Eliminations

Elimination ReactionsElimination ReactionsE1 Reaction E2 Reaction

Weak nucleophile Strong nucleophile

General Mechanism General Mechanism

Most commonly used bases:

E1 Reaction: Stereochemistry

Substitution predominates largelyAndElimination is a minor process!

Zaitsev’s Rule is followed here, strictly!

E2 Reaction: Stereochemistry

Syn Elimination: Uncommon Anti Elimination: Very common

Example:Example:

The requirement of trans relationship

E2 Reaction: Direction of Elimination

Zaitsev’s rule: More substituted olefin is favored! Hofmann’s rule: Least substituted olefin is favored!

Reasons: Acidity and Sterics!

Steric and Electronic Factors in Eliminations:

More conjugatedand not More substituted!

Summary of Eliminations

Elimination Reactions: Synthetic Applications

Dehydrohalogenations:

Dehydrations:Oxidations: Loss of H2

Competition Between Elimination and Substitutions

SN2 versus E2N

• A good base/nucleophile (avoids SN1) favors SN2/E2• Sterically bulky base can favor E2 (pentacoordinated TS not possible)!

All SN2 or E2!

Tertiary, yet E2 with a strong base/nucleophile!

All SN2 or E2!

• Strong base/nucleophile always promotes elimination anda weaker base/nucleophile always yields substitution products prediminantly!

Competition Between Elimination and Substitutions

SN1 versus E1N

CH3L:   No -carbon, exellent substrate for SN2, no SN1 possible, elimination cannot occur!

RCH2L:   Less sterics, exellent substrate for SN2, but predominantly E2 with a strong base!2 , , p y g

R2CHL:   SN2 with CH3COO-, CN-, RS-, etc.)E2 with OH-, OR-, DBU, DBN, etc.In a polar solvent: SN1 and E1 in the absence of a good nucleophile or base

R3CL:   No SN2, no SN1 if substittuion is needed (no base!)E cellent Elimination ith a strong base b E2!Excellent Elimination with a strong base by E2!

Addition Reactions

Addition of Oxygen to Olefins: Epoxidation

Dih d l ti f Ol fiDihydroxylation of Olefins:

Trans‐dihydroxylation

Cis‐dihydroxylation

Hydrationby Oxymercuration

Hydroboration by Hydroboration

Terminal Alkyne:

Internal Alkyne:

Conjugate Addition: 1,2 versus 1,4 Addition

Conjugate Additions(Michael ReactionMi h l Additi )Michael Addition)

Bromination of Olefins

Addition of Br2 to Triple Bonds

Reduction of Alkynes

Lindlar Catalyst: Pd/CaCO3 or BaSO4 deactivated with Lead Tetraacetate and QuinolineLindlar Catalyst: Pd/CaCO3 or BaSO4 deactivated with Lead Tetraacetate and Quinoline

Trans addition of H2Trans addition of H2

Industrial Synthesis of Vitamin A by Hoffmann-LaRoche Pharmaceutical Company

Involves reduction (Lindlar) followed by thermal isomerization!

Cyclopropane Synthesis

Addition is Stereospecific!

Simmons-Smith Reaction

Carbenoid, a carbene like!

Additions are stereospecific!

Radical Additions