1. Unit 3 Stereochemistry

2.  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 enantiomers geometric isomers (diastereomers)

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 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: 2 H (or D) (deuterium) has higher priority than 1 H. 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. Assign priorities. 2 1 32 3 Put lowest priority in back. Draw an arrow: 1-2-3. 1 4 (S)

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

18. Nomenclature  Below is the template you will use to build the name of ANY organic compound. stereo- isomerism substituents main chain unsaturation functional group

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, H, C: tie for priority 2. But the next C is H,H,H: priority 3. 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, H: priority 4

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

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. 1.Identify the chiral C. 2.Assign priorities to the four groups on the C atom. 3.Put the lowest priority group in back.

26. Drawing the Structure of a Chiral Compound  Draw the structure of (S)-2-bromobutane. 4.Put the highest priority group on top. 5.For (R), put the priority #2 group on the right and the priority #3 group on the left. 6.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. 7.Double check your structure to make sure it has the specified configuration.

28. Drawing the Structure of a Chiral Compound  Alanine, NH 2 CH(CH 3 )CO 2 H, is an amino acid. Draw (R)-alanine and (S)-alanine.  Nearly all naturally-occurring amino acids have the (S) configuration on the α C.

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