TOPICITY

Top face

X
Relation
A C B between
X&Y
Y
Bottom face
By
Dr. G. Krishnaswamy
Faculty
DOS & R in Organic Chemistry
Tumkur University
Tumakuru
10/6/2019 1
 (TOPOs in Greek means place)

Earlier part of stereochemistry was concentrated on the stereo

center.
Stereo center

X
*
A C B
Y
Now we start to see the relationship between the ligands
attached to stereo center if the attached ligands are
homomorphic in nature.
X
Relation
A C B between
X&Y
10/6/2019 Y 2
 Homomorphic Groups / Ligands / Atoms
The Groups / ligands / atoms which are in isolation look the
same or super imposable mirror images of each other are
called homomorphic groups / ligands / atoms.
Homo in greek means same
Morph in greek means form

CH3
H C H Homomorphic
groups
CH3
Homomorphic atoms
10/6/2019 3
In case of atoms, they must be of same element example two
H’s or two Br atoms.
If we isolate the two H’s, then they are same and super
imposable to each other hence they are called homomorphic
hydrogen's.
Isolated CH3 Isolated

H C H
CH3

H H
Identical and super imposable
10/6/2019 4
In case of groups, they must have same constitution and
configuration. Example two methyl or two Ph groups of same
chirality R or S.
They are called homomorphic groups / ligands / atoms.

TOPICITY can be defined as geometrical or

sterochemical relationship between homorphic groups / ligands
/ atoms and structure of the molecule.

Different types of relationships are possible for homorphic

ligands / groups / atoms.

1. Homo topic (Homo-same; topo-place)

2. Hetero topic (Hetero-different; topo-place)

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Ligands can not by itself be called homotopic or heterotopic, in
order to use this terminologies a comparison with other
homomorphic ligand or ligands present either in the same
molecule (internal comparison) or in a different molecule
(external comparison) is necessary.

Two criteria are used to decide whether the ligands / groups are
equivalent or not

1. Substitution-addition criteria

2. Symmetry criteria

Are employed to determine the topic relationship of

homomorphic ligands

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1. (a) Homo topic ligands

Two or more ligands that are identical when viewed in isolation

but individual replacement of two identical ligands by another
give rise to identical molecule, then they are called homotopic
ligands.

1. Substitution-addition criteria

Two homomorphic ligands are homotopic if substitution

(replacement) of first one and other by different test ligand
leads to homomers or identical product.

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 Br
Ha D
D H
Br Br
Identical
Ha Hb product

Br Br
H D
Hb D
HOMOTOPIC Br
Hence, Ha & Hb are
homotopic atoms
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 H X
Ha X
C C C
H Ha H H
Identical
C C C product

H Hb H H
Hence, Ha & Hb are
C C C
Hb X
homotopic atoms
H X

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 COOH
Ha F
F H
H
COOH COOH
Identical
Ha Hb H F products
Hb F
Hc H
Hence, Ha, Hb & Hc are COOH
homotopic atoms
H H
Hc F
F
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 COOH
Ha D D OH
HO H
COOH COOH
Ha OH Turn the Identical
molecule 180o in products
HO Hb plane

COOH COOH
Hence, Ha & Hb are H OH
homotopic atoms Hb D HO D
COOH
10/6/2019 11
1. (b) Homo topic faces
Two faces of a pi system or a double bond are homotopic
if addition to either face gives same or identical product.

Top face

Front face

Back face
OR

Bottom face
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 Top face

Front face

Back face
O
O OR

Bottom face

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 H
NaBH4 H3C
H

H3C OH
H3C
Identical
O products

H3C OH
H3C
H NaBH4
H3C H

Two products are homomers. Hence,

acetone has homotopic face
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 Br H
Br2
H
Br2
H
H Br
H H
Identical
products

H H Br
H H
Br2
Br2 H
H Br
Hence, ethylene has homotopic face
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2. Symmetry criteria
2. (a) Homo topic ligands
Two homomorphic ligands are homotopic if they can
interchange position by rotation around Cn axis.
C2

H3 C CH3 H3 C CH3
180o
rotation
Ha Hb Hb Ha

10/6/2019
They are identical and hence homotopic ligands 16
 C2

H 3C CH3 H 3C CH3

C C

180o
C C
rotation
C C
Ha Hb Hb Ha

They are identical and hence homotopic ligands

10/6/2019 17
2. (b) Homo topic faces
Two faces of pi system are homotopic if they can
interchange face result in same structure by rotation
around C2 axis.

C2

H3C CH3 H3C CH3

180o
C C C C
rotation
H H H H

10/6/2019
They are identical and hence it has homotopic face 18
 C2

O O

H H H H
180o
rotation
H H H H

They are identical and hence it has homotopic face

10/6/2019 19
 NMR Spectroscopy of Homotopic Hydrogen
If the hydrogen atoms in the molecule are homotopic, then
they are chemically equivalent. Hence they will resonate at
same chemical shift values.
O
H H
H
C H C
Cl C C
H
Cl H
H H

10/6/2019 20
 SUMMARY
Between homotopic groups and faces no differentiation is
possible either by enzyme or by NMR or by human being
because they are homomers or identical.

Substitution-
Symmetry
Topicity addition Reactivity
criteria
criteria
Homotopic No
Homomers /
groups and Cn or C2 differentiation
Identical
faces possible

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2. Hetero topic ligands
Two or more ligands that are identical when viewed in
isolation but individual replacement of two identical ligands
by another ligand give rise to two structurally different
(isomeric) molecule, then they are called heterotopic
ligands.

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 Heterotopic ligands

Same connectivity
NO YES

Constitutionally heterotopic Stereo chemically heterotopic

Enantiomers Diastereomers

Enantiotopic Diastereotopic
10/6/2019 23
 Constitutionally Hetero topic ligands
Two or more ligands in a molecule that are identical on
individual replacement by another ligand give rise to two
molecule that constitutional isomers of each other, then the
original two ligands are said to be constitutionally
heterotopic ligands.

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 H COOH

C C

H3C CH3

CH3 X CH3 X

H COOH H COOH
1 1
C C C C
3 2 3 2
X CH3 H 3C X
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 NO2

H F H F

NO2 NO2

F H

10/6/2019 H F 26
 Stereo chemically heterotopic

Two or more ligands in a molecule that are identical on

individual replacement by another ligand give rise to two
molecule that are enantiomers / super imposable mirror
images of each other, then the original two ligands are said
to be enantiotopic ligands.

Two or more ligands in a molecule that are identical on

individual replacement by another ligand give rise to two
molecule that are diastereomers / non super imposable not
mirror images of each other, then the original two ligands
are said to be diastereotopic ligands.

10/6/2019 27
(a) Enantiotopic ligands
1. Substitution-addition criteria
Two homomorphic ligands are enantiotopic if substitution
(replacement) of first one and other by different test ligand
leads to enantiomers. 2
COOH


Br C H
Br 1 4
COOH Ha CH3 (S)
3 They are
enantiomers and
Ha C Hb 2 hence enantiotopic
COOH ligands
Hb
CH3
Br 
H C Br
4 1
CH3
(R)
10/6/2019 3 28
 Hb Cl

C C C

Ha H

Ha Cl Hb Cl

4 1 4 1
H Cl H Cl

C C C C C C

Cl H Cl H
3 2 3 2
(S) (R)
They are enantiomers and hence enantiotopic ligands
10/6/2019 29
 Hb Ha
OH

Ha D Hb D

H D
D H
OH
OH

O
O
(R) (S)
They are enantiomers and hence Ha & Hb are enantiotopic ligands
10/6/2019 30
 Hb
Ha
CH3
H3C

H H

Ha D Hb D

H D
D H
CH3 CH3
H 3C H3C
H H H H
(S) (R)
They are enantiomers and hence Ha & Hb are enantiotopic ligands
10/6/2019 31
(b) Enantiotopic faces
Two faces of a pi system or a double bond are enantiotopic if
addition to either face gives enantiomeric product.
Top face

O
Ph Addition reaction
Bottom face
from either face leads
to formation of
EtMgBr
enantiomers and
EtMgBr
hence two faces are
enantiotopic
Et OH
H H

 
Ph OH Ph Et

10/6/2019 (R) (S) 32

 CN
H

Top face 
HCN Ph OH
H (S)
O
OH
Ph H
HCN
Bottom face

Ph CN
(R)
Addition reaction from either face leads to formation of
enantiomers and hence two faces are enantiotopic
10/6/2019 33
Molecules having stereo heterotopic ligands (enantiotopic)
exhibit prostereoisomerism or prochirality

Prostereoisomerism or Prochirality
Prochiral molecules are those which are achiral can be
converted into chiral molecule in a single step.

Prochirality may be the result of substitution reaction of Sp3

carbon substituent (usually hydrogen) with other substituent
results in chiral center.

OR

Prochirality may be the result of addition reaction of an Sp2

carbon to a chiral Sp3 carbon with nucleophile.
10/6/2019 34
Prochirality may be the result of substitution reaction of Sp3
carbon substituent. CH 3 PROCHIRAL
C
Hb PROCHIRAL
HYDROGENS
Ha

Ha Cl Hb Cl

CHIRAL 3 CHIRAL
3 CH CH3
3

2 C  2 C 1
4
H Cl
Cl H
1 4
4th group on wedge bond hence
clock wise "S" configuration

10/6/2019
(R) (S) 35
Prochirality may be the result of addition reaction of an Sp2
carbon. H3C PROCHIRAL

C O

H 3C CH2

NaBH4 NaBH4

CHIRAL 1
H4 OH CHIRAL
3
3 H 3C  H 3C
C C
H3C C OH H3C C H
H2 1 H2 4
2 2
(S) (R)
View the molecule through C-H bond for assigning the
10/6/2019 configuration 36
2. Symmetry criteria
(a) Enantiotopic ligands
Two homomorphic ligands are enantiotopic if they can
interchangeable through plane of symmetry or center of
inversion or Sn axis.

COOH

Ha OH
plane of symmetry

Hb OH

COOH

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 Ha Hb Hb
Hb Ha Ha

H3C OH HO CH3 H3C OH

Rotation Reflection

OH
Cl

Inversion center

Cl
10/6/2019
OH 38
(b) Enantiotopic faces
Two faces are enantiotopic if they can interchangeable
through plane of symmetry or center of inversion or Sn axis.

Top face Top face

H Ph
O O
Ph H
Bottom face Bottom face

Structure is not same upon rotation hence mirror plane

exists.

10/6/2019 39
 Top face

Ph
O Molecular mirror plane exists
H

Bottom face

10/6/2019 40
 NMR Spectroscopy of Enantiotopic Hydrogen
If the hydrogen atoms in the molecule are enantiotopic, then
they are chemically equivalent. Hence they will resonate at
same chemical shift values.

10/6/2019 41
 SUMMARY
Between enantiotopic groups and faces differentiation is
possible either by enzyme or by NMR in chiral reagent or
catalyst.

Substitution-
Symmetry
Topicity addition Reactivity
criteria
criteria

Enantiotopic
Differentiatio
groups and Enantiomers σh or Sn
n possible
faces

10/6/2019 42
(a) Diastereotopic ligands

Substitution-addition criteria

Two homomorphic ligands are diastereotopic if substitution

(replacement) of first one and other by different test ligand
not already attached to the molecule leads to diastereomers
/ non super imposable not mirror images.

10/6/2019 43
 H Cl

C C
Cl
Ha
H3C H
H Ha
-CH3 & -Cl
C C are
Trans
H3C Hb H H
Hb
Cl C C

H3C Cl
-CH3 & -Cl
are
Cis
Substitution of Ha & Hb by Cl leads to formation of trans
and cis products which are diastereomers and hence two
hydrogens
10/6/2019
are diastereotopic 44
 Br
Cl

H
Cl H
Br -Br & -Cl
are
Ha
Ha Cis

Hb Br
H
Cl H
Hb

H
Cl
-Br & -Cl
are
Trans
Substitution of Ha & Hb by Cl leads to formation of trans
and cis products which are diastereomers and hence two
hydrogens
10/6/2019
are diastereotopic 45
Geminal methylene protons adjacent to a stereocenter on
substitution test by other ligands not already present in the
molecule usually leads to diastereomers and are usually
diastereotopic.

O Stereo center


Hb Ha

Adjacent to a stereo
center hence they are
usually diastereotopic
10/6/2019 46
 O
Enantiomers
 RR SS

Diastereomers

Diastereomers
Hb Ha
Diastereomers

Hb
Ha RS
Enantiomers
SR

Cl Cl

O O Substitution of Ha
 & Hb by Cl leads to

 formation of

diastereomers and
Cl H H Cl
hence two
(R) (R) hydrogens are
diastereotopic
(S) (R)
10/6/2019 47
 (R)
CH3
 Substitution of Ha
H Cl
& Hb by D leads to
Hb Ha
formation of
Cl diastereomers and
hence two
hydrogens are
Hb diastereotopic
Ha

D D
(R) (R)
CH3 CH3
 
H Cl H Cl

D H H D

Cl Cl
(R)
10/6/2019 (S) 48
(b) Diastereotopic faces
Two faces of a carbonyl group adjacent to a stereo center on
addition reaction leads to diastereomers and possess
diastereotopic face.

CH3
Two faces of a
O carbonyl group
adjacent to a stereo
 center
H3C H
C6H5 Stereo center

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 CH3 Top face

O

H 3C H Bottom face

C 6 H5 Additon of HCN two

(R) face of carbonyl adjcent
to stereo center leads to
formation of
diastereomers and hence
HC C N
N H two faces are
diastereotopic.

(S) (R)
CH3 CH3
 
NC OH HO CN
 
H 3C H H3 C H
C 6 H5 C6H5
(R)
10/6/2019
(R) 50
 NMR Spectroscopy of Diastereotopic Hydrogen
If the hydrogen atoms in the molecule are diastereotopic,
then they are chemically and magnetically non equivalent.
Hence they will resonate at different chemical shift values.
Diastereotopic hydrogens
H
H Due to non equivalent nature of protons
H it splits into multiplet.

CH3
HO

10/6/2019 51
 SUMMARY
Between diastereotopic groups and faces differentiation is
possible either by enzyme or by reagent or by NMR.

Substitution-
Symmetry
Topicity addition Reactivity
criteria
criteria

Diastereotopic
Not Differentiation
groups and Diastereomers
applicable possible
faces

10/6/2019 52
 EXAMPLES
H D

Substitution of Ha &
trans Hb by D leads to
H Ha Br H formation of
diastereomers and
H H hence two hydrogens
are diastereotopic.

Br Hb

Br D Cis

10/6/2019 53
 D
H

Ha Substitution of Ha & Hb by D
Hb leads to formation of
homomers and hence two
H hydrogens are homotopic.
D

D H

MeO OMe Substitution of H & H by D

H leads to formation of
H
homomers and hence two
H D hydrogens are homotopic.
MeO OMe

MeO OMe
10/6/2019 54
 Cl Cl

R R
D H
Substitution of H & H by D
Cl Cl
leads to formation of
homomers and hence two
R R Cl Cl hydrogens are homotopic.
H H
R R
H D

C2

H H H H H & H are
interchangeable by C2
rotation and hence two
O O O O hydrogens are homotopic.
Ph CH3 Ph CH3
H3C Ph H3 C Ph
10/6/2019 55
 H
D
H Substitution of H & H by D
leads to formation of homomers
H
D and hence two hydrogens are
homotopic.
H

D
H Substitution of H & H by D
leads to formation of
H
H enantiomers and hence two
hydrogens are enantiotopic.
H
D

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 Cl
H

H H H

Cl Cl D H

H D
D H H D Exo Endo

Substitution of H & H by D Substitution of H & H by D

leads to formation of leads to formation of
enantiomers and hence two diastereomers and hence two
hydrogens are enantiotopic. hydrogens are diastereotopic.
10/6/2019 57
 D
H
Substitution of H & H by D
H leads to formation of
H diastereomers and hence two
H
hydrogens are diastereotopic.
D

10/6/2019 58