Chapter 3 Stereochemistry and Conformational Analysis

1. Conformational analysis2. Strain3. 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.

F-Gauche effect

Wiberg bent bond model

ACR 1996, 29, 229.

Gauche interaction0.9 kcal

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

Bond lengths (pm)

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

154

134

120

147

143

182

135

177

C Br

C I

194

214

O O

O O

N N

F F

Cl Cl

Br Br

I I

148

121

145

142

199

228

267

N N 110

Strain

- 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.

C C

Ar

Ar

ArAr

ArAr

Ar =

1.64-5 A

JACS 1988, 110, 6670.

II 1.463 A

JACS 1999, 121, 4111.

SiMe3

SiMe3

SiMe3Me3Si

Me3Si

Me3Si

1.436 A

ACIE 2005, 44, 5821.

- Bond length strain (normal C-C bond length ~ 1.54 A)

128o

Medium rings (8-11)Bond angles enlarged from ideal 109.5o to 115-120o to reduceTransannular interactions.

1.47 A

1.38 A

Strain (continued)

- Torsional strainDeviation 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 interactionsAnalogous 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.

Group increments for heat of formation

• CH3 -10.05 Kcal/mol

• CH2 -5.13 Kcal/mol

• CH -2.16 Kcal/mol• C -0.30 Kcal/mol

H3CCH3

Strained Hydrocarbons: What is the Strained Hydrocarbons: What is the limit? Exotic polyhedra: The Five limit? Exotic polyhedra: The Five Platonic Platonic or or Cosmic Solids Cosmic Solids (Plato 350 (Plato 350 BC)BC)

TetrahedronTetrahedron(fire)(fire)

CubeCube(earth)(earth)

DodecahedronDodecahedron(“ether”)(“ether”)

Can we make the corresponding hydrocarbon frames (CH)Can we make the corresponding hydrocarbon frames (CH)n n ??

There are two more: icosahedron (water) and octahedron (air)There are two more: icosahedron (water) and octahedron (air)

Maier, Sekiguchi, 2002,Maier, Sekiguchi, 2002,tetrakis(trimethylsilyl)-tetrakis(trimethylsilyl)-tetrahedranetetrahedrane..

m.p. 135°C m.p. 135°C

!! Strain: Strain: 130 kcal 130 kcal molmol-1-1

Strain: Strain: 166 kcal 166 kcal molmol-1-1

Strain: Strain: 60 kcal 60 kcal molmol-1-1

Eaton, 1964,Eaton, 1964,cubanecubane, , CC88HH88

Maier, 1978, Maier, 1978, tetra-tetra-tt-Bu--Bu-tetrahedranetetrahedrane..Substituted Substituted CC44HH44

Paquette, 1982, Paquette, 1982, dodecadodecahedranehedrane, , CC2020HH2020, 12 , 12 facesfaces

m.p. 202°C m.p. 202°C

m.p. 126°C m.p. 126°C

m.p. m.p. 430°C !430°C !

Octanitrocubane: a New Explosive and Rocket Fuel

Eaton, Eaton, Adv. MatAdv. Mat., ., 2000.2000.

Stereochemistry-a brief review

• Absolute configurationFischer’s Definition on D and L

CPI Notation

• Enantiomers vs diastereomers• Meso form vs dl form• Enantiotopic vs diastereotopic

Ph O

HH

PhOH

HHPhH

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

• Stereoselectivity. The preferential formation of one stereoisomer ov

er another in a chemical reaction. If the stereoisomers are enantiomers, on

e speaks of enantioselectivity [quantified by enantiomer excess]; if they are

diastereomers, one speaks of diastereoselectivity. The term enantioselectiv

e may be applied to the ultimate outcome of a sequence of reactions, even i

f individual steps are diastereoselective.

• Stereospecific. A reaction is termed stereospecific if, in such a reacti

on, starting materials differing only in their configuration are converted to ste

reoisomerically distinct products. According to this definition, a stereospecifi

c process is necessarily stereoselective, but stereoselectivity does not nece

ssarily imply stereospecificity.

Examples: Bromine addition to cis- and trans-stilbenes

The use of the term “stereospecific” merely to mean “highly stereoselective” is discouraged.