation of intermediates which are air and moisture stable, prior to the metallation step. Finally, the importance, limitations and future prospects of the weak base route are discussed.
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- 2021
12. A simple synthesis of [RuCl2(NHC)(p-cymene)] complexes and their use in olefin oxidation catalysis
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Steven P. Nolan, Sébastien G. Guillet, Kristof Van Hecke, Xinyuan Ma, and Min Peng
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Inorganic Chemistry ,Olefin fiber ,chemistry.chemical_compound ,p-Cymene ,Chemistry ,Weak base ,Medicinal chemistry ,Catalysis - Abstract
A simple and efficient synthetic route to [RuCl2(NHC)(p-cymene)] and [Ru(CO3)(NHC)(p-cymene)] complexes making use of a weak base, under aerobic conditions, is reported. This method enables access to a series of NHC-ruthenium compounds with moderate to good yields under mild conditions. The Ru pre-catalysts were successfully used in olefin oxidation catalysis at low catalyst loading and reach complete conversion in short times.
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- 2021
13. Defluorinative [4 + 1] annulation of perfluoroalkyl N-mesylhydrazones with primary amines provides 5-fluoroalkyl 1,2,3-triazoles
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Giuseppe Zanoni, Xihe Bi, Hongwei Wang, Shuang Li, Steven P. Nolan, Yongquan Ning, and Paramasivam Sivaguru
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Annulation ,Primary (chemistry) ,Chemistry ,Yield (chemistry) ,Bioactive molecules ,Reagent ,Environmental Chemistry ,Pollution ,Combinatorial chemistry - Abstract
Fluoroalkyl 1,2,3-triazoles have great potential as medicinal chemistry building blocks. However, only a few synthetic routes to these compounds are currently available. Herein, we report on a novel method to access 5-fluoroalkyl 1,2,3-triazoles from easily prepared bench-stable perfluoroalkyl N-mesylhydrazone (PFHZ-Ms), a reagent that can transform amines to 5 fluoroalkyl 1,2,3-triazoles via defluorinative [4 + 1] annulation. The simple reaction protocol can be applied to a variety of amines containing a range of functional groups, delivering 1,2,3-triazoles in good to excellent yield. The utility of this method was demonstrated in the late-stage modification of bioactive molecules.
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- 2021
14. Suzuki–Miyaura cross-coupling of esters by selective O–C(O) cleavage mediated by air- and moisture-stable [Pd(NHC)(μ-Cl)Cl]2 precatalysts: catalyst evaluation and mechanism
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Steven P. Nolan, Albert Poater, Tongliang Zhou, Shiyi Yang, Michal Szostak, and Luigi Cavallo
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chemistry.chemical_classification ,chemistry.chemical_compound ,Ketone ,Catalytic cycle ,Chemistry ,Aryl ,Surface modification ,Reactivity (chemistry) ,Cleavage (embryo) ,Chemical synthesis ,Medicinal chemistry ,Catalysis - Abstract
The cross-coupling of aryl esters has emerged as a powerful platform for the functionalization of otherwise inert acyl C–O bonds in chemical synthesis and catalysis. Herein, we report a combined experimental and computational study on the acyl Suzuki–Miyaura cross-coupling of aryl esters mediated by well-defined, air- and moisture-stable Pd(II)–NHC precatalysts [Pd(NHC)(μ-Cl)Cl]2. We present a comprehensive evaluation of [Pd(NHC)(μ-Cl)Cl]2 precatalysts and compare them with the present state-of-the-art [(Pd(NHC)allyl] precatalysts bearing allyl-type throw-away ligands. Most importantly, the study reveals [Pd(NHC)(μ-Cl)Cl]2 as the most reactive precatalysts discovered to date in this reactivity manifold. The unique synthetic utility of this unconventional O–C(O) cross-coupling is highlighted in the late-stage functionalization of pharmaceuticals and sequential chemoselective cross-coupling, providing access to valuable ketone products by a catalytic mechanism involving Pd insertion into the aryl ester bond. Furthermore, we present a comprehensive study of the catalytic cycle by DFT methods. Considering the clear advantages of [Pd(NHC)(μ-Cl)Cl]2 precatalysts on several levels, including facile one-pot synthesis, superior atom-economic profile to all other Pd(II)–NHC catalysts, and versatile reactivity, these should be considered as the ‘first-choice’ catalysts for all routine applications in ester O–C(O) bond activation.
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- 2021
15. Simple synthesis of [Ru(CO3)(NHC)(p-cymene)] complexes and their use in transfer hydrogenation catalysis
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Sébastien G. Guillet, Yaxu Liu, Steven P. Nolan, Xinyuan Ma, and Catherine S. J. Cazin
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Tetrafluoroborate ,p-Cymene ,Hydrogen ,NHC ,PALLADIUM ,chemistry.chemical_element ,MILD ,Transfer hydrogenation ,Medicinal chemistry ,TRANSITION-METAL-COMPLEXES ,Ruthenium ,Catalysis ,ACTIVATION ,Inorganic Chemistry ,Chemistry ,chemistry.chemical_compound ,1 ATM ,N-HETEROCYCLIC CARBENE ,chemistry ,LIGANDS ,Weak base ,IRIDIUM ,CARBONATES - Abstract
A novel, efficient and facile protocol for the synthesis of a series of [Ru(NHC)(CO3)(p-cymene)] complexes is reported. This family of Ru-NHC complexes was obtained from imidazol(in)ium tetrafluoroborate or imidazolium hydrogen carbonate salts in moderate to excellent yields, employing sustainable weak base. The ruthenium complexes were successfully utilized in the transfer hydrogenation of ketones as highly active multifunctional catalysts.
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- 2021
16. Design Concepts for N-Heterocyclic Carbene Ligands
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David J. Nelson, Fady Nahra, and Steven P. Nolan
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Steric effects ,chemistry.chemical_compound ,Chemistry ,Supramolecular chemistry ,Homogeneous catalysis ,Reactivity (chemistry) ,General Chemistry ,Combinatorial chemistry ,Carbene ,TP155 ,Organometallic chemistry ,Electronic properties - Abstract
N-heterocyclic carbenes (NHCs) are a widely used class of ligands that have enabled an exciting variety of organometallic chemistry and catalysis. As researchers design and customize these ligands for specific applications, various design concepts have emerged. This review covers several of these design concepts and their impact on and promise for organometallic chemistry and catalysis. These concepts are bulky ligands that remain flexible for substrate binding and reactivity, ring-expanded NHCs with different steric and electronic properties, NHCs appended to supramolecular assemblies that control the microenvironment around the metal center; and NHCs with pendant labile functional groups.
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- 2020
17. Protocol for Palladium/N-Heterocyclic Carbene-Catalyzed Suzuki–Miyaura Cross-Coupling of Amides by N–C(O) Activation
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Jie An, Guangchen Li, Yun Ling, Michal Szostak, Peng Lei, and Steven P. Nolan
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010405 organic chemistry ,Chemistry ,Process development ,Organic Chemistry ,chemistry.chemical_element ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,Broad spectrum ,chemistry.chemical_compound ,Amide ,Amide bonds ,Carbene ,Palladium - Abstract
Amides are among the most important and ubiquitous functional groups in organic chemistry and process development. In this Practical Synthetic Procedure, a protocol for the Suzuki–Miyaura cross-coupling of amides by selective N–C(O) bond activation catalyzed by commercially available, air- and moisture-stable palladium/N-heterocyclic carbene (NHC) complexes is described. The procedure described involves [Pd(IPr)(cin)Cl] [IPr = 2,6-(diisopropylphenyl)imidazol-2-ylidene, cin = cinnamyl] at 0.10 mol% at room temperature and is performed on decagram scale. Furthermore, a procedure for the synthesis of amide starting materials is accomplished via selective N-tert-butoxycarbonylation, which is the preferred method over N-acylation. The present protocol carries advantages of operational simplicity, commercial availability of catalysts, and excellent conversions at low catalyst loadings. The method is generally useful for activation of N–C(O) amide bonds in a broad spectrum of amide precursors. The protocol should facilitate the implementation of amide cross-coupling reactions.
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- 2020
18. Reactions of N-heterocyclic carbene-based chalcogenoureas with halogens : a diverse range of outcomes
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Marina Saab, David J. Nelson, Matthew C. Leech, Kevin Lam, Steven P. Nolan, Fady Nahra, and Kristof Van Hecke
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STRUCTURAL-CHARACTERIZATION ,MAIN-GROUP ELEMENTS ,RAY CRYSTAL-STRUCTURES ,SELENIUM ,MOLECULAR ADDUCTS ,DIIODINE ADDUCTS ,Q1 ,Inorganic Chemistry ,Chemistry ,IMIDAZOLE-BASED THIONES ,CHARGE-TRANSFER ADDUCTS ,QD ,ANTITHYROID DRUGS ,SE - Abstract
We have investigated the reactions of chalcogenoureas derived from N-heterocyclic carbenes, referred to here as [E(NHC)], with halogens. Depending on the structure of the chalcogenourea and the identity of the halogen, a diverse range of reactivity was observed and a corresponding range of structures were obtained. Cyclic voltammetry was carried out to characterize the oxidation and reduction potentials of these [E(NHC)] species; selenoureas were found to be easier to oxidize than the corresponding thioureas. In some cases, a correlation was found between the oxidation potential of these compounds and the electronic properties of the corresponding NHC moiety. The reactivity of these chalcogenoureas with different halogenating reagents (Br2, SO2Cl2, I2) was then investigated, and products were characterized using NMR spectroscopy and single-crystal X-ray diffraction. X-ray analyses elucidated the solid-state coordination types of the obtained products, showing that a variety of possible adducts can be obtained. In some cases, we were able to extrapolate a structure/activity correlation to explain the observed trends in reactivity and oxidation potentials.
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- 2022
19. Synthetic Routes to Late Transition Metal–NHC Complexes
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Thomas Scattolin and Steven P. Nolan
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STRUCTURAL-CHARACTERIZATION ,ARYLATION ,synthesis ,EFFICIENT ,Homogeneous catalysis ,late transition-metal complexes ,Heterogeneous catalysis ,PALLADIUM COMPLEXES ,chemistry.chemical_compound ,N-HETEROCYCLIC CARBENE ,Transition metal ,OXIDATIVE ADDITION ,homogeneous catalysis ,N-heterocyclic carbenes ,weak base approach ,SILVER-FREE ,CATALYTIC-ACTIVITY ,GOLD ,COUPLING REACTIONS ,General Chemistry ,Combinatorial chemistry ,Chemistry ,chemistry ,Homogeneous ,Weak base ,Carbene - Abstract
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.
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- 2020
20. Using sodium acetate for the synthesis of [Au(NHC)X] complexes
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Thomas Scattolin, Nikolaos V. Tzouras, Laura Falivene, Luigi Cavallo, and Steven P. Nolan
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STRUCTURAL-CHARACTERIZATION ,chemistry.chemical_classification ,Base (chemistry) ,NHC ,EFFICIENT ,Inorganic Chemistry ,Chemistry ,chemistry.chemical_compound ,N-HETEROCYCLIC CARBENE ,chemistry ,Polymer chemistry ,Technical grade ,AU ,Sodium acetate - Abstract
The role of sodium acetate in the synthesis of [Au(NHC)Cl] complexes was examined. The use of this base was also investigated for the activation of C-H and S-H bonds by experimental and computational methods. The synthetic use of NaOAc to assemble these complexes is applicable to a wide range of NHCs and proceeds under air, under mild conditions and using technical grade green solvents.
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- 2020
21. Synthesis, reactivity and catalytic activity of Au-PAd3 complexes
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Sii Hong Lau, Vladislav A. Voloshkin, Steven P. Nolan, Kristof Van Hecke, Bradley Patrick Carrow, and Marina Saab
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Inorganic Chemistry ,Reaction conditions ,Steric effects ,chemistry.chemical_compound ,Chemistry ,Synthon ,Reactivity (chemistry) ,Medicinal chemistry ,Carbene ,Phosphine ,Catalysis ,Electronic properties - Abstract
Tri(1-adamantyl)phosphine (PAd3) possesses unique steric and electronic properties positioning it at the border between tertiary phosphines and N-heterocyclic carbenes (NHC). Novel Au-PAd3 complexes were synthesized from the known [Au(PAd3)Cl]. We have optimised reaction conditions for the synthesis of this useful synthon in order to circumvent the formation of the [Au(PAd3)2]Cl. [Au(PAd3)Cl] was used to access a number of derivatives and some were deployed as catalysts. The hydration of alkynes was targeted to gauge the reactivity of Au-PAd3 complexes and permit comparison with NHC and tertiary phosphine congeners.
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- 2020
22. Buchwald–Hartwig cross-coupling of amides (transamidation) by selective N–C(O) cleavage mediated by air- and moisture-stable [Pd(NHC)(allyl)Cl] precatalysts: catalyst evaluation and mechanism
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Guangchen Li, Tongliang Zhou, Michal Szostak, Albert Poater, Steven P. Nolan, and Luigi Cavallo
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SECONDARY AMIDES ,SUZUKI-MIYAURA ,ESTERS ,Cleavage (embryo) ,Combinatorial chemistry ,Catalysis ,Chemistry ,AMINATION ,chemistry.chemical_compound ,BOND FORMATION ,HETEROCYCLIC CARBENE COMPLEXES ,Catalytic cycle ,chemistry ,Amide ,Reagent ,Electrophile ,REAGENTS ,(NHC)PD(ALLYL)CL NHC ,AMIDATION ,Stoichiometry ,Amination - Abstract
The Pd-NHC-catalyzed acyl-type Buchwald-Hartwig cross-coupling of amides by N-C(O) cleavage (transamidation) provides a valuable alternative to the classical methods for amide synthesis. Herein, we report a combined experimental and computational study of the Buchwald-Hartwig cross-coupling of amides using well-defined, air- and moisture-stable [Pd(NHC)(allyl)Cl] precatalysts. Most crucially, we present a comprehensive evaluation of a series of distinct Pd(ii)-NHC precatalysts featuring different NHC scaffolds and throw-away ligands for the synthesis of functionalized amides that are not compatible with stoichiometric transition-metal-free transamidation methods. Furthermore, we present evaluation of the catalytic cycle by DFT methods for a series of different Pd(ii)-NHC precatalysts. The viability of accessing NHC-supported acyl-palladium(ii) amido complexes will have implications for the design and development of cross-coupling methods involving stable amide electrophiles.
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- 2020
23. Understanding existing and designing novel synthetic routes to Pd-PEPPSI-NHC and Pd-PEPPSI-PR3pre-catalysts
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Marina Saab, Sébastien G. Guillet, Fady Nahra, Marek Beliš, Vladislav A. Voloshkin, Kristof Van Hecke, and Steven P. Nolan
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Reaction mechanism ,Ligand ,Synthon ,Metals and Alloys ,chemistry.chemical_element ,General Chemistry ,Combinatorial chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,PEPPSI ,chemistry.chemical_compound ,chemistry ,Pyridine ,Materials Chemistry ,Ceramics and Composites ,Amination ,Palladium - Abstract
The reaction mechanism leading to the formation of cross-coupling palladium pre-catalysts of the PEPPSI family was investigated. Two intermediates were isolated and proved to be both suitable synthons to the pre-catalysts, with one permitting the design of a novel and greener user-friendly synthetic route. In light of this mechanistic understanding, the traditional one-pot method was shown to be possible using stoichiometric amounts of throw-away ligand, which represents a considerable synthetic improvement over the wasteful "in pyridine" approach.
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- 2020
24. A general protocol for the synthesis of Pt-NHC (NHC = N-heterocyclic carbene) hydrosilylation catalysts
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Steven P. Nolan, Marina Saab, Kristof Van Hecke, Benon P. Maliszewski, Nikolaos V. Tzouras, Sébastien G. Guillet, Fady Nahra, and Marek Beliš
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Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,010405 organic chemistry ,Hydrosilylation ,Pyridine ,010402 general chemistry ,01 natural sciences ,Carbene ,Medicinal chemistry ,0104 chemical sciences ,Catalysis - Abstract
A general, user-friendly synthetic route to [Pt(NHC)(L)Cl2] and [Pt(NHC)(dvtms)] (L = DMS, Py; DMS = dimethyl sulfide, dvtms = divinyltetramethylsiloxane, Py = pyridine) complexes has been developed. The procedure is applicable to a wide range of ligands and enables facile synthetic access to key Pt(0)- and Pt(ii)-NHC complexes used in hydrosilylation catalysis.
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- 2020
25. The anticancer activity of an air-stable Pd(<scp>i</scp>)-NHC (NHC = N-heterocyclic carbene) dimer
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Busra Dereli, Stefano Palazzolo, Enrica Bortolamiol, Tiziana Perin, Manoj V. Mane, Flavio Rizzolio, Nicola Demitri, Vincenzo Canzonieri, Steven P. Nolan, Isabella Caligiuri, Thomas Scattolin, Fabiano Visentin, and Luigi Cavallo
- Subjects
ISOCYANIDES ,Cell Survival ,Stereochemistry ,Dimer ,SUPPORTED PRECATALYSTS ,BRIDGING ALLYL ,Antineoplastic Agents ,Drug Screening Assays ,Catalysis ,Cell Line ,Dose-Response Relationship ,Structure-Activity Relationship ,chemistry.chemical_compound ,CYCLOPENTADIENYL ,Coordination Complexes ,Heterocyclic Compounds ,Cell Line, Tumor ,Cell Proliferation ,Dimerization ,Dose-Response Relationship, Drug ,Drug Screening Assays, Antitumor ,Humans ,Methane ,Molecular Structure ,Palladium ,Materials Chemistry ,Settore CHIM/03 - Chimica Generale e Inorganica ,Tumor ,Chemistry ,Metals and Alloys ,Antitumor ,General Chemistry ,REACTIVITY ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,UNUSUAL COORDINATION BEHAVIOR ,DINUCLEAR PALLADIUM(I) ,Ceramics and Composites ,BINUCLEAR PALLADIUM(I) COMPLEXES ,LIGANDS ,Drug ,BOND ,Carbene - Abstract
A new dinuclear Pd(i) complex coordinating two bis(NHC) ligands revealed an unsuspected stability despite the unsaturation of the two metal centres. Even more surprisingly, the compound showed high and selective antiproliferative activity against different cancer cell lines and ovarian cancer tumoroids, and the mechanism of action was different from that of cisplatin.
- Published
- 2020
26. Silver-catalyzed site-selective C(sp(3))-H benzylation of ethers with N-triftosylhydrazones
- Author
-
Zhaohong Liu, Hongwei Wang, Paramasivam Sivaguru, Steven P. Nolan, Qingmin Song, Weijie Yu, Xinyu Jiang, Edward A. Anderson, and Xihe Bi
- Subjects
CARBENE INSERTION ,Multidisciplinary ,CONSTRUCTION ,CARBON-HYDROGEN BONDS ,General Physics and Astronomy ,General Chemistry ,ALKYLATION ,DONOR ,General Biochemistry, Genetics and Molecular Biology ,TOSYLHYDRAZONES ,ACTIVATION ,Chemistry ,C-H INSERTION ,FUNCTIONALIZATION ,ENANTIOSELECTIVE SYNTHESIS - Abstract
A state-of-the-art tool in synthetic organic chemistry is a rhodium diazocarbene species, which despite its flexibility, is derived from expensive and highly reactive species. Here the authors present a methodology for C-H benzylation of ethers via an analogous silver carbene species, obtained from a more common metal and a more stable starting material. The insertion of carbenes into the alpha-C-H bonds of ethers represents one of the most powerful approaches to access polysubstituted alpha-branched ethers. However, intermolecular carbene insertions remain challenging, since current approaches are generally limited to the use of toxic and potentially explosive alpha-diazocarbonyl compounds. We now report a silver-catalyzed alpha-C-H benzylation of ethers using bench-stable N-triftosylhydrazones as safe and convenient carbene precursors. This approach is well suited for both inter- and intramolecular insertions to deliver medicinally relevant homobenzylic ethers and 5-8-membered oxacycles in good yields. The synthetic utility of this strategy is demonstrated by its easy scalability, broad scope with valuable functional groups, high regioselectivity, and late-stage functionalization of complex oxygen-containing molecules. The relative reactivities of different types of silver carbenes and C-H bonds were also investigated by experments and DFT calculations.
- Published
- 2022
27. A simple synthetic route to well-defined [Pd(NHC)Cl(1-tBu-indenyl)] pre-catalysts for cross-coupling reactions
- Author
-
Alberto Gobbo, Yaxu Liu, Kristof Van Hecke, Catherine S. J. Cazin, Thomas Scattolin, Marek Beliš, and Steven P. Nolan
- Subjects
Weak base route ,Chemistry ,Palladium indenyl complexes ,SUZUKI-MIYAURA REACTION ,Buchwald–Hartwig amination ,PRECATALYST ,Coupling reaction ,REACTIVITY ,Catalysis ,Inorganic Chemistry ,HETEROCYCLIC CARBENE COMPLEXES ,Simple (abstract algebra) ,Computational chemistry ,GENERAL-METHOD ,PD-PEPPSIC-N ,Buchwald-Hartwig amination ,LIGANDS ,Well-defined ,N-heterocyclic carbene ligands ,(NHC)PD(ALLYL)CL NHC ,Suzuki-Miyaura cross-coupling ,PD(I) - Abstract
The development of robust, more efficient, general, easily accessible Pd(II)-NHC pre-catalysts remains a key issue in cross-coupling applications. A selection of well-defined, air and moisture stable [Pd(NHC)Cl(1-Bu-t-indenyl)] (NHC=IPr, IPrCl, IMes, SIMes, IPr*) pre-catalysts have been synthesized in good to excellent yields by reacting [Pd(1-Bu-t-indenyl)(mu-Cl)](2) and various NHC.HCl precursors in the presence of the weak base K2CO3 in green acetone. The synthesized Pd(II)-NHC derivatives displayed excellent catalytic activity in classical Suzuki-Miyaura and Buchwald-Hartwig reactions, especially when IPrCl is employed as ancillary ligand. Additionally, in the challenging Suzuki-Miyaura reaction between esters and arylboronic acids, the [Pd(IPr*)Cl(1-Bu-t-indenyl)] complex exhibited the optimum catalytic activity under very mild reaction conditions.
- Published
- 2022
28. Gold N-heterocyclic carbene catalysts for the hydrofluorination of alkynes using hydrofluoric acid : reaction scope, mechanistic studies and the tracking of elusive intermediates
- Author
-
Marina Saab, Sandrine Bédard, Jean-François Paquin, Kristof Van Hecke, Ziyun Zhang, Nikolaos V. Tzouras, Raphaël Gauthier, Steven P. Nolan, Luigi Cavallo, and Laura Falivene
- Subjects
inorganic chemicals ,reaction Intermediates ,EFFICIENT ,Reaction intermediate ,HYDROGEN-FLUORIDE ,010402 general chemistry ,01 natural sciences ,DFT ,Hydrofluoric Acid ,Catalysis ,FLUORINATION ,chemistry.chemical_compound ,COUNTERION ,Heterocyclic Compounds ,ALKENES ,MONO ,Chemoselectivity ,chemistry.chemical_classification ,hydrogen fluoride ,010405 organic chemistry ,gold-NHC ,HYDRATION ,Organic Chemistry ,General Chemistry ,alkyne hydrofluorination ,Combinatorial chemistry ,REAGENT ,0104 chemical sciences ,ALKOXYLATION ,Bifluoride ,Chemistry ,STEREOSELECTIVE-SYNTHESIS ,Gold ,Methane ,Alkynes ,chemistry ,Catalytic cycle ,Counterion ,Carbene ,Trifluoromethanesulfonate - Abstract
An efficient and chemoselective methodology deploying gold- N -heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Bronsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailor-designed gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine- and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.
- Published
- 2022
29. Reaction Parameterization as a Tool for Development in Organometallic Catalysis
- Author
-
Steven P. Nolan and Thomas Scattolin
- Subjects
Development (topology) ,Chemistry ,Computational chemistry ,Organometallic catalysis - Published
- 2022
30. Theoretical study on the mechanism, chemo- and enantioselectivity of the Ag- vs. Rh-catalyzed intramolecular carbene transfer reaction of diazoacetamides
- Author
-
Qingmin Song, Jiayi Wu, Nikolaos V. Tzoukras, Yong Wu, and Steven P. Nolan
- Subjects
Chemistry ,SILVER ,General Chemical Engineering ,DEAROMATIZATION ,ACID ,INSERTION ,FUNCTIONALIZATION ,C-H BOND ,General Chemistry ,PHENOLS - Abstract
To explore the mechanism of silver and rhodium catalysis and reveal the origin of the chemo- and enantioselectivity of the reaction, density functional theory calculations were performed on the first silver-catalyzed highly enantioselective carbene transfer reaction. The calculation results reveal that when silver is used as a catalyst, due to the participation of the phosphate anion in the transition state, the enhanced nucleophilicity of the alpha-diazoacetamide unit promotes smooth dearomatization before generation of the silver carbene. Because the generated rhodium carbene has stronger electrophilicity, typical carbene reactions (C-H insertion and the Buchner reaction) are favored. In addition, in the process of silver catalyzed dearomatization, the formation of an R-type transition state is determined by the small torsion energy and strong interaction energy.
- Published
- 2022
31. Merging gold(I) catalysis with amine transaminases in cascade catalysis : chemoenzymatic transformation of propargylic alcohols into enantioenriched allylic amines
- Author
-
Sergio González‐Granda, Nikolaos V. Tzouras, Steven P. Nolan, Iván Lavandera, and Vicente Gotor‐Fernández
- Subjects
HYDRATION ,Gold catalysis ,General Chemistry ,DONOR ,ONE-POT SYNTHESIS ,Chemistry ,BIOCATALYTIC ,Meyer-Schuster rearrangement ,CHIRAL AMINES ,N-Heterocyclic carbene ,ROUTES ,ALKYNES ,ASYMMETRIC-SYNTHESIS ,COMBINATION ,Transaminases - Abstract
The compatibility between gold(I) catalysts and amine transaminases has been explored to transform racemic propargylic alcohols into enantioenriched allylic amines in a straightforward and selective manner. The synthetic approach consists of a gold(I)-catalysed Meyer-Schuster rearrangement of a series of 2-arylpent-3-yn-2-ols and a subsequent stereoselective enzyme-catalysed transamination of the resulting alpha,beta-unsaturated prochiral ketones. The design of cascade processes involving sequential or concurrent approaches has been studied in our search for ideal reaction conditions to produce the desired amines. Thus, the N-heterocyclic carbene complex [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]-[bis(trifluoromethanesulfonyl)-imide]gold(I) ([Au(IPr)(NTf2)] (A) in aqueous medium was found to be an ideal catalyst, while selective, made-in-house and commercial amine transaminases permitted the asymmetric synthesis of both (E)-4-arylpent-3-en-2-amine enantiomers in good isolated yields (53-84%) and excellent stereoselectivities (97 to >99% enantiomeric excess).
- Published
- 2022
32. Continuous flow synthesis of NHC‐coinage metal amido and thiolato complexes : a mechanism‐based process development
- Author
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Thibault Cauwenbergh, Nikolaos V. Tzouras, Thomas Scattolin, Andreas Simoens, Christian V. Stevens, Catherine S. J. Cazin, and Steven P. Nolan
- Subjects
Chemistry ,General Medicine - Abstract
The first continuous flow syntheses of amido and thiolato families are reported. Our studies focused on [M(NHC)(Cbz)] (Cbz=carbazolyl) and [M(NHC)(SPh)] (NHC=N-heterocyclic carbene) as general proof-of-concepts and has led to a simple protocol with unprecedented short reaction times and high product yields. The scope of supporting ligands and substrates permits to assess the versatility of the process and a one-pot synthesis starting from the imidazolium salt, metal source and carbazole substrate highlights the simplicity and sustainability of this operating design. The process was made possible through a detailed mechanistic understanding of the underlying reaction chemistry.
- Published
- 2022
33. Indenyl and Allyl Palladate Complexes Bearing N ???Heterocyclic Carbene Ligands: an Easily Accessible Class of New Anticancer Drug Candidates
- Author
-
Thomas Scattolin, Ilenia Pessotto, Enrico Cavarzerani, Vincenzo Canzonieri, Laura Orian, Nicola Demitri, Claudia Schmidt, Angela Casini, Enrica Bortolamiol, Fabiano Visentin, Flavio Rizzolio, and Steven P. Nolan
- Subjects
Settore CHIM/03 - Chimica Generale e Inorganica ,SCREENING MODEL ,Allyl and indenyl palladium complexes ,NHC ,DERIVATIVES ,INHIBITION ,OVARIAN-CANCER ,REACTIVITY ,Anticancer activity ,Mechanochemistry ,N-heterocyclic carbenes ,Thioredoxin reductase inhibition ,Inorganic Chemistry ,ENERGY ,Chemistry ,DESIGN ,AGENTS - Abstract
The mechanochemical syntheses of allyl and indenyl palladate complexes are reported. All compounds were obtained in quantitative yields and microanalytically pure without the need of any workup. These complexes are stable in chlorinated and polar (DMSO or DMSO/H2O solutions) solvents. In chlorinated solvents, they appear as ionic pairs of which crystals suitable for single X-ray diffraction studies have been obtained. Bonding and solvation properties are rationalized through scalar relativistic DFT calculations. Moreover, most complexes showed excellent cytotoxicity towards ovarian cancer cell lines, with IC50 values comparable or lower than cisplatin. The potent anticancer activity of two IPrCl and IPr*-based palladate complexes was examined in a high-grade serous ovarian cancer (HGSOC) patient-derived tumoroid. Moreover, the inhibition of the antioxidant enzyme thioredoxin reductase (TrxR) was noticed, and structure-activity relationships could be derived, suggesting the ROS detoxifying system is involved in the mode of action.
- Published
- 2022
34. N-heterocyclic carbene gold complexes in a photocatalytic CO2 reduction reaction
- Author
-
Dinesh Nugegoda, Nikolaos V. Tzouras, Steven P. Nolan, and Jared H. Delcamp
- Subjects
Inorganic Chemistry ,Chemistry ,CARBON-DIOXIDE ,CONVERSION ,DESIGN ,ELECTROCATALYTIC REDUCTION ,CATALYSIS ,NHC ,FUELS ,SYNTHETIC ROUTES ,Physical and Theoretical Chemistry ,VISIBLE-LIGHT - Abstract
Molecular catalysts that are durable and highly selective in the photocatalytic CO2 reduction reaction (PCO2RR) are in high demand. Molecular gold complexes are underexplored in the CO2RR manifold despite heterogeneous gold- CO2 reduction catalyst counterparts being frequently studied. In this report, a series of N-heterocyclic carbene (NHC)-ligated Au complexes are evaluated in the PCO2RR with an added photosensitizer (tris(2-phenylpyridine)iridium, Ir(ppy)3). The complexes were each studied with and without an added activator used to open a coordination site on the Au complexes. Results show an example of an exceptionally durable PCO2RR catalyst lasting >100 h with high product selectivity for CO. Heterogeneity tests reveal no evidence of a nonhomogeneous active catalyst, and structure-activity relationships of the molecular complexes are discussed.
- Published
- 2022
35. One-Pot Multicomponent Synthesis of Allyl and Alkylamines Using a Catalytic System Composed of Ruthenium Nanoparticles on Copper N-Heterocyclic Carbene-Modified Silica
- Author
-
Deepti Kalsi, Savarithai J. Louis Anandaraj, Manisha Durai, Claudia Weidenthaler, Meike Emondts, Steven P. Nolan, Alexis Bordet, and Walter Leitner
- Subjects
SILP CATALYSTS ,DUAL CATALYSIS ,AMINES ,General Chemistry ,Catalysis ,HYDROAMINOMETHYLATION ,Chemistry ,AMINATION ,alkylamines ,allylamines ,ddc:540 ,formaldehyde and terminal alkynes ,HYDROGENATION - Abstract
ACS catalysis 12(24), 14902-14910 (2022). doi:10.1021/acscatal.2c04044, Published by ACS, Washington, DC
- Published
- 2022
36. 2‐Methyltetrahydrofuran (2‐MeTHF): A Green Solvent for Pd−NHC‐Catalyzed Amide and Ester Suzuki‐Miyaura Cross‐Coupling by N−C/O−C Cleavage
- Author
-
Jie An, Michal Szostak, Peng Lei, Steven P. Nolan, and Yun Ling
- Subjects
Solvent ,chemistry.chemical_compound ,Chemistry ,2-Methyltetrahydrofuran ,Amide ,Polymer chemistry ,Cleavage (crystal) ,General Chemistry ,Catalysis - Published
- 2019
37. Frontispiece: Mechanistic Aspects of the Palladium‐Catalyzed Suzuki‐Miyaura Cross‐Coupling Reaction
- Author
-
Èric Casals-Cruañas, Nikolaos V. Tzouras, Giovanni Talarico, Massimo Christian D'Alterio, Albert Poater, and Steven P. Nolan
- Subjects
Chemistry ,Organic Chemistry ,chemistry.chemical_element ,General Chemistry ,Combinatorial chemistry ,Catalysis ,Coupling reaction ,Palladium - Published
- 2021
38. Recent advances in the synthesis and derivatization of N-heterocyclic carbene metal complexes
- Author
-
Nikolaos V. Tzouras, Vladislav A. Voloshkin, and Steven P. Nolan
- Subjects
Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Derivatization ,Combinatorial chemistry ,Carbene - Abstract
N-heterocyclic carbene (NHC) metal complexes have gained an incredible amount of attention in the course of the last two decades and have become indispensable as an intricate part of a plethora of applications. The areas of their synthesis and derivatization are constantly evolving and bring new, more sustainable, cost-effective and simpler approaches to the design of existing and next generation catalysts and materials. This article provides an overview of the latest developments, focusing on those which have appeared during the last two years.
- Published
- 2021
39. The effect of cocoa alkalization on the non-volatile and volatile mood-enhancing compounds
- Author
-
Eleni Sioriki, Emmy Tuenter, Davy Van de Walle, Valérie Lemarcq, Catherine S.J. Cazin, Steven P. Nolan, Luc Pieters, and Koen Dewettinck
- Subjects
Volatiles ,Technology and Engineering ,ALKYLPYRAZINES ,IMPACT ,Phytochemicals ,Non-volatiles ,BEANS ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,Alkalization ,ANTIOXIDANT CAPACITY ,Cocoa ,Mood ,Medicine and Health Sciences ,COLOR ,Chocolate ,Cacao ,Volatile Organic Compounds ,Pharmacology. Therapy ,Polyphenols ,General Medicine ,FLAVANOL ,PRODUCTS ,Chemistry ,Odorants ,CHOCOLATE ,Food Science - Abstract
Alkalization is a process to improve color, dispersibility and flavor of cocoa powder but is likely to have a negative effect on the phytochemicals. Hereto, the impact of alkalization degree (none, medium and high) on the potential mood-enhancing compounds corresponding to the four levels of the mood pyramid model (flavanols, methylxanthines, biogenic amines and orosensory properties) was investigated. The phytochemical content, analyzed via UPLC-HRMS, showed reduction of specific potential mood-enhancing compounds upon alkalization, implying a decrease in bitterness and astringency. Moreover, volatile compounds analysis via HS-SPME-GC–MS indicated that alkalization reduced the levels of volatile compounds, responsible for acidity, fruity, floral and cocoa aromas. With respect to the orosensory properties, the cocoa powder palatability was suggested to be increased due to reduced acidity, bitterness, and astringency, while the desired volatile compounds were reduced. However, sensorial analysis is required to link the volatile results with the overall effect on the flavor perception.
- Published
- 2021
40. Au⋅⋅⋅H-C Hydrogen Bonds as Design Principle in Gold(I) Catalysis
- Author
-
Marina Saab, Nikolaos V. Tzouras, Kristof Van Hecke, Viktoria H. Däschlein-Gessner, Steven P. Nolan, Kai-Stephan Feichtner, Thorsten Scherpf, Heidar Darmandeh, Busra Dereli, Sofie M. P. Vanden Broeck, Julian Löffler, Catherine S. J. Cazin, and Luigi Cavallo
- Subjects
steric and electronic properties ,010402 general chemistry ,01 natural sciences ,Catalysis ,ATOMS ,chemistry.chemical_compound ,General chemistry ,Gold Catalysis ,Moiety ,Research Articles ,CENTER-DOT-AU ,catalysis ,010405 organic chemistry ,Hydrogen bond ,Ligand ,Chemistry ,General Medicine ,General Chemistry ,Onium ,gold ,Combinatorial chemistry ,3. Good health ,0104 chemical sciences ,phosphines ,SILVER ,CYCLOADDITIONS ,secondary interactions ,COMPLEXES ,LIGANDS ,Hydroamination ,METALS ,Phosphine ,Research Article - Abstract
Secondary ligand–metal interactions are decisive in many catalytic transformations. While arene–gold interactions have repeatedly been reported as critical structural feature in many high‐performance gold catalysts, we herein report that these interactions can also be replaced by Au⋅⋅⋅H−C hydrogen bonds without suffering any reduction in catalytic performance. Systematic experimental and computational studies on a series of ylide‐substituted phosphines featuring either a PPh3 (PhYPhos) or PCy3 (CyYPhos) moiety showed that the arene‐gold interaction in the aryl‐substituted compounds is efficiently compensated by the formation of Au⋅⋅⋅H−C hydrogen bonds. The strongest interaction is found with the C−H moiety next to the onium center, which due to the polarization results in remarkably strong interactions with the shortest Au⋅⋅⋅H−C hydrogen bonds reported to date. Calorimetric studies on the formation of the gold complexes further confirmed that the PhYPhos and CyYPhos ligands form similarly stable complexes. Consequently, both ligands showed the same catalytic performance in the hydroamination, hydrophenoxylation and hydrocarboxylation of alkynes, thus demonstrating that Au⋅⋅⋅H−C hydrogen bonds are equally suited for the generation of highly effective gold catalysts than gold‐arene interactions. The generality of this observation was confirmed by a comparative study between a biaryl phosphine ligand and its cyclohexyl‐substituted derivative, which again showed identical catalytic performance. These observations clearly support Au⋅⋅⋅H−C hydrogen bonds as fundamental secondary interactions in gold catalysts, thus further increasing the number of design elements that can be used for future catalyst construction., Experimental and computational studies on PPh3 and PCy3‐substituted ylide‐functionalized phosphines as well as on a biaryl and a cyclohexyl‐aryl phosphine demonstrate that Au⋅⋅⋅H−C hydrogen bonds can serve as secondary metal ligand interactions similar to gold–arene interactions often used in ligand design for the stabilization of catalytically active species. Remarkably short Au−H bonds are observed.
- Published
- 2021
41. Platinum-Catalyzed Alkene Hydrosilylation: Solvent-Free Process Development from Batch to a Membrane-Integrated Continuous Process
- Author
-
Dominic Ormerod, Tahani Al Chami Al Bayrakdar, Steven P. Nolan, Fady Nahra, and Benon P. Maliszewski
- Subjects
chemistry.chemical_classification ,Chemistry ,Hydrosilylation ,Alkene ,General Chemical Engineering ,chemistry.chemical_element ,Homogeneous catalysis ,Combinatorial chemistry ,Catalysis ,chemistry.chemical_compound ,General Energy ,Membrane ,Imidazolidine ,Yield (chemistry) ,Environmental Chemistry ,General Materials Science ,Platinum - Abstract
The integration of a membrane separation protocol with the platinum-catalyzed hydrosilylation of olefins is investigated. The catalytic reaction is first optimized in batch where [Pt(IPr*)(dms)Cl2 ] (IPr*=1,3-bis[2,6-bis(diphenylmethyl)-4-methylphenyl]imidazol-2-ylidene, dms=dimethyl sulfide) demonstrates superior activity compared to the less sterically encumbered [Pt(SIPr)(dms)Cl2 ] (SIPr=1,3-bis(2,6-diisopropylphenyl)imidazolidine) congener. Filtration conditions are identified in membrane screening experiments. Hydrosilylation of 1-octene catalyzed by [Pt(IPr*)(dms)Cl2 ] is conducted in continuous mode and the platinum catalyst is separated efficiently over the commercially available Borsig oNF-2 membrane, all under solvent-free conditions. An advantage of this process is that both reaction and separation are coupled in a single step. Moreover, at the end of the process the intact catalyst was recovered in 80 % yield as an off-white solid without any further purification.
- Published
- 2021
42. Mechanistic Aspects of the Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction
- Author
-
Èric Casals-Cruañas, Steven P. Nolan, Giovanni Talarico, Albert Poater, Nikolaos V. Tzouras, Massimo Christian D'Alterio, Agencia Estatal de Investigación, D'Alterio, M. C., Casals-Cruanas, E., Tzouras, N. V., Talarico, G., Nolan, S. P., and Poater, A.
- Subjects
Reaction mechanism ,preactivation ,ARYL HALIDES ,Pal·ladi ,chemistry.chemical_element ,Reviews ,Review ,C-C bond formation ,DFT ,C-O BOND ,Coupling reaction ,Catalysis ,Suzuki-Miyaura ,OLEFIN METATHESIS ,Catàlisi ,Computational chemistry ,OXIDATIVE ADDITION ,N-HETEROCYCLIC CARBENES ,GRIGNARD-REAGENTS ,Density functionals ,Funcional de densitat, Teoria del ,PD-NHC PRECATALYST ,Chemistry ,Organic Chemistry ,Activació (Química) ,General Chemistry ,Bond formation ,Rate-determining step ,palladium ,CARBON-CARBON ,ROOM-TEMPERATURE ,Activation (Chemistry) ,C−C bond formation ,REDUCTIVE ELIMINATION ,Cross coupling ,Palladium - Abstract
The story of C−C bond formation includes several reactions, and surely Suzuki‐Miyaura is among the most outstanding ones. Herein, a brief historical overview of insights regarding the reaction mechanism is provided. In particular, the formation of the catalytically active species is probably the main concern, thus the preactivation is in competition with, or even assumes the role of the rate determining step (rds) of the overall reaction. Computational chemistry is key in identifying the rds and thus leading to milder conditions on an experimental level by means of predictive catalysis., The complexity of the Pd‐catalyzed Suzuki‐Miyaura C−C bond formation reaction lies in the indivdual steps of the cycle, as well as in the generation of the catalytically active species. An overview of the topic is provided from a historical perspective.
- Published
- 2021
43. Synthesis of gold(I)-trifluoromethyl complexes and their role in generating spectroscopic evidence for a gold(I)-difluorocarbene species
- Author
-
Steven P. Nolan, Alexandra M. Z. Slawin, Fady Nahra, Kristof Van Hecke, David J. Nelson, Alba Collado, Laura Falivene, Catherine S. J. Cazin, Sofie M. P. Vanden Broeck, David B. Cordes, Luigi Cavallo, University of St Andrews. School of Chemistry, and University of St Andrews. EaSTCHEM
- Subjects
difluorocarbenes ,fluoride abstraction ,gold(I) ,N-heterocyclic carbenes ,trifluoromethyl ,PHARMACEUTICALS ,EFFICIENT ,Fluoride abstraction ,Gold(I) ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,Trifluoromethyl ,chemistry.chemical_compound ,QD ,CATALYZED ,Difluorocarbene ,010405 organic chemistry ,Trifluoromethylation ,Organic Chemistry ,FLUOROFORM-DERIVED CUCF3 ,DAS ,General Chemistry ,QD Chemistry ,0104 chemical sciences ,carbenes ,Chemistry ,chemistry ,ARENES ,N-heterocyclic ,TRIFLUOROMETHYLATION ,ARYL ,N-heterocyclic carbene ,FLUORINE - Abstract
We thank the Ghent University (IoF), the Special Research Fund (BOF) starting (SPN, CSJC) and advanced (SPN, KVH) grants and Research Foundation Flanders (FWO) (fellowship to SVB and grant to CSJC and KVH) for funding. Readily-prepared and bench-stable [Au(CF3)(NHC)] compounds were synthesized using new methodologies, starting from [Au(OH)(NHC)], [Au(Cl)(NHC)] or [Au(L)(NHC)]HF2 precursors (NHC = N-heterocyclic carbene). The mechanism of formation of these species was investigated. Consequently, a new and straightforward strategy for the mild and selective cleavage of a single carbon-fluorine bond from [Au(CF3)(NHC)] complexes was attempted and found to be reversible in the presence of an additional nucleophilic fluoride source. This straightforward technique has led to the unprecedented spectroscopic observation of a gold(I)-NHC difluorocarbene species. Postprint
- Published
- 2021
44. In vitro and in cellulo anti-diabetic activity of AuI- and AuIII-isothiourea complexes
- Author
-
M. Iqbal Choudhary, Steven P. Nolan, Muniza Shaikh, Andrew D. Smith, Danila Gasperini, Sharmeen Fayyaz, and University of St Andrews. School of Chemistry
- Subjects
Steric effects ,Incretin ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,E-NDAS ,law.invention ,Bioinorganic chemistry ,Inorganic Chemistry ,SDG 3 - Good Health and Well-being ,law ,Diabetes type 2 ,Materials Chemistry ,Ic50 values ,medicine ,QD ,Physical and Theoretical Chemistry ,Caco-2 cells ,chemistry.chemical_classification ,Isothiourea ,021001 nanoscience & nanotechnology ,QD Chemistry ,Combinatorial chemistry ,In vitro ,0104 chemical sciences ,Enzyme ,chemistry ,Cell culture ,Sitagliptin ,Recombinant DNA ,Dipeptidyl peptdase-IV ,0210 nano-technology ,Gold complexes ,medicine.drug - Abstract
Authors are grateful to the Higher Education Commission (HEC), Pakistan, for providing financial support under the Indigenous Ph. D. Fellowship for 5000 Scholars Phase-II program for providing financial support. About 100 million people worldwide have type II diabetes (T2D), making it one of the most common metabolic disease. DPP-IV inhibitors are new class of anti-diabetic drug. Gold complexes are known for diverse biological activities. Considering these precedents, and growing interest in developing metal-based enzyme inhibitors, we report here the dipeptidyl peptidase-IV (DPP-IV) inhibitory potential of cationic, and neutral chiral gold (I), and gold (III) isothiourea complexes. Colorimetric assay with recombinant DPP-IV enzyme was employed for initial screening. Kinetic based mechanistic studies were also performed for most active complexes. Efficiency of identified inhibitors in biological environment was assessed in in cellulo assay, using Caco-2 cell line. These complexes showed a good to moderate inhibition of DPP-IV with IC50 values in the range of 22.0 – 99.0 µM, as compared to standard inhibitor, sitagliptin (IC50 = 0.033 ± 0.04 µM). It was observed that steric, and electronic properties of the isothiourea ligands have profound effect on the DPP-IV inhibitory activity of these complexes. To the best of our knowledge this study reports for the first time isothiourea based gold complexes as inhibitors of DPP-IV enzyme. These results thus provide an approach for exploring new insights into the development of effective agents against diabetes using incretin-based therapy. Postprint
- Published
- 2021
45. N-Heterocyclic carbene complexes enabling the α-arylation of carbonyl compounds
- Author
-
Sylwia Ostrowska, Thomas Scattolin, and Steven P. Nolan
- Subjects
Steric effects ,Research groups ,Aryl ,Metals and Alloys ,chemistry.chemical_element ,Context (language use) ,General Chemistry ,Combinatorial chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,chemistry.chemical_compound ,chemistry ,Materials Chemistry ,Ceramics and Composites ,Carbene ,Palladium - Abstract
The considerable importance of α-arylated carbonyl compounds, which are widely used as final products or as key intermediates in the pharmaceutical industry, has prompted numerous research groups to develop efficient synthetic strategies for their preparation in recent decades. In this context, the α-arylation of carbonyl compounds catalyzed by transition-metal complexes have been particularly helpful in constructing this motif. As illustrated in this contribution, tremendous advances have taken place using palladium– and nickel–NHC (NHC = N-heterocyclic carbene) complexes as pre-catalysts for the arylation of a wide range of ketones, aldehydes, esters and amides with electron-rich, electron-neutral, electron-poor, and sterically hindered aryl halides or pseudo-halides. Despite significant progress, especially in asymmetric α-arylations promoted by chiral NHC ligands, there are numerous challenges which have and continue to encourage further studies on this topic. Some of these are presented in this report.
- Published
- 2021
46. Investigating the Biological Activity of Imidazolium Aurate Salts
- Author
-
Sheeba Wajid, M. Iqbal Choudhary, Danish Sharif, Steven P. Nolan, Rehan Imad, Sharmeen Fayyaz, Fady Nahra, Eleni Sioriki, Sylvain Gaillard, Fiza Arshad, and Khair Ullah
- Subjects
chemistry.chemical_classification ,biology ,Tyrosinase ,Biological activity ,General Chemistry ,Dipeptidyl peptidase ,Enzyme ,chemistry ,Prolyl endopeptidase ,Biochemistry ,Carbonic anhydrase ,medicine ,biology.protein ,Moiety ,Cytotoxicity ,medicine.drug - Abstract
We report herein the biological activities of several imidazolium aurate(I) salts. The cytotoxicity on three cell-lines (i. e. Hela, H460 and 3T3), enzyme inhibition on a panel of five enzymes (i. e. prolyl endopeptidase, butyrylcholinesterase, tyrosinase, dipeptidyl peptidase and carbonic anhydrase), iron chelation and in vitro Leishmanicidal assay for promastigotes are described. A comparison with other data found in the literature using similar standards to our control experiment is also discussed. Finally, all these data lead us to establish some structure-activity correlations and to determine the potential importance of the gold moiety in these salts.
- Published
- 2019
47. Palladate Precatalysts for the Formation of C–N and C–C Bonds
- Author
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Katie G. Warren, Catherine S. J. Cazin, Steven P. Nolan, Assem Barakat, Abdullah Mohammed Al-Majid, Fady Nahra, Mohammad Shahidul Islam, and Caroline M. Zinser
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Chemistry ,SUZUKI-MIYAURA ,Organic Chemistry ,Medicinal chemistry ,ALPHA-ARYLATION ,Catalysis ,Inorganic Chemistry ,AMINATION ,HETEROCYCLIC CARBENE COMPLEXES ,CROSS-COUPLING REACTIONS ,BUCHWALD-HARTWIG ,LIGANDS ,CATALYTIC-ACTIVITY ,Physical and Theoretical Chemistry ,(NHC)PD(ALLYL)CL NHC ,ARYL - Abstract
A series of imidazolium-based palladate precatalysts has been synthesized and the catalytic activity of these air- and moisture-stable complexes evaluated as a function of the nature of the imidazolium counterion. These precatalysts can be converted under catalytic conditions to Pd-NHC species capable of enabling the Buchwald-Hartwig aryl amination and the alpha-arylation of ketones. Both reactions can be carried out efficiently under very mild operating conditions. The effectiveness of the protocol was tested on functionality-laden substrates.
- Published
- 2019
48. Synthesis of Di-Substituted Alkynes via Palladium-Catalyzed Decarboxylative Coupling and C-H Activation
- Author
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Marcel Brill, Frédéric Izquierdo, Catherine S. J. Cazin, Steven P. Nolan, Fady Nahra, Jiufeng Wu, and Alberto Gómez-Herrera
- Subjects
Internal alkyne ,NHC ,Decarboxylation ,SUZUKI-MIYAURA ,chemistry.chemical_element ,FREE SONOGASHIRA REACTION ,Catalysis ,CARBON ,Coupling ,PRE-CATALYST ,HETEROCYCLIC CARBENE ,Polymer chemistry ,ARYL CHLORIDES ,CARBOXYLIC-ACIDS ,Chemistry ,COPPER-FREE ,General Chemistry ,DIARYLALKYNES ,Coupling (electronics) ,Aryl bromide ,Fluoroenyne ,COMPLEXES ,Palladium - Abstract
A straightforward methodology for the decarboxylative cross-coupling of aryl bromides and phenylpropiolic acid using a Pd(II)-NHC catalyst has been developed. Various aryl bromides have been successfully transformed into the corresponding di-substituted alkynes using environmentally benign conditions (weak base and ethanol as solvent). This efficient catalytic system also proved useful for the copper-free Sonogashira coupling of aryl and alkenyl bromides with various terminal alkynes. The synthetic utility of these methodologies was highlighted in the synthesis of a polyaromatic compound and various fluoroenynes.
- Published
- 2019
49. Synthesis and reactivity of [Au(NHC)(Bpin)] complexes
- Author
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Luigi Cavallo, Alexandra M. Z. Slawin, Steven P. Nolan, Caroline M. Zinser, David B. Cordes, Fady Nahra, Laura Falivene, Catherine S. J. Cazin, Marcel Brill, The Royal Society, University of St Andrews. School of Chemistry, and University of St Andrews. EaSTCHEM
- Subjects
010405 organic chemistry ,Chemistry ,Metals and Alloys ,Alpha (ethology) ,chemistry.chemical_element ,DAS ,General Chemistry ,QD Chemistry ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,Catalysis ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Materials Chemistry ,Ceramics and Composites ,QD ,Reactivity (chemistry) ,Experimental methods ,Boron - Abstract
The authors gratefully acknowledge the Royal Society (University Research Fellowship to C.S.J.C.), AstraZeneca (Studenship to C.M.Z) and VLAIO (CO2PERATE) for support of this work. We thank King Saud University (DSF Program) and KAUST (Award No.OSR-2015-CCF-1974-03) for support. A new class of [Au(NHC)(Bpin)] complexes has been synthesized and their unusual reactivity was investigated using computational and experimental methods. The gold-boryl complexes exhibit unexpected high stability and reactivity. Postprint
- Published
- 2019
50. Quantifying electronic similarities between NHC–gold(<scp>i</scp>) complexes and their isolobal imidazolium precursors
- Author
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Sai V. C. Vummaleti, Richard M. P. Veenboer, Laura Falivene, Albert Poater, Steven P. Nolan, Luis Miguel Azofra, and Luigi Cavallo
- Subjects
Carbon atom ,Proton ,Ligand ,Chemistry ,General Physics and Astronomy ,Isolobal principle ,Protonation ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Paramagnetism ,Crystallography ,chemistry.chemical_compound ,Molecule ,Physical and Theoretical Chemistry ,0210 nano-technology ,Carbene - Abstract
A series of NHC-gold(i) (NHC = N-heterocyclic carbene) complexes has been studied by DFT calculations, enabling comparison of electronic and NMR behaviour with related protonated and free NHC molecules. Based on calculations, the NMR resonances of the carbenic C2 carbon atom in [Au(NHC)(Cl)] and [NHC(H)][Cl] exhibit increased shielding when compared to the free N-heterocyclic carbenes by an average of 46.6 ± 2.2 and 73.7 ± 4.3 ppm, respectively. A similar trend is observed when analysing the paramagnetic term of the magnetic shielding tensor. Although gold(i) and proton are considered isolobal fragments, imidazolium compounds lack π-backdonation due to the energetic unavailability of d-orbitals in H+. We propose that NHC-gold(i) complexes exhibit important π-backdonation irrespective of the relative amount of σ-donation between the NHC and gold(i)-X (X = anionic ligand) moieties in Au-NHC complexes. Interestingly, a correlation exists between the calculated shielding for gold (197Au) and the π-donation and π-backdonation contributions. We describe that this correlation also exists when analysing the σ-backdonation term, a property generally ignored yet representing a significant energetic contribution to the stability of the C2-Au bond.
- Published
- 2019
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