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Updated: Jan 1, 2026

Isolating Free Carbenes, their Mixed Dimers and Organic Radicals
Published on: April 19, 2019
Fragment Coupling Reactions in Total Synthesis That Form Carbon-Carbon Bonds via Carbanionic or Free Radical
Martin Tomanik1, Ian Tingyung Hsu1, Seth B Herzon1,2
1Department of Chemistry, Yale University, 225 Prospect St, New Haven, CT, USA.
Abstract:
Fragment coupling reactions that form carbon-carbon bonds are valuable transformations in synthetic design. Advances in metal-catalyzed cross-coupling reactions in the early 2000s brought a high level of predictability and reliability to carbon-carbon bond constructions involving the union of unsaturated fragments. By comparison, recent years have witnessed an increase in fragment couplings proceeding via carbanionic and open-shell (free radical) intermediates. The latter has been driven by advances in methods to generate and utilize carbon-centered radicals under mild conditions. In this Review, we survey a selection of recent syntheses that have implemented carbanion- or radical-based fragment couplings to form carbon-carbon bonds. We aim to highlight the strategic value of these disconnections in their respective settings and to identify extensible lessons from each example that might be instructive to students.
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