-1-
ALICYCLIC CHEMISTRY NOTES
More complicated due to the many available conformations. Different conformations
may show different stereoselectivity. Need conformational bias to allow existing
stereocentres to allow the creation of new ones (i.e. asymmetric induction).
Conformation
Cyclopropane, cyclobutane, cyclopentane – almost planar (dependent on
substituents).
Cyclopropane has eclipsing CH2 units, and sp2 character at the carbons.
Cyclobutane puckers –
Non-planar geometry reduces torsional strain (Baeyer strain).
Equatorial Br’s are more stable.
Cyclopentane –
Envelope conformation favoured to minimise eclipsing
interactions (Pfitzer Strain).
Cyclohexane –
Three forms, of which chair is the most stable (eclipsing).
Twisted boat is flexible, so there is a large positive entropy gain. The energy profile
looks like this:
Decalins –
The trans decalin is fixed, with a “flat” C skeleton an ax,ax
bridge substituents:
The cis decalin is a flexible, curved molecule with
ax,eq bridge substituents.
Energetics
Angle (Baeyer) Strain – due to angles not being 109o, i.e. when 3/4 membered rings,
or when double bonds present. Both lead to decrease in angle. 8-10 membered rings
increase bond angle.
Torsional (Pitzer) Strain – can’t rotate, so functional groups interact. Hence, not
planar (less eclipsing).
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
This interaction is very significant in determining mechanisms and syntheses. For
example,
Also, for similar reasons, a tertiary butyl group or similar alkyl is always equatorially
placed, to avoid these bad interactions.
Increase in ring size increases negative entropy of Activation for the reaction. Thus,
forming C = 3/4 is irreversible and favoured thermodynamically, but the activation
energy is often too high due to Baeyer Strain. However, rings are typically 6
membered due to kinetic factors (and prevents larger ring formation).
Stereoselectivity
Baldwin’s Rules
Guidelines for predicting the relative facility of ring-forming reactions.
Ring closure reactions can be characterised in terms of three parameters:
5 - exo - trig
(a) (b) (c)
a) represents the number of atoms in the ring being formed.
b) indicates that the breaking bond ends up outside the final ring – exocyclic, cf.
endo:
c) denotes the geometry of the atom being attacked (*) – trigonal (sp2) in this case,
cf. tet and dig.
The following rules can then be applied to suggest the favoured or disfavoured
nature of ring closure, based on the stereoelectronic requirements of the transition
state:
Exo Endo
Ring Size
tet (sp3) trig (sp2) dig (sp) tet (sp3) trig (sp2) dig (sp)
3 3 3 2 2 3
4 3 3 2 2 3
5 3 3 3 2 2 3
6 3 3 3 2 3 3
7 3 3 3 3 3
So 5-endo-trig is disfavoured:
The system is flat and little overlap is possible between the nitrogen lone pair and the
LUMO (π∗) of the sp2 carbon being attacked.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
ALICYCLIC CHEMISTRY NOTES
More complicated due to the many available conformations. Different conformations
may show different stereoselectivity. Need conformational bias to allow existing
stereocentres to allow the creation of new ones (i.e. asymmetric induction).
Conformation
Cyclopropane, cyclobutane, cyclopentane – almost planar (dependent on
substituents).
Cyclopropane has eclipsing CH2 units, and sp2 character at the carbons.
Cyclobutane puckers –
Non-planar geometry reduces torsional strain (Baeyer strain).
Equatorial Br’s are more stable.
Cyclopentane –
Envelope conformation favoured to minimise eclipsing
interactions (Pfitzer Strain).
Cyclohexane –
Three forms, of which chair is the most stable (eclipsing).
Twisted boat is flexible, so there is a large positive entropy gain. The energy profile
looks like this:
Decalins –
The trans decalin is fixed, with a “flat” C skeleton an ax,ax
bridge substituents:
The cis decalin is a flexible, curved molecule with
ax,eq bridge substituents.
Energetics
Angle (Baeyer) Strain – due to angles not being 109o, i.e. when 3/4 membered rings,
or when double bonds present. Both lead to decrease in angle. 8-10 membered rings
increase bond angle.
Torsional (Pitzer) Strain – can’t rotate, so functional groups interact. Hence, not
planar (less eclipsing).
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
This interaction is very significant in determining mechanisms and syntheses. For
example,
Also, for similar reasons, a tertiary butyl group or similar alkyl is always equatorially
placed, to avoid these bad interactions.
Increase in ring size increases negative entropy of Activation for the reaction. Thus,
forming C = 3/4 is irreversible and favoured thermodynamically, but the activation
energy is often too high due to Baeyer Strain. However, rings are typically 6
membered due to kinetic factors (and prevents larger ring formation).
Stereoselectivity
Baldwin’s Rules
Guidelines for predicting the relative facility of ring-forming reactions.
Ring closure reactions can be characterised in terms of three parameters:
5 - exo - trig
(a) (b) (c)
a) represents the number of atoms in the ring being formed.
b) indicates that the breaking bond ends up outside the final ring – exocyclic, cf.
endo:
c) denotes the geometry of the atom being attacked (*) – trigonal (sp2) in this case,
cf. tet and dig.
The following rules can then be applied to suggest the favoured or disfavoured
nature of ring closure, based on the stereoelectronic requirements of the transition
state:
Exo Endo
Ring Size
tet (sp3) trig (sp2) dig (sp) tet (sp3) trig (sp2) dig (sp)
3 3 3 2 2 3
4 3 3 2 2 3
5 3 3 3 2 2 3
6 3 3 3 2 3 3
7 3 3 3 3 3
So 5-endo-trig is disfavoured:
The system is flat and little overlap is possible between the nitrogen lone pair and the
LUMO (π∗) of the sp2 carbon being attacked.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
