Stereochirality R or S

8/8/2019 Stereochirality R or S

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SN2 Substitution, Nucleophilic, Bimolecular

Rate = k[CH3CH2OTs] [ Nu- ] ---------Bimolecular

Backside NucleophilicAttack InversioninConfiguration

ConcertedMechanism

Optically ActiveEnantiomericaly Pure

C Br

H3C

HC6H13

HO

CHO

CH3

H C6H13Br

CH3

HOC6H13

H

Transition StateR-(-)-2-BromooctaneS-(+)-2-Octanol

Inversion of Stereochemistry

C OTsH3C

H

HNu

CNu

CH3

H H

OTs

CH3Nu

HH

Transition State


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SN1 Substitution, Nucleophilic, Unimolecular( ) l 2 ( ) 2

+l-

Professor George OlahNobel Prize 1994

Carbocation is sp2-planar

CH3

CH3C

CH3

Cl

CH2

CH3H3C

+ Cl

Slow Step (RDS)

Aided by polar Solvent Stable 3o Carbocation

ions are stabilized via solvation

CH2

CH3H3C

Fast Step

HO

H

Front or Backside Attack

CH3

CH3C

CH3

O

tert-Butyl alcohol

H

H

CH3

CH3C

CH3

O H

- H+

C C

HC

H

H

> >

gr r l tr r l i g- l li t iti rg

mor t bl


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H3CH2CH2C

C BrH3CH2C

H3C CH2CH2CH3

CHO

CH2CH3CH3

H3CH2CH2C

C OH

H3CH2C

H3C

+

- HBr

S-3-Bromo-3-methylhexane

1:1 Mixture of R- and S-3-Methyl-3-hexanol

The Carbocation intermediate is

attacked by water from eitherside by the same rate


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STEREOCHEMISTRY


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Enantiomers are stereoisomers whose molecules arenonsuperimposable mirror images of one another

Objects that are superimposable on theirmirror images are said to be achiral

CH3

CH2

CHHO

CH3

CH2

CH

CH3 CH3OH Interchanging any two groups at a chiral

centre (stereocentre) that bears four

different groups converts one enantiomer

into another

I l t tr r l 3 at

CH3 C

OH

CH2 CH3

2-Butanol

H

ChiralCentre


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Nobel Prize2001

For synthesis of optically active compounds asymmetric synthesis

Professor William KnowlesProfessor oji Noyori

Professor K. arry ar less

C r

H3C

H

C6H13HO

CHO

CH3

H C6H13

r

CH3HO

C6H13

H

Transition tateR-(-)-2- romooctaneS-(+)-2-Octanol

InversionofStereoc emistry

SN

2


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One structure can be superimposed on another

If any of the groups

attached to thetetrahedral atom arethe same, the centreis achiral.

The ultimate way to test for

molecular chirality is to construct

models of the molecule and its

mirror image and then determine

whether they are superimposable

A molecule will not be chiral if it possess acentre or plane ofSymmetry

2-Propanol

CH3

C OHH

CH3

C

CH3

HHO

CH3

Screwdriver is achiralSocks are achiralGolf club is chiral

Gloves are chiral


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Properties of Enantiomers

Enantiomers have identical melting points and boiling pointsEnantiomers have identical solubilities in solvents

Enantiomers have identical spectra and refractive indexEnantiomers interact, and react with achiral molecules in thesame manner

Enantiomers interact andreact it ot er

c iral molecules at different rates

Enantiomers rotate lane- olarised lig t byequal amounts but in o osite directions

Plane-polarised lig t

Oscillationofelectrical fieldofordinary lig toccurs inall possibledirections

Polarimeter is a devise used to measure t e effect of lane-

olarised

lig t on

an

o tically active com ound

Chiral molecules areoptically active


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No Correlationbetweenthe directionofrotationofplanepolarisedlightandthe absolute configurationofa molecule

Clockwise Rotation(+) dextrorotatoryAnti-Clockwise Rotation(-) levorotatory

C

CH2CH3

H2CCH3

H

HOC

CH2CH3

H2CCH3

H

Cl

(R)-( )-2- et yl-1-butanol (R)-(-)-1-Chloro-2-methylbutanol

Same Configuration

Anequimolarmixture oftwo enantiomersiscalleda RacemicMixtureItisOptically Inactive


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H

O

S-(+)-Carvone

O

R-(-)-Carvone

H

rinciple component ofCaraway seed oil andresponsible for the

characteristic odour

rinciple componentof Spearmint oil andresponsible for the

characteristic odour

Receptor Sites in the Nose are hiral


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Enantiomers

Isomers that are non-superimposable

mirror-images

W

CXZ

Y

W

C XY

Z


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Locating a Stereocenter (Chiral

Carbon)

CH3 CH C

OH

OH

O

Lactic acid

*


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Locating a Stereocenter

CH3 CH2 CH2 CH2 CH2 C CH2 CH2 CH2 CH3

Br

H

*


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Locating a StereocenterO

CH3

H

*


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Locating a StereocenterH CH3

no stereocenter


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Locating a StereocenterCH3

Cl

no stereocenter


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Coniine: The Compound that

Killed Socrates

N

H

CH2CH2

CH3*


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Is there a stereocenter?

CH3

HO C CH

No e!


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Serine: one of the essential

amino acids

H2N CH C

CH2

OH

O

OH

*


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Carvone: mirror-image isomers

have different flavors and odors!O

CH3

C

CH3

CH2

*


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Muscone: the sex attractant of

the musk deer

CH3

O

*


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Cholesterol: how many

stereocenters can you find?

HO

CH3

CH3CH

CH3CH2

CH2 CH2

CHCH3

CH3

*

* *

*

*

*

*


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Crystals of Sodium Ammonium

Tartrate


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Optical Isomerism Difference in the way that isomers interact

with polarized light

Differences arise from molecular symmetry

properties

this is another type ofstereoisomerism.


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Ordinary Light

(showing magnetic and electric field vectors)


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Double Refraction


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The Picket Fence Analogy


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Optical Activity


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The Polarimeter


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Specific Rotation

[EA!tP

E

c l


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Configuration

Arrangement in space of atoms or groups

around the chiral part of the molecule


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Specification of Configuration

CC

112

2

33

44

R S


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Specification of Configuration SEQUENCE RULE 1: If the four atoms

attached to the chiral carbon are all

different, priority depends on atomicnumber, with the atom of higher atomic

number receiving the higher priority.

COROLLARY: If two atoms are isotopesof the same element, the heavier isotope is

assigned the higher priority


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I

CBrCl

F

I

CClBr

F

R S


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Specification of Configuration SEQUENCE RULE 2: If the relative

priority of two groups cannot be decided by

Rule 1, it shall be determined by a similarcomparison of the next atoms in the groups

(and so on, if necessary), working outward

in ranks from the chiral carbon. hydrogen atoms are ignored when the atoms

within a rank are compared to each other.


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Specification of Configuration

SEQUENCE RULE 3: A doubly-bondedatom A is treated as if there were two C-A

single bonds.

Priorities in the expanded representations

are assigned on the basis of Rule 2.

A

CC

A (C)

(A)


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REMEMBER!!!The atoms shown in parentheses (the

duplicate representations) do not exist!

They are written only for purposes of

assigning priorities.


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More...A triply-bonded atom A is treated as if there

were three C-A bonds, as in:

C A C A

(A)

(A)

(C)

(C)


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Corollary of Rule 3 If no other distinction can be made, a real

atom outranks a fictional atom.

NOTE CAREFULLY: This exception is

used only as a last resort!


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3-Chloro-2-butanol

C

C

CH3

CH3

OHH

ClH

C

C

CH3

CH3

HOH

HCl

C

C

CH3

CH3

HOH

ClH

C

C

CH3

CH3

OHH

HCl

enantiomers enantiomers

diastereomers


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Diastereomers Non-mirror-image stereoisomers

Differ in configuration about some, but not

all, chiral atoms

have different physical properties

can be separated by ordinary physical methods

differ in (R)/(S) sequence


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How Many Stereoisomers Are

Possible?

number of stereoisomers = 2

n

,

where n = number of chiral atoms


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2,3-Dichlorobutane

C

C

CH3

CH3

ClH

ClH

C

C

CH3

CH3

HCl

HCl

C

C

CH3

CH3

HCl

ClH

C

C

CH3

CH3

ClH

HCl

enantiomers

meso


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n = 1

n = 2 or more

Is there a

stereocenter?ACHIRAL

NO

STEREOISOMERS

YES

ENANTIOMERS

mirror-image

DIASTEREOMERS

OPTICALLY

ACTIVE meso

always plane of

symmetry

no plane of

symmetry

non-mirror-image

OPTICALLY

INACTIVE


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Glyceraldehyde

(an aldotriose)

C

C

CH2

H OH

OH

OH

C

C

CH2

OH H

OH

OH

(+) (-)


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The Aldotetroses

C

CH2OH

OHH

OHH

OHC

CH2OH

HOH

HOH

OH

C

CH2

OH

HOH

OHH

OH

C

CH2

OH

OHH

HOH

OH

(-) (+)

(-) (+)

Erythrose

Threose


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The AldopentosesCHO

CH2OH

OHH

OHH

OHH

CHO

CH2

OH

HOH

HOH

HOH

CHO

CH2

OH

HOH

OHH

OHH

CHO

CH2

OH

OHH

HOH

HOH

CHO

CH2

OH

OHH

HOH

OHH

CHO

CH2

OH

HOH

OHH

HOH

CHO

CH2OH

HOH

HOH

OHH

CHO

CH2

OH

OHH

OHH

HOH

Rib s Ar bi s

X l s L x s

(-) (+) (-) (+)

(+) (-) (-) (+)


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The AldohexosesCHO

CH2OH

OHH

OHH

OHH

OHH

CHO

CH2OH

HOH

OHH

OHH

OHH

CHO

CH2OH

OHH

HOH

OHH

OHH

CHO

CH2OH

HOH

HOH

OHH

OHH

CHO

CH2OH

OHH

OHH

HOH

OHH

CHO

CH2OH

HOH

OHH

HOH

OHH

CHO

CH2OH

OHH

HOH

HOH

OHH

CHO

CH2OH

HOH

HOH

HOH

OHH

(+)- All s (+)- Altr s (+)-Gluc s (+)-Mannos

(-)-Gulos (-)-Idos (+)-Galactos (+)-Talos


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The Aldohexoses (the other half)

(-)-Allose (-)-Altrose (-)- l cose (-)- annose

(+)- ulose (+)-Idose (-)- alactose (-)-Talose

CHO

CH2

OH

OH H

OH H

OH H

OH H

CHO

CH2OH

H OH

OH H

OH H

OH H

CHO

CH2

OH

OH H

H OH

OH H

OH H

CHO

CH2

OH

OH H

H OH

H OH

OH H

CHO

CH2

OH

H OH

OH H

H OH

OH H

CHO

CH2OH

OH H

OH H

H OH

OH H

CHO

CH2OH

H OH

H OH

H OH

OH H

CHO

CH2OH

H OH

H OH

OH H

OH H


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Stereochirality R or S