Direct δ-Lactone Synthesis From Free Alcohols via Photoinduced δ-C(sp³)-H Carbonylation in Flow

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Photochemistry

Background:

• Direct carbonylation of unactivated C(sp3)─H bonds is a significant synthetic challenge.
• Existing methods often require harsh conditions or specific substrates.

Purpose of the Study:

• To develop a photo-flow strategy for the direct C(sp3)─H carbonylative lactonization of free alcohols.
• To enable the synthesis of delta-lactones from readily available alcohol feedstocks.

Main Methods:

• Utilizing a photo-flow reactor system for continuous processing.
• Employing an acridinium photocatalyst for radical generation.
• Leveraging 1,5-hydrogen atom transfer and carbon monoxide trapping.
• Facilitating radical-polar crossover for cyclization.

Main Results:

• Successful synthesis of delta-lactones via direct C(sp3)─H carbonylation.
• Demonstrated tolerance of diverse functional groups.
• Achieved efficient gas-liquid mass transfer and scalability under flow conditions.
• Short reaction times and safe handling of carbon monoxide.

Conclusions:

• The developed photo-flow strategy provides a robust and scalable method for delta-lactone synthesis.
• This approach overcomes limitations of traditional carbonylation methods.
• Offers direct access to complex and bioactive lactone motifs from simple alcohols.