Paper XIV (MSC II, Sem IV)

Stereochemistry
UNIT- II: Conformational analysis and reactivity
of cyclic compounds other than six membered

Dr. Siddhesh Jadhav

Willingdon College, Sangli.
Syllabus:

. g l i
D
UNIT- II: Conformational analysis and reactivity of cyclic compounds other than six membered (15 h)

S . an
S
(A) Fused rings (10 h)

a v e
Types of fused ring systems; (a) Fused bicycles: cis and trans-decalins, octalins, decalols,(b)

h g
Fused polybicycles: perhydroanthracene,

J ad l l e
o
(B) Bridged rings (5 h)

r C
Types of bridged ring systems, nomenclature, bridged bicycles: heptanes and octane, stereo

D on
chemical restrictions, Bredt’s rule.

gd
i l l i n
W
2
 Strains in Cycloalkanes

Transannular strain :

•Transannular strain is defined as the crowding of the two nonadjacent groups in a ring.
In organic chemistry, the transannular strain is the unfavorable interaction of ring
substituents on non-adjacent carbons. It is medium-sized ring (8-11) compounds, the
strain due to repulsive interactions between substituents attached to non-adjacent ring
atoms. These interactions, called transannular interactions, arise from a lack of space in the
interior of the ring, which forces substituents into conflict with one another..

10
10

3
 Fused Bicycles: Conformations of Decalin

Compounds with two rings fused together are known as bicycles. Bicyclic systems can be
either fused or bridged bycyclic.

Decalin
Bicyclo[4.4.0]decan
Decahydronaphthalene

8 1
7 9 2

6 3
10 4
5

4
 Conformations of Decalin

Decalin has two cyclohexane rings fused together which are most stable in their chair form. So it is expected that the two
fused cyclohexane rings in decalin should exist in their chair form.

strain-free puckered structure

No angle or torsional strain

5
 Conformations of Decalin

Decalin has two cyclohexane rings fused together which are most stable in their chair form. So it is expected that the two
fused cyclohexane rings in decalin should exist in their chair form.

6
Conformational Locking in Decalin

Note that while trans-decalin is not capable of ring flipping, cis-decalin can readily engage in
ring flipping operations.

. D . g l i
a v S an
d h g e S By virtue of bulky substituents or

a
ring fusion, some cyclohexanes are

r J
D n Co l l e “locked” and cannot engage in ring
flip:

g d o
il l in
W
7
 Ring flipping in trans-decalins

Trans- Decalin : Ring flipping is highly prohibited as it is not possible to have a six membered ring build with two of its
bonds in diagonally opposite directions.

. D . g l i
a v S an
S
conformationally locked

a d h g e
r J
D n Co l l e
g d o
il l in Trans decalin showing axes of symmetry

W
Ring flipping in trans decalin would
lead to breakage of C-C bond.
e,e-trans decalin has a centre of
symmetry and achiral

8
 Conformations of Cis-Decalin

The cis decalin is more like a tent shaped molecule with convex (less hindered) and concave (more hindered) sides.

. D . l i
Although in both the cases the cyclohexane rings are in their most stable chair conformations

g
a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
9
 Conformations of Cis-Decalin

Two cyclohexane rings are joined through an equatorial and an axial bond. The ring flipping is permissible in this case which

. D . l i
converts one cis form into another and converts the equatorial bonds to axial and vice versa (i.e. The e,a-cis decalin on ring

g
flipping will result in a,e- cis decalin

a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
Conformational analysis of cis decalin shows that it is a chiral molecule though it has no chiral carbon. It has a non-
superimposable mirror image. However, a rapid ring flipping cancels its chirality and converts it into its mirror image!
Thus the two chiral forms are not resolvable (due to the rapid ring inversion) and exist as racemic mixture

10
 Conformations of Stability of Decalins

Trans decalin is more stable than cis decalin by 10.5 kJ/mol.

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
Gauche interactions and non-bonding interactions in cis decalin

11
 Conformations of Stability of Mono substituted Decalins

Trans decalin is more stable than cis decalin by 10.5 kJ/mol.

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co Gauche interactions and non-bonding interactions in cis decalin

g d o
more stable

il l in
cis-9-methyldecalin, the methyl group occupies the convex face over the concave. However, it is less stable than trans-9-methyldecalin due to larger amount of

W
gausche interactions in the latter. Introduction of a substituent on the bridgehead carbon imparts destabilization equivalent to four butane gausche interactions in
trans decalin (two with each ring) as the substituent is axial to both the rings. On the other hand, in cis decaline, the substituent imparts destabilization equivalent
to two butane gausche interactions as it is axial to only one ring. Thus, in all, there are four butane gausche interactions in trans decalin and five in cis decalin
thereby reducing the energy gap between cis and trans decalins to only one butane gausche interaction.

12
 Conformations of Stability of Mono substituted Decalins

Classification of conformations of cis decalin as steroidal and non-steroidal

. D . g l i
cis isomer exists in a particular conformation

a v S an
in these natural products especially in
d h g e S
r
steroids. Thus the conformations of cis-
J a l l e
D n Co
decalin can be classified as steroidal and

d
non-steroidal since its occurrence in these

g o
natural products as in Figure.

il l in
W
13
 Conformations of Decalols

Introduction of a substituent other than on bridgehead carbons gives rise to a new chiral centre in the decalins
and thus increases the number of stereoisomers.
. D . g l i
a v S an
The substituent not only generates the chiral centre at the point of substitution but also makes the bridgehead

d h g e S
carbons chiral by disrupting the symmetry in decalin. Hence, decalols will have three chiral centres.

r J a l l e
D n Co
g d o
il l in
W
Theoretically, eight stereoisomers (four pairs of enantiomers) are expected for decalols having three chiral
centres. for decalols, 23 = 8. Actually all the eight forms have been isolated, however, their configurations
have not yet been established with certainty.

14
 Conformations of trans-Decalols

.
we know, the trans decalol is conformationally locked (it

S . D
cannot undergo ring flipping), it is not possible to interconvert

n g l i
a v
the axially substituted hydroxyl to equatorially substituted

h S a
hydroxyl.

J a d l e g e
r
D n Co l
Consequently, both would exist as diastereomers. Further, these
diastereomers would have non- superimposable mirror images.

g d o
Thus, trans-2-decalol exists as two pairs of enantiomers as

n
More

il l i
shown in figure. Conformational analysis predicts the Stable

W
equatorially substituted trans decalol to be more stable than the Eq. OH

axial isomer (due to 1,3-diaxial interactions in the latter).

15
 Conformations of cis-Decalols

. D . g l i
S
The cis-isomer, ring inversion would convert the axially substituted

a v S
hydroxyl to equatorially substituted hydroxyl after ring flipping. Each
an
d h
of the isomers shown would have their non-superimposable mirror

a g e
r J l l e
images to add on to the number of isomers. Conformational analysis of

D n Co
cis-2-decalols suggests the bottom equilibrium to be more stable than

o
the one shown on top due to the non-equivalence of the convex and
concave sides.

in g d
il l
The axial hydroxyl group on the concave side would experience 1,3-

W
diaxial interactions making it less stable. The equatorially substituted
hydroxyls in both the equilibriums have same energy as they do not
face any steric repulsions. Both the equatorially substituted decalols
are more stable than their axial counterparts and hence contribute
more towards the actual state of the molecule.

16
 Fused Polycycles :Conformations of Perhydroanthracene

Perhydroanthracene can be analysed stereochemically with only two point of distinction. In detailed five possible
stereoisomers for perhydroanthracene.

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
All the four chiral center are equivalent. Hence, the system is called AAAA type. So in that the number

W
of stereoisomers are less. Cis and trans define the stereochemistry of ring junction. i.e. it used to
describe nature of bond fusion of two rings.

17
 Fused Polycycles :Conformations of Perhydroanthracene

β protons

Ref.
Kalenchuk, A.N. et
al. Hydrogenation of
Anthracene and
Dehydrogenation of
Perhydroanthracene on
Pt/C Catalysts. Russ. J.
Phys. Chem. 92, 663–
668 (2018).
https://doi.org/10.1134/S0
036024418040106

18
 Fused Polycycles :Conformations of Perhydroanthracene
In detailed five possible stereoisomers for perhydroanthracene, Have been studied very well due to basic ring system is

.
simple and of wide occurrence in nature, the relative stabilities of the possible stereoisomers are of interest

S . D n g l i
h a v S a
J a d l e g e
(4aα,8aα,9aβ,10aα)
trans-syn-trans-meso
(4aα,�8aα,�9aα,�10aβ)
cis-trans�(ct)
r
D n Co l
(4aα, 8aβ, 9aα, 10aβ)
cis,anti,cis
Cis-syn-cis�(csc)�chair�meso
(4aα,8aα,9aα,10aα)
trans-anti-trans�(tat)�dl

g d o
il l in
∆H, kJ/ mol= 0 W 11 23.3 34 24.5

19
 Fused Polycycles :Conformations, Stability and energy of Perhydroanthracene

1) trans-cisoid-trans (trans-syn-trans; meso; tst)

. D . l i
2) trans-cisoid-cis (cis-transoid-trans, cis-trans, ct)

g
a v S an
dl(± )pair

d h g e S
r J a l l e
D n Co
g d o
il l in
Plane of symmetry: Yes W
Energy of conformation: 0 kJ/mole

Gauche butane interaction(s): 0

Energy of conformation: 11 kJ/mole
Gauche butane interaction(s): 3
Stability: Stable
10-13-5-6, 11-9-14-8, 13-10-14-8

20
 Fused Polycycles :Conformations, Stability and energy of Perhydroanthracene

3) cis-transoid-cis (cis-anti-cis; cac; meso) 4) cis-cisoid-cis (cis-syn-cis, csc; meso)

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
Energy of conformation: 23 kJ/mole
Gauche butane interaction(s): 6
10-12-4-3, 9-14-8-7, 1-11-9-14
Energy of conformation: 35 kJ/mole
1,3-synaxial interaction
10-12-11-1, 9-14-13-5, 5-13-10-12 Stability: Least Stable

21
 Fused Polycycles :Conformations, Stability and energy of Perhydroanthracene

5) trans-transoid-trans (trans-anti-trans; tat, dl pair)

. D . g l i
S
Energy of conformation: 24.5 kJ/mole

a v an
Central ring in a boat or twist boat

S
a d h g e
Stability order:
r J
D n Co l l e
g d o
1) trans-
cisoid-trans
il l
2) trans-cisoid-
i
cis (cis-transoidn 3) cis- 5) trans-
4)cis-cisoid-

W
transoid-cis transoid-trans
(trans-syn- -trans, cis-trans, (cis-anti-cis; (trans-anti- cis (cis-syn-
trans; meso; ct) dl(± )pair cac; meso) trans; tat, dl
tst) cis, csc; meso)
pair)

Exact reverse order for reactivity

22
 Fused Ring System: Conformations of Octahydronapthalenes (Octalins)

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
Octalin is Octahydronapthalene
∆1,9-Octaline has ring A in deformed half-chair
form and ring B in deformed chair form.

g d o
l in
ü Chiral center at C-10 so exist as a (±)pair.

W il
ü Interconvertible from VIa to VIb by ring inversion.
ü Newman projections (VIc and VId) are viewed along
C9 and C10.
ü The First conformer VIc is flat almost like trans-
decalin.

23 Reference Book: Stereochemistry of Organic Compounds by D. Nasipuri

 Conformations of Octahydronapthalenes (Octalins)

v ∆1-9-Octaline has double bond at the junction with two cyclohexene rings in half chair-conformation.

. D . g l i
v ∆1,2-Octaline and ∆2,3-Octaline have double bond away from the ring junction with ring A in flexible half-chair conformation
and ring B in chair conformation.

a v S an
d h g e S
r J a l l e
D n Co
g d o
∆1-9-Octaline
l
∆1,2-Octaline

il in ∆2,3-Octaline

W
Reference Book: Stereochemistry of Organic Compounds by D. Nasipuri
24
 Bridged Ring system

Fused Rings, Bridged Bicyclic Rings, And Spiro Rings:

. D . g l i
a v S an
S
In “bridged bicyclic”
molecules, the two

a d h g e
J e
bridgeheads are

r
D n Co
separated by “bridges”
containing at least one l l
o
carbon.

in g d In “spiro” fused

il l molecules, the two

W
rings are both
joined at the same
carbon.
In fused/condensed
bicyclic compounds,
two rings share two
adjacent atoms.
25
 Bridged Bicyclic Ring system

In “bridged bicyclic” molecules, the two bridgeheads are separated by “bridges”

D . i
containing at least one carbon. System in which two adjacent carbon atoms are not

. g l
S
common between ring is called bridged ring system.

a v S an
h
One important note about bridged bicyclic molecules is that,

a d g e
generally the two carbons forming each bridge will always be “cis” to each other,

J l e
r l
never trans, relative to the other ring.

D n Co
g d o
n
The picture shows a model of this

il l i molecule highlighting the angle strain

W and Van Der Waals strain resulting

from this arrangement.

26
 Bridged Bicyclic Ring system
It’s the same thing as the “top down” view, just drawn from a different perspective.

.
Using the “top down” view is a perfectly acceptable way to draw these molecules –

. D l i
however, it’s vital to be able to interpret these “perspective” drawings as many bicyclic
molecules will be shown in this way.
S n g
h a v S a
J a d l e g e
r
D n Co l
g d o
il l in
W
27
 Naming Bridged Bicyclic Molecules – A Five-Step Guide

28
 Naming Bridged Bicyclic Molecules – A Five-Step Guide

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
29
 Naming Bridged Bicyclic Molecules – Examples

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
30
 Examples

Bicyclo [ 1.1.1] pentane

. D . g l i
Bicyclo [ 2.2.1] heptane ( Norborane)

S
ü C-1 & C-4 are joined by methylene bridge to
ü Smallest bridge ring system

a v an
give boat conformation.

S
h
ü Bridged head C are very close due to very

e
ü System is strained because of two eclipsed

J a d
small endocyclic valency angle i.e..72.5 0

l e g butane units in boat.

r l
ü Unstable and converts to 1,4 pentadiene ü Out of the 6 H’s at C-2, C-3, C-5, C-6 HA, HA`

D n Co
on heating. - boat – equatorial orientation HB, HB`- boat –
axial orientation

g d o
il l in
W
31
 Examples

. D . g l i
a v S an
d h g e S
r J a l l e
D n Co
g d o
tricyclo[2.2.1.0²,⁶]heptane

il l in
W Tricyclo[2.2.1.0(2,6)]heptane

32
 Examples

Bicyclo [ 2.2.2] octane

. D . g l i
S
ü C-1 & C-4 are joined by ethylene bridge.

v an
ü In its idealized form the system has all the adjacent positions

a S
h
eclipsed.

J a d l e g e
r
D n Co l
g d o
il l in
W
tricyclo[2.2.1.0²,⁶]heptane

33
 Bredt’s rule
Double bonds cannot be placed at the bridgehead of a bridged ring system.

. D . g l i
A double bond cannot be placed at the bridgehead of

S
a bridged ring system unless the rings are large
enough

a v S an
Imagine drawing a version of

a d h g e
J
bicyclo[2.2.1]heptane (also called

r
D n Co
“norbornane”) with 1 double bond.
l l e
d o
3 different constitutional isomers are possible. But only one has ever been

g
in
observed.

il l
W
34
 Bredt’s rule

Back in 1924, German chemist Julius Bredt was working on bicyclic molecules with these

. D . g l i
(and related) ring systems, and made the following generalization:

a v S an
d h g e S
r J a l l e
D n Co
g d o
il l in
W
This observations are known as “Bredt’s rule”.

35
 Thank you
Can connect with me at
siddheshwar.jadhav@despune.org