Forging Medium Rings via I(I)/I(III)-Catalyzed Diene Carbofunctionalization

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Accessing medium-sized carbocycles, particularly 8-membered rings, remains a synthetic challenge.
• Developing efficient and versatile methods for carbocycle synthesis is crucial in medicinal and materials chemistry.

Purpose of the Study:

• To disclose a main-group catalysis-based strategy for the direct carbofunctionalization of 2-phenethyl-substituted 1,3-dienes.
• To establish a method for synthesizing densely functionalized, fluorinated benzocyclooctenes.

Main Methods:

• Utilizing an iodine(I)/iodine(III) catalysis cycle for carbocyclization.
• Employing direct carbofunctionalization of 1,3-dienes.
• Modulating oxidation/activation regimes and external nucleophiles.

Main Results:

• Successful synthesis of fluorinated benzocyclooctenes via a main-group catalysis approach.
• Demonstrated extension of the process to form allylic C-O, C-N, and C-C bonds (>30 examples).
• Product derivatization, X-ray conformational analysis, and preliminary enantioselective catalysis validation were achieved.

Conclusions:

• The developed method provides an operationally simple route to valuable 8-membered carbocycles.
• The strategy offers broad scope, enabling the formation of diverse functionalized benzocyclooctenes.
• Scalable resolution protocols and enantioselective catalysis pave the way for further applications.