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.