Visible-Light-Induced Intramolecular Dehydrogenative Cyclization of o-Aryl Benzaldehydes

Area of Science:

• Organic Chemistry
• Photochemistry
• Synthetic Methodology

Background:

• Visible-light photocatalysis is a rapidly growing field in organic synthesis.
• Fluorenones are important structural motifs found in various natural products and pharmaceuticals.
• Developing efficient and mild methods for fluorenone synthesis remains a key challenge.

Purpose of the Study:

• To develop a novel visible-light-induced dehydrogenative cyclization for fluorenone synthesis.
• To utilize a bench-stable N-aminopyridinium salt as a hydrogen atom transfer (HAT) reagent and oxidant.
• To demonstrate the applicability of the method for the synthesis of natural products.

Main Methods:

• Visible-light irradiation of o-aryl benzaldehydes in the presence of N-aminopyridinium salt.
• Employing the N-aminopyridinium salt as both a HAT reagent and a mild oxidant.
• Mechanistic studies involving photoinduced homocleavage and radical chain processes.

Main Results:

• A wide range of fluorenones with diverse substitution patterns were synthesized in moderate to excellent yields.
• The protocol was successfully applied to the de novo synthesis of the natural product Nobilone.
• Mechanism investigations supported a radical chain pathway initiated by photoinduced homocleavage.

Conclusions:

• A novel and efficient visible-light-mediated protocol for fluorenone synthesis has been established.
• The developed method offers a mild and versatile approach for constructing complex fluorenone derivatives.
• This methodology provides a valuable tool for both synthetic chemists and natural product synthesis.