Dinitrogen Cleavage by a Heterometallic Cluster Featuring Multiple Uranium-Rhodium Bonds.

Reduction of dinitrogen (N2) is a major challenge for chemists. Cooperation of multiple metal centers to break the strong N2 triple bond has been identified as a crucial step in both the industrial and the natural ammonia syntheses. However, reports of the cleavage of N2 by a multimetallic uranium complex remain extremely rare, although uranium species were used as catalyst in the early Harber-Bosch process. Here we report the cleavage of N2 to two nitrides by a multimetallic uranium-rhodium cluster at ambient temperature and pressure. The nitride product further reacts with acid to give substantial yields of ammonium. The presence of uranium-rhodium bond in this multimetallic cluster was revealed by X-ray crystallographic and computational studies. This study demonstrates that the multimetallic clusters containing uranium and transition metals are promising materials for N2 fixation and reduction.

A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.

Genetic polymorphism and environment each influence individual variability in drug metabolism and disposition. It is preferable to predict such variability, which may affect drug efficacy and toxicity, before drug administration. We examined individual differences in the pharmacokinetics of atorvastatin by applying gas chromatography-mass spectrometry-based metabolic profiling to predose plasma samples from 48 healthy volunteers. We determined the level of atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With the endogenous molecules, which showed a good correlation with pharmacokinetic parameters, a refined partial least-squares model was calculated based on predose data from a training set of 36 individuals and exhibited good predictive capability for the other 12 individuals in the prediction set. In addition, the model was successfully used to predictively classify individual pharmacokinetic responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as candidate markers for predicting by showing better predictive capability for explaining individual differences than a conventional physiological index. These results suggest that a pharmacometabonomic approach offers the potential to predict individual differences in pharmacokinetics and therefore to facilitate individualized drug therapy.

Tandem halogenation/Michael-initiated ring-closing reaction of α,ß-unsaturated nitriles and activated methylene compounds: one-pot diastereoselective synthesis of functionalized cyclopropanes.

An efficient one-pot synthetic route to highly substituted cyclopropanes has been developed from readily available α,ß-unsaturated nitriles and doubly activated methylene compounds under very mild conditions in a highly diastereoselective manner, which involves halogenation, Michael addition and intramolecular ring-closing reaction sequences.

Divergent synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from 2,4-pentadienenitriles and isocyanides.

An efficient and divergent one-pot synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from readily accessible 2,4-pentadienenitriles with isocyanide based on reaction condition selection has been described. The reaction of 2,4-pentadienenitriles with ethyl isocyanoacetate undergoes a formal [2 + 3] annulation either to generate 2,3-dihydro-1H-pyrroles in the presence of DBU (0.3 equiv.) in EtOH at room temperature or to give 3-alkyl-1H-pyrroles in the presence of DBU (2.0 equiv.) in EtOH under reflux. Moreover, the 2,3-dihydro-1H-pyrroles could be converted to 3-alkenyl-1H-pyrroles with DDQ as an oxidant.

Homogeneous and stereoselective copper(II)-catalyzed monohydration of methylenemalononitriles to 2-cyanoacrylamides.

A facile and efficient route for the homogeneous and highly stereoselective monohydration of substituted methylenemalononitriles to (E)-2-cyanoacrylamides catalyzed by copper(II) acetate monohydrate in acetic acid containing 2% water is described, and a mechanism is proposed. The protocol has proved to be suitable for the monohydration of dicyanobenzenes and 2-substituted malononitriles.

[5C + 1N] Annulation of 2,4-pentadienenitriles with hydroxylamine: a synthetic route to multi-substituted 2-aminopyridines.

A facile and efficient synthetic route to multi-substituted 2-aminopyridines has been developed via a formal [5C + 1N] annulation of readily available 2,4-pentadienenitriles with hydroxylamine (NH(2)OH) under very mild conditions, which involves sequential intermolecular aza-nucleophilic addition of hydroxylamine, intramolecular aza-cyclization, and dehydration reactions.

Dinitrogen cleavage and hydrogenation to ammonia with a uranium complex.

The Haber-Bosch process produces ammonia (NH3) from dinitrogen (N2) and dihydrogen (H2), but requires high temperature and pressure. Before iron-based catalysts were exploited in the current industrial Haber-Bosch process, uranium-based materials served as effective catalysts for production of NH3 from N2. Although some molecular uranium complexes are known to be capable of combining with N2, further hydrogenation with H2 forming NH3 has not been reported to date. Here, we describe the first example of N2 cleavage and hydrogenation with H2 to NH3 with a molecular uranium complex. The N2 cleavage product contains three uranium centers that are bridged by three imido µ 2-NH ligands and one nitrido µ 3-N ligand. Labeling experiments with 15N demonstrate that the nitrido ligand in the product originates from N2. Reaction of the N2-cleaved complex with H2 or H+ forms NH3 under mild conditions. A synthetic cycle has been established by the reaction of the N2-cleaved complex with trimethylsilyl chloride. The isolation of this trinuclear imido-nitrido product implies that a multi-metallic uranium assembly plays an important role in the activation of N2.

Photochemical Synthesis of Transition Metal-Stabilized Uranium(VI) Nitride Complexes.

Uranium nitrides play important roles in dinitrogen activation and functionalization and in chemistry for nuclear fuels, but the synthesis and isolation of the highly reactive uranium(VI) nitrides remains challenging. Here, we report an example of transition metal (TM) stabilized U(VI) nitride complexes, which are generated by the photolysis of azide-bridged U(IV)-TM (TM = Rh, Ir) precursors. The U(V) nitride intermediates with bridged azide ligands are isolated successfully by careful control of the irradiation time, suggesting that the photolysis of azide-bridged U(IV)-TM precursors is a stepwise process. The presence of two U(VI) nitrides stabilized by three TMs is clearly demonstrated by an X-ray crystallographic study. These TM stabilized U(V) nitride intermediates and U(VI) nitride products exhibit excellent stability both in the solid-state and in THF solution under ambient light. Density functional theory calculations show that the photolysis necessary to break the N-N bond of the azide ligands implies excitation from uranium f-orbital to the lowest unoccupied molecular orbital (LUMO), as suggested by the strong antibonding N-(N2) character present in the latter.

Isolation of heterometallic cerium(iii) complexes with a multidentate nitrogen-phosphorus ligand.

Heterometallic complexes play an important role in catalysis and activation of small molecules due to the synergistic effects from different metals. Here we report a straightforward strategy to construct a series of heterobimetallic complexes of bromine bridged cerium(iii)-alkali metal or group 9 metals using a multidentate nitrogen-phosphorus ligand.

Formal [4+2] annulation of enaminones and cyanomethyl sulfur ylide: one-pot access to polysubstituted pyridin-2(1H)-ones.

A facile and efficient one-pot synthesis of polysubstituted pyridin-2(1H)-ones from readily available enaminones and the cyanomethyl sulfonium bromide salt in the presence of cesium carbonate is developed, and a mechanism involving sequential nucleophilic vinylic substitution (S(N)V), intramolecular nucleophilic cyclization and dealkylation reactions is proposed.

PPA-mediated C-C bond formation: a synthetic route to substituted indeno[2,1-c]quinolin-6(7H)-ones.

A facile and efficient synthesis of substituted indeno[2,1-c]quinolin-6(7H)-ones from a variety of α-acyl N-arylcinnamamides mediated by polyphosphoric acid (PPA) is described, and a mechanism involving the formation of a dicationic superelectrophile and subsequent double intramolecular nucleophilic cyclization reactions is proposed.

Copper-catalyzed three-component reaction: solvent-controlled regioselective synthesis of 4-amino- and 6-amino-2-iminopyridines.

Regioselective synthesis of multisubstituted 4-amino- and 6-amino-2-iminopyridines has been developed via the copper-catalyzed three-component reaction based on the reaction conditions selection. The reaction of sulfonyl azides, alkynes, and 2-[(amino)methylene]malononitriles catalyzed by copper(I) iodide in tetrahydrofuran at room temperature afforded substituted 4-amino-2-iminopyridines, whereas, in N,N-dimethylformamide at 50 °C under N2, it generated substituted 6-amino-2-iminopyridines as predominant products.

Regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles from enaminones.

A highly regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles from enaminones based on reaction condition selection is reported. 3-Arylaminoisoxazoles were produced by treating enaminones with aqueous hydroxylamine in DMF at 100 °C, whereas 5-arylaminoisoxazoles were synthesized by subjecting enaminones to aqueous hydroxylamine in the presence of KOH and TBAB in water under reflux. A mechanism for the regioselective synthesis of 3-arylamino- and 5-arylaminoisoxazoles is proposed.