Lanthanum-pyBOX complexes as catalysts for the enantioselective conjugate addition of malonate esters to beta-gamma-unsaturated alfa-ketimino esters

"This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Coordination Chemistry on 2018, available online: https://doi.org/10.1080/00958972.2018.1437422."[EN] In this paper, we report the application of chiral complexes of La(III) with pyBOX ligands as Lewis acid catalysts in the conjugate addition of malonic esters to N-tosyl imines derived from ß,gamma-unsaturated alfa-keto esters to give the corresponding chiral alfa,ß-dehydroamino esters. pyBOX complexes with La(III), Yb(III), Sc(III), and In(III) triflates were assessed in this reaction but only La(III) showed good activity and enantioselectivity, while Yb(III) provided the expected product with low yield and stereoselectivity, and the Sc(III) and In(III) complexes were completely inactive. The complex of La(OTf)3 with the diphenyl-pyBOX ligand prepared in situ provided the best results and allowed obtaining chiral ¿,ß-dehydroamino esters 3 with excellent yields, E:Z diastereomeric ratios (29:71-99:1) and high enantiomeric excesses (20-95%). The reaction could be applied to imines having a substituted aromatic ring or a heterocycle attached to the double bond, although the presence of electron-withdrawing groups on the aromatic ring was detrimental for stereoselectivity. The reaction products were obtained with the S configuration at the stereogenic center and the Z configuration at the enamine double bond as determined by NOESY experiments and X-ray analysis. Based on the experimental results a stereochemical model involving a nine-coordinate La(III) species has been proposed.This work was supported by the Ministerio de Economia y Competitividad (MINECO-Gobierno de Espana) [grant number CTQ2013-47494-P].Espinosa, M.; Blay, G.; Cardona, L.; Fernández, I.; Muñoz Roca, MDC.; Pedro, J. (2018). Lanthanum-pyBOX complexes as catalysts for the enantioselective conjugate addition of malonate esters to beta-gamma-unsaturated alfa-ketimino esters. Journal of Coordination Chemistry. 71(6):864-873. https://doi.org/10.1080/00958972.2018.1437422S864873716Yukawa, T., Seelig, B., Xu, Y., Morimoto, H., Matsunaga, S., Berkessel, A., & Shibasaki, M. (2010). Catalytic Asymmetric Aza-Morita−Baylis−Hillman Reaction of Methyl Acrylate: Role of a Bifunctional La(O-iPr)3/Linked-BINOL Complex. Journal of the American Chemical Society, 132(34), 11988-11992. doi:10.1021/ja103294aKodama, H., Ito, J., Hori, K., Ohta, T., & Furukawa, I. (2000). Lanthanide-catalyzed asymmetric 1,3-dipolar cycloaddition of nitrones to alkenes using 3,3′-bis(2-oxazolyl)-1,1′-bi-2-naphthol (BINOL-Box) ligands. Journal of Organometallic Chemistry, 603(1), 6-12. doi:10.1016/s0022-328x(00)00024-3De Bettencourt-Dias, A., Barber, P. S., & Bauer, S. (2012). A Water-Soluble Pybox Derivative and Its Highly Luminescent Lanthanide Ion Complexes. Journal of the American Chemical Society, 134(16), 6987-6994. doi:10.1021/ja209572mComelles, J., Pericas, À., Moreno-Mañas, M., Vallribera, A., Drudis-Solé, G., Lledos, A., … Roces-Fernández, L. (2007). Highly Enantioselective Electrophilic Amination and Michael Addition of Cyclic β-Ketoesters Induced by Lanthanides and (S,S)-ip-pybox:  The Mechanism⊥. The Journal of Organic Chemistry, 72(6), 2077-2087. doi:10.1021/jo0622678Sanchez-Blanco, A. I., Gothelf, K. V., & Jørgensen, K. A. (1997). Lanthanide-catalyzed endo- and enantioselective 1,3-dipolar cycloaddition reactions of nitrones with alkenes. Tetrahedron Letters, 38(45), 7923-7926. doi:10.1016/s0040-4039(97)10048-xDesimoni, G., Faita, G., Guala, M., & Pratelli, C. (2003). Different Lanthanide Ions and the Pybox Substituents Induce the Reverse of the Sense of Induction in the Enantioselective Diels−Alder Reaction between Acryloyloxazolidinone and Cyclopentadiene. The Journal of Organic Chemistry, 68(20), 7862-7866. doi:10.1021/jo034215dDesimoni, G., Faita, G., Filippone, S., Mella, M., Zampori, M. G., & Zema, M. (2001). A new and highly efficient catalyst for the enantioselective Mukaiyama–Michael reaction between ( E )-3-crotonoyl-1,3-oxazolidin-2-one and 2-trimethylsilyloxyfuran. Tetrahedron, 57(51), 10203-10212. doi:10.1016/s0040-4020(01)01055-9Sammis, G. M., Danjo, H., & Jacobsen, E. N. (2004). Cooperative Dual Catalysis:  Application to the Highly Enantioselective Conjugate Cyanation of Unsaturated Imides. Journal of the American Chemical Society, 126(32), 9928-9929. doi:10.1021/ja046653nJiang, J., Ma, Z., & Castle, S. L. (2015). Bulky α,β-dehydroamino acids: their occurrence in nature, synthesis, and applications. Tetrahedron, 71(34), 5431-5451. doi:10.1016/j.tet.2015.06.001Li, B., Cooper, L. E., & van der Donk, W. A. (2009). Chapter 21 In Vitro Studies of Lantibiotic Biosynthesis. Methods in Enzymology, 533-558. doi:10.1016/s0076-6879(09)04821-6M.A. Blaskovich. In Handbook on Syntheses of Amino Acids. General Route to Amino Acids, p. 225, ACS and Oxford University Press, New York (2010).Espinosa, M., García-Ortiz, A., Blay, G., Cardona, L., Muñoz, M. C., & Pedro, J. R. (2016). E,Z-Stereodivergent synthesis of N-tosyl α,β-dehydroamino esters via a Mukaiyama–Michael addition. RSC Advances, 6(19), 15655-15659. doi:10.1039/c5ra27354dEspinosa, M., Blay, G., Cardona, L., & Pedro, J. R. (2013). Corrigendum: Asymmetric Conjugate Addition of Malonate Esters to α,β-UnsaturatedN-Sulfonyl Imines: An Expeditious Route to Chiral δ-Aminoesters and Piperidones. Chemistry - A European Journal, 19(52), 17632-17632. doi:10.1002/chem.201304285X-ray data for compound 3bl: crystallized from hexane-EtOAc; C25H29SN1O8; Mr = 503.55; triclinic; space group = P1; a = 6.2550(2), b = 10.2870(4), c = 11.1380(5) Å; α = 69.333(2), β = 78.688(2), γ = 82.555(2)°; V = 656.11(5) Å3; Z = 1; ρcalcd = 1.274 Mg m−3; μ = 0.170 mm−1; F(0 0 0) = 266. A colorless crystal of 0.04 × 0.08 × 0.08 mm3 was used; 5797 [R(int) = 0.0682] total reflections were collected on a Enraf Nonius Kappa CCD equipped with a graphite monochromator and Mo Kα (λ = 0.71073 Å) radiation. The structures were solved by using direct methods with SHELXS-2014 and refined by using full matrix least squares on F2 with SHELXL-2014 [16]. Non-hydrogen atoms were refined anisotropically and hydrogens were obtained or placed in calculated positions refined by using idealized geometries (riding model) and assigned fixed isotropic displacement parameters. Final values were R = 0.0469 and ωR = 0.1054. CCDC-1581116 contains the supplementary crystallographic data for this compound. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.Parsons, S., Flack, H. D., & Wagner, T. (2013). Use of intensity quotients and differences in absolute structure refinement. Acta Crystallographica Section B Structural Science Crystal Engineering and Materials, 69(3), 249-259. doi:10.1107/s205251921301001

s-Channel Production of MSSM Higgs Bosons at a Muon Collider with Explicit CP Violation

A muon collider with controllable energy resolution and transverse beam polarization provides a powerful probe of the Higgs sector in the minimal supersymmetric standard model with explicit CP violation, through s-channel production of Higgs bosons. The production rates and the CP-even and CP-odd transverse-polarization asymmetries are complementary in diagnosing CP violation in the Higgs sector.Comment: 12 pages, 5 figures. Some statements for clarity and references added. To appear in Phys. Rev.

The STACEE-32 Ground Based Gamma-ray Detector

We describe the design and performance of the Solar Tower Atmospheric Cherenkov Effect Experiment detector in its initial configuration (STACEE-32). STACEE is a new ground-based gamma ray detector using the atmospheric Cherenkov technique. In STACEE, the heliostats of a solar energy research array are used to collect and focus the Cherenkov photons produced in gamma-ray induced air showers. The large Cherenkov photon collection area of STACEE results in a gamma-ray energy threshold below that of previous detectors.Comment: 45 pages, 25 figures, Accepted for publication in Nuclear Instruments and Methods

CP violation in chargino decays in the MSSM

In the minimal supersymmetric standard model (MSSM) with complex parameters, supersymmetric loop effects can lead to \emph{CP} violation. We calculate the rate asymmetries of decays of charginos into the lightest neutralino and a $W$ boson on the basis of the most important loop contributions in the third generation squark sectors. It turns out that the \emph{CP} violating asymmetries can be a few per cent in typical regions of the parameter space of the MSSM. These processes would provide very promising channels for probing \emph{CP} violation in the MSSM at future high-energy colliders.Comment: 15 pages, 5 figures, LaTeX2

Roentgen cephalometric analysis of ridge resorption and changes in jaw and occlusal relationships in immediate complete denture wearers

In eighteen subjects assigned for immediate complete upper and lower dentures, roentgen cephalometric recordings were made before extraction of the residual anterior dentition and 3 weeks, 3 months, 6 months and 1 year after denture insertion. The cephalometric analysis was based on electronic measurements of linear and angular morphological variables and computer head plots generated from 177 reference points (Walker, 1967), derived for each subject for each of the five observation stages. The reduction of the alveolar ridges was most rapid during the first 3 months of denture wear and particularly during the post-extraction period of 3 weeks. The reduction in anterior height of the lower ridge was on average twice as great as that of the upper ridge. The ridge resorption and the accompanying settling of the dentures on the basal seats, measured from lead shots inserted in the dentures, brought about an upward rotation of the mandible with a resulting decrease in occlusal vertical dimension and reduction in overjet of the dentures. In accordance with the amount of ridge reduction, these changes showed great individual variation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73577/1/j.1365-2842.1980.tb01466.x.pd

The Potential for Neutrino Physics at Muon Colliders and Dedicated High Current Muon Storage Rings

Conceptual design studies are underway for muon colliders and other high-current muon storage rings that have the potential to become the first true ``neutrino factories''. Muon decays in long straight sections of the storage rings would produce precisely characterized beams of electron and muon type neutrinos of unprecedented intensity. This article reviews the prospects for these facilities to greatly extend our capabilities for neutrino experiments, largely emphasizing the physics of neutrino interactions.Comment: 107 pages, 16 figures, to be published in Physics Report

Exploring Flavor Structure of Supersymmetry Breaking at B factories

We investigate quark flavor signals in three different supersymmetric models, the minimal supergravity, the SU(5) SUSY GUT with right handed neutrinos, and the minimal supersymmetric standard model with U(2) flavor symmetry, in order to study physics potential of the present and future $B$ factories. We evaluate CP asymmetries in various B decay modes, $\Delta m_{B_s}$, $\Delta m_{B_d}$, and $\epsilon_K$. The allowed regions of the CP asymmetry in $B\to J/\psi K_S$ and $\Delta m_{B_s}/\Delta m_{B_d}$ are different for the three models so that precise determinations of these observables in near future experiments are useful to distinguish the three models. We also investigate possible deviations from the standard model predictions of CP asymmetries in other B decay modes. In particular, a large deviation is possible for the U(2) model. The consistency check of the unitarity triangle including $B\to \pi\pi,\rho\pi,D^{(*)}K^{(*)},D^{(*)}\pi,D^{*}\rho$, and so on, at future high luminosity $e^+e^-$ $B$ factories and hadronic $B$ experiments is therefore important to distinguish flavor structures of different supersymmetric models.Comment: revtex4, 31 pages, 7 figure

Charged lepton electric dipole moments with the localized leptons and the new Higgs doublet in the two Higgs doublet model

We study the lepton electric dipole moments in the split fermion scenario, in the two Higgs doublet model, where the new Higgs scalars are localized around the origin in the extra dimension, with the help of the localizer field. We observe that the numerical value of the electron (muon, tau) electric dipole moment is at the order of the magnitude of 10^{-31} (10^{-24}, 10^{-22}) (e-cm) and this quantity is sensitive the new Higgs localization in the extra dimension.Comment: 20 pages, 7 figure

Probing the MSSM Higgs Boson Sector with Explicit CP Violation through Third Generation Fermion Pair Production at Muon Colliders

We perform a systematic study of the production of a third-generation fermion-pair, $\mu^+\mu^-\to f\bar{f}$ for $f=\tau^-,b$, and t in the minimal supersymmetric standard model (MSSM) with explicit CP violation, which is induced radiatively by soft trilinear interactions related to squarks of the third generation. We classify all the observables for probing the CP property of the Higgs bosons constructed by the initial muon beam polarization along with the unpolarized final fermions and with the final-fermion polarization configuration of equal helicity, respectively. The observables allow for complete determination of CP property of the neutral Higgs bosons. The interference between the Higgs boson and gauge boson contributions also could provide a powerful method for the determination of the CP property of two heavy Higgs bosons in the top-quark pair production near the energy region of the Higgs-boson resonances. For the lightest Higgs-boson mass there is no sizable interference between scalar and vector contributions for the determination of the CP property of the lightest Higgs boson. We give a detailed numerical analysis to show how the radiatively-induced CP violation in the Higgs sector of the MSSM can be measured.Comment: 30 pages, 7 figures including 5 eps ones. Typos corrected and references added. To appear in Phys. Rev.

Muon anomalous magnetic moment, lepton flavor violation, and flavor changing neutral current processes in SUSY GUT with right-handed neutrino

Motivated by the large mixing angle solutions for the atmospheric and solar neutrino anomalies, flavor changing neutral current processes and lepton flavor violating processes as well as the muon anomalous magnetic moment are analyzed in the framework of SU(5) SUSY GUT with right-handed neutrino. In order to explain realistic mass relations for quarks and leptons, we take into account effects of higher dimensional operators above the GUT scale. It is shown that the supersymmetric (SUSY) contributions to the CP violation parameter in $K^0-\bar{K}^0$ mixing, $\epsilon_K$, the $\mu \to e \gamma$ branching ratio, and the muon anomalous magnetic moment become large in a wide range of parameter space. We also investigate correlations among these quantities. Within the current experimental bound of $\text{B}(\mu \to e \gamma)$, large SUSY contributions are possible either in the muon anomalous magnetic moment or in $\epsilon_K$. In the former case, the favorable value of the recent muon anomalous magnetic moment measurement at the BNL E821 experiment can be accommodated. In the latter case, the allowed region of the Kobayashi-Maskawa phase can be different from the prediction within the Standard Model (SM) and therefore the measurements of the CP asymmetry of $B\to J/\psi K_S$ mode and $\Delta m_{B_s}$ could discriminate this case from the SM. We also show that the $\tau \to \mu \gamma$ branching ratio can be close to the current experimental upperbound and the mixing induced CP asymmetry of the radiative B decay can be enhanced in the case where the neutrino parameters correspond to the Mikheyev-Smirnov-Wolfenstein small mixing angle solution.Comment: 70 pages, 14 figure