Stereoselectivity in E1 (E or Z) : Favoured
Stereoselectivity in E1 (E or Z) : Favoured
Stereoselectivity in E1 (E or Z) : Favoured
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
..& 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
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
Cl
1:3
Me Me
NaOEt
250 times
SLOWER
Cl
8
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
H
CH3
X H
H OR H OR
methyl hydrogen
ring hydrogens hindered easily accessible
by 1,3-diaxial interaction
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