General acid-mediated aminolactone formation using unactivated alkenes

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Synthetic Chemistry

Background:

• Spirocyclic butyrolactones and butenolides are common structural units in biologically active compounds.
• Existing methods for preparing these structures from exocyclic alkenes are often complex or lack efficiency, especially for late-stage synthesis.

Purpose of the Study:

• To develop a straightforward and efficient method for the direct synthesis of spirocyclic aminolactones from unactivated alkenes.
• To provide a versatile route for accessing complex molecular scaffolds with potential applications in drug discovery.

Main Methods:

• The study employed a novel cationic aminoalkylation pathway.
• Utilized cheap and commercially available starting materials and reagents.
• Demonstrated the method's effectiveness with unactivated alkenes.

Main Results:

• Successfully synthesized a range of (spiro)aminolactones with high functional group tolerance and chemoselectivity.
• The developed method is suitable for late-stage functionalization.
• Showcased the synthetic utility of the products through various transformations, including stereospecific rearrangements to create sterically hindered scaffolds.

Conclusions:

• This work presents a significant advancement in the synthesis of spirocyclic aminolactones.
• The method offers a practical and versatile approach for accessing valuable chemical entities.
• The ability to generate complex and sterically hindered structures opens new avenues for medicinal chemistry and drug development.