Retrosynthesis involves thinking about chemical reactions in reverse.
Focus on retro-aldol reactions, which are the reverse of aldol condensations.
Example used: cinnamaldehyde, which through retro-aldol reaction with sodium carbonate forms benzaldehyde and acetaldehyde.
Cinnamaldehyde to Benzaldehyde and Acetaldehyde
Cinnamaldehyde: Smells like cinnamon.
Benzaldehyde: Smells like almonds.
Mechanism Overview:
Identify alpha and beta carbons surrounding the carbonyl group.
Break the double bond, converting cinnamaldehyde into its component molecules.
Add H2 (hydrogens) to the alpha carbon and water (H2O) to the beta carbon.
Retrosynthesis
Useful for synthesizing enones and enals by thinking about retro-aldol reactions.
Example given for synthesizing an enone:
Identify alpha and beta carbons in the target enone.
Break double bond between these carbons.
Formulate starting ketone and aldehyde for synthesis.
Reaction Conditions: Use sodium hydroxide in water and ethanol for aldol condensation.
Directed Aldol Addition
When target compound is an aldol, not an enone or enal.
Identify alpha and beta carbons and break the bond connecting them.
Use LDA to form a lithium enolate for controlled addition.
Example given for synthesizing an aldol:
Start with ketone, use LDA to form an enolate, then add aldehyde.
Workup with water to obtain the aldol product.
Intramolecular Aldol Condensation
Example of synthesizing a cyclic compound via intramolecular aldol condensation.
Steps:
Identify alpha and beta carbons in the ring.
Break the internal double bond and identify carbons involved.
Use a base to facilitate the intramolecular condensation.
Conclusion
Retro-aldol reactions and retrosynthesis offer strategic ways to approach synthesis problems by breaking down complex molecules into simpler precursors.
Upcoming discussions on intramolecular aldol condensation in further detail.