Walsh, Jamie M., Galzignato, Marco, Hattori, Shusuke, Triacca, Marylise and Lam, Kevin ORCID: https://orcid.org/0000-0003-1481-9212 (2026) eCyclopropanation: a safe and scalable electrochemical route to cyclopropanes. Chemical Science. ISSN 2041-6520 (Print), 2041-6539 (Online) (doi:10.1039/D5SC08940A)

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Abstract

Diazo compounds are among the most versatile intermediates in organic synthesis, enabling high-value transformations such as cyclopropanation, X–H insertion, and heterocycle formation. However, their intrinsic instability and hazardous nature have severely restricted their practical use, particularly at scale, largely due to the need to generate, isolate, or accumulate diazo species in solution. Here, we report a safe, one-pot, scalable, and operationally simple electrochemical strategy for the in situ generation of diazo compounds from tert-butylhydrazones, directly coupled to Rh(II)-catalysed cyclopropanation. In contrast to established approaches, the diazo intermediates in this platform are generated and consumed continuously, with no detectable accumulation at any stage of the process. This transient mode of operation fundamentally alters the safety profile of diazo chemistry, enabling electricity-driven oxidation under mild conditions without hazardous oxidants, isolated diazo compounds, or highly toxic additives. The use of a bench-stable mono-protected hydrazone precursor and a weakly nucleophilic electrolyte ensures efficient carbene transfer, delivering cyclopropanes in high yields across a broad range of hydrazones and olefins. The method readily translates to continuous flow, enabling gram-scale synthesis with good productivity. By preventing the accumulation of free diazo species in solution, this work removes a key barrier to the safe and scalable use of diazo chemistry and provides a general blueprint for modern carbene-transfer processes that are inherently safer, more sustainable, and industrially relevant.

Item Type:	Article
Uncontrolled Keywords:	Diazo, explosion, electrosynthesis, carbene, cyclopropanes
Subjects:	Q Science > Q Science (General) Q Science > QD Chemistry T Technology > T Technology (General)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	13 Feb 2026 14:25
URI:	https://gala.gre.ac.uk/id/eprint/52493

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