Lecture 12-4: Grignard Synthesis

Introduction

• Focus on performing Grignard synthesis in multi-step problems.
• Last recording for Chapter 12.
• Detailed examples in class worksheets.

General Guidelines for Grignard Synthesis

• Target Molecule: Synthesize from smaller pieces using available stockroom materials.
• Alcohol Group Identification: Mark this with a dot for new carbon-carbon bond formation.
• Alcohol Type:
  • Primary, Secondary, or Tertiary determines the oxygen-containing compound needed (aldehyde, ketone, ester, epoxide).
• Stockroom: Verify availability of required compounds.
  • Convert available compounds if necessary (e.g., to oxygen-containing compounds or alkyl halides).

Example Reactions

Example 1: Ketone to Tertiary Alcohol

• Approach: Given reactant and reagents, predict the product.
• Steps:
  1. Dot the two carbons where the new bond will form (carbon with halogen and carbon in oxygen-containing compound).
  2. Form new carbon-carbon bond between these dots.
  3. Add functional groups to respective carbons.
  4. Result: Tertiary alcohol (ketones always produce tertiary alcohols).

Example 2: Aldehyde to Secondary Alcohol

• Strategy: Use dot technique, as outlined previously.
• Steps:
  1. Dot the carbon containing the alkyl halide and the oxygen.
  2. Draw dots and add appropriate functional groups.
  3. Result: Aldehydes produce secondary alcohols.

Example 3: Ester to Tertiary Alcohol

• Requirement: Two Grignard reagents.
• Steps:
  1. Dot appropriate positions: two red dots connected to the black dot.
  2. First red dot removes part of the reactant, second red dot adds to it.
  3. Result: Formation of two new covalent bonds.
  4. Esters lead to tertiary alcohols due to dual alkyl group addition.

Example 4: Using Epoxides

• Versatility: Can form primary, secondary, or tertiary alcohols.
• Addition Rule: Grignard reagent adds to least substituted carbon.
• Example:
  1. Red dot on carbon with halogen, black dot on least substituted carbon.
  2. Form new bond with red and black dots.
  3. Consider position of OH group (not on carbon with black dot).
  4. Result depends on substitution pattern:
     • Two R groups = primary alcohol.
     • One R group = secondary alcohol.
     • Both R groups (alkyl) = tertiary alcohol.

Future Class Activities

• Additional problem-solving with target molecules.
• Reverse synthesis: Starting with target and deducing reactants.

Conclusion

• End of Chapter 12.