Mass spectrometry of heterocyclic compounds. I—the behaviour of some quaternary heterocyclic iodides under electron impact

The mass spectra of five quaternary heterocyclic iodides have been investigated. The main thermal process is the anhydro base formation by HI elimination. The influence of the second heteroatom, X, on the fragmentation mode of the thermally produced anhydro bases is analysed.     

The total synthesis of (±)-arisugacin A

A 20-step total synthesis of (±)-arisugacin A with an overall yield of 2.1% is described here in detail. This synthesis features a formal [3+3] cycloaddition reaction of α,β-unsaturated iminium salts with 6-aryl-4-hydroxy-2-pyrones through a highly stereoselective 6π-electron electrocyclic ring-closure of 1-oxatriene. A strategic dihydroxylation-deoxygenation protocol leading to the desired angular C12a-OH was developed to serve as a critical step in leading to the final total syntheses of arisugacin A. This synthetic endeavor also led to an interesting and unexpected retro-aldol-aldol sequence in the AB-ring.     

Metal-bridging mechanism for O-O bond cleavage in cytochrome C oxidase

Density functional theory (B3LYP) has been applied to large models of the Fe(II)-Cu(I) binuclear center in cytochrome oxidase, investigating the mechanism of O-O bond cleavage in the mixed valence form of the enzyme. To comply with experimental information, the O(2) molecule is assumed to be bridging between iron and copper during the O-O bond cleavage, leading to the formation of a ferryl-oxo group and a cupric hydroxide. In accord with previous suggestions, the calculations show that it is energetically feasible to take the fourth electron needed in this reaction from the tyrosine residue that is cross-linked to one of the copper ligands, resulting in the formation of a neutral tyrosyl radical. However, the calculations indicate that simultaneous transfer of an electron and a proton from the tyrosine to dioxygen during bond cleavage leads to a barrier more than 10 kcal/mol higher than that experimentally determined. This may be overcome in two ways. If an extra proton in the binuclear center assists in the mechanism, the calculated reaction barrier agrees with experiment. Alternatively, the fourth electron might initially be supplied by a residue in the vicinity other than the tyrosine.     

Metal Complexes with Macrocyclic Ligands. Part XLIII. Tetraazamacrocyclic nickel(II) and copper(II) complexes with aliphatic methylthio- and methoxy-substituted pendant chains

The 14-membered tetraazamacrocyclic Ni²⁺ and Cu²⁺ complexes of 4 (1, 4, 8-trimethyl-11-[(2-methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), 5 . (1, 4-dimethyl-8, 11-bis[2-(methylthio)ethyl]-l, 4, 8, 11-tetraazacyclotetradecane), and 7 (1, 4, 8, ll-tetrakis[2-(methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), with pne, two, and four methylthio-substituted pendant chains, respectively, and the Ni²⁺ complex of 6 (1, 4-dimethyl-8, 11-bis (2-methoxyethyl)-1, 4, 8, 11-tetraazacyclotetradecane), with two methoxy-substituted pendant chains, were synthesized and their chemistry studied with regard to modelling F430. Solution spectra in H₂O, MeCN, and DMF indicate participation of the side chain in metal coordination when the donor group is a thioether, whereas no coordination with the metal ion is observed with the ether group. Similarly the X-ray structures of the thioether-containing compounds [Ni( 5 )](ClO₄)₂, [Cu( 5 )](ClO₄)₂, and [Cu( 7 )](ClO₄)₂ show a coordination number of 5, whereas that of [Ni( 6 )](ClO₄)₂ with ether pendant chains, shows a coordination number of 4. Cyclic voltammetry of these complexes in MeCN reveals that Ni²⁺ is reversibly reduced to Ni⁺ between ?0.64 and ?0.77 V vs. SCE, the potential being influenced by the nature and number of the pendant chains. At more negative potentials, the thioether is cleaved, whereby a thiol is formed; the thiol is then oxidized at ca. + 0.8 V vs. SCE, when a glassy carbon electrode is used, or at ca. 0 V vs. SCE at a dropping Hg electrode. No cleavage of the ether bond in [Ni( 6 )](ClO₄)₂ is observed under similar conditions.     

Metal Complexes with Macrocyclic Ligands. Part XLVI. Synthesis and structures of dinuclear metal complexes of bis-macrocycles having a pyrazole bridging unit

Three bis-macrocyclic ligands consisting of two N₃-, N₂S-, or NS₂-cyclononane rings, i.e., of two octahydro-1H-1,4,7-triazonine, octahydro-1,4,7-thiadiazonine, or hexahydro-5H-1,4-7-dithiazonine rings, connected by a 1H-pyrazolediyl unit were prepared. They form dinuclear Cu^II and Ni^II complexes which are able to bind one additional exogenous bridging molecule such as Cl^?, Br^?, N, SO, and 1H-pyrazol-1-ide. The structures determined by X-ray diffraction show that each Cu²⁺ is coordinated by the three donor atoms of the macrocyclic ring, by a pyrazolidodiyl N-atom, by an atom of the exogenous bridging ligand, and sometimes by a solvent molecule. In the majority of the Cu²⁺ cases, the metal ion exhibits square-pyramidal or trigonal-bipyramidal coordination geometry, except in the sulfato-bridged complex, in which one Cu²⁺ is hexacoordinated with the participation of a water molecule. The X-ray structure of the azide-bridged dinuclear Ni²⁺ complex was also solved and shows that both Ni²⁺ centres have octahedral coordination geometries. In all complexes, the 1H-pyrazolediyl group connecting the macrocycles is deprotonated and bridges the two metal centres, which, depending on the exogenous ligand, have distances between 3.6 and 4.5 Å. In the dinuclear Cu²⁺ complexes, antiferromagnetic coupling is present. The azido-bridged complex shows a very strong interaction with ?2J ≥ 1040 cm^?1; in contrast, the H-pyrazol-1-ide and chloride bridged species have ?2J values of 300 and 272cm^?1, respectively. Cyclic voltammetry of the Cu²⁺ complexes in MeCN reveals a strong dependence of the potentials Cu^II/Cu-^II → Cu^II/Cu^I → Cu^I/Cu^I on the nature of the donor atoms of the macrocycle as well as on the type of bridging molecule. The more S-donors are present in the macrocycle, the higher is the potential, indicating a stabilization of the Cu¹ oxidation state.     

Synthesis,X‐Ray Crystal‐Structure Analysis,and NMR Studies of (η3‐Allyl)palladium(II) Complexes Containing a Novel Dihydro(phosphinoaryl)oxazine Ligand: Application in Palladium‐Catalyzed Asymmetric Synthesis

The novel chiral P,N‐ligand 2‐[2‐(diphenylphosphino)phenyl]‐5,6‐dihydro‐4‐phenyl‐4H‐1,3‐oxazine ( 4 ) was synthesized. The corresponding {dihydro[(phosphino‐ϰP)aryl]oxazine‐ϰN} (η³‐diphenylallyl)palladium(II) hexafluorophosphate 5 and the analogous [Pd(η³‐1,3‐dimethylallyl)] complex 6 were investigated by X‐ray analysis and 1D‐ and 2D‐NMR spectroscopy. The complex 5 exists as `exo'‐syn‐syn isomer in the solid state (Fig. 1). In solution, the same isomer exceeds with 90%. The X‐ray crystal structure of 6 reveals that the dihydro(phosphinoaryl)oxazine ligand coordinates in a pseudo‐enantiomeric conformation compared with that of 5 (Fig. 3). A syn‐anti arrangement of the allyl substituents of 6 is favored in the solid state. <sup>1</sup>H‐NMR Spectroscopic investigations suggest that the auxiliary 6 adopts two conformations. This conformational instability together with `exo'/`endo' and syn/anti isomerization leads to the formation of 6 isomers (Fig. 4). The asymmetric allylic substitution reaction of 1,3‐diphenylallyl acetate with dimethyl malonate in the presence of 4 proceeds with a selectivity of 99% ee. The ee induced by 4 in the catalytic allylic substitution of 1‐methylbut‐2‐enyl acetate is moderate (54%).     

A characterization of the tight 3‐sphere II

Recall that every closed, oriented, connected 3‐manifold M admits a contact form λ. We shall give conditions on a periodic orbit P₀ of the Reeb vector field defined by λ that allows the construction of an open book decomposition of M \ P₀ into embedded planes asymptotic to P₀ such that P₀ is the binding orbit of the decomposition. It follows that M is the tight 3‐sphere. As a by‐product, a new dynamical criterion for the tightness of a contact structure is derived in the proof. The results extend earlier results. © 1999 John Wiley & Sons, Inc.     

Reaction mechanism of apocarotenoid oxygenase (ACO): a DFT study

The mechanism of the oxidative cleavage catalyzed by apocarotenoid oxygenase (ACO) was studied by using a quantum chemical (DFT: B3 LYP) method. Based on the available crystal structure, relatively large models of the unusual active-site region, in which a ferrous ion is coordinated by four histidines and no negatively charged ligand, were selected and used in the computational investigation of the reaction mechanism. The results suggest that binding of dioxygen to the ferrous ion in the active site promotes one-electron oxidation of carotenoid leading to a substrate radical cation and a Fe-bound superoxide radical. Recombination of the two radicals, which can be realized in at least two different ways, yields a reactive peroxo species that subsequently evolves into either a dioxetane or an epoxide intermediate. The former easily decays into the final aldehyde products, whereas the oxidation of the epoxide to the proper products of the reaction requires involvement of a water molecule. The calculated activation barriers favor the dioxetane mechanism, yet the mechanism involving the epoxide intermediate cannot be ruled out.