Cyclometallation Reactions Research Articles

Phosphorescent Pt(II) complexes of C^N^N type tridentate ligands augmented for liquid crystallinity

ABSTRACT Using the cyclometallation reaction, Pt(II) complexes of diarylbipyridynic ligands bearing alkoxy-groups were prepared and then modified with phenylаcetylene derivatives. The target compounds were characterised by absorption and emission spectroscopy, differential scanning calorimetry, small angle X-ray scattering, polarisation microscopy, and DTF calculations. The mesomorphic properties of the obtained compounds were investigated and their liquid crystallinity was confirmed.

Mesoionic Carbene Complexes of Uranium(IV) and Thorium(IV).

We report the synthesis and characterization of uranium(IV) and thorium(IV) mesoionic carbene complexes [An{N(SiMe3)2}2(CH2SiMe2NSiMe3){MIC}] (An = U, 4U and Th, 4Th; MIC = {CN(Me)C(Me)N(Me)CH}), which represent rare examples of actinide mesoionic carbene linkages and the first example of a thorium mesoionic carbene complex. Complexes 4U and 4Th were prepared via a C–H activation intramolecular cyclometallation reaction of actinide halides, with concomitant formal 1,4-proton migration of an N-heterocyclic olefin (NHO). Quantum chemical calculations suggest that the An–carbene bond comprises only a σ-component, in contrast to the uranium(III) analogue [U{N(SiMe3)2}3(MIC)] (1) where computational studies suggested that the 5f3 uranium(III) ion engages in a weak one-electron π-backbond to the MIC. This highlights the varying nature of actinide-MIC bonding as a function of actinide oxidation state. In solution, 4Th exists in equilibrium with the Th(IV) metallacycle [Th{N(SiMe3)2}2(CH2SiMe2NSiMe3)] (6Th) and free NHO (3). The thermodynamic parameters of this equilibrium were probed using variable-temperature NMR spectroscopy yielding an entropically favored but enthalpically endothermic process with an overall reaction free energy of ΔG298.15K = 0.89 kcal mol–1. Energy decomposition analysis (EDA-NOCV) of the actinide–carbon bonds in 4U and 4Th reveals that the former is enthalpically stronger and more covalent than the latter, which accounts for the respective stabilities of these two complexes.

Reactions of a Bis(pentalene)dititanium complex with alkenes; the molecular structure of the butadiene complex [Ti2(µ: η5,η5-Pn††)2(μ: η2,η2-s-trans-C4H6)] (Pn†† = 1,4-(SiiPr3)2-C8H4)

Reaction of the syn-bimetallic complex [Ti2(µ:η5,η5-Pn††)2] (1) (Pn†† = 1,4-(SiiPr3)2-C8H4) with 1,3-trans-butadiene in toluene results in the clean formation of the 1:1 adduct [Ti2(µ:η5,η5-Pn††)2(μ: η2,η2-s-trans-C4H6)] (2) featuring an essentially planar butadiene ligand. Complex (2) represents the first example of a bimetallic early transition metal complex where a coordinated butadiene adopts such a conformation. When (1) is reacted with propene an unexpected “tuck-over” alkene π-complex (3) is formed with co-current loss of propane. Complex (3) features a coordinated η2,η1 vinylic (H2C = CMe)-SiiPr2-Pn† moiety as a result of CH activation of one of the isopropyl substituents of the SiiPr3 groups on the Pn†† supporting ligand. One of the hydrogens of this secondary vinylic moiety is significantly shifted upfield in the 1H NMR spectrum of (3) and a single crystal XRD study shows an interaction between this hydrogen and one of the Ti centres. Preliminary kinetic studies of the formation of (3) show a slightly negative entropy of activation and 1st order consumption of (1) both of which suggest the involvement of a Ti-H(iPr) agostic interaction during the cyclometallation reaction.

Reductive Hydrogenation under Single-Site Control: Generation and Reactivity of a Transient NHC-Stabilized Tantalum(III) Alkoxide.

One of the most attractive routes for the preparation of reactive tantalum(III) species relies on the efficient salt-free hydrogenolysis of tantalum(V) alkyls or tantalum(V) alkylidenes, a process known as reductive hydrogenation. For silica-crafted tantalum alkyls and alkylidenes, this process necessarily proceeds at well-separated tantalum centers, while related reductive hydrogenations in homogeneous solution commonly involve dimeric complexes. Herein, an NHC scaffold was coordinated to a novel tri(alkoxido)tantalum(V) alkylidene to circumvent the formation of dimers during reductive hydrogenation. Employing this new model system, a key intermediate of the process, namely a hydrido-tantalum alkyl, was isolated for the first time and shown to exhibit a bidirectional reactivity. Upon being heated, the latter complex was found to undergo either an α-elimination or a reductive alkane elimination. In the (overall unproductive) α-elimination step, H2 and the parent alkylidene were regenerated, while the sought-after transient d2-configured tantalum(III) derivative was produced along the reaction coordinate of the reductive alkane elimination. The reactive low-valence metal center was found to rapidly attack one of the NHC substituents via an oxidative C-H activation, which led to the formation of a cyclometalated tantalum(V) hydride. The proposed elemental steps are in line with kinetic data, deuterium labeling experiments, and density functional theory (DFT) modeling studies. DFT calculations also indicated that the S = 0 spin ground state of the Ta(III) center plays a crucial role in the cyclometalation reaction. The cyclometalated Ta(V) hydride was further investigated and reacted with several alkenes and alkynes. In addition to a rich insertion and isomerization chemistry, these studies also revealed that the former hydride may undergo a formal cycloreversion and thus serve as a tantalum(III) synthon, although the original tantalum(III) intermediate is not involved in this process. The latter reactivity was observed upon reaction with internal alkynes and led to the corresponding η2-alkyne derivatives via vinyl intermediates, which rearrange via a remarkable, hitherto unprecedented, hydrogen shift reaction.

Rollover Cyclometalation as a Valuable Tool for Regioselective C-H Bond Activation and Functionalization.

Rollover cyclometalation constitutes a particular case of cyclometallation reaction. This reaction occurs when a chelated heterocyclic ligand loses its bidentate coordination mode and undergoes an internal rotation, after which a remote C–H bond is regioselectively activated, affording an uncommon cyclometalated complex, called “rollover cyclometalated complex”. The key of the process is the internal rotation of the ligand, which occurs before the C–H bond activation and releases from coordination a donor atom. The new “rollover” ligand has peculiar properties, being a ligand with multiple personalities, no more a spectator in the reactivity of the complex. The main reason of this peculiarity is the presence of an uncoordinated donor atom (the one initially involved in the chelation), able to promote a series of reactions not available for classic cyclometalated complexes. The rollover reaction is highly regioselective, because the activated C–H bond is usually in a symmetric position with respect to the donor atom which detaches from the metal stating the rollover process. Due to this novel behavior, a series of potential applications have appeared in the literature, in fields such as catalysis, organic synthesis, and advanced materials.

Cyclometalation in the (η3-C5H5)Co(η2-C2H2)(PMe3) and (η3-C9H7)Co(η2-C2H2) (PMe3) complexes: A computational investigation

This research examined the cyclometalation in the (η3-C5H5)Co(η2-C2H2)(PMe3) and (η3-C9H7)Co(η2-C2H2)(PMe3) complexes by using mPW1PW91 functional. Thermodynamic and kinetic parameters of this reaction were computed. The solvent effects were studied by the self-consistent reaction field theory (SCRF) based on conductor-like polarizable continuum model (CPCM). The solvent effects were explored on the energy barrier, frontier orbitals energies, and reactivity parameters (hardness, chemical potential, electrophilicity). The Hirshfeld population analysis was performed based on optimized structures. The rate constant of the cyclometalation reaction was computed from 300 to 1200 K, in the gas phase. In addition, the synchronicity values of this reaction were determined. Our findings revealed, this reaction was favorable energetically in both gas and solution phases. The larger rate constant values were in the presence of Cp ring than In ring.

Direct Base-Assisted C‒H Cyclonickelation of 6-Phenyl-2,2'-bipyridine.

The organonickel complexes [Ni(Phbpy)X] (X = Br, OAc, CN) were obtained for the first time in a direct base-assisted arene C(sp2)–H cyclometalation reaction from the rather unreactive precursor materials NiX2 and HPhbpy (6-phenyl-2,2′-bipyridine) or from the versatile precursor [Ni(HPhbpy)Br2]2. Different from previously necessary C‒Br oxidative addition at Ni(0), an extended scan of reaction conditions allowed quantitative access to the title compound from Ni(II) on synthetically useful timescales through base-assisted C‒H activation in nonpolar media at elevated temperature. Optimisation of the reaction conditions (various bases, solvents, methods) identified 1:2 mixtures of acetate and carbonate as unrivalled synergetic base pairs in the optimum protocol that holds promise as a readily usable and easily tuneable access to a wide range of direct nickelation products. While for the base-assisted C‒H metalation of the noble metals Ru, Ir, Rh, or Pd, this acetate/carbonate method has been established for a few years, our study represents the leap into the world of the base metals of the 3d series.

Dynamics of the efficient cyclometalation of the undercoordinated organoplatinum complex [Pt(COD)(neoPh)]+ (neoPh = 2-methyl-2-phenylpropyl)

The cyclometalation reaction of [Pt(COD)(κ1-neoPh)]+ (neoPh = 2-methyl-2-phenylpropyl) to [Pt(COD)(κ2-neoPh)] was studied experimentally and mechanistically using DFT and MD simulations.

The Influence of Cyclometalated Ligand Motifs on the Solid-State Assemblies and Luminescent Properties of Pt(II)-Tl(I) Complexes

We have synthesized the HC^Npz ligand, 1-(naphthalen-2-yl)-1H-pyrazole (1A), and carried out its cyclometalation reaction with [{Pt(η3-C4H7)(μ-Cl)}2] to give [{Pt(Naph^N)(μ-Cl)}2]. This process takes place via the intermediate [Pt(η3-C4H7)Cl(HNaph^N-κN)] (2A) which could be isolated and fully characterized. Compound [{Pt(Naph^N)(μ-Cl)}2] and the analogous N-heterocyclic carbene complex [{Pt(Naph^C*)(μ-Cl)}2] (HNaph^C*-κC* = 3-methyl-1-(naphthalen-2-yl)-1H-imidazol-2-ylidene) were used to prepare the bis-cyanide anionic derivatives NnBu4[Pt(Naph^E)(CN)2] (E = Npz 4A, C*carbene 4B) which subsequently react with TlPF6 to afford the corresponding complexes [PtTl(Naph^E)(CN)2] (5A and 5B). The X-ray structures of 5A and 5B show the presence of 2D extended networks created by organometallic “PtTl(Naph^E)(CN)2” entities, each one containing a Pt→Tl dative bond (d Pt–Tl = 3.0205(3) A 5A, 2.9395(4) A 5B). These units are linked together through additional Tl···N≡C and Tl···π contacts, which, in the case of 5B, ren...

Cyclometallation reactions of a three-coordinate cobalt(i) complex bearing a nonsymmetric N-heterocyclic carbene ligand.

The reactions of a three-coordinate cobalt(i) complex [(IAdMes)(PPh3)CoCl] (1) (IAdMes = 1-mesityl-3-adamantyl-4,5-dimethylimidazol-2-ylidene) with LiCH3, LiCH2SiMe3 and NaCp gave ligand-based C(sp3)-H bond activation products [(IAd'Mes)Co(η6-C6H5PPh2)] (2), [(IAdMes')(PPh3)Co(CH2SiMe3)] (4) and [(IAd'Mes)Co(η5-Cp)] (5), respectively (IAd'Mes and IAdMes' denote adamantyl- and mesityl-cyclometallated N-heterocyclic carbene (NHC) ligands, respectively). All the cobalt-NHC complexes have been characterized by various spectroscopic methods, and their structures have been established by single-crystal X-ray diffraction studies. These cyclometallation reactions are among the rare examples of C(sp3)-H bond activation reactions observed in structurally well-defined low-valent cobalt complexes. Different cyclometallated NHC ligands ([IAd'Mes]1-versus [IAdMes']1-) and different oxidation states of the metal center (cobalt(i) versus cobalt(ii)) in the resultant cobalt complexes hint at different mechanisms for these cobalt-mediated C(sp3)-H bond activation reactions.

Efficient Synthesis of Malonate Functionalized Chiral Phosphapalladacycles and their Catalytic Evaluation in Asymmetric Hydrophosphination of Chalcone

Four chiral phosphapalladacycle complexes functionalized with the malonate moiety at the chiral carbon have been synthesized via a consecutive asymmetric hydrophosphination and cyclometallation protocol. High conversions were achieved in the P–H addition reaction, which was itself catalyzed by a phosphapalladacycle. Moderate to good enantioselectivities, were obtained for this step depending on the nature of the functional groups present on the naphthalene backbone. In contrast, the outcome of the subsequent cyclometallation reaction relies highly on the character of the functional groups. The catalytic potential of the synthesized phosphapalladacycle complexes was evaluated in the hydrophosphination reaction of chalcone with moderate results.

Iridium-Induced Regioselective B-H and C-C Activations at Azo-Substituted o-Carboranes.

p-Methoxybenzeneazo-substituted o-carboranes have been synthesized and their reactivity with half-sandwich iridium and rhodium complexes has been investigated in detail. A variety of solvent- and base-dependent, highly site-selective B-H and C-C σ-bond activations at the C/B cage have been observed. While the use of CH3 OH leads to the formation of metallacarboranes, o-carborane clusters undergo cyclometallation reactions involving B(6)-H, B(4)-H or a rare B(7)-H activation in CH2 Cl2 . The synthesis of a unique pseudo-closo-iridacarborane through a very unconventional metal-mediated Ccage -Ccage activation is described in this contribution.

Synthesis, structures, and reactivity studies of cyclometalated N-heterocyclic carbene complexes of ruthenium.

An unusual cyclometalation reaction results from a C-C bond activation in Cp*(IPr)RuCl to give Cp*(IPr')Ru(L) featuring a NHC-C(sp2) chelating ligand (5-L; L = propene, N2; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; IPr' = 1-(6-isopropylphenyl)-3-(2,6-diisopropylphenyl)imidazol-2-ylidene). DFT calculations were employed to elucidate the C-C bond activation pathway. Reactions of cyclometalated ruthenium complexes bearing NHC-C(sp2) and NHC-C(sp3) ligands (5-L and Cp*(IXy-H)Ru(N2), 1a, respectively where IXy = 1,3-bis(2,6-dimethylphenyl)-imidazol-2-ylidene; IXy-H is the deprotonated form of (IXy)) are reported. Deprotonation of 1a by an equimolar mixture of benzyl potassium and 18-crown-6 afforded a doubly-cyclometalated complex [Cp*(IXy-2H)Ru][K(18-crown-6)] (7). A lower CO stretching frequency in Cp*(IXy-H)Ru(CO) (8) vs. Cp*(IPr')Ru(CO) (9) suggests that the NHC-C(sp3) ligand is more electron donating. Complexes 5-L reacted with H2 to give the dihydride Cp*(IPr')RuH2 (11). In comparison, after an initial oxidative addition of H2, complex 1a with its more reactive Ru-C(sp3) bond underwent C-H bond reductive elimination, and a second oxidative addition of H2 afforded the trihydride Cp*(IXy)RuH3 (10). Reaction of 1a with B(C6F5)3 resulted in a zwitterionic complex Cp*Ru(IXy'') (12; IXy'' = 1-[2-((C6F5)3BCH2)C6H3-6-methyl]-3-(2,6-dimethylphenyl)imidazol-2-ylidene-1-yl) by the formation of a new C-B bond. In contrast, B(C6F5)3 abstracted a hydride from 5-L and promoted a very unusual C-C bond formation involving insertion of an allyl ligand into a Ru-C bond to form [Cp*Ru(IPr'')][HB(C6F5)3] (IPr'' = 1-[2-(CH2[double bond, length as m-dash]CHCH2)C6H3-6-isopropyl]-3-(2,6-diisopropyl)imidazol-2-ylidene-1-yl) (13).

New Scandium Borylimido Chemistry: Synthesis, Bonding, and Reactivity.

We report a combined synthetic, mechanistic, and theoretical study of the first borylimido complex of a rare earth metal, (NacNacNMe2)Sc{NB(NAr'CH)2} (25, Ar' = 2,6-C6H3iPr2, NacNacNMe2 = Ar'NC(Me)CHC(Me)NCH2CH2NMe2). Thermolysis of the methyl-borylamide (NacNacNMe2)Sc(Me){NHB(NAr'CH)2} (18) generated transient imide 25 via rate-determining, first-order methane elimination (KIE ≈ 8.7). In the absence of external substrate, 25 underwent a reversible cyclometalation reaction (sp3 C-H bond addition to Sc═Nimide) with a methyl group of the NacNacNMe2 ligand forming {MeC(NC6H3iPrCH(Me)CH2)CHC(Me)NCH2CH2NMe2}Sc{NHB(NAr'CH)2} (21). In the presence of pyridine or DMAP, reversible sp2 C-H bond activation occurred, forming orthometalated complexes (NacNacNMe2)Sc{NHB(NAr'CH)2}(η2-4-NC5H3R) (R = H or NMe2). In situ reaction of 25 with HCCTol gives irreversible sp C-H bond activation under kinetic control, and with MeCCPh [2+2] cycloaddition to Sc═Nimide takes place. These reactions represent the first substrate activation processes for any metal-bound borylimide. The bonding in 25 and the mechanism and thermodynamics of the reactions have been studied using density functional theory (DFT), supported by quantum theory of atoms in molecules and natural bond orbital analysis. Although the borylimido and arylimido dianions studied here are formally isoelectronic and possess comparable frontier molecular orbitals, the borylimido ligand is both a better π-donor and σ-donor, forming stronger and shorter metal-nitrogen bonds with somewhat reduced ionicity. Despite this, reactions of these types of borylimides with C-H or C≡C bonds are all more exothermic and more strongly activating than for the corresponding arylimides. DFT calculations on model systems of differing steric bulk unpicked the underlying thermodynamic factors controlling the reactions of 25 and its reaction partners, and a detailed comparison was made with the previously described arylimido homologues.

Csp3 -H Activation without Chelation Assistance in an Iridium Pincer Complex Forming Cyclometallated Products.

Cyclometallation of 8-methylquinoline and 2-(dimethylamino)-pyridine in an iridium-based pincer complex is described. The C-H activation of 2-(dimethylamino)pyridine is not chelation assisted, which has not been described before for Csp3 -H bonds in cyclometallation reactions. The mechanism of the cyclometallation of 2-(dimethylamino)pyridine was studied by DFT calculations and kinetic measurements.

Chasing the agostic interaction in ligand assisted cyclometallation reactions of palladium(ii).

A 500 MHz NMR study of the reaction between 1-tetralone oxime and PdCl42- in CD3OD shows resonances attributable to a potential agostic intermediate prior to the formation of the insoluble cyclopalladated product which itself was characterised by X-ray crystallography. Calculated structural, spectroscopic, QTAIM, NBO and NCI analysis results obtained from density functional theory (DFT) calculations give a full description of the putative agostic intermediate [PdCl2(1-tetralone oxime)] (1) which is shown to include a previously unrecognised π-electron density donation from the aromatic ring to the metal in close proximity to the agostic carbon atom. Changing the (N)-OH donor to (N)-OMe does not effect the magnitude of these interactions. (N)-OH and (N)-OMe acetophenone imines in which the aromatic ring has the potential to rotate show similar agostic and π-electron donation to the alicyclic ring counterparts. 1-Tetralone which coordinates to the metal by a Pd-O bond that is much weaker than the Pd-N complexes has a slightly stronger agostic component and slightly weaker π-electron donation than the oxime counterpart.

Substitution and cyclometallation reactions on Pt(II) phosphite complexes

This paper describes the formation of newseries of platinum(II) complexes with phosphite and phosphine ligands. Treatment of cis,cis-[Me2Pt(μ-SMe2)2PtMe2] with 2 equimolar of L, L = P(OiPr)3orP(OPh)3, then adding 2 equimolar of L′, L′ = PPh3 or 4-MePy, gavecis-[Me2PtLL′] complexes,1a–4a, with some side products. Otherwise, reaction of cis,cis-[Me2Pt(μ-SMe2)2PtMe2] with 4 equimolar of Me2SO, then adding 2 equimolar of PPh3, gavecis-[Me2Pt(Me2SO−κS)(PPh3)]. Addition of 1 equimolar of L, L = P(OPh)3 andP(OiPr)3 and substitution of Me2SO occurred to givecis-[Me2PtLL′]complexes, 2a and 4a with more selectivity. In order tocontrol steric and electronic effects of the ligands, 2 and 4 equimolar of P(OPh)3 were added to cis,cis-[Me2Pt(μ-SMe2)2PtMe2] during refluxing and complexes 1b, [MePt(CˆP))SMe2)] and 2b, [MePt(CˆP){P(OPh)3}],(CˆP = {(κ2-C,P)P(OPh)2(OC6H4)})were formed respectively. With adding 1 equimolar of L, L = PPh3, 4-MePy to complex 1b, the products of substitution reactions were [MePt(CˆP)L], 3b and4b.

The biphosphinic paladacycle complex induces melanoma cell death through lysosomal–mitochondrial axis modulation and impaired autophagy

Recently, palladium complexes have been extensively studied as cyclization of these complexes by cyclometallation reactions increased their stability making them promising antitumor compounds. In this study, we have investigated apoptosis induced by the Biphosphinic Paladacycle Complex (BPC11) and possible cross talk between apoptosis and autophagy in cell line models of metastatic (Tm5) and non-metastatic (4C11-) melanoma. The BPC11-induced cell death in melanoma involved the lysosomal–mitochondrial axis, which is characterized by LMP, CatB activation and increased Bax protein levels following its translocation to mitochondria. Mitochondrial hyperpolarization, followed by membrane potential dissipation and cleavage of caspase-3, also resulted in cell death after 24 h of incubation. We also found that BPC11-mediated LC3II formation and increased p62 protein levels, suggesting blocked autophagy, probably due to LMP. Interestingly, the treatment of Tm5 and 4C11− cells with 3-methyladenine (3-MA), an inhibitor of the initial stage of autophagy, potentiated the effects of BPC11. We conclude that BPC11 is an anti-melanoma agent and that autophagy may be acting as a mechanism of melanoma cells resistance. Also, these data highlight the importance of studies involving autophagy and apoptosis during pre-clinical studies of new drugs with anticancer properties.

Role of anagostic interactions in cycloplatination of telluroethers: Synthesis and structural characterization

Reactions of K2PtCl4 with TeRRʹ gave complexes of composition [PtCl2(TeRRʹ)2] (R/Rʹ = Ph2(1a), o-tol2 (1b), Mes2(1c), Ph/Mes (1d), o-tol/Mes (1e)). The complex [PtCl2(TeMes2)2] in refluxing THF afforded a mononuclear cyclometalated complex [PtCl{(CH2C6H2Me2-4,6)TeMes}(TeMes2)] (2). It tends to remain in equilibrium with a binuclear derivative [Pt(μ-Cl){(CH2C6H2Me2-4,6)TeMes}]2 (3) in CDCl3 solution. The complexes 1d and 1e did not undergo cyclometalation reaction under similar reaction conditions. The 2 on treatment with PPh3 gave [PtCl{(CH2C6H2Me2-4,6)TeMes}(PPh3)] (4). All the complexes have been characterized by elemental analysis and NMR (1H, 31P, 125Te, 195Pt) spectroscopy. Anagostic interactions have been recognised for facilitation of cyclometalation reactions. The molecular structures of trans-[PtCl2(TeMes2)2] (1c), trans-[PtCl2(PhTeMes)2] (1d), trans-[PtCl2(o-tolTeMes)2] (1e), [PtCl{(CH2C6H2Me2-4,6)TeMes}(TeMes2)] (2) and [PtCl{(CH2C6H2Me2-4,6)TeMes}(PPh3)] (4) have been established unambiguously by single crystal X-ray diffraction analyses.

A Diels-Alder reaction triggered by a [4 + 3] metallacycloaddition.

The Tp(Me2)Ir(III) complex 1-OH2 (Tp(Me2) = hydrotris(3,5-dimethylpyrazolyl)borate), which contains a labile molecule of water and an iridium-bonded alkenyl moiety (-C(R)═C(R)-(R=CO2Me)) as part of a benzo-annulated five-membered iridacycle, reacts readily with the conjugated dienes butadiene and 2,3-dimethylbutadiene to afford the corresponding Diels-Alder products. Experimental and DFT studies are in accordance with an initial [4 + 3] cyclometalation reaction between the diene and the five-coordinated 16-electron organometallic fragment 1 (generated from 1-OH2 by facile water dissociation). The reaction can be extended to a related TpIr(III) complex (Tp = hydrotris(pyrazolyl)borate) that also features a labile ligand (i.e., 2-THF).