Ch 5 Lect.

2 Fischer Projections
I. Simple Fischer Projections
A. Fischer Projections are a method to draw 3D molecules in 2D
1) A A A

D C D C D
B C S B S B S
2) There are multiple Fischer Projections for each molecule
D D
B A B A
C S C S
B. Rotating Fischer Projections may change the Stereochemistry (R/S)
1) 90 degree rotation interconverts enantiomers
2) 180 degree rotation retains enantiomer
R S Br R CH3
H 90o o
90
Br CH2CH3 H3C H CH2CH3 Br
CH3 CH2CH3 H
 C) Switching Substituents on a Fischer Projection
1) Any single (odd #) exchange of 2 substituents gives the other enantiomer
2) Any two (even #) of exchanges gives the same enantiomer
R H S CH3 R CH3
H/CH3 Br/Et
Br CH2CH3 Br CH2CH3 CH3CH2 Br
exchange exchange
CH3 H H

D) Absolute Configuration from Fischer Projection

1) For Dashed-Wedged line drawing you must visualize in 3D
2) Fisher Projections: becomes a 2D visualization (less error)
3) Rules
a) Draw any Fischer Projection of any chiral molecule
b) Rank substituents as in R/S nomenclature
c) Exchange once to put lowest priority substituent at the top
d) Exchange any 2 substituents to retain original stereochemistry
e) Clockwise a-b-c = R; Counterclockwise a-b-c = S

CH3 S
CH3 CH3 H H

F Cl F Cl F Cl F F Cl
H Cl H H CH3 CH3
II. Fischer Projections with Multiple Stereocenters
A) 2-Bromo-3-chlorobutane (Figure 5-7)

1) RR, RS, SR, and SS possibilities

2) Fischer Projection has all substituents eclipsed, so to draw the Fischer
from Dashed-Wedged or Newman, make eclipsed first
3) To assign R/S to each stereocenter, treat just as a substituted methane
B) Relationships of 2-stereocenter Stereoisomers
1) RR and SS are non-superimposable mirror images = Enantiomers
2) RS and SR are non-superimposable mirror images = Enantiomers
3) RR-RS, RR-SR, SS-RS, and SS-SR aren’t mirror images = Diastereomers

C) Two stereocenters with identical substitution: 2,3-dibromobutane

1) RR/SS Enantiomeric pair
2) RS/SR are mirror images, superimposable = Identical = Achiral
3) Meso = multiple stereocenters, superimposable with mirror image
a) Have a mirror plane
b) Look at eclipsed conformation
D) cis/trans Isomers
1) Just like butane, Cyclobutane has RR, SS, RS, SR configurations
2) RR, SS = trans; RS, SR = cis
3) cis and trans isomers are Diastereomers (for all 1,2-disub-cycloalkanes)

E) More than 2 stereocenters

1) For n stereocenters, 2n stereoisomers possible (maybe less--meso)
2) n = 3 RRR RRS RSS SRS
Enantiomeric Pairs
SSS SSR SRR RSR
III. Stereochemistry in Reactions
A) Bromination of Butane

1) Optically Inactive Reactants give

Optically Inactive Products

2) Achiral to Chiral gives Racemate

B) Chlorination of (S)-2-bromobutane
1) Chlorination at C1/ C4 give Achiral

2) Optically ActiveOptically Active

3)Original Stereocenter untouched

H H H
Cl Cl
ClCH2 C CH3 C CH3 C
CH3CH2 Br CH3CH2 Br ClCH2CH2 Br
R S S
4) Chlorination at C2 (the stereocenter) gives a racemate Cl
C
S
CH3
H CH3CH2 Br
Cl CH3 Cl2
CH C C Br
SCH3CH32 Br CH3CH2 CH3CH2 Br
CH3 C
R
Cl

5) Chlorination at C3
a) Form another C*, 4 diastereomers
b) Transition state is chiral
c) Stereoselective = when a reaction
gives major product when several
stereoisomers are possible
d) Sterics of TS control favored prod
e) Hard to control in Organic Chem
because always get some minors
f) Enzymes do this very well
IV. Resolution of Enantiomers

A) Separate the members of a racemate to get pure enantiomers

1) Amino acids, carbohydrates, nucleic acids often are single enantiomers
2) Drug molecules often only work in one enantiomeric form

B) Methods
1) Crystallization and manual separation (LUCK!)
2) Chemical Separation: enantiomers have same physical properties
3) React Enantiomers to make them Diastereomers (different properties)
4) Do chemical separation: crystallization, distillation, etc…
5) React to get pure enantiomers back
Resolution of Enantiomers