Sequential Formal (4 + 1)-Spirocycloaddition/Oxidative Cleavage between Indoles and β‑Nitrostyrenes: One-Pot Route to...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Isoxazoles are important heterocyclic compounds with diverse biological activities.
• Benzamide derivatives are prevalent in pharmaceuticals.
• Efficient synthesis of highly substituted isoxazoles remains a challenge.

Purpose of the Study:

• To develop an effective and versatile protocol for synthesizing 3,4,5-substituted benzamide-containing isoxazoles.
• To explore a novel one-pot reaction strategy for constructing functionalized isoxazole scaffolds.

Main Methods:

• A formal (4 + 1)-spirocycloaddition reaction between indoles and β-nitrostyrenes.
• Subsequent oxidative cleavage using acetic anhydride and hydrogen peroxide.
• Purification and characterization of synthesized isoxazole derivatives.

Main Results:

• Successfully synthesized 33 novel benzamide-containing isoxazoles.
• Achieved yields ranging from 44% to 91%.
• Demonstrated excellent functional group tolerance in the developed protocol.

Conclusions:

• The developed one-pot protocol provides an efficient route to highly functionalized benzamide isoxazoles.
• This method offers a valuable tool for accessing diverse isoxazole libraries for drug discovery.
• The reaction's robustness and broad scope make it suitable for further synthetic applications.