Advanced Organic Chemistry - Chapter 1

Advanced Organic Chemistry - Chapter 1

• This chapter covers alcohols, carbonyls, and redox reactions, organometallic compounds, organolithium and magnesium compounds, reactions of organolithium/magnesium species, alcohols from Grignard reactions, and lithium dialkylcuprates.

The Carbonyl Functional Group

• The carbonyl group features a carbon atom double-bonded to an oxygen atom.
• Common carbonyl functional groups include aldehydes, ketones, carboxylic acids, and esters.
• The carbonyl group is planar and sp² hybridized.
• The carbonyl group has one sigma (σ) bond and one pi (π) bond.
• The carbonyl group is quite polarized (Cδ+, Oδ-).
• Resonance structures can be used describe the polarization of the bond

General Reactions of Carbonyls

• Nucleophilic addition to carbonyls.
• The addition product is tetrahedral.
• Oxidation of alcohols/reduction of carbonyls.
• Oxidation generally decreases hydrogen content and increases oxygen content.
• Reduction generally increases hydrogen content and decreases oxygen content.

Oxidation/Reduction Reactions

• Oxidation-reduction reactions are commonly termed "redox" reactions.
• Oxidation involves loss of electrons.
• Reduction involves gain of electrons.
• Organic chemists often use alternative definitions for redox reactions.
• Reduction: Increase hydrogen content (decrease oxygen)
• Oxidation: Decrease hydrogen content (increase oxygen)
• Oxidizing/reducing agents are usually inorganic compounds.
• Oxidizing agents get reduced during redox reactions.
• Reducing agents get oxidized during redox reactions.

Oxidation States of Carbon: Organics

• Oxidation state of carbons are calculated based on electronegativity differences with bonded atoms.
• Carbon bonded to more electronegative atom gets higher positive oxidation state.
• Carbon attached to less electronegative atom gets higher negative oxidation state.

Alcohol Synthesis: Carbonyl Reduction

• Carbonyls are reduced to alcohols using various hydrogen sources
• Aldehydes are reduced to primary alcohols.
• Ketones are reduced to secondary alcohols.
• Carboxylic acids and esters can also be reduced to alcohols.
• Common reducing agents include NaBH4 and LiAlH4

Reducing Agents: 1° and 2° Alcohols

• Sodium borohydride (NaBH4)
• Lithium aluminum hydride (LiAlH4)
• Hydrogen/transition metal catalyst (CuO/CuCr2O7)
• NaBH4 and LiAlH4 are hydride transfer agents.
• Hydride (H-) acts as a nucleophile.
• Carbonyls have varying degrees of ease of reduction.

Selection of a Reducing Agent

• The choice of reducing agent impacts the reaction products.
• LiAlH4 reduces carboxylates/esters to alcohols in preference over NaBH4.

NaBH4/LiAlH4 Reduction Examples

• Examples of NaBH4/LiAlH4 reductions of various carbonyl compounds

Oxidizing Agents in Organic Chemistry

• PCC (Pyridinium chlorochromate): mild oxidant, 1° alcohol → aldehyde.
• Jones Reagent (H₂CrO₄): Harsher oxidant, 1° alcohol → carboxylic acid.

General Oxidizing Agent Selection

• Oxidizing agents can determine oxidation products (e.g., PCC, Cr6+, KMnO4.)
• These agents are commonly used to oxidize alcohols to aldehydes or carboxylic acids.
• Oxidizing agents generally do not oxidize tertiary alcohols.

Oxidation of 1°, 2° Alcohols

• PCC, H₂CrO₄, and KMnO₄ are common oxidants used for different types of alcohols.
• PCC is effective for oxidizing primary alcohols to aldehydes.
• H₂CrO₄ and KMnO₄ are effective for oxidizing primary alcohols to carboxylic acids and for oxidizing secondary alcohols to ketones.

Oxidation Mechanisms: Chromate Esters

• Mechanisms of chromium-based oxidations are complex but often involve protonation and loss of water leading to chromate esters.

Organometallic Compounds

• Organometallic compounds contain carbon-metal bonds.
• Bonds range from ionic to primarily covalent
• Ionic C-M bonds include C-Na, C-K.
• Primarily covalent C-M bonds include C-Pb, C-Sn, C-Hg.
• Intermediate C-M bonds include compounds with C-Mg and C-Li.
• Reactivity increases with ionic character of C-M bond.

Organolithium Reagents

• Organolithium reagents are reactive carbanion-like species.
• They react slowly with ethers.
• Halide reactivity: RI > RBr > RCI

Grignard Reagents

• Grignard reagents are organometallic compounds.
• They are prepared by reacting alkyl halides with magnesium in an ether solvent.
• Halide reactivity of Grignard reagents is similar to organolithium reagents.
• Grignard reagents generally exist as complexes, often viewed as RMgX.

Organometallic Reactions: Notes

• Organometallic compounds can act as nucleophiles towards polarized carbonyl groups.
• They are very strong Lewis bases, reacting with acidic protons.
• Dry conditions are necessary for organometallic reactions to avoid reactions with water.

Grignard Reactions: Epoxides

• Grignard reagents open epoxides via nucleophilic attack to the less-substituted carbon due to steric hindrance.

Grignard Reactions w/ Carbonyls

• Grignard reagent react with carbonyls to form alcohols.

Grignard Reactions: Esters

• Grignard reagents react with esters to form tertiary alcohols.
• Esters react twice with Grignard.

Reactions of Organolithium Compounds

• Organolithium reagents react similarly to Grignard reagents.
• Same limitations to Grignard reagents apply to organolithium reagents.

Lithium Dialkylcuprates

• Lithium dialkylcuprates are used in carbon-carbon bond formation.
• They are quite versatile in forming carbon-carbon bonds.

Oxidation and Reduction (General Reactions)

• Various types of oxidizing and reducing agents are used in organic chemistry.
• These agents are commonly used in reactions for functional group transformations.

Oxidation and Reduction (Specific Reactions)

• Various types of oxidation and reduction reactions.