Stereochemistry

 

Challenge: explain enantiomers to someone who is not a chemist!

 

Properties:

Enantiomers:

Same chemical and physical properties in achiral environments.

A mixture of these cannot be separated by normal GC or HPLC techniques

Different chemical and physical properties in chiral environments.

A mixture of these can (theoretically) be separated by chiral GC or HPLC techniques

Diastereomers:

Different physical/chemical properties in chiral/achiral environments.

 

Naproxen An Over-the -Counter Chiral Auxillary

Brinkman, J. A., Sowa, J. R., Jr. In Catalysis of Organic Reactions, Herkes, F. E., Ed., Marcel Dekker: New York, 1998, p. 543 - 549.

Stereogenic center (stereocenter) - a point in a molecule bearing groups such that an interchange of any two groups will produce a stereoisomer.

 

Number of possible stereoisomers = 2n , n = # of stereocenters.

For Crixivan determine # possible stereoisomers?

 

 

Relative vs. Absolute Configurations

Relative configuration - 3-D structure is not known but it is known that one structure is the mirror image of the other.

(+) or d - dextrorotatory - cpd that rotates light to the right.

(-) or l - levorotatory - cpd that rotates light to the left.

() - racemic mixture - 1:1 mixture of (+) and (-) cpds, zero rotation.

Enantiomeric excess:

 

 

Absolute configuration - 3-D structure is known.

R, S Nomenclature

(-)-alanine

  1. Prioritize - assign a priority to the groups around the stereocenter
  1. increasing atomic mass of the atom attached to stereocenter
  2.  

  3. in case of a tie move to the next atom

 

  1. Place - place the lowest priority group in the back.
  2.  

     

  3. Connect a ® b® c

 

Always draw the arrow on paper as you mind can easily reverse itself!

Shortcut: if lowest priority group is unambiguously in the front then reverse assignment.

Examples:

Try these:

Draw the structure of (S)-penicillamine (used for treatment of arthritis):

How many stereocenters are present; label each stereo center as R/S:

 

 

 

 

 

Reading Fischer Projections

 

Groups along the horizontal plane are facing forward. Groups along the vertical plane are facing back.

 

 

Haworth Projections - good for cyclic compounds.

E/Z Nomenclature - It's E/Z!

1. Split double bond in half.

 

  1. Prioritize - assign a priority to the groups attached to each carbon (same rules as R/S)
  2.  

     

  3. E - entgegen (opposite) - highest priority groups are on the opposite sides.

Z - zusammen (together) - highest priority groups are on the same side.

 

Stereochemical Reactions

Inversion of Configuration

SN2 reactions are an excellent example of reactions that go with inversion of configuration.

 

 

Retention of Configuration

Tosylation

Derivativization Reactions

 

Racemization

Epimerization - a form of racemization

May occur with enolizable carbons:

 

Examples

 

 

Separation of Enantiomers

 

A) Pasteur's Method

 

 

    1. Resolution
    2.  

    3. Resolution-Racemization

 

Asymmetric Synthesis

  1. Diastereoselective synthesis:

Example:

 

 

  1. Enantioselective synthesis:

 

Example:

  1. Kinetic Resolution