A Fluxional Copper Acetylide Cluster in CuAAC Catalysis

A molecularly defined copper acetylide cluster with ancillary N‐heterocyclic carbene (NHC) ligands was prepared under acidic reaction conditions. This cluster is the first molecular copper acetylide complex that features high activity in copper‐catalyzed azide–alkyne cycloadditions (CuAAC) with added acetic acid even at ?5 °C. Ethyl propiolate protonates the acetate ligands of the dinuclear precursor complex to release acetic acid and replaces one out of four ancillary ligands. Two copper(I) ions are thereby liberated to form the core of a yellow dicationic C₂‐symmetric hexa‐NHC octacopper hexaacetylide cluster. Coalescence phenomena in low‐temperature NMR experiments reveal fluxionality that leads to the facile interconversion of all of the NHC and acetylide positions. Kinetic investigations provide insight into the influence of copper acetylide coordination modes and the acetic acid on catalytic activity. The interdependence of “click” activity and copper acetylide aggregation beyond dinuclear intermediates adds a new dimension of complexity to our mechanistic understanding of the CuAAC reaction.     

Structural Diversity of Copper(I)–N‐Heterocyclic Carbene Complexes; Ligand Tuning Facilitates Isolation of the First Structurally Characterised Copper(I)–NHC Containing a Copper(I)–Alkene Interaction

The preparation of a series of imidazolium salts bearing N‐allyl substituents, and a range of substituents on the second nitrogen atom that have varying electronic and steric properties, is reported. The ligands have been coordinated to a copper(I) centre and the resulting copper(I)–NHC (NHC=N‐heterocyclic carbene) complexes have been thoroughly examined, both in solution and in the solid‐state. The solid‐state structures are highly diverse and exhibit a range of unusual geometries and cuprophilic interactions. The first structurally characterised copper(I)–NHC complex containing a copper(I)–alkene interaction is reported. An N‐pyridyl substituent, which forms a dative bond with the copper(I) centre, stabilises an interaction between the metal centre and the allyl substituent of a neighbouring ligand, to form a 1D coordination polymer. The stabilisation is attributed to the pyridyl substituent increasing the electron density at the copper(I) centre, and thus enhancing the metal(d)‐to‐alkene(π*) back‐bonding. In addition, components other than charge transfer appear to have a role in copper(I)–alkene stabilisation because further increases in the Lewis basicity of the ligand disfavours copper(I)–alkene binding.     

Triptycene‐Based Chiral and meso‐N‐Heterocyclic Carbene Ligands and Metal Complexes

Based on 1‐amino‐4‐hydroxy‐triptycene, new saturated and unsaturated triptycene‐NHC (N‐heterocyclic carbene) ligands were synthesized from glyoxal‐derived diimines. The respective carbenes were converted into metal complexes [(NHC)MX] (M=Cu, Ag, Au; X=Cl, Br) and [(NHC)MCl(cod)] (M=Rh, Ir; cod=1,5‐cyclooctadiene) in good yields. The new azolium salts and metal complexes suffer from limited solubility in common organic solvents. Consequently, the introduction of solubilizing groups (such as 2‐ethylhexyl or 1‐hexyl by O‐alkylation) is essential to render the complexes soluble. The triptycene unit infers special steric properties onto the metal complexes that enable the steric shielding of selected areas close to the metal center. Next, chiral and meso‐triptycene based N‐heterocyclic carbene ligands were prepared. The key step in the synthesis of the chiral ligand is the Buchwald–Hartwig amination of 1‐bromo‐4‐butoxy‐triptycene with (1S,2S)‐1,2‐diphenyl‐1,2‐diaminoethane, followed by cyclization to the azolinium salt with HC(OEt)₃. The analogous reaction with meso‐1,2‐diphenyl‐1,2‐diaminoethane provides the respective meso‐azolinium salt. Both the chiral and meso‐azolinium salts were converted into metal complexes including [(NHC)AuCl], [(NHC)RhCl(cod)], [(NHC)IrCl(cod)], and [(NHC)PdCl(allyl)]. An in situ prepared chiral copper complex was tested in the enantioselective borylation of α,β‐unsaturated esters and found to give an excellent enantiomeric ratio (er close to 90:10).     

Nickel N‐heterocyclic carbene complexes in the vinyl polymerization of norbornene

Vinyl polymerized norbornene has some useful properties such as good mechanical strength, optical transparency and heat resistance. Several transition metal complexes have been described in the literature as active catalysts for the vinyl polymerization of norbornene. We now report the use of three types of nickel(II) complexes with N‐heterocyclic carbene (NHC) ligands in the catalytic vinyl polymerization of norbornene under a range of conditions. Specifically, two nickel complexes bearing a chelating bis(NHC) ligand, two nickel complexes bearing two chelating anionic N‐donor functionalized NHC ligands as well as one diiodidonickel(II) complex with two monodentate NHC ligands were tested. The solid‐state structure of bis(1,3‐dimethylimidazol‐2‐ylidene)diiodidonickel(II), as determined by X‐ray crystallography, is presented. The highest polymerization activity of 2.6 × 10⁷ g (mol cat)^?1 h^?1 was observed using the latter nickel complex as catalyst, activated by methylaluminoxane. The norbornene polymers thus obtained are of high molecular weight but with rather low polydispersity. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis,Structure and Catalytic Activity of NHC–AgI Carboxylate Complexes

A general synthetic route was used to prepare 15 new N‐heterocyclic carbene (NHC)–Ag^I complexes bearing anionic carboxylate ligands [Ag(NHC)(O₂CR)], including a homologous series of complexes of sterically flexible ITent ligands, which permit a systematic spectroscopic and theoretical study of the structural and electronic features of these compounds. The complexes displayed a significant ligand‐accelerated effect in the intramolecular cyclisation of propargylic amides to oxazolidines. The substrate scope is highly complementary to that previously achieved by NHC–Au and pyridyl–Ag^I complexes.     

Copper(I)‐catalyzed multicomponent reactions in sustainable media

Multicomponent reactions including Biginelli reaction and A³ coupling are useful synthetic methodologies as they can provide valuable intermediates and building blocks for the synthesis of bioactive natural compounds. The heterocyclic products of these transformations represent antibacterial, antitumor or anti‐inflammatory properties. In presented study, copper‐mediated protocols for Biginelli reaction and A³ coupling in sustainable solvents were reported. At first, charged NHC copper complexes were synthesized in few steps and characterized using spectroscopic methods followed by preliminary activity tests in sustainable media. Later in this study, Biginelli reaction and A³ coupling were proceeded using prepared copper catalytic systems under mild conditions. Desired nitrogen‐bearing products were obtained with moderate to very high yields. Some attempts to recycle one of the received NHC copper initiators were also investigated.     

Chemodivergent Metathesis of Dienynes Catalyzed by Ruthenium–Indenylidene Complexes: An Experimental and Computational Study

A study on the enyne metathesis reaction leading to the formation cyclic compounds using ruthenium–indenylidene complexes is presented. Several 1,11‐dien‐6‐ynes have been subjected to ruthenium metathesis cyclization by using ruthenium–indenylidene complexes bearing various phosphine and N‐heterocyclic carbene (NHC) ligands. Interestingly, for some substrates chemodivergent metathesis occurs and is a function of the catalyst employed. This led us to investigate the competing “ene‐then‐yne” or “yne‐then‐ene” reaction pathways apparently at play in these systems using both experimental observations and DFT calculations. Experimental and computational studies were found in good agreement and permit to conclude that for phosphine‐containing catalysts, the “ene‐then‐yne” pathway is exclusively adopted. On the other hand, for catalysts bearing NHC ligands, both pathways are possible.     

Structure and spectroscopic properties of the dimeric copper(I) N‐heterocyclic carbene complex [Cu2(CNCt‐Bu)2](PF6)2

In recent years, the use of copper N‐heterocyclic carbene (NHC) complexes has expanded to fields besides catalysis, namely medicinal chemistry and luminescence applications. In the latter case, multinuclear copper NHC compounds have attracted interest, however, the number of these complexes in the literature is still quite limited. Bis[μ‐1,3‐bis(3‐tert‐butylimidazolin‐2‐yliden‐1‐yl)pyridine]‐1κ⁴C²,N:N,C^2′;2κ⁴C²,N:N,C^2′‐dicopper(I) bis(hexafluoridophosphate), [Cu₂(C₁₉H₂₅N₅)₂](PF₆)₂, is a dimeric copper(I) complex bridged by two CNC, i.e. bis(N‐heterocyclic carbene)pyridine, ligands. Each Cu^I atom is almost linearly coordinated by two NHC ligands and interactions are observed between the pyridine N atoms and the metal centres, while no cuprophilic interactions were observed. Very strong absorption bands are evident in the UV–Vis spectrum at 236 and 274 nm, and an emission band is observed at 450 nm. The reported complex is a new example of a multinuclear copper NHC complex and a member of a compound class which has only rarely been reported.     

N‐Heterocyclic Carbene Copper(I) Rotaxanes Mediate Sequential Click Ligations with All Reagents Premixed

We have prepared NHC‐Cu^I complexes with a rotaxane structure and used them as sterically sensitive catalysts for one‐pot sequential copper‐catalyzed azide/alkyne cycloadditions in solutions containing all of the coupling partners premixed in unprotected form. Most notably, a photolabile and sterically encumbered complex first catalyzed the coupling of a less bulky azide/alkyne pair; after removing the protective macrocyclic component from the rotaxane structure, through irradiation with light, the exposed dumbbell‐shaped NHC‐Cu^I complex catalyzed the second click reaction of a bulkier azide/alkyne pair. Using this approach, we obtained predominantly, from a single sealed pot, a bis‐triazole product (84 %) from a mixture of two sterically distinct azides and a diyne.     

Synthesis,structural characterization and catalytic activity of benzimidazole‐functionalized Pd(II) N‐heterocyclic carbene complexes

Two Pd(II)–NHC complexes bearing benzimidazole and pyridine groups have been successfully prepared and fully characterized by NMR and X‐ray diffraction analysis. The structure of palladium complexes are a typical square‐planar with palladium surrounded by two pairs of trans‐arranged benzimidazole and carbene ligands. The Pd–NHC complexes have been proved to be a highly efficient catalyst for the Mizoroki–Heck coupling reaction of aryl halides with various substituted acrylates under mild conditions in excellent yields. Copyright © 2013 John Wiley & Sons, Ltd.     

Refinement of Copper(II) Azide with 1‐Alkyl‐5H‐tetrazoles: Adaptable Energetic Complexes

A concept for stabilizing highly sensitive and explosive copper(II) azide with 1‐N‐substituted tetrazoles is described. It was possible to stabilize the system by the use of highly endothermic, nitrogen‐rich ligands. The sensitivities of the resulting energetic copper coordination compounds can be tuned further by variation of the alkyl chain of the ligands and by phlegmatization of the complexes with classical additives during the synthesis. It is demonstrated, using the compound based on 1‐methyl‐5H‐tetrazole ([Cu(N₃)₂(MTZ)], 1 ) that this class of complexes can be applied as a potential replacement for both lead azide (LA) and lead styphnate (LS). The complex was extensively investigated according to its chemical (elemental analysis, single‐crystal and powder X‐ray diffraction, IR spectroscopy, scanning electron microscopy) and physico‐chemical properties (differential thermal analysis, sensitivities towards impact, friction, and electrostatic discharge) compared to pure copper(II) azide.     

Copper‐Catalyzed Azide–Ynamide Cyclization to Generate α‐Imino Copper Carbenes: Divergent and Enantioselective Access to Polycyclic N‐Heterocycles

Here an efficient copper‐catalyzed cascade cyclization of azide‐ynamides via α‐imino copper carbene intermediates is reported, representing the first generation of α‐imino copper carbenes from alkynes. This protocol enables the practical and divergent synthesis of an array of polycyclic N‐heterocycles in generally good to excellent yields with broad substrate scope and excellent diastereoselectivities. Moreover, an asymmetric azide–ynamide cyclization has been achieved with high enantioselectivities (up to 98:2 e.r.) by employing BOX‐Cu complexes as chiral catalysts. Thus, this protocol constitutes the first example of an asymmetric azide–alkyne cyclization. The proposed mechanistic rationale for this cascade cyclization is further supported by theoretical calculations.     

Enantioselective Generation of Adjacent Stereocenters in a Copper‐Catalyzed Three‐Component Coupling of Imines,Allenes, and Diboranes

A highly enantio‐ and diastereoselective copper‐catalyzed three‐component coupling affords the first general synthesis of homoallylic amines bearing adjacent stereocenters from achiral starting materials. The method utilizes a commercially available NHC ligand and copper source, operates at ambient temperature, couples readily available simple imines, allenes, and diboranes, and yields high‐value homoallylic amines that exhibit versatile amino, alkenyl, and boryl units.     

Synthesis and characterization of polymer linked copper(I) bis(N‐heterocyclic carbene) mechanocatalysts

In this paper, the synthesis and characterization of a series of latent polymeric bis(N‐heterocyclic carbene) (NHC) copper(I) complexes is reported, which can be activated for the copper(I)‐catalyzed azide/alkyne cycloaddition (CuAAC) via ultrasound. To prove the influence of chain length and nature of the polymer towards the activation, poly(isobutylene) (PIB), poly(styrene) (PS) and poly(tetrahydrofuran) (PTHF) are synthesized via living polymerization techniques (LCCP, ATRP, CROP) obtaining different chain lengths (from 2500 to 9000 g/mol), followed by quaternization with N‐methylimidazole, generating the corresponding N‐methylimidazolium‐telechelic polymers. The deprotonation of these macroligands via strong bases like sodium tert‐butoxide (NaO^tBu) or potassium hexamethyldisilazide (KHMDS) yields the free N‐heterocyclic carbenes (NHCs), which are used to coordinate to tetrakis(acetonitrile)copper(I) hexafluorophosphate, forming the final polymer‐based mono‐ and bis(N‐methylimidazole‐2‐ylidene) copper(I)X complexes. The structural proof of these complexes is accomplished via ¹H‐NMR spectroscopy, MALDI‐TOF‐MS and GPC‐techniques. The activation of the copper(I) biscarbene catalysts by ultrasound is studied by GPC, revealing the cleavage of one shielding NHC‐ligand. The initial catalytic latency and the via ultrasound introduced catalytic activation is successfully demonstrated monitoring a CuAAC “click” reaction of benzyl azide and phenylacetylene by in situ ¹H‐NMR spectroscopy introducing thus “click” conversions up to 97%. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3893–3907     

α-Amino-iso-Butyric Acid Foldamers Terminated with Rhodium(I) N-Heterocyclic Carbene Catalysts

To investigate how remotely induced changes in ligand folding might affect catalysis by organometallic complexes, dynamic α-amino-iso-butyric acid (Aib) peptide foldamers bearing rhodium(I) N-heterocyclic carbene (NHC) complexes have been synthesized and studied. X-ray crystallography of a foldamer with an N-terminal azide and a C-terminal Rh(NHC)(Cl)(diene) complex showed a racemate with a chiral axis in the Rh(NHC) complex and a distorted 3₁₀ helical body. Replacing the azide with either one or two chiral L-α-methylvaline (L-αMeVal) residues gave diastereoisomeric foldamers that each possessed point, helical and axial chirality. NMR spectroscopy revealed an unequal ratio of diastereoisomers for some foldamers, indicating that the chiral conformational preference of the N-terminal residue(s) was relayed down the 1 nm helical body to the axially chiral Rh(NHC) complex. Although the remote chiral residue(s) did not affect the stereoselectivity of hydrosilylation reactions catalysed by these foldamers, these studies suggest a potential pathway towards remote conformational control of organometallic catalysts.     

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

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

NHC–Copper(I) Halide‐Catalyzed Direct Alkynylation of Trifluoromethyl Ketones on Water

An efficient and easily scalable NHC–copper(I) halide‐catalyzed addition of terminal alkynes to 1,1,1‐trifluoromethyl ketones, carried out on water for the first time, is reported. A series of addition reactions were performed with as little as 0.1–2.0 mol % of [(NHC)CuX] (X=Cl, Br, I, OAc, OTf) complexes, providing tertiary propargylic trifluoromethyl alcohols in high yields and with excellent chemoselectivity from a broad range of aryl‐ and more challenging alkyl‐substituted trifluoromethyl ketones (TFMKs). DFT calculations were performed to rationalize the correlation between the yield of catalytic alkynylation and the sterics of N‐heterocyclic carbenes (NHCs), expressed as buried volume (%VBur), indicating that steric effects dominate the yield of the reaction. Additional DFT calculations shed some light on the differential reactivity of [(NHC)CuX] complexes in the alkynylation of TFMKs. The first enantioselective version of a direct alkynylation in the presence of C₁‐symmetric NHC–copper(I) complexes is also presented.     

Synthesis of rhodium N-heterocyclic carbene complexes and their catalytic activity in the hydrosilylation of alkenes in ionic liquid medium

Rhodium complexes bearing N-heterocyclic carbene (NHC) ligands were prepared from bis(η⁴-1,5-cyclooctadiene) dichlorodirhodium and 1-alkyl-3-methylimidazolium-2-carboxylate, and the catalytic properties of rhodium complexes prepared in the hydrosilylation of alkenes in ionic liquid media were investigated. It was found that both the catalytic activity and selectivity of the rhodium complexes bearing NHC ligands were influenced by the attached substituents of the imidazolium cation. Additionally, rhodium complexes bearing NHC ligands in ionic liquid BMimPF₆ could be reused without noticeable loss of catalytic activity and selectivity.     

Chiral boron-bridged bisoxazoline (borabox) ligands: structures and reactivities of Pd and Cu complexes

Anionic boron-bridged bisoxazolines (borabox ligands) have been synthesized and characterized in their protonated forms. The ligands are tuneable over a wide range, allowing either alkyl or aryl substituents at the oxazoline rings and the central bridging boron atom. The structural parameters of this new ligand type have been investigated by X-ray analyses of palladium and copper complexes. Electronic properties have been studied by (13)C NMR spectroscopy and by DFT calculations on palladium allyl complexes and compared to those of analogous bisoxazoline (box) complexes. Borabox complexes are more electron-rich at the metal center than their neutral box congeners, and as a consequence of the longer bonds between the bridging atom and the oxazoline rings, their bite angles are larger. Palladium(II) complexes bearing an unsubstituted allyl ligand and homoleptic copper(II) complexes each possess an almost flat chelate ring. NMR analysis of a (1,3-diphenylallyl)(borabox)palladium complex showed a 92:8 mixture of (syn,syn) and (anti,syn) allyl isomers, in contrast with a previously reported box analogue that existed exclusively in the (syn,syn) form. Comparison of the corresponding crystal structures revealed that the distance between the bisoxazoline and the allyl ligand in the borabox complex is shorter. In the copper-catalyzed allylic oxidation of cyclohexene and cyclopentene with tert-butyl perbenzoate, borabox ligands gave results similar-and in some cases superior-to those obtained with analogous box ligands.     

A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs

Rhodium(I) complexes bearing N‐heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry, but there are very few reports of biological properties of these organometallics. A series of Rh^I‐NHC derivatives with 1,5‐cyclooctadiene and CO as secondary ligands were synthesized, characterized, and biologically investigated as prospective antitumor drug candidates. Pronounced antiproliferative effects were noted for all complexes, along with moderate inhibitory activity of thioredoxin reductase (TrxR) and efficient binding to biomolecules (DNA, albumin). Biodistribution studies showed that the presence of albumin lowered the cellular uptake and confirmed the transport of rhodium into the nuclei. Changes in the mitochondrial membrane potential (MMP) were observed as well as DNA fragmentation in wild‐type and daunorubicin‐ or vincristine‐resistant Nalm‐6 leukemia cells. Overall, these studies indicated that Rh^I‐NHC fragments could be used as partial structures of new antitumor agents, in particular in those drugs designed to address resistant malignant tissues.