Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf ·...

41
1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship between isomers. ISOMERS if different connectivity if they have same connectivity CONSITUTIONAL ISOMERS STEREOISOMERS DIASTEREOISOMERS if a rotation about σ bond makes them identical if they are not nonsuperimposable mirror images if they have no stereogenic centers Z, E ISOMERS (DIASTEREOMERS) CONFIGURATIONAL ISOMERS if they are nonsuperimposable mirror images ENANTIOMERS if bonds must be broken and reformed to make them identical CONFORMATIONAL ISOMERS

Transcript of Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf ·...

Page 1: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

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Chapter 4 Stereochemistry and Chirality

Flow chart for determining the relationship between isomers.

ISOMERSif differentconnectivity

if they havesame connectivityCONSITUTIONAL

ISOMERS

STEREOISOMERS

DIASTEREOISOMERS

if a rotation about σbond makes

them identical

if they are notnonsuperimposable

mirror images

if they haveno stereogenic

centers

Z, E ISOMERS(DIASTEREOMERS)

CONFIGURATIONALISOMERS

if they arenonsuperimposable

mirror images

ENANTIOMERS

if bonds must be broken andreformed to make them identical

CONFORMATIONALISOMERS

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Symmetry Elements

A mirror plane in Cartesian coordinates that includes the y and z axis

means that for every point {x,y,z} there is a corresponding point {–x,y,z}. Ifa

molecule has a mirror plane, then for every atom on one side of the plane there

is an equivalent atom that is the mirror equivalent on the opposite side of the

plane. When two identical groups are on one carbon, there is an internal mirror

plane passing through the molecule.

H H

O

H H

HHHH

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Symmetry Elements (continued)

An inversion center takes every point {x,y,z} to an equivalent point

{–x,–y,–z}:

CH3

H

Br

HH

H3C

H

Br

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Chirality

The word "chirality" (from the Greek) refers to the property of "handedness".

To first approximation your right and left hands are mirror images that cannot

be superimposed on top of each other.

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Chirality (continued)

Molecules that lack both a mirror plane and an inversion center can have non-

superimposable mirror images and are said to be chiral. A chiral center

usually is a tetrahedral carbon with four different groups attached to it. Chiral

carbons are also referred to as stereocenters, stereogenic centers, or

asymmmetric centers.

1-Bromo-1-chloroethane is chiral:

1

24

3

H

CH3Cl

Br

H

H3CBr

Cl

H

H3CCl

Br

H

H3CBr

Cl

CH3

HBr

Cl

H

H3CBr

Cl

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Chirality (continued)

Any molecule that has an internal mirror plane is achiral.

Br

ClH

H

H3C

ClBr

CH3

ClBr

H3C

ClBr

CH3

ClBr

A molecule that has an inversion center is achiral.

CH3

H

Br

HH

H3C

H

Br

H3C

H

Br

H H

CH3

H

Br

CH3

H

H

BrH

H3C

Br

H

CH3

H

Br

HH

H3C

H

Br

rotate 90°

rotate 180°

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Chirality (continued)

Further examples of achiral and chiral molecules:

H

H BrBr

H HCl

Cl

HO OH

achiral achiral achiral

Cl

H CH3Br

H3C

Br

H HCl

Cl

HO OH

chiral chiral chiral

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Stereoisomers: Enantiomers

Molecules that are mirror images but are not superimposable are called

enantiomers. Enantiomers are stereoisomers. That is, they are isomers that

have the same connectivity, but have groups that occupy different regions of

space.

Enantiomers have the same physical properties (e.g. melting points,

boiling points, etc) but differ in the way they interact with other chiral objects

(e.g. polarized light or different chiral molecules).

It is possible to have a molecule with no chiral center that is chiral.

Consider 1,3-dimethylallene, shown below:

H

CH3

HH3C

H

H3C

HCH3

H

•H

CH3

H3C

H3C

CH3

HH

H

•CH3

HH3C

H

CH3

HH3C

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Stereoisomers: Diastereomers

Stereoisomers that are not enantiomers are called diastereomers.

H3C

ClBr

C2H5

BrCl

H3C

BrCl

C2H5

BrCl

For a molecule with multiple chiral centers, the number of possible

stereoisomers is given by:

x = 2n

where x is the number of possible isomers and n is the number of chiral centers.

Thus, for molecules with two chiral centers there are four possible

stereoisomers. (e.g. cholesterol, which has eight stereogenic centers, has 256

possible stereoisomers!! )

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Stereoisomers: Meso compounds

Another type of stereoisomer is called a meso compound.

• A meso compound contains at least two stereogenic centers, yet the

molecule itself is not chiral.

• Meso compounds contain an internal plane of symmetry.

H3C

ClBr

CH3

ClBr

H3C

ClBr

CH3

ClBr

.

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Cahn-Ingold-Prelog Convention for Assigning Absolute Configurations

The rules for assignment of priorities in order to assign absolute configuration

are based on the same set of rules for assigning E and Z stereochemistry. Use

the Cahn-Ingold-Prelog scheme to assign priorities to the groups attached to

the carbon atom as follows:

I. Consider each group attached to the carbon in question separately.

II. Rank the priority of the substituent on the carbon as follows.

A. The atom with the higher molecular weight takes top priority. If

there are two isotopes of the same atom, the isotope with the higher

mass takes priority.

B. If this does not distinguish, then move down the chain of the

substituent assigning priorities until you reach the first point of

difference.

III. Multiple bonds count as multiples of that same atom.

IV. Once the priorities have been assigned, rotate the molecule in space so

that the lowest priority group is pointing back.

V. Connect the three remaining groups in order of decreasing priority and

examine the direction of the resulting rotation.

VI. Clockwise rotation is termed R (rectus; right) and counterclockwise

rotation is termed S (sinister; left).

• Alternatively, if the lowest priority is NOT in the back simply switch the

group that is lowest priority with another group. You have just made the

mirror image of the molecule. Now assign R or S to the compound as it

IS drawn, and then SWITCH THE R AND S LABEL TO GET THE

ORIGINAL COMPOUNDS.

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Cahn-Ingold-Prelog Convention for Assigning Absolute Configurations

4

32

1

H

H3CBr

Cl

Cl

H3C

H

Br

120° rotation

2

31

4

120° rotation

Counterclockwise = S

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Fischer Projections

The conversion of a perspective drawing to a Fischer projection requires

rotating the molecule so that the "top" and "bottom" groups are oriented back,

away from you as is shown for the two molecules below.

CH2OH

H

OHH3C

H

CH2OH

OHH3C

H

OHHO

HH

OHH

OHCH2OH

CHO

OHH

HO

OH

HHO

H

H

CHO

CH2OH

A Fischer projection can be used to assign absolute configuration (R or S).

2

4

13

4

2

13

R

2

4

31

4

2

31

S

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A rotation of three groups, as shown below, is equivalent to rotating the

molecule around a single bond (here the CH3-Ccentral bond).

HOH2C H

OH

H3C

HO CH2OH

H

H3C

A 180 degree rotation of the entire molecule regenerates the identical

configuration.

CH2OHH

OH

CH3

H CH2OH

OH

CH3

S

HOH2C H

OH

H3C

HHOH2C

OH

CH3

S

Are we having fun yet??

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A 90 degree rotation of the entire molecule generates the enantiomer of the

original molecule.

CH2OH

H

OHH3C

H

CH2OH

OHH3C

R

CH2OHH

OH

CH3

H CH2OH

OH

CH3

S

If you flip the molecule out of the page, you generate the enantiomer of the

original molecule.

CH2OH

H

OHH3C

H

CH2OH

OHH3C

R

CH2OH

H

HO CH3

H

CH2OH

HO CH3

S

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Fischer projections are also very convenient for identifying whether pairs of

molecules are identical, enantiomers or diastereomers.

For example:

OH

H

H3C

H

CH2OHHO

HO

H

CH3

H

HOH2C OH

CH3

H

HO

H

CH2OHHO

Dia

ster

eom

ers

Enantiomers

Enantiomers

Diastereomers

H3C

H

OH

H

HOH2C OH

Dia

ster

eom

ers

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In summary:

• Exchanging any two groups around a Fischer projection generates the

enantiomer of the original compound.

• Rotating 90° generates enantiomers.

• Flipping the molecule out of the page generates enantiomers.

• Rotating 180° regenerates the same molecule.

• Rotating three groups is like a rotation about a bond and does not change

the configuration.

• Exchanging groups twice regenerates the original stereochemistry.

Review:

• A molecule with one chiral center will be chiral.

• A molecule need not have a chiral center to be chiral.

• A molecule with an inversion center cannot be chiral.

• A molecule with one or more internal mirror planes cannot be chiral.

A molecule can have more than one chiral center and not be chiral (if the chiral

centers are symmetry related by a mirror plane or an inversion center).

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If you have a molecule with two chiral centers with different sets of things

attached (1 and 2) either which can be R or S, there are four possible molecules

that can result:

(1R, 2S), (1R, 2R), (1S, 2S), (1S, 2R).

• Since for a single chiral center R and S are related by mirror symmetry then

if in a molecule all possible centers are switched from R to S and vice versa,

then the resultant molecule will be an enantiomer of the original molecule.

• If one or more chiral centers, but not all centers are switched from R to S, the

molecules will not be related by mirror images, and therefore are not

enantiomers. Such molecules are called diastereomers and they have

different physical and chemical properties.

This is illustrated in the example below:

Cl

OH

Cl

OH

Cl

OH

Cl

OH

12

Diastereomers

Ena

ntio

mer

s

Ena

ntio

mer

s

Diastereomers

Diastereomers

(1R, 2R) (1S, 2R)

(1S, 2S) (1R, 2S)

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If you have a molecule with two chiral centers with the same sets of things

attached (1 and 2) either which can be R or S, four possible molecules that can

result:

(1R, 2S), (1R, 2R), (1S, 2S), (1S, 2R)

The following relations will hold as illustrated below:

H3C

H3C HOH

HH3C

H3C OHH

OH

H3C

H3COH

H

HH3C

H3CH

OH

OH

12

Enantiomers

Dia

ster

eom

ers

Dia

ster

eom

ers

Identical, MESO

(1R, 2R) (1S, 2S)

(1R, 2S) (1S, 2R)

OH H

OH H

The chemical and physical properties of diastereomers can be completely

different. Thus, they will react at different rates and can have different melting

and boiling points etc.

The properties of enantiomers will be identical (so long as they are not

interacting with a chiral perturbation as will be described in more detail later).

Thus, they react with achiral materials at the same rates and have identical

melting points.

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Disubstituted Cyclohexanes

Cis and trans isomers can be drawn as planar views that are convenient for

looking for symmetry elements. Thus cis 1,2-dimethylcyclohexane can be

drawn as shown below. Note: that the isomers with both methyl groups up out

of the page is related to that with both into the page by rotating 180° about an

axis as shown below:

Note also that in the planar view there is a mirror plane perpendicular to the

page bisecting the C-C bonds with the methyl groups attached, thus we

conclude that the molecule is achiral. This is not obvious looking at the mirror

image in the chair form until you take into account that the molecule is

conformationally flexible and a rotation followed by a chair-chair-flip makes

the mirror images congruent.

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chair-chairflip

rotate 120°

rotate 120°

noncongruent

Note that if you cooled cis 1,2-diethycyclohexane to a temperature at which the

chair-chair flip was extremely slow, then the two mirror images would be

nonconguent and in principle you could separate each of the enantiomers.

In contrast the trans form of 1,2-dimethylcyclohexane has no mirror plane

when drawn in the planar form. It does however have a two-fold axis of rotation

which relates the up and down methyl groups.

Since there is no mirror (and no inversion center) the trans form is chiral and

we would therefore expect the mirror image not to be superimposable on the

original molecule as shown below.

rotate 120°rotate 180°

noncongruentnoncongruent

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1,3-dimethylcyclohexane

• If we consider cis and trans 1,3-dimethylcyclohexane then we see again that

the cis isomer has a mirror plane and the trans isomer does not.

• Note also that in the chair form both the axial-axial, and the equatorial-

equatorial forms have mirrors as drawn and thus are achiral even when each

form is frozen out at low temperature.

chair-chairflip

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Equivalence

Homotopic hydrogens: If you have two identical molecules each with a

methylene group of the form X- CH(1)H(2)-X, and you replace one of the

hydrogens of the H(1) in one molecule with a dummy atom (Y) and then you

independently replace the H(2) in the other molecule with a dummy atom(Y), if

then the two molecules thus created will be identical to each other, the

hydrogens are said to be homotopic. (e.g. The protons on a methyl group are

homotopic)

XC

XH H

XC

XY H

XC

XH Y

Identical

Enantiotopic: If you have a methylene group of the form X- CH2-Z, and you

replace one of the hydrogens of the CH2 with a dummy atom and then you

independently replace the other hydrogen of the CH2 group with a dummy

atom (Y), the two molecules thus created will be enantiomers of each other.

The protons are said to be enantiotopic. In a nonchiral environment

enantiotopic protons are equivalent. However, in a chiral environment such as

a chiral solvent, they can, in principle, have different chemical shifts.

ZC

XH H

ZC

XY H

ZC

XH Y

Enantiomers

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Diastereotopic: If you have a methylene group for example, in a chiral

molecule X- CH2-Z* (where the * indicates that Z is a chiral group), and you

replace one of the hydrogens of the CH2 with a dummy atom (Y) and then you

independently replace the other hydrogen of the CH2 group with a dummy

atom the two molecules thus created will be diastereomers to each other. Thus,

in principle, the two hydrogens should have different chemical shifts.

Z*C

XH H

Z*C

XY H

Z*C

XH Y

Diastereomers

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On The Interaction of Enantiomers with Chiral Perturbations:

A chiral perturbation is any physical or chemical perturbation that has a

handedness.

• Let us assume that we have a pair of chiral acids that are enantiomers. If a

solution is made up of equal amounts of the R and S isomers, the mixture is

said to be racemic.

• If sodium hydroxide is added to the solution, then the acids will be

deprotonated and will result in a racemic solution of the carboxylate anions.

• We then crystallize them with a chiral cation as shown below:

COOHH3C

H3C

COOH3CH

H3C

NH3C

H

H3C

COOH3CH

H3C

NH3C

H

H3C

NH3C

H

H3C

COOHH3C

H3C

SR

S

S SSR

Enantiomers

Diastereomers

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• In such a case the two salts that are formed are diastereomers. (Remember:

they will have different physical properties including melting points and

solubility)

• As a result of these different physical properties, one salt may preferentially

crystallize from the solution leaving the other behind. If the crystallized salt

is isolated and then acidified, the chiral acid of just one of the enatiomers

will be regenerated. Such as process is call a chemical resolution of

enantiomers.

Note: There are many examples of interactions of chiral molecules with

chiral perturbations leading to diastereomeric interactions.

• Different molecules can be separated by chromatography. If the stationary

phase is chiral, then each enantiomer in a racemic solution will interact

differently with the stationary phase since the interactions will be

diastereomeric. As a result, each enantiomer may move through the chiral

material at a different speed. Thus, a chiral resolution can be effected.

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The Interaction of Chiral Molecules with Light

• Plane polarized light is light wherein the electric field oscillates in one plane.

• Plane polarized light can be thought of being made up of a superposition of

two chiral and opposite circularly polarized electric fields.

• If we now consider each hand of the circularly polarized light interacting

with one enantiomer of the chiral carboxylate that we considered above, we

see that the interaction of the light with the molecule is a diastereomeric

interaction.

• Accordingly, the index of refraction (speed of light in the solution relative to

that of light in a vacuum) for the left and right circularly polarized light will

be different. Thus, one hand of the circularly polarized light will get slowed

down more.

COOHH3C

H3C

COOHH3C

H3C

RR

diasteriomeric interaction with eachhand of circularly polarized light

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• As a result when the light passes through a cell containing a non-racemic

assembly of chiral molecules, the phase shift of one hand of the circularly

polarized light relative to the other will result in the plane of light being

rotated by angle α. Such a solution is optically active. 0

in

outα

• Since a racemic solution has equal amounts of chiral molecules that have

opposite configurations, for each molecule rotating the light in one direction,

there will be a molecule of opposite configuration rotating the light in the

opposite direction. Thus, the two rotations will cancel, and there will be no

net rotation of light. Such a solution is not optically active. = 0

Note: A solution of a meso compound is not chiral, and it is not racemic. A

racemic solution is made up of an equal mixture of chiral molecules. Since a

meso compound is not chiral, it is not optically active. = 0

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Amine Inversions

Tertiary amines substituted with three different groups in frozen configurations

are chiral. Thus, their mirror images are not superimposable.

H3C

N

H

CH2OHCH3

N

H

HOH2C

.

However there is a process called amine inversion wherein the substituents on

the nitrogen distort through a plane transition state such that there is an

inversion of configuration:

H3C

H

CH2OH

H3C

N

H

CH2OH

H3C

N

H

CH2OH

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Such a process creates the enantiomer of the original molecule:

H3C

N

H

CH2OH

H3C

N

H

CH2OHCH3

N

H

HOH2C

• This inversion process, which is an equilibrium, will take a single chiral

isomer into a racemic mixture. Any process that allows one chiral isomer to

interconvert with its enantiomer is termed racemization.

• Since amine inversion can be fast at room temperature, it is often impossible

to isolate one enantiomer of chiral amines. For example in ammonia the

barrier for inversion is 5.8 kcal/mol (the rate at ambient temperature is about

2 x 1011/ sec), and for methylamine the barrier for inversion is 4.8 kcal/mol.

If a chiral amine has the nitrogen tied down into a bicyclic ring system, then it

would be impossible for the nitrogen to invert without introducing an

unreasonable amount of strain into the molecule. In such cases, it should be

possible to isolate one enantiomer:

N

1

23

R

It is possible to assign configurations to chiral amines. Simply use the Cahn-

Ingold-Prelog convention and always assign the lone pair the lowest priority.

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Stereoselective and Stereospecific Reactions.

• Regioselective reaction: A reaction in which one structural isomer is

formed preferentially over another. (In some cases, this preference can be

extremely lopsided such that essentially only one isomeric product is

formed. In such cases, this is termed a regiospecific reaction.)

• Stereoselective reaction: Is a reaction in which one stereoisomer in a

mixture is created or consumed more quickly than other, such that one

stereoisomeric product is preferentially formed.

Note: a reaction can be moderately or very stereoselective.

• Stereospecific reaction: A reaction in which relative chemistry of starting

materials defines, due to the mechanism of the reaction relative

stereochemistry of the products is stereospecific

Note: all stereospecific reactions are stereoselective, but the reverse is not

necessarily so.

Consider the reaction of Br2 with Z, and E-2-butene:

H3C

CH3

Br2H3C

H

Br H

Br

CH3

H3C CH3 Br2H3C

Br

Br H

HCH3 H3C

H

HBr

BrCH3

meso

R,R S,S

Here the mechansim, i.e. anti addition of the bromine to the double in combination

with the stereochemistry of the starting materials (cis or trans) determines the

stereochemistry of the products.

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Enantiomeric and Diastereomeric Transition States

Achiral molecule reacts with an achiral reactant: If an achiral molecule or

intermediate interacts with an achiral reactant then the transition state will be

either be achiral or enantiomeric (if a chiral center is being formed).

H3C

CH2CH3

H

Br

H3C CH2CH3

H

Br

H3CCH2CH3

H

Br

Br

+

R S

Enantiomeric transition states have the same energy. Thus, the R and S isomer

will form at identical rates and a racemic mixture will always result.

Achiral

R S

SR

Chiral molecule reacts with a chiral reactant: If a chiral molecule or

intermediate interacts with a chiral reactant then the transition state will be

diastereomeric.

Ph

HCH3

B

H

BH

CH3

HPh

BHCH3

HPh

BH

Ph

HCH3

BH

Ph

HCH3

R

RR

S

R

CH3

HPH

S

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33

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34

Enantiomeric and Diastereomeric Transition States (continued)

Therefore, each transition state will be a different energy and the diasteriomeric

products will be formed at different rates, and they will have different energies.

S RR

S RR

R RR

R RR

S and R

Achiral molecule reacts with a chiral resolved reagent: If an achiral

molecule interacts with a chiral resolved reagent (such as an enzyme) in such a

manner that in the transition state one or more chiral centers is being formed,

then the transition states for the R or S center will be diastereomeric. Therefore,

the R and S product will form at different rates.

OOC HH COO

OH

CH2COOOOC

H

S

fumarase

H2O

AchiralS

OOC HH COO

S

fumarase

Achiral

HHO

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35

Enantiomeric and Diastereomeric Transition States (continued)

S RR

S RR

R RR

R RR

S and R

In the case of an enzyme this stereoselectivity (i.e. the preferential formation of

one stereoisomer over another) can be very high such that in biological systems

often only one isomer is formed.

This means that the two diastereomeric transition states are most likely different

in energy by 3 kcal/mol or more.

Tremendous effort has been devoted toward developing reagents and catalysts

for use in organic synthesis that work in much then same manner such that a

chemist can select the chiral configuration of a given center. (A Nobel Prize

was awarded for this last year).

Page 36: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

36

Inversion of Configuration

In a nucleophilic substitution reaction that is concerted (i.e. bonds are being

made and broken at the same time), the nucleophile (Nu) attacks the molecule

from the side opposite from the group that will leave (called the leaving group,

LG) (left).

LG

C

BA

C

BA

Nu

C

BA

Nu LGNu LG

• As this happens the other groups distort to accommodate the incoming

group and the molecule goes through a transition state that is basically

symmetrical (middle).

• Then as the bond forming step with the nucleophile is completed and the

leaving group departs, the geometry of the rest of the molecule continues to

relax in such a way to restore tetrahedral geometry about the central carbon

atom (right).

• This process involves a net inversion of configuration as illustrated in the

example below.

Cl

D

H3CH

D

CH3H

Cl

D

CH3H

Cl ClCl Cl

S R

δ δ

• Note that with this degenerate substitution of Cl- for Cl- the configuration is

inverted.

Page 37: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

37

BA

C D

A BD

C

D BC A

BA

C D

E

B

C D

ENu

AB

C D

B

Nu

A

E

C D

DB

C

A

E

D

B

C

A

E

NuA

Nu

Nu Nu

E-Nu E-Nu E-Nu

Stereochemistry of "Carbocation" - Addition to Alkenes

E

Nu

B

C D

E

NuA

Nu

D

BCA

E Nu

E

Nu

BA

DC

top or bottomaddition

A B

ECD

A

C E

D

BAC D

A

Nu

BE

C D

DB

C

A

E

D

B

C

E

Nu

B

Nu

Nu

Nu

E-Nu E-Nu E-Nu

E

Nu

A

C E

D

Nu B

Nu

D

BCA

E Nu

E Nu

A

BDC

top or bottomaddition

STARTHERE!!

Nu

A

Page 38: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

38

BA

C D

A BD

C

D BC A

Stereochemistry of Syn- Addition to Alkenes

D B

C A

X YXY

BAD

C

BA

CD

Y

X

BA

C D

Y

X

rotatate60°

Y

A B

X

D

C

D B

C

A

XY

X Y X Y X Y

D B

C A

X YXY

BA DC

XC

A

Y

D

B

XC

A Y

D

B

rotatate60°

Y

A

BX

DCD B

C

A

XY

X Y X Y X Y

STARTHERE!!

Page 39: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

39

BA

C D

A BD

C

D BC A

BA

C D

E

A B

C D

E

Nu

E

ABCD

B

Nu

AE

C D

D B

C A

E

D

B

C

A

E

Nu

BA

C D

E

B

C D

E

Nu

E

A BC D

B

Nu

AE

C D

D B

C A

E

D

B

C

A

E

NuA

E-Nu

Nu

inversion

Nu

E-Nu E-Nu

Nu

inversion inversion

Nu

inversion

Nu

Nu

inversion inversion

E-Nu E-Nu E-Nu

Stereochemistry of Anti- Addition to Alkenes

STARTHERE

Page 40: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

40

Addition to 1-Methyl Cyclohexane

E

E Nu

E

Nu

E

E

E

Nu

E

Nu

E

Nu

E E

D

D

D

D

E E

Nu

Nu

EE Nu

E Nu

E Nu

X2Hg(OAc)2HOXwhere X = Br Cl

E Nu

HX (DX)HX (DX), H2OHX (DX), ROHwhere X = Br Cl

X X

X

E

X Y

X

Y

Y, (Y')

Y, (Y')

Y

X Y

1. 2. step 2

H2BHOOs(O)2OOMn(O)2OH-H, catalyst

substitutionwith

INVERSION

syn addition

syn andantiaddition Nu

Page 41: Chapter 4 Stereochemistry and Chiralityww2.chemistry.gatech.edu/class/2311/marder/Stereochem.pdf · 1 Chapter 4 Stereochemistry and Chirality Flow chart for determining the relationship

41

E

E Nu

E

Nu

E

E

E

H

H

H

Nu

E

Nu

H

E

H

Nu

E

Nu

H

E

D

D

D

D

E ENu

Nu

EE Nu

E Nu

E Nu

X2Hg(OAc)2HOXwhere X = Br Cl

E Nu

HX (DX)HX (DX), H2OHX (DX), ROHwhere X = Br Cl

H

H

X

H

H

X

H

X

E

X Y

X

Y

Y, (Y')

Y, (Y')

Y

X Y

1. 2. step 2

H2BHOOs(O)2OOMn(O)2OH-H, catalyst

substitutionwith

INVERSION

syn addition

syn andantiaddition

H

H

H

H

H

H

H

H

H

H

H

H H

H

H

H

H

H

H

H

HNu

E

H

H

E

Nu

H

X

Y, (Y')H

X

Y

X

Y

H

X

Y, (Y')H

Addition to Cis Double Bonds

Homework draw out all the products for each of these additions for (E)-2-

pentene.