1. Stereochemistry

2. 2 Chirality Handedness“ Handedness ”: Right glove doesn’t fit the left hand. Mirror-imageMirror-image object is different from the original object.

3. 3 Achiral achiral.Objects that can be superposed are achiral.

4. 4 Stereoisomers Enantiomers Nonsuperimposable mirror images, different molecules with different properties. Enantiomers: Nonsuperimposable mirror images, different molecules with different properties.

5. 5 Chiral Carbons four different atoms or groups are chiralCarbons attached with four different atoms or groups are chiral. enantiomerIt’s mirror image will be a different compound (enantiomer).

6. 6 Achiral Compounds Take this mirror image and try to superimpose it on the one to the left matching all the atoms. Everything will match. When the images can be superposed the compound is achiral.

7. 7 Planes of Symmetry A molecule that has a plane of symmetry is achiral is achiral.

8. 8 Cis and Trans Cyclic Compounds Cis-1,2-dichlorocyclopentane: ICis-1,2-dichlorocyclopentane: Is achiral because the molecule has an internal plane of symmetry. Both structures above can be superimposed. rans-1,2-dichlorocyclopentaneTrans-1,2-dichlorocyclopentane does not have a plane of symmetry so the images are nonsuperimposable and the molecule will have two enantiomers.

9. 9 (R) and (S) Nomenclature enantiomersDifferent molecules (enantiomers) must have different names. biologically activeUsually only one enantiomer will be biologically active. Configurationchiral carbon RSConfiguration around the chiral carbon is specified with (R) and (S).

10. 10 Cahn–Ingold–Prelog Rules priorityAssign a priority number to each group attached to the chiral carbon. Priority highest priority #1.Priority is assigned according to atomic number. The highest atomic number assigned is the highest priority #1. In case of ties, look at the next atoms along the chain. Double and triple bonds are treated like bonds to duplicate atomsIn case of ties, look at the next atoms along the chain. Double and triple bonds are treated like bonds to duplicate atoms.

11. 11 Assign (R ) or (S ) Working in 3-D, rotate the molecule so that the lowest priority group is in back.Working in 3-D, rotate the molecule so that the lowest priority group is in back. Draw an arrow from highest to lowest priority group. Clockwise = (R), Counterclockwise = (S)Draw an arrow from highest to lowest priority group. Clockwise = (R), Counterclockwise = (S)

12. 12 Assign Priorities Atomic number: F > N > C > H Once priorities have been assigned, the lowest priority group (#4) should be moved to the back if necessary.

13. 13 Assign Priorities 23 4 Draw an arrow from Group 1 to Group 2 to Group 3 and back to Group 1. Ignore Group 4. S Clockwise = (R) and Counterclockwise = (S) Counterclockwise (S) (S)

14. 14 Example When rotating to put the lowest priority group in the back, keep one group in place and rotate the other three. Clockwise (R)

15. Treatment of Multiple Bonds 15

16. 16 Example (Continued) 1 2 3 4 Counterclockwise (S)

17. 17 Draw the enantiomers of 1,3-dibromobutane and label them as (R) and (S). (Making a model is particularly helpful for this type of problem.) The third carbon atom in 1,3-dibromobutane is asymmetric. The bromine atom receives first priority, the (–CH 2 CH 2 Br) group second priority, the methyl group third, and the hydrogen fourth. The following mirror images are drawn with the hydrogen atom back, ready to assign (R) or (S) as shown. Solved Problem 1 Solution

18. 18 Properties of Enantiomers Same boiling point, melting point, and density. Same refractive index. in opposite directionsRotate the plane of polarized light in the same magnitude, but in opposite directions. Different interaction with other chiral molecules: –Active site of enzymes is selective for a specific enantiomer. –Taste buds and scent receptors are also chiral. Enantiomers may have different smells.

19. 19 Optical Activity Enantiomers :Enantiomers : rotate the plane of polarized light in opposite directions, but same number of degrees.

20. 20 Polarimeter Clockwise Dextrorotatory (+) Counterclockwise Levorotatory (-) Not related to (R) and (S)

21. 21 Specific Rotation Observed rotation Observed rotation depends on the length of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light. [  ] =  (observed) c  l Where  (observed Where  (observed) is the rotation observed in the polarimeter, c is concentration in g/mL and l is length of sample cell in decimeters.

22. 22 When one of the enantiomers of 2-butanol is placed in a polarimeter, the observed rotation is 4.05° counterclockwise. The solution was made by diluting 6 g of 2-butanol to a total of 40 mL, and the solution was placed into a 200-mm polarimeter tube for the measurement. Determine the specific rotation for this enantiomer of 2-butanol. Since it is levorotatory, this must be (–)-2-butanol The concentration is 6 g per 40 mL = 0.15 g/ml, and the path length is 200 mm = 2 dm. The specific rotation is [][] D 25 = – 4.05° (0.15)(2) = –13.5° Solved Problem 2 Solution

23. 23 Biological Discrimination

24. 24 Racemic Mixtures Equal quantitiesEqual quantities of d- and l- enantiomers. Notation: (d, l ) or (  ) No optical activity. The mixture may have different boiling point (b. p.) and melting point (m. p.) from the enantiomers!

25. 25 Racemic Products If optically inactive reagents If optically inactive reagents combine to form a chiral molecule, a racemic mixture is formed.

26. 26 Optical Purity Optical purity o. p e. eOptical purity (o. p.) is sometimes called enantiomeric excess (e. e.). One enantiomerOne enantiomer is present in greater amounts. observed rotation rotation of pure enantiomer X 100o.p. =

27. 27 Calculate % Composition The specific rotation of (S)-2-iodobutane is +15.90 . - Determine the % composition of a mixture of (R)- and (S)-2-iodobutane if the specific rotation of the mixture is -3.18 . 3.18 15.90 X 100o.p. == 20% 2l = 120% l = 60% d = 40% Sign is from the enantiomer in excess: levorotatory.

28. 28 Chirality of Conformers If equilibrium exists between two chiral conformers, the molecule is not chiral. Judge chiralityJudge chirality by looking at the most symmetrical conformer. Cyclohexane can be considered to be planar,Cyclohexane can be considered to be planar, on average.

29. 29 Chirality of Conformational Isomers cis-1,2- The two chair conformations of cis-1,2-dibromocyclohexane are nonsuperimposable, but the interconversion is fast and the molecules are in equilibrium. Any sample would be racemic and, as such, optically inactive.

30. 30 Nonmobile Conformers C—CThe planar conformation of the biphenyl derivative is too sterically crowded. The compound has no rotation around the central C—C bond and thus it is conformationally locked. The staggered conformations are chiral: They are nonsuperimposable mirror images.

31. 31 Allen's Some allen's are chiral even though they do not have a chiral carbon. Central carbon is sp hybridized. To be chiral, the groups at the end carbons must have different groups.

32. 32 2,3-Pentadiene Is Chiral

33. 33 Fischer Projections a 3-D moleculeFlat representation of a 3-D molecule. A chiral carbon is at the intersection of horizontal and vertical lines. Horizontal lines are forward, out-of-plane. Vertical lines are behind the plane.

34. 34 Fischer Projections (Continu.)

35. 35 Fischer Rules Carbon chain is on the vertical line. Highest oxidized carbon is at top. Rotation of 180  in plane doesn’t change molecule. Do not rotate 90  !

36. 36 180° Rotation A rotation of 180° is allowed because it will not change the configuration.

37. 37 90° Rotation A 90° rotation will change the orientation of the horizontal and vertical groups. Do not rotate a Fischer projection 90°.

38. 38 Fischer Mirror Images Fisher projections are easy to draw and make it easier to find enantiomers and internal mirror planes when the molecule has 2 or more chiral centers. CH 3 HCl ClH CH 3

39. 39 Fischer (R) and (S) forward backwardsLowest priority (usually H) comes forward, so assignment rules are backwards! Clockwise 1-2-3 is (S) and counterclockwise 1- 2-3 is (R). Example:Example: (S)(S) (S) CH 3 HCl ClH CH 3

40. 40 Diastereomers Molecules with two or more chiral carbons.Molecules with two or more chiral carbons. Stereoisomers that are not mirror imagesStereoisomers that are not mirror images.

41. 41 Alkenes Cis-transCis-trans isomers are not mirror images, so these are diastereomers.

42. 42 Two or More Chiral Carbons enantiomersdiastereomers meso isomersWhen compounds have two or more chiral centers they have enantiomers, diastereomers, or meso isomers. Enantiomers chiral carbonEnantiomers have opposite configurations at each corresponding chiral carbon. DiastereomersDiastereomers have some matching, some opposite configurations. Meso compoundsMeso compounds have internal mirror planes. 2 n n = the number of chiral carbons.Maximum number of isomers is 2 n, where n = the number of chiral carbons.

43. 43 Comparing Structures

44. 44 Meso compounds have a plane of symmetry.Meso compounds have a plane of symmetry. If one image was rotated 180°, then it could be superimposed on the other image.If one image was rotated 180°, then it could be superimposed on the other image. Meso compounds are achiral even though they have chiral centersMeso compounds are achiral even though they have chiral centers. Meso Compounds

45. 45 Number of Stereoisomers The 2 n rule will not apply to compounds that may have a plane of symmetry. 2,3-dibromo butane has only 3 stereoisomers: (±) diastereomer and the meso diastereomer.

46. 46 Properties of Diastereomers Diastereomers haveDiastereomers have different physical properties, so they can be easily separated. Enantiomers differEnantiomers differ only in reaction with other chiral molecules and the direction in which polarized light is rotated. EnantiomersEnantiomers are difficult to separate. Convert enantiomersdiastereo- mersConvert enantiomers into diastereo- mers to be able to separate them.

47. 47 Resolution of Enantiomers React the racemic mixture with a pure chiral compound, such as tartaric acid, to form diastereomers, then separate them.

48. 48 Chromatographic Resolution of Enantiomers