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.

Constitutional isomers Isomerism : Compounds with the same molecular formula but different structures Stereochemistry Stereoisomer Constitutional isomers Conformation Configuration Geometrical Diastereomer Enantiomer Trans Cis

Stereochemistry of Tetrahedral Carbons Is the chemistry of the molecules in three dimensions 3

Definitions Configuration isomers - differ from each other only in arrangement of their atoms in space Chiral compounds( asymmetric carbon) (stereogenic center or stereo center) – sp3 carbon with 4 different atoms or groups attached & don’t have plane of symmetry (that is optically active and are called optical isomers) . achiral compound – a compounds have two or more atoms or groups that are the same (that is optically inactive) Optical activity – the ability to rotate the plane of plane –polarized light Polarimeter – device that measures the optical rotation of the chiral compound

More 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 Racemic mixtures – a mixture of enanatiomers with the same amount of each ( are optically inactive and donated by +/-)

Plane-Polarized Light through an Achiral Compound

Plane-Polarized Light through a Chiral Compound

c = concentration in g/mL Specific Rotation, [α] [α] = α / cl a = 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 [a] # * centers Penicillin V +233.0 3 Sucrose +66.5 10 Camphor +44.3 2 MSG +25.5 1 Cholesterol -31.3 8 Morphine -132.0 5

Chirality Center Carbon has four different groups attached

Enantiomers nonsuperimposible mirror images

NAMING ENANTIOMERS Since two enantiomers are different compounds, we will need to have nomenclature which distinguishes them from each other. The convention which is used is called the (R,S) system (absolute configuration) because one enantiomer is assinged as the R enantiomer and the other as the S enantiomer. What are the rules which govern which is which? The conversion of a perspective drawing to a Fischer projection requires rotating the molecule so that the "top" and "bottom" groups are oriented back, away from you. This places the "right" and "left" groups in a position where they are projecting outward towards you, as in a "bow-tie"

These rules are restated below, with examples: 1.Examine the four atoms directly attached to the chiral center in question. Assign priorities in order of decreasing atomic number; the atom with the highest atomic number is #1, the next is #2, etc. 2. If a decision regarding priority cannot be reached using Rule #1, compare the atomic numbers of the second atoms in each substituent, then the third, etc., until a difference is found.Example: 3-Ethoxy-2-chlorohexane

3. Multiple bonds count twice (or three times) when examining substituents. 3-Ethyl-4-chloro-pentene

C.I.P. Priorities

Enantiomeric Excess (Optical Purity)

Diastereomers Molecules with more than one chirality center have mirror image stereoisomers that are enantiomers . In addition they can have stereoisomeric forms that are not mirror images

Fischer Projections with 2 Chiral Centers

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; 2n = 8

A Carbohydrate

Internal Planes of Symmetry

Asymmetric Centers on Rings

Allenes can be Chiral

Mycomycin, an antibiotic

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

a-(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