Acyclic Palladium(II)‐N‐heterocyclic Carbene Metallacrown Ether Complexes: Synthesis,Structure and Catalytic Activity

Novel acyclic Pd(II)‐N‐heterocyclic carbene (NHC) metallacrown ethers 5a , 5b have been synthesized. Reaction of the imidazolium salts bearing a long polyether chain with Ag₂O afforded Ag‐NHC complexes, which then reacted as carbene transfer agent with PdCl₂(MeCN)₂ to give the desired acyclic Pd(II)‐NHC metallacrown ether complexes 5a and 5b . The ¹H NMR and ¹³C NMR spectra show 5a and 5b exist as mixtures of cis and trans isomers in solution. The trans isomer of 5a was characterized by X‐ray diffraction, which clearly demonstrated two pseudo‐crown ether cavities in trans‐ 5a . Pd(II)‐NHC complexes 5a and 5b have been shown to be highly effective in the Suzuki‐Miyaura reactions of a variety of aryl bromides in neat water without the need of inert gas protection.     

Novel (N‐heterocyclic carbene)Pd(pyridine)Br2 complexes for carbonylative Sonogashira coupling reactions: Catalytic efficiency and scope for arylalkynes,alkylalkynes and dialkynes

New N,N′‐substituted imidazolium salts and their corresponding dibromidopyridine–palladium(II) complexes were successfully synthesized and characterized. Reactions of palladium bromide with the newly synthesized N,N′‐substituted imidazolium bromides ( 2a and 2b ) in pyridine afforded the corresponding new N‐heterocyclic carbene pyridine palladium(II) complexes ( 3a and 3b ) in high yields. Their single‐crystal X‐ray structures show a distorted square planar geometry with the carbene and pyridine ligands in trans position. Both complexes show a high catalytic activity in carbonylative Sonogashira coupling reactions of aryl iodides and aryl diiodides with arylalkynes, alkylalkynes and dialkynes.     

Elucidating the Reactivity of Vicinal Dicarbenoids: From Lewis Adduct Formation to B−C Bond Activation

The reactivity of the diaminoacetylene Pip‐C≡C‐Pip (Pip=piperidyl=NC₅H₁₀) towards phenyldichloro‐ and triphenylborane is presented. In the case of the less Lewis acidic PhBCl₂, the first example of a double Lewis adduct of a vicinal dicarbenoid is reported. For the more Lewis acidic triphenylborane, coordination to the bifunctional carbene leads to a mild B?C bond activation, resulting in a syn‐1,2‐carboboration. Ensuing cis/trans isomerization yields a novel ethylene‐bridged frustrated Lewis pair (FLP). The compounds were characterized using multinuclear NMR spectroscopy, structural analysis, and mass spectrometry. Reactivity studies of both isomers with the N‐heterocyclic carbene 1,3‐dimethylimidazol‐2‐ylidene (IMe) aided in elucidating the proposed isomerization pathway. DFT calculations were carried out to elucidate the reaction mechanism. The rather low free energy of activation is consistent with the observation that the reaction proceeds smoothly at room temperature.     

Imine‐N‐Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p‐Cymene Anticancer Complexes: A Structure–Activity Relationship Study

A family of novel imine‐N‐heterocyclic carbene ruthenium(II) complexes of the general formula [(η⁶‐p‐cymene)Ru(C^N)Cl]PF₆⁻ (where C^N is an imine‐N‐heterocyclic carbene chelating ligand with varying substituents) have been prepared and characterized. In this imine‐N‐heterocyclic carbene chelating ligand framework, there are three potential sites that can be modified, which distinguishes this class of ligand and provides a body of flexibilities and opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The influence of substituent effects of three tunable domains on the anticancer activity and catalytic ability in converting coenzyme NADH to NAD⁺ is investigated. This family of complexes displays an exceedingly distinct anticancer activity against A549 cancer cells, despite their close structural similarity. Complex 9 shows the highest anticancer activity in this series against A549 cancer cells (IC₅₀=14.36 μm ), with an approximately 1.5‐fold better activity than the clinical platinum drug cisplatin (IC₅₀=21.30 μm ) in A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death mainly through cell stress, including cell cycle arrest, inducing apoptosis, increasing intracellular reactive oxygen species (ROS) levels, and depolarization of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is also detected by confocal microscopy.     

cis-trans Isomerization of bis(Dialkylsulfide)Dihaloplatinum(II) Complexes in Solution

The equilibrium energetics and the kinetics of cis-trans isomerization of some bis(dialkylsulfide)dihaloplatinum(II) complexes have been examined by ¹H-NMR. spectroscopy. The isomers are stable in chloroform but each form isomerizes to an equilibrium mixture when free dialkylsulfide is added. The cis to trans process is endothermic and the position of the equilibrium is markedly dependent on the nature of the donor atoms and of the solvent. The rate of isomerization of Pt(Me₂S)₂Cl₂ is first order in complex and in Me₂S. The isomerization proceeds by a double displacement mechanism as it is shown that the tris(dimethylsulfide)chloroplatinum(II) cation is an isolable intermediate of the reaction. When free Me₂S is added to trans-Pd(Me₂S)₂Cl₂, isomerization does not occur and one observes instead a fast ligand exchange. Its mechanism is the usual associative one for substitutions in square planar d⁸complexes.     

The keto→enol photoisomerization of N‐salicilydenemethylfurylamine: Nonadiabatic ab initio dynamics simulation

The photoinduced isomerization of cis‐keto and trans‐keto isomers in N‐salicilydenemethylfurylamine has been studied using the surface‐hopping approach at the CASSCF level of theory. After the cis‐keto or trans‐keto isomer is excited to S₁ state, the molecule initially moves to a excited‐state local minimum. The torsional motion around relative bonds in the chain drives the molecule to approach a keto‐form conical intersection and then nonadiabatic transition occurs. According to our full‐dimensional dynamics simulations, the trans‐keto and enol photoproducts are responsible for the photochromic effect of cis‐keto isomer excited to S₁ state, while no enol isomer was obtained in the photoisomerization of trans keto on excitation. The cis keto to enol and cis keto to trans keto isomerizations are reversible photochemical reactions. It is confirmed that this aromatic Schiff base is a potential molecular switch. Furthermore, the torsion of C N bond occurs in the radiationless decay of trans‐keto isomer, while it is completely suppressed by an intramolecular hydrogen bonding interaction in the dynamics of cis‐keto form. Moreover, the excited‐state lifetime of cis keto is longer than that of trans‐keto form due to the O···H N hydrogen bond.     

CH–π and CF–π Interactions Lead to Structural Changes of N‐Heterocyclic Carbene Palladium Complexes

The role of CH–π and CF–π interactions in determining the structure of N‐heterocyclic carbene (NHC) palladium complexes were studied using ¹H NMR spectroscopy, X‐ray crystallography, and DFT calculations. The CH–π interactions led to the formation of the cis‐anti isomers in 1‐aryl‐3‐isopropylimidazol‐2‐ylidene‐based [(NHC)₂PdX₂] complexes, while CF–π interactions led to the exclusive formation of the cis‐syn isomer of diiodobis(3‐isopropyl‐1‐pentafluorophenylimidazol‐2‐ylidene) palladium(II).     

Steric and Electronic Effects of Bidentate Phosphine Ligands on Ruthenium(II)‐Catalyzed Hydrogenation of Carbon Dioxide

The reactivity difference between the hydrogenation of CO₂ catalyzed by various ruthenium bidentate phosphine complexes was explored by DFT. In addition to the ligand dmpe (Me₂PCH₂CH₂PMe₂), which was studied experimentally previously, a more bulky diphosphine ligand, dmpp (Me₂PCH₂CH₂CH₂PMe₂), together with a more electron‐withdrawing diphosphine ligand, PN^MeP (Me₂PCH₂N^MeCH₂PMe₂), have been studied theoretically to analyze the steric and electronic effects on these catalyzed reactions. Results show that all of the most favorable pathways for the hydrogenation of CO₂ catalyzed by bidentate phosphine ruthenium dihydride complexes undergo three major steps: cis–trans isomerization of ruthenium dihydride complex, CO₂ insertion into the Ru?H bond, and H₂ insertion into the ruthenium formate ion. Of these steps, CO₂ insertion into the Ru?H bond has the lowest barrier compared with the other two steps in each preferred pathway. For the hydrogenation of CO₂ catalyzed by ruthenium complexes of dmpe and dmpp, cis–trans isomerization of ruthenium dihydride complex has a similar barrier to that of H₂ insertion into the ruthenium formate ion. However, in the reaction catalyzed by the PN^MePRu complex, cis–trans isomerization of the ruthenium dihydride complex has a lower barrier than H₂ insertion into the ruthenium formate ion. These results suggest that the steric effect caused by the change of the outer sphere of the diphosphine ligand on the reaction is not clear, although the electronic effect is significant to cis–trans isomerization and H₂ insertion. This finding refreshes understanding of the mechanism and provides necessary insights for ligand design in transition‐metal‐catalyzed CO₂ transformation.     

Uranium–Carbene–Imido Metalla‐Allenes: Ancillary‐Ligand‐Controlled cis‐/trans‐Isomerisation and Assessment of trans Influence in the R2C=UIV=NR′ Unit (R=Ph2PNSiMe3; R′=CPh3)

Uranium(IV)–carbene–imido complexes [U(BIPM^TMS)(NCPh₃)(κ²‐N,N′‐BIPY)] ( 2 ; BIPM^TMS=C(PPh₂NSiMe₃)₂; BIPY=2,2‐bipyridine) and [U(BIPM^TMS)(NCPh₃)(DMAP)₂] ( 3 ; DMAP=4‐dimethylamino‐pyridine) that contain unprecedented, discrete R₂C=U=NR′ units are reported. These complexes complete the family of E=U=E (E=CR₂, NR, O) metalla‐allenes with feasible first‐row hetero‐element combinations. Intriguingly, 2 and 3 contain cis‐ and trans‐C=U=N units, respectively, representing rare examples of controllable cis/trans isomerisation in f‐block chemistry. This work reveals a clear‐cut example of the trans influence in a mid‐valent uranium system, and thus a strong preference for the cis isomer, which is computed in a co‐ligand‐free truncated model—to isolate the electronic trans influence from steric contributions—to be more stable than the trans isomer by approximately 12 kJ mol^?1 with an isomerisation barrier of approximately 14 kJ mol^?1.     

Highly Efficient Deep‐Blue Emitters Based on cis and trans N‐Heterocyclic Carbene PtII Acetylide Complexes: Synthesis,Photophysical Properties,and Mechanistic Studies

We have synthesized cis and trans N‐heterocyclic carbene (NHC) platinum(II) complexes bearing σ‐alkynyl ancillary ligands, namely [Pt(dbim)₂(C?CR)₂] [DBIM=N,N′‐didodecylbenzimidazoline‐2‐ylidene; R=C₆H₄F ( 4 ), C₆H₅ ( 5 ), C₆H₂(OMe)₃ ( 6 ), C₄H₃S ( 7 ), and C₆H₄C?CC₆H₅ ( 8 )] and [Pt(ibim)₂(C?CC₆H₅)₂] ( 9 ) (ibim=N,N′‐diisopropylbenzimidazoline‐2‐ylidene), starting from [Pt(cod)(C?CR)₂] (COD=cyclooctadiene) and 2 equivalents of [dbimH]Br ([ibimH]Br for complexes 9 ) in the presence of tBuOK and THF. Mechanistic investigations aimed at uncovering the cis to trans isomerization reaction have been performed on the representative cis complex 5 a [Pt(dbim)₂(C?CC₆H₅)₂] and revealed the isomerization to progress smoothly in good yield when 5 a was treated with catalytic amounts of [Pt(cod)(C?CR)₂] at 75 °C in THF or when 5 a was heated at 200 °C in the solid state under an inert atmosphere. Detailed examination of the reactions points to the possible involvement, in a catalytic fashion, of a solvent‐stabilized Pt^II dialkyne complex in the former case and a Pt⁰ NHC complex in the latter case, for the transformation of the cis isomer to the corresponding trans complex. Thermal stability and the isomerization process in the solid state have been further investigated on the basis of TGA and DSC measurements. X‐ray diffraction studies have been carried out to confirm the solid‐state structures of 4 b , 5 a , 5 b , and 9 b . All of the synthesized dialkyne complexes 4 – 9 exhibit phosphorescence in solution, in the solid state at room temperature (RT), and also in frozen solvent glasses at 77 K. The emission wavelengths and quantum yields have been found to be highly tunable as a function of the alkynyl ligand. In particular, the trans isomer of complex 9 in a spin‐coated film (10 wt % in poly(methyl methacrylate), PMMA) exhibits a high phosphorescence quantum yield of 80 %, which is the highest reported for Pt^II‐based deep‐blue emitters. Experimental observations and time‐dependent density functional theory (TD‐DFT) calculations are strongly indicative of the emission being mainly governed by metal‐perturbed interligand (³IL) charge transfer.     

Ruthenium(II) Complexes Containing Lutidine‐Derived Pincer CNC Ligands: Synthesis,Structure, and Catalytic Hydrogenation of CN bonds

A series of Ru complexes containing lutidine‐derived pincer CNC ligands have been prepared by transmetalation with the corresponding silver‐carbene derivatives. Characterization of these derivatives shows both mer and fac coordination of the CNC ligands depending on the wingtips of the N‐heterocyclic carbene fragments. In the presence of tBuOK, the Ru‐CNC complexes are active in the hydrogenation of a series of imines. In addition, these complexes catalyze the reversible hydrogenation of phenantridine. Detailed NMR spectroscopic studies have shown the capability of the CNC ligand to be deprotonated and get involved in ligand‐assisted activation of dihydrogen. More interestingly, upon deprotonation, the Ru‐CNC complex 5 e (BF₄) is able to add aldimines to the metal–ligand framework to yield an amido complex. Finally, investigation of the mechanism of the hydrogenation of imines has been carried out by means of DFT calculations. The calculated mechanism involves outer‐sphere stepwise hydrogen transfer to the C?N bond assisted either by the pincer ligand or a second coordinated H₂ molecule.     

Barrierless Single‐Electron‐Induced cis–trans Isomerization

Lowering the activation energy of a chemical reaction is an essential part in controlling chemical reactions. By attaching a single electron, a barrierless path for the cis–trans isomerization of maleonitrile on the anionic surface is formed. The anionic activation can be applied in both reaction directions, yielding the desired isomer. We identify the microscopic mechanism that leads to the formation of the barrierless route for the electron‐induced isomerization. The generalization to other chemical reactions is discussed.     

Coupling Between the Retinal Thermal Isomerization and the Glu194 Residue of Bacteriorhodopsin†

Glu194 is a residue located at the end of F helix on the extracellular side of the light‐induced proton pump bacteriorhodopsin (BR). Currently, it is well recognized that Glu194 and Glu204 residues, along with water clusters, constitute the proton release group of BR. Here we report that the replacement of Glu194 for Gln affects not only the photocycle of the protein but also has tremendous effect on the all‐trans to 13‐cis thermal isomerization. We studied the pH dependence of the dark adaptation of the E194Q mutant and performed HPLC analysis of the isomer compositions of the light‐ and partially dark‐adapted states of the mutant at several pH values. Our data confirmed that E194Q exhibits extremely slow dark adaptation over a wide range of pH. HPLC data showed that a significantly larger concentration of all‐trans isomer was present in the samples of the E194Q mutant even after prolonged dark adaptation. After 14 days in the dark the 13‐cis to all‐trans ratio was 1:3 in the mutant, compared to 2:1 in the wild type. These data clearly indicate the involvement of Glu194 in control of the rate of all‐trans to 13‐cis thermal isomerization.     

NMR signal assignment of cis/trans‐conformational segments in MEH‐CN‐PPV

Poly[2‐(2′‐ethylhexyloxy)‐5‐methoxy‐1,4‐phenylene‐(1‐cyanovinylene)] MEH‐CN‐PPV and its all‐trans model compound 1,4‐bis(α‐cyanostyryl)‐2‐(2‐ethylhexyloxy)‐5‐methyloxybenzene were synthesized via Knoevenagel condensation. All‐cis isomer and cis–trans isomer of 1,4‐bis(α‐cyanostyryl)‐2‐(2‐ethylhexyloxy)‐5‐methyloxybenzene were prepared by the photoisomerization reaction. Comparison of the ¹H NMR spectra between MEH‐CN‐PPV and three model compounds proved the occurrence of cis‐vinylene in the backbone of MEH‐CN‐PPV. According to the ratio between the cis‐vinylene signal and trans‐vinylene signal, the content of the cis‐vinylene could be estimated to be 15% in MEH‐CN‐PPV. This large cis‐vinylene content came from the rapid photochemical isomerization of cyanovinylene and was likely relative to the poor electroluminescence property of MEH‐CN‐PPV. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1105–1113, 2008     

A Conformational Study of Cyclohexane‐1,3,5‐tricarbonitrile Derivatives

Cyclohexane‐1,3,5‐tricarbonitrile reached equilibrium having 1,3‐cis‐1,5‐cis and 1,3‐cis‐1,5‐trans isomers in a ratio of 3:7. The cis, cis‐isomer preferred the conformation with three equatorial cyano groups, where as the cis, trans‐isomer displayed two cyano groups on equatorial positions and another cyano group on axial position. Condensation of cis, cis‐cyclohexane‐1,3,5‐tricarbonitrile with L‐(S)‐valinol by the catalysis of ZnCl₂ in refluxing 1,2‐dichlorobenzene afforded two isomeric cyclohexane‐1,3,5‐trioxazolines in favor of the 1,3‐cis‐1,5‐trans isomer. Metalation of cis, cis‐cyclohexane‐1,3,5‐tricarbonitrile, followed by alkylations with dimethyl sulfate, benzyl bromide or allyl bromide, gave the cor responding trialkylation products with predominance of 1,3‐cis‐1,5‐trans isomers. The cis, trans‐isomer showed two cyano groups on axial positions and another cyano group on equatorial position, where as the cis, cis‐isomer exhibited three axial cyano groups. Treatment of trimethyl cis, cis‐cyclohexane‐1,3,5‐tricarboxylate with lithium diisopropylamide and dimethyl sulfate afforded mainly the trimethyl ester of Kemp's triacid, which showed three axial carboxylate groups. Two competitive factors, i.e. the steric effect of in coming electrophiles and the dipole‐dipole inter actions of the cyano or carboxylate groups, might inter play to give different stereoselectivities in these reaction systems.     

Oxygen‐Initiated Stereoselective Thermal Isomerisation of a Cyclobutane Derivative in the Solid State

Solid‐state [2+2] photochemical cycloaddition reactions have been extensively studied after the classical work of Schmidt in the 1960s. Of these, trans‐1,2‐bis(4′‐pyridyl)ethylene (bpe) is one of the well‐studied alkenes to synthesize tetrakis(4‐pyridyl)cyclobutane (tpcb). However, almost all the solid‐state [2+2] cycloaddition reactions of bpe yielded, almost exclusively, one of the four possible isomers, namely, the rctt‐tpcb (r=regio c=cis and t=trans). Here we describe a stereoselective synthesis of the tetrahedrally disposed rtct‐tpcb by the solid‐state thermal isomerization of the rctt‐isomer in atmospheric air. We propose that this isomerization occurs through a topochemical unimolecular mechanism by a radical chain pathway, initiated by molecular oxygen. This is supported by the nature of products formed in air and nitrogen, detection of a radical in ESR spectral studies, ESI‐MS crossover experiments, VT PXRD studies along with QM, MD and docking calculations. The formation of a unique isomer by thermal isomerization may be a general phenomenon to quantitatively synthesize other useful stereoisomers from the existing isomers of cyclobutane derivatives.     

A facile route to ruthenium–carbene complexes and their application in furfural hydrogenation

A number of new N‐heterocyclic carbene (NHC) ligands were synthesized via a multicomponent reaction, wherein an aldehyde or ketone, a primary amine and an α‐acidic isocyanide were reacted, giving the corresponding 2H‐2‐imidazolines. These were easily alkylated with an alkyl halide at position N‐3, yielding the final NHC precursors, that were then complexed with Ru in situ. The resulting complexes are shown to be active and selective catalysts for the transfer hydrogenation of furfural to furfurol, using isopropanol as the hydrogen source. Importantly, the carbene ligand remains coordinated to the ruthenium center throughout the reaction. Copyright © 2009 John Wiley & Sons, Ltd.     

Computational Study of Metathesis Degradation of Rubber, 3. Distribution of Cyclic and Linear Oligomers via Intermolecular Degradation of cis‐Poly(butadiene)

The molecular modeling of the product distributions for the intermolecular metathesis degradation of cis‐poly(butadiene) (cis‐PB) in the presence of ethylene as chain‐transfer agent (CTA) at 298.15 K using the B3LYP/6‐31G (d, p) level of theory reveals that chain–ring and chain‐chain equilibria are shifted toward the formation of 1,5‐hexadiene. The amount of cyclic oligomers at equilibrium with linear molecules is negligible. The α,ω‐vinyl‐terminated butadiene oligomers–1,5‐hexadiene equilibrium constant depends on the cis/trans isomer ratio in linear butadiene molecules. While the concentration of 1,5‐hexadiene at equilibrium with cis‐butadiene oligomers is 86 mol‐%, this value for trans‐butadiene oligomers corresponds to 50 mol‐% of 1,5‐hexadiene. The results of calculations are in reasonable agreement with recent experimental data on the intermolecular metathesis of 1,4‐cis‐PB with ethylene using a well‐defined ruthenium alkylidene catalyst. The calculations predict that cis‐butene as a CTA is more efficient in the metathesis depolymerization of cis‐PB compared with ethylene.     

Light-induced cis/trans isomerization of cis-[Pd(L-S,O)2] and cis-[Pt(L-S,O)2] complexes of chelating N,N-dialkyl-N′-acylthioureas: key to the formation and isolation of trans isomers

Irradiation cis-[M(Lⁿ-S,O)₂] complexes (M = Pt^II, Pd^II) derived from N,N-dialkyl-N′-benzoylthioureas (HLⁿ) with various sources of intense visible polychromatic or monochromatic light with λ < 500 nm leads to light-induced cis?→?trans isomerization in organic solvents. In all cases, white light derived from several sources or monochromatic blue-violet laser 405 nm light, efficiently results in substantial amounts of the trans isomer appearing in solution, as shown by ¹H NMR and/or reversed-phase HPLC separation in dilute solutions at room temperature. The extent and relative rates of cis/trans isomerization induced by in situ laser light (λ = 405 nm) of cis-[Pd(L²-S,O)₂] was directly monitored by ¹H NMR and ¹⁹⁵Pt NMR spectroscopy of selected cis-[Pt(L-S,O)₂] compounds in chloroform-d; both with and without light irradiation allows the δ(¹⁹⁵Pt) chemical shifts cis/trans isomer pairs to be recorded. The cis/trans isomers appear to be in a photo-thermal equilibrium between the thermodynamically favored cis isomer and its trans counterpart. In the dark, the trans isomer reverts back to the cis complex in what is probably a thermal process. The light-induced cis/trans process is the key to preparing and isolating the rare trans complexes which cannot be prepared by conventional synthesis as confirmed by the first example of trans-[Pd(L-S,O)₂] characterized by single-crystal X-ray diffraction, deliberately prepared after photo-induced isomerization in acetonitrile solution.     

Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis

Geometric isomerization can expand the scope of biological activities of natural products. The observed chemical diversity among the pseurotin‐type fungal secondary metabolites is in part generated by a trans to cis isomerization of an olefin. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione S‐transferase PsoE requires participation of the bifunctional C‐methyltransferase/epoxidase PsoF to complete the trans to cis isomerization of the pathway intermediate presynerazol. The crystal structure of the PsoE/glutathione/presynerazol complex indicated stereospecific glutathione–presynerazol conjugate formation is the principal function of PsoE. Moreover, PsoF was identified to have an additional, unexpected oxidative isomerase activity, thus making it a trifunctional enzyme which is key to the complexity generation in pseurotin biosynthesis. Through the study, we identified a novel mechanism of accomplishing a seemingly simple trans to cis isomerization reaction.