Accessing Dihydroazepines and Cyclopentanes from Enynyl Ketones

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Constructing polycyclic molecules, especially medium-sized rings, is challenging due to strain and flexibility.
• Efficient synthesis of complex molecular architectures is crucial for drug discovery and materials science.

Purpose of the Study:

• To develop a stereocontrolled strategy for synthesizing polysubstituted dihydroazepines.
• To establish a method for converting dihydroazepines into cyclopentanes with multiple stereocenters.

Main Methods:

• A tandem cyclization reaction was employed to convert linear precursors into dihydroazepines.
• Acid-promoted ring contraction was used to transform dihydroazepines into cyclopentanes.

Main Results:

• The developed strategy successfully produced polysubstituted dihydroazepines.
• The subsequent ring contraction yielded cyclopentanes featuring five contiguous stereocenters.
• The method demonstrated broad substrate scope and functional group tolerance.

Conclusions:

• This work presents an efficient and streamlined route to sterically congested azepine- and cyclopentane-fused dihydrofurans.
• The strategy offers a valuable tool for accessing complex polycyclic compounds with precise stereochemical control.