Arylhydrazines: Convenient Homogeneous Reductants for Scalable Cross‐Coupling
Year: 2026
Type: article
Abstract: ABSTRACT Reductive cross‐couplings have emerged as a powerful strategy for forging C–C bonds directly from electrophiles, circumventing the need for preformed organometallic reagents, yet they often suffer from limitations associated with heterogeneous reductants like Zn (e.g., poor reproducibility and scalability) or costly homogeneous alternatives such as TDAE. Inspired by prior explorations of hydrazide chemistry, we disclose arylhydrazines as inexpensive, readily available homogeneous sacrificial reductants that enable Ni‐catalyzed sp 2 ‐sp 3 cross‐coupling of aryl halides with secondary alkyl iodides under mild, operationally simple conditions using a Ni II precursor, bipyridine ligand, and hindered amine base. Optimization, substrate scope studies, and direct comparisons reveal superior yields and selectivity relative to Zn‐based methods, particularly for heterocyclic and electron‐rich partners, while calorimetry‐guided safety assessments and decagram‐scale demonstrations highlight enhanced thermal control, reproducibility, and practicality. Mechanistic investigations via UV–vis spectroscopy, 19 F NMR, and reaction calorimetry support a pathway involving hydrazine‐mediated Ni II reduction to initiate a Ni I /Ni III cycle, with benign byproducts (N 2 and arene), positioning arylhydrazines as versatile reagents for executing reductive coupling on scale.
Source: Angewandte Chemie
DOI: 10.1002/ange.9252206
Institutions: Scripps Research Institute, AbbVie (United States)
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
OpenAlex ID: W7128027154