Deracemization of Atropisomeric Biaryls Enabled by Copper Catalysis

Area of Science:

• Organic Chemistry
• Asymmetric Synthesis
• Catalysis

Background:

• Atropisomeric biaryls are essential chiral building blocks for catalysts and ligands.
• Developing efficient methods for accessing enantiomerically pure biaryls remains a significant challenge in organic synthesis.

Purpose of the Study:

• To develop an efficient crystallization-induced deracemization (CID) method for the scalable synthesis of chiral biaryls.
• To utilize copper catalysis with chiral ammonium salts for enantioselective deracemization.

Main Methods:

• Copper-catalyzed racemization of biaryl skeletons using bidentate diamine ligands.
• Enantioselective cocrystal formation with a chiral ammonium salt.
• Acid-quenching to directly isolate chiral biaryls without chromatography.

Main Results:

• The developed CID method efficiently produces chiral biaryls from racemates.
• The process is scalable and allows for the recovery of the chiral ammonium salt.
• Ligand studies indicated bulky alkyl substitution is crucial for efficient racemization, likely via a radical-cation intermediate.

Conclusions:

• The CID method offers a practical and scalable route to enantiomerically pure atropisomeric biaryls.
• This approach simplifies purification and reduces waste compared to traditional methods.
• The findings provide insights into the mechanism of copper-catalyzed racemization and deracemization.