Chap. 2 Stereochemistry § Structural Representations That Convey 3-D Information

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Chap. 2 Stereochemistry § Structural Representations That Convey 3-D Information Chap. 2 Stereochemistry § Structural representations that convey 3-D information CH3 CH3 CH3 CH3 Cl H ≡ Cl H Cl Cl H CH CH CH2CH3 CH2CH3 H 2 3 CH2CH3 Fischer projection. Ball & Stick CH3 H CH3 CH H H H H 3 H Cl H H C H Cl H 3 CH3 Cl H3C Sawhorse Newman projection representation. O AcO O H OH Ph N O H Ph O H O HO H AcO OCPh Taxol O § Isomerism Isomers : Different compounds that have the same molecular formula. Conformational Isomer:Stereoisomers that are superimposable by rotation around a single bond. Enantiomer : Isomers that are non-superimposable mirror images to each other.→chiral Diastereomer:Isomers that are non-superimposable, not mirror images. -Cis-trans isomer ( geometric isomer ) configurational isomers differ around a double bond or cyclic structure. § Symmetric, Asymmetric, Dissymmetric and Nondissymmetric molecules. -Symmetry operation reflection in a plane(對稱面):σ inversion through a center(對稱中心):i rotation about a proper axis(對稱軸):Cn , for 360° /n rotation about an improper axis(更迭對稱軸):Sn ( = rotation about an axis, followed by reflection though a plane perpendicular to the axis ) H3C CH3 H CH3 C2, σv, σv’ C2, σh H H CH3 H H Cl2 H 2 Cl1 D1 i D2 F F F 1 F2 2 1 D2 D1 C2+σh=i =S Cl1 H H1 2 Cl2 C2 σh D2 F1 H2 Cl 2 Cl1 H1 F2 D1 XY XX X Ci Cs C2 YX X X X X X XXD X C2v C2h X 2h X D2d X X X Chirality:Molecules that are not superimposable with their mirror image chiral. (enantiomeric ) →dissymmetric molecules : molecules without Sn axis (including n=1). Dissymmetric molecules are chiral, chiral molecules are dissymmetric. Dissymmetrical with a chiral center (asymmetric): →asymmetric molecules:molecules without any symmetry element, except C1. CH2CH3 Br O S P H3CH2CH2C F CH3 Cl H3C Ph CO2H 2 N 3 CH3 Nu HO2C N 1 R slow inversion, chiral 3 achiral due to fast inversion H CO2H Br Dissymmetrical molecules belonging to Cn or Dn group O O O O O H H O O C C O C 3 2 O O O 6 O H H H O O H HH D D2 D2 3 chirality along an axis H CH H CH CH axis of 3 2 3 C CC C CC chirality axis of H3C H H3C H chirality has C2, chiral, C dissymmetric 1 Cl H H CH3 H3C H2N NH2 axis of Cl chiral chirality CO2H O2N chiral due to axis of restricted rotation (atropisomer) chirality NO2 HO2C chirality about a plane (CH2)2 * * * CO2H Non-dissymmetric molecules:having Ci, Cs, Cnv, Cnh, Dnh, H C 3 H Dnd, Td, Oh or Sn symmetry. CH H N 3 ( S =σ, S =i ) H CH3 1 2 H3C H ≡ H3C CH3 achiral N with S4 symmetry, achiral CH3 CH3 § Designation of Molecular Configuration (Cahn- Ingold-Prelog convention) Chirality about a point 1. Determine the priority of four groups. 2. With least priority group pointing away, determine the direction of 1→2→3 priority, clockwise →R, counterclockwise →S Criteria for priority 1. higher atomic number ⇒higher priority Br > Cl > C > H … 2.if the two have same atomic number, count substituent next to it. 3. double bond counted twice, triple bond counted three times for both ends 4. tricoordinate:a group of atomic number of “0” assigned for the long pair -CH2Cl < -CHCl2 -CH2CHFCH3 > -CH2CH2CH2Cl -COOH > -COCH3 > -CHO O CCCO O C OH C CH3 C H O O O CN> CH NH> C CH> CH CH 2 > CH 2 CH 3 HO H H3C OCH3 (S) CH HC C CH CH2CH3 H3C CH3 Cl CH3 Cl H2C CH2 H2CCH C HC C HC CH2 (S) H H2CHC H HC CH2 OH OH 3 3 CH3 CH3 H H 2 (R) (S) 1 ClH2C BrH2C CHCl CHCl 2 1 2 2 CH3 HO 4' 8' CH3 2 (2R, 4’R, 8’R) H3C O CH3 H CH3 H CH3 CH3 CH3 CH2OH H 20 C OH CH3 17 H 13 1 2 P H3CH2CH2C OH (S) H3C 3 13R, 17S, 20R Chirality about an axis Start from the near end to determine the priority, then to the far end. CO2H C HO2C CO2H C CC H CO2H R B A H H D H NO2 C O2N CO2H O2N CO2H S HO2C NO2 A B CO H 2 D Fischer Projection, popular in sugar chemistry, relate the config. at an assym. center to that of (+)glyceraldehyde, the standard HO H H OH Rules: C C 1.most highly HOH2C CHO HOH2C CHO oxidized D-(+)-glyceraldehyle L-(-)-glyceraldehyle carbon on top. ≣ ≣ 2.vertical bonds CHO CHO CHO point backward 3.horizontal ≣ HOHHO H H OH bonds point forward CH2OH CH2OH CH2OH DL Compare the configuration around an asymm. center, and assign D、L CHO CHO highest no. CHO There is no direct H OH HO H2N H correlation between HOH* * OH R R 、 S and D 、 L, CH2OH CH2OH configuration D-erythrose D-threose “L-alanine” H CH 2OH H CH 2OH O O HO HO H H H H H OH HO HO OH OH H OH H H α-D-Glucopyranose β -D-Glucopyranose ≣ CH 2 OH H O H H OH H OH OH H OH epi CHO CHO HO H HO H HO H epimeric HO H OH HO H OH HOH CH2OH CHO D-(+)-Mannose D-(+) Talose epimers meso CHO Cl CH3 CH3 HO H Cl CH2OH Similar to threose erythro- threo- CH2OH H2N H OH CHO CHO H OH CH OH HOH HO H 2 ≣ NH HOH HOH 2 H3CS CH OH CH OH 2 2 SCH3 D-Erythrose D-Threose Threo-(1R,2R)-2-amino- Other Stereochemical Nomenclature close a reference Cl CO 2H Br CH t-4-bromo-c-4-chloro-1-methyl-r- 3 cyclohexanecarboxylic acid Alkene cis,trans based on the shape of the molecules E, Z based on priority rule used for R,S. H 3C CO 2H Cl CH 3 A B B B H Cl Br I B cis- A A ? A E- Z- OH N N H 3CH 2C H 3CH 2C OH sym-based on size anti-propiophenone oxime Z- E- For bicyclo systems:exo-, endo-, outside H C H 3C H 3 CH 3 ins H CH 3 ide H H exo, endo-2,4-dimethyl exo, exo-2,4-dimethyl exo H HN OH exo AcO 6-exo-(acetyloxy)-8- Cl inside H azabicyclo-[3.2.1]octan- endo-2-chloronorbornane 2-exo-ol H HO HO H 3-α-Cholestanol 3-β -Cholestanol Stereoselective Reaction:A reaction in which one stereoisomer (or pair of enantiomer) is formed or destroyed at greater rate or to a greater extent than other possible stereoisomer. O H HO LAN OH H 90% 10% HCO2H O OCH CH3 CH3 OH CH3 OH H CH3MgI H H CHO H CH3 Ph Ph CH3 Ph H erythro 67% threo 33% Stereospecific Reaction:A reaction in which stereoisomerically different reactants yield stereoisomerically different products. H3C Br H3C Ph Ph KOCH2CH3 Ph H H Ph H H3C Br H3C H Ph KOCH2CH3 H H Ph Ph Ph H OTs PhS H NaSPh CH3 CH3 H C H C CH3 CH3 H3C H3C TsO H H SPh NaSPh CH3 CH3 H C H C CH3 CH3 H3C H3C homotopic vs. heterotopic HD HO OH HH ≣ HO OH DH homotopic HO OH HO OH prochiral center pro-R HD HO OH HO OH ≠ H H pro- S HO OH S R HH enantiotopic heterotopic DH (if other chiral center present) re face vs. si face diastereotopic OH HS HR - CO2 re O re H C H 3 + clockwise H NH3 H3C H si OH Counter si clockwise H3C H Vinylmagnesium bromide Optical Activity Enantiomers can exhibit optical activity-rotation of plane polarized light. The two enantiomers rotate light to opposite direction, but to the same magnitude. rotation clockwise →+ (d) counterclockwise →- ( l) for pure (+)-glyceraldehyde, specific rot. +14° for a mixture of enantiomeric glyceraldehyde giving +12.6°, 12.6 the excess is = 90% → 95%(+)-and 5% (-)-cpd. 14 Configuration and Optical Activity R,S, D,L,- erythro- threo- are artificial molecular notation, based on arbitrary rules. +,- are molecular property, obtained by expt’l observation. Configuration and optical activity are not directly related. CO2H Fischer H OH assigned HO H (+)-Tartaric acid →confirmed by X-ray CO2H To relate absolute config. and configuration Prediction of optical activity: B if polarizability is A >B >C >D AC Dextrorotatory, +, Ph D Br CH3 H correlating chlorination CO2H CO2H CO2H rxn H 2NH H 2NH H 2NH CH2OCOCH2 NH2 CH2OH CH2Cl (S)-(-)-Azaserine (S)-(-)-Serine (R)-( - )-2-Amino-3- chloropropanoic acid by X-ray by expt’l by assigning the bonds connected to chiral center are not broken the abs. configuration remains. CO H CO H 2 OH- 2 Cl H HOH inversion CH 3 CH 3 (S)-(-)-2-Chloropropanoic acid (R)-(-)-Lactic acid.
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