Catalyst-Free Assembly of δ-Lactam-Based Hydrazide-Hydrazone Compounds from 3-Arylglutaconic Anhydrides and Aldazines

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Cyclic hydrazide-hydrazone scaffolds are important in medicinal chemistry.
• Developing efficient and versatile synthetic routes to these compounds is crucial.
• Existing methods may lack simplicity, selectivity, or broad applicability.

Purpose of the Study:

• To develop a novel, general, and efficient approach for synthesizing cyclic hydrazide-hydrazone compounds.
• To explore the synthesis of compounds featuring a dihydropyridine-2-one core.
• To demonstrate the synthetic versatility and potential for chemical diversification.

Main Methods:

• Annulation reaction between symmetrical aldazines and 3-arylglutaconic anhydrides.
• Utilizing reaction temperature control to switch between isomeric dihydropyridine-2-one cores.
• Performing post-modification reactions on the synthesized compounds.

Main Results:

• A straightforward and catalyst-free synthetic procedure was established.
• The reaction demonstrated high diastereoselectivity.
• Two distinct isomeric dihydropyridine-2-one cores were accessible.
• Post-modification studies confirmed the synthetic utility of the products.

Conclusions:

• The developed annulation strategy provides a versatile route to diverse cyclic hydrazide-hydrazone compounds.
• This method significantly expands the chemical space of medicinally relevant N-functionalized delta-lactams.
• The approach offers advantages in terms of simplicity, selectivity, and control over isomer formation.