Efficient and selective Cu/nitroxyl-catalyzed methods for aerobic oxidative lactonization of diols

Area of Science:

• Organic Chemistry
• Catalysis
• Green Chemistry

Background:

• Oxidative lactonization is a crucial transformation in organic synthesis.
• Developing efficient and selective catalytic systems for this reaction remains a challenge.
• Utilizing ambient air as a sustainable oxidant is highly desirable.

Purpose of the Study:

• To identify novel copper/nitroxyl catalyst systems for aerobic oxidative lactonization of diols.
• To investigate the influence of nitroxyl cocatalyst identity on reaction selectivity.
• To establish the scope and limitations of these catalytic systems.

Main Methods:

• Aerobic oxidative lactonization reactions were performed using various diols.
• Copper catalysts were paired with different nitroxyl cocatalysts, specifically 9-azabicyclo[3.3.1]nonan-N-oxyl (ABNO) and 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl (TEMPO).
• Reaction conditions were optimized for efficiency and selectivity.

Main Results:

• Highly efficient and selective aerobic oxidative lactonization of diols was achieved under mild conditions.
• The Cu/ABNO system demonstrated excellent reactivity with symmetrical and hindered unsymmetrical diols.
• The Cu/TEMPO system exhibited superior chemo- and regioselectivity for less hindered unsymmetrical diols.
• Catalyst systems showed compatibility with diverse alcohol classes (benzylic, allylic, aliphatic) and functional groups (alkenes, heterocycles).

Conclusions:

• Novel Cu/nitroxyl catalysts provide a powerful platform for aerobic oxidative lactonization.
• Tunable chemo- and regioselectivity can be achieved by judicious selection of the nitroxyl cocatalyst.
• These methods offer a sustainable and versatile approach for synthesizing lactones from diols.