Mechanochemical Deracemization: A Sustainable Approach to Enantiopurity.

Area of Science:

• Organic Chemistry
• Green Chemistry
• Materials Science

Background:

• Traditional deracemization methods often rely on solvents, posing environmental and economic challenges.
• Developing solvent-minimized or solvent-free synthetic strategies is crucial for sustainable chemical practices.

Purpose of the Study:

• To introduce and validate mechanochemical deracemization (MCDR) as an efficient and sustainable alternative to solvent-based methods.
• To demonstrate the transposition of various deracemization reactions into a solvent-minimized ball milling environment.

Main Methods:

• Systematic investigation of mechanochemical deracemization (MCDR) using ball milling.
• Optimization of key parameters including milling material, ball characteristics, bulk material addition, and liquid-assisted grinding (LAG).
• Application of MCDR to a diverse range of substrates: ketone, isoindolinones, imines, ester, and an inorganic compound.

Main Results:

• Successful deracemization of six archetypal reactions in a solvent-minimized ball milling setup.
• Achieved quantitative enantiomeric excesses (ee) for the target enantiopure compounds.
• Reduced reaction times by up to 97% and achieved 100% solvent reduction compared to conventional methods.

Conclusions:

• Mechanochemical deracemization (MCDR) is established as a versatile and sustainable strategy for producing enantiopure compounds.
• The study highlights the generalizability of MCDR across various chemical structures and reaction types.
• MCDR presents a significant advancement in green chemistry, offering substantial waste reduction and efficiency gains.