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Stereochemistry

Dr. Balasaheb P. Pagar

Department of Chemistry,

S. V. K. T. College, Deolali Camp, Nashik

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Stereochemistry

Stereoisomers
Chirality
(R) and (S) Nomenclature
Depicting Asymmetric Carbons
Diastereomers
Fischer Projections
Stereochemical Relationships
Optical Activity
Resolution of Enantiomers

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Stereochemistry

Stereochemistry:

The study of the three-dimensional structure of molecules

Structural (constitutional) isomers:

same molecular formula but different bonding sequence

Stereoisomers:

same molecular formula, same bonding sequence, different spatial orientation

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Stereochemistry

Stereochemistry plays an important role in determining the properties and reactions of organic compounds:

Caraway seed

spearmint

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Stereochemistry

The properties of many drugs depends on their stereochemistry:

(S)-ketamine

(R)-ketamine

anesthetic

hallucinogen

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Stereochemistry

Enzymes are capable of distinguishing between stereoisomers:

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Types of Stereoisomers

Two types of stereoisomers:

enantiomers

two compounds that are nonsuperimposable mirror images of each other

diastereomers

Two stereoisomers that are not mirror images of each other

Geometric isomers (cis-trans isomers) are one 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 threads slope 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 to chirality in organic compounds is the presence of an asymmetric (or chiral) carbon atom.

A carbon atom that is bonded to four different 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 carbons present in the following compounds.

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Achiral

Many molecules and objects are achiral:

identical to its mirror image
not chiral

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Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane contains two asymmetric carbons but is achiral.

contains an internal mirror plane of symmetry

Any molecule that has an internal mirror plane of symmetry is achiral even if it contains asymmetric carbon atoms.

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Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane is a meso compound:

an achiral compound that contains chiral centers
often contains an internal mirror plane of symmetry

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Internal Plane of Symmetry

Example: Which of the following compounds contain an internal mirror plane of symmetry?

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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 plane of symmetry?

Yes: achiral
No:

If mirror image is non-superimposable, then it’s chiral.
If mirror image is superimposable, then it’s achiral.

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Conformationally Mobile Systems

Alkanes and cycloalkanes are conformationally mobile.

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 as chiral or achiral.

trans-1,3-dibromocyclohexane

ethylcyclohexane

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(R) And (S) Nomenclature

Stereoisomers are different compounds and often have different properties.

Each stereoisomer must have a unique name.�
The Cahn-Ingold-Prelog convention is used to identify the configuration of each asymmetric carbon 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

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(R) and (S) Nomenclature

Assign a numerical priority to each group bonded 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 asymmetric carbon)

Atoms with higher atomic numbers have higher priority

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(R) and (S) Nomenclature

Example priorities:

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

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(R) and (S) Nomenclature

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

CH(CH₃)₂ > CH₂CH₂Br > CH₃CH₂

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(R) and (S) Nomenclature

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

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(R) and (S) Nomenclature

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

Look at the molecule along the bond between the asymmetric carbon and the 4th priority group.

Draw an arrow from the 1^st priority group to the 2^nd group to the 3^rd group.

Clockwise arrow (R) configuration
Counterclockwise arrow (S) configuration

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(R) and (S) Nomenclature

Example: Identify the asymmetric carbon(s) in each of the following compounds and determine whether it has the (R) or (S) configuration.

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(R) and (S) Nomenclature

Example: Name the following compounds.

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(R) and (S) Nomenclature

When naming compounds containing multiple chiral atoms, you must give the configuration around each chiral atom:

position number and configuration of each chiral atom in numerical order, separated by commas, all in ( ) at the start of the compound name

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

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