Baran Team Unveils 2-sp3 Nickel Coupling That Preserves Chirality in Chiral Molecules
Updated
Updated · Chemical & Engineering News · Jun 4
Baran Team Unveils 2-sp3 Nickel Coupling That Preserves Chirality in Chiral Molecules
1 articles · Updated · Chemical & Engineering News · Jun 4
Summary
A Science paper reports a nickel-catalyzed radical cross-coupling that joins two sp3 carbons while retaining the stereochemistry of an enantioenriched partner—defying the usual expectation that chiral carbon radicals rapidly racemize.
The reaction generates one radical from a sulfonylhydrazide and another from a primary or secondary alkyl halide, then uses a nickel diazene complex to expel N2 and trap the chiral radical in a metal “cage” before coupling.
That setup gives easier access to chiral products such as substituted piperidines and pyrrolidines that previously required multistep syntheses, and it does so without chiral ligands or directing groups.
Daniel Weix of the University of Wisconsin–Madison called the stereoretentive radical capture in solution remarkable, saying the approach could become extremely powerful as its substrate scope expands.
The method still works best with cyclic sulfonylhydrazides; acyclic versions showed low stereoretention, making scope expansion the next hurdle after Baran’s 2025 alkyl-aryl cross-coupling advance.
This breakthrough is 'astounding' but has limits. What is the key challenge to making it a universal chemistry tool?
A new reaction breaks a fundamental chemistry rule. How will this accelerate the creation of life-saving drugs?
Breaking the Stereochemistry Barrier: Baran Team’s 90% Stereoretentive Radical Cross-Coupling Revolutionizes Pharmaceutical Synthesis
Overview
In 2025, the Baran team introduced a groundbreaking method for stereoretentive radical cross-coupling, marking a major shift in organic chemistry. This innovation overturned the long-held belief that radical reactions always destroy molecular stereochemistry, which had led chemists to avoid radical pathways when precise 3D control was needed. By directly challenging this assumption, the Baran team showed that radical reactions can actually preserve stereochemistry with high fidelity. Their method is simple to use and scalable, making it highly practical for real-world chemical applications and opening new possibilities for efficient synthesis of complex molecules.