7.7 Fischer Projections

1. 7.7 Fischer Projections • Purpose of Fischer projections is to show configuration at chirality center without necessity of drawing wedges and dashes or using models.

2. Rules for Fischer projections Arrange the molecule so that horizontal bonds at chirality center point toward you and vertical bonds point away from you. H Cl Br F

3. Rules for Fischer projections H Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back. Br Cl F

4. Rules for Fischer projections H Projection of molecule on page is a cross. When represented this way it is understood that horizontal bonds project outward, vertical bonds are back. Br Cl F

5. 7.8Physical Properties of Enantiomers

6. Physical properties of enantiomers Same: melting point, boiling point, density, etc Different: properties that depend on shape of molecule (biological-physiological properties) can be different

7. Odor CH3 CH3 O O H3C H3C CH2 CH2 (–)-Carvonespearmint oil (+)-Carvonecaraway seed oil

8. H H3C CH2CH(CH3)2 C C HO O Chiral drugs Ibuprofen is chiral, but normally sold asa racemic mixture. The S enantiomer is the one responsible for its analgesic and antiinflammatory properties.

9. 7.9Reactions That Create A Chiral Center

10. Many reactions convert achiral reactants to chiral products. It is important to recognize, however, that if all of the components of the starting state (reactants, catalysts, solvents, etc.) are achiral, any chiral product will be formed as a racemic mixture. This generalization can be more simply stated as "Optically inactive starting materials can't give optically active products."(Remember: In order for a substance to be optically active, it must be chiral and one enantiomer must be present in greater amounts than the other.

11. O H CH3COOH CH3CH H3C CH2 C CH2 O Example Chiral, but racemic Achiral

12. epoxidation from this direction gives R epoxide R

13. epoxidation from this direction gives R epoxide R S epoxidation from this direction gives S epoxide

14. epoxidation from this direction gives R epoxide 50% R 50% S epoxidation from this direction gives S epoxide

15. CH3CH CH2 Example Chiral, but racemic Br2, H2O CH3CHCH2Br OH Achiral

16. CH3CH CHCH3 Example Chiral, but racemic HBr CH3CHCH2CH3 Br Achiral

17. Many reactions convert chiral reactants to chiral products. However, if the reactant is racemic, the product will be racemic also. Remember: "Optically inactive starting materials can't give optically active products."

18. CH3CHCH2CH3 CH3CHCH2CH3 OH Br Example HBr Chiral, but racemic Chiral, but racemic

19. Many biochemical reactions convertan achiral reactant to a singleenantiomer of a chiral product Reactions in living systems are catalyzed by enzymes, which are enantiomerically homogeneous. The enzyme (catalyst) is part of the reacting system, so such reactions don't violate the generalization that "Optically inactive starting materials can't give optically active products."

20. H HO2C C OH C C HO2CCH2 Example HO2C H H2O fumarase CO2H H Fumaric acid (S)-(–)-Malic acid Achiral Single enantiomer

21. 7.10Chiral MoleculeswithTwo Chirality Centers How many stereoisomers when a particular molecule contains two chiral centers?

22. O CH3CHCHCOH HO OH 2,3-Dihydroxybutanoic acid 2 3 What are all the possible R and S combinations of the two chirality centers in this molecule?

23. O CH3CHCHCOH HO OH 2,3-Dihydroxybutanoic acid 2 3 What are all the possible R and S combinations of the two chirality centers in this molecule? Carbon-2 R R S S Carbon-3 R S R S

24. O CH3CHCHCOH HO OH 2,3-Dihydroxybutanoic acid 2 3 4 Combinations = 4 Stereoisomers Carbon-2 R R S S Carbon-3 R S R S

25. O CH3CHCHCOH HO OH 2,3-Dihydroxybutanoic acid 2 3 4 Combinations = 4 Stereoisomers What is the relationship between these stereoisomers? Carbon-2 R R S S Carbon-3 R S R S

26. O CH3CHCHCOH HO OH 2,3-Dihydroxybutanoic acid 2 3 enantiomers: 2R,3R and 2S,3S 2R,3S and 2S,3R Carbon-2 R R S S Carbon-3 R S R S

27. CO2H CO2H R S HO OH H H OH HO H H R S CH3 CH3 CO2H CO2H S R OH HO H H OH H HO H R S CH3 CH3 [a] = -9.5° [a] = +9.5° enantiomers enantiomers [a] = +17.8° [a] = -17.8°

28. O CH3CHCHCOH HO OH 2,3-Dihydroxybutanoic acid 3 2 stereoisomers that are not enantiomers are: diastereomers……. similar but not identical chemical and physical properties but not all relationships are enantiomeric Carbon-2 R R S S Carbon-3 R S R S

29. Isomers constitutional isomers stereoisomers enantiomers diastereomers

30. CO2H CO2H R S HO OH H H OH HO H H R S CH3 CH3 CO2H CO2H S R OH HO H H OH H HO H R S CH3 CH3 [a] = -9.5° [a] = +9.5° enantiomers diastereomers enantiomers [a] = +17.8° [a] = -17.8°

31. Fischer Projections CO2H recall for Fischer projection: horizontal bonds point toward you; vertical bonds point away staggered conformation does not have correct orientation of bonds for Fischer projection CH3

32. Fischer projections transform molecule to eclipsed conformation in order to construct Fischer projection

33. CO2H OH H H OH CH3 Fischer projections

34. Erythro and Threo stereochemical prefixes used to specify relative configuration in molecules with two chirality centers easiest to apply using Fischer projections orientation: vertical carbon chain

35. CO2H OH H H OH CH3 Erythro when carbon chain is vertical, same (or analogous) substituents on same side of Fischer projection CO2H H HO HO H CH3 –9.5° +9.5°

36. CO2H CO2H OH H H HO HO H OH H CH3 CH3 Threo when carbon chain is vertical, same (or analogous) substituents on opposite sides of Fischer projection +17.8° –17.8°

37. Two chirality centers in a ring nonsuperposable mirror images; enantiomers R S R S trans-1-Bromo-2-chlorocyclopropane

38. Two chirality centers in a ring nonsuperposable mirror images; enantiomers S S R R cis-1-Bromo-2-chlorocyclopropane

39. Two chirality centers in a ring stereoisomers that are not enantiomers; diastereomers S S R R cis-1-Bromo-2-chloro-cyclopropane trans-1-Bromo-2-chloro-cyclopropane

40. 7.11Achiral MoleculeswithTwo Chirality Centers It is possible for a molecule to have chirality centers yet be achiral.

41. CH3CHCHCH3 HO OH 2,3-Butanediol 3 2 Consider a molecule with two equivalently substituted chirality centers such as 2,3 butanediol.

42. Three stereoisomers of 2,3-butanediol 2R,3R 2S,3S 2R,3S chiral chiral achiral

43. CH3 CH3 CH3 H HO OH OH H H HO OH H OH H H CH3 CH3 CH3 Three stereoisomers of 2,3-butanediol 2R,3R 2S,3S 2R,3S chiral chiral achiral

44. Three stereoisomers of 2,3-butanediol these two areenantiomers 2R,3R 2S,3S chiral chiral

45. CH3 CH3 H HO OH H HO OH H H CH3 CH3 Three stereoisomers of 2,3-butanediol these two areenantiomers 2R,3R 2S,3S chiral chiral

46. Three stereoisomers of 2,3-butanediol the third structure is superposable on its mirror image 2R,3S achiral

47. Three stereoisomers of 2,3-butanediol therefore, this structure and its mirror imageare the same it is called a meso form a meso form is an achiral molecule that has chirality centers 2R,3S achiral

48. CH3 OH H OH H CH3 Three stereoisomers of 2,3-butanediol CH3 therefore, this structure and its mirror image are the same it is called a meso form a meso form is an achiral molecule that has chirality centers H HO H HO CH3 2R,3S achiral

49. Three stereoisomers of 2,3-butanediol meso forms have a plane of symmetry and/or a center of symmetry plane of symmetry is most common case top half of molecule is mirror image of bottom half 2R,3S achiral

50. CH3 CH3 H HO OH H OH H HO H CH3 CH3 Three stereoisomers of 2,3-butanediol A line drawnthe center ofthe Fischer projection of ameso formbisects it intotwo mirror-image halves. 2R,3S achiral