Substituents R1 Research Articles

Hafnocene Catalysts for Selective Propylene Oligomerization: Efficient Synthesis of 4-Methyl-1-pentene by β-Methyl Transfer

A series of hafnocene complexes (eta5-C5Me4R1)(eta5-C5Me4R2)HfCl2 with [R1, R2] = [H, H] (1), [Me, H] (2), [Me, Me] (3), [Et, Me] (4), [(i)Pr, Me] (5), [SiMe(3), Me] (6), [(t)Bu, Me] (7), [(n)Bu, Me] (8), [(i)Bu, Me] (9), [Et, Et] (10), [(n)Bu, (n)Bu] (11), [(i)Bu, (i)Bu] (12) was tested as catalyst precursors for propylene oligomerization. Upon activation with methylaluminoxane or [Ph(3)C][B(C(6)F(5))(4)]/Al(i)Bu(3), complexes 2-4 and 8-12 catalyzed the dimerization of propylene to produce 4-methyl-1-pentene with selectivities ranging from 23.9 to 61.6 wt % in the product mixture. The selectivity was dependent on the nature of the substituents R(1) and R(2), with the highest value found for (eta5-C5Me4(i)Bu)2HfCl2 (12). Rapid deactivation was observed for 5-7, whereas (eta5-C5Me4H)2HfCl2 (1) polymerized propylene. 4-Methyl-1-pentene is proposed to form by repeated 1,2-insertion of propylene into the hafnocene methyl cation, followed by selective beta-methyl elimination. Detailed analysis of the byproduct distribution (isobutene, 1-pentene, 2-methyl-1-pentene, 2,4-dimethyl-1-pentene, 4-methyl-1-heptene, 4,6-dimethyl-1-heptene), determined by gas chromatography, was performed with the aid of a stochastic simulation involving rate constants for the propagation by insertion, beta-hydride elimination, and beta-methyl elimination. The rate of termination is dependent on the structure of the growing chain of the active species as well as on the bulkiness of the cyclopentadienyl ligands. The selectivity highly depends on the reaction conditions (pressure, temperature, concentration of methylaluminoxane). The rates of beta-methyl elimination leading to 4-methyl-1-pentene were proportional to propylene pressure for 2-4 and 8-10 but practically independent from propylene pressure for the sterically bulkier derivatives 11-12.

Ethylene–propylene copolymerization with bis(β‐enaminoketonato) titanium complexes activated with modified methylaluminoxane

AbstractEthylene–propylene copolymerization, using [(Ph)NC(R2)CHC(R1)O]2TiCl2 (R1 = CF3, Ph, or t‐Bu; R2 = CH3 or CF3) titanium complexes activated with modified methylaluminoxane as a cocatalyst, was investigated. High‐molecular‐weight ethylene–propylene copolymers with relatively narrow molecular weight distributions and a broad range of chemical compositions were obtained. Substituents R1 and R2 influenced the copolymerization behavior, including the copolymerization activity, methylene sequence distribution, molecular weight, and polydispersity. With small steric hindrance at R1 and R2, one complex (R1 = CF3; R2 = CH3) displayed high catalytic activity and produced copolymers with high propylene incorporation but low molecular weight. The microstructures of the copolymers were analyzed with 13C NMR to determine the methylene sequence distribution and number‐average sequence lengths of uninterrupted methylene carbons. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5846–5854, 2006

Synthesis and Transformations of Fused Bicyclic Heteroaryl Borates

The synthesis of complex benzo[b]thiophenes, benzo[b]furans, and 2,6-disubstituted imidazo[1,2-a ]pyridines using a microwave-assisted, one-pot cyclization-Suzuki coupling approach is reported. The heterocycles were obtained in moderate to good yields depending on the substituent R1 by treatment of boronate precursors, which are prepared in advance, with 6-bromoquinazolin-2-amine, and α-bromoketone.

(Benzylideneamino)thioureas – Chromogenic Interactions with Anions and N–H Deprotonation

AbstractA family of neutral N‐(R1‐substituted‐benzylideneamino)‐N′‐(R2‐substituted‐phenyl)thioureas (LH) were designed as anion receptors, and their interactions with anions in MeCN solution were investigated through spectrophotometric and 1H NMR titration experiments. While oxo anions (e.g., CH3COO–, H2PO4–) form genuine H‐bond complexes based on complementary N–H···O interactions with LH receptors, the fluoride ion undergoes a two‐step interaction, involving (i) formation of the [LH···F]– complex, and (ii) release of an HF molecule to give [HF2]– and the deprotonated form of the receptor (L–). Deprotonation takes place at the N–H fragment closer to the R2‐substituted phenyl ring, as indicated by 1H NMR spectroscopy. The log K values for the formation of the [LH···CH3COO]– H‐bond complexes vary over the 3.1–3.8 range and are scarcely affected by the natures of the R1 and R2 substituents. The investigated systems may be of interest in the design of molecular devices in which the optical properties of different and distant substituents are modulated through the interaction of a chosen anion at the thiourea site.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Supramolecular Co(II)-[2 × 2] Grids: Metamagnetic Behavior in a Single Molecule

The magnetic anisotropy of the supramolecular [2 x 2] grid [Co(II)4L4]8+, with a bis(bipyridyl)-pyrimidine-based ligand L, was investigated by single-crystal magnetization measurements at low temperatures. The magnetization curves exhibit metamagnetic-like behavior and are explained by the weak-exchange limit of a minimal spin Hamiltonian including Heisenberg exchange, easy-axis ligand fields, and the Zeeman term. It is also shown that the magnetic coupling strength can be varied by the substituent R1 in the two-position on the central pyrimidine group of the ligand L.

Ethylene Oligomerisation and Polymerisation with Nickel Phosphanylenolates Bearing Electron‐Withdrawing Substituents: Structure–Reactivity Relationships

Three SHOP-type catalysts, in which the C=C(O) double bond was substituted by electron-withdrawing substituents, [Ni{Ph2PC(R1)=C(R2)O}Ph(PPh3)] (2: R1,R2 = -C(Me)=NN(Ph)-; 3: R1 = CO2Et, R2 = Ph; 4: R1 = CO2Et, R2 = CF3), were assessed as ethylene-oligomerisation and -polymerisation catalysts and compared to Keim's complex, [Ni{Ph2PCH=C(Ph)O}Ph(PPh3)] (1). A rationale for the influence of the double-bond substituents of the P,O-chelate unit on the catalytic properties is proposed, on the basis of X-ray diffraction studies, spectroscopic data and DFT-B3 LYP calculations. Whatever their relative electron-withdrawing strength, the R1 and R2 substituents induce an increase in activity with respect to catalyst 1. For those systems in which the basicity of the oxygen atom is decreased relative to that of the phosphorus atom, the chain-propagation rate increases with respect to that for catalyst 1. Reduction of the basicity of the P relative to that of the O, however, induces higher chain-termination rates.

Dearomatization Route to Cyclohexadienone Spirolactams

An interesting combined ruthe­nium complex mediated dearomatization-Horner-Wardsworth-Emmons route to cyclohexa­diene spirolactams is reported. The reactions proceed in good yields using several aliphatic and aromatic aldehydes leading to products with exclusive (Z)-configuration. The oxidative decomplexation is achieved using copper(II) salts to give either azaspirocyclic dienones or hydroxy-substituted dienes as a function of the R2 substituent.

Structural basis for the extended substrate spectrum of CMY‐10, a plasmid‐encoded class C β‐lactamase

The emergence and dissemination of extended-spectrum (ES) beta-lactamases induce therapeutic failure and a lack of eradication of clinical isolates even by third-generation beta-lactam antibiotics like ceftazidime. CMY-10 is a plasmid-encoded class C beta-lactamase with a wide spectrum of substrates. Unlike the well-studied class C ES beta-lactamase from Enterobacter cloacae GC1, the Omega-loop does not affect the active site conformation and the catalytic activity of CMY-10. Instead, a three-amino-acid deletion in the R2-loop appears to be responsible for the ES activity of CMY-10. According to the crystal structure solved at 1.55 A resolution, the deletion significantly widens the R2 active site, which accommodates the R2 side-chains of beta-lactam antibiotics. This observation led us to demonstrate the hydrolysing activity of CMY-10 towards imipenem with a long R2 substituent. The forced mutational analyses of P99 beta-lactamase reveal that the introduction of deletion mutations into the R2-loop is able to extend the substrate spectrum of class C non-ES beta-lactamases, which is compatible with the isolation of natural class C ES enzymes harbouring deletion mutations in the R2-loop. Consequently, the opening of the R2 active site by the deletion of some residues in the R2-loop can be considered as an operative molecular strategy of class C beta-lactamases to extend their substrate spectrum.

Ethylene/α‐olefin copolymerization with bis(β‐enaminoketonato) titanium complexes activated with modified methylaluminoxane

AbstractCopolymerizations of ethylene with α‐olefins (i.e., 1‐hexene, 1‐octene, allylbenzene, and 4‐phenyl‐1‐butene) using the bis(β‐enaminoketonato) titanium complexes [(Ph)NC(R2)CHC(R1)O]2TiCl2 (1a: R1 = CF3, R2 = CH3; 1b: R1 = Ph, R2 = CF3; and 1c: R1 = t‐Bu, R2 = CF3), activated with modified methylaluminoxane as a cocatalyst, have been investigated. The catalyst activity, comonomer incorporation, and molecular weight, and molecular weight distribution of the polymers produced can be controlled over a wide range by the variation of the catalyst structure, α‐olefin, and reaction parameters such as the comonomer feed concentration. The substituents R1 and R2 of the ligands affect considerably both the catalyst activity and comonomer incorporation. Precatalyst 1a exhibits high catalytic activity and produces high‐molecular‐weight copolymers with high α‐olefin insertion. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 6323–6330, 2005

Crystal Structure of the Actinomadura R39 DD-peptidase Reveals New Domains in Penicillin-binding Proteins

Actinomadura sp. R39 produces an exocellular DD-peptidase/penicillin-binding protein (PBP) whose primary structure is similar to that of Escherichia coli PBP4. It is characterized by a high beta-lactam-binding activity (second order rate constant for the acylation of the active site serine by benzylpenicillin: k2/K = 300 mm(-1) s(-1)). The crystal structure of the DD-peptidase from Actinomadura R39 was solved at a resolution of 1.8 angstroms by single anomalous dispersion at the cobalt resonance wavelength. The structure is composed of three domains: a penicillin-binding domain similar to the penicillin-binding domain of E. coli PBP5 and two domains of unknown function. In most multimodular PBPs, additional domains are generally located at the C or N termini of the penicillin-binding domain. In R39, the other two domains are inserted in the penicillin-binding domain, between the SXXK and SXN motifs, in a manner similar to "Matryoshka dolls." One of these domains is composed of a five-stranded beta-sheet with two helices on one side, and the other domain is a double three-stranded beta-sheet inserted in the previous domain. Additionally, the 2.4-angstroms structure of the acyl-enzyme complex of R39 with nitrocefin reveals the absence of active site conformational change upon binding the beta-lactams.

New Synthetic Methods for η5-Cyclopentadienyl Nickel(III) Dithiolene Complexes Derived from Nickelocene

The reactions of nickelocene with the neutral square-planar metal dithiolene complexes [M(S2C2(R1)(R2))2] gave the η5-cyclopentadienyl nickel(III) dithiolene complexes [CpNi(S2C2(R1)(R2))] (R1, R2 = Ph (2); R1 = Ph, R2 = H (3); R1, R2 = Me (4)) in 58−62% yields. The monoanions of the square-planar dithiolene complexes [M(S2C2(R1)(R2))2]- reacted with nickelocenium to form [CpNi(S2C2(R1)(R2))] (R1, R2 = COOMe (5) or CN (6)) in 67% or 68% yield, respectively, when the R1 and R2 substituents are electron-withdrawing groups. The CpNi dithiolene complexes 3 and 5 were also obtained by the thermal reactions or photoreactions of nickelocene with 1,3-dithiol-2-one or 1,3-dithiol-2-thione derivatives, [EC(S2C2(R1)(R2))] (E = O, S; R1 = Ph, R2 = H; R1, R2 = COOMe). The most efficient synthetic method for the CpNi dithiolene complex was the reaction of the hexacoordinated platinum dithiolene complex [Pt(S2C2Ph2)2(dppe)] (dppe = bis(diphenylphosphino)ethane) with nickelocene (96% yield for complex 2). The structure of complex 6 was determined by X-ray crystal structure analysis. The electronic and ESR properties of the CpNi dithiolene complexes 2−6 were investigated.

β-Acyloxysulfonyl Tethers for Intramolecular Diels−Alder Cycloaddition Reactions

[reaction: see text]. beta-Hydroxy sulfone-based tethers were employed for the first time to achieve thermally mediated intramolecular Diels-Alder cycloaddition. The reactions proceeded with complete regioselectivity and high (10/1) to complete endo/exo-selectivity and resulted in the preferential formation of one of the two possible endo-cycloadducts. The yields and stereoselectivities were proportional to the bulk of the R(1) substituent on the beta-acyloxysulfonyl tether.

Palladacycles with a Metal‐Bonded sp3‐Hybridized Carbon as Intermediates in the Synthesis of 2,2,3,4‐Tetrasubstituted 2H‐1‐Benzopyrans and 1,2‐Dihydroquinolines. Effects of Auxiliary Ligands and Substitution at a Palladium‐Bonded Tertiary Carbon.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Carbon−Carbon Bond Formation in the Surprising Rearrangement of Diorganylzirconium Dialkoxides: Linear Dimerization of Terminal Olefins1

The mechanism of the rearrangement of diorganylzirconium dialkoxides, such as R1(R2CH2)Zr(OEt)2, into organylzirconium hydride alkoxides of the type R1R2CHZr(OEt)2H, has been investigated as a function of the R1 and R2 substituents and been found to involve optimally an intramolecular migration of R1 to an sp3-hybridized C−H center. A remarkably rapid transfer hydrozirconation between Bun2Zr(OEt)2 and the olefin RCHCH2 now permits the synthesis of (RCH2CH2)2Zr(OEt)2, whose rearrangement offers a route to the linear olefin dimer R(CH2)4R.

Isospecific Styrene Polymerization by Chiral Titanium Complexes That Contain a Tetradentate [OSSO]-Type Bis(phenolato) Ligand

A series of titanium dichloro and di(isopropoxy) complexes with a 1,4-dithiabutanediyl-linked bis(4,6-disubstituted phenolato) ligand [Ti(OC6H2-6-R1-4-R2)2{S(CH2)2S}X2] (X = Cl, 2a−i, OiPr, 3a−i; R1 = H, Me, iPr, tBu, 2-phenyl-2-propyl; R2 = H, Me, tBu, OMe, 2-phenyl-2-propyl) were synthesized by reacting the corresponding linked bis(phenol) (HOC6H2-6-R1-4-R2)2{S(CH2)2S} (1a−i) with the titanium precursor TiX4. The NMR spectra of the dichloro complexes Ti(OC6H2-6-R1-4-R2)2{S(CH2)2S}Cl2] (2a−d) with small ortho substituents R1 = H, Me, iPr are in agreement with a C2-symmetrical helical structure, but the complexes become fluxional at higher temperatures. The corresponding di(isopropoxy) complexes [Ti(OC6H2-6-R1-4-R2)2{S(CH2)2S}(OiPr)2] (3a−d) are fluxional in solution at room temperature due to rapid interconversion between the Δ and Λ isomers. In contrast, both dichloro and di(isopropoxy) complexes 2e−i and 3e−i with bulky ortho substituents R1 = tBu and 2-phenyl-2-propyl exhibit a rigid C2-symmetrical he...

Computational Rationalization of the Dependence of the Enantioselectivity on the Nature of the Catalyst in the Vanadium-Catalyzed Oxidation of Sulfides by Hydrogen Peroxide

A computational study with the IMOMM(Becke3LYP:MM3) method is carried out on the mechanism of the enantioselective reaction of complex V(O)(L)(OOH), L= bulky tridentate Schiff base, and bis(tert-butyl) disulfide. The reaction with a given L ligand A is first systematically studied: different conformers of the catalyst are optimized, and the large number of associated transition states are systematically searched. The study is then extended to the geometry optimization of selected transition states associated to other ligands B, C, and D, similar to A but differing in the nature of certain substituents R1, R2, R3. The experimental trends in selectivity for catalysts based on ligands A to D are faithfully reproduced by the calculations. Analysis of the computational results leads finally to the formulation of a simple model that can explain one of the most remarkable aspect of this reaction, namely the large effect on enantioselectivity of ligands seemingly far from each other in the catalyst.

Palladacycles with a Metal-Bonded sp3-Hybridized Carbon as Intermediates in the Synthesis of 2,2,3,4-Tetrasubstituted 2H-1-Benzopyrans and 1,2-Dihydroquinolines. Effects of Auxiliary Ligands and Substitution at a Palladium-Bonded Tertiary Carbon

Prompted by the failure to prepare stable oxapalladacycles L2Pd-1-C6H4-2-OC(R1)COOEt with PPh3 ligands (L = PPh3) and substituents R1 other than hydrogen, systematic studies on the effects of steric and electronic properties of auxiliary ligands L and substituents R1 (alkyl, aryl) on the feasibility of formation, stability, and reactivity of the oxapalladacycles were performed. Using N,N,N‘,N‘-tetramethyl-1,2-ethylenediamine bidentate ligand (L−L = TMEDA), stable palladacycles featuring substituents R1 (Me, Et, i-Pr, and Ph) were prepared, and the presence of palladium-bonded tertiary sp3-hybridized carbons was confirmed by X-ray crystallographic analyses on palladacycles with i-Pr and Ph substituents R1. Relying on 31P NMR analyses of crude reaction mixtures, ligand displacement reactions of palladacycles (TMEDA)Pd-1-C6H4-2-OC(R1)COOEt with monodentate phosphines (PPh3 and PPh2Me) were studied, as well as base-mediated ring-closure reactions of arylpalladium(II) iodo complexes (PPh3)2Pd(-1-C6H4-2-OCHR1COOEt)I and (PPh2Me)2Pd(-1-C6H4-2-OCHR1COOEt)I. In both series, higher conversions to corresponding palladacycles L2Pd-1-C6H4-2-OC(R1)COOEt were achieved with PPh2Me ligands, and both the transformations were negatively affected by an increase in the steric bulk of substituents R1. Although the palladacycles with monodentate phosphines could not be isolated as stable entities, IR spectroscopic analyses supported the presence of a Csp3−Pd bond. On the basis of these studies, a one-pot conversion of stable arylpalladium(II) iodo complexes with PPh2Me ligands into 2,2,3,4-tetrasubstituted 2H-1-benzopyrans and 1,2-dihydroquinolines via the insertion of unsymmetrical alkynes into in situ formed palladacycles was developed, providing the heterocycles in good yields (44−80%) as single regioisomers.

Quantitative structure–activity relationship analysis of 2,3-diaryl indoles as selective cyclooxygenase-2 inhibitors

Quantitative structure–activity relationship (QSAR) studies have been performed on a combined series of 2-sulfonylphenyl-3-phenyl-indoles and 2-phenyl-3-sulfonylphenyl-indoles with a common 2,3 vicinal diaryl indole scaffold, recently reported as selective COX-2 inhibitors. This study is aimed to throw light on this, special class of diaryl heterocyclic family of selective COX-2 inhibitors. A preliminary Fujita-Ban analysis on 32 compounds provided valuable insights about the role of different substituents R1 and R2 around the 2,3 vicinal diaryl rings and R3, at position-5 of the central indole moiety in explaining their in vitro COX-2 inhibitory activity. The contribution of R1, R2, R3 towards COX-2 inhibitory activity resulted in statistically significant linear multiple regression equation with r = 0.942, r2 = 0.888, s = 0.532 and F = 7.92, q2 = 0.516 for 29 compounds. Fujita-Ban model shows a negative contribution of SO2NH2 and SO2CH3 at the R1 position; a negative contribution of 4-Cl, 2-Cl, 3-Cl, 3-CH3, 4-SO2CH3, 4-Br and a positive contribution of 4-OCH3, 4-CH3 substituents at the R2 position. At the R3 position a negative contribution of F, Br and a positive contribution of Cl, CH3 is encountered. In the light of our preliminary investigation that electron donating groups at the para position of R2 are conducive for COX-2 inhibitory activity from the Fujita-Ban model, we attempted to correlate the COX-2 inhibitory activity with quantum chemical descriptors of semi-empirical AM1 optimized geometries of the title compounds. Correlation analysis showed the molecular electronic descriptor, MOPAC total energy as crucial in governing COX-2 inhibitory activity of all the reported 41 compounds.

Synthesis and Radical Polymerization of Various 2‐Cyclopropylacrylates

AbstractFourteen new alkyl 2‐cyclopropylacrylates 1a−n with various substituents R1−R5 were synthesized from readily available precursors by applying standard transformations such as cyanohydrin formation from an aldehyde, alcoholysis to an α‐hydroxycarboxylic ester, oxidation and Wittig methylenation of an α‐oxocarboxylic ester. Overall yields ranged from 33 to 54%. A new method for the hydrolysis of dimethyl cyclopropanedicarboxylates to the corresponding half‐esters was developed. The α‐oxocarboxylates 7g−n were prepared by dirhodium tetraacetate catalyzed cyclopropanation of alkenes 8g−n with methyl or ethyl diazopyruvate in 32−58% yield. The monomers 1a−n were characterized by 1H, 13C NMR spectroscopy, mass spectrometry and elemental analysis. The radical homopolymerizations of 1a−n were carried out with 2,2′‐azabisisobutyronitrile (AIBN) as initiator in chlorobenzene at 65 °C. The highest polymer yields were obtained in the polymerizations of 1f and 1h or 1k and 1l, i.e. from monomers with an annelated five‐ or six‐membered ring. In the case of 1h and 1k, both the polymer yields (99 and 98%, respectively) and the glass transition temperatures (Tg) of 57 and 93 °C were significantly higher than those observed for the polymer from 1,1‐bis(ethoxycarbonyl)‐2‐vinylcyclopropane (DECVCP), which was used as a benchmark for the monomer reactivities in the radical polymerizations of all the vinylcyclopropane derivatives 1a−n. The bicyclic monomers 1h and 1k also demonstrated drastically improved reactivities in the radical copolymerization with methyl methacrylate when compared to DECVCP. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Enecarbamates as Selective Substrates in Oxidations: Chiral‐Auxiliary‐Controlled Mode Selectivity and Diastereoselectivity in the [2 + 2] Cycloaddition and Ene Reaction of Singlet Oxygen and in the Epoxidation by DMD and mCPBA.

AbstractFor Abstract see ChemInform Abstract in Full Text.