Arylhydrazines: Convenient Homogeneous Reductants for Scalable Cross-Coupling

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Reductive cross-couplings form C-C bonds using electrophiles, avoiding preformed organometallics.
• Existing methods often use heterogeneous reductants (e.g., Zn) with poor reproducibility or costly homogeneous alternatives (e.g., TDAE).

Purpose of the Study:

• To introduce arylhydrazines as novel, inexpensive, homogeneous sacrificial reductants for nickel-catalyzed reductive cross-coupling reactions.
• To develop a mild, operationally simple, and scalable method for sp²-sp³ cross-coupling.

Main Methods:

• Utilized nickel(II) precursor, bipyridine ligand, and hindered amine base with arylhydrazines.
• Conducted optimization studies, substrate scope analysis, and direct comparisons with existing methods.
• Employed UV-vis spectroscopy, ¹⁹F NMR, and reaction calorimetry for mechanistic investigations.

Main Results:

• Achieved efficient Ni-catalyzed sp²-sp³ cross-coupling of aryl halides with secondary alkyl iodides.
• Demonstrated superior yields and selectivity over Zn-based methods, especially for heterocyclic and electron-rich substrates.
• Verified enhanced thermal control, reproducibility, and practicality through calorimetry and decagram-scale reactions.

Conclusions:

• Arylhydrazines serve as versatile, cost-effective homogeneous reductants for reductive cross-coupling.
• The developed method offers a practical and scalable alternative to current reductive coupling strategies.
• Mechanistic studies support a Ni^I/Ni^III catalytic cycle initiated by hydrazine-mediated Ni^II reduction, producing benign N₂ and arene byproducts.