Visible Light-Promoted Aromatization-Driven Deconstructive Fluorination of Spiro Carbocycles

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Photochemistry

Background:

• Spiro carbocycles are important structural motifs in medicinal chemistry.
• Developing efficient methods for their functionalization, particularly with fluorine, remains a challenge.

Purpose of the Study:

• To develop a novel visible light-promoted deconstructive fluorination of spiro carbocycles.
• To explore the scope and limitations of this new synthetic methodology.

Main Methods:

• Visible light irradiation of spiro dihydroquinazolinones with N-fluorobenzenesulfonimide (NFSI).
• Analysis of reaction products using standard organic chemistry techniques.
• Mechanistic studies to elucidate the reaction pathway.

Main Results:

• Efficient synthesis of 2-(4-fluoroalkyl)quinazolin-4(3H)-ones in good yields.
• Demonstrated excellent functional group tolerance.
• Proposed a radical pathway involving C-C bond cleavage and F atom transfer.
• Successful application of ring-opening chlorination using N-chlorosuccinimide (NCS).

Conclusions:

• Visible light-promoted deconstructive fluorination offers a new route to valuable fluorinated heterocycles.
• The methodology is robust and tolerates various functional groups.
• The reaction proceeds via a radical mechanism, providing insights into C-C bond activation.