STEREOKIMIA 2012 1

Organic Chemistry 4th Edition

Paula Yurkanis Bruice

Irene LeeCase 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

Enantiomersnonsuperimposable 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

1

23

4

1. 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

Cl

H

CH2CH2CH3CH3CH2 (R)-3-chlorohexane

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

CH3

CH2CH3

OHH (S)-2-butanol

A Fischer projection can only be rotated 180° in the planeof the paper to yield the same molecule

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

CO2H

OH

CH3H

(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 specificrotation

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 of2n stereoisomers can be obtained

CH3CHCHCH3

Cl OH

* *

Identification of Asymmetric Carbons in Cyclic Compounds

H

CH3

H

Br*

*these two groupsare different

H

CH3

H

Br

H

Br

CH3

H

H

CH3

H

Br

CH3

H

H

Br

cis-1-bromo-3-methylcyclohexane trans-1-bromo-3-methylcyclohexane

Meso CompoundsHave 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 ofsymmetry

plane ofsymmetry

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

Reactions of compounds that contain an asymmetric carbon.

CH2CH2CH2Cl

CH3CH2 CH3

H

CH2CH2CH2OH

CH3CH2 CH3

HOH-

No reaction at the asymmetric carbon; both the reagent and theproduct have the same relative configuration.

CH

CH3CH2CH2 CH3

H

CH2 CH2CH3

CH3CH2CH2 CH3

H

H2

Pd/C

If a reaction breaks a bond at the asymmetric carbon, you need toknow the reaction mechanism in order to predict the relative configuration of the product.

Resolution of a Racemic Mixture

(R)-acid (S)-acidenantiomers

(S)-base(R,S)-salt (S,S)-salt

diastereomers

(R,S)-salt (S,S)-salt

HCl 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 chemicalreactivity 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

N+CH3CH2CH2 CH2CH3

H

CH3

N+CH2CH2CH3CH3CH2

H

CH3

Br- Br-

O

POCH2CH3

H

O

PCH3CH2O OCH3

HCH3O

Amine Inversion

A regioselective reaction: preferential formation of oneconstitutional 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 stereoselectiveNot 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

CH3CH2C CH2 HBr CH3CH2CHCH2Br

2-methyl-1-butene

CH3

+peroxide

CH3

*

1-bromo-2-methylbutane

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: synTwo substituents added to opposite sides of the double bond: anti

C C

CH3CH2 CH2CH3

CH3H3C

+ HCl CH3CH2CH

CH3

CCH2CH3

Cl

CH3

C C

CH3CH2

H3CCH2CH3

CH3

H

C C

C C

CH3CH2

H3CCl

CH2CH3

CH3

H

Cl

CH3CH2

CH2CH3

HCl

H3C

CH3 C C

CH3CH2

CH2CH3

HCH3

H3C

Cl

A radical reaction intermediate

Addition reactions that form two asymmetric carbons

Stereochemistry of Hydrogen Addition (Syn Addition)

Hydrogenation of Cyclic Alkenes

CH(CH3)2

H3C

+ H2Pt/C

H

CH3

H

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 ionintermediate (anti addition)