Stereochemistry I

Chemistry 355

Stereochemistry
Refers to the spatial arrangement of atoms. Stereochemistry is described in several terms.
Relative configuration
Relative to a standard compound Relative to another function in the molecule

Absolute configuration
Refers to absolute arrangement in space for enantiomers

Relative Stereochemistry
Cis
Rings
NH2

Trans
Rings
NH2

NH2

NH2

Alkenes
Z (zussamen together)

Alkenes
E (entgegen opposite)

Relative Stereochemistry
Syn
Same side Erythro (sugars) Absolute assignments preferred
R R NH2 R R NH2 H H R

Anti
Opposite side Threo (sugars)

R H H R NH2 R

R H

R NH2

H2N H2N

H2 N H2 N R

H2N H

H2 N H R

H NH2

NH2

Absolute Stereochemistry at Tetrahedral Atoms

Chirality
Non-superimposeable Mirror images Requires 4 different groups May or may not be stable (Amines) Called enantiomers Configuration R or S Build these models
OH

(R)

mirror
(S)

OH

Absolute Configuration
Cahn-Ingold-Prelog
Prioritize substituents
Highest atomic # When two of same, go one atom further Place lowest priority substituent to rear

1 OH
H

4 H
C

Multiple bonds are treated as two substituents

C=O is treated as O-C-O

3 3
C

2 2 S
C C

mirror

Sense of direction
Down priority list 1-3 R rectus Right (clockwise) H S sinistere Left (CCW)

1 OH

Diastereomers
Diastereomers have multiple stereocenters Differ by one or more, but not all configurational centers
NH2
(R) (R)

NH2

Diastereomers
OH

(R) (S)

Enantiomers

Enantiomers

OH

mirror
OH
(S) (S)

OH

Diastereomers

(R) (S)

NH2

NH2

meso-Compounds
A meso-compound (syn. mesosteroisomer, mesomer) is a diastereomer which is the same as its mirror image and therefore not chiral (achiral).
NH2
(R) (R)

NH2

Diastereomers
NH2

(R)

Same molecule

(S)

Enantiomers

NH2

mirror
NH2
(S) (S)

NH2

Diastereomers

(R) (S)

NH2

NH2

meso-Compounds
Most meso-Compounds have internal mirror planes* One half of the molecule is the reflection of the other. The stereocenters effectively oppose one another Chiral molecules contain no mirror planes
NH2 Cl

R S
NH2

mirror

H Cl

CH3

mirror

Mirror plane 2 stereocenters meso achiral

Mirror plane No stereocenters Not meso achiral

*Note: For true meso-compounds, these planes exist in representation only. In reality, they are often conformers that interconvert rapidly on a laboratory timescale. There are examples that do not and are chiral (atropisomers). The precise definition of a mesomer is an achiral member of a set of diastereomers that includes at least one chiral member.

Absolute Configuration
Use models
Physical models
Hand model (free and always with you) Styrofoam balls and toothpicks H (cheap) Model Kit ($10-$50 but worth every penny) available for use in class. May be checked out.

1 OH 4 H
C C

3 3
C

2 2 S
C C

mirror

Virtual model
Chem3D Hyperchem RasMol H Online versions available Freeware Best in conjunction with a physical model

1 OH

Optical Rotation
Chiral compounds have a property called helicity When light interacts with the molecule it is rotated slightly with respect to the incident light. This is observed by irradiating with light that has been plane polarized using filters

Cl CH3

Sample

Polarimetry
2 polarizing filters 1 rotatable Measure angle of rotation on scale Sample rotation

T
Specific rotation
[] T = c l
concentration in g/mL length in decimeters

Specific Rotation
Defined temperature Defined wavelength
Sodium D line 589 nm Often denoted as subscript D

T= [] c l
c is concentration in g/mL density for neat liquids (NOTE: reported as g/100mL) l is cell length in decimeters

25 25.3 (c = 2, EtOH) [] D
Rotation at 25oC at 589 nm with a concentration of 2 grams per 100 mL in ethanol

Wavelength Dependence
Optical rotation is dependent on wavelength Depends on absorbance () Light interacts with various features Greater leads to greater rotation

Stereochemical effects
Stereochemistry is involved many chemical reactions
As a consequence (creation of a new stereocenter) As an influence (diastereoselection)

It is intimately linked to the mechanism of reactions Stereocenters may be created, destroyed or altered
X H H OH O CH3

Substitution

CH3

Oxidation

CH3

O H

OH

HO

Reduction
CH3 CH3

CH3

Substitution
H Br H
-

H OH OH CH3 CH3

OH

Br

CH3

SN2

SN 1

H2O

inversion

+
H OH HO H

-H+
CH3 CH3

CH3

racemization

Elimination
CH3

Br

H2SO4 E1 +
Ph H3C Ph H

tBuOE2
H

Ph H

H3C Ph Br

CH3 Ph Ph H Ph

CH3 H Ph Ph

CH3 Ph

Elimination
O H O O O O O H O O

TsO

O H

O O O O

O H

Elimination
O H O O O O O H O O

TsO

O H

O O O O

O H

Reduction
O H OH HO H

BH3
CH3 Ph CH3

Ph

CH3

BR2 H CH3

R B H

R H O Ph CH3 OH

CH3

CH3

Nucleophilic attack
HCH3 O OH

CH3Li
CH3 O OH

OH O

CH3Li
CH3

Oxidation

R O O O H

OsO4
O O Os O H O Ph H

RCO3H

H Ph H

Ph

Ph

OH O O

OH Ph

+
Ph Ph Ph Ph Ph OH

+
Ph OH

Ph