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Stereoismerism Jeannecrassou CHIRASKOOL Jeanne Crassous Phosphore et Matériaux Moléculaires http://pmm.univ-rennes1.fr/ Institut des Sciences Chimiques de Rennes UMR CNRS 6226 Université Rennes1, Av. du Général Leclerc 35042 C Rennes Cedex, France, H I [email protected] R A F U N Historical aspects and properties of enantiomers Definitions Symmetry aspects Symmetry point groups for achiral molecules Symmetry point groups for chiral molecules Molecules with stereogenic centers Asymmetric carbon, chiral amines, sulfoxides, phosphines, … Half-sandwich complexes, metallocenes Tetrahedral or spiro-type complexes Octahedral Complexes Molecules displaying axial chirality Examples of allenes Atropoisomerism and axial chirality Planar chirality Inherent chirality Helicenes, fullerenes Trefoil knots and topological chirality Selected examples: stereochemistry of helicene derivatives Some (simplified) history… Bartholin (1669) birefringence Iceland Spar – Spath d’Islande (CaCO3) Malus (1808) Polarization of light Direction of propagation Wave seen Polarization plane by the observer Abbey Haüy (1809) modern crystallography, hemihedry Mitscherlich (1819) polymorphism Arago (1811) Herschel (1820) Hemihedral crystals of quartz They ‘turn the light’ : they have a rotatory power The Biot’s polarimeter (1815) Solutions of camphor, glucose, tartaric acid They ‘turn the light’ : they have a rotatory power (optical rotation) Camphor tree Grapes (tartaric acid) The tartrates by Pasteur (1848) 1820 Kessler (Alsacian chemist) Synthesis of a mysterious acid after refining the potassium acid tartrate from vinification Was named paratartaric acid or racemic (Gay-Lussac 1828) Berzelius : same composition as tartaric acid but different crystals (isomerim) Mitscherlich (1844) : the crystals of double salts of sodium and ammonium of tartaric acid and of racemic acid are identical! Biot ‘s polarimeter: optical rotation was zero The tartrates by Pasteur (1848) 168 years ago! Tartrate In alcohol 1848 Pasteur : hemihedral crystals (microscope) Louis PASTEUR 1822-1895 First spontaneous resolution ! Pictures given by Dr. Thierry RUCHON (CEA) Tartrate Tartrate ‘Left’ ‘right’ Tartrate solutions They ‘turn the light’ : they have an optical rotation Solutions of racemic tartrate Optical rotation: zero Link between crystal and substance (molecule)! Le Bel and van’t Hoff (1874) Theory of the asymmetric carbon Joseph Achille LE BEL (1847-1930) Jacobus Henricus VAN’T HOFF (1852-1911) « Sur les relations qui existent entre les formules atomiques des corps organiques et le pouvoir rotatoire de leur dissolution » « La chimie dans l’espace » First Nobel prize in chemistry (1901) There exist two products corresponding to a tetrasubstituted methane Cl H C F Br Lord Kelvin (Sir William Thompson) Baltimore Lectures, 1884 I call any geometrical figure, or group of points, chiral, and say that it has chirality, if its image in a plane mirror, ideally realized, cannot be brought to coincide with itself. « J’appelle chiral toute figure géométrique ou tout ensemble de points qui n’est pas superposable à son image dans un miroir. Je parle alors de chiralité ». Laurence Barron (1980’s) A more recent physical definition: True and False chirality True chirality is shown by systems existing in two distinct enantiomeric states that are interconverted by space inversion, but not by time reversal combined with any proper spatial rotation. Pointing the role of time reversal symmetry in optical activity and pointed out that time-even pseudoscalar observables are the hallmark of genuine chirality. Circularly polarized light: true chiral influence B.k: true chiral influence Only B: cannot induce an enantiomeric excess Absolute asymmetric synthesis under physical fields: facts and fictions. Chem. Rev. 98, 2391-2404. « L’univers est dissymétrique » Pasteur (1883) Louis PASTEUR 1822-1895 « Me demanderez-vous : quelles sont les forces dissymétriques qui président à l’élaboration des principes immédiats naturels? … les forces cosmiques dissymétriques…. Un des liens entre la vie à la surface de la terre et le cosmos…. » Recent results Photon energy-Controlled Symmetry Breaking with Circularly Polarized Light L. Nahon (GDR), U. Meierhenrich, Angew. Chem. 2014, 53, 210 (See also Bonner, Kagan, Nicoud,….) Synchrotron wavelength at 200 nm CPL light on an amorphous film Alanine with ee up to 4.2 % A. Fresnel (1817) Circular birefringence A. Cotton (1895) Circular Dichroism (Cotton effect), then Magnetic CD Chirality, magnetism and light, L. D. Barron, Nature 2000, 405, 895 Magneto-optical properties of chiral systems Breaking of parity symmetry by chirality leads to optical activity. Breaking of time reversal symmetry by a magnetic field leads to the Faraday effect. Breaking both symmetries leads to an additional new effect: magnetochiral anisotropy. Dielectric constant for CPL: DL/ DL/ DL/ ( ,,)()k B () k ()B () k B - dependent on relative orientation of light and field Luminescence of Eu(D/L)tfc - independent of polarization 3 DL L-tfcL - enantioselective: 1,0 0,5 ) II()()B k B k 3 g - II()()B k B k 0,0 g (10 0,0 -0,5 ) 3 - Rikken, Raupach, g (10 -1,0 -0,3 Nature 1997, 390, 493 D-tfcD 0,0 0,5 B (T) N. Avarvari, C. Train (GDR) 590 600 610 620 (nm) Tastes and odors H2NCOCH2 CO2H H2NCOCH2 CO2H asparagine H2N H H NH2 S amère R sucrée O O carvone S odeur de cumin R odeur de menthe verte limonène R odeur d'orange S odeur de citron Mint candies Eight different forms (left and right-handed) refreshing R R ( ) (+ ) ( + ) ( + ) R - R O H O H O H O H R S n é o i s o m e n t h o l m e n t h o l n é o m e n t h o l i s o m e n t h o l O H O H O H O H (- ) (+ ) ( -) (- ) Different physical properties between racemates and enantiomers see teaching course 2 (Laure Guy) What about natural and medicinal compounds? Different properties of enantiomers O O O O H NH HN N OH N * O O N Quinquina H3CO H H O O N R-(+)-thalidomide S-(–)-thalidoqmuiidneine anti-vomitif tératogène O O O OH OH OHO NH HN H H ON * O O O N NHiPr NHiPr H HO O O NCH3 R-(+)-thalidomide S-(–)-thalidomide S-propanolol : -bloquant R-propanolol : contraceptif anti-vomitif térHatOogène Anti-vomitive teratogen morphine OH OH H H HCO2H HO2C H O O NMHeiPr MeNHiPr MeO OMe S naproxeneS naSp-rporxoèpna:e nanti o: laonl t:-i iinflamatoryn-fblalomqmuaantotire RRR-p nrnaproxeneoapparonxoèlonle : :c oinna:t crinactiveaticf eptif Different pharmacodynamics and pharmacokinetics of enantiomeric pharmaceuticals HO CO H H 2 HO H CO2H CO2H HO2C H NH H NH Me 2 Me 2 HO HO MeO OMe L-DOPA : anti-Parkinson D-DOPA : maladies oculaires S naproxène : antiinflammatoire R naproxène : inactif HO CO2H HO CO2H H NH2 H NH2 HO HO L-DOPA : anti-Parkinson D-DOPA : maladies oculaires « L’univers est dissymétrique » Pasteur (1883) Louis PASTEUR 1822-1895 « Me demanderez-vous : quelles sont les forces dissymétriques qui président à l’élaboration des principes immédiats naturels? … les forces cosmiques dissymétriques…. Un des liens entre la vie à la surface de la terre et le cosmos…. » « J’ai fait vivre des petites graines de penicillium glaucum, de cette moisissure qu’on trouve partout, à la surface de cendres et d’acide paratartrique, et j’ai vu l’acide tartrique gauche apparaître. » The firt enzymatic resolution! “Most natural organic products, the essential products of life, are asymmetric and possess such asymmetry that they are not superimposable on their images.” Why? The Universe is dissymmetric The 20 amino-acids essential for life are L All natural sugars are D What is its origin? Extraterrestrial life CPL in space (Orion) Parity violation (matter is intrinsically chiral) DNA Parity : a broken symmetry P Parity operation : (x, y, z) (-x, -y, -z) 1956 1957 Lee and Yang Wu et al. Prediction of Parity First experimental violation in weak observation interaction in -decay of cobalt 60 Chen Ning Yang Tsung-Dao Lee Chien-Shiung Wu (Nobel prize in Physics 1957) Wu experiment on beta decay of Cobalt-60. 1957 : Wu et al. – First experimental observation in -decay of cobalt 60. Beta emission is preferentially in the direction opposite to the nuclear spin … Wu 1957 1974 : M.-A and C. Bouchiat – PV effects in highly forbidden transitions in cesium 1979 : Barkov and Zolotorev Optical rotation in heavy metals vapors (Bi,Cs,Pb) What about molecules? Parity violation (PV) in molecules: a fundamental effect The broken mirror Comes from the weak nuclear interaction (one of the four fundamental forces: electromagnetic, gravitational, weak and strong nuclear forces): R S Interaction between elementary particles DEPV = 2EPV -17 A fundamental effect DEPV c.a. 10 kT Provoques a spatial symmetry breaking A big challenge to measure it! between the right and the left-handed molecules PV measurements by highly-accurate IR spectroscopy C. Chardonnet, C. Daussy, A. Amy-Klein, C. Bordé, B. Darquié… Laboratoire de Physique des Lasers, Villetaneuse, Villetaneuse Chardonnet et al., Phys. Rev. Lett. 1999, 83, 1554 Review: Simultanous measurement of transition frequencies Crassous et al., Org. Biomol . Chem. 2005, 3, 2218 In the two enantiomers of CHFClBr The broken mirror Due to parity violation two enantiomers do not have the same absorption spectrum F F Letokhov, Phys. Lett. 1975, 53A, 275 C H H C Cl Br Br Cl R S DEPV D n -17 DEPV c.a. 10 kT nv4 4= 1 1 Proposition to search for PV effect h n ultrastable (R ) in CHFClBr spectrum h n ( S ) CO2 laser Kompanents et al., Opt. Commun. 1976, 19, 414 nv4 4= 0 0 e i g r e n E C–F Upper limit : 10 Hz (~ 1000 cm-1) New molecules for PV measurements Theoretical calculations of PV effects : 5 EPV Z relativistic calculations Pr Schwerdtfeger, Aukland (New Zealand) T. Saue, R. Bast, Université Paul Sabatier, Toulouse (France) Z: atomic numberF F F F C H Os Re F FC H PH CH Cl Cl Os 3 O 3 C H Br C H I Cl PH Re Os3 Cl CH3 Cl Cl C H Cl C H Cl PH O Re Br I Cl 3 CH3 DCnPl NC = B1.r7 mHz DCnPl NC = 2I 4 mHz Cl Cl OCl Cl Cl DnPNC f=o r1 C.7– mF Hstzretching DnPNC f=o r2 C4 –mFH sztretching Cl for C–FD nsPtrNeCtc =h i1n.g7 mHz for C–FD nstPrNeCtc =h i2n4g mHz Cl for C–F stretching for C–F stretching DnPNC = 1,30 Hz DnPNC = 1,09 Hz P.
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