208
NUCLEOPHILIC REACTIONS: NUCLEOPHILIC SUBSTITUTION
The nucleophile approaches from the side opposite the electronegative leaving group – electrostatic
repulsion discourages attack in the region of the leaving group. With the substrate in the favoured staggered conformation, we describe this arrangement of
atoms as anti-periplanar.
The requirement for the proton electrophile and
the leaving group involved in the elimination to be
anti to each other is demonstrated by the nature of
the product obtained from a suitable substrate, e.g.
(1R,2R)-1-bromo-1,2-diphenylpropane, when treated
with base. The only product formed is (Z)-1,2diphenylprop-1-ene. This is the product from an anti
elimination of H and Br when the substrate is in a
staggered conformer. If H and Br were positioned on
the same side of the conformer, then it would need to
be in an unfavourable eclipsed conformer to line up
the orbitals. Elimination of H and Br in this fashion
is termed a syn elimination, and would lead to the
E-product. However, this is not the product formed,
and, in general, syn eliminations are very rare.
Me
H
Ph
Ph
Br
H
Ph
Me
H
Ph
Br
H
H
Ph
Me
Ph
H
Ph
Ph
Me
base
H
Br
H
Me
Ph
Ph
≡
≡
H
Br
H
Ph
Ph
Me
staggered, H/Br anti
eclipsed, H/Br syn
Z isomer is
only product
E isomer is
not formed
− HBr
(1R,2R)-1-bromo1,2-diphenylpropane
(Z)-1,2-diphenylprop-1-ene
(E)-1,2-diphenylprop-1-ene
It is particularly evident that the anti stereochemical relationship is obligatory by observing elimination reactions in suitable cyclohexane derivatives.
The only way to achieve a planar arrangement of
the H–C–C–L atoms is when H and L are both
axial and, consequently, trans to each other (transdiaxial). Thus, consider menthyl chloride and neomenthyl chloride, which are stereoisomers differing
in configuration at just one centre.
Cl
Cl
neomenthyl chloride
menthyl chloride
NaOEt
EtOH
NaOEt
EtOH
+
2-menthene 3-menthene
2-menthene
fast
slow
Cl
H
H
H
H
Cl
H
Cl
H
H
EtO
Cl
H
H
EtO
EtO
two hydrogens are anti-periplanar with Cl;
there are two possible elimination products
no hydrogen
anti-periplanar to Cl
ring flip produces a
less-favoured conformer
one hydrogen now anti-periplanar to Cl;
elimination gives single product
(25%)
(75%)
NUCLEOPHILIC REACTIONS: NUCLEOPHILIC SUBSTITUTION
The nucleophile approaches from the side opposite the electronegative leaving group – electrostatic
repulsion discourages attack in the region of the leaving group. With the substrate in the favoured staggered conformation, we describe this arrangement of
atoms as anti-periplanar.
The requirement for the proton electrophile and
the leaving group involved in the elimination to be
anti to each other is demonstrated by the nature of
the product obtained from a suitable substrate, e.g.
(1R,2R)-1-bromo-1,2-diphenylpropane, when treated
with base. The only product formed is (Z)-1,2diphenylprop-1-ene. This is the product from an anti
elimination of H and Br when the substrate is in a
staggered conformer. If H and Br were positioned on
the same side of the conformer, then it would need to
be in an unfavourable eclipsed conformer to line up
the orbitals. Elimination of H and Br in this fashion
is termed a syn elimination, and would lead to the
E-product. However, this is not the product formed,
and, in general, syn eliminations are very rare.
Me
H
Ph
Ph
Br
H
Ph
Me
H
Ph
Br
H
H
Ph
Me
Ph
H
Ph
Ph
Me
base
H
Br
H
Me
Ph
Ph
≡
≡
H
Br
H
Ph
Ph
Me
staggered, H/Br anti
eclipsed, H/Br syn
Z isomer is
only product
E isomer is
not formed
− HBr
(1R,2R)-1-bromo1,2-diphenylpropane
(Z)-1,2-diphenylprop-1-ene
(E)-1,2-diphenylprop-1-ene
It is particularly evident that the anti stereochemical relationship is obligatory by observing elimination reactions in suitable cyclohexane derivatives.
The only way to achieve a planar arrangement of
the H–C–C–L atoms is when H and L are both
axial and, consequently, trans to each other (transdiaxial). Thus, consider menthyl chloride and neomenthyl chloride, which are stereoisomers differing
in configuration at just one centre.
Cl
Cl
neomenthyl chloride
menthyl chloride
NaOEt
EtOH
NaOEt
EtOH
+
2-menthene 3-menthene
2-menthene
fast
slow
Cl
H
H
H
H
Cl
H
Cl
H
H
EtO
Cl
H
H
EtO
EtO
two hydrogens are anti-periplanar with Cl;
there are two possible elimination products
no hydrogen
anti-periplanar to Cl
ring flip produces a
less-favoured conformer
one hydrogen now anti-periplanar to Cl;
elimination gives single product
(25%)
(75%)