Grob-type fragmentation of 5-oxabicyclo[2.1.1]hexane system: a strategy for synthesis of annulated and 2,2,5-trisubstituted tetrahydrofurans

Acid mediated, efficient Grob-type fragmentation reaction facilitated by vicinal ketal and ester moieties in variety of 5-oxabicyclo[2.1.1]hexanes leading to the corresponding annulated and 2,2,5-trisubstituted tetrahydrofurans is reported. Among the Brønsted and Lewis acids tested, BF₃·OEt₂ appears to give the best results, furnishing near quantitative yield (>99%) of tetrahydrofuran tricarboxylate derivatives under mild reaction condition. In case of unsymmetrical monosubstituted 5-oxabicyclo[2.1.1]hexanes two regioisomeric products are obtained. A strategy to transform one of the ester groups of the title compounds to protected hydroxymethyl moiety was evolved, which allows access to differentially protected 2-hydroxymethyl THF derivatives upon fragmentation. Employing TiCl₄/R or S-BINOL as chiral Lewis acid, an enantioselective fragmentation (up to 66% ee) was described for the meso bis-furan derivative.     

Monomer-isomerization polymerization. XXIII.. Monomer-isomerization polymerization of 5-phenyl-2-pentene with ziegler–natta catalysts

5-Phenyl-2-pentene (5Ph2P) was found to undergo monomer-isomerization polymerization with TiCl₃–R₃Al (R = C₂H₅ or i-C₄H₉, Al/Ti > 2) catalysts to give a polymer consisting of exclusively 5-phenyl-1-pentene (5Ph1P) unit. The geometric and positional isomerizations of 5Ph2P to its terminal and other internal isomers were observed to occur during polymerization. The catalyst activity of alkylaluminum examined to TiCl₃ was in the following order: (C₂H₅)₃Al > (i-C₄H₉)₃Al > (C₂H₅)₂AlCl. The rate of monomer-isomerization polymerization of 5Ph2P with TiCl₃–(C₂H₅)₃Al catalyst was influenced by both the Al/Ti molar ratio and the addition of nickel acetylacetonate [Ni(acac)₂], and the maximum rate was observed at Al/Ti = 2.0 and Ni/Ti = 0.4 in molar ratios.     

Monomer-isomerization polymerization. XX. Monomer-isomerization polymerization of 2-, 3-, and 4-octenes with Ziegler–Natta catalyst

A study of the monomer isomerization polymerization of 2-, 3-, and 4-octenes has been made with TiCl₃–(C₂H₅)₃Al catalyst at 80°C in comparison with the ordinary polymerization of 1-octene. It was found that all these octenes underwent monomer-isomerization polymerization to give high-molecular-weight homopolymer consisting exclusively of the 1-octene unit. The addition of an isomerization catalyst such as nickel acetylacetonate accelerated this polymerization. The rates of polymerization were found to decrease in the following order: 1-octene > 2-octene > 3-octene > 4-octene. These results indicate that the isomerization proceeded by a stepwise double-bond migration. It was also found that the monomer-isomerization copolymerization of 2-octene and 2-butene occurred under similar conditions and produced copolymers of both 1-olefin units.     

Effects of nano graphene oxide as support on the product properties and performance of Ziegler–Natta catalyst in production of UHMWPE

The synthesis of mono‐ and bi‐supported Ziegler–Natta catalysts using magnesium etoxide Mg(OEt)₂ and graphene oxide (GO) as catalyst support for production of Ultra High Molecular Weight Polyethylene (UHMWPE) is reported in this investigation. Nano‐graphene oxide was prepared by the modified Hummer's method and its structure was analyzed by XRD and FTIR indicating the presence of hydroxyl groups on graphene oxide and the formation of an exfoliated structure. The activity of TiCl₄/Mg(OEt)₂, TiCl₄/Mg(OEt)₂‐GO, and TiCl₄/GO catalysts in terms of grams of PE produced per mmol of Ti per hour was experimentally obtained for catalysts with different ratios of co‐catalyst (triisobutylaluminium) to TiCl₄. For all three series of catalysts, the activity curve showed an optimum point at a specific Al/Ti molar ratio. Catalyst activity was highest for TiCl₄/Mg(OEt)₂ and lowest for TiCl₄/GO. The characterization of UHMWPE products indicated that the viscosity average molecular weight (Mv) was highest for the polymer produced by TiCl₄/Mg(OEt)₂ and lowest for the polymer produced by TiCl₄/GO. Furthermore, thermogravimetric analysis (TGA), dynamic mechanical thermal analysis (DMTA), and mechanical tensile testing were conducted on the prepared polymers indicating that the polymer produced by TiCl₄/GO had the highest thermal and mechanical properties, while these properties were at their minimum for polymers produced by TiCl₄/Mg(OEt)₂. Copyright © 2015 John Wiley & Sons, Ltd.     

An Efficient and Practical Synthesis of Dibenzo[d,f][1,3]‐dioxepines from 2,2′‐Dihydroxybiphenyl with Terminal Alkynes Catalyzed by Lewis Acid TiCl4

A synthetic strategy toward the cyclic addition of 2,2′‐dihydroxybiphenyl to terminal alkynes has been developed using Lewis acid TiCl₄ as catalyst. The reactions generated dibenzo[d,f][1,3]dioxepines derivatives in good yields with excellent regio‐selectivity in the presence of catalytic amount of TiCl₄ under mild reaction conditions.     

Solvothermal synthesis of TiO2: anatase nanocrystals and rutile nanofibres from TiCl4 in acetone

This work reports a new synthetic approach for single‐phase TiO₂ nanomaterials by solvothermal treatment of titanium tetrachloride in acetone at 80–110 °C. Small, uniform, and yet size‐tunable (5–10 nm) anatase titania nanocrystallites were obtained using a low concentration of TiCl₄ in acetone (i.e., at molar ratios of TiCl₄/acetone ≤ 1:15) in the temperature range of 80–110 °C, while rutile nanofibers were synthesized using a high concentration of TiCl₄ (e.g., TiCl₄/acetone = 1:10) at 110 °C. Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis of Chlorotitanium(IV) Schiff‐Base Complexes and their Application to Styrene Polymerization

Summary: A [TiCl₂(salen)] complex and its derivatives with the formula [TiCl₂(L)] [L = salen(tBu), salen(di‐Me), salen(di‐tBu), salen(Me)] were synthesized in high yield by reacting the Schiff‐base ligands with TiCl₄. [TiCl₂{salen(tBu)}] and [TiCl₂{salen(di‐tBu)}] have been characterized by single‐crystal X‐ray diffraction. Styrene polymerizations carried out with [TiCl₂(salen)] and its derivatives co‐catalyzed by MAO yielded syndiotactic polystyrenes. The catalytic activity and syndiospecificity were dependent on the bulkiness of the ortho substituents in the aryl ring of ligand.

     

New epoxide initiators for the controlled synthesis of functionalized polyisobutylenes

The mechanism of initiation was investigated in isobutylene (IB) polymerizations initiated by epoxidized α‐methylstyrene (MSE) and 1,2‐epoxy‐2,4,4‐trimethylpentane (TMPO) in conjunction with TiCl₄. The proposed mechanism predicts primary OH head groups and tertiary Cl end groups in the PIB. Model studies conducted with MSE/TiCl₄ and diisobutylene lead to ring closure yielding a substituted furanyl structure. Real‐time fiber‐optic refractive index monitoring was used to follow the initiation with the TMPO/TiCl₄ system. It was found that the cleavage of TMPO proceeds simultaneously by S_N1 and S_N2 mechanisms as proposed. The carbocation forming by the S_N1 route is proposed to initiate the polymerization of IB, but it was shown that excess TiCl₄ relative to TMPO was necessary for propagation. Isomerization and polyether formation by the S_N2 pathway lead to side reactions, reducing the initiating efficiency.     

Diastereoselectivity control in the TiCl4-mediated addition reaction of allyltrimethylsilane to N,O-protected (l)-serinals

The TiCl₄- and SnCl₄-mediated addition reactions of allyltrimethylsilane (1) to protected ( )-serinals (2–5) were studied, and in the case of TiCl₄ a large influence of the N- and O-protecting groups on the stereochemical course was observed.     

Lewis Acid‐Mediated Addition of Amino Acid‐Substituted α‐Allylsilanes to Aromatic Acetals

Unnatural amino acids extend the pharmacological formulator's toolkit. Strategies to prepare unnatural amino acid derivatives using Lewis acid‐activated allylsilane reactions are few. In this regard, we examined the utility of allylsilanes bearing an amino acid substituent in the reaction. Diastereoselective addition of methyl 2‐(N‐PG‐amino)‐3‐(trimethylsilyl)pent‐4‐enoate and methyl (E)‐2‐(N‐PG‐amino)‐3‐(trimethylsilyl)hex‐4‐enoate (PG=protecting group), 2 and 13 , respectively, to aromatic acetals in the presence of Lewis acids is described. Of those examined, TiCl₄ was found to be the most effective Lewis acid for promoting the addition. At least 1 equiv. of TiCl₄ was required to achieve high yields, whereas 2 equiv. of BF₃?OEt₂ were required for comparable outcomes. Excellent selectivity (>99% syn/anti) and high yield (up to 89%) were obtained with halo‐substituted aromatic acetals, while more electron‐rich electrophiles led to both lower yields and diastereoselectivities.     

Regioselective synthesis and biological activity of oxidized chitosan derivatives

Oxidized chitosan derivatives with various degrees of oxidation (DS, 0.1–1.0) were prepared by the treatment of chitosan with CrO₃/aq HClO₄ or by the oxidation of ­3‐O‐ and N‐protected chitosan with 30% aq H₂O₂/Na₂WO₄ followed by 3‐O‐ and N‐deprotection. The oxidized products were then N‐acetylated with Ac₂O in order to improve their water‐solubility. Although the oxidized chitosan derivative of DS 0.28 and the degree of N‐acetylation of chitosan (DA) 38% was insoluble in the pH 3–8 region, that of DS 0.26 and DA 76% was soluble in the neutral pH range. The newly‐prepared acetylated and oxidized chitosan derivatives were found to suppress the chemiluminescence response of inflammatory cells such as canine polymorphonuclear cells (PMNs). Analysis by the surface plasmon resonance method revealed that the bind and release behavior of PMNs to acetylated oxidized chitosan derivatives was similar to that against carboxymethylated chitosan derivatives. The amount of water‐soluble chitosan derivative bound to cytokine IL‐8 was found to be affected by the structural and electronic features of the chitosan substituents in the chitosan chain. Copyright © 2003 John Wiley & Sons, Ltd.     

Highly 2,3‐Selective Polymerization of Phenylallene and Its Derivatives with Rare‐Earth Metal Catalysts: From Amorphous to Crystalline Products

Rare‐earth metal complexes (Flu‐CH₂‐Py)Ln(CH₂SiMe₃)₂(THF)_n (Ln=Sc( 1 ), Lu( 2 ), Tm( 3 ), Y( 4 ) and Gd( 5 )), upon the activation of [Ph₃C][B(C₆F₅)₄] and Alⁱ Bu₃, were employed to catalyze the polymerization of allene derivatives under mild conditions. The Gd, Y, Tm, Lu metal based precursors exhibited distinguished 2,3‐selectivity (>99.9 %) for phenylallene (PA) polymerization, whereas the smallest Sc metal based precursor showed a moderate 2,3‐selectivity. The activity increased with the central metal size following the trend of Gd( 5 )>Tm( 4 )>Y( 3 )>Lu( 2 )>Sc( 1 ). Moreover, Gd( 5 ) also realized the purely 2,3‐selective polymerizations of polar or nonpolar allene derivatives, para ‐methylphenylallene, para ‐flourophenylallene and para ‐methoxyphenylallene, regardless of electron‐donating or ‐withdrawing substituents. Owing to the highly regular backbones, these polymers (except PPA) were crystalline, thus being the first crystalline polymers based on allene derivatives.     

Trimethylsilylcyanation of heterocyclic imines catalysed by Lewis acids

The addition of Me₃SiCN to Schiff bases 1a–8a, synthesized by the reaction of furan and thiophene aldehydes with 3‐ and 4‐aminobenzotrifluorides, has been studied in the presence of various Lewis acids. A series of the corresponding trifluoromethyl derivatives of heterocyclic α‐aminonitriles 1–8 was synthesized in 38–80% isolated yields. It was found that 4A molecular sieves (MS) accelerate the addition and increase the yields of the products. The investigated catalysts are ranked by their activity in the following order: AlBr₃ + 4AMS > AlBr₃ > AlCl₃ > Ti[O(iPr)]₄. A single crystal of N‐(5‐methyl‐2‐thienylcyanomethyl)‐3‐trifluoromethylaniline was obtained and studied by X‐ray diffraction. The results showed that it was the crystal of the (R) isomer of this compound. Copyright © 2000 John Wiley & Sons, Ltd.     

Preparation of (S,S)‐Fmoc‐β2hIle‐OH, (S)‐Fmoc‐β2hMet‐OH,and (S)‐Fmoc‐β2hTyr(tBu)‐OH for Solid‐Phase Syntheses of β2‐ and β2/β3‐Peptides

The preparation of three new N‐Fmoc‐protected (Fmoc=[(9H‐fluoren‐9‐yl)methoxy]carbonyl) β²‐homoamino acids with proteinogenic side chains (from Ile, Tyr, and Met) is described, the key step being a diastereoselective amidomethylation of the corresponding Ti‐enolates of 3‐acyl‐4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐ones with CbzNHCH₂OMe/TiCl₄ (Cbz=(benzyloxy)carbonyl) in yields of 60–70% and with diastereoselectivities of >90%. Removal of the chiral auxiliary with LiOH or NaOH gives the N‐Cbz‐protected β‐amino acids, which were subjected to an N‐Cbz/N‐Fmoc (Fmoc=[(9H‐fluoren‐9‐yl)methoxy]carbonyl) protective‐group exchange. The method is suitable for large‐scale preparation of Fmoc‐β²hXaa‐OH for solid‐phase syntheses of β‐peptides. The Fmoc‐amino acids and all compounds leading to them have been fully characterized by melting points, optical rotations, IR, ¹H‐ and ¹³C‐NMR, and mass spectra, as well as by elemental analyses.     

Polymerization of vinylcyclohexane with ziegler–natta catalyst

Polymerization of vinylcyclohexane (VCHA) with TiCl₃–aluminum alkyl catalysts was investigated. The polymerization rate of VCHA was low due to the branch at the position adjacent to the reacting double bond. The effects of aluminum alkyl on the polymerization and monomer-isomerization were observed; the polymer yield decreased in the following order: (CH₃)₃Al > (i–C₄H₉)₃Al > (C₂H₅)₃Al. Isomerization of VCHA was observed with the TiCl₃–(i–C₄H₉)₃Al and the TiCl₃–(C₂H₅)₃Al catalysts during the polymerization, while with the TiCl₃–(CH₃)₃Al catalyst such isomerization was not observed. Monomer-isomerization copolymerization of VCHA and trans-2-butene took place to give copolymers consisting of VCHA and 1-butene units.     

Polymerization of 1‐olefins by zirconium/titanium precatalysts with O,N,O‐ligating atoms—can aggregation of catalyst be inferred from the reaction profile?

The 2‐[benzyl‐(2‐hydroxy‐2‐phenylethyl)‐amino]‐1‐phenylethanol ligand (1‐H₂) prepared as a diastereomeric mixture or in racemic and meso forms, from known procedure, has been disodiated and complexed with ZrCl₄. The precatalysts (mix‐1‐ZrCl₂, rac‐1‐ZrCl₂, and meso‐1‐ZrCl₂) were used in combination with methylaluminoxane and found to be active for the polymerization of 1‐hexene and 1‐octene. The high molecular weight polyhexenes (PHs) and polyoctenes (POs) thus obtained were isotactic in nature and showed a negligible amount of end groups arising from the chain termination reactions. In PHs and POs, there was linear correlation in the modified Arrhenius plot (the natural logarithm of the number‐average molecular weight vs. the reciprocal of the temperature), indicating the presence of a single active species. The enantiomerically pure titanium precatalyst ((R,R)‐1‐TiCl₂), when employed for the polymerization of 1‐hexene, was found to be active and the modified Arrhenius plot showed linear dependence demonstrating presence of a single active species. The analogous titanium precatalysts (mix‐1‐TiCl₂, rac‐1‐TiCl₂, and meso‐1‐TiCl₂) obtained from known procedures were also found to be active for the polymerization of 1‐octene. The rac‐1‐TiCl₂ precatalyst demonstrated a sigmoidal behavior in the modified Arrhenius plot for the POs and the mix‐1‐TiCl₂ precatalyst showed an exponential type of behavior. The obtained POs seemed to have small amounts of chain termination via β‐hydride elimination alone. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3599–3610, 2007     

Synthesis of ethylene/propylene elastomers containing a terminal reactive group: The combination of metallocene catalysis and control chain transfer reaction

This article discusses a chemical route to prepare new ethylene/propylene copolymers (EP) containing a terminal reactive group, such as ?‐CH₃ and OH. The chemistry involves metallocene‐mediated ethylene/propylene copolymerization in the presence of a consecutive chain transfer agent—a mixture of hydrogen and styrene derivatives carrying a CH₃ (p‐MS) or a silane‐protected OH (St‐OSi). The major challenge is to find suitable reaction conditions that can simultaneously carry out effective ethylene/propylene copolymerization and incorporation of the styrenic molecule (St‐f) at the polymer chain end, in other words, altering the St‐f incorporation mode from copolymerization to chain transfer. A systematic study was conducted to examine several metallocene catalyst systems and reaction conditions. Both [(C₅Me₄)SiMe₂N(^t‐Bu)]TiCl₂ and rac‐Et(Ind)₂ZrCl₂, under certain H₂ pressures, were found to be suitable catalyst systems to perform the combined task. A broad range of St‐f terminated EP copolymers (EP‐t‐p‐MS and EP‐t‐St‐OH), with various compositions and molecular weights, have been prepared with polymer molecular weight inversely proportional to the molar ratio of [St‐f]/[monomer]. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1858–1872, 2005     

Facile conversion of O-silyl protected sugars into their corresponding formates using POCl3·DMF complex

The direct O-formylation of two selectively protected sugar derivatives using the Vilsmeier-Haack (V-H) complex POCl₃·DMF was studied. Primary O-TBDMS and O-TBDPS ethers of sucrose, the most common disaccharide, underwent regio and chemoselective O-formylation with this formylating agent. This conversion was also studied with a monosaccharide analogue.     

Low-valent Titanium Induced Intramolecular Reductive Coupling of Keto-enamines:A Facile Synthesis of 2,3,5-Trisubstituted Pyrroles

Promoted by low-valent titaium reagent which was generated in situ from Sm/TiCl4 system,keto-enamine derivatives underwent efficient intromolecular deoxygenative coupling reactions and afforded the corresponding 2,3,5-trisubstituted pyrroles in moderate to good yields under mild reaction conditions.     

Novel Porphyrazine Derivatives show Promise for Photodynamic Therapy despite Restrictions in Hydrophilicity

Complexing of ligands to photosensitizers (Ps) has gained popularity by enhancing solubility, cell‐surface recognition and tissue specificity for applications in Photodynamic Therapy (PDT) and fluorescence‐based diagnostics. Here we report on nine carbohydrate‐functionalized porphyrazine (Pz‐galactopyranose/methyl‐ribose) derivatives bearing either H₂, Zn(II) or Ni(II) cores for potential use in PDT. Derivatives proved soluble only in organic solvents; dichloromethane (DCM) and tetrahydrofuran (THF). Derivatives were subsequently solubilized using DCM‐based PEG‐DSPE₅₀₀₀‐PBS encapsulation for biological studies due to THF cytotoxicity. Absorption spectra analyses viewed no correlation between core ion, carbohydrate type and peripheral position though encapsulation efficiency (%EE) followed a general order of Zn(II) (60–92%) > H₂ (5–34%) > Ni(II) (4–21%). As such, phototoxicity of Zn(II)Pz derivatives were far superior to H₂Pz and Ni(II)Pz counterparts following 631.4 nm excitation of MCF‐7 breast cancer cells. Variation was attributed to persistent aggregation and low %EE when regarding the absorption properties recorded. It is therefore believed that revision of the encapsulation method for H₂Pz and Ni(II)Pz derivatives would render improved phototoxicity. Zn(II)Pz derivatives show promise as agents for PDT of cancer.