1. Stereochemistry, Conformation, and Stereoselectivity

2. Stereochemistry: What is It?
Isomers
Molecules with same chemical formula but different spatial arrangement of atoms
Jöns Jakob Berzelius, 1830
Constitutional isomers
Differ in sequence of atom connectivity
Urea
CH4N2O
Ammonium cyanate
CH4N2O

3. Stereochemistry: What is It? Isomers
Conformational isomers
Same sequence of connectivity, but can be interconverted by rotation around a single bond
Butane C4H10
Staggered conformation
click on movie to play
rotate around
C2-C3 bond
Butane C4H10
Eclipsed conformation
Are other isomers possible?
Tetrahedral carbon...

4. Historical Background Timeline A: Light
1678: Christiaan Huygens discovers plane-polarized light
light beam
Iceland spar crystal
(natural CaCO3)
many vibrational planes
nonpolarized light
one vibrational plane
plane-polarized light

5. Historical Background Timeline A: Light
1815: Jean Baptiste Biot notes some natural substances rotate plane-polarized light
plane-polarized light
polarization plane shifted
tube of liquid organic
compound or solution
Optically active: the ability to rotate plane-polarized light
Optically inactive: does not rotate plane-polarized light

6. Historical Background Timeline A: Light
Optical activity
Dextrorotatory: rotates plane-polarized light in a clockwise direction (+)
Levorotatory: rotates plane-polarized light in a counterclockwise direction (-)
(+)-Methamphetamine
(-)-Nicotine

7. Historical Background Timeline B: Tartaric Acid
1769: Carl Wilhelm Scheele examines tartar (deposited in casks
during wine fermentation); isolates tartaric acid
1819: Paul Kester isolates racemic acid from tartar
From Latin racemus: bunch of grapes
1828: Joseph Louis Gay-Lussac shows tartaric acid and racemic
acid are isomers
Tartaric acid
Racemic acid

8. Historical Background Timeline B: Tartaric Acid
1832: Jean Baptiste-Biot notes tartaric acid is optically active
1838: Biot notes racemic acid is optically inactive
1847: Louis Pasteur separates ammonium sodium salt of racemic acid into (+) and (-) crystals

9. Historical Background Timeline B: Tartaric Acid
Pasteur’s separation of racemic acid
(+)-tartaric acid
optically active
identical to Scheele’s tartaric acid
Ammonium sodium racemate
optically inactive
separate crystals
Quantity: equal
Optical activity: equal but opposite
(-)-tartaric acid
optically active
Conclusion: Racemic acid is a 1:1 mixture of two optically-active substances

10. Historical Background Timeline B: Tartaric Acid
1853: Pasteur investigates mesotartaric acid
Mesotartaric acid
Artificial, optically-inactive isomer of tartaric acid
Cannot be separated into (+) and (-) forms
1854: Pasteur notes a certain plant mold metabolizes (+) but not (-)-tartaric acid
Tartaric acid isomers have different biological properties

11. Historical Background Timeline C: Tetrahedral Carbon
1874: Joseph Achille Le Bel (age 27) and Jacobus Henricus van’t Hoff (age 22)
A molecule having a tetrahedral carbon atom with four unequal attachments exists as a pair of isomers.
propose:

12. Historical Background Timeline C: Tetrahedral Carbon
Example: 2-chlorobutane
Same atom connectivity sequence
Constitutional isomers?
Conformational isomers?
Cannot be made superposable by bond rotation
Verify with models
Identical?
Not superposable Verify with models
Stereoisomers: isomers that differ only in the position of atoms in space, and cannot be interconverted by rotation around a single bond

13. Historical Background Timeline C: Tetrahedral Carbon
The 2-chlorobutane stereoisomers have another relationship:
mirror
Observations:
mirror images
Verify with models }
nonsuperposable
Enantiomers: stereoisomers that are nonsuperposable mirror images

14. Historical Background Timeline C: Tetrahedral Carbon
Other useful stereochemistry vocabulary:
Stereocenter: a carbon atom bearing four different substituents.
In general: an atom bearing two or more different substituents whose juxtaposition leads to stereoisomers.
CH3, CH3CH2, Cl, H
A stereocenter
CH3, CH3, Cl, H
Not a stereocenter
Chiral: any object that is not superposable on its mirror image
Example: your hands
Not same meaning as enantiomers
Achiral: any object that is not chiral

15. Historical Background

16. Historical Background Timeline C: Tetrahedral Carbon
At first the “stereoisomer theory” was not well accepted...
Hermann Kolbe comments on “The Arrangement of Atoms in Space” (van’t Hoff’s PhD thesis) in which tetrahedral carbon isomers were proposed.
1877:
“Not long ago, I expressed the view that the lack of general education and of thorough training in chemistry was one of ... the causes of the deterioration of chemical research in Germany..”
Nobel Prize in Chemistry 1901: J. H. van’t Hoff for his studies of chemical dynamics and osmotic pressure

17. Historical Background Timeline C: Tetrahedral Carbon
Why tetrahedral carbon stereoisomer theory not accepted?
All physical properties of enantiomers identical
Exception: direction of plane-polarized light rotation
Physical properties used to separate substances
Enantiomers could not be separated, so their existence was questioned

18. Stereochemistry
Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.

19. Definitions
Stereoisomers – compounds with the same connectivity, different arrangement in space
Enantiomers – stereoisomers that are non- superimposible mirror images; only properties that differ are direction (+ or -) of optical rotation
Diastereomers – stereoisomers that are not mirror images; different compounds with different physical properties

20. More Definitions
Asymmetric center – sp3 carbon with 4 different groups attached
Optical activity – the ability to rotate the plane of plane –polarized light
Chiral compound – a compound that is optically active (achiral compound will not rotate light)
Polarimeter – device that measures the optical rotation of the chiral compound

21. Optically Active
Refers to molecules that interact with plane-polarized light
Jean Baptiste Biot
French Physicist
He discovered that some natural substances (glucose, nicotine, sucrose) rotate the plane of plane-polarized light and that others did not.