Recording-2025-02-12T17:16:00.901Z

Key Concepts in Organometallic Chemistry

Preparation of Organolithiums and Grignards

• Organolithiums and Grignards are important reagents in organic synthesis.

• These are prepared from alkyl halides.

• The R group in the alkyl halide must be limited to:

  • Alkyl

  • Vinyl

  • Aryl

• R groups containing functional groups like aldehydes, ketones, etc., are prohibited because they can react with the Grignard or organolithium reagents.

Impact on Synthesis Problems

• When faced with synthesis problems, avoid overcomplicating by introducing multiple functional groups in a single step as this complicates the reaction and can lead to failure.

• Understand the nature of the alkyl halide to ensure successful reactions involving Grignards and organolithiums.

Review of Sodium Acetylides

• Sodium acetylides are formed from the reaction of terminal alkynes with a strong base, such as sodium amide.

• The terminal alkyne acts as the acid with a pKa of 25, while the resulting conjugate acid (ammonia) has a pKa of approximately 35.

• In reactions, the carbonyl carbon functions as the electrophilic site, while the deprotonated terminal carbon acts as a nucleophile.

Mechanistic Differences

• Organolithiums and Grignards:

  • Characterized by polar covalent bonds and do not display significant ionic character.

  • Mechanism: The nucleophilic carbon attacks the electrophile based on polarity.

• Sodium acetylides:

  • Exhibit some net ionic character. Mechanism involves attacks from a lone pair on carbon rather than a metal-carbon bond.

Overview of Key Reactions

• Different types of alcohols can be synthesized based on the reagent:

  • Using ketones yields tertiary alcohols.

  • Using aldehydes yields secondary alcohols.

  • To yield primary alcohols, the reagent used should be formaldehyde or ethylene oxide (which introduces a second carbon).

Reduction Reactions

• Alkene and carbonyl reductions using hydrogen can be achieved via various conditions:

  • Aldehydes and ketones can be reduced using H2, incorporating hydrogen to saturate double bonds.

  • Resulting alcohols vary:

    • Ketones -> Secondary alcohols.

    • Aldehydes -> Primary alcohols.

Chemoselectivity in Reactions

• Chemoselectivity refers to the preference of a reagent for one functional group over another.

• Traditional hydrogen sources lack chemoselectivity, meaning both functional groups will react.

• Use of hydride reducing agents can improve selectivity, targeting carbonyls while sparing alkenes.

Key Reducing Agents

• Lithium aluminum hydride (LiAlH4): a strong reducing agent that acts in a two-step process:

  • Step 1: Reacts with the carbonyl.

  • Step 2: Protonation in a separate step often using a source such as methanol.

• Sodium borohydride (NaBH4): used as a milder reducing agent under conditions conducive to selective reduction.