Stereoisomerism and Chirality

Isomers

Constitutional Isomers

Functional Group Isomers Positional Isomers Geometric Isomers Enantiomers Diastereomers Meso Compounds Eclipsed, gauche, staggered, syn-clinal, anti-clinal forms Chair, boat

Stereoisomers

Conformational Isomers

Enantiomers and Diastereomers

Two kinds of Stereoisomers

Enantiomers: stereoisomers which are mirror objects of each other. Enantiomers are different objects, not superimposable. Diastereomers: stereoisomers which are not mirror objects of each other.

If a molecule has one or more tetrahedral carbons having four different substituents then enantiomers will occur. If there are two or more such carbons then diastereomers may also occur.

Enantiomer/Diastereomer/Identik?

Mirror Objects Carbon with 4 different substituents. We expect enantiomers (mirror objects).

The mirror plane still relates the two structures. Notice that we can characterize or name the molecules by putting the blue in the back,drawing a circle from purple,to red,to green.Clockwise on the right and counterclockwise on the left.Arbitrarily call them R and S.

Reflect!

Notice how the reflection is done, straight through the mirror! Arrange both structures with the light blue atoms towards the rear. These are mirror objects. Are they the same thing just viewed differently ? Can we superimpose them? We can superimpose two atoms. but not all four atoms.

Urutan Prioritas : 1. Ungu, 2. Merah, 3. Hijau, 4. Biru

Recap: Tetrahedral Carbon with four Different Substituents. Enantiomers

Mirror objects. Different, not superimposable. Simple Rotation, Same Simple Rotation, Same

Enantiomers

But the reflection might have been done differently. Position the mirror differently.

Again. all three objects on the right are the mirror object of the structure above. They are different views of the enantiomer. A swap of two substituents is seen to be equivalent to a reflection at the carbon atom.

Reflection can give any of the following

Can you locate the mirror which would transform the original molecule into each mirror object?

What is common to each of these reflection operations?

In the course of each reflection, two substitutents are swapped. The other two remain unchanged.

All three of these structures are the same, just made by different mirrors. The structures are superimposable. What rotations of the whole molecules are needed to superimpose the structures?

Now Superimposable mirror objects: Tetrahedral Carbon with at least two identical substituents

Reflection can interchange the two red substituents. Clearly interchanging the two reds leads to the same structure, superimposable! Remember it does not make any difference where the mirror is held for the reflection. This molecule does not have an enantiomer; the mirror object is superimposable on the original, the same object.

Summary
A reflection on a tetrahedral carbon with four different substituents produces a different, non-superimposable structure, the enantiomer. A different three dimensional arrangement of the bonds is produced, a different configuration. Such a carbon is called chiral. The carbon is a chiral center, a stereogenic center. If a tetrahedral carbon has two or more substituents which are the same then reflection produces the same structure, the same configuration. Such a carbon is called achiral. The swapping two of the substituents on the chiral carbon is equivalent to a reflection. There is only one mirror object produced by reflection, no matter where the mirror is located. It is either the same as the original structure (superimposable) or it is different (non-superimposable), the enantiomer.

Multiple reflections
One reflection (swap of substituents) on a chiral carbon produce the enantiomer. Two reflections (swaps) yields the original back again. Even number (0, 2, 4) of reflections (swaps) on a chiral carbon yields the original structure. An odd number (1, 3, 5) yields the enantiomer. Enantiomers Enantiomers
HO Br Br OH

OH

One swap

Br
Second swap

Same molecule.

Repeating.
Three different substitutents. Reflection (in this plane) yields.

Same, not enantiomers. Four different substituents. Reflection (in this plane) yields.

Different, not superimposble, enantiomers.

Is a chiral carbon needed? No!

Recall allene:
C

Reflection (in this plane) yields.

Different, not superimposable, enantiomers. The (distorted) tetrahedral array of the substitutents (huh??) suffices to allow for enantiomers.

Naming of configurations.

A priority is assigned to each substituent on the chiral carbon Rotate the structure so that the lowest priority towards the rear. Draw an arc from the highest, to the next lower, to the next lower. If arc is clockwise it is R configuration. If arc is counterclockwise it is S.

Assigning Priorities 2
Start with first atom attached to chiral carbon

C vs. F

When the first atom is the same Examine what is bonded to it.
H O N H F O C H F F F H H

Start with first atom attached to chiral carbon. No decision!! Examine atoms bonded to first atom O vs O N vs C

Example: assigning Priorities

H

S configuration

Br

Substituents
H
H C H H C H H C H H

Br

H Highest,1 Lowest, 4 2 Assign on the basis of the atomic number of the first atom in the substituent.

If the atoms being compared are the same examine the sets bonded to the atoms being compared. C has priority over H!!

More If the first atom is the same and the second shell is the same then proceed to the atoms attached to the highest priority of the second shell.
H H

Examine the first atom, directly attached to the chiral atom.

Cl H N H H F

Examine the atoms bonded to the first atom (the second shell) . N vs N C vs C

F H N H Cl

H vs H

Examine atoms bonded to highest priority of second shell, N Cl vs F Cl wins!

Unsaturation
So far have not worried about double or triple bonds. Double and triple bonds are expanded as shown below.
H H

Expanded into

C C H

C N C

becomes

C N

Lets investigate what happens if low priority is positioned closer to us than chiral carbon
CH3

H towards the rear where it belongs

C2H5

H Cl

(S)-2-chlorobutane

Now lets swap any two substituents. We know that this produces the enantiomer, R. Swap the H and the Cl.
CH3

Arc going in wrong direction because the low priority substituent is closer to us than the chiral center!!!!!! We are looking at the molecule from the wrong side. INVERT NAMING if LOW PRIORITY IS CLOSER THAN CHIRAL CENTER: Clockwise is S Counterclockwise is R
Cl H

C2H5

(R)-2-chlorobutane

Physical Properties of Enantiomers

Enantiomers: different compounds but have same Melting Point Boiling Point Density Enantiomers rotate plane polarized light in opposite directions. OPTICALLY ACTIVE!! The enantiomers rotate plane polarized light the same amount but in opposite directions. One clockwise; the other counterclockwise.

Fischer Projection
Cl to Ethyl to Methyl
CH3

CH3
Reposition to

Cl C2H5

m fro t of ok n C2H5 Lo poi Cl s H thi w. (R)-2-chlorobutane vie

Standard Fischer projection orientation: vertical bonds recede horizontal bonds come forward CH3 Cl C2H5 H R and S designations may be assigned in Fischer Projection diagrams. Frequently there is an H horizontal making R CCW and S CW.

H,low priority substituent, is closer so CCW is R. Standard short notation:

Manipulating Fischer Projections

Even number of swaps yields same structure; odd number yields enantiomer.
CH3 Cl C2H5 H

1 swap
H

CH3 Cl C2H5

CH3

or

C2H5 Cl

R
or
Cl

H CH3 C2H5

Etc.

All of these represent the same structure, the enantiomer (different views)!!

Manipulating Fischer Projections

Even number of swaps yields same structure; odd number yields enantiomer.
CH3 Cl C2H5 H

2 swaps
H

Cl CH3 C2H5

Cl

or

C2H5 CH3

R
H3C

Cl H C2H5

C2H5

or

H CH3

Cl

Etc.

All of these represent the same structure, the original (different views)!!

Rotation of Entire Fischer Diagrams

CH3 H C2H5 Br

Rotate diagram by 180 deg Same Structure simply rotated: H & Br still forward; CH3 & C2H5 in back.

C2H5 Br CH3 H

This simple rotation is an example of proper rotation.

Rotation by 90 (or 270) degrees. Enantiomers. Non superimposable structures! Not only has rotation taken place but reflection as well (back to front). For example, the H is now towards the rear and ethyl is brought forward.
C 2 H5

H CH3 Br

This combination of a simple rotation and reflection is called an improper rotation.

Soal latihan

Jelaskan bahwa dari molekul abcd dapat digambarkan dengan banyak proyeksi Fiesher tetapi sebenarnya hanya merupakan sepasang enantiomer.

Multiple Chiral Centers

CH3 H Cl CH3 Br H

Do a single swap on each chiral center to get the enantiomeric molecule.

CH3 Br H CH3 H Cl

(2S,3S) 2-bromo-3-chlorobutane
CH3

Each S configuration has changed to R.

(2R,3R) 2-bromo-3-chlorobutane
CH3 H H CH3 Br Cl

R
Br Cl CH3 H H

Now do a single swap on only one chiral center to get a diastereomeric molecule (stereoisomers but not mirror objects).

S R

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

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

Multiple Chiral Centers

CH3 H Cl CH3 Br H

CH3

Enantiomers
Br H Cl CH3 H

(2S,3S) 2-bromo-3-chlorobutane
CH3

(2R,3R) 2-bromo-3-chlorobutane
CH3

R
Br Cl CH3 H H H Br Cl CH3

S R

S Enantiomers

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

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

Multiple Chiral Centers

CH3 H Cl CH3 Br H

S
Br

CH3 H Cl CH3

Diastereomers S
H

(2S,3S) 2-bromo-3-chlorobutane
CH3

(2R,3R) 2-bromo-3-chlorobutane
CH3

R
Br Cl CH3 H H

Diastereomers S

H H CH3

Br Cl

S R

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

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

Diastereomers
Everyday example: shaking hands. Right and Left hands are mirror objects R --- R is enantiomer of L --- L and have equivalent fit to each other. R --- L and L --- R are enantiomeric, have equivalent fit, but fit differently than R --- R or L L.

Diastereomers

Require the presence of two or more chiral centers. Have different physical and chemical properties. May be separated by physical and chemical techniques.

Meso Compounds
Must have same set of substituents on corresponding chiral carbons.
CH3 H Cl CH3 Cl H
CH3

Cl H CH3

H Cl

R R

S As we had before here are the four structures produced by systematically varying the configuration at each chiral carbon.
H H CH3

CH3 Cl Cl

CH3 Cl Cl CH3

R S

H H

S R

Meso Compounds
CH3 H Cl CH3

What are the stereochemical relationships?

CH3

Cl H

Enantiomers

Cl H CH3

H Cl

R R

Mirror images, not superimposable. Diastereomers. S

CH3 Cl Cl CH3 H H

CH3

R S Mirror images! But superimposable via a 180 degree rotation. Same compound.

H H CH3

Cl Cl

S R

Meso

Meso Compounds: Characteristics

Has at least two chiral carbons. Corresponding carbons are of opposite configuration. Can be superimposed on mirror object, optically inactive. Can demonstrate mirror plane of symmetry Molecule is achiral. Optically inactive. Specific rotation is zero.
CH3 Cl Cl CH3 H H CH3

R S

H H CH3

Cl Cl

S R

Meso

Can be superimposed by 180 deg rotation.

Resolution of mixture into separate enantiomers.

Mixtures of enantiomers are difficult to separate because the enantiomers have the same boiling point, etc. The technique is to convert the pair of enantiomers into a pair of diastereomers and to utilize the different physical characteristics of diastereomers. Formation of diastereomeric salts. Racemic mixture of anions allowed to form salts with pure cation enantiomer. Racemic mixture reacted with chiral enzyme. One enantiomer is selectively reacted. Racemic mixture is put through column packed with chiral material. One enantiomer passes through more quickly.

Mengapa Mempelajari Konfigurasi R dan S

O NHCH3 O NHCH3

Cl

Cl

S-(+)-Ketamine

R-(-)-Ketamine

2-4 times more potent than R-(-)-ketamine in anaesthesia

Causes spontaneous motor activity and post-emergent distress

All three substituents Chirality in the Biological World match up with sites on the A schematic diagram of an enzyme enzyme.

If two are matched up then the third will fai!

surface capable of binding with (R)-glyceraldehyde but not with (S)glyceraldehyde.

Sumber

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