DISCONNECTION APPROACH - CONTROL IN CARBONYL CONDENSATION M.Pharmacy 1st Year 2025 (2024-2025) Previous Year's Question Papers/Notes Download - HK Technical PGIMS

the disconnection approach for controlling chemoselectivity and regioselectivity in carbonyl condensation reactions, a cornerstone of organic synthesis. Key highlights include:

• Core Challenges:

  • Chemoselectivity & Regioselectivity: Ensuring unambiguous enolization and electrophile selection in enone synthesis (e.g., avoiding competing aldehyde enolization).

  • Self-Condensation: Simplifying selectivity using symmetrical ketones/aldehydes (e.g., diethyl carbonate).

• Strategies for Control:

  • Intramolecular Reactions: Thermodynamic preference for 5-6 membered rings (e.g., diketone cyclization).

  • Non-Enolizable Electrophiles: Compounds like aryl halides or formaldehyde (Mannich reaction) to direct reactivity.

  • Specific Enol Equivalents:

    • Malonates (Knoevenagel Reaction): Selective enolization for aldol-type condensations.

    • Enamines & Organometallics: Reformatsky reagents and Wittig reactions for β-hydroxy compound synthesis.

• Advanced Techniques:

  • Enamine Acylation: Synthesis of 1,3-dicarbonyl compounds.

  • Activating Groups (COOEt): Regioselective alkylation and condensation control.