Unit 3

1. Unit 3 Stereochemistry

2. Stereochemistry • Chirality and Stereoisomers • Configuration vs. Conformation • (R) and (S) Configurations • Optical Activity • Fischer Projections • Diastereomers • Relative Configurations - The D-L System • Resolution of Enantiomers

3. Stereochemistry • Stereochemistry is the study of the three-dimensional structure of molecules. • Central to this study is the notion of chirality. An object is chiral if it has a nonsuperimposable mirror image. • An object is achiral if it is identical to its mirror image.

4. Mirror Images and Chirality From Wikipedia, “Mirror Images”

5. Chirality in Organic Compounds • We are, of course, interested in organic compounds. How do we decide if a compound is chiral? • 0 asymmetric C atoms* in the compound: usually achiral. • 1 asymmetric C atom* in the compound: chiral. • >1 asymmetric C atoms in the compound: may or may not be chiral. *The asymmetric atom can be an element other than C.

6. Asymmetric C Atoms • An asymmetric C atom is the same as a chiral C atom. • It is a C atom bonded to four different groups. • A chiral C atom is designated by an asterisk (*).

7. Asymmetric Atom Equals Chiral Atom N is the asymmetric atom here.

8. Stereocenter • This is a broader term than chiral C atom. • A stereocenter is any atom at which the interchange of two groups gives a stereoisomer. • Chiral C atoms are stereocenters. • But so are the double-bonded C atoms in cis-trans isomers.

9. Stereoisomers • Isomers are compounds with the same molecular formula. • Structural isomers have different bonding patterns (different connections between the atoms). • Stereoisomers have identical bonding patterns but differ in how the atoms are oriented in space. • Enantiomers are mirror image isomers. • Diastereomers are stereoisomers that are not mirror images.

10. Stereocenters stereocenters geometric isomers (diastereomers) enantiomers

11. Drawing a Mirror Image • Leave the vertical arrangement alone. • Switch left and right.

12. Mirror Plane of Symmetry • Any molecule with an internal mirror plane of symmetry cannot be chiral, even if it has chiral C atoms. achiral Where is the plane of symmetry? chiral, enantiomers achiral diastereomers

13. Configuration vs Conformation • In this unit, we talk about the configuration of molecules. • Configuration refers to the 3D arrangement of atoms in space. • Conformations come from a single configuration as groups are rotated around their sigma bonds.

14. (R) and (S) Nomenclature of Asymmetric C Atoms • Cahn-Ingold-Prelog Convention • Each asymmetric C atom is assigned (R) or (S) based on its 3D configuration. • Each of the four groups on the asymmetric C atom is assigned a priority: 1(highest), 2, 3, 4(lowest). • Place group 4 behind the C atom, then draw a curved arrow from group 1 to group 2 to group 3. • If the arrow goes clockwise (CW): (R) • If the arrow goes counterclockwise (CCW): (S)

15. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • The higher the atomic number Z, the higher the priority. • The isotope with the higher mass number has higher priority: 2H (or D) (deuterium) has higher priority than 1H. • In case of a tie, use the Z of the next atom along. • Treat double and triple bonds as if each were a bond to a separate atom.

16. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • The higher the atomic number Z, the higher the priority. 3 4 (S) 2 1 1 3 2 Assign priorities. Put lowest priority in back. Draw an arrow: 1-2-3.

17. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • The higher the atomic number Z, the higher the priority. 3 The arrow goes CCW, so the configuration is (S). 1 2 (S)-1-bromo-1-chloroethane

18. Nomenclature • Below is the template you will use to build the name of ANY organic compound.

19. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • In case of a tie, use the next atom along. C bonded to H, C, C: priority 1 C bonded to H, H, C: tie for 2. But the next C is also bonded to H,H,C: priority 2. C bonded to H, H, C: tie for priority 2. But the next C is H,H,H: priority 3. C bonded to H, H, H: priority 4

20. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • In case of a tie, use the next atom along. 1 (R) 3 3 2 2 4 1 Put lowest priority in back. 1-2-3 arrow is CW: (R)

21. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • In case of a tie, use the next atom along. 3 (R) 2 1 (R)-3-ethyl-2,3-dimethylhexane

22. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • Treat double and triple bonds as if each were a bond to a separate atom.

23. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • Treat double and triple bonds as if each were a bond to a separate atom. (R)-2,3-dihydroxypropanal

24. (R) and (S) Nomenclature of Asymmetric C Atoms • Assigning priorities • Treat double and triple bonds as if each were a bond to a separate atom. (S)-carvone *

25. Drawing the Structure of a Chiral Compound • Draw the structure of (S)-2-bromobutane. • Identify the chiral C. • Assign priorities to the four groups on the C atom. • Put the lowest priority group in back.

26. Drawing the Structure of a Chiral Compound • Draw the structure of (S)-2-bromobutane. • Put the highest priority group on top. • For (R), put the priority #2 group on the right and the priority #3 group on the left. • For (S), put the priority #3 group on the right and the priority #2 group on the left.

27. Drawing the Structure of a Chiral Compound • Draw the structure of (S)-2-bromobutane. • Double check your structure to make sure it has the specified configuration.

28. Drawing the Structure of a Chiral Compound • Alanine, NH2CH(CH3)CO2H, is an amino acid. • Draw (R)-alanine and (S)-alanine. • Nearly all naturally-occurring amino acids have the (S) configuration on theαC.

29. Name This Compound • First, get the “nonstereochemical” name: • 3-bromo-1,1-dimethylcyclopentane • Then bring in the stereochemistry: • (R)-3-bromo-1,1-dimethylcyclopentane