Stereochemistry Stereochemistry refers to the 3-dimensional properties and reactions of molecules. It has its own language and terms that need to be learned in order to fully communicate and understand the concepts.

Definitions Stereoisomers – compounds with the same connectivity, different arrangement in space Enantiomers – stereoisomers that are non- superimposible mirror images; only properties that differ are direction (+ or -) of optical rotation Diastereomers – stereoisomers that are not mirror images; different compounds with different physical properties

More Definitions Asymmetric center – sp 3 carbon with 4 different groups attached Optical activity – the ability to rotate the plane of plane –polarized light Chiral compound – a compound that is optically active (achiral compound will not rotate light) Polarimeter – device that measures the optical rotation of the chiral compound

Plane-Polarized Light

Plane-Polarized Light through an Achiral Compound

Plane-Polarized Light through a Chiral Compound

Polarimeter Measures Optical Rotation

Specific Rotation, [α] [α] = α / cl  = observed rotation c = concentration in g/mL l = length of tube in dm Dextrorotary designated as d or (+), clockwise rotation Levorotary designated as l or (-), counter- clockwise rotation

Specific Rotations of some Common Organic Compounds Compound[  ]# * centers Penicillin V Sucrose Camphor MSG Cholesterol Morphine

Chirality Center Carbon has four different groups attached

Enantiomers nonsuperimposible mirror images

Enantiomeric Excess (Optical Purity)

Biological Activity

SSRI Efficacy depends on Stereochemistry Lexapro® and Celexa® are both prescription medications classified as selective serotonin reuptake inhibitors, licensed to treat depression.

Absolute Configuration

Assign Priority to each Group on Asymmetric Center

Lactic Acid

C.I.P. Priorities

Fischer Projections

Assigning Absolute Configuration to Fischer Projections

Rotation of the Projection 90 o Reverses Absolute Configuration

Exercise: (1)Assign R/S configurations to the ff molecules: (2)Draw a tetrahedral representation of (S)-2- hydroxypentane.

Lexapro and Celexa are formulations of an anti-depressant drug. Celexa was available first and is a mixture of R and S enantiomers of citalopram. Lexapro is just the S enantiomer of citalopram. Draw the molecular structure of each enantiomer.

Celexa was available first and is a mixture of R and S enantiomers of citalopram. Lexapro is just the S enantiomer of citalopram. Which one is Lexapro? Which one is Celexa?

Diastereomers Stereoisomers That Are Not Mirror Images

Fischer Projections with 2 Chiral Centers

2 Chiral Centers 4 Stereoisomers

Identical, Enantiomers or Diastereomers?

Tartaric Acids

Racemic Mixture

Meso Compound Internal Plane of Symmetry Optically Inactive

2,3,4-trichlorohexane How many stereoisomers?

n = 3; 2 n = 8

A Carbohydrate

Internal Planes of Symmetry

Asymmetric Centers on Rings

Which are meso compounds?

Reactions that Generate Chirality Centers Hydrogenation, syn

Bromination Trans is formed exclusively No Meso is formed (cis)

Bromonium Ion is Opened Equally from Both Sides

trans alkene + anti addition = MESO

cis Alkene + anti addition = racemic mixture

Brominations Often Generate Asymmetric Centers

Asymmetric Center is Generated Racemic Mixture Formed

Asymmetric Induction

Preparation of (L)-Dopa for Treatment of Parkinson’s

Relevance of Stereochemistry

One-step synthesis

 -(p-isobutylphenyl)propionic acid

Model of Thalidomide

How Sweet it is! Sucralose is 600 times sweeter and does not get metabolized.

Sildenafil (Viagra) and Caffeine

Radiosensitizer of Choice Until 2004