Organic Chemistry

Lecture 3:
Stereoisomers

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 Importance of Stereochemistry

Thalidomide

• Identified in 1950s as a neurologically active molecule that can quell morning

sickness in pregnant women.
• But born children displayed extremely shortened arms and hands, defected
eyes and hearts… 2000+ kids died and 10000+ had serious birth defects.
• This tragic lead to the creation of modern drug testing and approval regime in
USA and EU.

R was therapeutically active

S was not only ineffective, it was

the source of the birth defects!
S R

Stereoisomers
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Isomers

cis-trans stereoisomerism

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 cis and trans Isomers

Overlap of p orbitals -> no free rotation of C=C bond

cis or trans? 2 substituents on same position

-> no cis/trans 4
https://www.youtube.com/watch?v=JS-iAuCIexk
 Chirality

An object that is superimposable An object that is NOT superimposable

on its mirror image. on its mirror image

Achiral objects Chiral objects

Other chiral objects:

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 Molecular Chirality

Carbon atom with 4 different groups

“chiral center, stereocenter, stereogenic
center or asymmetric center”

Example:

2-Butanol

??

No chiral center

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 Chirality

Propoxyphene, sold under the trade name Darvon,

is an analgesic (painkiller) and antitussive (cough
suppressant). Identify all chiral centers.

sp2, CH2, CH3 cannot

be chiral centers

Chiral centers

Chiral or not?

Chiral 7
 Enantiomers

A chiral compound will have one nonsuperimposable mirror image called enantiomer
Exactly one enantiomer (never more, never less)

Amphetamine is a prescription stimulant used in

the treatment of ADHD (attention-deficit
hyperactivity disorder) and chronic fatigue
syndrome. During World War II it was used
heavily by soldiers to reduce fatigue and increase
alertness. Draw the enantiomer of amphetamine.

3 places to put the mirror

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Enantiomers

Replace all dashes with wedges

and all wedges with dashes
(easiest way)

Same compound

1
0
 Enantiomers

Draw the enantiomer of each of the following compounds:

(c)

Simply replace all dashes with wedges and vice versa (mirror behind)

With cyclic molecule, easier to place the mirror

next or beneath the molecule

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 The Nose as a Stereochemist
• Can you easily distinguish different types of spices?
• To have an odor, an object must release organic compounds to the air
• At room T, plastic and metal items do not release molecules into the air -> order-less.
• But spices have very strong odor (because they release a lot of organic compounds)
• The org. compounds bind to receptors as they enter your nose -> signals to your brain
• If receptor is chiral, the smell of enantiomers will be different

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Nomenclature using Cahn-Ingold-Prelog System
1. Assigning priorities to each group attached
to the chiral center, based on descending
atomic number

2. Then rotate the molecule so that the 4th

priority is behind the page

3.Then, look to see if the sequence 1-2-3

is clockwise or counterclockwise. This
case is counterclockwise (S)

S – sinister (left)
R – rectus (right)

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 Assigning Priorities

Which C is priority?

Make the list of 3 atoms on either side

and compare
Identical -> move further from chiral center

Left is priority

• Based on first point of

difference, not sum of atomic
numbers (O > C) 14
 Assigning Priorities

• Double bond = 2 separated single bonds

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 Rotating the Molecule

Switching any 2 groups twice -> Same molecule

= rotating the molecules

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 Examples

This is one enantiomer of 2-amino-3-(3,4-dihydroxyphenyl)propanoic

acid, used in the treatment of Parkinson’s disease. Assign the
configuration of the chiral center in this compound.

rotate Counterclockwise
(S)

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 Practice Problems

Each of the following compounds possesses carbon atoms that are chiral centers. Locate
each of these chiral centers and identify the configuration of each one:

R, S S, R S, R

IUPAC Nomenclature

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 Chiral Drugs
Drug-receptor interaction

• Only one enantiomer can fit with

the receptor
• Enantiomers produce different
biological responses

S is painkiller while R is inactive

S treats high blood pressure while

R treats glaucoma

S treats chronic arthritis while

R is highly toxic
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Optical Activity

How to physically determine the

enantiomers?

Chiral molecules are optically active

Enantiomers exhibit different behavior
when exposed to plane polarized light

Polarimeter 19
 Optical Activity
Dextrorotatory (clockwise) rotations are (+) or (d). dexios
Levorotatory (counterclockwise) rotations are (-) or (l). laevus
Enantiomeric compounds rotate the plane of polarized light by exactly the same
amount but in opposite directions.
We cannot predict which direction a particular enantiomer [(R) or (S)] will
rotate the plane of polarized light (determine experimentally).

𝛼 depends on wavelength of light source and temperature [𝛼]λ𝑇

25 25
𝛼 𝐷 of (R)-Carvone = - 61 𝛼 𝐷 of (S)-Carvone = + 61
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 Optical Activity

1. When 0.300 g of sucrose is dissolved in 10.0 mL of water and placed in a sample cell
10.0 cm in length, the observed rotation is +1.99° (using the D line of sodium at 20°C).
Calculate the specific rotation of sucrose.

2. Levetiracetam is used for the treatment of seizures in patients with epilepsy. For
patients who have a hard time swallowing the needed pills twice daily, relief is in sight
now that the FDA has granted approval for the use of rapidly dissolving, porous tablets
produced with a 3D printer. Levetiracetam has a specific rotation of [α]20 = −93.4.

(a) If a 500-mg tablet of levetiracetam is dissolved in

10.0 mL of acetone and placed in a sample cell with
a length of 10.0 cm, what observed rotation is
expected?
−4.67°
(b) Levetiracetam is the (S ) enantiomer of the memory-
enhancing racemic drug called etiracetam. What do you
think inspired the name of levetiracetam? 21
 Enantiomeric Excess

A solution of a single enantiomer is optically pure, or enantiomerically pure.

A solution with equal amounts of both enantiomers is racemic mixture and will be
optically inactive.

A solution with both enantiomers in unequal amounts will be optically active

Example: solution of 2-butanol

70% (R)-2-butanol and 30% (S)-2-butanol

→ 40% excess of the R (70% − 30%).

Enantiomeric excess (ee) = Optical purity (op) = 40 %

% op =

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 Enantiomeric Excess

Example:

1. The specific rotation of optically pure adrenaline in water (at 25°C) is −53. A chemist
devised a synthetic route to prepare optically pure adrenaline, but it was suspected that
the product was contaminated with a small amount of the undesirable enantiomer. The
observed rotation was found to be −45°. Calculate the % ee of the product.

85%

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Diastereomers

Same physical properties Different physical properties

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 Diastereomers

3 chiral centers

8 stereoisomers

Max no. of stereoisomers: 2n

n: number of chiral centers

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 Diastereomers

Identify whether each pair of compounds are enantiomers or diastereomers:

Enantiomers: all chiral centers

have to be opposite
-> diastereomers

Enantiomers

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 Symmetry and Chirality

Any molecule with one chiral center is always chiral

Compound of two or more chiral centers : may or may not be chiral

chiral achiral
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Example: meso compound which contains a

plane of symmetry or a mirror plane

▪ Not optically active

▪ Superimposable on its mirror image (achiral)
 Practice Problems

Draw all possible stereoisomers of 1,3-dimethylcyclopentane

Same compound!

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Fisher Projection

Primarily used to analyze sugars

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https://www.youtube.com/watch?v=uAROk_akvzo&ab_channel=LabileEducation
 Fisher Projection

Assign the configuration of the chiral center in the following compound:

R
~

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E and Z Designations for Diastereomeric Alkenes

cis vs. trans ??

Z E
-> Based on priority of the substituents

Priority on the same side: Z

Priority on opposite side: E

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 Practice Problems

Identify the configuration of the following alkene:

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