Programmable Piperazine Synthesis via Organic Photoredox Catalysis

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Catalysis

Background:

• Piperazine cores are crucial in pharmaceutical development.
• Synthesizing diverse C-substituted piperazines is challenging.
• Existing methods often require prefunctionalized substrates.

Purpose of the Study:

• To develop a programmable and highly diversifiable synthesis of piperazine cores.
• To circumvent the need for radical precursors in piperazine synthesis.
• To establish an operationally simple method using organic photoredox catalysis.

Main Methods:

• Utilizing organic photoredox catalysis for direct substrate oxidation.
• Employing a 6-endo-trig radical cyclization with in situ generated imines.
• Applying photoredox-catalyzed anti-Markovnikov hydroamination of ene-carbamates.

Main Results:

• A novel, programmable approach to piperazine core synthesis was established.
• The method is operationally simple and avoids prefunctionalized substrates.
• Compatible with a wide range of carbonyl and amine partners, yielding good to excellent results.

Conclusions:

• The developed method provides a versatile and efficient route to diverse piperazine scaffolds.
• This approach simplifies the synthesis of complex diamine starting materials.
• Facilitates the development of new pharmaceutical compounds leveraging piperazine structures.