Institut des Sciences Moléculaires de Marseille

The umpolung strategy encompasses all the methods that make organic molecules react in an inverse manner compared to their innate polarity-driven reactivity. This concept entered the field of organocatalysis when it was recognized that N-heterocyclic carbenes (NHCs) can provide catalytic access to acyl anion equivalents. Since then, tremendous efforts have followed to develop a broad variety of NHC-catalyzed reactions. In addition to this, more recent research developments have shown that other families of organocatalysts are also able to mediate transformations in which inversion of polarity is involved. This tutorial review aims at offering a didactic overview of organocatalytic umpolung and should serve as an inspiration for further progress in this field.

Electronic and steric ligand effects both play major roles in organometallic chemistry and consequently in metal-mediated catalysis. Quantifying such parameters is of interest to better understand not only the parameters governing catalyst performance but also reaction mechanisms. Nowadays, ligand molecular architectures are becoming significantly more elaborate and existing models describing ligand sterics prove lacking. This review presents the development of a more general method to determine the steric parameter of organometallic ligands. Two case studies are presented: the tertiary phosphines and the N-heterocyclic carbenes.

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTStereocontrolled Domino ReactionsHélène Pellissier*View Author Information Aix-Marseille Université, UMR CNRS 7313 Institut des Sciences Moléculaires de Marseille Equipe Chirosciences, Case 561, Campus Saint Jérôme Avenue Esc. Normandie-Niemen, 13397 Marseille Cedex 20, France*Tel.: +33 4 91 28 27 65. E-mail: [email protected]Cite this: Chem. Rev. 2013, 113, 1, 442–524Publication Date (Web):November 16, 2012Publication History Received5 July 2012Published online16 November 2012Published inissue 9 January 2013https://pubs.acs.org/doi/10.1021/cr300271khttps://doi.org/10.1021/cr300271kreview-articleACS PublicationsCopyright © 2012 American Chemical SocietyRequest reuse permissionsArticle Views13508Altmetric-Citations606LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Addition reactions,Aldehydes,Chemical reactions,Multicomponent reactions,Stereoselectivity Get e-Alerts

Abstract Since about the year 2000, the research area of asymmetric organocatalysis has grown rapidly to become one of the most fascinating and current fields in organic chemistry. In the last years, asymmetric domino reactions have widely benefited from this fast‐growing field, as exemplified by the development of an explosive number of novel and powerful asymmetric organocatalytic domino processes, which allowed the easy construction of complex chiral molecular architectures from simple materials with high yields and very often remarkable enantioselectivities in a metal‐free environment. Indeed, the possibility to join two or more organocatalytic reactions in one asymmetric domino process has become a challenging goal for chemists, due to several advantages from economical and environmental points of view, avoiding costly protecting groups and time‐consuming purification procedures after each step, for example. This review aims to update the latest developments of this hot and fascinating field, covering the literature since the beginning of 2009. Abbreviations: Ac: acetyl; Ar: aryl; BDHP: 1,1′‐binaphth‐2,2′‐diyl hydrogen phosphate; BA: Brønsted acid; BINAPO: 2‐diphenylphosphino‐2′‐diphenylphosphinyl‐1,1′‐binaphthalene; BINOL: 1,1′‐bi‐2‐naphthol; Boc: tert ‐butoxycarbonyl; Bn: benzyl; Bu: butyl; Bz: benzoyl; CSA: camphorsulfonic acid; Cy: cyclohexyl; Cbz: benzyloxycarbonyl; DABCO: 1,4‐diazabicyclo[2.2.2]octane; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCE: dichloroethane; de : diastereomeric excess; DFT: density functional theory; DHQ: hydroquinine; DHQD: dihydroquinidine; DIPEA: diisopropylethylamine; DKR: dynamic kinetic resolution; DMAD: dimethyl acetylenedicarboxylate; E: electrophile; ee : enantiomeric excess; ESI: electrospray ionization; Et: ethyl; Fu: furyl; Hept: heptyl; Hex: hexyl; HOMO: highest occupied molecular orbital; IBX: o ‐iodoxybenzoic acid; LB: Lewis base; LUMO: lowest unoccupied molecular orbital; Me: methyl; MOM: methoxymethyl; Mes: mesyl; MS: mass spectroscopy; MTBE: methyl tert ‐butyl ether; NADH: nicotinamide adenine dinucleotide; Naph: naphthyl; NHC: N‐heterocyclic carbene; NMM: N ‐methylmorpholine; NMP: N ‐methylpyrrolidinone; Ns: nosyl; Nu: nucleophile; Oct: octyl; PCC: pyridinium chlorochromate; Pent: pentyl; PFBA: pentafluorobenzoic acid; Ph: phenyl; PMB: para ‐methoxybenzyl; Pr: propyl; Py: pyridine; r.t.: room temperature; TBA: tribromoacetic acid; TBS: tert ‐butyldimethylsilyl; TCBA: 2,4,6‐trichlorobenzoic acid; TES: triethylsilyl; TFA: trifluoroacetic acid; THF: tetrahydrofuran; Thio: thiophene; TMEDA: tetramethylethylenediamine; TMS: trimethylsilyl; Tol: tolyl; Ts: 4‐toluenesulfonyl (tosyl).

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTMetal-Free Multicomponent Syntheses of PyridinesChristophe Allais, Jean-Marie Grassot, Jean Rodriguez*, and Thierry Constantieux*View Author Information Aix Marseille Université, Centrale Marseille, CNRS, iSm2 UMR 7313, 13397 MARSEILLE, France*E-mail: [email protected]*E-mail: [email protected]Cite this: Chem. Rev. 2014, 114, 21, 10829–10868Publication Date (Web):October 10, 2014Publication History Received19 February 2014Published online10 October 2014Published inissue 12 November 2014https://pubs.acs.org/doi/10.1021/cr500099bhttps://doi.org/10.1021/cr500099breview-articleACS PublicationsCopyright © 2014 American Chemical SocietyRequest reuse permissionsArticle Views9483Altmetric-Citations417LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Aldehydes,Aromatic compounds,Cations,Pyridines,Reaction products Get e-Alerts

The efficiency of a chemical synthesis can be nowadays measured, not only by parameters like selectivity and overall yield, but also by its raw material, time, human resources and energy requirements, as well as the toxicity and hazard of the chemicals and the protocols involved. The development of multicomponent reactions (MCRs) in the presence of task-specific ionic liquids (ILs), used not only as environmentally benign reaction media, but also as catalysts, is a new approach that meet with the requirements of sustainable chemistry. The aim of this tutorial review is to highlight the synergistic effect of the combined use of MCRs and ILs for the development of new eco-compatible methodologies for heterocyclic chemistry.

Mycotoxins are fungal secondary metabolites contaminating food and causing toxicity to animals and humans. Among the various mycotoxins found in crops used for food and feed production, the trichothecene toxin deoxynivalenol (DON or vomitoxin) is one of the most prevalent and hazardous. In addition to native toxins, food also contains a large amount of plant and fungal derivatives of DON, including acetyl-DON (3 and 15ADON), glucoside-DON (D3G), and potentially animal derivatives such as glucuronide metabolites (D3 and D15GA) present in animal tissues (e.g., blood, muscle and liver tissue). The present review summarizes previous and very recent experimental data collected in vivo and in vitro regarding the transport, detoxification/metabolism and physiological impact of DON and its derivatives on intestinal, immune, endocrine and neurologic functions during their journey from the gut to the brain.

Abstract While tremendous advances have been made in asymmetric synthesis, the resolution of racemates is still the most important industrial approach to the synthesis of chiral compounds. The use of enzymes for the kinetic resolution (KR) of racemic substrates to afford enantiopure compounds in high enantioselectivity and good yield has long been a popular strategy in synthesis. However, transition metal‐mediated and more recently organocatalyzed KRs have gained popularity within the synthetic community over the last two decades due to the progress made in the development of chiral catalysts for asymmetric reactions. Many catalytic non‐enzymatic procedures have been developed providing high enantioselectivity and yield for both products and recovered starting materials. Indeed, the non‐enzymatic KR of racemic compounds based on the use of a chiral catalyst is presently an area of great importance in asymmetric organic synthesis. The goal of this review is to provide an update on the principal developments of catalytic non‐enzymatic KR covering the literature since 2004. This review is subdivided into seven sections, according to the different types of compounds that have been resolved through catalytic non‐enzymatic KR, such as alcohols, epoxides, amines, alkenes, carbonyl derivatives, sulfur compounds and ferrocenes. Abbreviations: Ac: acetyl; acac: acetylacetone; AQN: anthraquinone; Ar: aryl; Atm: atmosphere; BINAM: 1,1′‐binaphthalenyl‐2,2′‐diamine; BINAP: 2,2′‐bis(diphenylphosphanyl)‐1,1′‐binaphthyl; BINEPINE: phenylbinaphthophosphepine; BINOL: 1,1′‐bi‐2‐naphthol; Bmim: 1‐butyl‐3‐methylimidazolium; Bn: benzyl; Boc: tert‐butoxycarbonyl; Box: bisoxazoline; BSA: bis(trimethylsilyl)acetamide; Bu: butyl; Bz: benzoyl; c: cyclo; CBS: Corey–Bakshi–Shibata; Cbz: benzyloxycarbonyl; COD: cyclooctadiene; COE: cyclooctene; Cy: cyclohexyl; Dba: (E,E)‐dibenzylideneacetone; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCC: N,N′‐dicyclohexylcarbodiimide; de: diastereomeric excess; DEAD: diethyl azodicarboxylate; Dec: decanyl; DHQD: dihydroquinidine; Difluorphos: 5,5′‐bis(diphenylphosphino)‐2,2,2′,2′‐tetrafluoro‐4,4′‐bi‐1,3‐benzodioxole; DIPEA: diisopropylethylamine: DKR: dynamic kinetic resolution; DMAP: 4‐dimethylaminopyridine; DMSO: dimethyl sulfoxide; DNA: deoxyribonucleic acid; DOSP: N‐(dodecylbenzenesulfonyl)prolinate; DTBM: di‐tert‐butylmethoxy; ee: enantiomeric excess; Et: ethyl; equiv.: equivalent; Fu: furyl; Hex: hexyl; HIV: human immunodeficiency virus; HMDS: hexamethyldisilazide; KR: kinetic resolution; L: ligand; LDA: lithium diisopropylamide; MAO: methylaluminoxane; Me: methyl; Ms: mesyl; MTBE: methyl tert‐butyl ether; Naph: naphthyl; nbd: norbornadiene; NBS: N‐bromosuccinimide; NIS: N‐iodosuccinimide; Pent: pentyl; Ph: phenyl; Piv: pivaloyl; PMB: p‐methoxybenzoyl; Pr: propyl Py: pyridyl; r.t.: room temperature; s: selectivity factor; Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole; (S,S′,R,R′)‐Tangphos: (1S,1S′,2R,2R′)‐1,1′‐di‐tert‐butyl‐(2,2′)‐diphospholane; TBS: tert‐butyldimethylsilyl; TBDPS: tert‐butyldiphenylsilyl; TCCA: trichloroisocyanuric acid ; TEA: triethylamine; TEMPO: tetramethylpentahydropyridine oxide; THF: tetrahydrofuran; Thio: thiophene; Tf: trifluoromethanesulfonyl; TMS: trimethylsilyl; Tol: tolyl; Ts: 4‐toluenesulfonyl (tosyl)

Sucrose is the main form of assimilated carbon which is produced during photosynthesis and then transported from source to sink tissues via the phloem. This disaccharide is known to have important roles as signaling molecule and it is involved in many metabolic processes in plants. Essential for plant growth and development, sucrose is engaged in plant defense by activating plant immune responses against pathogens. During infection, pathogens reallocate the plant sugars for their own needs forcing the plants to modify their sugar content and triggering their defense responses. Among enzymes that hydrolyze sucrose and alter carbohydrate partitioning, invertases have been reported to be affected during plant-pathogen interactions. Recent highlights on the role of invertases in the establishment of plant defense responses suggest a more complex regulation of sugar signaling in plant-pathogen interaction.

Cells have evolved multiple mechanisms to apprehend and adapt finely to their environment. Here we report a new cellular ability, which we term "curvotaxis" that enables the cells to respond to cell-scale curvature variations, a ubiquitous trait of cellular biotopes. We develop ultra-smooth sinusoidal surfaces presenting modulations of curvature in all directions, and monitor cell behavior on these topographic landscapes. We show that adherent cells avoid convex regions during their migration and position themselves in concave valleys. Live imaging combined with functional analysis shows that curvotaxis relies on a dynamic interplay between the nucleus and the cytoskeleton-the nucleus acting as a mechanical sensor that leads the migrating cell toward concave curvatures. Further analyses show that substratum curvature affects focal adhesions organization and dynamics, nuclear shape, and gene expression. Altogether, this work identifies curvotaxis as a new cellular guiding mechanism and promotes cell-scale curvature as an essential physical cue.

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Pseudomonas aeruginosa regulates the production of many exoproteins and secondary metabolites via a hierarchical quorum-sensing cascade through LasR and RhlR and their cognate signal molecules N-(3-oxododecanoyl)-L-homoserine lactone (3O-C12-HSL) and N-(butanoyl)-L-homoserine lactone (C4-HSL). In this study, we found that transcription of the quorum sensing-regulated genes lecA (coding for PA-IL lectin), lasB (coding for elastase), and rpoS appeared to be growth phase dependent and their expression could not be advanced to the logarithmic phase in cells growing in batch culture by the addition of exogenous C4-HSL and 3O-C12-HSL. To identify novel regulators responsible for this growth phase dependency, a P. aeruginosa lecA::lux reporter strain was subjected to random transposon mutagenesis. A number of mutants affected in lecA expression were found that exhibited altered production of multiple quorum sensing-dependent phenotypes. While some mutations were mapped to new loci such as clpA and mvaT and a putative efflux system, a number of mutations were also mapped to known regulators such as lasR, rhlR, and rpoS. MvaT was identified as a novel global regulator of virulence gene expression, as a mutation in mvaT resulted in enhanced lecA expression and pyocyanin production. This mutant also showed altered swarming ability and production of the LasB and LasA proteases, 3O-C12-HSL, and C4-HSL. Furthermore, addition of exogenous 3O-C12-HSL and C4-HSL to the mvaT mutant significantly advanced lecA expression, suggesting that MvaT is involved in the growth phase-dependent regulation of the lecA gene.

Lowering the boom: 3,4,5-trinitro-1H-pyrazole (TNP, see picture) has been prepared by the unexpected nitration of 3,5-dinitropyrazole with a super-electrophile generated from 20–30 % sulfuric oleum mixed with nitric acid. The remarkable stability of TNP results from the preservation of the ring geometry and the specific conformation of the nitro group at C4 which confers low acidity on the material.

In Gram-negative bacteria, the envelope is a sophisticated barrier protecting the cell against external toxic compounds. Membrane transporters, e.g., porins or efflux pumps, are main filters regulating the internal accumulation of various hydrophilic molecules. Regarding bacterial susceptibility towards antibacterial agents, membrane permeability is part of the early bacterial defense. The bacterium manages the translocation process, influx and efflux, to control the intracellular concentration of various molecules. Antibiotics and biocides are substrates of these mechanisms and the continuing emergence of multidrug resistant isolates is a growing worldwide health concern. Different strategies could be proposed to bypass the bacterial membrane barrier, comprising influx and efflux mechanisms, in order to restore the activity of antibiotics against resistant bacteria.

For the first time, enantiomerically enriched atropoisomeric furans have been accessed using a central-to-axial chirality conversion strategy. Hence, oxidation of the enantioenriched dihydrofuran precursors gave rise to axially chiral furans with high enantiopurities accounting from excellent conversion percentages (cp) in most cases.

Achiral or chiral phosphines are widely used in two main domains: ligands in organometallic catalysis and organocatalysis. For this reason, the obtention of optically pure phosphine has always been challenging in the development of asymmetric catalysis. The simplest method to obtain phosphines is the reduction of phosphine oxides. The essential difficulty is the strength of the P=O bond which involves new procedures to maintain a high chemio- and stereoselectivity. The reduction can occur with retention or inversion of the stereogenic phosphorus atom depending on the nature of the reducing agent and the presence of additives. In fact, the reactivity of the phosphine oxides and the mechanism of the reduction are not always well understood. Since the first work in the 1950's, numerous studies have been realised in order to develop methodologies with different reagents or to understand the mechanism of the reaction. In the last decade, efficient stereospecific methodologies have been developed to obtain optically pure tertiary phosphines from P-stereogenic phosphine oxides. In this review, we intend to provide a comprehensive and critical overview of these methodologies.

In this letter we show that the Marangoni flow contribution to the evaporation rate of small heated water droplets resting on hot substrates is negligible. We compare data of evaporating droplet experiments with numerical results and assess the effect of Marangoni flow and its contribution to the evaporation process. We demonstrate that heat conduction inside these water droplets is sufficient to give an accurate estimate of evaporation rates. Although convection in evaporating water droplets remains an open problem, our aim in this study is to demonstrate that these effects can be neglected in the investigation of evaporation rate evaluation. It is worth noting that the presented results apply to volatile heated drops which might differ from spontaneously evaporating cases.

Organo-click reaction: A new and complementary method to Huisgen's metal-catalyzed triazole synthesis is described using unactivated ketones and arylazides as the substrates and proline as an organocatalyst. Dramatic acceleration was observed for this reaction using microwave activation and high regio- and chemoselectivities were obtained for a wide range of ketones and arylazides (see scheme).

This review covers recent developments relating to organocatalyzed transformations by chiral isothioureas (ITUs) since their original introduction by Birman in 2006. This class of nucleophilic heterocycles was first involved in anhydride activation in enantioselective acyl transfer reactions, but it was more recently shown that activation of other reagents was possible, considerably enlarging their number of catalytic enantioselective transformations. Four main modes of activation as Lewis bases can currently be listed: (1) acylisothiouronium intermediates involved in acyl transfer, (2) silylisothiouronium species involved in silyl transfer, (3) acylisothiouronium enolates involved in several concerted and formal pericyclic transformations, and (4) α,β‐unsaturated acylisothiouronium species involved in domino transformations. This review is organized according to these different modes of activation of chiral isothioureas.

Abstract The rapid generation of molecular complexity in a relatively easy manner has made the [5+2] cycloaddition approach a highly useful tool in the synthesis of a wide number of complex natural products and important biologically active products containing seven‐membered rings. Besides the common and highly efficient [5+2] cycloadditions of oxidopyrylium and oxidopyridinium ions with π‐systems which offer an easy access to a wide range of novel heterocyclic seven‐membered ring molecules with a oxygen or nitrogen bridge, and the less employed [5+2] photocycloadditions, the metal‐catalyzed [5+2] cycloadditions have attracted a lot of attention and have become one of the most popular ways of constructing seven‐membered ring products. All these cycloadducts can be synthetically manipulated easily toward a number of interesting molecular structures with high potential applications. Abbreviations: Ac: acetyl; Ar: aryl; Bar F : tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate; BINAP: 2,2′‐bis(diphenylphosphanyl)‐1,1′‐binaphthyl; Bn: benzyl; Boc: tert ‐butoxycarbonyl; Bu: butyl; Bz: benzoyl; Cbz: benzyloxycarbonyl; cod: cyclooctadiene; Cp: cyclopentadienyl; DBU: 1,8‐diazabicyclo[5.4.0]undec‐7‐ene; DCE: 1,2‐dichloroethane; de : diastereomeric excess; DFT: density functional theory; DMF: dimethylformamide; DMSO: dimethyl sulfoxide; dppb: 1,4‐bis(diphenylphosphino)butane; dppe: 1,2‐bis(diphenylphosphine)ethane; dppp: 1,3‐bis(diphenylphosphino)propane; ee : enantiomeric excess; Et: ethyl; HFIP: hexafluoroisopropyl alcohol; L: ligand; M: metal; Me: methyl; MOM: methoxymethyl; Ms: mesyl; Ph: phenyl; PMB: para ‐methoxybenzoyl; Pr: propyl; Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole; TBDPS: tert ‐butyldiphenylsilyl; TBS: tert ‐butyldimethylsilyl; TEA: triethylamine; Tf: trifluoromethanesulfonyl; TFE: trifluoroethanol; THP: tetrahydropyran; TIPS: triisopropylsilyl; TMS: trimethylsilyl; Tol: tolyl; Tp: hydridotris(pyrazolyl)borate; Ts: 4‐toluenesulfonyl (tosyl); VCP: vinylcyclopropane.