1

Stereoselectivity in E1 (E or Z)
• Potential for two products, E or Z alkene
• E normally favoured as substituents far apart
OH
H + Ph
Ph
Ph
E-alkene Z-alkene
95 % 5%
• First cation formation
• Second bond rotation to align empty p orbital & C–H σ bond
HO H H
H H2O H
Me Me Me
Ph Ph
Ph
H H H H H H

• Conformation with Me H H2O H H2O

..& Ph on opposite faces H H
..is lower in energy Ph
Me
Ph
H
• Favoured H Me

• Conformation with Me
..& Ph on same face is H H
..higher in energy as they H
..are closer together Ph
Me
Ph
• Disfavoured H Me
2

Regioselectivity in E1
OH
HBr, H2O

major product minor product

• Two possible products depending on position of double bond

• Most stable alkene is formed
• Reason for stability is controversial...
• Overlap with π* creates stronger sp2-sp3 bond - more stable
H H H
H H
H CH3 H3C CH3
H H H
π* π* H H π*
H H H H H
σ σ
H H H σ
no C–H bonds H H H H
parallel with π* H H
H
most stable least stable
R R1 R R1 R H R H

R2
C C
R3
> H
C C
R3
> H
C C
R3
> H
C C
H
tetrasubstituted trisubstituted disubstituted monosubstituted
3

Stereochemistry in E2
• New π bond formed by overlap of C–H σ orbital and C–X σ* orbital
• Optimum overlap if orbitals are parallel
• Allows selectivity
• 2 possibilities...
Syn-periplanar
BASE

orbital
overlap σ∗
σ orbital
orbital

HX Base H X R R

R R R
R R R R R R
R
4

Stereochemistry in E2 II
BASE
Anti-periplanar

σ
orbital

σ∗
orbital orbital
overlap

H
Base H R R R
R R R
R
R R R X R R
X
• E2 occurs via anti-periplanar transition state when possible because...
• Orbitals are truly parallel
• Staggered conformation more stable
• Base and leaving group are on opposite faces, out of each others way
• Electron flow occurs via all-backside displacements like SN2
5

Stereoselectivity in E2
• Stereoselectivity - mechanistically there is a choice of two
products but one is favoured - there is a choice
• If two protons can be eliminated the reaction will proceed via the
anti-periplanar transition state that suffers least steric hindrance

H H H Me
Me NaOEt Me Me
or
Me Me H
Br H H H
major minor

H H
Me H
Me H Me H
Me Me
H Me
Me H H Me
H H
Br Br
minor two methyl two methyl anti- major
groups gauche periplanar
more hindered less hindered
6

Stereospecificity in E2
• Stereospecific - mechanistically only one outcome; different
stereoisomers of starting material give different stereoisomer of
alkene - there is no choice
• If only one proton can be eliminated then geometry of alkene
depends on stereochemistry of starting material
Me H Ph H Me Me
NaOH NaOH
Ph Ph
Ph Ph
FAST SLOW
Br H Me Ph Br H Ph Ph

rotation rotation
Br Br
Me Br Me Ph Ph Br Ph Me
Ph Me
Ph Ph H Ph Ph H
H H H H
HO H HO H
H & Br H & Br
anti-periplanar anti-periplanar

(1S,2R) gives E alkene (1S,2S) gives Z alkene

7

E2 Eliminations from cyclohexanes

H H H
HO
H
X
H
H
H H H H
X
C–X anti- C–X anti-
periplanar to C–C periplanar to C–H
E2 impossible E2 possible

• Necessity for anti-periplanar conformation has a huge effect in cyclohexanes

• For E2 we must have C–H & C–X both axial (trans-diaxial)
• Below shows the effect of this requirement...
Me Me Me
NaOEt
+

Cl
1:3
Me Me
NaOEt

250 times
SLOWER
Cl
8

E2 Eliminations from cyclohexanes II

disfavoured: i-Pr axial favoured: i-Pr equatorial
E2 not possible E2 possible
no anti-periplanar C–H 2 anti-periplanar C–H

Me CH3 HO H OH
ring
inversion H
≡ H H CH3
Cl
Cl H Cl

Me Me

Me CH3
H ring Cl
H inversion
≡ Cl CH3
H H

Cl H H OH
favoured: i-Pr equatorial disfavoured: i-Pr axial
E2 not possible but E2 possible
no anti-periplanar C–H Slow as rarely in this
conformation
9

Regiochemistry in E2
OH H3PO4 Cl
120˚C KOCEt3

E2
E1

• E1 gives thermodynamically more stable - more substituted alkene

• E2 can give both - more hindered the system, the more of the less
substituted alkene
Cl
Cl H

H
CH3
X H

H OR H OR
methyl hydrogen
ring hydrogens hindered easily accessible
by 1,3-diaxial interaction

Hindered base can change selectivity

base
Br
NaOEt 69% 31%

t-BuOK 28% 72%

10

Summary
Strongly basic, Stgrongly basic,
Poor nucleophile Weakly basic
unhindered hindered nucleophile
(e.g. H2O, ROH) nucleophile
nucleophile (e.g. (e.g. DBU, DBN,
acid conditions (e.g. I–, RS–)
RO–) t-BuO–)

H3C
X no reaction SN2 SN2 SN2
methyl

X
primary no reaction SN2 SN2 E2
(unhindered)

X
no reaction SN2 E2 E2
primary
(hindered)

SN1, E1 (slow)
SN2 E2 E2
X
secondary

E1 or SN1 SN1, E1 E2 E2
X
tertiary
11

Summary II
• Methyl halides will never eliminate (no protons in correct place)
• Increasing branching (more substituents) on substrate will favour
elimination
• Strongly basic hindered nucleophiles will always eliminate unless
no option
• Good nucleophiles will go via SN2 unless substrate tertiary then
E1 and SN1 compete
• Weaker bases that are good nucleophiles give substitution
• Normally observe E1 products when SN1 occurs!
• Best LG give weakest bases as products

These mechanisms are just extremes

Real life can be somewhere inbetween!
There are other substitution and elimination mechanisms!