Biomimetic Interaction between FeII and O2: Effect of the Second Coordination Sphere on O2 Binding to FeII Complexes: Evidence of Coordination at the Metal Centre by a Dissociative Mechanism in the Formation of μ‐Oxo Diferric Complexes

We report that the formation of μ‐oxo diferric compounds from O₂ and FeCl₂ complexes within the tris(2‐pyridylmethyl)amine series (N. K. Thallaj et al. Chem. Eur. J., 2008 , 14, 6742–6753) involves coordination of O₂ to the metal centre and that this reaction occurs following initial dissociation of the bound equatorial chloride anion. We also report evidence of the formation of a reduced form of dioxygen by an inner‐sphere mechanism, thus leading to modification of the ligand. The solid‐state structures of [FeCl₂L] complexes (L¹=mono(α‐pivalamidopyridylmethyl)bis(2‐pyridylmethyl)amine, L²=mono(α‐pivalesteropyridylmethyl)bis(2‐pyridylmethyl)amine, L³=bis(α‐pivalamidopyridylmethyl)mono(2‐pyridylmethyl)amine are described, and spectroscopic data support the structural retention in solution. In [FeCl₂L³], the two amide hydrogen atoms stabilise the equatorial chloride anion in such a way that its exchange by a weak ligand is impossible: [FeCl₂L³] is perfectly oxygen‐stable. In [FeCl₂L²], the equatorial chloride anion is completely free to move and coordination of O₂ can take place. The reaction product with [FeCl₂L²] is a μ‐oxo diferric complex in which the ester function has been transformed into a phenol group. This conversion can be seen as a hydrolysis reaction in basic medium, hence supporting the initial formation of a reduced form of dioxygen in the medium. Complex [FeCl₂L¹] exhibits a very weak reactivity with O₂, in line with a semistabilised equatorial chloride counteranion.     

Exploiting the Distal Reactivity of Indolyl Methylenemalononitriles: An Asymmetric Organocatalyzed [4+2] Cycloaddition with Enals Enables the Assembly of Elusive Dihydrocarbazoles

An unprecedented technique for the in situ generation of indolyl ortho‐quinodimethanes from 2‐methylindole‐based methylenemalononitriles by amine‐mediated remote C(sp³)?H deprotonation was developed. These intermediates were efficiently trapped by diverse enals to provide a rapid entry to 2,9‐dihydro‐1H‐carbazole‐3‐carboxyaldehyde structures through a formal asymmetric [4+2] eliminative cycloaddition governed by a α,α‐diphenylprolinol trimethylsilyl ether catalyst.     

Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine

The formation of amides and peptides often necessitates powerful yet mild reagent systems. The reagents used, however, are often expensive and highly elaborate. New atom‐economical and practical methods that achieve such goals are highly desirable. Ideally, the methods should start with substrates that are readily available in both chiral and non‐chiral forms and utilize cheap reagents that are compatible with a wide variety of functional groups, steric encumberance, and epimerizable stereocenters. A direct oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I₂ and K₂CO₃ under O₂. Contrary to expectations, a 1:1 halogen‐bonded complex forms between the iodonium source and the amine, which reacts with nitronates to form α‐iodo nitroalkanes as precursors to the amides.     

Structural analysis of pentacyclic triterpenes from the gum resin of Boswellia serrata by NMR spectroscopy

3α‐Acetyl‐β‐boswellic acid ( 1 ), 3α‐acetyl‐α‐boswellic acid ( 2 ), 3α‐acetyl‐9,11‐dehydro‐β‐boswellic acid ( 3 ), 3α‐acetyl‐9,11‐dehydro‐α‐boswellic acid ( 4 ) and 3α‐acetyl‐11‐keto‐β‐boswellic acid ( 5 ) were isolated from the gum resin of Boswellia serrata. 1D and 2D NMR (COSY45, HMQC, HMBC, ROESY) spectra at 500 MHz were used for shift assignments and structure verification. All boswellic acids investigated share the cis conformation at ring D/E and the 3α orientation of the acetyl ester group. Owing to high‐order spectra, NMR could not determine the exact conformation of H‐20/H‐30 of the β‐boswellic acids. 3α‐Acetyl‐β‐boswellic acid methyl ester ( 1 ^′) was synthesized for experiments with a shift reagent, Eu(fod)₃, that enhanced the resolution considerably. The oxygen atoms of the 3α‐acetyl group form the apparent complex binding site for the shift reagent. Copyright © 2003 John Wiley & Sons, Ltd.     

A 13C-NMR spectral study of cellulose and glucopyranose dissolved in the NH3/NH4SCN solvent system

The ¹³C-NMR chemical shifts of a cellulose with a DP_w of 23 dissolved in the NH₃/NH₄SCN solvent system were found to be very similar to those of cellulose dissolved in DMSO (cellulose oligomers), in the LiCl/DMAC system and in the N-methylmorpholine N-oxide/DMSO system. It was concluded from this that cellulose does not react with the NH₃/NH₄SCN solvent. It was found, however, that glucose reacts with the solvent at C-1 to form β-D -glucopyranosy-lamine. Separation of this compound from the solvent resulted in another compound which was determined to be β,β-di-D -glucopyranosylamine. The compounds β-D -glucopyranosylamine, N-acetyl-2,3,4,6-tetra-O-acetyl-β-D -glucopyranosylamine, β,β-di-D -glucopyranosylamine, α,β-di-D -glucopyranosylamine, 2,3,4,6,2′,3′,4′,6′-octa-O-acetyl-α,β-di-D -glucopyranosylamine were all synthesized and the ¹³C-NMR chemical shifts of these compounds are reported. It was also found that for the low-DP cellulose sample which was used the reducing end group existed and had reacted with the solvent to form an amine at C-1.     

Kinetics of Complexation of Uranium with 2-(5-Bromo-2-Pyridylazo)-5-(Diethylamino) Phenol (Br-PADAP) in a 1:1 Water-Ethanol Medium

2-(5-Bromo-2-pyridylazo)-5-(diethylamino) phenol (Br-PADAP) forms a 1:1 complex with the uranyl ion in the presence of sulphosalicylic acid, which acts as stabilizer for this complex in the triethanol amine/perchloric acid buffer system. A change in the stoichiometry of the complex was seen at pH<5. Kinetic measurements were carried out using stopped-flow spectrophotometer in the presence of an excess concentration of U(VI) in the pH range 6.5 to 8. The dependence of the pseudo-first-order rate constant, k(obs), on the concentrations of U(VI), ligand and hydrogen ion showed that Br-PADAP reacts with UO₂(OH)⁺ to form an intermediate species (equilibrium constant = 1.28×10⁴mol.dm⁻³) that then rearranges (rate constant = 5.6×10⁻²s⁻¹) to form the product species. UO₂(OH)⁺ is present in equilibrium with the unreactive species UO₂(OH)₂, as well as with the unreactive sulfosalicylic acid complex.     

Experiment and Theory Clarify: Sc+ Receives One Oxygen Atom from SO2 to Form ScO+, which Proves to be a Catalyst for the Hidden Oxygen-Exchange with SO2

Using Fourier-transform ion cyclotron resonance mass spectrometry, it was experimentally determined that Sc⁺ in the highly diluted gas phase reacts with SO₂ to form ScO⁺ and SO. By ¹⁸O labeling, ScO⁺ was shown to play the role of a catalyst when further reacting with SO₂ in a Mars-van Krevelen-like (MvK) oxygen exchange process, where a solid catalyst actively reacts with the substrate but emerges apparently unchanged at the end of the cycle. High-level quantum chemical calculations confirmed that the multi-step process to form ScO⁺ and SO is exoergic and that all intermediates and transition states in between are located energetically below the entrance level. The reaction starts from the triplet surface; although three spin-crossing points with minimal energy have been identified by computational means, there is no evidence that a two-state scenario is involved in the course of the reaction, by which the reactants could switch from the triplet to the singlet surface and back. Pivotal to the oxygen exchange reaction of ScO⁺ with SO₂ is the occurrence of a highly symmetric four-membered cyclic intermediate by which two oxygen atoms become equivalent.     

N‐Silylation of Amines Mediated by Et3SiH/KOtBu

Silylation of primary and secondary amines is reported, using triethylsilane as the silylating reagent in the presence of potassium tert‐butoxide (KO^tBu). The reaction proceeds well in the presence of 0.2 equiv. of KO^tBu. In competition experiments, aniline is selectively silylated over aliphatic amines. Computational studies support a catalytic mechanism which is initiated by KO^tBu interacting with the silane to form KH and silylated amine. The KH then takes over the role of base in the propagation of the cyclic mechanism and deprotonates the amine. This reacts with R₃SiH to afford the product R₃SiNR′R′′ and regenerate KH.     

A Selective C−H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine

Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot from either commercially available aryl iodides or arylboronic acids. The aryne intermediates are generated by ortho‐C?H deprotonation of aryl(mesityl)iodonium salt with a commercially available amide base and trapped in a cycloaddition reaction with furan in moderate to good yields. Coupling partners for the aryne intermediates beyond furan are also described, including benzyl azide and alicyclic amine nucleophiles. The regio‐ and chemoselectivity of this reaction is discussed and evidence for the spectator aryl ligand of the iodonium salt as a critical control element in selectivity is presented.     

Palladium‐Catalyzed Fluoroarylation of gem‐Difluoroalkenes

A Pd‐catalyzed fluoroarylation of gem ‐difluoroalkenes with aryl halides is reported. By taking advantage of the in situ generated α‐CF₃‐benzylsilver intermediates derived from the nucleophilic addition of silver fluoride to gem ‐difluoroalkenes, this strategy bypasses the use of a strong base, thus enabling a mild and general synthetic method for ready access to non‐symmetric α,α‐disubstituted trifluoroethane derivatives.     

Synthesis and characterization of new platinum(II) phosphinate complexes

The syntheses of platinum(II) complexes of bis(dimethylphosphinylmethylene)amine and bis(aminomethyl)phosphinic acid were investigated. In the case of bis(dimethyl-phosphinylmethylene)amine the reaction with K₂[PtCl₄] yields the potassium amino-trichloroplatinate K[PtCl₃L] (L?=?bis(dimethylphosphinylmethylene)amine), which was characterized by multinuclear (¹H, ¹³C, ³¹P, and ¹⁹⁵Pt) NMR spectroscopy in solution. Bis(aminomethyl)phosphinic acid reacts with K₂[PtCl₄] under strictly controlled pH conditions to give colorless crystals of the cisplatin analog K[PtCl₂L′] (L′?=?bis(aminomethyl)phosphinate). This complex was characterized by multinuclear NMR spectroscopy in solution as well as by single-crystal X-ray diffraction in the solid state. The bis(aminomethyl)phosphinate coordinates to platinum via both amino functions, thus acting as a chelating ligand.     

The effect of oxygen on the three‐component radical photoinitiator system: Methylene blue,N‐methyldiethanolamine,and diphenyliodonium chloride

In this article, we extend our mechanistic study of the three‐component radical photoinitiator system, consisting of methylene blue (MB), N‐methyldiethanolamine, and diphenyliodonium chloride, by investigating the influence of oxygen on the rate of the consumption of MB dye. The mechanism involves electron transfer/proton transfer from the amine to the dye as the primary photochemical reaction. Oxygen quenches the triplet state of the dye, leading to retardation of the reaction. We used time‐resolved steady‐state fluorescence monitoring to observe the MB concentration in situ in both a constant oxygen environment and a sealed reactor as the dye is consumed via photoreaction. In the sealed reactor, we observed a retardation period (attributed to the presence of oxygen) followed by rapid exponential decay of the MB fluorescence after the oxygen was depleted. On the basis of the impact of the amine and iodonium concentrations on the fluorescence intensity and the duration of the retardation period, our proposed mechanism includes an oxygen‐scavenging pathway, in which the tertiary amine radicals formed in the primary photochemical process consume the oxygen via a cyclic reaction mechanism. The iodonium salt is an electron acceptor, acting to reoxidize the neutral dye radical back to its original state and allowing it to reenter the primary photochemical process. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3336–3346, 2000     

Investigations on the Reactivity of Copper(I) Complexes with a N3S Thioether Ligand System

In the active site of several copper monooxygenases, thioether residues are coordinated through the sulfur atom, e. g. dopamine-β-monooxygenase (DβM). The reaction of dioxygen with a series of copper(I) complexes with thioether groups in tripodal ligands based on either derivatives of tris(2-pyridylmethyl)amine (TMPA) or a guanidine system were investigated by low-temperature stopped-flow measurements. The formation of labile intermediates, an end-on superoxido complex, and μ-1,2-trans-peroxido copper(II) complexes were spectroscopically detected and a kinetic analysis allowed the calculation of activation parameters for these reactions supporting the postulated mechanism. Most interesting was the finding that replacing the ethyl group in the tren-guanidine derivative (^TMGEt)₂(SEt^Et)N with a methyl group allowed a dramatic increase in the stability of the formed superoxido copper complex. Measurements with ozone were performed in order to find an alternative way to obtain and stabilize the labile intermediates.     

A mechanistic investigation of a three‐component radical photoinitiator system comprising methylene blue,N‐methyldiethanolamine,and diphenyliodonium chloride

Three‐component systems, which contain a light‐absorbing species (typically a dye), an electron donor (typically an amine), and a third component (usually an iodonium salt), have emerged as efficient, visible‐light‐sensitive photoinitiators. Although three‐component systems have been consistently found to be faster and more efficient than their two‐component counterparts, these systems are not well understood and a number of distinct mechanisms have been reported in the literature. In this contribution, photodifferential scanning calorimetry and in situ, time‐resolved, laser‐induced, steady‐state fluorescence spectroscopy were used to study the initiation mechanism of the three‐component system methylene blue, N‐methyldiethanolamine and diphenyliodonium chloride. Kinetic studies based upon photodifferential scanning calorimetry reveal a significant increase in polymerization rate with increasing concentration of either the amine or the iodonium salt. However, the laser‐induced fluorescence experiments show that while increasing the amine concentration dramatically increases the rate of dye fluorescence decay, increasing the DPI concentration actually slows consumption of the dye. We concluded that the primary photochemical reaction involves electron transfer from the amine to the dye. We suggest that the iodonium salt reacts with the resulting dye‐based radical (which is active only for termination) to regenerate the original dye and simultaneously produce a phenyl radical (active in initiation) derived from the diphenyliodonium salt. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 2057–2066, 2000     

Iridium α-Carboxyimine Complexes Hyperpolarized with para-Hydrogen Exist in Nuclear Singlet States before Conversion into Iridium Carbonates

The formation and hyperpolarization of an [Ir(H)₂(amine)(IMes)(η²-imine)]Cl complex that can be created in a hyperpolarized nuclear singlet state is reported. These complexes are formed when an equilibrium mixture of pyruvate, amine (benzylamine or phenylethylamine), and the corresponding imine condensation product, react with preformed [Ir(H)₂(amine)₃(IMes)]Cl. These iridium α-carboxyimine complexes exist as two regioisomers differentiated by the position of amine. When examined with para-hydrogen the hydride resonances of the isomer with amine trans to hydride become strongly hyperpolarized. The initial hydride singlet states readily transfer to the corresponding ¹³C₂ state in the labelled imine and exhibit magnetic state lifetimes of up to 11 seconds. Their ¹³C signals have been detected with up to 420 fold signal gains at 9.4 T. On a longer timescale, and in the absence of H₂, further reaction leads to the formation of neutral carbonate containing [Ir(amine)(η²-CO₃)(IMes)(η²-imine)]. Complexes are characterized by, IR, MS, NMR and X-ray diffraction.     

Reaction of catalytic enantioselective reductive aminolysis of δ2-oxazolin-5-ones as a method of asymmetric synthesis of α-amino acids

This investigation is devoted to the interaction of Δ²-oxazolin-5-ones, S(—)-α-phenylethy lamine and H₂ in the presence of PdCl₂ which yields α-phenylethylamides of acylamino acids of the S,S configuration, hydrolysis of the latter compounds resulting in the formation of optically pure amino acids and providing for chiral amine recycling. In DME, double bond saturation and ring opening in Δ²-oxazolin-5-one occur within the catalytic complex sphere without the intermediate formation of saturated oxazolinones or unsaturated amides. In t-BuOH, saturated oxazolinones are formed as intermediates. The catalyst formed in situ was shown to be a zero-valent Pd complex with S(—)-α-phenylethylamine stabilized by substrate coordination. The stereochemical pathway of the reactions has been traced. Reductive aminolysis involves cis-addition of H₂, while in reductive methanolysis H₂ trarns-addition occurs. The suggested process mechanism accounts for the ratio of aminolysis and racemization rates for saturated oxazolinones and the ratio of diastereomers of α-phenylethylamides of acylamino acids obtained by reacting unsaturated Δ²oxazolin-5-ones with S(—)-α-phenyl-ethylamine. In agreement with the postulated mechanism, the catalyst enantioselectivity is observed at the steps of substrate addition to the catalyst and proton transfer to the α-C-center, provided the process is carried out in DME. In the case of t-BuOH, the enantiodifferentiating action of the catalyst vanishes as a result of racemization, and process stereo selectivity appears at the step of saturated oxazolinone aminolysis with a chiral amine.     

Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic Substitution of Aryliodonium Salts

Aryliodonium salts have become precursors of choice for the synthesis of ¹⁸F‐labeled tracers for nuclear imaging. However, little is known on the reactivity of these compounds with heavy halides, that is, radioiodide and astatide, at the radiotracer scale. In the first comparative study of radiohalogenation of aryliodonium salts with ¹²⁵I^? and ²¹¹At^?, initial experiments on a model compound highlight the higher reactivity of astatide compared to iodide, which could not be anticipated from the trends previously observed within the halogen series. Kinetic studies indicate a significant difference in activation energy (E_a=23.5 and 17.1 kcal mol^?1 with ¹²⁵I^? and ²¹¹At^?, respectively). Quantum chemical calculations suggest that astatination occurs via the monomeric form of an iodonium complex whereas iodination occurs via a heterodimeric iodonium intermediate. The good to excellent regioselectivity of halogenation and high yields achieved with diversely substituted aryliodonium salts indicate that this class of compounds is a promising alternative to the stannane chemistry currently used for heavy radiohalogen labeling of tracers in nuclear medicine.     

Second-order polarization propagator calculations of dynamic dipole polarizabilities and C6 coefficients

The frequency-dependent dipole polarizability, α(E), is calculated using the second-order polarization propagator approximation (SOPPA ). We have shown how to express α(E) as a function of E² and thus obtained a form of α(E) that can be used to compute C₆-coefficients without invoking complex arithmetic. For He we find that SOPPA recovers a large fraction of the correlation contribution for all frequencies, whereas for H₂ where the correlation contributions are much smaller and also basis set-dependent, we find a less definite trend of SOPPA relative to RPA .     

On the mechanism of interaction between copper (I) and O2

The mechanism of the interaction of Cu⁺-α,α-dipyridyl complex (Cu⁺L₂) with O₂ in both neutral and acid media was studied by the stopped-flow method. The dependence of the mechanism on the acidity of the medium was established. In an acid medium H⁺ participated in a direct O₂ reduction to HO₂ by interaction with an oxygen adduct L₂Cu⁺O₂ formed without displacement of ligand molecules. In a neutral medium the reaction rate was limited by inner sphere charge transfer from Cu⁺ to O₂ to form an oxygen “charge transfer” complex L₂CuO⁺₂. The latter interacted either with the second ion Cu⁺L₂ or with the free ligand, or else it dissociated, reversibly or irreversibly, to form a radical anion O^?₂. The bimolecular rate constants of the oxygen “adduct” and “charge transfer” complex formation appeared to be k_bi = (1.0 ± 0.1) × 10⁵ and (1.5 ± 0.2) × 10⁴M^?1?sec^?1, respectively. The effective termolecular rate constants of O₂ reduction to HO₂ in an acid medium (with contribution from H⁺) and to O^?₂ in a neutral medium (with contribution from α,α-dipyridyl) were k_ter = 2.7 × 10⁸ and 10⁷M^?2?sec^?1. The rate constants of the elementary steps were estimated. The auto-oxidation mechanism of the aquoion and complexes of Cu⁺ is discussed in terms of the results obtained.