Iridium-catalyzed H/D exchange: ligand complexes with improved efficiency and scope

Area of Science:

• Organic Chemistry
• Catalysis
• Isotope Chemistry

Background:

• Hydrogen isotope exchange (HIE) is a key method for introducing deuterium or tritium into organic molecules.
• Iridium complexes with N,P-ligands are known for asymmetric reductions but their HIE potential is explored here.

Purpose of the Study:

• To evaluate the efficacy of iridium-N,P-ligand complexes for hydrogen isotope exchange reactions.
• To identify optimal ligand structures and reaction conditions for efficient deuterium incorporation.

Main Methods:

• Screening of iridium complexes featuring various N,P-ligands for HIE activity.
• Testing a range of organic substrates with different functional groups for deuterium labeling.
• Investigating the effect of additives like tris(pentafluorophenyl) borane on reaction efficiency.

Main Results:

• Electron-rich N,P-ligands, specifically those with dicyclohexylphosphines or phosphinites, demonstrated high catalytic activity for HIE.
• Efficient deuterium incorporation was achieved for substrates bearing strong directing groups (pyridines, ketones, amides) and weak ligating units (nitro, sulfones, sulfonamides).
• The addition of tris(pentafluorophenyl) borane allowed for the successful labeling of substrates with deactivating nitrile substituents.
• A structurally simplified, achiral ligand derived from the chiral ThrePhox ligand yielded an iridium complex that is a powerful catalyst for HIE.

Conclusions:

• Iridium complexes with specifically designed N,P-ligands are highly effective catalysts for hydrogen isotope exchange.
• The developed catalytic system demonstrates broad substrate scope and functional group tolerance, including challenging nitriles.
• This work provides a powerful and versatile tool for the deuteration of organic compounds.