Of the ortho effect in palladium/norbornene-catalyzed reactions: a theoretical investigation

Mechanistic questions concerning palladium and norbornene catalyzed aryl-aryl coupling reactions are treated in this paper: how aryl halides react with the intermediate palladacycles, formed by interaction of the two catalysts with an aryl halide, and what is the rational explanation of the "ortho effect" (caused by an ortho substituent in the starting aryl halide), which leads to aryl-aryl coupling with a second molecule of aryl halide rather than to aryl-norbornyl coupling. Two possible pathways have been proposed, one involving aryl halide oxidative addition to the palladacycle, the other passing through a palladium(II) transmetalation, also involving the palladacycle, as previously proposed by Cardenas and Echavarren. Our DFT calculations using M06 show that, in palladium-catalyzed reaction of aryl halides, not containing ortho substituents, and norbornene, the intermediate palladacycle formed has a good probability to undergo transmetalation, energetically favored over the oxidative addition leading to Pd(IV). The unselective sp(2)-sp(2) and sp(2)-sp(3) coupling, experimentally observed in this case, can be explained in the framework of the transmetalation pathway since the energetic difference between aryl attack onto the aryl or norbornyl carbon of the palladacycle intermediate is quite small. On the other hand, according to the experimentally observed "ortho effect", selective aryl-aryl coupling only occurs in the reactions of ortho-substituted metallacycles. The present work offers the first possible rationalization of this finding. These in situ formed palladacycles containing an ortho substituent could more easily undergo oxidative addition of an aryl halide rather than reductive elimination from the transmetalation intermediate as a result of a steric clash in the transition state of the latter. The now energetically accessible Pd(IV) intermediate, featuring a Y-distorted trigonal bipyramidal structure, can account for the reported selective aryl-aryl coupling through a reductive elimination which is easier than aryl-norbornyl coupling. Thus, the steric effect represents the main factor that dictates the energetic convenience of the system to follow the Pd(IV) or the transmetalation pathway. Ortho substituents cause a higher energy transition state for reductive elimination from the transmetalation intermediate than for oxidative addition to the metallacycle palladium(II) and the pathway based on the latter predominates.     

Asymmetrical Bifunctional Organic Peroxides as Initiators for the High-Pressure Polymerization of Ethylene

As a follow-up to earlier investigations into the high-pressure polymerization of ethylene with symmetrically substituted bifunctional peroxides, the suitability of 2,5-dimethylhexane-2-t-butylperoxy-5-perpivalate, a peroxide with different substituents on both O—O groups, has been tested. The polymerization tests were carried out in continuous operation in a stirred autoclave at 1700 bar, 240–285°C, a residence time of 60 s, and an initiator concentration of 3–25 mol ppm in the feed. Conversions of up to 30% were achieved. The specific initiator consumption was 0.2–1 g initiator per kg polyethylene. The density of the polymers obtained was 0.915–0.925 g/mL, their average molecular weight was 40 × 10³ to 60 × 10³, and their melt flow index was 0.001–100 g/10 min. On the basis of the molecular weight distribution, polydispersities of 4–7 were obtained.     

Scaling behavior of nonisothermal phase separation

The phase separation process in a critical mixture of polydimethylsiloxane and polyethylmethylsiloxane (PDMS/PEMS, a system with an upper critical solution temperature) was investigated by time-resolved light scattering during continuous quenches from the one-phase into the two-phase region. Continuous quenches were realized by cooling ramps with different cooling rates kappa. Phase separation kinetics is studied by means of the temporal evolution of the scattering vector qm and the intensity Im at the scattering peak. The curves qm(t) for different cooling rates can be shifted onto a single mastercurve. The curves Im(t) show similar behavior. As shift factors, a characteristic length Lc and a characteristic time tc are introduced. Both characteristic quantities depend on the cooling rate through power laws: Lc approximately kappa(-delta) and tc approximately kappa(-rho). Scaling behavior in isothermal critical demixing is well known. There the temporal evolutions of qm and Im for different quench depths DeltaT can be scaled with the correlation length xi and the interdiffusion coefficient D, both depending on DeltaT through critical power laws. We show in this paper that the cooling rate scaling in nonisothermal demixing is a consequence of the quench depth scaling in the isothermal case. The exponents delta and rho are related to the critical exponents nu and nu* of xi and D, respectively. The structure growth during nonisothermal demixing can be described with a semiempirical model based on the hydrodynamic coarsening mechanism well known in the isothermal case. In very late stages of nonisothermal phase separation a secondary scattering maximum appears. This is due to secondary demixing. We explain the onset of secondary demixing by a competition between interdiffusion and coarsening.     

PtCl2-catalyzed cycloisomerizations of 5-en-1-yn-3-ol systems

5-En-1-yn-3-ol substrates bearing a free hydroxyl group or an acyl group are highly versatile partners for PtCl2-catalyzed cycloisomerizations. Electrophilic activation of the alkyne moiety triggers at wish a hydride or an O-acyl migration yielding at the end to regioisomeric keto derivatives. The efficient preparation of Sabina ketone, an important monoterpene precursor, has been worked out.     

Synthesis and characterization of heavier dioxouranium(VI) dihalides

The synthesis and characterization of the dioxouranium(VI) dibromide and iodide hydrates, UO(2)Br(2)x3H(2)O (1), [UO(2)Br(2)(OH(2))(2)](2) (2), and UO(2)I(2)x2H(2)Ox4Et(2)O (3), are reported. Moreover, adducts of UO(2)I(2) and UO(2)Br(2) with large, bulky OP(NMe(2))(3) and OPPh(3) ligands such as UO(2)I(2)(OP(NMe(2))(3))(2) (4), UO(2)Br(2)(OP(NMe(2))(3))(2) (5), and UO(2)I(2)(OPPh(3))(2)(6) are discussed. The structures of the following compounds were determined using single-crystal X-ray diffraction techniques: (1) monoclinic, P2(1)/c, a = 9.7376(8) A, b = 6.5471(5) A, c = 12.817(1) A, beta = 94.104(1) degrees , V = 815.0(1) A(3), Z = 4; (2) monoclinic, P2(1)/c, a = 6.0568(7) A, b = 10.5117(9) A, c = 10.362(1) A, beta = 99.62(1) degrees , V = 650.5(1) A(3), Z = 2; (4) tetragonal, P4(1)2(1)2, a = 10.6519(3) A, b = 10.6519(3) A, c = 24.0758(6) A, V = 2731.7(1) A(3), Z = 4; (5) tetragonal, P4(1)2(1)2, a = 10.4645(1) A, b = 10.4645(1) A, c = 23.7805(3) A, V = 2604.10(5) A(3), Z = 4, and (6) monoclinic, P2(1)/c, a = 9.6543(1) A, b = 18.8968(3) A, c = 10.9042(2) A, beta =115.2134(5) degrees , V = 1783.01(5) A(3), Z = 2. Whereas 1 and 2 are the first UO(2)Br(2) hydrates and the last missing members of the UO(2)X(2) hydrate (X = Cl --> I) series to be structurally characterized, 4 and 6 contain room-temperature stable U(VI)-I bonds with 4 being the first structurally characterized room temperature stable U(VI)-I compound which can be conveniently prepared on a gram scale in quantitative yield. The synthesis and characterization of 5 using an analogous halogen exchange reaction to that used for the preparation of 4 is also reported.     

Insights into the biosynthesis of hormaomycin, an exceptionally complex bacterial signaling metabolite

Hormaomycin produced by Streptomyces griseoflavus is a structurally highly modified depsipeptide that contains several unique building blocks with cyclopropyl, nitro, and chlorine moieties. Within the genus Streptomyces, it acts as a bacterial hormone that induces morphological differentiation and the production of bioactive secondary metabolites. In addition, hormaomycin is an extremely potent narrow-spectrum antibiotic. In this study, we shed light on hormaomycin biosynthesis by a combination of feeding studies, isolation of the biosynthetic nonribosomal peptide synthetase (NRPS) gene cluster, and in vivo and in vitro functional analysis of enzymes. In addition, several nonnatural hormaomycin congeners were generated by feeding-induced metabolic rerouting. The NRPS contains numerous highly repetitive regions that suggest an evolutionary scenario for this unusual bacterial hormone, providing new opportunities for evolution-inspired metabolic engineering of novel nonribosomal peptides.     

MALDI-MS/MS with Traveling Wave Ion Mobility for the Structural Analysis of N-Linked Glycans

The preference for singly charged ion formation by MALDI makes it a better choice than electrospray ionization for profiling mixtures of N-glycans. For structural analysis, fragmentation of negative ions often yields more informative spectra than fragmentation of positive ones but such ions are more difficult to produce from neutral glycans under MALDI conditions. This work investigates conditions for the formation of both positive and negative ions by MALDI from N-linked glycans released from glycoproteins and their subsequent MS/MS and ion mobility behaviour. 2,4,6-Trihydroxyacetophenone (THAP) doped with ammonium nitrate was found to give optimal ion yields in negative ion mode. Ammonium chloride or phosphate also yielded prominent adducts but anionic carbohydrates such as sulfated N-glycans tended to ionize preferentially. Carbohydrates adducted with all three adducts (phosphate, chloride, and nitrate) produced good negative ion CID spectra but those adducted with iodide and sulfate did not yield fragment ions although they gave stronger signals. Fragmentation paralleled that seen following electrospray ionization providing superior spectra than could be obtained by PSD on MALDI-TOF instruments or with ion traps. In addition, ion mobility drift times of the adducted glycans and the ability of this technique to separate isomers also mirrored those obtained following ESI sample introduction. Ion mobility also allowed profiles to be obtained from samples whose MALDI spectra showed no evidence of such ions allowing the technique to be used in conditions where sample amounts were limiting. The method was applied to N-glycans released from the recombinant human immunodeficiency virus glycoprotein, gp120.     

Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometric analysis of the recombinant human macrophage colony stimulating factor β and derivatives

The potential of electrospray ionization (ESI) Fourier transform ion cyclotron mass spectrometry (FTICR-MS) to assist in the structural characterization of monomeric and dimeric derivatives of the macrophage colony stimulating factor beta (rhM-CSF beta) was assessed. Mass spectrometric analysis of the 49 kDa protein required the use of sustained off-resonance irradiation (SORI) in-trap cleanup to reduce adduction. High resolution mass spectra were acquired for a fully reduced and a fully S-cyanylated monomeric derivative (approximately 25 kDa). Mass accuracy for monomeric derivatives was better than 5 ppm, after applying a new calibration method (i.e., DeCAL) which eliminates space charge effects upon high accuracy mass measurements. This high mass accuracy allowed the direct determination of the exact number of incorporated cyanyl groups. Collisionally induced dissociation using SORI yielded b- and y-fragment ions within the N- and C-terminal regions for the monomeric derivatives, but obtaining information on other regions required proteolytic digestion, or potentially the use of alternative dissociation methods.     

Chemoselective Catalysis with Organosoluble Lewis Acidic Polyoxotungstates

The preparation of new organosoluble Lewis acidic polyoxometalates (POMs) is reported. These complexes were prepared by the incorporation of Zr, Sc, and Y atoms into the corresponding monolacunary Dawson [P₂W₁₇O₆₁]^10? and Keggin [PW₁₁O₃₉]^7? polyoxotungstates. The catalytic activity of these compounds was evaluated for C? C bond formation in the Diels–Alder, Mannich, and Mukaiyama‐type reactions. Comparisons with previously described Lewis acidic POMs are reported. Competitive reactions between imines and aldehydes or between various imines demonstrated that fine tuning of the reactivity could be reached by varying the metal atom incorporated into the polyanionic framework. A series of experiments that employed pyridine derivatives allowed us to distinguish between the Lewis and induced Brønsted acidity of the POMs. These catalysts activate imines in a Lewis acidic way, whereas aldehydes are activated by indirect Brønsted catalysis.