Chapter 3 Stereochemistry and Conformational
Analysis
1. Conformational analysis
2. Strain
3. 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.

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 .

Wiberg bent bond model
ACR 1996 , 29 , 229.

Gauche interaction
0.9 kcal

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

H H
H C
H N
H O
H F
H Cl
H Br
H I
74
109
101
96
92
127
141
161
C C
C C
C C
C N
C O
C S
C F
C Cl
C Br
C I
154
134
120
147
143
182
135
177
194
214
O O
O O
N N
N N
F F
Cl Cl
Br Br
I I
148
121
145
110
142
199
228
267

- Bond length strain
(normal C-C bond length ~ 1.54 A )
Ar
Ar
Ar
Ar
C C
Ar
Ar
Ar =
1.64-5 A
JACS 1988 , 110 , 6670.
1.38 A
I
1.47 A
I
1.463 A
JACS 1999 , 121 , 4111.
Me
3
Si
Me
3
Si
Me
3
Si
SiMe
3
SiMe
3
SiMe
3
1.436 A
ACIE 2005 , 44 , 5821.
- Angle strain-small rings and medium rings
For cyclopropane, reduction of “bond angles from ideal 109.5
o to 60 o , 27.5
Kcal/mol of strain energy .
128 o
Medium rings (8-11)
Bond angles enlarged from ideal 109.5
o to 115-120 o to reduce
Transannular interactions.

- Torsional strain
Deviation from ideal dihedral angle of 60 o 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.

H
3
CCH
3
• CH
3
-10.05 Kcal/mol
• CH
2
-5.13 Kcal/mol
• CH -2.16 Kcal/mol
• C -0.30 Kcal/mol

Tetrahedron
(fire)
Cube
(earth)
Dodecahedron
(“ether”)
There are two more: icosahedron (water) and octahedron (air)
Can we make the corresponding hydrocarbon frames (CH) n
?

Maier, 1978, tetra-t-Butetrahedrane .
Substituted C
4
H
4 m.p. 135 ° C !
Strain:
130 kcal mol -1 m.p. 202
°
C
Maier, Sekiguchi, 2002, tetrakis(trimethylsilyl)tetrahedrane .
Eaton, 1964, cubane , C
8
H
8 m.p. 126
°
C
Strain:
166 kcal mol -1 m.p.
430
°
C !
Strain:
60 kcal mol -1
Paquette, 1982, dodecahedrane , C
12 faces
20
H
20
,

Eaton, Adv. Mat., 2000.

• Absolute configuration
Fischer’s Definition on D and L
CPI Notation
• Enantiomers vs diastereomers
• Meso form vs dl form
• Enantiotopic vs diastereotopic
H H
Ph O
H
Ph
H H
OH
Ph

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

• 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 .