Ligand Hydrogenation during Hydroformylation Catalysis Detected by In Situ High-Pressure Infra-Red Spectroscopic Analysis of a Rhodium/Phospholene-Phosphite Catalyst.

Phospholane-phosphites are known to show highly unusual selectivity towards branched aldehydes in the hydroformylation of terminal alkenes. This paper describes the synthesis of hitherto unknown unsaturated phospholene borane precursors and their conversion to the corresponding phospholene-phosphites. The relative stereochemistry of one of these ligands and its Pd complex was assigned with the aid of X-ray crystal structure determinations. These ligands were able to approach the level of selectivity observed for phospholane-phosphites in the rhodium-catalysed hydroformylation of propene. High-pressure infra-red (HPIR) spectroscopic monitoring of the catalyst formation revealed that whilst the catalysts showed good thermal stability with respect to fragmentation, the C=C bond in the phospholene moiety was slowly hydrogenated in the presence of rhodium and syngas. The ability of this spectroscopic tool to detect even subtle changes in structure, remotely from the carbonyl ligands, underlines the usefulness of HPIR spectroscopy in hydroformylation catalyst development.

CuO-NPs Improve Biosynthesis of Bioactive Compounds in Lettuce.

The application of metallic nanoparticles improves the yield and content of bioactive compounds in plants. The aim of the present study was to determine the effects of the foliar application of copper nanoparticles (CuO-NPs) in the yield and content of bioactive compounds in lettuce. Different concentrations of CuO-NPs (0, 0.5, 1, 2, 4, and 6 mg mL-1) were applied in lettuce. The yield, nutraceutical quality, and enzymatic activity were determined. Foliar spraying of CuO-NPs induced an increase in the biosynthesis of bioactive compounds. In addition to an increase in the activity of the enzymes superoxide dismutase (SOD) and catalase (CAT) in lettuce plants, there were no negative effects on yield. Therefore, with the application of CuO-NPs, better quality lettuces are produced for the human diet due to the higher production of bioactive compounds.

Effects of the Morphology, Surface Modification and Application Methods of ZnO-NPs on the Growth and Biomass of Tomato Plants.

Benefits of nanotechnology in agriculture include reduced fertilizer loss, improved seed germination rate and increased crops quality and yield. The objective of this research was to evaluate the effects of zinc oxide nanoparticles (ZnO-NPs), at 1500 ppm, on tomato (Solanum lycopersicum L.) growth. ZnO-NPs were synthetized to produce either spherical or hexagonal morphologies. In this research, we also studied two application methods (foliar and drench) and nanoparticles' (NPs) surface modification with maltodextrin. The results obtained indicate that ZnO-NP-treated tomato plants significantly increased plant height, stem diameter and plant organs (leaves, stem and root) dry weight compared to plants without NP treatment.

High iso Aldehyde Selectivity in the Hydroformylation of Short-Chain Alkenes.

The hydroformylation of propene to give predominantly iso-butanal has been achieved; class-leading selectivity is possible even at higher temperatures that deliver fast conversion. Racemic rhodium complexes of bidentate phospholane phosphites derived from tropos-biphenols and unusual solvent systems are the key to the selectivity observed.

Understanding a Hydroformylation Catalyst that Produces Branched Aldehydes from Alkyl Alkenes.

This paper reports experimental and computational studies on the mechanism of a rhodium-catalyzed hydroformylation that is selective for branched aldehyde products from unbiased alkene substrates. This highly unusual selectivity relies on a phospholane-phosphite ligand prosaically called BOBPHOS. Kinetic studies using in situ high pressure IR (HPIR) and the reaction progress kinetic analysis methodology suggested two steps in the catalytic cycle were involved as turnover determining. Negative order in CO and positive orders in alkene and H2 were found and the effect of hydrogen and carbon monoxide partial pressures on selectivity were measured. Labeling studies found rhodium hydride addition to the alkene to be largely irreversible. Detailed spectroscopic HPIR and NMR characterization of activated rhodium-hydrido dicarbonyl species were carried out. In the absence of H2, reaction of the rhodium-hydrido dicarbonyl with allylbenzene allowed further detailed spectroscopic characterization of four- and five-coordinate rhodium-acyl species. Under single-turnover conditions, the ratios of branched to linear acyl species were preserved in the final ratios of aldehyde products. Theoretical investigations uncovered unexpected stabilizing CH-π interactions between the ligand and substrate which influenced the high branched selectivity by causing potentially low energy pathways to become unproductive. Energy span and degree of TOF control analysis strongly support experimental observations and mechanistic rationale. A three-dimensional quadrant model was built to represent the structural origins of regio- and enantioselectivity.

Diastereoselective and Branched-Aldehyde-Selective Tandem Hydroformylation-Hemiaminal Formation: Synthesis of Functionalized Piperidines and Amino Alcohols.

Starting from readily available allylglycine, a tandem hydroformylation-hemiaminal formation reaction has been developed for the synthesis of chiral functionalized piperidines, with very good diastereoselectivity and branched regioselectivity using Rh/(S,S,S)-BOBPHOS catalysts. Tandem hydroformylation-hemiacetal formation also proceeds with good diastereoselectivity (88:12), with the hemiacetal product being hydrogenated with retention of stereochemistry to give a chiral intermediate used in the synthesis of the new antibiotic nemonoxacin.

On the Functional Group Tolerance of Ester Hydrogenation and Polyester Depolymerisation Catalysed by Ruthenium Complexes of Tridentate Aminophosphine Ligands.

The synthesis of a range of phosphine-diamine, phosphine-amino-alcohol, and phosphine-amino-amide ligands and their ruthenium(II) complexes are reported. Five of these were characterised by X-ray crystallography. The activities of this collection of catalysts were initially compared for the hydrogenation of two model ester hydrogenations. Catalyst turnover frequencies up to 2400 h(-1) were observed at 85 °C. However, turnover is slow at near ambient temperatures. By using a phosphine-diamine Ru(II) complex, identified as the most active catalyst, a range of aromatic esters were reduced in high yield. The hydrogenation of alkene-, diene-, and alkyne-functionalised esters was also studied. Substrates with a remote, but reactive terminal alkene substituent could be reduced chemoselectively in the presence of 4-dimethylaminopyridine (DMAP) co-catalyst. The chemoselective reduction of the ester function in conjugated dienoate ethyl sorbate could deliver (2E,4E)-hexa-2,4-dien-1-ol, a precursor to leaf alcohol. The monounsaturated alcohol (E)-hex-4-en-1-ol was produced with reasonable selectivity, but complete chemoselectivity of C=O over the diene is elusive. High chemoselectivity for the reduction of an ester over an alkyne group was observed in the hydrogenation of an alkynoate for the first time. The catalysts were also active in the depolymerisation reduction of samples of waste poly(ethylene terephthalate) (PET) to produce benzene dimethanol. These depolymerisations were found to be poisoned by the ethylene glycol side product, although good yields could still be achieved.

Rapid Asymmetric Transfer Hydroformylation (ATHF) of Disubstituted Alkenes Using Paraformaldehyde as a Syngas Surrogate.

As an alternative to conventional asymmetric hydroformylation (AHF), asymmetric transfer hydroformylation (ATHF) by using formaldehyde as a surrogate for syngas is reported. A catalyst derived from commercially available [Rh(acac)(CO)2 ] (acac=acetylacetonate) and 1,2-bis[(2S,5S)-2,5-diphenylphospholano]ethane(1,5-cyclooctadiene) (Ph-BPE) stands out in terms of both activity and enantioselectivity. Remarkably, not only are high selectivities achievable, the reactions are very simple to perform, and higher enantioselectivity (up to 96 % ee) and/or turnover frequencies than those achievable by using the same catalyst (or other leading catalysts) can be obtained by using typical conditions for AHF.

Highly enantioselective hydrogenation and transfer hydrogenation of cycloalkyl and heterocyclic ketones catalysed by an iridium complex of a tridentate phosphine-diamine ligand.

Ir complexes of chiral phosphine-diamine ligands catalyse the hydrogenation and transfer hydrogenation of aryl-piperidin-4-yl methanones, and ketones bearing both an aryl group and secondary alkyl substituent with up to 98% e.e., and with substrate to catalyst ratios of up to 4000.

Hypophagia and induction of serotonin transporter gene expression in raphe nuclei of male and female rats after short-term fluoxetine treatment.

Serotonin (5-HT) is one of the regulators of feeding in humans. Drugs acting on the serotoninergic system are used to treat bulimia nervosa and to enhance the effect of hypocaloric diets in overweight subjects. They act rapidly to normalise feeding when used to treat eating-related problems. To explore the role of the 5-HT transporter (serotonin transporter (SERT)) in the short-term action of serotonin selective reuptake inhibitor fluoxetine, rats were i.p. given the drug for five consecutive days. Acute administration of fluoxetine in male and female rats produced a strong reduction in food intake, an effect that held up when daily treatment was maintained for five consecutive days. This reduction translated into a diminution of body weight that was statistically significant in the case of the males. As a reflection of the body weight change in rats killed after the fifth daily drug injection, retroperitoneal fat pad also decreased; a diminution that was statistically significant in the case of male rats. In these conditions, plasma leptin levels of both male and female rats were lower than in untreated animals. While acute fluoxetine administration did not modify SERT gene expression, subchronic drug treatment increased the content of SERT mRNA in the midbrain raphe complex of both rat genders. These findings may contribute to explain the role of SERT in fluoxetine action on binging and as an adjunct to hypocaloric diets.

New phosphine-diamine and phosphine-amino-alcohol tridentate ligands for ruthenium catalysed enantioselective hydrogenation of ketones and a concise lactone synthesis enabled by asymmetric reduction of cyano-ketones.

Enantioselective hydrogenation of ketones is a key reaction in organic chemistry. In the past, we have attempted to deal with some unsolved challenges in this arena by introducing chiral tridentate phosphine-diamine/Ru catalysts. New catalysts and new applications are presented here, including the synthesis of phosphine-amino-alcohol P,N,OH ligands derived from (R,S)-1-amino-2-indanol, (S,S)-1-amino-2-indanol and a new chiral P,N,N ligand derived from (R,R)-1,2-diphenylethylenediamine. Ruthenium pre-catalysts of type [RuCl2(L)(DMSO)] were isolated and then examined in the hydrogenation of ketones. While the new P,N,OH ligand based catalysts are poor, the new P,N,N system gives up to 98% e.e. on substrates that do not react at all with most catalysts. A preliminary attempt at realising a new delta lactone synthesis by organocatalytic Michael addition between acetophenone and acrylonitrile, followed by asymmetric hydrogenation of the nitrile functionalised ketone is challenging in part due to the Michael addition chemistry, but also since Noyori pressure hydrogenation catalysts gave massively reduced reactivity relative to their performance for other acetophenone derivatives. The Ru phosphine-diamine system allowed quantitative conversion and around 50% e.e. The product can be converted into a delta lactone by treatment with KOH with complete retention of enantiomeric excess. This approach potentially offers access to this class of chiral molecules in three steps from the extremely cheap building blocks acrylonitrile and methyl-ketones; we encourage researchers to improve on our efforts in this potentially useful but currently flawed process.

Convenient and improved protocols for the hydrogenation of esters using Ru catalysts derived from (P,P), (P,N,N) and (P,N,O) ligands.

An improved protocol where a pre-cursor, [Ru(Cl)(2)(NBD)(Py)(2)], is treated with ligands to form [RuCl(2)(bidentate ligand)(diamine)] pre-catalysts for ester hydrogenation is reported. This family of catalysts, as well as a range of ruthenium complexes of tridentate P^N^X (X = NR(2), OH) ligands have been investigated in the hydrogenation of aromatic esters. A range of aromatic esters can be hydrogenated in high yields at temperatures between 30 °C and 100 °C.

Changes in NPY and POMC, but not serotonin transporter, following a restricted feeding/repletion protocol in rats.

Serotonin (5-HT) plays a key role in controlling food intake and feeding behaviour and drugs targeting the 5-HT transporter (SERT) at the synaptic cleft have been used to treat feeding related disorders. To test the hypothesis that SERT might be one of the etiologic factors in the rebound hyperphagia that frequently follows the abandoning of calorie restriction diets, brain SERT content and gene expression were assessed in a restricted feeding/repletion (RFR) protocol in female rats. Animals were food-restricted (2 h access to food per day) for 7 consecutive days and then allowed constant free access to food (FAF). This intermittent fasting protocol resulted in rebound hyperphagia. Higher levels of plasma corticosterone during fasting in food-deprived rats were used as an index of hypothalamic-pituitary-adrenal axis activation. Neither brain SERT density nor expression was modified following the RFR protocol. Nevertheless, with respect to other messengers involved in eating behaviour, in the presence of low plasma leptin levels, an increase in NPY expression and a parallel decrease in POMC expression were observed in the hypothalamic arcuate nucleus of rats killed just before rebound hyperphagia. Food-restricted animals provide a tool for the further study of neurochemical alterations and for the development of new drugs to treat alterations that may occur in humans when dieting is abandoned.

Palladium-catalysed synthesis of aryl-alkyl ethers using alkoxysilanes as nucleophiles.

Changing the activator from tetrabutyl ammonium fluoride (TBAF) to sodium hydroxide unexpectedly switches the catalytic pathway of the Hiyama coupling reaction of vinyl trialkoxysilanes with aryl bromides into a Pd catalysed C-O bond forming reaction; if the correct conditions are used, high yields of aryl-alkyl ethers are observed. In addition, coupling between readily available tetraalkoxysilanes and aryl bromides can also be realised with NaOH or TBAF activation. The reactions take place in only 20 minutes if microwave heating is employed.