1. Chapter 3 Stereochemistry and Conformational Analysis
Strain
A brief review on stereochemistry
Suggested Readings:
Please refresh your 1st year organic chemistry on this topic.
E. V. Anslyn and D. A. Dougherty “Modern Physical Organic Chemistry”, University Science Books, 2006, Chapters 2 and 8.
E. L. Eliel and S. H. Wilen “Stereochemistry of Organic Compounds”, Wiley, 1994, Chapters 10 and 11.

3. This symbol (☮) was adopted as its badge by the Campaign for Nuclear Disarmament
in Britain, and originally, its use was confined to supporters of that organization.
It was later generalised to become an icon of the 1960s anti-war movement, and was also
adopted by the counterculture of the time. It was designed and completed February 21,
1958 by Gerald Holtom, a commercial designer and artist in Britain.

6. F-Gauche effect
Wiberg bent bond model
ACR 1996, 29, 229.

9. Gauche interaction
0.9 kcal

10. Fluorine atom is small !!
Schlosser, M. Tetrahedron 1978, 34, 3.

16. Bond lengths (pm)

17. Strain - Bond length strain (normal C-C bond length ~ 1.54 A)
JACS 1988, 110, 6670.
1.47 A
1.436 A
ACIE 2005, 44, 5821.
1.463 A
JACS 1999, 121, 4111.
- Angle strain-small rings and medium rings
For cyclopropane, reduction of “bond angles from ideal 109.5o to 60o, 27.5 Kcal/mol of strain energy.
Medium rings (8-11)
Bond angles enlarged from ideal 109.5o to o to reduce
Transannular interactions.

18. Strain (continued) - Torsional strain - Nonbonding interactions
Deviation from ideal dihedral angle of 60o and approach an eclipsing interaction.
5-, 6- and 7-membered rings are largely unstrained and
the strain that is present is largely torsional strain.
- Nonbonding interactions
Analogous to 1,3-diaxial interactions in cyclohexanes,
but can be 1,3-, 1,4-, or 1,5-… This kind of interaction is commonly seen in
medium rings (8-11).
Large rings (12-membered and up) have little or no strain.

19. Group increments for heat of formation
CH Kcal/mol
CH Kcal/mol
CH Kcal/mol
C Kcal/mol

21. Strained Hydrocarbons: What is the limit
Strained Hydrocarbons: What is the limit? Exotic polyhedra: The Five Platonic or Cosmic Solids (Plato 350 BC)
The Platonic solids, also called the regular solids or regular polyhedra, are convex polyhedra with equivalent faces composed of congruent convex regular polygons. There are exactly five such solids (Steinhaus 1999, pp ): the cube, dodecahedron, icosahedron, octahedron, and tetrahedron, as was proved by Euclid  in the last proposition of the Elements. The Platonic solids are sometimes also called "cosmic figures" (Cromwell 1997), although this term is sometimes used to refer collectively to both the Platonic solids and Kepler-Poinsot solids (Coxeter 1973).
The Platonic solids were known to the ancient Greeks, and were described by Plato  in his Timaeus ca. 350 BC  . In this work, Plato equated the tetrahedron with the "element" fire, the cube with earth, the icosahedron with water, the octahedron with air, and the dodecahedron with the stuff of which the constellations and heavens were made (Cromwell 1997).
Tetrahedron
(fire)
Cube
(earth)
Dodecahedron
(“ether”)
There are two more: icosahedron (water) and octahedron (air)
Can we make the corresponding hydrocarbon frames (CH)n ?

22. Paquette, 1982, dodecahedrane, C20H20, 12 faces
m.p. 135°C !
m.p. 126°C
Strain: 130 kcal mol-1
Strain: 166 kcal mol-1
Maier, 1978,
tetra-t-Bu-
tetrahedrane.
Substituted C4H4
Eaton, 1964,
cubane, C8H8
m.p.
430°C !
m.p. 202°C
Strain: 60 kcal mol-1
Dodecahedrane 23 steps from cyclopentadiene. 1.5mg in first synthesis. Prinzbach grams.
Paquette, 1982, dodecahedrane, C20H20, faces
Maier, Sekiguchi, 2002,
tetrakis(trimethylsilyl)-
tetrahedrane.

23. Octanitrocubane: a New Explosive and Rocket Fuel
Eaton, Adv. Mat., 2000.

24. Stereochemistry-a brief review
Absolute configuration
Fischer’s Definition on D and L
CPI Notation
Enantiomers vs diastereomers
Meso form vs dl form
Enantiotopic vs diastereotopic

25. 1H-1H Couplings-A Review
Any two nuclei with nuclear spin spaced by no more than three covalent bonds may couple.
Coupling constants between two 1H nuclei depends on several factors:
- dihedral angle
- geminal coupling
- number of covalent bonds between these two nuclei
- long range coupling

26. Stereoselectivity. The preferential formation of one stereoisomer over another in a chemical reaction. If the stereoisomers are enantiomers, one speaks of enantioselectivity [quantified by enantiomer excess]; if they are diastereomers, one speaks of diastereoselectivity. The term enantioselective may be applied to the ultimate outcome of a sequence of reactions, even if individual steps are diastereoselective.
Stereospecific. A reaction is termed stereospecific if, in such a reaction, starting materials differing only in their configuration are converted to stereoisomerically distinct products. According to this definition, a stereospecific process is necessarily stereoselective, but stereoselectivity does not necessarily imply stereospecificity.
Examples: Bromine addition to cis- and trans-stilbenes
The use of the term “stereospecific” merely to mean “highly stereoselective” is discouraged.