# Arylhydrazines: Convenient Homogeneous Reductants for Scalable Cross‐Coupling

## TL;DR

Arylhydrazines are introduced as a new, scalable, and efficient reductant for nickel-catalyzed cross-coupling reactions, offering better yields and practicality compared to traditional methods.

## Contribution

Arylhydrazines are proposed as a novel, homogeneous, and cost-effective reductant for scalable nickel-catalyzed cross-coupling reactions.

## Key findings

- Arylhydrazines enable efficient Ni-catalyzed sp2–sp3 cross-coupling with improved yields and selectivity over Zn-based methods.
- Mechanistic studies confirm hydrazine-mediated NiII reduction leading to a NiI/NiIII cycle with benign byproducts.
- Decagram-scale demonstrations and calorimetry assessments confirm enhanced reproducibility and thermal control.

## 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 sp2‐sp3 cross‐coupling of aryl halides with secondary alkyl iodides under mild, operationally simple conditions using a NiII 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, 19F NMR, and reaction calorimetry support a pathway involving hydrazine‐mediated NiII reduction to initiate a NiI/NiIII cycle, with benign byproducts (N2 and arene), positioning arylhydrazines as versatile reagents for executing reductive coupling on scale.

Reductive cross‐couplings enable efficient C–C bond formation but are limited by the heterogeneity of Zn or costly reagents like TDAE. We report arylhydrazines as inexpensive, convenient reductants for Ni‐catalyzed sp2–sp3 coupling of aryl halides and secondary alkyl iodides. Mechanistic studies support hydrazine‐mediated NiII reduction for a NiI/NiIII cycle, delivering improved yields, reproducibility, and scalability over Zn‐based methods.