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In the context of materials science, six-membered phosphorus heterocycles are intriguing building blocks due to their tunable properties through phosphorus post-functionalization and their unique hyperconjugative effects arising from the phosphorus substituents that contribute to further tuning the optoelectronic properties of the system. Seeking for the discovery of improved materials, the latter features have triggered an astonishing evolution of molecular architectures based on phosphorus heterocycles. Theoretical calculations showed that the hyperconjugation causes a reduction in the S0–S1gap, which strongly depends on the nature of both the P-substituent and the π–conjugated core, but where are the limits? Outlining the hyperconjugative effects of six-membered phosphorus heterocycles would allow scientists to know how to design next-generation organophosphorus systems with enhanced properties. Herein, we discovered that, in cationic six-membered phosphorus heterocycles, an increase in the hyperconjugation does not affect the S0–S1gap anymore; i.e., quaternizing the phosphorus atoms leads to properties that go beyond those provoked by hyperconjugative effects. DFT calculations revealed that the latter is particularly marked in phosphaspiro derivatives. Our detailed investigations spotlight the potential of π-extended systems based on six-membered phosphorus spiroheterocycles for accessing properties beyond those achieved to date through hyperconjugative effects, thus laying the groundwork for new research possibilities toward improved organophosphorus systems.

The straightforward synthesis of three organotin clusters endowed with six triarylamine-based moieties is reported herein. The optoelectronic properties of the molecules, as well as their ability to form gels, were investigated. The association ability of the compounds was studied as well by means of variable temperature nuclear magnetic resonance (NMR) and ultraviolet–visible (UV–vis) spectroscopy. The optimization of the geometry of the compounds has been performed and compared to the X-ray diffraction of the crystals. The results obtained through this comparison are useful for the explanation of their different gelation behaviors. In fact, organostannoxane drum 1exhibits a strong ability to form organized supramolecular structures by means of a number of noncovalent short contacts that finally yield luminescent organogels in aromatic solvents.

Here we report the highly enantio- and syn-selective synthesis of β-hydroxy α-amino acids from glycine imine derivatives under Brønsted base (BB) catalysis. The key of this approach is the use of benzophenone-derived imine of glycine o-nitroanilide as a pronucleophile, where the o-nitroanilide framework provides an efficient hydrogen-bonding platform that accounts for nucleophile reactivity and diastereoselectivity.

Catalytic enantioselective 1,3-dipolar cycloaddition between imino esters and electrophilic alkenes, employing chiral metal complexes derived from copper(I) and silver(I) salts and (S)-DM- or (S)-DTBM-Segphos as ligands produces diastereodivergently exo- or endo-cycloadducts, respectively. The effect of the functional group of the dipolarophile and the fine tuning of the catalyst plays an important role in promoting reverse diastereoselectivities. The origins of experimentally observed enantioselectivity and diastereoselectivity data, as well as the origin of the observed switched endo/exo ratios, are also explained by means of density functional theory calculations.

ABSTRACTRewilding seeks to foster the wildness of an area or to return it to wilderness. As the number of rewilding initiatives has increased around the world, so has the controversy surrounding its feasibility, desirability and even the coherence of the concept. This paper makes a pragmatist defense of rewilding, understood as a collective exploration of the boundary between the wild and the human, an endless process of composing a common world based on mutual respect. In addition, it argues that an approach inspired by the methodological contributions of Bruno Latour (and actor-network theory) eludes the main philosophical criticism against rewilding.

A study on the reactivity of rigid 1-azadienes derived from methylene γ-lactams is reported. Through the functionalization of 1-amino α,β-unsaturated γ-lactam derivatives, easily available from a multicomponent reaction of amines, aldehydes, and pyruvates, it is possible to in situ generate rigid 1-azadienes locked by a γ-lactam core. The 4π-electron system of those rigid 1-azadienes can behave as both diene and dienophile species through a spontaneous cyclodimerization reaction or exclusively as dienes or dienophiles if they are trapped with imines or cyclopentadiene, respectively. The use of chiral rigid 1-azadienes as dienophiles in the cycloaddition reaction with cyclopentadiene leads to the formation of spiro-γ-lactams bearing four stereogenic centers in a highly stereospecific manner, reporting the first example of the use of methylene-γ-lactams in the synthesis of spirocycles.

DrosophilaBet1 and Slh, needed for vesicle trafficking at the Golgi, are required also for mitochondrial quality control. When they are deficient, a signature of bioenergetic dysfunction and intramitochondrial proteotoxic stress results and cells enter a senescencelike state. Slh-deficient cells lose coassociation of mitochondria and lysosomes with Bet1.

ABSTRACTThe discovery and development of new antimalarial drugs are becoming imperative because of the spread of resistance to current clinical treatments. The lack of robustly validated antimalarial targets and the difficulties with the building in of whole-cell activity in screening hits are hampering target-based approaches. However, phenotypic screens of structurally diverse molecule libraries are offering new opportunities for the identification of novel antimalarials. Several methodologies can be used to determine the whole-cell in vitropotencies of antimalarial hits. The [3H]hypoxanthine incorporation assay is considered the “gold standard” assay for measurement of the activity of antimalarial compounds against intraerythrocytic forms of Plasmodium falciparum. However, the method has important limitations, as the assay is not amenable for high-throughput screening since it remains associated with the 96-well plate format. We have overcome this drawback by adapting the [3H]hypoxanthine incorporation method to a 384-well high-density format by coupling a homogeneous scintillation proximity assay (SPA) and thus eliminating the limiting filtration step. This SPA has been validated using a diverse set of 1,000 molecules, including both a representative set from the Tres Cantos Antimalarial Set (TCAMS) of compounds and molecules inactive against whole cells. The results were compared with those from the P. falciparumlactate dehydrogenase whole-cell assay, another method that is well established as a surrogate for parasite growth and is amenable for high-throughput screening. The results obtained demonstrate that the SPA-based [3H]hypoxanthine incorporation assay is a suitable design that is adaptable to high-throughput antimalarial drug screening and that maintains the features, robustness, and reliability of the standard filtration hypoxanthine incorporation method.

The 1,3‐dipolar cycloaddition between azomethine ylides and alkenes is efficiently catalysed by [{(Sa)‐Binap‐Au(tfa)}2] (Binap=2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl; tfa=trifluoroacetyl). Maleimides, 1,2‐bis(phenylsulfonyl)ethylene, chalcone and nitrostyrene were suitable dipolarophiles even when using sterically hindered 1,3‐dipole precursors. The results obtained in these transformations improve the analogous ones obtained in the same reactions catalysed by [Binap–Ag(tfa)]. In addition, computational studies have also been carried out to demonstrate both the high enantioselectivity exhibited by the chiral gold(I) complex, and the non‐linear effect observed in this transformation.

Freie Wahl der Stereochemie: Die erste enantioselektive Cycladdition N‐metallierter Azomethin‐ylide an das C70‐Molekül liefert abhängig vom verwendeten chiralen Metallkomplex beide Pyrrolidino[70]fulleren‐Enantiomere mit ee‐Werten über 90 % (siehe Bild). Die hohe Regioselektivität ließ sich anhand der nucleophilen und electrophilen Fukui‐Indizes erklären, die theoretisch bestimmt wurden.

Make your choice of stereochemistry: The first enantioselective cycloaddition of N‐metalated azomethine ylides to the C70molecule affords both pyrrolidino[70]fullerene enantiomers, with eevalues over 90 %, depending on the chiral metal complex used (see picture). The high site‐ and regioselectivity observed has been accounted for by the nucleophilic and electrophilic Fukui indexes determined by theoretical calculations.

Two P or not two P: The synthesis of the first stable disilyne bisphosphine adduct is reported. Its X‐ray structure, showing a short SiSi bond with a certain multiple‐bond character, illustrates the peculiar ligand effect of phosphine towards SiIcompared to other ligands. The disilyne derivative rapidly reacts with CO2at room temperature, thus allowing the non‐metal‐mediated direct reduction of CO2to CO (see picture).

Der gewisse Unterschied: Das erste stabile Disilinbisphosphan‐Addukt wurde synthetisiert. Seine Molekülstruktur, mit einer kurzen Si‐Si‐Bindung von gewissem Mehrfachbindungscharakter, verdeutlicht den besonderen Ligandeneffekt von Phosphan auf SiIim Vergleich zum Effekt anderer Liganden. Das Disilinderivat reagiert schnell mit CO2bei Raumtemperatur und ermöglicht so die metallfreie, direkte Reduktion von CO2zu CO (siehe Schema).

The thermal [4+3] cycloaddition reaction between allenes and tethered dienes (1,3‐butadiene and furan) assisted by transition metals (AuI, AuIII, PdII, and PtII) was studied computationally within the density functional theory framework and compared to the analogous non‐organometallic process in terms of activation barriers, synchronicity and aromaticity of the corresponding transition states. It was found that the metal‐mediated cycloaddition reaction is concerted and takes place via transition structures that can be even more synchronous and more aromatic than their non‐organometallic analogues. However, the processes exhibit slightly to moderately higher activation barriers than the parent cycloaddition involving the hydroxyallylic cation. The bond polarization induced by the metal moiety is clearly related to the interaction of the transition metal with the allylic π* molecular orbital, which constitutes the LUMO of the initial reactant. Finally, replacement of the 1,3‐butadiene by furan caused the transformation to occur stepwise in both the non‐organometallic and metal‐assisted processes.

Silin im Visier: Das erste isolierbare, durch einen Phosphanliganden stabilisierte Silin wurde synthetisiert (siehe Bild). Eine Röntgenstrukturanalyse ergab eine sehr kurze Silicium‐Kohlenstoff‐Bindung, was mit Rechnungen zu SiC‐Bindungen in Einklang ist. Die Verbindung ist zu einem gewissen Grad carbenisch, sodass das Phosphoniumsilaylid‐Fragment als starker π‐Donor und π‐Akzeptor zu wirken scheint.

The endodiastereo and enantioselective 1,3dipolar cycloaddition of azomethine ylides and electrophilic alkenes is efficiently catalysed by chiral phosphoramidite–silverI perchlorate complexes. The reaction allows the presence of different types of substituents in the 1,3dipole and can be applied to the synthesis of enantiomerically enriched, highly substituted prolines. This methodology was applied to the total synthesis of the inhibitors of the hepatitis C virus HCV. Computational studies support a twostep mechanism predicting exactly the experimental results and the origin of both the diastereo and enantioselections, as well as a reasonable explanation concerning the different reaction rates observed for some substrates.© WileyVCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009

Highly endo-diastereoselective 1,3-dipolar cycloadditions between acrylates derived from methyl (R)- and (S)-lactate, as chiral dipolarophiles, and azomethine ylides derived from glycine and α-substituted amino acids are described. The origins of the observed excellent stereocontrol are interpreted on the basis of computational studies on model systems. This methodology was successfully employed for the first asymmetric synthesis of both enantiomers, as well as of its racemic form, of a biologically active pyrrolidine (hepatitis C virus inhibitor) incorporating a leucine residue and a 2-thienyl group. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

On and off: The concerted [2+1] cycloaddition reaction of phosphine–silylene complexes with ethylene affords the corresponding pentacoordinate siliranes. The conversion is strongly related to the ethylene pressure, and the reaction is reversible at room temperature. The structure of one silirane was determined by X‐ray diffraction analysis.

An, aus, an, aus: Die konzertierte [2+1]‐Cycloaddition zwischen Phosphan‐Silylen‐Komplexen und Ethylen liefert die entsprechenden pentakoordinierten Silirane. Die Reaktion wird vom Ethylendruck erheblich beeinflusst, und sie ist bei Raumtemperatur reversibel. Von einem der Silirane wird das Ergebnis der Röntgenstrukturanalyse vorgestellt.

Selektivitätstellt in der Fullerenforschung immer noch eine große Herausforderung dar. In der Zuschrift auf S. 6184 ff.beschreiben N. Martín, F. Cossío und Mitarbeiter, wie mit geeigneten chiralen Katalysatoren die Addition von Fullerenen an beide Seiten eines 1,3‐Dipols kontrolliert und damit das stereochemische Ergebnis bestimmt werden kann. Die sorgfältige Auswahl der experimentellen Bedingungen führt zu chiralen [70]Fullerenderivaten mit ungewöhnlich hohen Orts‐ und Regioselektivitäten.

Selectivityis still a major challenge in fullerene research. In their Communication on page 6060 ff. N. Martín, F. Cossío, and co‐workers describe how the use of a suitable chiral catalyst controls the addition of fullerenes to both faces of a 1,3‐dipole, thus determining the stereochemical outcome. The careful choice of the experimental conditions affords chiral [70]fullerene derivatives with unusually high site‐ and regioselectivity.