Fischer Projections Fischer projection: a two- dimensional representation showing the configuration of a stereocenter –horizontal lines represent bonds projecting forward –vertical lines represent bonds projecting to the rear –the only atom in the plane of the paper is the stereocenter

Fischer Projections 1. Orient the stereocenter so that bonds projecting away from you are vertical and bonds projecting toward you are horizontal 2. Flatten it to two dimensions

Fischer Projections Example: convert each three-dimensional representation to a Fischer projection with the carbon chain vertical. Assign an R,S configuration to each stereocenter

Enantiomers & Diastereomers For a molecule with 1 stereocenter, 2 1 = 2 stereoisomers are possible For a molecule with 2 stereocenters, a maximum of 2 2 = 4 stereoisomers are possible For a molecule with n stereocenters, a maximum of 2 n stereoisomers are possible

Enantiomers & Diastereomers 2,3,4-Trihydroxybutanal; –two stereocenters; 2 2 = 4 stereoisomers exist

Enantiomers & Diastereomers 2,3-Dihydroxybutanedioic acid (tartaric acid) –two stereocenters; 2 n = 4, but for this molecule, only three stereoisomers exist

Enantiomers & Diastereomers For tartaric acid, the three possible stereoisomers are one meso compound and a pair of enantiomers Meso compound: an achiral compound possessing two or more stereocenters.

Enantiomers & Diastereomers cis-3-Methylcyclohexanol

Enantiomers & Diastereomers trans-3-Methylcyclohexanol

Enantiomers & Diastereomers 2-Methylcyclopentanol

Enantiomers & Diastereomers 1,2-cyclopentanediol

Properties of Stereoisomers Enantiomers have identical physical and chemical properties in achiral environments Diastereomers are different compounds and have different physical and chemical properties Meso-tartaric acid, for example, has different physical and chemical properties from its enantiomers (see Table 4.1, p 138).

Plane Polarized Light Ordinary light: consists of waves vibrating in all planes perpendicular to its direction of propagation Plane polarized light: consists of waves vibrating only in one plane Plane polarized light is an equal mixture of left and right-circularly polarized light. These two forms are nonsuperposable mirror images and, therefore, enantiomers.

Optical Activity Observed rotation: the number of degrees, , through which a compound rotates the plane of polarized light Dextrorotatory (+): rotation of the plane of polarized light to the right Levorotatory (-): rotation of the plane of polarized light to the left

Optical Activity Specific rotation: Observed rotation of the plane of polarized light when a sample is placed in a tube 1.0 dm in length and at a concentration of 1g/mL.

Optical Activity For a pair of enantiomers, the value of the specific rotation of each is the same, but opposite in sign

Enantiomeric Excess When dealing with a mixture of enantiomers, it is essential to describe the composition of the mixture and the degree to which one enantiomer is in excess The most common designation is enantiomeric excess (ee)

Enantiomeric Excess Example: A commercial synthesis of Naproxen, a nonsteroidal antiinflammatory agent, gives this enantiomer in 97% ee. Assign an R,S configuration to its stereocenter, and calculate the % R and S enantiomers in the mixture.

Resolution Racemic mixture: an equimolar mixture of two enantiomers –because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific activity is zero. Resolution: the separation of a racemic mixture into its enantiomers

Resolution One means of resolution is to convert the pair of enantiomers into two diastereomers –diastereomers are different compounds and have different physical properties A common reaction for chemical resolution is salt formation –after separation of the diastereomers, the enantiomerically pure acids are recovered

Resolution Examples of enantiomerically pure bases