Lecture 3 - Recap

Different types of isomersStereochemistrySymmetry and asymmetryChiralityAsymmetric centre/ Chiral CarbonStereogenic CentreEnantiomersPlane of symmetry & center of symmetry

Stereochemistry-II

ConfigurationConfiguration of a molecule is the detailed

stereochemical picture including how the atoms are arranged in space.

It is represented (specified) by letter ‘R’ or ‘S’.For doing this, we assign priority numbers

according to Cahn-Ingold-Prelog system and see which way the priority numbers are arranged.

If priority numbers are arranged clockwise, then specification is ‘R’.

If priority numbers are arranged anticlockwise, then specification is ‘S’.

Wedge – Dash & Fischer Projections

How do we represent a three dimensional molecule on to a two dimensional plane i.e. blackboard or paper?

By, Wedge-and-dash drawing (perspective diagram) or

By Fischer’s projection formula (also called cross formula).

We will concentrate in our discussions on molecular representation by Fischer’s formula mainly as it is difficult to represent molecules with many chiral carbon atoms by Wedge and dash form.

Wedge – Dash RepresentationUsually drawn with two bonds in the plane of the page, one in front, and one behind to give the molecule perspective. When drawing wedge-dash it is a good practice to visualize the tetrahedral arrangement of the groups and try to make the diagram "fit“ this.

Fischer ProjectionsHow is Fischer’s formula drawn?

We draw two lines (one vertical and one/( two or more) horizontal line(s)) depending upon the number of stereocenter/(s) in the molecule.

The point of intersection of these lines is considered as representing the stereocenter.

The formula can be drawn only for molecules with stereocenter.

Fischer’s formula for Lactic acid is

Fischer ProjectionsThe horizontal lines represent wedges (bonds) coming out of the plane of paper.

The vertical lines represent dashed lines (bonds) going into the plane of the paper.

When drawing Fischer Projection the carbon chain is drawn along the vertical line of the projection, with the most highly oxidized carbon substituent at the top.

Conversion of Wedge – Dash to Fischer Projections

ConfigurationWhile assigning configurations using fisher Projections:

If the lowest priority number is along vertical line (may be above or below) then assigned specification remains same.

If the lowest priority number is along horizontal line (on the left or right of the stereocenter) then assigned specification will be opposite to the specification we got.

Cahn-Ingold-Prelog RulesAssign a priority number to each group

attached to the chiral carbon.Atom with highest atomic number -

assigned the highest priority #1.In case of ties, look at the next atoms along

the chain.Double and triple bonds are treated like

bonds to duplicate atoms.

Cahn-Ingold-Prelog Rules

Rule 1: Priority number isassigned on the basis ofatomic number of atombonded to stereocenter. I > S > O > N > 13C > 12C > Li > 3H (T) > 2H (D) > H

Example 1 In this example the priority numbers are arranged anticlockwise and the lowest priority number is along vertical.

Therefore specification is ‘S’ (Latin, sinister = left).

Cahn-Ingold-Prelog Rules

Rule 2: Priority number isassigned on the basis of mass number if isotopes are bonded to stereocenter.

Example 2 In this example the priority numbers are arranged clockwise and the lowest priority number is along vertical.

Therefore specification is ‘R’ (Latin, rectus = upright).

2CH3

H

1Cl

3D

(R) and (S) Assignments

(a)The molecule is drawn is 3 dimensions, and arranged in such a way that the bond between the chiral carbon and the lowest priority groupheads back into the paper.

(b) Draw an arrow from the group of highest priority, to the second, to the third priority group.

NH2

CH

CO2H

C*

NH2

CO2HH3C

*

NH2

CH

HO2C

C*

NH2

CH3HO2C

*

(R) enantiomer (S) enantiomer

H3CCH3

(1)

(2)

(3) (4)

(1)

(4)

(2)

(3)

(1) (1)

(2)(2) (3)(3)

unnatural alanine

naturalalanine

Assign (R) or (S)Working in 3D, rotate molecule so that lowest

priority group is in back.Draw an arrow from highest to lowest

priority group.Clockwise = (R), Anticlockwise = (S)

Assign (R) or (S)

CH3

C3H7C2H5

12

3

R

2

Cahn-Ingold-Prelog Rules

Rule 3: In the case of the same atoms being bound directly to the chiral carbon, we go to the next atoms along the chain till Priority number is determined.

Example 3 In this example the specification is ‘S’.

2C

1Cl

H

3CHCH3

CH3

CH3

CH3CH3

-CH2Br > -CHCl2 > -C(CH3)3 > -CH(CH3)CH2F > -CH(CH3)2 > -CH2CH3

C

Cl

H

CCCH

C

HC

C

ClH

H

H H

CH3OH

OH

H H

HH

1

4

??

C(C,C,H) and C(C,C,H) do not show any difference

Example

C

Cl

H

CCCH

C

HC

C

ClH

H

H H

CH3OH

OH

H H

HH

C(C,C,H) and C(C,C,H) do not show any difference

Two sub-branches on right are arranged:

C(O,C,H) >

C (O,H,H)

Two sub-branches

on left are

arranged: C(Cl,H,H)

> C(H,H,H)

Considering senior sub-branches it yields C(Cl,H,H) > C(O,C,H). (No need to consider junior sub-branches).

Example contd..

C

Cl

H

CCCH

C

HC

C

ClH

H

H H

CH3OH

OH

H H

HH

1

4

32

Priority of left hand side group is higher than right hand side

1

2 3

S

Example contd..

Cahn-Ingold-Prelog RulesRule 4: Double and triple bonds are treated as if each bond were to a separate atom. (Imagine that each bond is broken and that the atoms at both ends were duplicated. When a bond is broken only two imaginary atoms are added).

Cl

CH

CH2CH3

H

H2COH

H

O OH

O

HO

S

SH3CH2C

CH2CH3H3C

H

HCH3

3S and 4S

NH

CH3

Cl

O

HO

HO

CH2NHCH3

H

OH

S R