stereochemistry - organic chemistry notes at examville.com

8/9/2019 Stereochemistry - Organic Chemistry Notes at Examville.com

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Unit One Part 8:stereochemistry

the lecture everyone

(but me) hates...


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Alice's Adventure in Wonderland - Lew"Carrol

...How would you like to live in

Looking-glass House, Kitty? Iwonder if they'd give you milk inthere? Perhaps Looking-glassmilk isn't good to drink?


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Alice's Adventure in Wonderland - Lew"Carrol

...How would you like to live in

Looking-glass House, Kitty? Iwonder if they'd give you milk inthere? Perhaps Looking-glassmilk isn't good to drink?

its a good

question...and itturns out looking-

glass milk would not

be good for

Kitty...but why?


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stereoisomers

shape &chirality

8Unit One

Part


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bond pattern

different

happy with isomershaving the same

atoms...


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bond pattern

different

...and structural

isomers have these

atoms arranged

differently (different

bonding)...


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OH

cyclopentanolC5H10O

OH

(E)-pent-3-en-1-olC5H10O

O

4-methoxybut-1-eneC5H10O

O

3-methylbutan-2-oneC5H10O

HO H

(S)-pent-1-en-3-olC5H10O

structural isomers

all these have the

same formula but are

obviously (!) very

different


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s a m e

stereoisomers havethe same atoms andthe same bonds...so

same number of C

C, CH etc bonds


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s a m e

...they only differ by how these

bonds are arranged in space

(how they are orientated

relative to each other)


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B

A C

D

A

B C

D

stereoisomerismor configurational isomerism

alkenes are the easiest to

understand...these two have all the

same bonds but differ because D & Care on different sides of the molecule


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B

A C

D

A

B C

D


these are NOT different

conformations...to change between

the two stereoisomers we have tobreak a bond...


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B

A C

D

A

B C

D


breakdouble bond

A C

B D

remember: we cannot

rotate double bonds...so

we must break the bond, then...


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B

A C

D

A

B C

D


breakdouble bond

A C

B Drotate

single bond

A D

B C

...rotate central CC

bond...


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B

A C

D

A

B C

D


breakdouble bond

reformdouble bond

A C

B Drotate

single bond

A D

B C


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CO2Me

MeO2C

H

H

dimethyl fumaratetrans (E)

mp 103Cbp 193C

H

MeO2C

H

CO2Me

dimethyl maleatecis (Z)

mp 19Cbp 202C

diastereoisomers

diastereoisomers are different

compounds with different chemical

and physical properties


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cyclic molecules& diastereoisomers

relative stereochemistry

Cl

Cl

cyclic molecules can exist asdiastereoisomers dependingon the relative orientation of

substituents...


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change the relativestereochemistry to give new

diastereoisomers


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Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl

trans-1,2-dichlorocylohexane

(anti)

cis-1,2-dichlorocylohexane

(syn)


(syn)


(anti)


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Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl


(anti)


(syn)


(syn)


(anti)

here we have TWO diastereoisomers...either both the chlorines are on the same side

or they are on opposite sides


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Cl

Cl

Cl

Cl

Cl

Cl

Cl

Cl


(anti)


(syn)


(syn)


(anti)

two questions arise from this slide...which

conformation of each diastereoisomer is

preferred (easy)...and, why have I draw four

molecules (hard)?


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what will the favouredconformation be?

i


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cis

axial

alwaysone

substituent

H

1Cl

2Cl

H

1Cl

H

2Cl

H

Cl

Cl

i


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cis

axial

alwaysone

substituent

H

1Cl

2Cl

H

1Cl

H

2Cl

H

Cl

Cl

in this example...both

conformations of the cis

diastereoisomer are identical...both

have one axial & one equatorialsubstituent

t


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H

2Cl

H

1Cl

2

Cl

H

H

1Cl

transCl

Cl

for the transdiastereomerthe twoconformations are very different...one

has two axial substituents and the otherhas two equatorial substituents...which

is preferred?

t


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H

2Cl

H

1Cl

2

Cl

H

H

1Cl

trans

equatorialfavoured

Cl

Cl


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H

tBu

OH

H

tBu

H

H

HO

what happens if we have two

different substituents (two different

groups on the ring)?


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H

tBu

Me

H

equatorial

largest groupfavours

tBu

H

H

Me

true for all substitution patterns

(it doesnt matter where you put

the big group it will be equatorial


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decalinsH

H2stereoisomers

fused ring system found in

many natural products (such

as steroids) can exist as two

diastereoisomers...

t d li


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trans-decalinsH

H

H

H

trans-decalin equatorial, equatorialring fusion

they cannot undergo ring

flip so they are stuck in

these conformations

i d li


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H

H

H

H

cis-decalin equatorial, axialring fusion

cis-decalins


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the one you all hate...


33/88bond pattern

s a m e


34/88bond pattern

s a m e

a special kind of (pain)

stereosiomer...a pair ofenantiomers are identical in

always except...


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...an object that is

nonsuperposable onits mirror image...

hi lit i t


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chirality in nature

chirality

in nature hi lit i t


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chirality in nature

chirality

in nature

our hands are

mirror images...


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chirality

in nature


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chirality

in nature

they look identical

(barring scars etc)


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chirality

in nature

but can never

occupy the same

space...they are

chiral


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chirality

in naturephotograph: Willi Rolfes

snail shells are

either clockwise or

anti-clockwise...


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chirality

in naturephotograph: Willi Rolfes

...and clockwise snails

will only mate with

clockwise snails....

hi l


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chiral

objects

windmills and

propellers are left or

right handed as are...


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chiral

objects

corkscrews


45/88chiral molecules

molecules can be leftor right handed


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MirrorplaneAchiral

compounds

if we take a molecule

and its...


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MirrorplaneAchiral

compounds

...mirror image...and

we then start to...


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Mirrorplane

rotate

Achiralcompounds

...rotate that molecule

A hi l


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Mirrorplane

Achiral compounds

A hi l


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Mirrorplane

rotate

Achiral compounds

A hi l


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Mirrorplane

Achiral compounds

...we can get to a point

were the molecules are

identical and can be...

A hi l


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Mirrorplane

Achiral compounds

A hi l


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Mirrorplane

Achiral compounds

superposed upon each

other...then those

molecules are achiral

Chi l


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Chiral compoundsMirrorplane

rotate

...it doesnt matter how

many times and

directions you rotate a

chiral object...

Chi l


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Chiral compoundsMirrorplane

it can never be

superposed...


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the two isomers are calledenantiomers

such mirror images

are called...


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they are identical in all ways...

physical properties


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9 8 7 6 5 4 3 2

180 160 140 120 100 80 60 40

physical properties

(R)-(-)-mandelic acidmp 131-133C

Ph CO2H

H OH

(S)-(+)-mandelic acidmp 130-132C

Ph CO2H

HO H

NMR (see lecture 9) identical for

both enantiomers as is the melting

points and all standard chemical

reactions


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excepttwoproperties...

but they do differ

under certain

circumstances

(otherwise why would

we care...)

physical properties


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(R)-(-)-mandelic acid

[]23153D

Ph CO2H

H OH

(S)-(+)-mandelic acid

[]23 +153D

Ph CO2H

HO H

lightsource

polariser planepolarised light

sample

cell length l (dm)readinglight ()

physical properties

physical properties


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(R)-(-)-mandelic acid

[]23153D

Ph CO2H

H OH

(S)-(+)-mandelic acid

[]23 +153D

Ph CO2H

HO H

lightsource

polariser planepolarised light

sample

cell length l (dm)readinglight ()

physical properties

each enantiomer rotates plane

polarised light in a different

direction and more importantly...


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other chiral objects


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other chiral objects

...how they interact with other chiralobjects is very different (imagine trying to

put your left foot in your right shoe...its a

tad more difficult than putting the right

foot in the right shoe)


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65/88hi l

so chiral molecules will

interact with us in

different ways...

smell


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CH3

(S)-limonene

lemons

CH3

H

CH3

H

H3C(R)-limonene

oranges

smell

taste


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taste

Patrick J. Lynch 2006

(R)-carvone

spearmint

(S)-carvone

caraway

CH3 CH3

H

CH3

H

H3C

O O

taste


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taste

Patrick J. Lynch 2006

(R)-carvone

spearmint

(S)-carvone

caraway

CH3 CH3

H

CH3

H

H3C

O O

...but these differences are

trivial compared to...

chirality and drugs


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chirality and drugs

Me2N

Me

Ph O

Et

O

darvonpainkiller

NMe2

Me

PhO

Et

O

novradcough-suppressant

chirality and drugs


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chirality and drugs

Me2N

Me

Ph O

Et

O

darvonpainkiller

NMe2

Me

PhO

Et

O

novradcough-suppressant

both are commercially available and look

what those comical chemists have done

with the names!


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Me CO2H

NH2

D-alanine

bacterial cell wall

Me CO2H

NH2

L-alanine

mammalian amino acid

drugs that target bacterial

alanine wont hurt us (but

cause bacteria to burst!)

chirality and drugs


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N

H

O O

HN

O

O

(R)-thalidomide(morning sickness)

N

H

OO

HN

O

O

(S)-thalidomide(teratogenic)

chirality and drugs

but we have to be very careful otherwise

we can have horrific problems such as the

limbless children born because of the useof thalidomide

www.massey.ac.nz/~gjrowlan/teaching.html


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y gj g

more information about chirality

can be found on my web site (if

youre sad or sick of mind)


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why does nature onlyproduce one enantiomer?

not part of thecourse but a

wonderful

philosophical

question...


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Me CO2H

NH2

21 = 2stereoisomers

a molecule with one carbon

atom with four different

groups coming off it can exist

as 2 enantiomers


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H2NNH

CO2CH3

O

HO2Caspartame

22 = 4stereoisomers

a molecule with two carbon

atoms each with four different

groups coming off them can

exist as 4 stereoisomers

if it has three atoms


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23 = 8stereoisomers

HOCHO

OH OH

OH

t t t

(stereocentres) with 4 different

groups then it can have 8

stereoisomers...

insulin(monomer)


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251 = 2.25 x 1015stereoisomers

(monomer)has 51 stereocentres so it can exist

as a large number of stereoisomers

insulin(monomer)


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(monomer)

we have seen the problems

with just a 50:50 choice

(does it smell of lemons or

oranges?)

insulin(monomer)


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(monomer)so we must have a single form of

insulin so it always does the same

thing...but insulin aint particularlybig...

DNApolymerase


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>2342 = >8.96 x 10102stereoisomers

polymerase

342

this number is

meaningless to me!

DNApolymerase


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>2342 = >8.96 x 10102stereoisomers

polymerase

342

but it gets

worse...consider

our genes...

46


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46 46 chromosomescomprising of...

and each base pair istwo molecules with three

stereocentres so we


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O N

HO

OH N

NNH

NH2

O

>3 billionb i

stereocentres...so we

have a possibility of...

Benny Herudek 3D Hifi - High Fidelity 3d Graphics Solutions


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29,000,000,000 =stereoisomers

Benny Herudek 3D Hifi - High Fidelity 3d Graphics Solutions

if d j t


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29,000,000,000 =stereoisomers

if we produce just one

isomer then we dont

have this problem...

?


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?of course, why we have one enantiomer and

not its mirror image is another question

entirely...one which I will not comment on in

order to avoid offending the religious

amongst you...

what have


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the shapeof molecules

....welearnt?

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