Lecture Notes on Organometallic Reagents and Reactions

Introduction

• Excitement about the engagement of students in organic chemistry homework.
• Today’s focus: Chapter 20 on organometallic reagents and their reactions with carbonyl compounds, carboxylic acids, hydride nucleophiles, and synthesis.

Hydride Nucleophiles

• Previous discussion on hydride reagents with ketones and aldehydes.
  • Generic representation of ketone/aldehyde:
    • Can have alkyl, aromatic, or hydrogen groups.
• Reaction with hydride nucleophile (e.g., lithium aluminum hydride, sodium borohydride).
  • Workup with aqueous acid (e.g., H3O+) or water.
  • Results in reduction to form alcohol.

Carbon-Based Nucleophiles

• Introducing carbon nucleophiles which can form C-C bonds.
• Organometallic reagent example: Grignard reagents (e.g., butyl magnesium bromide).
  • Formation: Alkyl halide treated with magnesium in ether (e.g., THF).
  • Grignard reagents are reactive, used to build complex molecules.

Grignard Reaction Example

• Butyl bromide + magnesium + ether → Butyl magnesium bromide.
• Addition of carbonyl compound (e.g., acetone) and aqueous workup.
  • Result: Formation of 2-methyl-2-hexanol.
• Importance: Utilizing small molecules to create complex structures like insect pheromones.

Properties of Organometallic Reagents

• Metal-carbon bonds are polar covalent or ionic due to electronegativity difference.
• Grignard reagents are strong bases; pKa values and their implications discussed.
• Reactions with water yield hydrocarbons and metal hydroxides.

Organolithium Reagents

• Similar to Grignard reagents, written as RLi.
  • React with alkyl/aryl halides using lithium.
• Reaction example with an aldehyde leading to carbon-carbon bond formation.
  • Generates racemic mixture due to chiral center formation.

Acetylide Ions

• Alkynes are weak acids (pKa ~25) but strong enough to form acetylide ions.
• Example: Reaction of alkyne with sodium amide yielding sodium acetylide and ammonia.
• Synthesis examples using acetylide anions for nucleophilic addition to carbonyls.

Addition-Elimination Reactions

• Overview of reactions in the carboxylic acid family (esters, acid chlorides, amides).
• Lithium aluminum hydride reduces esters to alcohols, involving tetrahedral intermediates.
• Reaction example with methyl benzoate reducing to benzyl alcohol and methanol.

Synthetic Strategy: Retrosynthetic Analysis

• Using retrosynthetic analysis to synthesize complex molecules (e.g., 4-ethyl-4-octanol).
  • Start from desired compound, work backward to simpler precursors.
  • Identify suitable organometallic reagents for each step.
• Example synthesis:
  1. Target Compound: 4-ethyl-4-octanol.
  2. Step 1: Form ketone (2-heptanone) from alcohol (3-hexanol) via oxidation.
  3. Step 2: Use Grignard reagent to add carbon nucleophile for alcohol formation.

Conclusion

• Importance of organometallic reagents in forming carbon-carbon bonds and building complex molecules.
• Organic chemistry connects to practical applications and synthesis.
• Reminder of next class: quiz.