Microflow, Sequential Coupling and Cyclization Approach for Synthesis of Cyclic Phosphotriesters from PCl₃

Area of Science:

• Organic Chemistry
• Chemical Engineering
• Materials Science

Background:

• Cyclic phosphotriesters are valuable compounds with diverse applications.
• Synthesizing these molecules presents challenges due to substrates with multiple reactive sites.
• Previous methods often struggle with controlling side reactions and achieving desired ring sizes.

Purpose of the Study:

• To develop a novel and efficient approach for synthesizing cyclic phosphotriesters.
• To overcome the challenge of suppressing undesired reactions in multi-site substrates.
• To explore the synthesis of various ring sizes, specifically 5- to 8-membered rings.

Main Methods:

• Utilized microflow technology for precise control over reaction time and temperature.
• Employed phosphorus trichloride and diols as primary reactants.
• Optimized two distinct reaction conditions based on cyclization kinetics.

Main Results:

• Successfully suppressed undesired reactions through microflow technology.
• Synthesized fifteen different cyclic phosphotriesters and their analogs.
• Demonstrated the ability to produce compounds with 5- to 8-membered rings.

Conclusions:

• Microflow technology is highly effective in controlling complex organic reactions.
• The developed method provides a robust route to diverse cyclic phosphotriesters.
• A plausible mechanism for the suppression of side reactions has been proposed.