Organic Chemistry

4th Edition Paula Yurkanis Bruice

Chapter 5
Stereochemistry
The Arrangement of Atoms in Space; The Stereochemistry of Addition Reactions

Irene Lee Case Western Reserve University Cleveland, OH 2004, Prentice Hall

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

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 carbon
1 4

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
Cl CH3CH2 H CH2CH2CH3

(R)-3-chlorohexane

2. If the lowest priority is on a horizontal bond, the naming is opposite to the direction of the arrow
CH3 H OH CH2CH3

(S)-2-butanol

3. The arrow can go from group 1 to 2, passing group 4, but not group 3

CO2H H OH CH3
(S)-lactic acid

A Fischer projection can only be rotated 180 in the plane of the paper to yield the same molecule

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 (a)

T is the temp in C
is the wavelength a 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
observed specific rotation optical purity = specific rotation of the pure enantiomer

enantiomeric excess =

excess of a single enantiomer

entire mixture

Isomers with more than one chiral carbon: a maximum of 2n stereoisomers can be obtained
* * CH3CHCHCH3
Cl OH

Diastereomers are stereoisomers that are not enantiomers

Identification of Asymmetric Carbons in Cyclic Compounds

H

these two groups * are different

Br

*
CH3

H H Br CH3 CH3 H

H CH3 CH3

Br

Br H H

Br

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.

CH2CH2CH2Cl H CH3CH2 CH3 OHCH3CH2 CH2CH2CH2OH H CH3

CH CH3CH2CH2

CH2

H2 Pd/C CH3CH2CH2

CH2CH3 H CH3

H CH3

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 HCl

(S)-baseH+ (S)-baseH+ + + (S)-acid (R)-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

CH3 BrCH3CH2CH2 N+ H CH2CH3

CH3 N+ BrH CH2CH2CH3 CH3CH2

O P CH3CH2O H OCH3

O H P OCH2CH3 CH3O

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

CH3 CH3CH2C CH2 + HBr peroxide

CH3 CH3CH2CHCH2Br * 1-bromo-2-methylbutane

2-methyl-1-butene

Addition reactions that form an additional asymmetric carbon

Addition reactions that form two asymmetric carbons

A carbocation reaction intermediate
CH3CH2 C H3C CH2CH3 C CH3 + HCl CH3CH2CH Cl CCH2CH3

CH3 CH3 CH3CH2 Cl C H3C H3C C H CH3CH2 C CH3 H CH2CH3

CH3CH2 H3C Cl H3C C C C

CH3 H CH2CH3

CH2CH3 C

CH2CH3 C Cl

CH3 H CH3CH2 Cl

CH3

Two substituents added to the same side of the double bond: syn Two substituents added to opposite sides of the double bond: anti

Addition reactions that form two asymmetric carbons A radical reaction intermediate

Stereochemistry of Hydrogen Addition (Syn Addition)

Hydrogenation of Cyclic Alkenes

H
+

H2

Pt/C CH3 CH(CH3)2

H3C CH(CH3)2 H3C H CH(CH3)2 H

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)