Efficient construction of a β-naphthol library under continuous flow conditions

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Flow Chemistry

Background:

• β-naphthols are valuable scaffolds in medicinal chemistry and materials science.
• Efficient and scalable synthesis of functionalized β-naphthols remains a challenge.

Purpose of the Study:

• To develop a rapid, reliable, and scalable continuous flow method for constructing a β-naphthol library.
• To explore the synthesis of diverse functionalized β-naphthols.

Main Methods:

• Utilizing a tandem Friedel-Crafts reaction in a mild continuous flow system.
• Employing readily available arylacetyl chlorides and alkynes as starting materials.
• Optimizing reaction conditions for efficient product formation within seconds.

Main Results:

• Successfully constructed a library of functionalized β-naphthols in high yields (up to 83%) within 160 seconds.
• Demonstrated the formation of spirofused triene diones using electron-rich phenylacetyl chloride derivatives.
• Achieved a scale-up throughput of 4.70 g/h, indicating large-scale applicability.

Conclusions:

• The developed continuous flow procedure offers a rapid and efficient route to diverse β-naphthols.
• This method presents a significant advancement for the scalable synthesis of β-naphthol derivatives.
• The approach is versatile and amenable to the generation of compound libraries for various applications.