NiII Species Research Articles

Competing H2 versus Intramolecular C–H Activation at a Dinuclear Nickel Complex via Metal–Metal Cooperative Oxidative Addition

Nickel(I) metalloradicals bear great potential for the reductive activation of challenging substrates but are often too unstable to be isolated. Similar chemistry may be enabled by nickel(II) hydrides that store the reducing equivalents in hydride bonds and reductively eliminate H2 upon substrate binding. Here we present a pyrazolate-based bis(β-diketiminato) ligand [LPh]3- with bulky m-terphenyl substituents that can host two Ni-H units in close proximity. Complexes [LPh(NiII-H)2]- (3) are prone to intramolecular reductive H2 elimination, and an equilibrium between 3 and orthometalated dinickel(II) monohydride complexes 2 is evidenced. 2 is shown to form via intramolecular metal-metal cooperative phenyl group C(sp2)-H oxidative addition to the dinickel(I) intermediate [LPhNiI2]- (4). While NiI species have been implicated in catalytic C-H functionalization, discrete activation of C-H bonds at NiI complexes has rarely been described. The reversible H2 and C-H reductive elimination/oxidative addition equilibrium smoothly unmasks the powerful 2-electron reductant 4 from either 2 or 3, which is demonstrated by reaction with benzaldehyde. A dramatic cation effect is observed for the rate of interconversion of 2 and 3 and also for subsequent thermally driven formation of a twice orthometalated dinickel(II) complex 6. X-ray crystallographic and NMR titration studies indicate distinct interaction of the Lewis acidic cation with 2 and 3. The present system allows for the unmasking of a highly reactive [LPhNiI2]- intermediate 4 either via elimination of H2 from dihydride 3 or via reductive C-H elimination from monohydride 2. The latter does not release any H2 byproduct and adds a distinct platform for metal-metal cooperative two-electron substrate reductions while circumventing the isolation of any unstable superreduced form of the bimetallic scaffold.

Transfer hydrogenation of aldehydes and ketones catalyzed using an aminophosphinite POCNH pincer complex of Ni(ii).

The aminophosphinite pincer complex (POCNH)NiBr was found to effectively catalyze the transfer hydrogenation of aldehydes and ketones with 2-propanol and KOtBu as a base, presenting a rare example of bifunctional nickel transfer hydrogenation catalysts. The transfer hydrogenation of aldehydes and ketones was found to be selective, tolerating a wide range of other functional groups, including those prone to reduction, such as esters, amides, alkenes, pyridines, and nitriles. The reactions were suggested to proceed via the metal-ligand cooperative mechanism with an intermediacy of an amido (POCN)NiII species.

Nickel-Catalyzed Domino Heck-Type Reactions Using Methyl Esters as Cross-Coupling Electrophiles.

While esters are frequently used as traditional electrophiles in substitution chemistry, their application in cross-coupling chemistry is still in its infancy. This work demonstrates that methyl esters can be used as coupling electrophiles in Ni-catalyzed Heck-type reactions through the challenging cleavage of the C(acyl)-O bond under relatively mild reaction conditions at either 80 or 100 °C. With the σ-NiII intermediate generated from the insertion of acyl NiII species into the tethered C=C bond, carbonyl-retentive products were formed by domino Heck/Suzuki-Miyaura coupling and Heck/reduction pathways when organoboron and mild hydride nucleophiles are used.

Nickel‐Catalyzed Domino Heck‐Type Reactions Using Methyl Esters as Cross‐Coupling Electrophiles

AbstractWhile esters are frequently used as traditional electrophiles in substitution chemistry, their application in cross‐coupling chemistry is still in its infancy. This work demonstrates that methyl esters can be used as coupling electrophiles in Ni‐catalyzed Heck‐type reactions through the challenging cleavage of the C(acyl)−O bond under relatively mild reaction conditions at either 80 or 100 °C. With the σ‐NiII intermediate generated from the insertion of acyl NiII species into the tethered C=C bond, carbonyl‐retentive products were formed by domino Heck/Suzuki–Miyaura coupling and Heck/reduction pathways when organoboron and mild hydride nucleophiles are used.

Mononuclear Ni(II) Complexes with a S3O Coordination Sphere Based on a Tripodal Cysteine-Rich Ligand: pH Tuning of the Superoxide Dismutase Activity.

The superoxide dismutase (SOD) activity of mononuclear NiII complexes, whose structures are inspired by the NiSOD, has been investigated. They have been designed with a sulfur-rich pseudopeptide ligand, derived from nitrilotriacetic acid (NTA), where the three acid functions are grafted with cysteines (L3S). Two mononuclear complexes, which exist in pH-dependent proportions, have been fully characterized by a combination of spectroscopic techniques including 1H NMR, UV-vis, circular dichroism, and X-ray absorption spectroscopy, together with theoretical calculations. They display similar square-planar S3O coordination, with the three thiolates of the three cysteine moieties from L3S coordinated to the NiII ion, together with either a water molecule at physiological pH, as [NiL3S(OH2)]-, or a hydroxo ion in more basic conditions, as [NiL3S(OH)]2-. The 1H NMR study has revealed that contrary to the hydroxo ligand, the bound water molecule is labile. The cyclic voltammogram of both complexes displays an irreversible one-electron oxidation process assigned to the NiII/NiIII redox system with Epa = 0.48 and 0.31 V versus SCE for NiL3S(OH2) and NiL3S(OH), respectively. The SOD activity of both complexes has been tested. On the basis of the xanthine oxidase assay, an IC50 of about 1 μM has been measured at pH 7.4, where NiL3S(OH2) is mainly present (93% of the NiII species), while the IC50 is larger than 100 μM at pH 9.6, where NiL3S(OH) is the major species (92% of the NiII species). Interestingly, only NiL3S(OH2) displays SOD activity, suggesting that the presence of a labile ligand is required. The SOD activity has been also evaluated under catalytic conditions at pH 7.75, where the ratio between NiL3S(OH2)/ NiL3S(OH) is about (86:14), and a rate constant, kcat = 1.8 × 105 M-1 s-1, has been measured. NiL3S(OH2) is thus the first low-molecular weight, synthetic, bioinspired Ni complex that displays catalytic SOD activity in water at physiological pH, although it does not contain any N-donor ligand in its first coordination sphere, as in the NiSOD. Overall, the data show that a key structural feature is the presence of a labile ligand in the coordination sphere of the NiII ion.

Access to Multifunctionalized Benzofurans by Aryl Nickelation of Alkynes: Efficient Synthesis of the Anti‐Arrhythmic Drug Amiodarone

An unconventional nickel-catalyzed reaction was developed for the synthesis of multifunctionalized benzofurans from alkyne-tethered phenolic esters. The transformation involves the generation of a nucleophilic vinyl NiII species by the regioselective syn-aryl nickelation of an alkyne, which then undergoes an intramolecular cyclization with phenol ester to yield highly functionalized 1,1-disubstituted alkenes with 3-benzofuranyl and (hetero)aryl substituents. The methodology can be used for the late-stage benzofuran incorporation of various drug molecules and natural products, such as 2-propylvaleric acid, gemfibrozil, biotin, and lithocholic acid. Furthermore, this arylative cyclization method was successfully applied for the efficient synthesis of the anti-arrhythmic drug amiodarone.

Access to Multifunctionalized Benzofurans by Aryl Nickelation of Alkynes: Efficient Synthesis of the Anti‐Arrhythmic Drug Amiodarone

AbstractAn unconventional nickel‐catalyzed reaction was developed for the synthesis of multifunctionalized benzofurans from alkyne‐tethered phenolic esters. The transformation involves the generation of a nucleophilic vinyl NiII species by the regioselective syn‐aryl nickelation of an alkyne, which then undergoes an intramolecular cyclization with phenol ester to yield highly functionalized 1,1‐disubstituted alkenes with 3‐benzofuranyl and (hetero)aryl substituents. The methodology can be used for the late‐stage benzofuran incorporation of various drug molecules and natural products, such as 2‐propylvaleric acid, gemfibrozil, biotin, and lithocholic acid. Furthermore, this arylative cyclization method was successfully applied for the efficient synthesis of the anti‐arrhythmic drug amiodarone.

Myoglobin Reconstituted with Ni Tetradehydrocorrin as a Methane‐Generating Model of Methyl‐coenzyme M Reductase

AbstractMyoglobin reconstituted with Ni tetradehydrocorrin was investigated as a model of F430‐containing methyl‐coenzyme M reductase, which catalyzes anaerobic methane generation. The NiII tetradehydrocorrin complex has a NiII/NiI redox potential of −0.34 V vs. SHE and EPR spectroscopy indicates the formation of a NiI species upon reduction by dithionite. This redox potential is approximately 0.31 V more positive than that of F430. The NiI tetradehydrocorrin moiety is bound to the apo‐form of myoglobin to yield the reconstituted protein. Methane gas is generated in the reaction of the model with methyl iodide in the presence of the reconstituted protein under reductive conditions, whereas the NiI complex itself does not produce methane gas. This is the first example of a protein‐based functional model of F430‐containing methyl‐coenzyme M reductase.

Myoglobin Reconstituted with Ni Tetradehydrocorrin as a Methane-Generating Model of Methyl-coenzyme M Reductase.

Myoglobin reconstituted with Ni tetradehydrocorrin was investigated as a model of F430-containing methyl-coenzyme M reductase, which catalyzes anaerobic methane generation. The NiII tetradehydrocorrin complex has a NiII /NiI redox potential of -0.34 V vs. SHE and EPR spectroscopy indicates the formation of a NiI species upon reduction by dithionite. This redox potential is approximately 0.31 V more positive than that of F430. The NiI tetradehydrocorrin moiety is bound to the apo-form of myoglobin to yield the reconstituted protein. Methane gas is generated in the reaction of the model with methyl iodide in the presence of the reconstituted protein under reductive conditions, whereas the NiI complex itself does not produce methane gas. This is the first example of a protein-based functional model of F430-containing methyl-coenzyme M reductase.

Insertion of CO2 Mediated by a (Xantphos)NiI–Alkyl Species

AbstractThe incorporation of CO2 into organometallic and organic molecules represents a sustainable way to prepare carboxylates. The mechanism of reductive carboxylation of alkyl halides has been proposed to proceed through the reduction of NiII to NiI by either Zn or Mn, followed by CO2 insertion into NiI‐alkyl species. No experimental evidence has been previously established to support the two proposed steps. Demonstrated herein is that the direct reduction of (tBu‐Xantphos)NiIIBr2 by Zn affords NiI species. (tBu‐Xantphos)NiI‐Me and (tBu‐Xantphos)NiI‐Et complexes undergo fast insertion of CO2 at 22 °C. The substantially faster rate, relative to that of NiII complexes, serves as the long‐sought‐after experimental support for the proposed mechanisms of Ni‐catalyzed carboxylation reactions.

Insertion of CO2 Mediated by a (Xantphos)NiI -Alkyl Species.

The incorporation of CO2 into organometallic and organic molecules represents a sustainable way to prepare carboxylates. The mechanism of reductive carboxylation of alkyl halides has been proposed to proceed through the reduction of NiII to NiI by either Zn or Mn, followed by CO2 insertion into NiI -alkyl species. No experimental evidence has been previously established to support the two proposed steps. Demonstrated herein is that the direct reduction of (tBu-Xantphos)NiII Br2 by Zn affords NiI species. (tBu-Xantphos)NiI -Me and (tBu-Xantphos)NiI -Et complexes undergo fast insertion of CO2 at 22 °C. The substantially faster rate, relative to that of NiII complexes, serves as the long-sought-after experimental support for the proposed mechanisms of Ni-catalyzed carboxylation reactions.

Tris(μ2-2-meth-oxy-6-{[(2-sulfido-eth-yl)imino]meth-yl}phenolato)trinickel(II) di-methyl-formamide monosolvate: crystal structure, spectroscopic characterization and anti-bacterial activity.

The title trinuclear nickel(II) complex, [Ni3(C10H11NO2S)3]·C3H7NO, with a Schiff base ligand formed in situ from 2-amino-ethane-thiol and o-vanillin crystallizes in the ortho-rhom-bic space group Pbca. Its asymmetric unit consists of one neutral Ni3 L 3 mol-ecule and one DMF solvent mol-ecule. The solid-state organization of the complex can be described as an insertion of the solvent mol-ecules within the crystallographically independent trinuclear NiII species. Several C-H⋯π edge-to-face inter-actions and π-π stacking inter-actions link the components in the crystal. A first example of a short inter-molecular C-H⋯Ni contact is found. Anti-bacterial in vitro screening revealed that the title compound has anti-bacterial activity, the best effect being against Acinetobacter baumannii.

Reaction of Nitrogen‐Radicals with Organometallics Under Ni‐Catalysis: N‐Arylations and Amino‐Functionalization Cascades

AbstractHerein, we report a strategy for the generation of nitrogen‐radicals by ground‐state single electron transfer with organyl–NiI species. Depending on the philicity of the N‐radical, two types of processes have been developed. In the case of nucleophilic aminyl radicals direct N‐arylation with aryl organozinc, organoboron, and organosilicon reagents was achieved. In the case of electrophilic amidyl radicals, cascade processes involving intramolecular cyclization, followed by reaction with both aryl and alkyl organometallics have been developed. The N‐cyclization–alkylation cascade introduces a novel retrosynthetic disconnection for the assembly of substituted lactams and pyrrolidines with its potential demonstrated in the short total synthesis of four venom alkaloids.

Reaction of Nitrogen-Radicals with Organometallics Under Ni-Catalysis: N-Arylations and Amino-Functionalization Cascades.

Herein, we report a strategy for the generation of nitrogen‐radicals by ground‐state single electron transfer with organyl–NiI species. Depending on the philicity of the N‐radical, two types of processes have been developed. In the case of nucleophilic aminyl radicals direct N‐arylation with aryl organozinc, organoboron, and organosilicon reagents was achieved. In the case of electrophilic amidyl radicals, cascade processes involving intramolecular cyclization, followed by reaction with both aryl and alkyl organometallics have been developed. The N‐cyclization–alkylation cascade introduces a novel retrosynthetic disconnection for the assembly of substituted lactams and pyrrolidines with its potential demonstrated in the short total synthesis of four venom alkaloids.

Four Oxidation States in a Single Photoredox Nickel-Based Catalytic Cycle: A Computational Study.

The computational characterization of the full catalytic cycle for the synthesis of indoline from the reaction between iodoacetanilide and a terminal alkene catalyzed by a nickel complex and a photoactive ruthenium species is presented. A variety of oxidation states of nickel, Ni0 , NiI , NiII , and NiIII , is shown to participate in the mechanism. Ni0 is necessary for the oxidative addition of the C-I bond, which goes through a NiI intermediate and results in a NiII species. The NiII species inserts into the alkene, but does not undergo the reductive elimination necessary for C-N bond formation. This oxidatively induced reductive elimination can be accomplished only after oxidation to NiIII by the photoactive ruthenium species. All the reaction steps are computationally characterized, and the barriers for the single-electron transfer steps calculated using a modified version of the Marcus Theory.

Four Oxidation States in a Single Photoredox Nickel‐Based Catalytic Cycle: A Computational Study

AbstractThe computational characterization of the full catalytic cycle for the synthesis of indoline from the reaction between iodoacetanilide and a terminal alkene catalyzed by a nickel complex and a photoactive ruthenium species is presented. A variety of oxidation states of nickel, Ni0, NiI, NiII, and NiIII, is shown to participate in the mechanism. Ni0 is necessary for the oxidative addition of the C−I bond, which goes through a NiI intermediate and results in a NiII species. The NiII species inserts into the alkene, but does not undergo the reductive elimination necessary for C−N bond formation. This oxidatively induced reductive elimination can be accomplished only after oxidation to NiIII by the photoactive ruthenium species. All the reaction steps are computationally characterized, and the barriers for the single‐electron transfer steps calculated using a modified version of the Marcus Theory.

Electronic and spin delocalization in a switchable trinuclear triphenylene trisemiquinone bridged Ni3 complex.

A trinuclear triphenylene trisemiquinone complex containing paramagnetic NiII is obtained under ambient conditions from the reaction of deprotonated tricatecholate hexahydroxytriphenylene (H6HHTP) with NiII capped with a trispyrazolyl borate tridentate ligand. The magnetic and EPR data are consistent with delocalization of the electronic spin over the three NiII species. The two-electron reduced complex shows an EPR spectrum corresponding to a S = 1/2 species due to a large antiferromagnetic coupling between the radical and only one of the NiII ions highlighting the localization of the electronic spin. No EPR signal is observed for the one- and three-electron reduced species consistent with the closed shell of the bridging ligand.

Rotaxane-Based Transition Metal Complexes: Effect of the Mechanical Bond on Structure and Electronic Properties

Early work by Sauvage revealed that mechanical bonding alters the stability and redox properties of their original catenane metal complexes. However, despite the importance of controlling metal ion properties for a range of applications, these effects have received relatively little attention since. Here we present a series of tri-, tetra-, and pentadentate rotaxane-based ligands and a detailed study of their metal binding behavior and, where possible, compare their redox and electronic properties with their noninterlocked counterparts. The rotaxane ligands form complexes with most of the metal ions investigated, and X-ray diffraction revealed that in some cases the mechanical bond enforces unusual coordination numbers and distorted arrangements as a result of the exclusion of exogenous ligands driven by the sterically crowded binding sites. In contrast, only the noninterlocked equivalent of the pentadentate rotaxane CuII complex could be formed selectively, and this exhibited compromised redox stability compared to its interlocked counterpart. Frozen-solution EPR data demonstrate the formation of an interesting biomimetic state for the tetradentate CuII rotaxane, as well as the formation of stable NiI species and the unusual coexistence of high- and low-spin CoII in the pentadentate framework. Our results demonstrate that readily available mechanically chelating rotaxanes give rise to complexes the noninterlocked equivalent of which are inaccessible, and that the mechanical bond augments the redox behavior of the bound metal ion in a manner analogous to the carefully tuned amino acid framework in metalloproteins.

Instant Detection of Hydrogen Cyanide Gas and Cyanide Salts in Solid Matrices and Water by using CuII and NiII Complexes of Intramolecularly Hydrogen Bonded Zwitterions.

A series of intramolecularly hydrogen-bonded zwitterionic compartmental ligands HL1-HL4, containing a pendent diamine arm that is monoprotonated and an aldehyde functionality at two different ortho-positions of a 4-halophenoxide, is reported herein. Single-crystal X-ray diffraction (SXRD) provides persuasive evidence for the identification of this class of proton-transferred zwitterions at room temperature. The solid-state photoluminescent nature of these zwitterions remains intact in aqueous and organic solutions. Grinding of HL1 and HL2 with Cu2+ /Ni2+ salts develop turn-on probes 1-4. Compounds 1 and 4 are dinuclear CuII and NiII species, respectively. Compound 2 is a tetranuclear CuII complex. Interestingly, compound 3 is a mononuclear NiII species in which both nitrogen atoms in the pendant diamine arm are protonated and, therefore, not coordinated to the NiII center. All these probes (1-4) display an instant response to the poison gas hydrogen cyanide (HCN) and cyanide salts present in both solid matrices and aqueous (100 % water) solution. Selective and rapid sensing of HCN gas and cyanide salts in solid/soil/water phases, without any interference, by the mechanosynthesized complexes 1-4 can be perceived easily by the naked eye under a hand-held UV lamp.

Mechanistic Insights into the Ni-Catalyzed Reductive Carboxylation of C-O Bonds in Aromatic Esters with CO2 : Understanding Remarkable Ligand and Traceless-Directing-Group Effects.

The mechanism of the Ni0 -catalyzed reductive carboxylation reaction of C(sp2 )-O and C(sp3 )-O bonds in aromatic esters with CO2 to access valuable carboxylic acids was comprehensively studied by using DFT calculations. Computational results revealed that this transformation was composed of several key steps: C-O bond cleavage, reductive elimination, and/or CO2 insertion. Of these steps, C-O bond cleavage was found to be rate-determining, and it occurred through either oxidative addition to form a NiII intermediate, or a radical pathway that involved a bimetallic species to generate two NiI species through homolytic dissociation of the C-O bond. DFT calculations revealed that the oxidative addition step was preferred in the reductive carboxylation reactions of C(sp2 )-O and C(sp3 )-O bonds in substrates with extended π systems. In contrast, oxidative addition was highly disfavored when traceless directing groups were involved in the reductive coupling of substrates without extended π systems. In such cases, the presence of traceless directing groups allowed for docking of a second Ni0 catalyst, and the reactions proceed through a bimetallic radical pathway, rather than through concerted oxidative addition, to afford two NiI species both kinetically and thermodynamically. These theoretical mechanistic insights into the reductive carboxylation reactions of C-O bonds were also employed to investigate several experimentally observed phenomena, including ligand-dependent reactivity and site-selectivity.