Chirality Handout

Chirality, Defined An object is chiral if the mirror image of the object in “non-superimposable” – that is, if you reflect an object through a mirror, that reflection is not identical to the original object. The most obvious example is the left and right hand; a left-handed glove will not fit on the right hand, because they are non-superimposable. Example:

Chirality in shells. On the right (b) are two differently-handed shells of the same snail species. Image modified from Grande, C.; Patel, N. H. Nature 2009, 1007-1011 The same definition applies to molecules. If a molecule has a non-identical mirror image, the molecule is chiral. If the mirror image is identical, it is achiral.

Examples: Chiral Molecules

CF3 C H Cl Br

CF3 C Cl H Br

O H 3C

Achiral Molecules

O OH

NH 2

CH 3

HO

NH 2

CH3

CF3 C H Cl H

CH 3

HO

CF3 C Cl H H

OH

Examples of chiral (left) and achiral (right) molecules. Another way to identify achiral molecules is to find a mirror plane in the molecule. A mirror plane means that two halves of a molecule are symmetrical; if you can find a way to duplicate half of a molecule to generate the other half, you’ve found a mirror plane. Example: cis-1,3 dimethylcyclohexane. As shown in the table above, cis-1,3 dimethylcyclohexane is achiral – its mirror image is superimposable. Rotate 120o

is identical to

Therefore, there must be a mirror plane in this molecule (dotted line). Split the ring in half along these two carbons.

Each half is identical!

The second example of an achiral molecule in chart 1 is less obvious, but there is indeed a mirror plane. Splitting the molecule through the carbon of the CF3 group, the chlorine, and the central carbon produces two identical halves.

Identifying Chiral Centers In organic chemistry, we’re primarily concerned with finding molecules that have point chirality, where one or more sp3 atoms are chiral centers. Any sp3 atom with four different groups bonded to it is a chiral center.

A

B

A

B

A and B are NOT IDENTICAL

Rotate to compare. B is the mirror image of A.

Common groups that can be chiral centers include alkyl carbons (CR4), phosphorus oxides (R3P=O), and ammonium cations (NR4+). Compounds with three bonded groups and a lone pair (i.e. amines) are not chiral, except under extraordinary circumstances. IMPORTANT: ALL HYDROGENS MAY NOT BE EXPLICITLY SHOWN! You need to be able to identify chiral centers, even if hydrogen atoms are not drawn in. In the third example on the top row below, the hydrogen is omitted from the chiral center. On an exam or a quiz, you may want to draw in missing hydrogens, so you don’t mis-assign chiral centers. Examples: O

CF3 ∗ C H Cl Br

∗

H 3C

∗

OH

NH2

H Br

CH 3 ∗

∗

∗

∗

HO

∗

∗

A menagerie of molecules with chiral centers. Each chiral center is marked with a red asterisk (*). Hydrogens may not be explicitly shown. Notice that the central molecule on the bottom row (cis-1,3 dimethylcyclohexane, boxed) is not chiral. A molecule can be achiral, but still have chiral centers. When this occurs, the compound is referred to as “meso”.

Assigning Priority The convention to indicate chirality in the name of a molecule is to use the terms R and S. An example would be the inhalation anesthetic Isoflurane, which is given the IUPAC name (R) or (S)-2-chloro-2-(difluoromethoxy)-1,1,1-trifluoro-ethane.

F F F O ( R) C C C F H F Cl H

F F

F C

(S)

O F C C H H Cl F

To assign a chiral center, you must assign the groups bonded to the chiral center priority. Priority is determined by atomic mass, which is usually equivalent to atomic number. The heaviest atom gets the highest priority, and the lightest atom gets lowest priority. Start by looking one bond away from the chiral center. In Isoflurane, the atoms are H, C, O, and Cl.

F F O C F C C F H F Cl H Chlorine is the heaviest atom, so it gets highest priority. The other atoms are assigned priority in decreasing order.

F3 2 F F O ( R) C C C F H F Cl H 4 1 Rules for assigning priority: 1. Heavier atoms > lighter atoms 2. Multiple bonds > single bonds. If you cannot distinguish between groups one bond away, keep stepping through bonds until a difference is reached. You can think of the atoms like a hand of cards, with heavier atoms “trumping” lighter atoms.

For instance:

H H 3 C H H2 N 1

H

H

3

C 2

∗

C

OH H

∗

2 OH

NH 2 1

4

If the stereocenter is in a ring, travel around the ring until different groups are reached.

4 1 H HO 3

2

Other examples: 3 CF3 ∗ 4 H C Cl Br 2 1

3 H3 C

O ∗

11

3

∗

2

2 OH

NH 2 1

H

2 H

3

∗

2

H ∗

3

H F 4 1

Assigning Stereocenters There are two ways to assign the stereocenter. If the lowest priority group is in the back (H, in this case), draw a curve connecting groups 1, 2, and 3, in that order. If the curve rotates clockwise, the center is R. If it rotates counterclockwise, it is S.

F3 F C F C C F H F Cl H 4 1 Clockwise = R! 2 O

You can also check using your hands, which is a more flexible method. Point your right thumb in the direction of the lowest priority group, and your fingers towards priority group 1 or 2. If your fingers curl in the direction of the 1-2-3 spiral, the stereocenter is R; otherwise it is S. This technique is more versatile because you don’t have to redraw the structure rotated with the low priority group in the back. If you do need to redraw a molecule with the low priority group in the back, simply rotate any three groups around the chiral center. The CF3 group rotates to take the former place of the H. 3 F F C HF2 C C F H Cl 1 4 2 O

Cl rotates to where the CF3 group was.

Move the lowest priority group to the back FIRST! H moves to the Cl position.

2 O

Cl 1 C F C H4 F F 3

HF2C

(S)

Counterclockwise = S!

Identifying Isomers: Stereoisomers, Enantiomers, and Diastereomers Any compounds with the same atom connectivity related by a difference in the geometry of atoms/bonds are stereosiomers. “Stereoisomer” is a broad term, and includes cyclohexane chair conformers, cis/trans double bond substitution, and molecules with identical chirality. Enantiomers are chiral molecules related by reflection through a mirror. For two molecules to be enentiomers, all the chiral centers have to be reversed. (R becomes S; R,R becomes S,S). Molecules that differ by one or more but not all of their stereocenters are diastereomers. D-Glucose has five different stereocenters, giving it a possible 25 (32) isomers. O

HO HO

OH OH

O

HO HO

OH

O

HO

L-Glucose

OH OH

O

HO HO

OH

O

HO

OH OH

O

HO HO

HO

OH OH

OH D-Talose

OH OH

OH L-Mannose

D-Mannose

O

OH

L-Galactose

OH

HO

OH

OH

D-Galactose

HO

OH OH

D-Glucose

HO

OH

O

HO HO

OH OH

OH L-Talose

Selected diastereomers of D-glucose. Pairs of enantiomers (mirror images) are indicated by double-headed arrows.