Organic Chemistry 6th Edition Paula Yurkanis Bruice Chapter 5 Stereochemistry The Arrangement of Atoms in Space; The Stereochemistry of Addition Reactions
Isomers Non-identical compounds having the same molecular formula
A stereocenter (or stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer
Achiral compounds have superimposable mirror images. • Chiral compounds have nonsuperimposable mirror images.
Using the -Plane to Determine if a Molecule is Chiral or Achiral • The -plane is an internal plane of symmetry passing through a molecule. • If there is one or more -planes, the molecule is achiral. • If there are no -planes, the molecule is chiral. The presence of asymmetric centers does not imply chirality!
Drawing Enantiomers Perspective formula Fischer projection
Naming Enantiomers The R,S system of nomenclature Rank the groups (atoms) bonded to the asymmetric center. Ranking Rules: Consider the atomic number of the atoms bonded directly to the asymmetric carbon. If there is a tie, consider the atoms attached to the tied atoms. Multiple bonds are treated as attachment of multiple single bonds using “divide-duplicate.” Rank the priorities by mass number in isotopes. Same rules as for E/Z assignments
Orient the lowest priority (4) away from you: • Clockwise = R configuration • Counterclockwise = S configuration
Naming from the Perspective Formula 1. Rank the groups bonded to the asymmetric center with the lowest priority group in the back.
2. If the group (or atom) with the lowest priority is in the front, assign S or R and then switch your answer to R or S respectively. Configuration is S 3. Alternatively, atoms or groups can be switched so as to place the lowest priority group in the back. One switch: configuration opposite; two switches, configuration unchanged.
Lowest priority group in back Configuration from the Fischer Projection 1. Consider the 3-dimensional equivalent to the Fischer Projection. 2. Rank the groups (or atoms) that are bonded to the asymmetric center and then draw an arrow from the highest priority (1) to the next highest priority (2).
Lowest priority group in front 3. If the lowest priority is on a horizontal bond, the configuration is opposite to the direction of the arrow.
D, because hydroxyl is on the right L, because amine is on the left D and L Nomenclature • Emil Fischer originally used Fischer Projections to show the stereochemistry of amino acids and carbohydrates. • These Fischer Projections have carbons on the vertical axis and Hs and OH or NH2 groups on the horizontal axis. • Commercial protein supplements have “L-glycine” as an ingredient. Is this nomenclature correct? • Most chiral amino acids have the S configuration. Which one has the R configuration?
Discrimination of Enantiomers by Biological Molecules Three-Point Binding:
Chiral Drugs Interacting with a Chiral Receptor The unnatural epinephrine enantiomer has the amine and hydroxyl groups reversed. Therefore no receptor binding.
Influence of Chirality on Drug Action Enantiomers can have different drug activity because of different receptor binding activity.
Clockwise (+) Counterclockwise (-) Different from R,S configuration Chiral compounds are optically active; they rotate the plane of polarized light. Achiral compounds do not rotate the plane of polarized light. They are optically inactive.
T is the temp in °C • is the wavelength • is the measured rotation in degrees • l is the path length in decimeters • c is the concentration in grams per mL A polarizer measures the degree of optical rotation of a compound The observed rotation (a): Specific Rotation Each optically active compound has a characteristic specific rotation.
observed specific rotation x 100% enantiomeric excess = specific rotation of the pure enantiomer • A racemic mixture, which contains an equal amount of the two enantiomers, is optically inactive. • The enantiomeric excess (ee) tells us how much of an excess of one enantiomer is in a mixture. • 2-Bromobutane, Four possibilities: • (S) - (+) - 2 – Bromobutane, a = + 23.1o • (R) - (-) - 2 – Bromobutane, a = + 23.1o • 2 – Bromobutane, racemic, zero rotation • An enantiomeric excess
Isomers with more than one asymmetric center: a maximum of 2n stereoisomers can be obtained Diastereomers are stereoisomers that are not enantiomers
Identification of Asymmetric Carbons in Cyclic Compounds
1-Bromo-4-methylcyclohexane has only one cis isomer and one trans isomer These compounds possess an internal plane of symmetry (-plane) and are therefore achiral.
Meso Compounds Have two or more asymmetric centers and an internal plane of symmetry (-plane) Meso compounds are achiral molecules with asymmetric centers
If a compound with two asymmetric centers has the same four groups bonded to each of the centers, one of its stereoisomers will be a meso compound
-Plane Present: No -Plane Present:
As long as any one conformer of a compound has a plane of symmetry, the compound will be achiral
Asymmetric Nitrogen Centers Rapid lone pair inversion prevents resolution of amine enantiomers: Quaternary amine-based enantiomers can be resolved because there is no lone pair:
Asymmetric Sulfur and Phosphorus Centers Lone pair inversion does not occur and enantiomers are resolvable
Naming Isomers with More Than One Asymmetric Center The OH group at C-2 has the highest priority, followed by Br in C-3 The isomer is named (2S, 3R)-3-bromo-2-butanol
A regioselective reaction: preferential formation of one constitutional isomer: A stereoselective reaction: preferential formation of a stereoisomer: • Enantioselectivity: selective formation of an enantiomer • Diastereoselectivity: selective formation of a diastereomer
A stereospecific reaction: each stereoisomeric reactant forms a different stereoisomeric product or a different set of stereoisomeric products • All stereospecific reactions are stereoselective • Not all stereoselective reactions are stereospecific
Excess of an enantiomer not observed Excess of an enantiomer not observed Predicting the Stereochemical Result of Reactions • An achiral or a racemic product results from achiral reactants and reagents:
Used to distinguish treated from untreated sewage • The formation of a product in enantiomeric excess from an achiral or racemic reactant requires an enantioselective catalyst:
Diastereomers formed in unequal amounts • The presence of an asymmetric center near a reacting center will result diastereoselectivity.
No reaction at the asymmetric center; both the reactant and the product have the same relative configuration.
If a reaction breaks a bond at the asymmetric center, you need to know the reaction mechanism in order to predict the configuration of the product. • SN1 Reaction: racemization • SN2 Reaction: inversion of configuration
Stereochemistry of Electrophilic Addition Reactions of Alkenes A regioselective reaction without stereoselectivity Racemic Mixture Results
Addition reactions that form products with two asymmetric centers All four possible stereoisomers result:
The Stereochemistry of Hydrogen Addition Exclusive Formation of Erythro Enantiomers:
Exclusive Formation of Meso Stereoisomer: Exclusive Formation of Threo Enantiomers:
Addition of H2 to cyclic alkene Racemic Mixture: Meso:
The Stereochemistry of Epoxidation The addition of a peroxyacid to an alkene to form an epoxide is a concerted reaction. Orientation of alkyl substituents remain unchanged.
The Stereochemistry of Hydroboration–Oxidation Syn addition of H2O Regioselective: OH on least substituted carbon Syn addition of H2O