Sulfonyl Hydrazides for Redox-Neutral Radical Cross-Couplings

The formation of carbon-carbon bonds is a long-standing challenge in synthetic organic chemistry primarily addressed in recent decades via cross-couplings. Cross-coupling has grown to be a powerful tool in organic synthesis in both research and industrial settings, winning the Nobel Prize in 2010. Traditional cross-couplings are primarily held back by the sensitivity of their reagents, and their limitations in forming saturated carbon-carbon bonds. To address these, researchers often look to the field of radical couplings. Literature on radical generation and coupling has exploded in recent years. Despite this surge, these reactions often suffer from issues of reaction complexity, scalability, reagent synthesis, stoichiometric additives, and stereochemical control. In early 2025, the Baran group reported a powerful technique of radical generation/coupling via sulfonyl hydrazides, a simple functionality accessible from feedstock chemicals. These undergo radical reactivity in mild conditions with simple setups, a cheap nickel catalyst, and no exogenous redox additives/systems. This reactivity is leveraged in a stereoretentive fashion to address the long-standing challenge of stereocenter inversion often experienced with radical chemistry.