Two-step continuous flow-driven synthesis of 1,1-cyclopropane aminoketones

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Flow Chemistry

Background:

• The synthesis of cyclopropane derivatives is crucial in medicinal chemistry.
• Developing efficient and scalable synthetic routes is essential for drug discovery.
• Continuous flow chemistry offers advantages in safety, efficiency, and scalability for complex syntheses.

Purpose of the Study:

• To develop a continuous flow telescoped synthesis for 1,1-cyclopropane aminoketones.
• To optimize the photocyclization of 1,2-diketones to 2-hydroxycyclobutanones (HCBs).
• To investigate the subsequent tandem reaction of HCBs with amines for C4-C3 ring contraction.

Main Methods:

• Optimization of photocyclization of 1,2-diketones.
• Tandem condensation and C4-C3 ring contraction reaction.
• Utilizing continuous flow reactor technology for telescoped synthesis.

Main Results:

• Achieved efficient synthesis of 1,1-cyclopropane aminoketones.
• Obtained a library of cyclopropylamines with good chemical yields.
• Demonstrated high productivity and short residence times in the continuous flow process.

Conclusions:

• The developed continuous flow method provides an efficient route to cyclopropane aminoketones.
• The telescoped synthesis is suitable for generating diverse libraries of cyclopropylamines.
• This approach offers a scalable and productive method for synthesizing valuable chemical entities.