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A highly diastereo- and enantioselective Ru(II)-catalyzed dynamic kinetic resolution–asymmetric transfer hydrogenation (DKR–ATH) of α-(N-sulfonylimino) and α-(N-sulfonylamino) aryl ketones to 4-hydroxy-benzo-δ- and 3-(α-hydroxy-arylmethyl)-benzo-γ-sultams is presented. By employing enantiopure ansa-Ru[PipSO2DPEN(CH2)4Ph] cat. II with S/C = 10 000 in a HCO2H/Et3N binary mix, up to >99.9% ee and dr >99:1 are obtained with 100% conversion under mild conditions. Application to access the stereopure “structurally simplified TsDPEN” N,N-ligand syn-3-(α-aminobenzyl)-benzo-γ-sultam (“syn-ULTAM”) and its structural isomer trans-4-amino-3-phenyl-benzo-δ-sultam (trans-4) is demonstrated.

A highly efficient enantio- and diastereoselective catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution (DKR-ATH) of α,β-dehydro-α-acetamido and α-acetamido benzocyclic ketones to ent- trans-β-amido alcohols is disclosed employing a new ansa-Ru(II) complex of an enantiomerically pure syn- N, N-ligand, i.e. ent- syn-ULTAM-(CH2)3Ph. DFT calculations of the transition state structures revealed an atypical two-pronged substrate attractive stabilization engaging the commonly encountered CH/π electrostatic interaction and a new additional O═S═O···HNAc H-bond hence favoring the trans-configured products.

The synthesis of new enantiopure syn- and anti-3-(α-aminobenzyl)-benzo-γ-sultam ligands 6 and their application in the ruthenium(ii)-catalyzed asymmetric transfer hydrogenation (ATH) of ketones using formic acid/triethylamine is described. In particular, benzo-fused cyclic ketones afforded excellent enantioselectivities in reasonable time employing a low loading of the syn ligand-containing catalyst. A never-before-seen dynamic kinetic resolution (DKR) during reduction of a γ-keto carboxylic ester (S7) derivative of 1-indanone is realized leading as well to excellent induction.

International audience; This paper is dedicated to the study of the influence of surface roughness on local stress and strain fields in polycrystalline aggregates. Finite element computations are performed with a crystal plasticity model on a 316L stainless steel polycrystalline material element with different roughness states on its free surface. The subsequent analysis of the plastic strain localization patterns shows that surface roughness strongly affects the plastic strain localization induced by crystallography. Nevertheless, this effect mainly takes place at the surface and vanishes under the first layer of grains, which implies the existence of a critical perturbed depth. A statistical analysis based on the plastic strain distribution obtained for different roughness levels provides a simple rule to define the size of the affected zone depending on the rough surface parameters.

The preparation of a rigid C1-symmetric P-stereogenic diphosphine series possessing a P-o-diphenylphosphinophenyl moiety and its use in RhI-catalyzed hydrogenation of benchmark olefins, is presented. This simplified ligand design, wherein some specific features (backbone flexibility, identical nature of P,P′-substituents) of related C2-symmetric ethylene-bridged diphosphines were knocked out, is a useful study-tool with which to better understand the role of essential motifs that guide catalysis in the original model.

This dissertation analyzes the overarching question of how the process of constitution-making affects the written constitution. To shed more light on this issue from a broad perspective, positive and normative research questions are dealt with. Besides an introductory chapter, which sets the stage for the dissertation and an overview of the key literature in chapter 2, this dissertation consists of four content chapters and a short concluding chapter. Chapter 3 deals with the question whether the process of constitution-making affects the choice of constitutional features. A rational-choice model shows how the introduction of a stage of constitution-making influences the constitutional choice of form of government. Chapter 4 looks further into the details of the constitution-making process and discusses which procedural rules can effectively constrain the drafters. To analyze this question, we use a theoretical model as well as a regression analysis. Following this positive analysis, chapter 5 and chapter 6 deal with more normative issues. Chapter 5 follows up on the issue referendums for the ratification of constitutions and discusses the advantages and disadvantages of simple and qualified majority requirements. Chapter 6 focuses on one specific channel through which drafters can influence the constitutional development in the future, namely unamendable provisions. A final chapter summarizes the findings in light of the limitations of this dissertation and discusses paths for future research.

In this paper, we argue that the joint use of ex-ante regulation and ex-post liability rules is efficient when there are uncertainty surrounding causal investigations and regulatory myopia. As these conditions are generally met in environmental cases, we provide an explanation for the frequent coexistence of these two instruments to control activities that create a risk for the environment. Moreover, we suggest that a joint use of liability and regulation should more frequently be optimal at the European (Federal) level than at the Country (State) level.

New 3rd generation designer ansa-ruthenium(II) complexes featuring N,C-alkylene-tethered N,N-dialkylsulfamoyl-DPEN/η6-arene ligands, exhibited good catalytic performance in the asymmetric transfer hydrogenation (ATH) of various classes of (het)aryl ketones in formic acid/triethylamine mixture. In particular, benzo-fused cyclic ketones furnished 98 to >99.9% ee using a low catalyst loading.

International audience; The aim of the present paper is to investigate the consequences of the loading on the free surface response in polycrystalline aggregates. The study is made on a 316L stainless steel. Finite element computations using a crystal plasticity model are performed to simulate a polycrystalline aggregate submitted to different cyclic loadings. A statistical analysis of the results is carried out to extract information concerning the local stress and local strain fields at the free surface. The analysis of plastic strain localization on surface maps and inside the bulk through transparent volumetric views allows to exhibit the effects of the grain orientation and of the loading on local mechanical fields. The computation of an indicator characterizing extrusion/intrusion steps give some information on the initiation sites.

A series of sterically hindered o-(branched alkoxy)-tert-butoxybenzenes was efficiently prepared in good yields owing to a new practical and simple preparation of o-tert-butoxyphenol starting from catechol and isobutene. Use of DMF di-tert-butyl acetal reagent instead of isobutene/H2SO4 (cat.) for O-tert-butylation was very convenient in case of ortho bulky phenols affording the corresponding tert-butyl ethers in high yield and purity. This general route proved to be useful since no reliable access was available to o-di-t-BuO-substituted arenes. Application to the synthesis of congested phosphorus-based compounds is presented.

The synthesis of new enantiopure syn- and anti-3-(α-aminobenzyl)-benzo-γ-sultam ligands 6 and their application in the ruthenium(II)-catalyzed asymmetric transfer hydrogenation (ATH) of ketones using formic acid/triethylamine is described. In particular, benzo-fused cyclic ketones afforded excellent enantioselectivities in reasonable time employing a low loading of the syn ligand-containing catalyst. A never-before-seen dynamic kinetic resolution (DKR) during reduction of a γ-keto carboxylic ester (S7) derivative of 1-indanone is realized leading as well to excellent induction.

A large series of bulky 1,2-dialkoxy- and 1,2,3-trialkoxy-benzenes was efficiently prepared via Williamson etherification. Preparation of their contiguous bromine-containing derivatives was also achieved.

An efficient and high-yielding (up to 57% overall yield) asymmetric route to enantiopure P -stereogenic 1,2-bis[( o -hydroxyaryl)(phenyl)phosphino- P -borane]ethanes wherein aryl = phenyl and naphthyl, is presented. The occurring P -stereomutation is confirmed through X-ray crystal structure analysis of key intermediates.

The X-ray structures of two α-substituted α-(2-pyridyl-N-oxide)ethanols, the α-phenyl- (3a) and α-trifluoromethyl- (3b) derivatives, were determined. On dehydration of 3a, compound 4a was obtained. This study brought a clear proof that the α-(2-pyridyl-N-oxide)ethanols are formed following oxidation with peroxides of their corresponding pyridines. A different molecular packing was observed for the α-trifluoromethyl derivative due to an additional hydrogen bonding. Compound 3a crystallized in the monoclinic space group P 21/n with unit cell parameters a = 5.7416(1) A, b = 14.3841(4) A, c = 13.2821(3) A, β = 94.918(2)°, V = 1092.90(4) A3, Z = 4, D = 1.308 Mg/m3. Compound 3b crystallized in the triclinic space group P −1 with unit cell parameters a = 6.1209(2) A, b = 8.1938(4) A, c = 9.4675(4) A, α = 73.363(3)°, β = 73.166(3)°, γ = 71.659(3)°, V = 421.32(3) A3, Z = 2, D = 1.633 Mg/m3. Compound 4a crystallized in the monoclinic space group P 21/n with unit cell parameters a = 9.3579(3) A, b = 12.7340(3) A, c = 9.8579(3) A, β = 117.3249(15)°, V = 1043.63(5) A3, Z = 4, D = 1.255 Mg/m3. The X-ray crystal structures of the title α-(2-pyridyl-N-oxide)ethanols were determined bringing a clear proof that these compounds are formed following the oxidation using peroxides of their corresponding pyridines. A different molecular packing was observed for the α-trifluoromethyl derivative due to an additional hydrogen bonding.

The synthesis of (1′S,3R,4R)-4-acetoxy-3-(1′-trimethylsilyloxy-2′,2′,2′-trifluoroethyl)-2-azetidinone (10) precursor of modified carbapenems is described relying upon [Ru(C6Me6)(S,S)–(CH2)5NSO2DPEN]-catalyzed asymmetric transfer hydrogenation under dynamic kinetic resolution using HCO2H–Et3N. This fluorine-containing precursor yielded the targeted trinems 1 and 2 via a stereoselective key step condensation with lithium (S)-6-methoxy-cyclohexenolate.

The conformational conversion of prion protein (PrP) from a native conformation to the amyloid form is a hallmark of transmissible spongiform encephalopathies. Conversion is usually monitored by fluorescent dyes, which bind generic amyloids and are less suited for living cell imaging. We report a new method for the synthesis of membrane-permeable and membrane-impermeable biarsenical reagents, which are then used to monitor murine PrP (mPrP) misfolding. We introduced tetracysteine (TC) tags into three different positions of mPrP, which folded into a native-like structure. Whereas mPrPs with a TC tag inserted at the N-terminus or C-terminus supported fibril formation, insertion into the helix 2-helix 3 loop inhibited conversion. We devised a quantitative protease-free method to determine the fraction of converted PrP, based on the ability of the fluorescein arsenical helix binder reagent to differentiate between the monomeric and fibrilized form of TC-tagged PrP, and showed that TC-tagged mPrP could be detected on transfected cells, thereby expanding the potential use of this method for the detection and study of conformational diseases.

A series of enantiopure P-stereogenic 1,2-bis[(o-RO-phenyl)(phenyl)phosphino]ethane (R-SMS-Phos) ligands wherein R = i-Pr, i-Bu, t-Bu, 3-Pen, and CH(2)TMS was assessed in the Rh(I)-catalyzed hydrogenation of an indicative set of olefins. The best performing t-Bu-SMS-Phos ligand was screened against a wide range of representative classes of standard and new olefinic substrates such as dehydroamido esters, dehydro-alpha-amido-phosphonates, enamides, itaconates, acrylates, enol acetates, alpha-phosphonovinyl benzoates, alpha-(2-pyridyl N-oxide)styrenes, and alpha-(1-hydroxyliminoethyl)styrenes. Excellent enantioselectivities and high TOFs were attained under mild conditions.

The enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has become an important drug target for breast cancer because it catalyzes the interconversion of estrone to the biologically more potent estradiol which also plays a crucial role in the etiology of breast cancer. Patients with an increased expression of the 17beta-HSD1 gene have a significantly worse outcome than patients without. Inhibitors for 17beta-HSD1 are therefore included in therapy development. Here we have studied binding of 17beta-HSD1 to substrates and a number of inhibitors using NMR spectroscopy. Ligand observed NMR spectra show a strong pH dependence for the phytoestrogens luteolin and apigenin but not for the natural ligands estradiol and estrone. Moreover, NMR competition experiments show that the phytoestrogens do not replace the estrogens despite their similar inhibition levels in the in vitro assay. These results strongly support an additional 17beta-HSD1 binding site for phytoestrogens which is neither the substrate nor the co-factor binding site. Docking experiments suggest the dimer interface as a possible location. An additional binding site for the phytoestrogens may open new opportunities for the design of inhibitors, not only for 17beta-HSD1, but also for other family members of the short chain dehydrogenases.

Switching Knowles DiPAMP's [DIPAMP = 1,2-bis[(o-anisyl)(phenyl)phosphino]-ethane} MeO groups with i-PrO ones led to the i-Pr-SMS-Phos {i-Pr-SMS-Phos = 1,2-bis[(o-isopropoxyphenyl)(phenyl)phosphino]ethane} ligand which displayed a boosted catalyst activity coupled with an enhanced enantioselectivity in the rhodium(I)-catalyzed hydrogenation of a wide-range of representative olefinic substrates (dehydro-α-amido acids, itaconates, acrylates, enamides, enol acetates, α,α-diarylethylenes, etc). The rhodium(I)-(i-Pr-SMS-Phos) catalytic profile was investigated revealing its structural attributes and robustness, and in contrast to the usual trend, 31 P NMR analysis revealed that its methyl (Z)-α-acetamidocinnamate (MAC) adduct consisted of a reversed diastereomeric ratio of 1.4:1 in favour of the most reactive diastereomer.

The introduction of 1,2-bis[(o-anisyl)-(phenyl)phosphino]ethane (DiPAMP) as a P-stereo-genic ligand for rhodium(I)-catalyzed hydrogenation by Knowles et al. came after their evaluation of several diphosphines. However, no in-depth study was carried out on incorporating various substituents on its P-o-anisyl groups. In this work, we have prepared a large series of enantiopure and closely related DiPAMP analogues possessing various substituents (MeO, TMS, t-Bu, Ph, fused benzene ring) on the o-anisyl rings. The new ligands were evaluated in rhodium-catalyzed hydrogenation of several model substrates: methyl α-acetamidoacrylate, methyl (Z)-α-acetamidocinnamate, methyl (Z)-β-acetamidocrotonate, dimethyl itaconate, and atropic acid. They displayed enhanced activities and increased enantioselectivities, particularly the P-(2,3,4,5-tetra-MeO-C 6 H)-substituted ligand (4MeBigFUS). Interestingly enough, 88% ee was obtained in the hydrogenation of atropic acid using the Rh-(4MeBigFUS) catalyst under mild conditions (10 bar H 2 , room temperature) versus 7% ee using Rh-DiPAMP. Conversely, the ligand possessing P-(2,6-di-MeO-C 6 H 3 ) groups proved to slow down considerably the hydrogenation. X-Ray structures of their corresponding Rh complexes are presented and discussed.

Further the through wall crack in an elbow of the Residual Heat Removal (RHR) system of Civaux 1 in 1998, a large investigation program has been completed on removed parts of pipes to better assess the factors responsible for thermal fatigue cracking in pipe components where hot and cold fluids mix together. This article presents the results of destructive investigations performed on numerous parts of the RHR system of EDF plants, on a nozzle of the primary system and on a nozzle of the secondary system and their contribution to understanding and assessing harmfulness of the phenomenon.The damage concerns only certain RHR mixing zones: the mixing tee at intersection between downstream the exchanger and the by-pass line and the mixing tee at location of intersection of two portions of minimum flow line. Deep cracks are always associated with high temperature differences and long times of operation. The deepest cracks are always located close to the welds, in areas showing geometrical singularities and minimal thickness. Crack networks in running parts concern only the very first millimeters of the inner wall.Other mixing zones have been investigated: destructive examinations of a charging line primary nozzle of the Chemical and Volume Control System (CVCS), of two tees between the main line and the minimum flow line of the RHR system and of one tee connecting the Feed Flow Control System (FFCS) to the Auxiliary Feedwater System (AFS) did not show any thermal fatigue crack.EDF has developed a method for identification of fluid mixing zones subject to thermal fatigue damage. This method is based on the assessment of a usage factor, using the knowledge acquired during a large R&D program. This program investigated the thermal loadings in mixing tees acquired through several thermohydraulic mockup tests and the austenitic steel behavior under high cycle thermo-mechanical loadings.The results of the destructive examinations have been used to strengthen the identification methodology of mixing zones potentially affected by thermal fatigue. Damage found in the destructive examinations are always correlated with usage factors a lot greater than 1.The methodology has been applied to all mixing zones of safety related circuits of plants operated by EDF. It has lead to identify the ones with a usage factor greater than unity and to an appropriate in-service inspection program based on volumic non-destructive examinations.

New 3rd generation designer ansa-ruthenium(II) complexes, featuring N,C-alkylene-tethered N,N-dialkylsulfamoyl-DPEN/η6-arene ligands, exhibit good catalytic performance in the asymmetric transfer hydrogenation of various classes of (het)aryl ketones in a HCOOH/Et3N mixture.

[1217437-07-4] C34H40O2P2 (MW 542.63) InChI = 1S/C34H40O2P2/c1-33(2,3)35-29-21-13-15-23-31(29)37(27-17-9-7-10-18-27)25-26-38(28-19-11-8-12-20-28)32-24-16-14-22-30(32)36-34(4,5)6/h7-24H,25-26H2,1-6H3 InChIKey = UBYPIFSGFFMMDD-UHFFFAOYSA-N (P-chiral diphosphine ligand for asymmetric catalysis;1-4 rhodium complexes are efficient catalyst precursors for highly enantioselective hydrogenation of α-carboxy or α-aryl amidoethylenes, α-phosphono amidoethylenes, itaconates, enol acetates, α-carboxy or α-phosphono enol carboxylates) Alternate Name: (R,R)-ethylenebis[(2-tert-butoxyphenyl)phenylphosphine]. Physical Data: −99.4 (c = 1.0, CHCl3). Solubility: sol MeOH, EtOH, THF, EtOAc, CH2Cl2, toluene. Form Supplied in: glassy or white solid; commercially available (as well as the (S,S)-enantiomer). Analysis of Reagent Purity: optical rotation, 1H NMR, 31P NMR, 13C NMR. Preparative Method: the ligand is prepared via the Juge-Stephan route from (−)-oxazaPB derived from (1S,2R)-(+)-ephedrine (eq 1).2, 3 The (S,S)-enantiomer is accessible from (1R,2S)-(−)-ephedrine. (1) Handling, Storage, and Precautions: relatively air stable but should be kept under inert atmosphere in the cold for prolonged storage.