INTRODUCTION TO STEREOCHEMISTRY

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Isomers are compounds with the same molecular formula but not identical structures

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Constitutional isomers are isomers which have the same molecular formula but differ in the way their atoms are connected

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Constitutional Isomers Constitutional isomers are isomers which have the same molecular formula but differ in the way their atoms are connected

H 3C C H2

H2 C CH 3
H3 C

CH 3 CH CH3

butane Chemical Formula: C4H10

2-methylpropane Chemical Formula: C4H10

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Stereoisomers have the same molecular formula, maintain the same connectivity, but differ in the way their atoms are arranged in space

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Conformational isomers (or conformers or rotational isomers or rotamers) are stereoisomers produced by rotation about single bonds, and are often rapidly interconverting at room temperature

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Conformations of Alkanes and Cycloalkanes Conformations of Ethane

H 3C
ethane Staggered conformation of ethane

CH 3
Eclipsed conformation of ethane
H

H H H H H H

H H
H

H H

H H
H H

H H
H

Newman Projection
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Sawhorse Representatio n

Newman Projection

Sawhorse Representatio n

ethane Staggered conformation of ethane

H H H H
H H H H

Eclipsed conformation of ethane

H H
H H

H H
H H

H H

H H

H H
H

Newman Projection

Sawhorse Representatio n

Newman Projection

Sawhorse Representatio n

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Configurational Isomers are stereoisomers that do not readily interconvert at room temperature and can (in principle at least) be separated.

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Geometric isomers are configurational isomers that differ in the spatial position around a bond with restricted rotation (e.g. a double bond):
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Geometric (Cis and Trans) Isomers Geometric (Cis and Trans) Isomers result from restriction rotation Compounds with double bonds cis isomer have same substituents on the same side of the double bond (= Z with more complex molecules having high priority groups on the same side) trans isomer have the same substituents on the opposite side of the double bond (= E with more complex molecules having high priority groups on opposite sides) Compounds with bonds in a ring: cis isomer have the same substituents on the same side of the ring trans isomer - have the same substituents on the opposite side of the ring

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Cis-trans (Geometric) isomerism in Alkenes

Cl C H C H Cl

H C Cl C

Cl

cis-1,2dichloroethene (Z)-1,2dichloroethene

trans-1,2dichloroethene (E)-1,2dichloroethene

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Cis-trans (Geometric) isomerism in Alkenes

*If one of the two carbon atoms of the double bond has two identical substituents, there are no cis-trans isomers for that molecule

H C H C

Cl

Cl

1,1dichloroethene

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Identifying cis and trans isomers of Alkenes

Example 11.3 Two isomers of 2-butene are shown below. Which is the cis isomer and which is the trans isomer

H C H 3C C

H C C

CH 3

CH 3

H 3C

cis-2-butene

trans-2-butene

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Naming cis and trans compounds

Example 11.4 Name the following geometric isomers.

H3 C

Cl H2 C H3 C C H2 C C Cl H2 C CH 3
H3 C

CH 2 C C CH3 H2 C C H2 H2 C CH 3

trans-3,4-dichloro-3heptene

cis-3,4-dimethyl-3octene

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Identifying Geometric Isomers Example 11.5 Determine whether each of the following molecules can exist as cis-trans isomers: (1) 1-pentene (2) 3-ethyl-3-hexene (3) 3-methyl-2-pentene
H C H C H
H3 CH2 C

CH2CH 2CH 3

H C C

CH 2CH 3

CH 2CH 3

1-pentene
H3 C C H3 CH2 C C H CH 3

3-ethyl-3-hexene
H3 C C H3 CH2 C C CH 3 H

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trans-3-methyl-2-pentene

Cis and Trans Fatty Acids

H H

cis-9-octadecenoic acid

OH

OH H

trans-9-octadecenoic acid
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Cis-trans (Geometric) isomerism in Cycloalkanes

Cis-trans isomers are molecules having the same arrangement of atoms but differ in the spatial orientation of their substituents.

H H H H H Cl

H H H H H Cl

H H H Cl H H

H H H H H Cl

cis-1,2dichlorocyclohexane
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trans-1,2dichlorocyclohexane

Naming cis-trans Isomers of Substituted Cycloalkanes Example 10.6 Determine whether the following susbstituted cycloalkanes are cis or trans isomers.

H H CH3 H H CH 3 H H
H CH3

H H H

H CH 3

trans-1,2dimethylcyclopentane
CH 3

cis-1,2dimethylcyclopentane

CH 3
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CH 3

CH 3

Conformations of Alkanes and Cycloalkanes Conformations of Cyclohexane

H H H H H H cyclohexane H H H H H H

Chair conformation of cyclohexane

A E E A A E A A E A
E

Boat conformation of cyclohexane

A E E A A A E A A E E

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Chair conformation of cyclohexane

A E E A A E A A E A
E

Boat conformation of cyclohexane

A E E A A A E A A E E

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Chair-Chair Interconversion

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Optical isomers are configurational isomers that differ in the 3D relationship of the substituents about one or more atoms.
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Diastereomers are optical isomers (stereoisomers) that are not enantiomers.

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Enantiomers are optical isomers that are non-superimposable mirror images.

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Chirality

Chiral objects are objects with left-handed and right-handed forms Achiral objects - objects that have superimposable mirror images Nonsuperimposable mirror images - a mirror image that is not the same as the image itself - chiral objects have nonsuperimposable 5/16/12 mirror images

Assymetric Center Chirality is not reserved just for objects - molecules can be chiral Chiral molecules - generally molecules containing an asymmetric center Asymmetric (chiral) center - tetrahedral atom bonded to four different groups - indicated with an asterisk (*)

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Enantiomers
nonsuperimposible mirror images
mirror plane OH H HO2C CH3 CH3 OH H CO2H

(S)(+) lactic acid

(R)(-) lactic acid

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from muscle tissue from milko o [] = +13.5 [ ] = -13.5

Enantiomeric Excess
(Optical Purity)
observed rotation rotation of pure enantiomer x 100 = enantiomeric excess (e.e.) observed rotation = +109 109.0 e.e. = 123.0 x 100 H (S)-(-) Limonene [] = 123.0 from lemons
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H (R)(+) Limonene [] = +123.0 from oranges

o o

= 88.6% e.e. 88.6% (+) 11.4% racemic actually 94.3% (+)

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Biological Activity
(R)(+) Th alidom ide
O N
H

(S )(-) Th alidomide
O O N O H

O N

H O

O a sedative and hypnotic

O a teratogen

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Chiral Molecules with One Asymmetric Center Molecules with one chiral center would have 2 enantiomers *Chiral molecules would have 2n enantiomers (where n is the number of chiral centers)

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Chiral vs Achiral

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How to Represent Enantiomers: Perspective Formulas

Perspective Formulas - shows two bonds of the asymmetric center as lines in the plane of the paper, another bond as a solid wedge protruding forward out of the paper, and the fourth bond as a hatched wedge extending behind the paper

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Fischer Projections Fisher Projection - representation of an asymmetric center as the point of intersection of two perpendicular lines Horizontal lines represent bonds that project out of the plane of the paper Vertical lines represent bonds that extend back from the plane of the paper away from the viewer

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Fischer Projections

Br H3 CH 2 C H CH 3

Br H3C H CH 2CH 3

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Naming Enantiomers -R,S System STEP 1. Rank the groups/atoms bonded to the asymmetric center in order of priority. priority. - rank in terms of atomic mass. Higher atomic mass, higher - lets have 1-chloro-1-ethanol as an example. Chlorine = 36 amu Oxygen = 16 amu Carbon = 12 amu Hydrogen = 1 amu

1.

2.

3.

4.

STEP 2. Rotate the molecule so that the lowest priority group is pointing away from the reader.

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Naming Enantiomers -R,S System Step 3. Trace your finger around the three highest priority groups in order of the priority. - If the circle is moving counterclockwise the CIP designation is S. If the circle is moving clockwise the CIP designation is R.

Step 4. Name the enantiomer in terms of its R or S configuration. - the name for this isomer is (S)-1-chloro-1-ethanol
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Naming Enantiomers -R,S System Assigning Priorities to Groups

1. 2.

3.

4.

Oxygen (from CH2OH) = 16 Carbon (from CH2CH3) = attached to carbon Carbon (from CH3) = attached to hydrogen Hydrogen = 1

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Naming Enantiomers -R,S System

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Lactic Acid
1 OH CH3 3 (S) CH3 3 1 OH H CO2H 2 (R) 4

4 H HO2C 2
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Plane-Polarized Light

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Plane-Polarized Light through an Achiral Compound

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Plane-Polarized Light through a Chiral Compound

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Polarimeter Measures Optical Rotation

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Specific Rotation, []
[] = / cl
= observed rotation c = concentration in g/mL l = length of tube in dm Dextrorotary designated as d or (+), clockwise rotation Levorotary designated as l or (-), counterclockwise rotation
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Specific Rotations of some Common Organic Compounds

Compound centers Sucrose Camphor MSG Cholesterol Morphine
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[] +66.5 +44.3 +25.5 -31.3 -132.0

# * 10 2 1 8 5

Diastereomers
Stereoisomers That Are Not Mirror Images

H OH
3 2

H OH
3 2

CO2H

CO2H

Br H H Br (2S,3S) (2S,3R) same stereochemistry at C 2 (S) opposite stereochemistry at C 3

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Fischer Projections with 2 Chiral Centers

CO2H H Br
2

CO2H H H
2

OH H

OH Br

CH3 (2S,3S)
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CH3 (2S,3R)

Tartaric Acids
R,R CO2H H HO OH H CO2H R,S CO2H H H
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S,S CO 2H HO H H OH CO 2H S,R CO2H HO HO H H CO2H

OH OH CO2H

Racemic Mixture
R,R CO2H H HO OH H CO2H HO H S,S CO2H H OH CO2H

Racemic Mixture (Racemate): 50/50 mixture of enantiomers

o

m.p. C (g/mL)
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(R,R) Tartaric acid 168-170 - 12 1.7598

(S,S) Tartaric Acid (+/-) Tartaric acid 168-170 210-212 + 12 1.7598 0 1.7723

[] (degrees)

Meso Compound
Internal Plane of Symmetry Optically Inactive
R,S CO2H mirror plane H H OH OH CO2H HO HO S,R CO2H H H CO2H rotate 180 superimposible
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2,3,4-trichlorohexane How many stereoisomers?

Cl * * *

Cl Cl 3 asymmetric centers 2n, n= # asymmetric centers (3) 8 stereoisomers

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n = 3; 2n = 8
CH3 S H S H RH Cl Cl Cl CH2CH3 CH3 H Cl H
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CH3 Cl Cl Cl H R H R H S CH2CH3 CH3 Cl H Cl H Cl H CH2CH3 Cl H H H H Cl

CH3 Cl Cl H CH2CH3 CH3 H Cl Cl CH2CH3 H Cl Cl Cl Cl H

CH3 H H Cl CH2CH3 CH3 Cl H H CH2CH3

Cl H Cl CH2CH3

A Carbohydrate
CHO H HO H H OH H OH OH CH2OH (+) D-Glucose
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R S R R

Internal Planes of Symmetry

Both are Meso CH3 CH3 CH3 CH3

CH3
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CH3

CH3

CH3

Asymmetric Centers on Rings

Br Br A Br Br Br B Meso Br

1(R),2(S) cis 1,2-dibromocyclohexane nonsuperimposible butA flips into B

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Relevance of Stereochemistry
Pseudophed

NHCH3

CH3

"desoxyephedrine" (methamphetamine) l-(R) - Vicks d-(S)- "Meth"

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-(p-isobutylphenyl)propionic acid

CH3

H CO 2H

H HO 2C

CH3

(S)(+) ibuprofen anti-inflammatory

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(R)(-) ibuprofen 80-90% metabolized to (S)(+)