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Organic Chemistry: Enantiomers and Diastereoisomers, Study Guides, Projects, Research of Stereochemistry

Pennsylvania State University - Greater AlleghenyStereochemistry

An in-depth exploration of enantiomers and diastereoisomers in organic chemistry. It covers their physical and chemical properties, differences, and applications in separating and determining their absolute configuration. The document also introduces various techniques for resolving enantiomers, such as chiral derivatising agents, chiral chromatography, and chiral shift reagents.

Typology: Study Guides, Projects, Research

2021/2022

Uploaded on 09/12/2022

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123.702 Organic Chemistry
enantiomers
cis
epoxide
mp = 98°C
Two chiral centres (diastereoisomers)
• A molecule with 1 stereogenic centre exists as 2 stereoisomers or enantiomers
• Enantiomers have identical physical properties in an achiral environment
1
NH2
HN
N
O
OH
NH2NH
N
O
HO
SR
Mirror
Two enantiomers
differ by absolute configuration
O
CO2Me
O2N
O
CO2Me
O2N
enantiomers
trans
epoxide
mp = 141°C
O
CO2Me
O2N
O
CO2Me
O2N
diastereoisomers
different mp
• A molecule with 2 stereogenic centres can exist as 4 stereoisomers
• Enantiomers (mirror images) still have identical physical properties
• Diastereoisomers (non-mirror images) have different properties
pf3
pf4
pf5
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pf9
pfa
pfd

Partial preview of the text

Download Organic Chemistry: Enantiomers and Diastereoisomers and more Study Guides, Projects, Research Stereochemistry in PDF only on Docsity!

enantiomers

cis

epoxide

mp = 98°C

Two chiral centres (diastereoisomers)

A molecule with 1 stereogenic centre exists as 2 stereoisomers or enantiomers

Enantiomers have identical physical properties in an achiral environment

NH

2 HN

N

O

OH

NH

2 NH

N

O

HO

S

R

Mirror

Two enantiomers

differ by absolute configuration

O

CO

2

Me

O

2

N

O

CO

2

Me

O

2

N

enantiomers

trans

epoxide

mp = 141°C

O

CO

2

Me

O

2

N

O

CO

2

Me

O

2

N

diastereoisomers

different mp

• A molecule with 2 stereogenic centres can exist as 4 stereoisomers

• Enantiomers (mirror images) still have identical physical properties

• Diastereoisomers (non-mirror images) have different properties

Diastereoisomers

Enantiomers differ only by their absolute stereochemistry ( R or S etc )

Diastereoisomers differ by their relative stereochemistry

Relative stereochemistry - defines configuration with respect to any other

stereogeneic element within the molecule but does NOT differentiate enantiomers

In simple systems the two different relative stereochemistries are defined as below:

NH

2

NH

2

NH

2

NH

2

2 HCl 2 HCl

chiral

solubility 0.1g/100ml EtOH

NH

2

NH

2

2 HCl

meso

solubility 3.3g/100ml EtOH

diastereoisomers

different solubility

seperable

Me

OH

NH

2

Me

OH

NH

2

syn

same face

anti

different face

• A molecule can only have one enantiomer but any number of diastereoisomers

• The different physical properties of diastereoisomers allow us to purify them

• The differences between diastereoisomers will be the basis for everything we do...

Meso compounds

Tartaric acid has 2 stereogenic centres. But does it have 4 diastereoisomers?

HO

2

C

CO

2

H

OH

OH

tartaric acid

HO

2

C

CO

2

H

OH

OH

HO

2

C

CO

2

H

OH

OH

HO

2

C

CO

2

H

OH

OH

HO

2

C

CO

2

H

OH

OH

diastereoisomers

enantiomers identical

HO

2

C

CO

2

H

OH

OH

O H

2 C

OC

2 H

H O

H O

H

O

2

C

C

O

2

H

O

H

O

H

H

O

2 C

C

O

2

H

O

H

O

H

• 2 diastereoisomers with different relative stereochemistry

• 2 mirror images with different relative stereochemistry

• 1 is an enantiomer

• The other is identical / same compound

• Simple rotation shows that the two mirror images are superimposable

HO

2

C

OH

CO

2

H

HO OH

CO

2

H

HO

HO

2

C

plane of

symmetry

Meso compounds II

Meso compounds - an achiral member of a set of diastereoisomers that also

includes at least one chiral member

Simplistically - a molecule that contains at least one stereogenic centre but has a

plane of symmetry and is thus achiral

Meso compounds have a plane of symmetry with ( R ) configuration on one side and

( S ) on the other

rotate LHS

HO

2

C

CO

2

HO H

OH

• Another example...

Cl

H

Cl

H

achiral

plane of symmetry

superimposable on

mirror image

(meso)

Cl

H

H

Cl

chiral

no plane of symmetry

non-superimposable

on mirror image

(but it is symmetric!)

Chiral derivatising agents: Mosher’s acid

Popular derivatising agent for alcohols and amines is α-methoxy-α-

trifluoromethylphenylacetic acid (MTPA) or Mosher’s acid

Difference in nmr signals between diastereoisomers (above):

H nmr Δδ = 0.08 (Me)

F nmr Δδ = 0. 17 (CF

Typical difference in chemical shifts in

H nmr 0.15 ppm

F nmr gives one signal for each diastereoisomer

No α-hydrogen so configurationally stable

Diastereoisomers can frequently be separated

In many cases use of both enantiomers of MTPA can be used to determine the

absolute configuration of a stereocentre (73JACS512, 73JOC2143 & 91JACS4092)

OH

CO

2

H

F

3

C OMe

R / S S

DCC, DMAP

CH

2

Cl 2

, – 10 °C

F

3

C OMe

O

O

Me

H

R– S & S– S

DCC - dicyclohexylcarbodiimide

N

C

N

Chiral derivatising agents: salts

No need to covalently attach chiral derivatising group can use diastereoisomeric

ionic salts

Benefit - normally easier to recover and reuse reagent

Use of non-covalent interactions allows other methods of resolving enantiomers...

O

OH

NH

R / S

HO

2

C

CO

2

H

OTol

OTol

O

OH

NH

2

O

2

C

CO

2

H

OTol

OTol

S diastereoisomer is insoluble so easily removed by filtration

NaOH

O

OH

NH

(–)-propranolol

β - blocker

Chiral chromatography

Measurements of ee by HPLC or GC are quick and accurate (±0.05%)

Chiral stationary phase may only work for limited types of compounds

Columns are expensive (>£1000)

Need both enantiomers to set-up an accurate method

Si

N

H

O

NO 2

NO 2

Si

Si O

Si O

O

O

O

Si O

Si O

O

O

O

O

O

Me

Me

silica chiral amine

chiral stationary phase

R S

R / S

R

S

S

R

inject mixture

on to column

chiral column

prepared from a

suitable chiral

stationary phase

(many different types)

R

NMR spectroscopy: chiral shift reagents

Chiral paramagnetic lanthanide complexes can bind reversibly to certain chiral

molecules via the metal centre

Process faster than nmr timescale and normally observe a downfield shift (higher

ppm)

Two diastereomeric complexes are formed on coordination; these may have different

nmr signals

Problems - as complexes are paramagnetic, line broadening is observed (especially

on high field machines)

Compound must contain Lewis basic lone pair (OH, NH

, C=O, CO

H etc )

Accuracy is only ±2%

O

EuL 2

O

C

3

F

7

substrate

Eu(hfc) 3

Eu(hfc) 3

- ••substrate

Enzymatic resolution

Enzymes are very useful for the resolution of certain compounds

Frequently they display very high selectivity

There can be limitations due to solubility, normally only one enantiomer exists and

can be too substrate specific

Below is the rationale for the selectivity observed above...

Bu

OEt

O

F

lipase PS from Pseudomonas

cepacia, 0. 05 M phosphate buffer,

pH 7 , 0. 1 M NaOH, 5 °C

60 % conversion

Bu

OEt

O

F

Bu

O

O

F

Na

R / S R

> 99 % ee

soluble in

organic phase

S

69 % ee

soluble in

aqueous phase

N N

H

O

N

H

O

H

O

R

O

Et

his

ser

O

Bu

H F

O

enzyme

diastereomeric interaction of enzyme

lone pair with σ * orbital of C–F of ( S)-

enantiomer favoured over interaction

with ( R)-enantiomer