Organic Chemistry 4 th Edition Paula Yurkanis Bruice Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall Chapter 5 Stereochemistry The Arrangement of Atoms in Space; The Stereochemistry of Addition Reactions

Isomers Nonidentical compounds having the same molecular formula

Cis-Trans Isomers

Achiral compounds have superimposable mirror images Chiral compounds have nonsuperimposable mirror images

Enantiomers nonsuperimposable mirror-image molecules

Drawing Enantiomers Perspective formula Fischer projection

A stereocenter (stereogenic center) is an atom at which the interchange of two groups produces a stereoisomer

Naming Enantiomers Rank the groups (atoms) bonded to the chirality center The R,S system of nomenclature

Orient the lowest priority (4) away from you Clockwise = R configuration Counterclockwise = S configuration

Naming from the Perspective Formula Rank the groups bonded to the asymmetric carbon 2. If the group (or atom) with the lowest priority is bonded by hatched wedge,

3. If necessary, rotate the molecule so that the lowest priority group (or atom) is bonded by a hatched wedge 4. You can draw group 1 to group 2, passing group 4, but never 3

Naming from the Fischer Projection 1. Rank the groups (or atom) that are bonded to the asymmetric carbon and draw an arrow with the highest priority to the lowest priority (R)-3-chlorohexane 2. If the lowest priority is on a horizontal bond, the naming is opposite to the direction of the arrow (S)-2-butanol

A Fischer projection can only be rotated 180 ° in the plane of the paper to yield the same molecule 3. The arrow can go from group 1 to 2, passing group 4, but not group 3 (S)-lactic acid

Chiral compounds are optically active; they rotate the plane of polarized light. Clockwise (+)Counterclockwise (-) Different from R,S configuration Achiral compounds do not rotate the plane of polarized light. They are optically inactive.

A polarizer measures the degree of optical rotation of a compound The observed rotation (  ) 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 Each optically active compound has a characteristic specific rotation

A racemic mixture, which contains an equal amount of the two enantiomers, is optically inactive optical purity = observed specific rotation specific rotation of the pure enantiomer enantiomeric excess = excess of a single enantiomer entire mixture

Diastereomers are stereoisomers that are not enantiomers Isomers with more than one chiral carbon: a maximum of 2 n stereoisomers can be obtained

Identification of Asymmetric Carbons in Cyclic Compounds these two groups are different cis-1-bromo-3-methylcyclohexane trans-1-bromo-3-methylcyclohexane

Meso Compounds Have two or more asymmetric carbons and a plane of symmetry They are achiral molecules

As long as any one conformer of a compound has a plane of symmetry, the compound will be achiral plane of symmetry plane of symmetry

The R,S nomenclature of isomers with more than one asymmetric carbon

Reactions of compounds that contain an asymmetric carbon. No reaction at the asymmetric carbon; both the reagent and the product have the same relative configuration. If a reaction breaks a bond at the asymmetric carbon, you need to know the reaction mechanism in order to predict the relative configuration of the product.

Resolution of a Racemic Mixture (R)-acid (S)-acid enantiomers (S)-base (R,S)-salt(S,S)-salt diastereomers (R,S)-salt(S,S)-salt HCl (S)-baseH + + (R)-acid (S)-baseH + + (S)-acid

Discrimination of Enantiomers by Biological Molecules

Terminologies Associated with Stereochemistry pro-R-hydrogen pro-S-hydrogen Enantiotopic hydrogens have the same chemical reactivity and cannot be distinguished by achiral agents, but they are not chemically equivalent toward chiral reagents

Diastereotopic hydrogens do not have the same reactivity with achiral reagents

Atoms other than carbon can be asymmetric

Amine Inversion

A regioselective reaction: preferential formation of one constitutional isomer A stereoselective reaction: preferential formation of a stereoisomer

A stereospecific reaction: each stereoisomeric reactant produces a different stereoisomeric product or a different set of products All stereospecific reactions are stereoselective Not all stereoselective reactions are stereospecific

Stereochemistry of Electrophilic Addition Reactions of Alkenes What is the absolute configuration of the product?

Addition reactions that form one asymmetric carbon

Addition reactions that form an additional asymmetric carbon

A carbocation reaction intermediate Addition reactions that form two asymmetric carbons Two substituents added to the same side of the double bond: syn Two substituents added to opposite sides of the double bond: anti

A radical reaction intermediate Addition reactions that form two asymmetric carbons

Stereochemistry of Hydrogen Addition (Syn Addition)

Hydrogenation of Cyclic Alkenes Only cis isomers are obtained with alkenes containing fewer than eight ring atoms Both cis and trans isomers are possible for rings containing eight or more ring atoms

Stereochemistry of Hydroboration– Oxidation

Addition reactions that form a bromonium ion intermediate (anti addition)