Synthesis of functionalized indolines and dihydrobenzofurans by iron and copper catalyzed aryl C-N and C-O bond formation

A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N- or O-arylation step leading to indolines, dihydrobenzofurans and six-membered analogues. The general applicability and functional group tolerance of this method was exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process

Evaluating genetic traceability methods for captive bred marine fish and their applications in fisheries management and wildlife forensics

Growing demands for marine fish products is leading to increased pressure on already depleted wild populations and a rise in the aquaculture production. Consequently, more captive bred fish are released into the wild through accidental escape or deliberate restocking, stock enhancement and sea ranching programs. The increased mixing of captive bred fish with wild conspecifics may affect the ecological and/or genetic integrity of wild fish populations. From a fisheries management perspective unambiguous identification tools for captive bred fish will be highly valuable to manage risks. Additionally there is great potential to use these tools in wildlife forensics (i.e. tracing back escapees to their origin and determining mislabelling of seafood products). Using SNP data from captive bred and wild populations of Atlantic cod (Gadus morhua L.) and sole (Solea solea L.), we explored the efficiency of population and parentage assignment techniques for the identification and tracing of captive bred fish. Simulated and empirical data were used to correct for stochastic genetic effects. Overall, parentage assignment performed well when a large effective population size characterizes the broodstock and escapees originate from early generations of captive breeding. Consequently, parentage assignments are particularly useful from a fisheries management perspective to monitor the effects of deliberate releases of captive bred fish on wild populations. Population assignment proved to be more efficient after several generations of captive breeding, which makes it a useful method in forensic applications for well-established aquaculture species. We suggest the implementation of a case by case strategy when choosing the best method

Switching the stereochemical outcome of 6-endo-trig cyclizations; Synthesis of 2,6-Cis-6-substituted 4-oxopipecolic acids

A base-mediated 6-endo-trig cyclization of readily accessible enone-derived α-amino acids has been developed for the direct synthesis of novel 2,6-cis-6- substituted-4-oxo-L-pipecolic acids. A range of aliphatic and aryl side chains were tolerated by this mild procedure to give the target compounds in good overall yields. Molecular modeling of the 6-endo-trig cyclization allowed some insight as to how these compounds were formed, with the enolate intermediate generated via an equilibrium process, followed by irreversible tautomerization/neutralization providing the driving force for product formation. Stereoselective reduction and deprotection of the resulting 2,6-cis-6-substituted 4-oxo-L-pipecolic acids to the corresponding 4-hydroxy-L-pipecolic acids was also performed

On the Unusual Weak Intramolecular C...C Interactions in Ru₃(CO)₁₂: A Case of Bond Path Artifacts Introduced by the Multipole Model?

In a recent publication in this journal, an experimental charge density analysis on the triruthenium cluster Ru₃(CO)₁₂ showed unusual C...C bond paths linking the axial carbonyl ligands [Gervasio, G.; Marabello, D.; Bianchi, R.; Forni, A. <i>J. Phys. Chem. A</i> <b>2010</b>, <i>114</i>, 9368, hereafter GMBF]. These were also observed in one theoretical DFT calculation, and are associated with very low values of ρ(<b>r</b>_b) and ∇²ρ(<b>r</b>_b). Our independent experimental charge density analysis on Ru₃(CO)₁₂ is entirely consistent with GMBF and confirms the presence of these apparent weak interactions in the multipole model density. However, we conclusively demonstrate that these unusual C...C bond paths between the axial carbonyl ligands are in fact artifacts arising from the Hansen-Coppens multipole model, which is used to analyze the experimental data. Numerous relativistic and nonrelativistic gas-phase DFT calculations, using very extensive basis sets and with corrections for dispersion effects, uniformly fail to reproduce these intramolecular features in the QTAIM topology of the electron density. Moreover, multipole fitting of theoretical static structure factors computed from these quantum electron densities results in the reappearance of the C...C bond paths between the axial carbonyl ligands in the derived molecular graphs. On the other hand, using the experimental structure factors to generate “experimental” X-ray constrained DFT wave functions once again yields molecular graphs which do not show these secondary C...C bond paths. The evidence therefore strongly implicates the multipole model as the source of these spurious features and in turn suggests that great caution should be applied in the interpretation of bond paths where the values of ρ(<b>r</b>_b) and ∇²ρ(<b>r</b>_b) are very low

On the Unusual Weak Intramolecular C...C Interactions in Ru₃(CO)₁₂: A Case of Bond Path Artifacts Introduced by the Multipole Model?

In a recent publication in this journal, an experimental charge density analysis on the triruthenium cluster Ru₃(CO)₁₂ showed unusual C...C bond paths linking the axial carbonyl ligands [Gervasio, G.; Marabello, D.; Bianchi, R.; Forni, A. <i>J. Phys. Chem. A</i> <b>2010</b>, <i>114</i>, 9368, hereafter GMBF]. These were also observed in one theoretical DFT calculation, and are associated with very low values of ρ(<b>r</b>_b) and ∇²ρ(<b>r</b>_b). Our independent experimental charge density analysis on Ru₃(CO)₁₂ is entirely consistent with GMBF and confirms the presence of these apparent weak interactions in the multipole model density. However, we conclusively demonstrate that these unusual C...C bond paths between the axial carbonyl ligands are in fact artifacts arising from the Hansen-Coppens multipole model, which is used to analyze the experimental data. Numerous relativistic and nonrelativistic gas-phase DFT calculations, using very extensive basis sets and with corrections for dispersion effects, uniformly fail to reproduce these intramolecular features in the QTAIM topology of the electron density. Moreover, multipole fitting of theoretical static structure factors computed from these quantum electron densities results in the reappearance of the C...C bond paths between the axial carbonyl ligands in the derived molecular graphs. On the other hand, using the experimental structure factors to generate “experimental” X-ray constrained DFT wave functions once again yields molecular graphs which do not show these secondary C...C bond paths. The evidence therefore strongly implicates the multipole model as the source of these spurious features and in turn suggests that great caution should be applied in the interpretation of bond paths where the values of ρ(<b>r</b>_b) and ∇²ρ(<b>r</b>_b) are very low

Ab Initio Study of the (5 R )- and (5 S )-TT Pyrimidine h 5 (6−4) Pyrimidone Photoproducts. Implications on the Design of New Biologically Relevant Analogues

International audienc

Electron density, disorder and polymorphism: high-resolution diffraction studies of the highly polymorphic neuralgic drug carbamazepine

Analysis of neutron and high-resolution X-ray diffraction data on form (III) of carbamazepine at 100 K using the atoms in molecules (AIM) topological approach afforded excellent agreement between the experimental results and theoretical densities from the optimized gas-phase structure and from multipole modelling of static theoretical structure factors. The charge density analysis provides experimental confirmation of the partially localized [pi]-bonding suggested by the conventional structural formula, but the evidence for any significant C-N [pi] bonding is not strong. Hirshfeld atom refinement (HAR) gives H atom positional and anisotropic displacement parameters that agree very well with the neutron parameters. X-ray and neutron diffraction data on the dihydrate of carbemazepine strongly indicate a disordered orthorhombic crystal structure in the space group Cmca, rather than a monoclinic crystal structure in space group P21/c. This disorder in the dihydrate structure has implications for both experimental and theoretical studies of polymorphism