Stereochemistry (2)

8/4/2019 Stereochemistry (2)

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Stereochemistry I

Chemistry 355



Stereochemistry• Refers to the spatial arrangement of

atoms.• Stereochemistry is described in several

terms.

– Relative configuration• Relative to a standard compound

• Relative to another function in the molecule

– Absolute configuration• Refers to absolute arrangement in space for

enantiomers



Relative Stereochemistry• Cis

– Rings

– Alkenes

• Z (zussamen – together)

• Trans

– Rings

– Alkenes

• E (entgegen – opposite)

NH2

NH2

NH2

NH2

H R

HR

H H

RR



Relative Stereochemistry• Syn

– Same side – Erythro (sugars)

– Absolute assignments

preferred

• Anti

– Opposite side – Threo (sugars)

R

R NH2

NH2

R

R

NH2H

HH2N

≡

R

R

NH2H

HH2N

≡

R

R NH2

NH2

R

R

HH2N

HH2N

≡

R

R

HH2N

HH2N

≡



Absolute Stereochemistry atTetrahedral Atoms

• Chirality

– Non-superimposeable – Mirror images

– Requires 4 different

groups – May or may not be

stable (Amines)

– Called enantiomers

– Configuration R or S

– Build these models

(R)

OH

(S)

OH

mirror



Absolute Configuration• Cahn-Ingold-Prelog

– Prioritize substituents

• Highest atomic #• When two of same, go one

atom further

• Place lowest prioritysubstituent to rear

– Multiple bonds are treated astwo substituents

• C=O is treated as O-C-O

– Sense of direction

• Down priority list 1-3• R – rectus – Right (clockwise)

• S – sinistere – Left (CCW)

C C

C

OH

mirror

H

1

23

4H

R

C C

C

OH

H

1

23

4H

S



Diastereomers

• Diastereomers have multiple stereocenters

• Differ by one or more, but not all configurationalcenters

(R)

(R)

NH2

OH

(S)

(R)

NH2

OH

(S)

(S)

NH2

OH

(R)

(S)

NH2

OH

mirror

E

n a n t i o m e r s

E n a n t i om e r s

Diastereomers

Diastereomers



meso -Compounds• A meso -compound (syn. mesosteroisomer,

mesomer) is a diastereomer which is the same as

it’s mirror image and therefore not chiral (achiral).

(R)

(R)

NH2

NH2

(S)

(R)

NH2

NH2

(S)

(S)

NH2

NH2

(R)

(S)

NH2

NH2

mirror

E n a n t i o m e r s

Diastereomers

Diastereomers

S a m e m ol e c ul e



meso -Compounds• Most meso -Compounds have internal mirror planes*

• One half of the molecule is the reflection of the other.

• The stereocenters effectively oppose one another

• Chiral molecules contain no mirror planes

Mirror plane2 stereocentersmeso

achiral

Mirror planeNo stereocentersNot meso

achiral

NH2

NH2

mirror H

Cl

CH3

Cl

mirrorR

S

*Note: For true meso -compounds, these planes exist in representation only. In reality, they are often conformers thatinterconvert rapidly on a laboratory timescale. There are examples that do not and are chiral (atropisomers). The precisedefinition of a mesomer is an achiral member of a set of diastereomers that includes at least one chiral member.



Absolute Configuration• Use models

– Physical models

• Hand model (free and always withyou)

• Styrofoam balls and toothpicks(cheap)

• Model Kit ($10-$50 but worth

every penny) – available for usein class. May be checked out.

– Virtual model• Chem3D

• Hyperchem

• RasMol• Online versions available

• Freeware

• Best in conjunction with a physicalmodel

C C

C

OH

mirror

H

1

23

4H

R

C C

C

OH

H

1

23

4H

S



Optical Rotation• Chiral compounds have a property called helicity

• When light interacts with the molecule it is rotated

slightly with respect to the incident light.• This is observed by irradiating with light that has

been plane polarized using filters

SampleH

CH3

Cl



Polarimetry• 2 polarizing filters

• 1 rotatable

• Measure angle ofrotation on scale

• Sample rotation

α Tλ

• Specific rotationα

[α] Tλ

Tλ

c l

=

concentration in g/mLlength in decimeters



Specific Rotation• Defined temperature

• Defined wavelength

– Sodium D line

– 589 nm

– Often denoted as subscript D

• Rotation at 25oC at 589 nmwith a concentration of 2grams per 100 mL in ethanol

[α]25D

25.3 (c = 2, EtOH)

α

[α] Tλ

Tλ

c l=

c is concentration in g/mLdensity for neat liquids

(NOTE: reported as g/100mL)

l is cell length in decimeters



Wavelength Dependence

• Optical rotation is dependent on wavelength

• Depends on absorbance (ε)

• Light interacts with various features

• Greater ε leads to greater rotation



Stereochemical effects• Stereochemistry is involved many chemical reactions

– As a consequence (creation of a new stereocenter)

– As an influence (diastereoselection)

• It is intimately linked to the mechanism of reactions

• Stereocenters may be created, destroyed or altered

CH3

OH

CH3

HH HO

+

Reduction

CH3

OHH

OxidationCH3

O

CH3

O

SubstitutionCH3

HX



Substitution

CH3

H-OH

SN2 CH3

HBr OH

CH3

OH

CH3

HH HO

+

SN1

CH3

OH

H

Br

CH3

H+

-

-H+

H2O inversion

racemization



Elimination

CH3

Br

H3C

Ph

H

H

Ph

Ph

CH3

Ph

H

Ph

CH3

H

Ph

H3C

Ph

H

H

Ph

Br

Ph

CH3

Ph

H

tBuO-

E2H2SO4

E1

+



EliminationO

O

O

O

O

TsO

H

H

O

O

O

O

O

H

O

O

O

O

O

H



EliminationO

O

O

O

O

TsO

H

H

O

O

O

O

O

H

O

O

O

O

O

H



Reduction

Ph CH3

OH

Ph CH3

HH HO

+

BH3

CH3

O

CH3

OHH

BR2

CH3

H

B

H

R R

O

CH3

CH3

Ph



Nucleophilic attack

O

OH

CH3

O

OH

CH3

H-

CH3Li

O

CH3

OH

CH3Li



Oxidation

H

Ph

O

H

Ph

O

Ph

OH

Ph

OH

RCO3H

OsO4

Os

OO

Ph

OH

Ph

OH

+

H

Ph H

Ph

O

O

O

H

R

Ph

Ph

Ph

Ph

+

O O

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Stereochemistry (2)