Organic3a

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Stereochemistry

Stereochemistry: The study of the three-dimensionalstructure of molecules

Structural (constitutional) isomers: same molecular formula but differentbonding sequence

Stereoisomers: same molecular formula, same bondingsequence, different spatial orientation

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Stereochemistry

Stereochemistry plays an important role indetermining the properties and reactions oforganic compounds:

CH2

H3C

H

O

CH3

H2C CH

3

O

CH3

H

Caraway seed spearmint

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Stereochemistry

The properties of many drugs depends on theirstereochemistry:

CH3

O

Cl

N

H

(S)-ketamine

CH3

O

Cl

NH

(R)-ketamine

anesthetic hallucinogen

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Stereochemistry

Enzymes arecapable ofdistinguishing

betweenstereoisomers:

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Types of Stereoisomers

Two types of stereoisomers: enantiomers

two compounds that are nonsuperimposable

mirror images of each other

diastereomersTwo stereoisomers that are not mirror

images of each otherGeometric isomers(cis-trans isomers) areone type of diastereomer.

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Chiral

Enantiomers are chiral: Chiral:

Not superimposable on its mirror image

Many natural and man-made objects are chiral: hands scissors

screws(left-handed vs. right-handed threads)Right hand threadsslope up to the right.

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Chiral

Some molecules are chiral:

Asymmetric

(chiral) carbon

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Asymmetric Carbons

The most common feature that leads tochirality in organic compounds is the presenceof an asymmetric (or chiral) carbon atom.

A carbon atom that is bonded to fourdifferent groups

In general:

no asymmetric C usually achiral 1 asymmetric C always chiral > 2 asymmetric C may or may not be

chiral

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Asymmetric Carbons

Example: Identify all asymmetric carbonspresent in the following compounds.

C C C C

OH

H

H

H

H

H

H H

H

H H3C

CH3CH2CH3

H H H

BrBr

Br CH3

Br

H

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Achiral

Many molecules and objects are achiral: identical to its mirror image not chiral

H H

ClCl

H H

ClCl

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Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane contains twoasymmetric carbons but is achiral. contains an internal mirror plane of

symmetry

Any molecule that has an internal mirror planeof symmetry is achiral even if it containsasymmetric carbon atoms.

H H

ClCl

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Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane is a mesocompound: an achiral compound that contains chiral

centers often contains an internal mirror plane ofsymmetry

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Chiral vs. Achiral

To determine if a compound is chiral: 0 asymmetric carbons: Usually achiral 1 asymmetric carbon: Always chiral 2 asymmetric carbons: Chiral or achiral

Does the compound have an internal planeof symmetry?Yes: achiral No:

If mirror image is non-superimposable, then its chiral.If mirror image is superimposable,then its achiral.

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Conformationally Mobile Systems

Alkanes and cycloalkanes are conformationallymobile. rapidly converting from one conformation to

another In order to determine whether a cycloalkane is

chiral, draw its most symmetrical conformation(a flat ring).

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Chiral vs. Achiral

Example: Identify the following molecules aschiral or achiral.

BrH

Br H H H

BrBr

CH3CCH2CH3

CH3

Cl

CH3

CHCH2

CH2

CH3

Cl

C CBr

BrH

HCH3CH2

CH2CH3

trans-1,3-dibromocyclohexane

ethylcyclohexane

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(R) And (S) Nomenclature

Stereoisomers are different compounds andoften have different properties.

Each stereoisomer must have a unique name. The Cahn-Ingold-Prelog convention is used to

identify the configuration of each asymmetriccarbon atom present in a stereoisomer. (R) and (S) configuration

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(R) and (S) Nomenclature

The two enantiomers of alanine are:

Natural alanine Unnatural alanine(S)-alanine (R)-alanine

CO2H

C

H2N

HCH3

CO2H

C

H3C NH2

H

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Assign a numerical priority to each groupbonded to the asymmetric carbon: group 1 = highest priority group 4 = lowest priority

Rules for assigning priorities: Compare the first atom in each group (i.e.the atom directly bonded to the asymmetriccarbon)Atoms with higher atomic numbers havehigher priority

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C

HH3C OCH2CH3

Cl


1

23

4

Example priorities:

I > Br > Cl > S > F > O > N > 13C > 12C > 3H > 2H >1H

C

CH3

NH2

F H1 2

3

4

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In case of ties, use the next atoms along thechain as tiebreakers.

CCH

3

CH2CH2Br

H

CH(CH3)2

CH2

CH(CH3)2 > CH2CH2Br > CH3CH2

4

2

3

1

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Treat double and triple bonds as if both atomsin the bond were duplicated or triplicated:

C Y C Y

Y C

C Y C Y

Y C

C

Y

C

C

H CH2OH

OH

O

C O

H

1

2

3

4

C

C

O

H CH2OH

OH

H

1

2

3

4

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Using a 3-D drawing or model, put the 4thpriority group in back.

Look at the molecule along the bond betweenthe asymmetric carbon and the 4th prioritygroup.

Draw an arrow from the 1stpriority group tothe 2ndgroup to the 3rdgroup. Clockwise arrow (R) configuration Counterclockwise arrow (S) configuration

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Example: Identify the asymmetric carbon(s) ineach of the following compounds and determinewhether it has the (R) or (S) configuration.

O

H

C

H

CH3

OHCH

2CH

3

C CH(CH3)2

H

BrCH

3

CCO

2H

Br

H

CH3

OH

Br

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Example: Name the following compounds.

C

H

Br

CH2CH

3

CH3

CH3Br

CH3H

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When naming compounds containing multiplechiral atoms, you must give the configurationaround each chiral atom: position number and configuration of each

chiral atom in numerical order, separated bycommas, all in ( ) at the start of thecompound name

CH3H3C

ClHHBr

(2S, 3S)-2-bromo-3-chlorobutane

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Depicting Structures with AsymmetricCarbons

Example: Draw a 3-dimensional formula for (R)-2-chloropentane.

Step 1: Identify the asymmetric carbon.

Step 2: Assign priorities to each group attached tothe asymmetric carbon.

CH3

C CH2CH2CH3

Cl

H

*

CH3

C CH2CH2CH3

Cl

H

1

23

4

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Step 4: Place the highest priority group at the top.

Step 3: Draw a skeleton with the asymmetric carbonin the center and the lowest priority group attached tothe dashed wedge (i.e. pointing away from you).

CH

CH

Cl

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Step 5: For (R) configuration, place the 2nd and3rd priority groups around the asymmetriccarbon in a clockwise direction.

CH

Cl

CH3

CH2CH

2CH

3

Step 6: Double-check your structure to makesure that it has the right groups and the rightconfiguration.

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Example:The R-enantiomer of ibuprofen is notbiologically active but is rapidly converted to theactive (S) enantiomer by the body. Draw thestructure of the R-enantiomer.

CH2CH(CH3)2HO2CCH

CH3

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Example: Captopril, used to treat high bloodpressure, has two asymmetric carbons, both withthe S configuration. Draw its structure.

N C CHCH2SH

O

CH3

CO2H

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