Show a synthetic pathway

Hint: Alkenes may be formed from alkyl halides by reaction with a strong base such as NaOCH 3 resulting elimination of HX.

Fill in the blanks.

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 (an 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

Absolute Configuration

Assign Priority to each Group on Asymmetric Center

Lactic Acid

C.I.P. Priorities

Enantiomeric Excess (Optical Purity)

SSRI Efficacy depends on Stereochemistry (+/-) Celexa(-) Lexapro Cost $17.10 per month$83.83 per month

Art in Chemistry Lexapro is the S enantiomer. Draw the structure of Lexapro.

Art in Chemistry Lexapro contains only the S enantiomer. Celexa is a racemic (50:50) mixture of both S and R forms.

Biological Activity In the 50’s, thalidomide was sold as a racemic mixture!

Thalidomide was prescribed as a sedative and used against nausea and to alleviate morning sickness in pregnant women.

Fischer Projections

Assigning Absolute Configuration to Fischer Projections

Rotation of the Projection 90 o Reverses Absolute Configuration Translation: If you rotate the Fisher projection 90 o you are drawing the opposite enantiomer!

Determine the stereochemistry at all chiral centers.

(7) Should be R, R, S, R from C-1; 5 th chiral center not included. 1

Diastereomers Stereoisomers That Are Not Mirror Images

Fischer Projections with 2 Chiral Centers

2 Chiral Centers 4 Stereoisomers

Identical, Enantiomers or Diastereomers?

S-2-Bromobutane (2R,3S)-3-aminobutan-2-ol

Tartaric Acids Solve one structure first. Make sure you do it correctly! Use it as reference for others.

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

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

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

Sildenafil (Viagra) and Caffeine

Radiosensitizer of Choice Until 2004

How is each Cpd related to X?

Enantiomers: A, C Diastereomers: B, E, F, H, I Identical: D, G