Orgo Final Reaction

Williamson Ether Synthesis

• Reagents?

• Product?

• Mechanism?

• Regiochemistry?

• Stereochemistry?

Reagents: RO⁻ + methyl or 1° alkyl halide/tosylate

Product: Ether

Mechanism: SN2

Regiochemistry: None

Stereochemistry: Inversion at attacked carbon

Limitations:

• Works best on methyl and 1° substrates

• 2° gives E2 competition

• 3° does not react by SN2

Alcohol Condensation

• Reagents?

• Product?

• Mechanism?

• Regiochemistry?

• Stereochemistry?

• Limitations?

Reagents: 2 ROH, H₂SO₄, heat

Product: Ether + H₂O

Mechanism:

• 1° alcohols: SN2

• 2°/3° alcohols: carbocation pathway

Regiochemistry: None

Stereochemistry:

• SN2 → inversion

• Carbocation → loss of stereochemistry

Limitations:

• Best for symmetrical ethers

• Rearrangements possible for 2°/3° alcohols

Alcohol → good leaving group via acid (HX)
• Reagents?
• Product?
• Mechanism?
• Stereochemistry?
• Substrate limitations?

Reagents: HCl, HBr, or HI
Product: Alkyl halide
Mechanism:
• 1° = SN2
• 3° = SN1
• 2° = either
Stereochemistry:
• SN2 → inversion
• SN1 → racemization
Substrate limitations:
• Carbocation rearrangements possible

Alcohol → Good Leaving group via PBr₃/PCl₃
• Reagents?
• Product?
• Mechanism?
• Stereochemistry?
• Substrate limitations?

Reagents: PBr₃/PCl₃
Product: Alkyl bromide
Mechanism: SN2
Stereochemistry: Inversion
Substrate limitations:
• Best for 1° and 2° alcohols
• No rearrangements

Acidic α-Halogenation of Carbonyls
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Substrate limitations?

Reagents: X₂, H⁺
Product: α-Halo carbonyl
Mechanism: Enol formation
Regiochemistry:
• Monohalogenation only
Substrate limitations:
• Stops after one halogen

Basic α-Halogenation of Carbonyls
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Substrate limitations?

Reagents: Excess X₂, OH⁻
Product: Polyhalogenated carbonyl
Mechanism: Enolate formation
Regiochemistry:
• Exhaustive halogenation
Substrate limitations:
• Methyl ketones undergo haloform reaction

Epoxide Opening (Acidic)
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?

Reagents: Nu + H⁺
Product: Alcohol containing nucleophile
Mechanism: Protonated epoxide attack
Regiochemistry:
• More substituted carbon attacked
Stereochemistry:
• Anti opening

Epoxide Opening (Basic)
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?

Reagents: Strong nucleophile
Product: Alcohol containing nucleophile
Mechanism: SN2
Regiochemistry:
• Less substituted carbon attacked
Stereochemistry:
• Anti opening

Halohydrin → Epoxide
• Reagents?
• Product?
• Mechanism?
• Stereochemistry?
• Substrate limitations?

Reagents: Base
Product: Epoxide
Mechanism: Intramolecular SN2
Stereochemistry:
• Inversion at attacked carbon
Substrate limitations:
• OH and leaving group must be adjacent

Carboxylic Acid → Methyl Ester via Diazomethane
• Reagents?
• Product?
• Mechanism?
• Substrate limitations?

Reagents: CH₂N₂
Product: Methyl ester
Mechanism:
• Acid-base followed by SN2
Substrate limitations:
• Only methyl esters formed

Alkyl Halide → Amine
• Reagents?
• Product?
• Mechanism?
• Substrate limitations?

Reagents: NH₃
Product: Amine
Mechanism: SN2
Substrate limitations:
• Overalkylation common

Alkyl Halide → Quaternary Ammonium Salt
• Reagents?
• Product?
• Mechanism?
• Substrate limitations?

Reagents: Excess amine
Product: Quaternary ammonium salt (NR₄⁺)
Mechanism: Repeated SN2 reactions
Substrate limitations:
• Requires unhindered substrate

Hofmann Elimination
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?

Reagents:
1. Excess CH₃I
2. Ag₂O, H₂O
3. Heat

Product: Alkene
Mechanism: E2
Regiochemistry:
• Hofmann product (less substituted alkene)
Stereochemistry:
• Anti-periplanar requirement

Alkyne Synthesis from Dihalides
• Reagents?
• Product?
• Mechanism?
• Substrate limitations?

Reagents: Excess NaNH₂
Product: Alkyne
Mechanism: Double E2
Substrate limitations:
• Requires vicinal or geminal dihalide

SN2 Reactions of Carbon Nucleophiles
• Reagents?
• Product?
• Mechanism?
• Stereochemistry?
• Substrate limitations?

Reagents:
• Acetylides
• CN⁻
• Enolates
• Other carbon nucleophiles

Product: New C-C bond
Mechanism: SN2
Stereochemistry:
• Inversion
Substrate limitations:
• Best with methyl and 1° substrates

α-Alkylation of Carbonyls
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Substrate limitations?

Reagents:
1. Base
2. Alkyl halide

Product: α-Alkylated carbonyl
Mechanism:
• Enolate formation
• SN2 alkylation

Regiochemistry:
• LDA, low temp → kinetic enolate
• Weak base/equilibrium → thermodynamic enolate

Substrate limitations:
• Alkyl halide should be methyl or 1°

Electrophilic Addition of HX to Alkenes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents: HCl, HBr, HI

Product: Alkyl halide

Mechanism:
• Protonation of alkene
• Carbocation formation
• Nucleophilic attack

Regiochemistry:
• Markovnikov addition
• H goes to less substituted carbon
• X goes to more substituted carbon

Stereochemistry:
• Not stereospecific
• Racemic mixture possible if stereocenter forms

Substrate limitations:
• Carbocation rearrangements possible
• Hydride and methyl shifts possible

Electrophilic Addition of HX to Alkynes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents: HCl, HBr, HI

Product:
• 1 equivalent → vinyl halide
• 2 equivalents → geminal dihalide

Mechanism:
• Protonation
• Vinyl cation formation
• Halide attack

Regiochemistry:
• Markovnikov addition

Stereochemistry:
• Usually not stereospecific

Substrate limitations:
• Excess HX gives second addition
• Product often continues reacting

Carbene Addition to Alkenes

• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
• CH₂N₂, hν

Product: Cyclopropane

Mechanism:
• Concerted addition

Regiochemistry:
• Both carbons of alkene bond to carbene carbon

Stereochemistry:
• Syn addition
• Stereospecific
• Cis alkene → cis cyclopropane
• Trans alkene → trans cyclopropane

Substrate limitations:
• Alkene geometry retained

Epoxidation with Peroxy Acids
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
• mCPBA
• Other peroxy acids

Product: Epoxide

Mechanism:
• Concerted oxygen transfer

Regiochemistry:
• Oxygen added across π bond

Stereochemistry:
• Syn addition
• Stereospecific
• Alkene stereochemistry retained

Substrate limitations:
• Requires alkene

Dihalogenation of Alkenes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
• Br₂
• Cl₂

Product: Vicinal dihalide

Mechanism:
• Halonium ion intermediate

Regiochemistry:
• One halogen added to each alkene carbon

Stereochemistry:
• Anti addition
• Trans relationship in cyclic systems

Substrate limitations:
• No carbocation rearrangements

Halohydrin Formation
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
• X₂
• H₂O

Product: Halohydrin

Mechanism:
• Halonium ion formation
• Water attack

Regiochemistry:
• OH goes to more substituted carbon
• X goes to less substituted carbon

Stereochemistry:
• Anti addition

Substrate limitations:
• No carbocation rearrangements

Oxymercuration-Reduction
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
1. Hg(OAc)₂, H₂O
2. NaBH₄

Product: Alcohol

Mechanism:
• Mercurinium ion formation
• Water attack
• Reduction replaces Hg with H

Regiochemistry:
• Markovnikov alcohol

Stereochemistry:
• Oxymercuration step is anti
• Final product often not stereospecific after reduction

Substrate limitations:
• No carbocation rearrangements

Hydroboration-Oxidation of Alkenes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
1. BH₃·THF
2. H₂O₂, OH⁻

Product: Alcohol

Mechanism:
• Concerted hydroboration
• Oxidation replaces B with OH

Regiochemistry:
• Anti-Markovnikov
• OH ends up on less substituted carbon

Stereochemistry:
• Syn addition

Substrate limitations:
• No carbocation rearrangements

Hydroboration-Oxidation of Alkynes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
1. R₂BH (bulky borane)
2. H₂O₂, OH⁻

Product:
• Terminal alkyne → aldehyde
• Internal alkyne → ketone

Mechanism:
• Syn hydroboration
• Oxidation
• Enol tautomerization

Regiochemistry:
• Anti-Markovnikov hydration

Stereochemistry:
• Syn addition during hydroboration

Substrate limitations:
• Terminal alkynes give aldehydes

Catalytic Hydrogenation of Alkenes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
• H₂
• Pd/C, Pt, or Ni

Product: Alkane

Mechanism:
• Surface catalysis

Regiochemistry:
• H added to both alkene carbons

Stereochemistry:
• Syn addition

Substrate limitations:
• Reduces C=C completely

Catalytic Hydrogenation of Alkynes
• Reagents?
• Product?
• Mechanism?
• Regiochemistry?
• Stereochemistry?
• Substrate limitations?

Reagents:
• Excess H₂
• Pd/C, Pt, or Ni

Product: Alkane

Mechanism:
• Surface catalysis

Regiochemistry:
• H added across π bonds

Stereochemistry:
• Syn additions

Substrate limitations:
• Usually proceeds all the way to alkane