Notes on N-Heterocyclic Carbenes and Nitrenes for Organic Chemistry

Introduction to N-Heterocyclic Carbenes (NHCs) and Nitrenes

  • Overview of Lecture

    • Focus on N-Heterocyclic Carbenes (NHCs) and nitrenes in organic chemistry.
    • Key points to be covered:
    • Stabilization of NHCs.
    • Reactions involving NHCs.
    • Formation and reactions of nitrenes.

  • Recommended Reading:

    • Organic Chemistry, J. Clayden et al., Chapters on carbenes.

N-Heterocyclic Carbenes (NHCs)

  • Definition and Characteristics:

    • NHCs are carbenes that have nitrogen in a cyclic structure.
    • Example: Imidazolium salts, which donate from nitrogen's lone pair into vacant p-orbital to form stable structures.

  • Stability of NHCs:

    • Aromatically stabilized NHCs have indefinite stability in the absence of air and moisture.
    • Example: Arduengo's Carbene melts at 240 °C without decomposition.

  • Applications:

    • Serve as efficient organocatalysts in various reactions due to their stability and reactivity.

Umpolung Chemistry

  • Concept of Umpolung:

    • Umpolung refers to the reversal of polarity at a functional group, allowing for unique reactivity.
    • Example: Benzoin condensation in presence of cyanide, producing benzoin through 1,2-addition of 'acyl anion' to an aldehyde.
    • Mechanism:
    • Reaction between cyanide and benzaldehyde to create an intermediate.
    • Rearrangement leads to polarity reversal, facilitating attack on a second carbonyl.

  • Importance of Umpolung:

    • Utilizes common reagents like cyanide and NHCs for new synthetic pathways.

Chemistry of Nitrenes

  • Definition of Nitrenes:

    • Analogous to carbenes but based on nitrogen.
    • Unstable intermediates characterized by the presence of two lone pairs and six electrons (2 bonds less than a normal amine).

  • Formation of Nitrenes:

    • Common methods include treatment of azides and amides under specific reaction conditions.
    • Main reactions:
    • Amination via C-H Insertion:
      • Nitrene generated from oximes treated with acetic anhydride under heat, facilitating C-H insertion.
    • Transformations of Nitrenes:
      • Aziridination reactions using tosyl azides (e.g., PhI=NTs) in the presence of transition metal catalysts to form aziridines.

  • Rearrangement Reactions:

    • Include important processes like Curtius rearrangement converting acyl azides into amines, removing a carbon atom in the process.
    • Hofmann Rearrangement: Conversion of an amide into an amine with loss of a carbon atom, often through nitrene intermediates.
    • Lossen Rearrangement: Hydroxamic acids converting into isocyanates through various derivatizations.

Key Reactions Involving Carbenes and Nitrenes

  • Breslow Intermediate:

    • Central to several NHC-catalyzed reactions, including the benzoin reaction demonstrating umpolung chemistry.

  • Curtius and Hofmann Rearrangements:

    • Highlighting their utility in amine synthesis and functional group transformations.

  • Organocatalytic Applications:

    • The role of NHCs in catalyzing reactions, enhancing reaction paths that involve nitrene and carbene intermediates.

Summary of Topics Covered

  • Understanding of NHCs and nitrenes and their reactivity.
  • Significance of umpolung in synthetic methods.
  • Key rearrangements and transformations involving nitrenes and carbenes.
  • Applications in organocatalysis and organic synthesis.