Bài giảng Organic Chemistry - Chapter 5: Image And Mirror Image

Chapter 5: Image And Mirror ImageImage And Mirror Image Of LimoneneSpruce treeOrange“Handedness”A New Type Of StereoisomerismRecall: a. Constitutional isomers (butane, 2-methylpropane) b. Stereoisomers (cis-trans cycloalkanes) c. Image-mirror image stereoisomers Remember the bromination of butane:Now:We thought these were identical..50:50 chance50:50mixtureThe two 2-bromobutanes are not identical, because they are not superimposable: They are image and mirror image.50:50 Mixture of enantiomers: Racemic mixture or racemateThe two isomers are labelled enantiomers. Molecules that lack reflection symmetry are called chiral (from Greek: cheir, hand  “handedness”).EnantiomersIf image and mirror image of a molecule are superimposable it is achiral. Quick test: presence of a mirror plane. Chiral molecules lack a mirror plane.Most organic molecules owe their chirality to the presence of a stereocenter, usually a carbon with 4 different substituents: an asymmetric carbon. StereocentersCStereocenter*labelledAsymmetric Carbon: No Mirror PlaneSymmetry In Nature 20,000 : 1 EscargotSymmetry is beautiful, or is it ?Symmetry in Art: M. C. EscherWaterfallDrawing Hands                                                    Mửbius StripAuguste Rodin: La CathedralThe Various Kinds Of IsomersTHeadsWalba“Handedness” (i.e., left or right) is called the absolute configuration. Measured by:X-ray crystal structure = “Photo.”Enantiomers: How To Tell Which Is WhichThe PolarimeterOne enantiomer (image)  rotates light dextrorotatory (clockwise), (+)-enantiomer The other enantiomer (mirror image)  rotates light levorotatory (counter-clockwise), (-)-enantiomer.2. Polarimeter: Rotation of plane polarized light[] is called specific rotationOptical rotation:[α]λt(ºC) = α lcMeasured rotationConcentration (g ml-1)Length of vessel (in dm, usually = 1)Note: Sign of rotation does not tell you absolute configurationCH3CH2CCH3BrHCCH2CH3H3CBrH-23.1+23.1*Mirrorplane*Enantiomers are optically active. Racemates are not.Optical RotationExamples of [α]Cahn-Ingold-Prelog R,S-NomenclatureLabel all substituents at stereocenter, starting at point of attachment, according to the sequence rules (to come next) in order of decreasing priority: a, b, c, d (note color scheme). Face the molecule, looking down C-d bond:a, b, c clockwise: Ra, b, c counterclockwise: SCadbcNaming EnantiomersOr, How To Describe Absolute Configuration At A StereocenterRCahn-Ingold-Prelog1966a, b, c, d Robert Sidney Cahn (1899-1981) Sir Christopher Kelk Ingold (1893–1970)Vladimir Prelog (1906–1998) 2. If same priority at first atom: Go to first point of difference. 1. Order by atomic number, i.e. H = 1, lowest. -CH2CH2SH-CH2CH2SCH3‹-CH2CH3-CCH3CH3H‹-CH2CH2OH-CHCH3CH3‹-CHCH3D‹-CH2CBr3CHCH3BrIcabdN:*RThe Sequence RulesdException: lone pair, # “zero”. E.g., amines:3. Multiple bonds: Add double or triple representations of atoms at the respective other end of the multiple bond.CCCCCCCCHHCCHHCOHOCOCHNCCNNCNCCCCCProcedure For Assignment Of R And STo help keeping schematic track of stereochemistry: A flat stencil for stereocentersBrHCCH3CH2CH3HBrCH3CH2CH3HBrEyes in the plane of the boardDepending on your starting dashed-wedged line structure, several Fischer projections are possible for the same molecule. Fischer ProjectionsEmil Fischer (1852–1919)A Mental Exercise1. Rotate by 180: absolute configuration stays same; rotate by 90: absolute configuration switches. 2. The single mutual exchange of any pair of substituents gives the other enantiomer. Hence: Two exchanges leave absolute configuration.BrCH3CH2CH3HCH2CH3BrCH3HHCH2CH3BrCH3RRRExample: (2R)-bromobutaneRules For Handling Fischer ProjectionsExample: a 2-bromobutane 1. Draw (any) Fischer projection. 2. Do two exchanges to place d on top (if not already there fortuitously).Note: There are three possible arrangements with d on top; all are R :cdbabdcaRBrbdcCH3CH2CH3HabdcaR !!bdcaRbdcaRUse Of Fischer Projections In Assigning R,SProblem: Are these two molecules the same or opposite enantiomers? R or S ?IFHCH3IFHCH3Solution:IFHCH3IFHCH3IFHCH3dabcdabcSIFHCH3abcddabcSTwo Stereocenters: C-3-chlorination of 2-bromobutane*BrBr*Cl*Cl2, hν-HClGenerates all combinations: RR, RS SR, SS Four stereoisomersDiastereomers are stereoisomers that are not related as image / mirror-image. RR SS and RS SR are enantiomer pairsDiastereomersDiastereomersC2C3Fischer ProjectionsJulien and Paloma: Two StereocentersRRSSRSRS=RRSSAssigning R,S In DiastereomersRemember: a b c d Fischer projection is “artificial”—eclipsedWalbaMozartR,R (and S,S) = transR,S (and S,R) = cisCyclic Cis And Trans Isomers Are Diastereomers!Link terminiAssigning R,S In Cyclic Analogs*BrBr*Br*Br2, hv-HBrWill give: SS SR RS RRCH3CH3HHBrBrCH3CH3BrBrHHCH3CH3BrHBrHCH3CH3HBrHBrThis diastereomer is special: Image is superimposable with mirror image!!! The molecule has an internal mirror plane.DiastereomersTwo Stereocenters With The Same SubstituentsThe diastereomer with a mirror plane is achiral; such diastereomers are called meso. 2,3,-Dibromobutane has only three stereoisomers.The Achiral Meso DiastereomerVisualizing The Mirror Plane In A Meso DiastereomerRoryWalbaThe Great KuduIs MesoTeaser: The Kiss of the ElephantsChiral or Meso?Cyclic Meso Molecules: CisachiralRRRRRSRSRSRRSSSSSRSRSRSSDiastereomersEnantiomers8 Stereoisomers (maximum): 4 Diastereomeric pairs of enantiomers. Less if meso present, e.g., meso-2,3,4–tribromopentane: BrHCH3CH3BrHBrHBrHCH3CH3HBrBrHThree Stereocentersn Stereocenters give rise to a maximum of 2n stereoisomers, e.g., 2, 4, 8, 16, 32Note: Stereocenters need not be adjacent for these relationships to hold:***Stereoisomerism Increases Chemical Space DrasticallyGround Rule: We cannot get excess of one enantiomer from achiral starting material or from a racemate. I.e., we cannot “engender” optical activity from optically inactive ingredients.Br*Br2, hv-HBrachiralChiral, but racemic50:50 mix of R and SStereochemistry In Chemical Reactionsachiral ingredientsWhy? The Intermediate Radical Is Achiral50/50 Chance of attack from either side: R :S = 1 : 1ClãHClCH3CH3HHBrHCH3CH3HClBrHCH3CH3HClBrHSame environment (mirror plane)Racemate Optically inactive Formed in equal amountsNote: If you start from the racemate: same outcome. CH2CH3CBrCH3-SSRCl2Mechanisms Are Important:chlorination Of (S)-2-bromobutane At C2Optically active 2CH3CH3HHBrHClãHClCH3CH3ClHBrHCH3CH3HHBrClDifferent environmentDiastereomers Both optically active Note: If you start from the racemate, you still form diastereomers, but they are racemic (not optically active).CCCH3HBrHCH3-SSSSRSCl2Formed in unequal amounts:“Stereoselectivity”Leaving The Stereocenter Untouched:Chlorination At C33Optically Active Or Racemic? Wrting ConventionsIf the starting material or products are optically active, it is indicated by the R/S notation, the sign of optical rotation, or some surrounding text. For example, Usually, it is assumed that all ingredients in a reaction are racemic. To save time, typically only one enantiomer is written. For example, the chlorination of racemic 2-bromobutane at C3 is written as follows: Equimolar presence of the other enantiomer is assumedStereoselectivity:Preferential formation of one stereoisomer overthe other.StereoselectivityPasteur was lucky: the enantiomers of racemic ammonium tartrate separate as two “enantiomeric crystals”. How Do We Get A Pure Enantiomer?Separation of enantiomers from the racemates:resolutionLouis Pasteur (1822–1895) Usually: Chemical Separation Of EnantiomersUse a cheap (typically a natural product) pure enantiomer as an auxiliary to bind to components of racemate: gives diastereomers, which can be separated. Like using a left hand (auxiliary) to sort another person’s right and left hands:After separation, the auxiliary is removed to leave pure enantiomers of original racemate.Similar valuecoincidentalFrom wine fermentationEnantioselectivity:Generating One Enantiomer From Achiral MaterialA “handed” reagent or catalyst can tell the difference between top and bottom: different energiesCH2CH3CBrCH3CXCH2CH3CH3Br*XEnantiomer Recognition In NatureReceptor sites in enzymes: the “active site”Enantiomers And Physiological ActivityThe Origin Of Our Enantiomer World:Many TheoriesSpace (begs the question), “spontaneous resolution” and amplification, crystal surfaces or clays, earth’s rotation, parity violation at the atomic level (measured in radioactive decay of 60Co), circularly polarized “chiral” lightNew Horizons spacecraft: PlutoJuly 18, 2015 02:00 pmIs there chiral life out there?