1. Stereoselectivity in E1 eliminations favors the E alkene product as substituents are farther apart in the anti-periplanar conformation, minimizing steric interactions.
2. In E2 eliminations, the anti-periplanar transition state is favored as it allows optimal orbital overlap while minimizing steric interactions between the base and the leaving group.
3. Stereospecific E2 eliminations from chiral starting materials give different alkene stereochemistry depending on the stereochemistry of the starting material and whether one or both protons can be eliminated.
1. Stereoselectivity in E1 eliminations favors the E alkene product as substituents are farther apart in the anti-periplanar conformation, minimizing steric interactions.
2. In E2 eliminations, the anti-periplanar transition state is favored as it allows optimal orbital overlap while minimizing steric interactions between the base and the leaving group.
3. Stereospecific E2 eliminations from chiral starting materials give different alkene stereochemistry depending on the stereochemistry of the starting material and whether one or both protons can be eliminated.
1. Stereoselectivity in E1 eliminations favors the E alkene product as substituents are farther apart in the anti-periplanar conformation, minimizing steric interactions.
2. In E2 eliminations, the anti-periplanar transition state is favored as it allows optimal orbital overlap while minimizing steric interactions between the base and the leaving group.
3. Stereospecific E2 eliminations from chiral starting materials give different alkene stereochemistry depending on the stereochemistry of the starting material and whether one or both protons can be eliminated.
1. Stereoselectivity in E1 eliminations favors the E alkene product as substituents are farther apart in the anti-periplanar conformation, minimizing steric interactions.
2. In E2 eliminations, the anti-periplanar transition state is favored as it allows optimal orbital overlap while minimizing steric interactions between the base and the leaving group.
3. Stereospecific E2 eliminations from chiral starting materials give different alkene stereochemistry depending on the stereochemistry of the starting material and whether one or both protons can be eliminated.
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
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!
