B₂pin₂-Mediated Cascade Cyclization/Aromatization Reaction: Facial Access to Functionalized Indolizines

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Heterocyclic Chemistry

Background:

• Indolizines are important heterocyclic scaffolds found in numerous biologically active compounds and materials.
• Efficient and versatile synthetic methods for constructing functionalized indolizines are highly sought after in organic synthesis.

Purpose of the Study:

• To develop a novel, metal-free synthetic strategy for the construction of functionalized indolizines.
• To explore a radical cascade cyclization/aromatization reaction involving enaminones and pyridine.

Main Methods:

• Utilized bis(pinacolato)diboron (B2pin2) as a key reagent for a radical cascade reaction.
• Employed enaminone and pyridine as starting materials.
• Conducted the reaction under metal-, external oxidant-, and base-free conditions.

Main Results:

• Successfully synthesized valuable functionalized indolizines.
• Demonstrated broad functional group tolerance, including halogens, π-systems, heterocycles, and ferrocenyl groups.
• Preliminary mechanistic studies suggested the involvement of an in situ generated pyridine-boryl radical.

Conclusions:

• The described B2pin2-mediated reaction provides a practical and efficient method for synthesizing diverse functionalized indolizines.
• The metal-free and base-free conditions make this strategy attractive for complex molecule synthesis.
• The reaction proceeds via a radical cascade pathway initiated by a pyridine-boryl radical.